Hospital Infections PDF

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Willliam R~ . Jarvis
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BENNETT & BRACHMAN'S
Hospital Infections
Sixth Edition
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Hospital Infections
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EDITOR.
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WILLIAM R. JARVIS, MD
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President, Jason andJarvis Associates, I.LC

Port Orford, Oregon;
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Hilton Head Island, South Carolina;

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San Francisoo, Califumia

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Library of Coogreu Cataloging-in-Pu.blicatioo Data
Bennett & Brachman's hospital infections I editor, William R. Jarvis.-Sixth edition.
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Bennett and Brachman's hospital infections
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Hospital infections
Includes bibliographical references and index.
ISBN 978-1-4511-7592-9- ISBN 1-4511-7592-2 s.
I. Jarvis, William R. (William Robert), 1948- editor of compilation. II. Title: Bennett and
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Brachman's hospital infections. ill. Title: Hospital infections.
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[DNLM: 1. Cross Infection-prevention & control. 2. Cross Infection-etiology. WX 167]

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10 9 8 7 6 5 4 3 2 1
To my wife Janine and our children Danielle and Ashley,
for their love, friendship, and never-ending support and
encouragement, as well as their unique ability to keep me
balanced, grounded, to put everything into perspective,
and to support my efforts to reduce healthcare-associated
infections throughout the world.
Contributors
Bcnedc:tta All.egranzi, MD, Joan Blanchard, MSS, BSN, Sara E. Cosgrove, MD, MS
DTM&H RN, CNOR, CIC Associate Profe.nor af Medicine, Division
Technical Lead, Clean Care h Safer Care NUDe Compliance Inapector, Health Fa- of Infectious Disease11,johna Hopkins
Programme, Department of Patient Safety, cilitieJ and Emergency Medical Senice1 Univemty School of Medicine, Director,
World Health Organization, Geneva, Division, Colorado Department of Public Antimicrobial Stewardahip Program, Johns
Switzerland Health, Denver, Colorado Hoplin1 Hospital, Baltimore, Maryland
Deveridt:J. Anderson, MD, MPH .Bliza.betb. A. Bolyard, RN, MPH Donald E. Craven, MD
.Associate Professor of Medi.cine, Duke National Center for Emerging and Zoe> Chair, Center for Infectious Diseaaes and
University Medical Center, Durham, North notic Infectious Diseases, Division of Prevention, Lahey Clinic Medical Center,
Carolina Healthcare Q;uality Promotion, Centers for Burlington, Massachusetts, Professor of
Disease Control and Prevention, Atlanta, Medicine, Tufts University School af Medi-
Mary Andrus, BA, RN, CIC Georgia cine, Boston, Massachusetts
President, Surveillance Systems Worldwide
lnc., Gainesville, Georgia Robert A. Bonomo, MD Kathleen Steger Craven,
Professor of Medicine, Phannacology, RN,MPH
unnox K. Archibald, MD, PhD, Molecular Biology, and Microbiology, Case Assistant Profeaaor of Family Medicine and
FRCP,DTM&H Westem Resene Univenity, Chief, Medical Community Health, University of Massa-
.Associate Professor ofMedi.cine, College of Service, Louis Stokes Cleveland Depart- chusetts Medical School, Director, Acquired
Medicine, Univemty of Florida, Hospital ment ofVeteran.'l Aflfairs Medical Center, Brain Injury Waiver Unit, Director of Clini-
Epidemiologist, Malcom Randall Veterans Cleveland, Ohio cal Services and Support!, Commonwealth
Adminiscntion Medical Center, GaineSYille, Medicine, Shrewabury, Massachusetts
Florida John M. Boyce, MD
Clinical Profe110r ofMedi.cine, Department
Daniel J. Diekem.a, MD
Matthew J. Arduino, MD, MPH of Medicine, Yale Univemty School of Professor of Medicine, University of Iowa,
Supervisory Research Microbiologist, Medicine, Director, H011pital Epidemiology Associate Director, ClinicaJ. Microbiology
Branch Chief, Clinical and En\'ironmental and Infection Control, Q.uali.ty Improve- Laboratory, University oflowa Hospital,
Microbiology Branch, Division of Health- ment Support Services, Yale-New Haven Iowa City, Iowa
care Q.uali.ty Promotion, National Center Hospital, New Haven, Connecticut
for Emerging and Zoonotic Infectious
Diseases, Centers for Disease Control and Carol B. Chenoweth, MD, MS Michael Edmond, MD,
Prevention, Atlanta, Geo~ Professor of Intemal Medicine, Dmaion of MPH,MPA
Infectious Diseases, Univemty of Michigan ProfeiiiOl', Internal Medicine, Epidemiology
Health Syatem, Ann Arbor, Michigan and Community Health, Vuginia Com-
Hilary M. Babc:ock, MD, MPH monwealth Univemty School of Medicine,
.Assiltant Professor, Department of Infec- Ho.spital Epidemiologist/Medical Director,
tious Dilease1, Washington Univenity Raymond Y. Chinn, MD Performance Improvement, Vuginia
School of Medicine, Medical Director, BJC Medical Director, Infection Prevention,
Commonwealth Univenity Medical Center
Infection Prevention and Epidemiology Hospital Epidemiologist, Sharp Hospital,
Consortium, BJC HealthCare, St. I..ouit, San Diego, California
Missouri Barry M. Farr, MD, MSc
Professor Emeritull, Department of Medi-
Teena Chopra, MD, MPH cine, University ofVuginia, Charlottesville,
Henri Ba1aguera, MD As.siatant Profe.uor af Medicine, Division af
Vuginia
Assistant Professor of ClinicaJ. Medi.cine, Infectious Diseases, Wayne State Univenity,
Tufts Univenity School of Medicine, Associate Corporate Director, Infection
Boston, Massachusetts Prevention, Epidemiology, and Antibiotic Sc:ott K. Fridtin, MD
Hospital Medicine, Lahey Hmpital Medical Stewardship, Kindred Hospital University Deputy Chief, Surveillance Branch, Divi-
Center, Burlington, Massachusetts Health Center, Detroit Medical Center, sion ofHealthcare Quality Promotion,
Detroit, Michigan Centen for Disease Control and Preven-
.Blhc M. Beltrami, MD, MPH tion, Atlanta., Georgia
Associate Director of Epidemiologic Sci- Bnmo P. Coignard, MD, MSc
ence, National Center for Emerging and Chief, Healthcare-AMOciated Infection Sur- Candace Friedman, MPH, CIC
Zoonotic Infectious Diseases, Centen for veillance, Infectious Di.Jeasel Department, Senior Project Manager, Office of Clinical
Disease Control and Prevention, Atlanta., Inadtut de Veille Sanitaire (InVS), Saint- Safety, University of Michigan Health
Georgia Maurice, France Syatem, Ann Arbor, Michigan
vi
Contributors vii
Axel Gamulin, MD William R. Jarvis, MD Janice I.o, MD

Senior Staff Surgeon, Faculty of Medicine, President, Jason and Jarvis A.!!Bociates, Consultant Medical Microbiologist,
University of Geneva, Senior Staff Surgeon, llC, Hilton Head Island, South Carolina, Virology Division, Public Health Labora-
Division of Orthopaedic and Trauma Port Orford, Oregon, San Francisco, tory Services Branch, Centre for Health
Surgery, University Hospitals of Geneva, California Protection, Department of Health, Hong
Geneva, Switzerland Kong, China
Mini Kamboj, MD
Robert P. Gaynes, MD Assistant Member, Infectious Disease Benjamin A. I.opman, PhD
Profe.!IBor of Medicine, Emory University Service, Department of Medicine, Memorial Division ofVrral Diseases, Centers for Dis-
School of Medicine, Attending Physician/ Sloan-Kettering Cancer Center, A.!!Boci- ease Control and Prevention, Adjunct~
Hospital Epidemiologist, Atlanta Veterans ate Director, Infection Control, Memorial sistant Profe.!IBor, Rollins School for Public
Hospital, Atlanta, Georgia Hospital, New York City, New York Health, Emory University, Al:lanta, Georgia
Sharon Giarrizzo-Wtlson, MS, Keith S. Kaye, MD, MPH Tammy S. Lundstrom, MD, JD
RN-BC, CNOR Profe.!IBOr of Medicine, Wayne State SVP, Chief Medical Officer, Premier
Measures Informatics Director, eMeasures University, Corporate Vice President, Health, Dayton, Ohio
Departtnent, Oklahoma Foundation for Patient Safety and Quality, Corporate
Medical Quality, Oklahoma City, Oklahoma Medical Director, Infection Prevention, Dennis G. Maki, MD
Hospital Epidemiology and Antimicrobial Professor Emeritus of Medicine, Section of
Stewardship, Detroit Medical Center, Infectiom Diseases, University of Wisconsin
Philip E. Grgurich, PharmD, MBA School of Medicine and Public Health,
Detroit, Michigan
A.!l.!listant Profe.!IBor of Pharmacy Practice,
Madison, Wisconsin
Massachusetts College of Pharmacy
and Health Sciences University, Boston, Faiz Ahmad Khan, MD, MPH
Massachusetts, Medical ICU Clinical Assbtant Profe.!IBor (Clinical) of Medicine, L. Clifford McDonald, MD
Pharmacut, Lahey Clinic Medical Center, McGill University, Physician, Division of Senior Advisor for Science and Integrity,
Burlington, Massachusetts Respiratory Medicine, McGill University Division of Healthcare Quality Promotion,
Health Centre, Montreal, Canada Centers for Disease Control and Preven-
tion, Atlanta, Georgia
Jennifer H. Han, MD, MSCE
Instructor of Medicine, DivWon oflnfectiom David T. Kuhar, MD
Diseases, University of Pennsylvania School Medical Officer, Division of Healthcare Dick Menzies, MD
Quality Promotion, Centers for Disease Professor, Departments of Medicine and
of Medicine, Philadelphia, Pennsylvania
Control and Prevention, Atlanta, Georgia Epidemiology & Biostatistics, Montreal Chest
Institute, McGill University, Montreal, Canada
Stephan A. Harbarth, MD, MS
A.!!Bociate Professor of Medicine, University Caroline Landelle, PharmD, PhD Leonard A. Mermel, DO, ScM,
of Geneva Medical Faculty, Head, Antimi- Research Fellow, Infection Control
crobial Stewardship Program, Infection Program, University of Geneva Hospitals,
Am (Hon), FSHEA, FIDSA,
Control Unit, Geneva University Hospitals, Geneva, Switzerland FACP
Geneva, Switzerland Profe.!IBOr of Medicine, Warren Alpert Med-
ical School of Brown University, Medical
Ebbing Lautenbach, MD, Director, Department of Epidemiology and
Mary K. Hayden, MD MPH,MSCE Infection Control, Rhode Island Hospital,
Profe.!IBor of Medicine (Infectiom Dueases) Profe.!IBOr of Medicine and Epidemiology, Providence, Rhode Island
and Pathology, Rush Medical College, Department of Medicine and
Director, Division of Clinical Microbiology, Epidemiology, University of Penmylvania,
Attending Physician, Infectiom Diseases,
David W. Mozingo, MD, FACS
Chief, Division of Infectious Diseases,
Profe.!IBOr of Surgery, University ofF1orida
Rush University Medical Center, Chicago, Hospital of the University of Pennsylvania,
College of Medicine, Director, Bum
Dlinois Philadelphia, Pennsylvania
Center, UF Academic Health Center,
Gainesville, F1orida
David K. Henderson, MD Daniel P. Lew, MD
Deputy Director for Clinical Care, Office Profe.!IBOr of Medicine, Specialities of In- Belinda Ostrowsky, MD, MPH
of the Director, Nlli Clinical Center, ternal Medicine, Service oflnfectiom Dis- Assutant Profe.!IBor of Internal Medicine,
Bethesda, Maryland eases, University of Geneva, Chief, Service Alben Einstein College of Medicine, Direc-
of Infectiom Dueases, University Hospitals tor, Antimicrobial Stewardship, Montefiore
Karen K. Hoffmann, RN, MS, of Geneva, Geneva, Switzerland Medical Center, New York City, New York
CIC, FSHEA
Clinical Instructor, Division of Infectious Michael Y. Lin, MD, MPH Robert C. Owens, Jr., PhannD
Dueases, University of North Carolina Assutant Profe.!IBor of Medicine, Section of Regional Medical Affuirs Director, Portland,
School of Medicine, Infection Prevention· Infectiom Dueases, Rush University Medi- Maine, United States, Durata Therapeutics
ist, CMS Survey and Certification Group, cal Center, Chicago, Dlinois Inc, Chicago, lliinois
Chapel Hill, North Carolina
Moi Lin Ling, MBBS, FRCPA Leonardo Pagani, MD
Teresa C. Horan, MPH Adjunct Assistant Profe.!IBor of Microbiol- Infection Control Program, Geneva
Adjunct Faculty, Departtnent of Epide- ogy, Duke-NUS Graduate Medical School, University Hospitals, Geneva, Switzerland,
miology, Rollins School of Public Health, Director, Infection Control, Singapore Senior Consultant, Infectiom Diseases Unit,
Emory University, Al:lanta, Georgia General Hospital, Singapore Balzano Central Hospital, Balzano, Italy
viii Contributors
Benjamin J. Park, MD Vuginia R. Roth,~, MBA Nalini Singh, MD, ~H, FAAP,
Surveillance Branch, Division of Healthcare Associate Professor of Medicine, FIDSA, FSHEA
Quality Promotion, Centers for Disease Epidemiology & Community Medicine, Professor of Pediatrics and Global Health,
Control and Prevention, Atlanta, Georgia University of Ottawa, Medical Director, The George Washington University,
Infection Prevention and Control, The Children's National Medical Center,
GopiPa~,MD,~S Ottawa Hospital, Ottawa, Ontario, Canada Washington, District of Columbia
Assistant Professor of Medicine, Division
of Infectious Diseases, Icahn School of William A. Rutala, PhD, MPH Rachel ~. Smith, MD, MPH
Medicine at Mount Sinai, The Mount Sinai Professor of Medicine, Division of Infectious Epidemic Intelligence Service Officer,
Hospital, New York City, New York Diseases, University of North Carolina Mycotic Diseases Branch, Centers for
School of Medicine, Hospital Epidemiology, Disease Control and Prevention, Atlanta,
Priti R. Patel, MD, ~H University of North Carolina Health Care Georgia
Division of Healthcare Quality Promotion, System, Chapel Hill, North Carolina
Centers for Disease Control and Preven- Barbara~- Soule, RN, MPA,
tion, Atlanta, Georgia Nasia Safdar, MD CIC, FSHEA
Associate Professor of Medicine, Division of Practice Leader, Infection Prevention
Eli N. Perencevich, MD, MS Infectious Disease, University of Wisconsin Services, Consulting Division, Joint Com-
Professor of Medicine, Divisions of General School of Medicine and Public Health, mission Resources/Joint Commission Inter-
Internal Medicine and Infectious Diseases, Madison, Wisconsin national, Oak Brook, Illinois
University oflowa Carver College of
Medicine, Iowa City VA Medical Center, Cassandra D. Salgado, MD, MS Susan Springthorpe, MSc
Iowa City, Iowa Associate Professor of Medicine, Director of Research, Centre for
Department of Internal Medicine, Infectious Research on Environmental Microbiology,
Kathleen H. Petersen, ~s Diseases, Medical Director for Infection University of Ottawa, Ottawa, Ontario,
Infection Control Practitioner, Department Control, Department of Infection Preven- Canada
of Infection Control and Epidemiology, tion and Control, Medical University of
University of Michigan Health System, Ann South Carolina, Charleston, South Carolina Wchael P. Stevens, MD, ~H
Arbor, Michigan Assistant Professor, Department of Internal
Thomas J. Sandora, MD, ~H Medicine, Division of Infectious Diseases,
Assistant Professor of Pediatrics, Harvard Vrrginia Commonwealth University, AJJ-
Michael A. Pfaller, MD
Medical School, Hospital Epidemiologist, sociate Hospital Epidemiologist, Vrrginia
Emeritus Professor of Pathology, University
Medical Director oflnfection Prevention Commonwealth University Medical Center,
of Iowa College of Medicine, Iowa City,
and Control, Boston Children's Hospital, Richmond, Virginia
Iowa, Consultant,JMI Laboratories, North
Liberty, Iowa Boston, Massachusetts
Andrew Stewardson, MBBS
Didier Pittet, MD, MS Syed A. Sattar, PhD Research Fellow, Faculty of Medicine,
Professor Emeritus of Microbiology, University of Geneva, Research Fellow,
Professor of Medicine, Faculty of Medicine,
Centre for Research on Environmental Infection Control Program, University of
University of Geneva, Director, Infection
Microbiology, University of Ottawa, Ottawa, Geneva Hospitals, Geneva, Switzerland
Control Program and WHO Collaborating
Ontario, Canada
Centre on Patient Safety, University of
Geneva Hospitals, Geneva, Switzerland Nimalie D. Stone, ~
W. Michael Scheid, MD Medical Epidemiologist for Long-Term
Professor of Infectious Diseases, Professor Care, Prevention and Response Branch,
Basil A. Pruitt, Jr., MD oflntemal Medicine, Clinical Professor Division of Healthcare Quality Promotion,
Clinical Professor of Surgery, University Centers for Disease Control and Preven-
ofNeurosurgery and Director of the
of Texas Health Science Center, Staff Sur- tion, Atlanta, Georgia
Pfizer Initiative in International Health,
geon, Trauma Division, University Health
University ofVirginia (UV) School of
System, San Antonio, Texas
Medicine, Charlottesville, Virginia Jeffrey~. Tessier, MD
Director, 'Ihmsplantation Infectious Diseases
L. Barth Rdler, MD Kent Sepkowitz, MD Service, Vrrginia Commonwealth University
Professor of Medicine and Pathology, Duke Professor of Medicine, Weill-Cornell Medi- School of Medicine, Richmond, VIrginia
University School of Medicine, Durham, cal College, Director, Hospital Infection
North Carolina Control, Memorial Sloan-Kettering Cancer I1ker UPtay, MD
Center, New York City, New York Lecturer, Specialities of Internal
Chesley L. Richards, Jr., MD, Medicine, Service of Infectious Diseases,
~H W'mg Hong Seto, MD Orthopaedic Surgery Service, Univenity
Division of Healthcare Quality Promotion, Director, WHO Collaborating Centre of Geneva, Attending Physician,
National Center for Infectious Diseases, for Infection Control, Senior Advisor Univenity Hospitals of Geneva,
Centers for Disease Control and (Infection Control), Hospital Authority, Geneva, Switzerland
Prevention, Atlanta, Georgia Hong Kong, China
August J. Valenti, MD, FACP,
Victor D. Rosenthal, MD, Bryan P. Simmons, MD FIDSA, FSHEA
CIC,MSc Clinical Professor of Medicine, University Professor of Medicine, Tufts University
International Nosocomial Infection ofTennessee, Medical Director, Infection School of Medicine, Boston, Massachusetts,
Control Consortium (INICC), Buenos Prevention, Methodist Le Bonheur Health- Hospital Epidemiologist, Maine Medical
Aires, Argentina care, Memphis, Tennessee Center, Portland, Maine
Contributors ix
David J. Weber, MD, MPH Sharon F. Weibel, MD Keith F. Woeltje, MD, PhD
Profe.!IBor of Medicine and Pediatrics, Associate Professor of Medicine, Professor of Infectious Diseases/Internal
Division of Infectious Diseases, University Rush University Medical Center, Medicine, Washington University School
of North Carolina School of Medicine, Director, Hospital Epidemiology and of Medicine, Director ofHealthcare Infor-
Hospital Epidemiology, University of North Infection Control, Infectious Disease matics, Center for Clinical Excellence, BJC
Carolina Health Care System, Chapel Hill, Physician HealthCare, SL Louis, Missouri
North Carolina
Michael L. Wtlson, MD
Robert A. Weinstein, MD Professor of Pathology, University of
Chairman, Department of Medicine, Colorado School of Medicine, Aurora,
John H. Stroger,Jr. Hospital, Cook County Colorado, Director, Department of
Health and Hospital System, Chicago, Pathology and Laboratory Services, Denver
lllinois Health, Denver, Colorado
Preface
Prevention and control of healthcare-as.sociated infections settings, hemodialysis centers, and even home healthcare. In-
(H.Ab) has become the focus of many efforts at the local, na- fection control is being applied in the entire continuum of
tional, and international levels. Although for decades infection healthcare. Each of these settings has unique issues to address
preventionists and others interested in healthcare epidemiol- in healthcare epidemiology and infection control. In addition,
ogy have focused their attention on surveillance and control the field of healthcare epidemiology has advanced to include
of HAia, it is only most recently that the public is demanding infectious and noninfectiow processes. In this new edition of
accountability for the prevention and control of preventable Bennett & Brachman :S Hospital In.ftcticm, we address many of
HAls. This has led to a movement of public reporting of HAl these issues by experts in the field from around the world.
rates in the United States and in other countries around the Nearly half the authors of chapters in this edition are new
world. Legislation has been passed at the state and national lev- to this work. In addition, many of the authors provide a view·
els in the United States requiring public reporting ofHAh and point from outside the United States, even practices for those
requiring an intensification of efforts to prevent and control in resource-poor countries. Thw, the material is new and up-
these infectioru through the implementation of multimodal dated to include the latest in the field. We have tried to address
strategies or bundles of prevention activities. In addition, the healthcare epidemiology and infection control issues in sur-
World Health Organization (WHO) has taken a more aggres- veillance, prevention, and patient safety and quality improve-
sive and visible role in the effort to prevent and control HAis ment. We have addressed infection control and prevention in
through its patient wety activities and worldwide hand hygiene all settings from small community hospitals to large referral
campaign. medical centers, inpatient and outpatient settings, in intensive
In the past, most infection control programs used "bench- care units, and on warda and the surgical suites. We provide
marlc.ing• or comparison to national surveillance data or pub- approaches to surveillance outlines from the CDC's NHSN
lished reports of HAl rates as a measure of their effectiveness. (HAl incidence surveillance) and that used more commonly
That is, if the healthcare facility's HAl rate was at or below the in Western Europe and throughout the world (HAl prevalence
median-reported rate for similar facilities (often compared surveillance). We provide insight into current and evolving
with the Centers for Disease Control and Prevention's [CDC's] multimodal strategies or bundles for the prevention of the hlg
National Healthcare Safety Network [NHSN; formerly the Na- four HAls--CLA-BSis, CA-lms, SSia, and VAE. We provide
tional Nosocomial Infections Surveillance (NNIS) system], approaches to cost and cost-benefit analyses of HAl preven-
then no further action was necessary. However, recent intel"' tion programs and emphasize the most important multimod.al
ventions illwtrate that an even greater proportion of HAls are strategies for the prevention of HAis, focusing on the evidence
preventable than previously estimated. In sDme facilities, cen- upon which the recommendations for the interventions are
tral line-associated bloodstream infection (CLA-BSI) rates are based.
<1 per 1,000 central catheter-days. Large reductions in cath- Antimicrobial-resistant pathogens (ARPs) have become a
eteNSSOciated urinary tract infections (CA-UTh), surgical site major public health crisis. Since the 1970s, MRSA has become
infections (SSls), ventilator-anociated events (VAE), and pneu- endemic in most healthcare facilities around the world, with a
monia (VAP) have been achieved. In addition, many have dra- few exceptions in Denmark, Holland, and Western Australia.
matically reduced the multidrug-resistant organiam infection Over the past decade, we have witnessed a remarkable reversal
rates, particularly by methicillin-resistant StapAylocot:t:WJ aumu of the endemic healthcare-associated MRSA (HA-MRSA) at the
(MRSA) or vancomycin-resistant enterococcus (VR.E). The goal same time that community-associated MRSA (CA-MRSA) has
of this sixth edition of Bennett & Brachman~ Hospit4l Infections is increased. Healthcare facilities adopting active detection and
to provide the reader with the latest in the field of healthcare isolation (ADI), which includes screening for colonization,
epidemiology and HAl prevention and control and to provide placement of MRSA-colonized or infected patients in contact
the tooh to move the field of healthcare epidemiology and in- isolation, hand hygiene, and environmental control (with or
fection control to zero tolerance for preventable HAis. without antimicrobial controls), have achieved remarkable de-
Over the past decade, there have been tremendous advances clines in their MRSA rates, something many in infection control
in the field of healthcare epidemiology and infection control. did not believe was achievable. Such interventions have second-
Like the deliveryofhealthcare, the field ofhealthcare epidemi- arily led to reductions in VRE as well as Clostridium difficileinfec-
ology and infection control has moved from surveilla:nce and tions. The emergence of C. dqjidl.Hssociated disease (CDAD)
control ofHAis in hospitah to include all inpatient and outpa- has focused attention both on improving antimicrobial stew-
tient healthcare settings, including long-term care, long-term ardahip and the importance of environmental cleaning and
acute care, rehabilitative care, acute care, acute step-down care, disinfection. A!5 a result, we have seen the introduction of new
transitional care, outpatient surgicenters, other outpatient technologies for terminal room disinfection, such as hydrogen
X
Preface xi
peroxide vapor or gas and ultraviolet germicidal irradiation world. We should learn from one another's experiences so that
(UVGI) machines. The issue of antimicrobial stewardship has we can improve the outcomes in our own patients.
taken on even more serious attention as we have witnessed the Over the past decade, we have seen the increased attention
emergence of pan-resistant Acinetobacter spp. and more recently given to infection control by the public in many countries. This
carbapenem-resistant Enterobacteriaceae (CRE). The preven- has led to public reporting of HAl rates; legislation requiring
tion of transmission of these and other multidrug-resistant screening for selected MDROs, especially MRSA; legislation
pathogens will be dependent upon the implementation of requiring implementation of certain multimodal strategies or
proven infection control measures. Improving the stewardship HAl prevention bundles; reduced or no reimbursement for se-
of antimicrobials may reduce the emergence of such strains, lected infections, monetary penalties for selected readmissions
but only the complete adherence to proven infection control within 30 days of discharge; and an emphasis on other HAl pre-
measures will prevent the transmission of such strains in our vention strategies. For decades we have known that infection
healthcare facilities. Because of the importance of this issue, prevention and control programs are cost-effective and that it
we have included several chapters addressing the topic from is less expensive to prevent rather than treat the HAl. Enor-
microbiologic (mechanisms of resistance and how to detect mous strides have been taken in the prevention and control of
them), epidemiologic (risk factors and modes of transmission), HAis in the past decade. This has led the U.S. Department of
and interventional (evidence-based methods to prevent the Health and Human Services (DHHS) to publish its action plan,
emergence or transmission of these pathogens) perspectives. which calls for dramatic reductions (25% to 50%) ofCLA-BSis,
Healthcare epidemiology and infection control activities are CA-UTis, SSis, MRSA, and so on in 5 years. Other countries
no longer just important in developed countries. Rather, the also are setting HAl reduction targets. It is one of the most
prevention and control of HAis is a critical component of ef- exciting times to be involved in healthcare epidemiology and
fective patient safety programs in all healthcare settings in the infection control. We in infection control and healthcare epi-
world. The worldwide spread of severe acute respiratory syn- demiology should lead the way to prevention through educat-
drome (SARS), CRE, new extended-11pectrum J-lactamase pro- ing our healthcare workers, hospital administrators, legislators,
ducers, or the novel covariant SARS illustrates how healthcare consumers, and others in the advances we have made and are
facilities around the world are linked into a small world. For making in the prevention and control of HAis. The healthcare
that reason, we have invited renowned authors from around epidemiology and infection control community should take
the world to address the critical elements of successful infec- the enormous advances in knowledge contained in this edition
tion control prevention and control programs, such as hand hy- of Bennett & Brackman's Hospital Infections and ensure that the
giene, pandemic influenza, and patient safety. We hope that by prevention interventions are fully implemented so that as many
including the perspective of those from throughout the world, preventable HAis as possible are prevented, with the ultimate
we can bring all healthcare epidemiology and infection control goal being that all preventable HAis are being prevented. We
communities together and enhance the speed with which we have entered the era of zero tolerance for preventable HAis,
improve infection control and healthcare epidemiology activi- and many more are preventable now than ever thought possi-
ties in all healthcare facilities throughout the world. For many ble. If prevention of these HAis is of primary importance, then
if not most HAis, the pathophysiologic mechanisms of infec- action is essential!
tion are the same regardless of age or geographic location.
We can learn from one another. A multimodal strategy used
in Switzerland will work in Thailand and vice versa. More and -WiUiamR.Jaruis, MD
more, advances in infection control and healthcare epidemi- Pmident
ology are being published from virtually every country in the jason andJarvis Associates, LLC
Contents
Contributors vi 10 Use of Computerized Systems

Preface x in Healthcare Epidemiology. • • • • • 112
KEITH F. WOBLTJE
SECTION 1: General 11 The Role of the Laboratory

Considerations of Hospital in Prevention of Healthcare-
Associated Infections • • • • • • • • • • • 119
Infections 1 MICHAEL A. PFALLERAND DANIEL J. DmKBMA
12 The Practice of Epidemiology

1 Epidemiology of Healthcare- in Community Hospitals • • • • • • • • 139
.Associated..lrlfections ••••••••••••• 1 AUGUST J. VALENTI
BELINDA OSTROWSI<Y
13 The Role of Professional,
2 The Healthcare Epidemiologist •••• 21 Governmental, and &gulatory
VIRGINIA R. ROTH AND BRYAN P. SIMMONS
Organizations in Infection
3 Hand Hygiene ••••••••••••••••• 26 Prevention and Control • • • • • • • • • 154
BENEDFITA ALLEGRANZI, ANDREW BARBARA M. SOULE, KAREN K. HOFFMANN,
STEWARDSON, AND DIDmRPITTBT AND TAMMY S. LUNDSTROM
4 Occupational Health Services •••••• 41 14 Antimicrobial Stewardship:
DAVID T. KUHAR, ELISE M. BELTRAMI, AND Programmatic Efforts to
EIJZABETH A. BOLYARD
Optimize Antimicrobial Use •••••• 169
5 The Development of Infection ROBERT C. OWENS, JR. AND WILIJAM R. JARVIS
Surveillance and Prevention 15 Multidrug-&sistant Organisms:
Programs • • • • • • • • • • • • • • • • • • • • • 57 Epidemiology and Control. • • • • • • 181
HII..ARY M. BABCOCK AND KEITH F. WOBLT}E
MICHAEL Y. LIN, ROBERT A. WEINSTEIN,
6 Surveillance ofHealthcare-Assodated AND MARY K. HAYDEN
In.f'ections ••••••••••••••••••••• 63 16 Molecular Biology of Resistance:
MARY ANDRUS, TERESA C. HORAN, AND ROBERT P. A Brief History of Resistance
GAYNES
Mechanisms and the Discovery
7 The Use of Prevalence Surveys for of Gene Transfer • • • • • • • • • • • • • • 208
Healthcare-Associated.. Infections GOPI PATEL AND ROBERT A. BONOMO
SllrVeillance ••••••••••••••••••• 75 17 Economic Evaluation of
BRUNO P. COIGNARD
Healthcare-Associated Infections
8 Investigating Endemic and and Infection-Control and
Epidemic Healthcare-Associated Antimicrobial-Stewardship
Infections. • • • • • • • • • • • • • • • • • • • • 8 5 In.tervcn.tion.s • • • • • • • • • • • • • • • • • 220
Wll.UAM R. JARVIS ELI N. PBRENCEVICH AND SARA B. COSGROVE
9 Epidemiologic Methods for 18 Epidemiology and Control

Investigating Infections in the of Healthcare-Acquired In.f'ections
Healthcare Setting • • • • • • • • • • • • • 102 in Limited-Resource Settings ••••• 230
]BNNIFERH. HAN AND EBBING LAUTENBACH VICTOR D. ROSENTHAL
Contents xili
SECTION II: Functional Areas SECTION III: Endemic and

of Concern 277 Epidemic Hospital Infections 451
19 The Inanimate Environment .••.. 277 30 Incidence and Nature of
JOHN M. BOYCE Endemic and Epidemic
20 Disinfection and Sterilization Healthcare-Associated Infections .. 451
in Healthcare Facilities .......... 293 LENNOX K. ARCHIBALD AND WILLIAM R JARVIS
WILLIAM A. RUTAIAAND DAVID J. 31 Urinary Tract Infections ........ 476
WEBER CAROLE. CHENOWETH
21 Foodborne Disease Prevention 32 Hospital-Acquired and
in Healthcare Facilities .......... 311 Ventilator-Associated Pneumonia •• 485
SYED A. SATrARAND SUSAN SPRINGTI:IORPE
DONALD E. CRAVEN, PHILIP E. GRGURICH,
22 Clinical Laboratory-Acquired KATHLEEN STEGER CRAVEN, AND HENRI
BAIAGUERA
Infections .................... 320
MICHAEL L. WILSON AND L. BARTI:I 33 Nosocomial Tuberculosis ........ 501
RELLER DICK MENZIES AND FAIZ AHMAD KHAN
23 Dialysis-Associated Complications 34 Infectious Gastroenteritis ........ 513
and Their Control ............. 329 L. CLIFFORD MCDONALD AND BENJAMIN A.
MAITHEW J. ARDUINO AND PRITI R PATEL LOPMAN
24 The Intensive Care Unit, Part A: 35 Central Nervous System Infections .. 531
HAl Epidemiology, Risk Factors, JEFFREY M. TESSIER AND W. MICHAEL SCHELD
Surveillance, Engineering and
Administrative Infection Control
36 Surgical Site Infections. . . . . . . . . . 540
TEENA CHOPRA, DEVERICK J. ANDERSON,
Practices, and Impact . . . . . . . . . . . 3 57 AND KEITH S. KAYE
DIDIERPITfET, CAROLINE LANDELLE,
AND STEPHAN A. HARBARTI:I 37 Infections of Burn WoWlds . . . . . . 552
DAVID W. MOZINGO AND BASIL A. PRUIIT, JR
25 The Intensive Care Unit,
Part B: Antibiotic Resistance 38 Infections due to Infusion
and Prevention of CVC-BSis, Therapy . . . . . . . . . . . . . . . . . . . . . 561
NASIA SAFDAR, DENNIS G. MAKI,
Catheter-Associated Urinary AND LEONARD A. MERMEL
Tract Infections, and C. difficile • .. 375
NASIA SAFDARAND DENNIS G. MAKI 39 Infections of Implantable Cardiac
26 The Newborn Nursery and the and Vascular Devices • • • • • • • • • • • 592
RAYMOND Y. CHINN
Neonatal Intensive Care Unit ..... 393
TI:IOMAS J. SANDORAAND NALINI SINGH 40 Infections in Skeletal Prosthesis
2 7 The Perioperative Suite ......... 417 and Allografts ................ 608
ILKER UvKAY, LEONARDO PAGANI, AXEL
JOAN BLANCHARD AND SHARON
GAMULIN, AND DANIEL P. LEW
GIARRIZZO-WILSON
28 Ambulatory Care Settings ....... 428 41 The Importance of Infection Control

CANDACE FRIEDMAN AND KATHLEEN H. in Controlling Antimicrobial-
PETERSEN Resistant Organisms ..••..•...•• 618
CASSANDRA D. SALGADO AND BARRY M. FARR
29 Infections in Long-Term
Care Facilities . . . . . . . . . . . . . . . . 440 42 Healthcare-Associated Respiratory
NIMALIE D. STONE AND CHESLEY L. Vual Infections ............... 632
RICHARDS, JR WING HONG SETO AND JANICE LO
xiv Crmtents
43 Preventing Transmission of 46 Miscellaneous Procedure-Related

Bloodborne Pathogens in the Infections ...•........•....... 720
Healthcare Setting ......••..... 644 SHARON F. WELBEL AND ROBERT A. WEINSTEIN
DAVID K. HENDERSON 47 Public Reporting of
44 Healthcare-Associated Fungal Healthcare-Associated
Infecti.ons ....••.......••..... 667 Infection B.a.tes . . . . . . . . • . . . . . . . 7 44
RACHEL M. SMITH, SCOTI K. FRIDKIN, MICHAEL EDMOND AND MICHAEL P. STEVENS
AND BENJAMIN J. PARK
48 Patient Safety•........•....... 752
45 Healthcare-Associated Infections MOILINLING
in Transplant Recipients ..••..... 691
MINI KAMBOJ AND KENT SEPKOWITZ Index 757
Gener.t Considert~tions
of Hospital Infections
I
I Belinda Ostrowsky
Epidetniolo gy of Healthcare -Associated

Infections
INTRODUCTION AND IMPORTANCE/ All of these have added to the challenge of preventing and
EXPANDING R.OLE OF EPIDEMIOLOGY controlling HAis (6). Even with these challenges, recent data
IN THE HBAL1HCARE FACILITIES have documented that a much greater proportion of HAis are
preventable than previously estimated. Facilities in many areas
The term epidemiology is derived from the Greek epi (on or have found that using bundled interventions and prevention
upon), demos (people or population), and logos (word or rea- measures have been able to substantially reduce HAia mch as
son). Literally, it means "the study of things that happen to peo- centralli.ne-usociated bloodstream infections (CLA-BSia) (7,8).
In recent yean, the incidence and severity of Clo.ttridiua
ple•; historically, it hu involved the study of epidemia (1,2).
The Harwrd. School of Public Health definea epidemiology aa diJ!icik infection have increased dnunatically. Since 2000,
"the study of the frequency, distribution and determinants of widespread regional outbreaks aasociated with a previously un-
disease in humans. Epidemiologisb use many approaches, but common hypervirulentstrain (B1NAP1) of C. diffieil8have oc-
the ultimate aim of epidemiologic research is the prevention curred in Nonh America and Europe. Moat likely becauae of
or effective control of human diaeue." (3) For many yean, the increased toxin production u well as other virulence facton,
this epidemic strain hat caused more severe and refractory dis-
population for discussion in this text would have been solely/
predominately hospitalized patients, and the terma hospital- ease leading to complications, including ICU admission, col-
acquired or nosocomial infection would have been used. Since ectomies, and death (9). Despite improvements in many other
the spectrum of healthcare and the interaction of different HAis, C. diffidk continues to be a challenge to the healthcare
types of healthcare facilities (including hospital, lon~term epidemiology community. It iB in this spirit that many health-
care, rehabilitation, or ambulatory care facilities) have ex- care epidemiology professionals have expanded their focus to
panded in recent yean, a more appropriate term healthcare- also promote sensible antimicrobial prescribing through more
associated infections (HAl) will be used in this chapter (still formal antimicrobial stewardship programs (10,11).
used interchangeably with nosocomial as appropriate) (4) . The 2009 H1Nl Influenza outbreaks tested the healthcare
In hospitals alone, HAis account for an estimated 2 million system, and in many institutions healthcare epidemiology pro-
infections, 90,000 deatlu, and $4.5 billion in excess healthcare fessionals took a lead in response. The surges of patienta, test-
costs annually (4,5). There has been a shift in the patient popu- ing challenges, iBolation challenges, and healtbcare worker
lation that healthcare facilities care for, especially in hospitals, (HCW) exposures presented a real-time experience in prepara-
to more complicated patients, including those who are more se- tion and response to a pandemic and other challenges (12).
verely ill (multiple comorbidities and the need for intensive care Since the last edition of this text, legislation that obligates
unit [ICU] level of care) and an increasing number of patients hospitala to report specific HAl information has been paased in
who are aeverely immunocompromised. More invaaive devices many states (1~). Professional infection control and healthcare
and procedures are used in patients and for longer duratioru epidemiology organilations and healthcare epidemiologists
of time. In recent cost-conacious times, there have been staff- throughout the United States aasisted in framing legislation
ing shortages (decreasing staff to patient ratios). In addition, and helping hospitals how to comply with these legislations
over several decades, multi.drug-resistant organisms (MDROs) (13--15). Each state wu able to choose the HAI.s, specific
and emerging infectious diseases have developed or increased. meam.res and mechanisms of reporting. Most have adapted
1
2 Sectron I • General Considerations of Hospital Infectiuns
definitions, templates, and reporting via the Center for Disease A carrier (or colonized person) is an individual colonized
Control and Prevention (CDC) and National Healthcare Safety with a specific microorganism and from whom the organism
Network (NHSN) (13). can be recovered (i.e., cultured) but who shows no overt ex-
In addition, the Centers for Medicare and Medicaid Services pression of the presence of the microorganism at the time it is
(CMS) has created a reportable "hospital-acquired conditions" isolated (1,19); a carrier may have a history of previous disease
(HAC) which are quality measures to reduce payments to hospi- due to that organism, such as typhoid.
tals for hospital-acquired complications of care. The CMS rule Colonization is a natural process in the development of
that went into effect in October 2008 stipulated that hospitals natural flora. In the neonate, this process occurs within days
would no longer receive additional reimbursement for ten HAC, to weeks of delivery after which the neonate's normal flora is
three of which were HAis, including ICU CIA-BSis (16,17). similar to that seen in adult!! (19). Whether colonization occurs
All of these challenges illustrate the important and evolving long or immediately before infection, it can play a major role
role that those in infection control and healthcare epidemiol- in the development of HAis. In many instances, colonization is
ogy have in healthcare facilities. Although the circumstances a necessary precedent to infection. It is worth discussing colo-
may change, it is the working knowledge of the principals of ep- nization in more detail since there is heated discussion in the
idemiology and especially of the subtleties that apply to HAl/ infection control/healthcare epidemiology community about
adverse event!! that is essential and setll us apart from other screening for colonization with MDROs and the role and extent
HCWs. The healthcare epidemiologist will be the one person of isolation policies/practices. Those who advocate screening
who has the skills to analytically review occurrences and design and aggressive infection control practices/isolation contend
studies to evaluate risk factors and interventions (i.e., wielding that colonized patients represent a large predominately unrec-
the power of epidemiology to impact prevention and control ognized population who can serve as an unchecked reservoir
ofHAis). for infection and that once the proportion of colonization
It is with this in mind that the focus of this chapter is to patient!! reaches a threshold, this may lead to high burden
review the basic principles of epidemiology with special em- of infection with these MDROs for which antimicrobial treat-
phasis on the relationship of these to HAis. This first chapter ment!! are limited (20,21). Those who oppose these screening
in earlier editions of this text, Hospital In.futions (1) had been programs point to limited resources/cost, competing emerging
relatively stable and written by one of the fathers of infectious issues and the concerns about the strength of studies/ data to
diseases epidemiology and nosocomial infections. Although support these efforts and practices (22). A recent study found
much of the basic format of this chapter is unchanged, the when patients with methicillin-resistant Staphylococcus aureus
author hopes to update this classic chapter including new no- (MRSA) and other antibiotic-resistant bacteria are isolated in
menclature, advanced epidemiological methods and updated the hospital, these contact precautions may reduce the number
examples, and references for the basic epidemiological princi- of visits by HCWs and outside visitors, but also increased com-
pals related to HAis. pliance with hand hygiene upon exit of patient!!' rooms. Fewer
visits and increased hand hygiene are important in prevent-
ing the spread HAis, but clinicians and epidemiologist!! need
to consider both the positive and negative aspects of these in-
DEFINITIONS terventions, including the effect to patients' mental well-being
and perception of care, whether patients are isolated for any
INFECTION AND COLONIZATION
MDRO or other pathogen (23) .
Although terms such as infection, infectious disease, subclini-
cal infection, and colonization are used frequently, the subtle-
DISSEMINATION AND RELATED CONCEPTS
ties of these terms often are confusing. The term "infection"
implies the successful multiplication of a microbe on or within Dissemination, or shedding of microorganisms, refers to the
a host. The term "infectious disease" applies when signs and movement of organisms from a person carrying them into
symptoms result from infection and its associated damage or the immediate environment ( 1). This could be illustrated by
altered physiology (1,18). culture samples of air, or surfaces, or other inanimate object!!
If the infection provokes an immune response only, without onto which microorganisms from the carrier may have been
overt clinical disease, it is a "subclinical or inapparent infec- deposited. Shedding studies may be conducted in specially con-
tion." "Colonization" implies the presence of a microorganism structed chambers designed to quantitate dissemination. While
in or on a host with growth and multiplication of the microor- shedding studies occasionally have been useful to document
ganism but without any overt clinical expression or detected unusual dissemination (24), they have generally not been use-
immune reaction at the time it is isolated (1). "Subclinical or ful in identifying carriers whose dissemination has resulted in
inapparent infection" refers to a relation between the host and infection in other persons. In the hospital setting, dissemina-
microorganism in which the microorganism is present; there tion is most effectively identified by means of HAl surveillance
is no overt expression of the presence of the microorganism, in which the occurrence of infection among contact!! is noted.
but there is interaction between the host and microorganism In some hospitals, culture surveys of all or selected asymp-
that result!! in a detectable immune response, such as a sero- tomatic staff may be conducted in an attempt to identify car-
logic reaction, a skin test conversion, or a proliferative response riers of certain organisms. Even in outbreak settings, such
of white blood cells to antigens from infecting organisms (1). surveys lack practical relevance, can be costly, and can actu-
Therefore, special testll to detect immune responses may be ally be misleading. This practice identifies only those who are
needed to differentiate colonization from subclinical infection. culture-positive and does not in itself reliably separate colo-
In many instances, there is an absence of such data and the situ- nized persons into disseminators vs. nondisseminators. The
ation is considered colonization. practice could erroneously identify a HCW as the "source" and
Chapt~ 1 • Epidemiology ofHealthcare-Associated Infectiuns 3
have serious ramifications for his or her future. Instead, culture away from a single patient and to standardize definitions to
surveys should be directed by sound surveillance and epidemi- consistently identify trends in HAis. In beginning to identify a
ologic investigation to identify the potential source (25). Addi- cluster or outbreak, one of the early and consistent steps is to
tional laboratory studies to confirm the presence of a suspected try to find a definition as to what constitutes a ~case" of the HAl
HCW or patient disseminator may then be undertaken. in question. Use of uniform definitions is critical if data col-
In some instances, dissemination from a carrier has been lected are to be used for intra- or interlacility comparisons or to
reported to be influenced by the occurrence of an unrelated data from aggregated systems (e.g., NHSN) (27-29) .
disease such as a second infection (26). One report, for exam- The NHSN system defines an HAl as a localized or systemic
ple, suggested that infants carrying staphylococci in their nares condition that results from adverse reaction to the presence of
disseminate staphylococci only after the onset of a viral respira- an infectious agent(s) or its toxin(s), which was not present or
tory infection. Such infants are called cloud babies. In another incubating at the time of admission to the hospital/facility. For
instance, a physician disseminated staphylococci from his skin bacterial HAis, this means that the infection usually becomes
because of a reactivation of chronic dermatitis. Desquamation evident ~48 hours (i.e., the typical incubation period) after
of his skin led to the transmission of staphylococci (probably admission. Since incubation periods vary with type of patho-
by skin squames) to patients with whom he had contact. Dis- gen and patient's underlying disease, each infection must be
semination of tetracycline-resistant S. aurms from individuals assessed individually.
carrying this organism who were treated with tetracycline has Two special situations that are usually HAis are infection
been reported. The risk of dissemination is generally greater in a neonate that results from passage through the birth canal
from individuals with disease caused by that organism than and infection that is acquired in the hospital but does not be-
from individuals with subclinical infection or colonization with come evident until after hospital discharge. The majority of
the organism (26). HAis becomes clinically apparent while the patients are still in
"Contamination" refers to microorganisms that are tran- the facility; however, different studies have given widely vary-
siently present on body surface (e.g., hands) without tissue ining estimates that between 12% and 84% of surgical site infec-
vasion or physiologic reaction. Contamination also refers to the tions (SSis) are detected after discharge from the hospital (31).
presence of microorganisms on or in an inanimate object. Since the length of postoperative stay continues to decrease,
many SS!s may not be detected for several weeks after discharge
and may not require readmission to the hospital where the op-
HEALTHCARE-ASSOCIATED/
eration occurred. In these instances, the patient became colo-
NOSOCOMIAL INFECTIONS
nized/infected while in the hospital, but the incubation period
In early editions of this text, the terms hospital-acquired or nos- was longer than the patient's hospital stay. This sequence also
ocomial infections would have been used, with the definition is seen in some infections of newborns and in most breast ab-
for hospital-acquired/nosocomial infections as infections that scesses of new mothers (since the length of postpartum stay
develop within a hospital or are produced by microorganisms also is brief) .
acquired during hospitalization. As discussed previously, the Two special situations that usually are not considered HAis
delivery and scope of healthcare and healthcare epidemiology are the complication or extension ofinfection(s) already pres-
is expanding. The CDC defines HAis as infections that patients ent on admission unless a change in pathogen or symptoms
acquire during the course of receiving treatment for other con- strongly suggests the acquisition of new infection and the infec-
ditions or that HCWs acquire while performing their duties tion in an infant that is known or proven to have been acquired
within a healthcare setting (4). In this spirit, even the branch of transplacentally (e.g., toxoplasmosis, syphilis) and becomes evi-
CDC that was formally the Hospital Infections Program broad- dent :::s48 hours after birth. Infections incubating at the time of
ened its name to the Division of Healthcare Quality Promotion the patient's admission to the facility are not considered HAis;
to reflect this sentiment in the last decade ( 4). they are community-acquired, unless they result from a previ-
The CDC's National Nosocomial Infections Surveillance ous healthcare exposure. However, community-acquired infec-
(NNIS) system was developed in the early 1970s to moni- tions can serve as a ready source of infection for other patients
tor the incidence of HAis and their associated risk factors or HCWs and thus must be considered in the total scope of
and pathogens (27,28). The NHSN was established in 2005 hospital-related infections.
to integrate NNIS with two other CDC surveillance systems, Two important principles of HAis relate to infections that
the Dialysis Surveillance Network, and the National Surveil- are preventable vs. those that are nonpreventable. The term
lance System for Healthcare Workers. NHSN data collection, preventable HAl implies that some event related to the infec-
reporting, and analysis are organized into three components: tion could have been altered and that such alteration would
Patient Safety, Healthcare Personnel Safety, and Biovigilance, have prevented the infection from occurring. A HCW who does
and use standardized methods and definitions in accordance not perform hygiene on his or her hands between contacts with
with specific module protocols. Decades ago NNIS had only the urinary collection equipment of two patients, for example,
about 300 facilities, NHSN now has > 11,000 participating may transmit pathogens from the first patient to the second,
facilities (29,30). which may result in a urinary tract infection (UTI). Hand hy-
Although the NHSN system is for HAl surveillance purposes giene might have prevented this infection from occurring.
and NHSN definitions are not necessarily to be held as a gold The identification of such an event in retrospect, however, is
standard for clinical/therapeutic decisions, some important difficult; it is necessary to distinguish this situation from cir-
points about HAis can be illustrated by NHSN (and former cumstances in which both patients developed infections from
NNIS) experience and definitions (28,29). The first is that a their own endogenous flora (e.g., from Escherichia colJ). It
major factor that specifically separates epidemiology and HAis often is impossible to identify the precise mode of acquisition
from other infectious diseases is that there is a quest to step of individual HAis. More than one mode of transmission may
contribute to the development of the same infection, and not detected, one must evaluate whether this represents a prob-
all modes may be preventable. lem, such as an outbreak. As discussed previously, exploring
A nonpreventable infection is one that will occur despite cases and arriving at a case definition is essential to identify
all possible precautions, for example, infection in an immuno- as many cases as possible. Comparing the rate of the event
suppressed patient due to endogenous flora. In the past it had during the cluster to a period before the cluster can establish
been estimated that approximately 30% of all reported HAis whether an outbreak is occurring. A few definitions are helpful
are preventable (1); however, more recent studies document- to characterize disease frequency, including sporadic, endemic
ing the near elimination of CLA-BSis in ICU patients suggest (hyperendemic), outbreak, and epidemic.
that an even higher percentage of HAis may be preventable "Sporadic" means that episodes occur occasionally and
(8,13). Many facilities and regions are teaming up and initiating irregularly without any specific pattern. "Endemic" means that
infection prevention bundles that focus on some combination the disease occurs with ongoing frequency in a specific geo-
of hand hygiene, maximal barrier precautions, chlorhexidine graphic area in a finite population and over a defined time pe-
with alcohol skin antisepsis, optimal site selection, and proper riod. "Hyperendemic" refers to what appears to be a gradual
maintenance/daily review/device removal whenever possible. increase in the occurrence of a disease in a defined area beyond
Outbreaks, especially those caused by a common vehicle, po- the expected number; however, it may not be certain whether
tentially are preventable; however, outbreaks/clusters account the disease will occur at epidemic proportions. An "epidemic"
for only a small number of HAis (5% to 10% of all HAis) is a definite increase in the incidence of a disease above its ex-
(32,33). Prompt investigation and the institution of rational pected endemic or background rate. "Outbreak" often is used
control measures should reduce the extent of the epidemic. interchangeably with epidemic; however, many use outbreak to
Endemic infections account for the m,Yority of HAis, and the mean an increased rate of occurrence but not at levels as seri-
consistent application of recognized, effective control and pre- ous as an epidemic (1).
vention measures for endemic infections probably is the single An occasional gas gangrene infection among postoperative
most important factor in reducing the overall level of HAis. patients is an example of a sporadic infection. An endemic HAl
is represented by the regular occurrence of infections either
in a particular site or at different sites that are due to the same
SOURCE: ENDOGENOUS (AUTOGENOUS)
organism, occur at a nearly constant rate, and are generally
OR EXOGENOUS
considered by the hospital staff to be within expected and ac-
Two terms, endogenous (autogenous) and exogenous, are ceptable limits. SSis due to a single organism that follow opera-
helpful in understanding HAis. Endogenous infections are tions classified as "contaminated surgery," for example, could
caused by the patient's own flora; exogenous infections result represent the endemic level of SSis. The recent high levels of
from transmission of organisms from a source other than the C. difftcile infections with the B1NP1 strain in facilities have
patient. For endogenous infections, the patient either was ad- been referred to as the hyperendemic strain (37). In hospitals
mitted to the facility colonized with these microorganisms or or healthcare facilities, most outbreaks are small clusters. Out-
became colonized at some point during his or her stay at the breaks will be discussed in detail later in this chapter and text.
hospital/facility after admission. It may not always be possible Plotting a histogram of the distribution of "cases" by time in
to determine whether a particular organism isolated from a an "epidemic curve" may aid in confirming the existence of an
patient with an HAl caused by that organism is exogenous or outbreak (vs. sporadic or endemic infections) and developing
endogenous, and the term autogenous should be used in this hypotheses about the mode of transmission (25,38,39). This
situation. Autogenous infection indicates that the infection was can be simply executed on graph paper or by using a variety
derived from the flora of the patient, whether or not the infect- of software packages, such as Microsoft Excel or PowerPoint.
ing organism became part of the patient's flora subsequent to Details on the construction of an epidemic curve are described
admission ( 1). Information about current infectious diseases/ in the descriptive epidemiology section (also Table 1.2 and
microorganism problems in the community or in hospital con- Figure 1.1) .
tacts may be useful in differentiating the two sources. For ex-
ample, in the past, if a patient had an infection with MRSA, it
MEASURES OF DISEASE FREQUENCY-INCIDENCE
probably would have been assumed that this infection was r~
AND PREVALENCE AND RELATED MEASURES
lated to acquisition in the healthcare facility. In the last several
years, however, episodes of community-acquired MRSA (34,35) To identify that a problem with HAis exists, it is important to
have increased and it may be helpful to know the local occur- be able to quantify the frequency of disease/event occurrence
rence of these community-acquired isolates in addition to the (counting cases). The two most commonly used measures of
patient's recent healthcar~related and antimicrobial expo- disease frequency are prevalence and incidence. Some unique
sures. Microbiologic characteristics of the organism such as issues that may occur with HAis related to these measures of
antibiograms, biochemical testing, susceptibility pattems, and frequency will be reviewed, and some additional measures of
molecular typing (e.g., pulsed-field gel electrophoresis) may incidence (incidence density and cumulative incidence) and
provide additional evidence to support healthcar~sociated prevalence are discussed. Each of these measures has uses in
vs. community origin of these strains/infections. healthcare epidemiology and advantages and disadvantages
(Table 1.1) .
Incidence is the number of new cases in a specific popu-
SPECTRUM OF OCCURRENCE OF CASES
lation in a defined time period (see Chapter 6) (40). Preva-
Often possible clusters of HAis are detected through clini- lence is a measure of status rather than newly occurring disease
cal microbiology, or infection control surveillance data, or by and of people who have the disease at a specific time (see
an astute laboratorian or clinician (25,36). Once a cluster is Chapter 7) ( 40) .
Epidemic CUrve- Conllnuou• Common Source
5r----------------------r.~~~~~
IRemoval or source I
Jl
s 4+---------------------""~""~~----------~
J
i 3
'li 2 + - - - - - - - - - - - - 1
l Removal or 90Urc& r
., I;i1+----------------------i
I
I 0+---~--r---r---r-~~~~~~~--~--~--~
~.1' $~ ; / ~.!' ~" / , / .;-~" / /

A lima nma B
-
II lr
c nma
Figure 1.1. Examples of epidemic curves. A: Point-source: This epidemic curve represents a point-source exposure. The patients are all
exposed to the same source and the curve rapidly rises to a peak and then resolves when the source is removed. B: Continuous common
source: This epidemic curve represents a continuous common-source outbreak. Exposure to the source is prolonged and thus the curve is less
peaked than the point-source curve. Here the downward slope of the curve quickly decreases with removal of the exposure. C: Propagated/
progressive source: This epidemic curve represents a propagated/progressive source. Each case is a source of infection for the subsequent
case. There are usually several peaks caused by person-to-person transmission.
Incidence can be described in several ways. Incidence density from the effect of daily risk. Examples where this is particularly
(also known as the incidence rate) is the number of new events useful in healthcare epidemiology are in comparisons of those
(disease onset) in a specified amount of person-time (hospital with short vs. long hospital stays and for peripheral intravenous
or healthcare facility-days) in a population at risk (40,41). Inci- lines vs. central venous catheters (41,42). In each of these in-
dence density usually is restricted to the first event (first HAl, stances, the time at risk is substantially longer for the second
i.e., BSI), since second events are not statistically independent group vs. the first.
events in the same individual (i.e., once the patient has had A question that arises with the incidence density is what to
one HAl, he or she is more likely to have a second one). The do with a second or additional event (e.g., second HAl; i.e.,
population at risk includes all patients who have not yet had second healthcare-a.ssociated BSI) since multiple studies has
the first event. Once a patient acquires the first HAl, he or she shown that the subsequent events are not independent. The
would not still be a part of the population at risk and would be first guidance is that for quantitative analysis of HAis, it would
withdrawn. Patients who never have an HAl would contribute be overly simplistic and misleading to sum these nonindepen-
all their hospital-/facility-days to the pool of days at risk for a dent events and put them over the denominator (41). The first
first event, but patients who became infected would contribute and each subsequent event actually would be a risk factor for
only those hospital-days before the onset of the first infection. the next infection, which is why it is best to restrict analysis to
Since the first event is just a number, incidence density has the first event.
the units of (1/time). In practical use in healthcare epidemiol- There are more complex methods to include first and
ogy, HAl rates usually are expressed as number of first events multiple/subsequent events in a study using different stra-
in 1,000 hospital-/facility-days (usually gives a single or double- tum (43). For example, one approach is to define the popu-
digit number of events per 1,000 hospital-days) (41,42). The lation at risk differently for each occurrence (40): The
advantage of using incidence density is that it allows a way to population at risk for the first event would consist of individuals
correct for time and separate out the duration of exposure who have not experienced the disease before; the population
6
Measure of
f.
Sectron I • General Considerations of Hospital Infectiuns
• . t§ :f ri j
Additional
Measurements of Occurrence (Terms for Incidence and Prevalence)
Uses in Healthcare
EpidemiologyI
Association Names Def'mition/Formula Units Advantages Disadvantages
Incidence Number of new events Cases/time, rate

or disease during
a time
Incidence Incidence rate Number of first events 1/time First events/ 1,000 Not clear what to do
density Observed time at facility-days with second and
risk for a first event Allows for correction for subsequent events
time and separates
out duration of
exposure
Cumulative Attack rate Sum of all first events No units, Helpful when point- Does not distinguish
incidence Sum of all person- expressed as% source considered fint from other
time at risk for first events, does not
events tale into account
ferent risk with
time
Prevalence Point prevalence, Proportion of Proportion, % For point-prevalence Influenced by
prevalence individuals surveys such as Incidence and
proportion, with disease or cross-sectional studies duration
prevalence rate condition at one
point in time
at risk for the second event or first recurrence would be limited be 10 infections from one very complicated patient, 10 from
to those who have experienced the event (infection) once and 10 different healthy patients, or some description between these
once only, and so on. An individual should contribute time to extremes; the extremes illustrate how this summary term could
the denominator of the incidence rate for first events only until be quite different in its clinical and epidemiological relevance
the time that the disease first occurs. At that point, the individ- and in what intervention methods might be necessary). Another
ual should cease contributing time to the denominator of that disadvantage is that since one patient could be counted mul-
rate and should begin contributing time to the denominator of tiple times, this would not take into account lack of statistical
the rate measuring the second occurrence. If and when there independence, thus making comparisons difficult ( 41) .
is a second event, the individual should stop contributing time Unlike incidence measures, which focus on events, preva-
to the rate measuring the second occurrence and begin con- lence focuses on disease status. "Prevalence" is defined as the
tributing to the denominator of the rate measuring the third proportion of a population that has disease at a specific point in
occurrence, and so forth. time (42). Several terms, such as point prevalence, prevalence
Cumulative incidence is the proportion ofall those at risk who proportion, and prevalence rate, often are used interchange-
ultimately suffer a first event (40-42). In traditional infectious ably. Prevalence depends on the incidence and the duration
disease epidemiology, this has been termed the attack rate (41). of the disease. As either of these increases, the prevalence in-
This is actually not a rate but a proportion. Cumulative incidence creases. The main useful measure for healthcare epidemiology
is derived from the incidence density and in simple terms could would be point prevalence for studies such as a croswectional
be thought of as the sum of all incidence densities for first events study (30) (i.e., a point-prevalence survey on a day using cul-
over all of the person-time at risk for the first event. This is a sim- tures to detect colonization/infections with an MDRO, such as
ple proportion and thus has no units. For overall HAis, the time vancomycin-resistant Enterococcus [VRE], Carbapenem-resistant
implied is the course of hospitalization (duration in the facility) Enterobacteriaceae [CRE], or MRSA). This could give an idea
nntil the first event or discharge without first event. There are a of the burden of a problem at a particular point in time to assist
few limitations to the cumulative incidence. First, there should in defining that a problem exists, guide decisions to pursue ad-
be follow-up for all at risk to determine whether they have the ditional studies, and allow for allocation of resources. Of note,
first event. However, patients do not all have the same length of populations are dynamic and since individuals are entering
hospital stay or remain at risk for the same amount of time. Also, and leaving the population, the prevalence can vary based on
HAis are time related, and comparing HAl rates among patients when it is measured.
with differing lengths of stay can be misleading. The cumula-
tive incidence could be of particular use with an HAl considered
to be from a point-source, such as a contaminated fluid or SSI EPIDEMIOWGIC METHODS
(operation as the point-source) (41,42).
In the past, HAis were reported as a cumulative incidence of Generally, three techniques are used in epidemiologic studies:
number of infections per 100 discharges. One disadvantage of descriptive, analytic, and experimental; all may be used in in-
this aggregation and presentation is that there was no distinc- vestigating HAis. Descriptive epidemiology is the foundation
tion between separate first infection from multiple infections in for evaluation of HAls and is used in both surveillance and
the same patients (thus, 10 infections per 100 discharges could most investigations of potential problems/ outbreaks. Once the
initial problem has been defined by descriptive epidemiology, There also may be agent and host factors that influence the
additional studies using analytic and/or experimental meth- seasonal trends. Another example is that healthcare-associated
ods can be conducted to develop more information about the Acinetobaaer spp. infections have a seasonal trend, increasing in
problem, confirm initial impressions, prove/disprove hypoth- the summer and fall ( 45) . The fourth type of time variation is
eses (including identifying risk factors/potential associations/ the acute or epidemic/ outbreak occurrence of a disease with
sources or causes), and evaluate the effectiveness of control its characteristic upsurge in incidence.
measures and/or prevention measures. As described previously, a graphic representation of the
The presentation of descriptive epidemiology can include "cases" can assist in confirming the existence of an outbreak,
case report/case series. A case report is the clinical description its source, its transmission, the point of an outbreak you are
of a single patient. A case series is a report of more than one in, and evaluating interventions. The overall shape of the epi-
patient. These types of studies/publications are easy to prepare demic curve depends on the interaction of many factors: char-
and can serve as examples to other healthcare epidemiologists. acteristics of the agent (i.e., pathogenicity, concentration, and
These studies also can serve as a resource to generate hypoth- incubation period), the method of transmission, host factors
eses and ideas for additional studies. The disadvantage of this (i.e., susceptibility and concentration of susceptible individu-
type of study is that patient numbers are small, and the findings als), and environmental factors (i.e., temperature, humidity,
may not be generalizable to other populations. In addition, no movement of air, and general housekeeping) . A step-by-step
comparison to other groups has been made. guide to creating an epidemic curve is included in Table 1.2
The analytic study section will discuss case-control and co- (25,38,39).
hort studies, which are the comparative studies frequently used The following are a few points to keep in mind while at-
in healthcare epidemiology, especially to explore outbreaks tempting to create/interpret an epidemic curve. The time scale
and healthcare epidemiology problems to identify risk fac- will vary according to the incubation or latency period, ranging
tors and potential associations. Additional analytic-type stud- from minutes, as in an outbreak of disease following exposure
ies that can be used for healthcare epidemiologic studies are to a toxin or a chemical, to months, as in an epidemic of hepa-
ecologic or cross-sectional studies. Experimental methods of titis B. The time scale (abcissa, hortizontal scale, x axis) should
studies include randomized control trials (RCTs; rarely used in be selected with three facts in mind: (a) The unit time interval
healthcare epidemiology) and quasi-experimental studies (to should be less than the average incubation period (commonly
evaluate an intervention without randomization). one-fourth to one-third of the probable incubation period) so
that the true nature of the epidemic curve will be apparent
(i.e., all the cases will not be bunched together); (b) the scale
DESCRIPTIVE EPIDEMIOWGY
should be extended far enough in time to allow all cases to be
Descriptive epidemiologic studies evaluate the occurrence of plotted; and (c) any cases that occurred before the epidemic
disease in terms of time, place, and person (1,38); each "case" should be plotted to give a basis for comparison with the epi-
of a disease is first characterized by describing these three attri- demic/outbreak experience (1,38,39)
butes. When data from the individual cases are combined and If the epidemic curve starts with the index case (i.e., the first
analyzed, the parameters of the outbreak or disease problem case in the outbreak), the time between the index case and
should be characterized. Issues that arise regarding time, place, onset of the next case reflects the incubation period if trans-
and person in general descriptive epidemiology and specifics to mission was from the index case directly to the next case--that
healthcare epidemiology are discussed next. is, from person-to-person. The upslope in the curve is deter-
mined by the incubation period, the number and concentra-
tion of exposed susceptible persons, the number of infected
Time
sources, and the ease of transmission. The height of the peak of
There are four time trends to consider: secular, periodic, sea- the curve is influenced by the total number of exposed suscep-
sonal, and acute (1). Secular trends are long-term trends in tible individuals and the time interval over which they occur.
the occurrence of a disease--that is, variations that occur over The downslope of the curve is usually more gradual than the
a period of years. An example in HAis would be the gradual upslope; its gradual change reflects cases with longer incuba-
increase in fungal BSis, including those that are nonalbicans tion periods and the decreasing number of susceptible indi-
Candida and azol resistant (44). Periodic trends are temporal viduals. The initiation of control measures may contribute to
interruptions of the secular trend and usually reflect changes the gradual decline or to a sudden decrease in the appearance
in the overall susceptibility to the disease in the population. of new cases (1).
The upsurge in Influenza A activity every 2 to 3 years, for in- When interpreting an epidemic curve, it is useful to look at
stance, reflects the periodic trend of this disease and generally the overall shape of the curve to assist in determining how the
is the result of antigenic drift of the Influenza A virus. Seasonal outbreak spread throughout the population and, potentially, if
trends are the annual variations in disease incidence related the disease is unknown, the initial diagnosis of the disease. For
in part to seasons. In general, the occurrence of a particular simplicity, there are three main patterns the epidemic curve
communicable disease increases when the circumstances that can take (Figure 1.1) (39). In a point-source epidemic, persons
influence its transmission are favorable. The seasonal pattern are exposed to the same exposure over a limited, defined pe-
of both community-acquired and healthcare-associated respira- riod of time, usually within one incubation period. The shape
tory disease, for example, is of high incidence in the fall and of this curve commonly rises rapidly and contains a definite
winter months when transmission is enhanced, because people peak at the top followed by a gradual decline. Sometimes cases
are together in rooms with closed windows and are breath- also may appear as a wave that follows a point-source by one
ing unfiltered, recirculating air. Thus, they have more close incubation period or time interval. This is called a point-source
contact with one another and with droplets/droplet nuclei. with secondary transmission.
Examples/Comments Specific for

Steps Details Healthcare-Associated Infections
Step 1: Identify the date Identify the date of onset of illness for each case. Likely date of diagnosis used such as in
of onset • For a disease with a very short incubation period, an outbreak of healthcare-associated
identify the time of onset to produce an epidemic bloodstream infections, the date of the
curve with enough detail to discern patterns in the culture collection would be used
outbreak.
• If the date of onset is unknown, use one of the
following dates: date of report, date of death, or
date of diagnosis.
Step 2": Set the time Set the time interval for the x axis.
interval • The time intervals are preferably based on the
incubation period of the disease, if known. The
time interval is critical because intervals that are too
short (e.g., hours, for diseases with long incubation
periods) or too long may obscure the underlying
pattern of the outbreak.
• As a rule of thumb, select a unit of about l/3-l/4
of the incubation period for the time interval on
the xaxis.
Step !!•: Create x axis lead lllustrate the time period before and after the
and end periods concentration of cases to possibly reveal source cases,
secondary transmission, and other outliers of interest.
The following steps can be used when establishing lead
and end periods:
• From the line listing, find the tint and last dates
of onset.
• To create the lead period, extend the scale back two
incubation periods from the first date of onset.
• To create the end period, extend the scale forward two
incubation periods after the last case.
Step 4: Draw tick marks • Draw the tick marks on the x axil! according to the
and label time intervals interval chosen.
• Begin putting labels, such as the interval or date
mark.en (i.e., dates of onset) on the x axis.
Step 5: Assign area equal IT drawn on paper, assign the area that will be equal to
to one case one case on the x axis, which ill usually square or
rectangular.
Step 6: Plot the cases on Now plot the cases on the graph.
the graph There should be no gaps between adjacent time intervals
because this is a histogram, not a bar graph.
Step 7: Mark the critical Labels are useful tools to identify or highlight events and Important events may include when
events on the graph cases of importance. a control of intervention was put into
and add graph labels In addition, title, legend, and axis labels provide the place
reader visual aids to assist in interpreting the curve.
Step 8: Interpreting an Through review of the different patterns illustrated in an
epidemic curve epidemic curve, it ill possible to hypothesize:
• How an epidemic spread throughout a population.
• At what point an epidemic currently ill.
• The diagnosili of the disease by establilihing the
potential incubation period.
When analyzing an epidemic curve, consider the following
factors to assilit in interpreting an outbreak:
• The overall pattern of the epidemic.
• The time period when the persons were exposed.
• Whether there any outliers.
Typically, epidemic curves fall into three different
classifications:
• Point-11ource
• Continuous common source
• Propagated (progressive source)
Steps in Constructing an Epidemic Curve (C.nrinwetl)

Examples/Comments Specif'lc for
Steps Details Healthcare-Associated Infections
Step 9: Viewing an Stratification is a mainstay of epidemiologic analysis This may include cases that fit a possible/
epidemic curve by because it provides an investigator a different probable V5. confirmed case defmition
characteristics perspective on key variables.
In the process of viewing an epidemic curve, it can
be helpful to divide a population into several
subgroups to:
• Illustrate a pattexn contained in potentially
unmeasured characteristic.. such as geography or
job classification.
• Provide a uniform baseline for comparison.
"When the disease and incubation periods are unknown, it is often necessary to draw an epidemic curve. Step 2 (setting the time interval)
and step 3 (creating the lead and end periods on the xaxis) will be slightly different in that case. Lead and end periods. When the incubation
period is unknown, use 1 to 2 weeks for the lead and end periods. Time intervals. If the disease is unknown, a good way to set the time interval
is to create at least three epidemic curves, each with a different time interval.
Adapted from CDC's ~EXCITE•: Epidemiology in the classroom, how to investigate an outbreak, steps of an outbreak investigation.
http:/ /www.cdc.govI excite/classroom/outhreak/steps.html.
In a continuous conunon-source epidemic, exposure to the was contaminated with SalmoneUa spp. The barium had been
source is prolonged over an extended period of time and may contaminated in the radiology department, and thus preventive
occur over > 1 incubation period. The downward slope of the measures directed there terminated the outbreak (1).
curve may be very sharp if the common source is removed or Because transfer of patients between hospital wards or units
gradual if the outbreak is allowed to exhaust itself (i.e., affect is common, it may be difficult to attribute an outbreak to a
all susceptible persons). particular geographic area. Infection rates can be calculated
A propagated (progressive source) epidemic occurs when for other areas of the hospital and compared with the area(s)
a case of disease serves as a source of infection for subsequent with the cluster to aid in identifying the location of the out-
cases, and those subsequent cases, in turn, serve as sources for break (25). In addition, a review of the geographic location of
later cases. The shape of the curve usually contains a series of cases using a spot map of the hospital or ICU may suggest the
successively larger peaks, reflective of the increasing number location or pattern of transmission (25,38).
of cases caused by person-to-person contact until the pool of
susceptibles is exhausted or control measures are implemented.
Person
In reality, mixed modes of transmission may occur, and the
epidemic curve could include both point-source and propa- The third major component of descriptive epidemiology is per-
gated cases. son. Careful evaluation of host factors related to the individual
person includes consideration of age, gender, race, immuniza-
tion status, immunocompetence, and presence of underlying
PIMe
disease that may influence susceptibility (acute or chronic),
Although outbreaks of HAl occur infrequently in some settings, therapeutic or diagnostic procedures, medications, and nutri-
such as ICUs, they can account for a substantial percentage of tional status. In essence, any host factor that can influence the
the HAis. In an investigation of HAis, three different places development of disease must be considered and described.
may be involved. The first is where the patient is when the dis- Those factors that increase the patient's chance of developing
ease is diagnosed, and the second is where contact occurred disease are known as risk factors.
between the patient and the agent. If a vehicle of infection is Age also can be an important clue to the source of an out-
involved, the third place is where the vehicle became contami- break of disease. If, in an apparent common-source outbreak,
nated. To implement the most appropriate control and preven- for example, all ages are involved, the source of the outbreak
tive measures, it is necessary to distinguish between these three must have been exposed patients scattered through at least sev-
geographic areas; certain actions may control additional spread eral wards. On the other hand, if all the patients involved in
from a specific focus but may not prevent new cases from occur- an epidemic are women of child-bearing age, in attempting to
ring if the source continues to contaminate/infect new vehicles. identify the place of the exposure, the investigation can be nar-
An example will help to emphasize the importance of care- rowed to the obstetric or, possibly, the gynecology ward.
fully describing the place or places involved in disease outbreaks. Consideration of therapeutic procedures may be of similar
In an outbreak of healthcare-associated salmonellosis, the pa- importance. If all patients who developed BSis due to the same
tients were located on various wards throughout the hospital at organism have received intravenous fluid therapy, a common
the time they developed disease. Individual control measures source of intravenous fluids could be suspected as the cause of
were directed at each patient on the various wards; however, the the outbreak.
place of infection was the radiology department, where barium In addition, knowledge of intrinsic host risk factors is use-
used for gastrointestinal tract roentgenographic examinations ful because separate risk-specific rates can be calculated, which
l0 S«tion I • General Considerations ofHospital Infections
allows for the comparison of HAis among patient!! with similar after a problem is recognized and often after the peak of the
risk. Severity of illness is a strong confounding variable in out- epidemic has passed. It also allows evaluation of many poten-
breaks in healthcare settings (46). The Acute Physiology and tial associated exposures and for outbreaks/problems that may
Chronic Health Evaluation (APACHE II) and Diagnostic R~ have persisted for lengthy periods of time.
lated Groups (DRGs) are well-known indices used to assess and One of the main controversies with this type of study is the ap-
control the severity of illness (47,48). These indices are used propriate choice of control-patient!! (50). In one investigation of
to predict the risk of death among ICU patient!! and for staff transmission ofVRE in 32 hospitals and long-term care facilities,
resource utilization. In pediatrics, severity of illness scores in- we wanted to explore the characteristics and exposures of those
cluding the modified abbreviated injury severity score (MISS) patient!! with VRE-colonization. The facilities varied in size and
and Score for Neonatal Acute Physiology (SNAP) have been provided a range of intensity of medical care. VRE-colonized
used to assess neonatal/pediatric populations (48,49). These patient!! were identified from several different facilities. Thus,
severity of illness scores have been shown to predict mortality for each cas~patient, we chose a control-patient from the same
and may be useful for controlling for severity of illness when facility, and the analysis was matched for the facility (51).
assessing risk factors for developing some HAis. In ICU outbreaks, since the patient!! are very different (e.g.,
more severely ill, have more devices, experience more proc~
dures, take more medications) from non-ICU patient!!, other
ANALYTIC EPIDEMIOLOGY
ICU patient!! may be the most appropriate controls (36,52,53).
Mter the descriptive epidemiologic review has been performed In some studies, controls may be matched to cases on certain
and hypotheses have been generated, one may need addi- factor(s), such as age, gender, or other factors known to pr~
tional studies to identify the source of a problem/ outbreak. dispose to the outcome. In general, random selection of con-
Settings in which additional efforts should be considered are trols is preferred (42,43). Two concerns about matching are
when resources are available, when the problem/outbreak is that special statistics are needed for matched analyses and that
associated with high mortality or severe disease, when new or when matching is performed, no comparisons can be made
unusual pathogens or methods of transmission are identified, between cas~ and control-patient!! on the factors on which
or when the problem/outbreak continues despite implement- matching was done (54).
ing control measures. Additionally, the principles involved in Review of the cas~patient!!' medical records should identify
these methods have application to surveillance; surveillance several potential sources/risk factors. In the case-<:ontrol study,
data commonly are analyzed by the descriptive method, and a comparison of the presence or absence of these factors in the
such analysis may suggest the need for analytic studies to iden- case-patient!! and controls is performed to see whether any of
tify certain features of a disease. The choice of analytical/ these exposures is more likely to be present in cases, suggesting
comparative study depends on resources, time, and size of the that this may be associated with the outbreak. Use of standard-
problem/ outbreak. ized data collection forms facilitates the systematic review of
A few basic epidemiologic principles should be reviewed with exposures.
an emphasis on how these concept!! vary or apply to HAis. These A pitfall in some healthcare outbreaks is that many expo-
are study designs/methods (emphasizing cas~ontrol or cohort sures can be collected. Only biologically plausible exposures
studies but also including ecologic and cross-sectional stud- should be evaluated. A rule of thumb is that if an exposure
ies), measures of association, strength of association, and bias/ is not present in at least 30% to 40% of the cases, even if it is
confounding. Although this chapter is not meant to be a primer more common in cases than controls, it will not account for
on general epidemiology, some key point!! will be reviewed. enough cases to be the source of the outbreak (attributable
risk-the amount or proportion of disease incidence/risk that
can be attributed to a specific exposure) (52,55,56).
Stutly Designs/Methods
Two important statistical principles should be reviewed at
Two frequently used analytic methods include cas~ontrol or this point relating to errors. Type I error (a error) relates to
cohort studies. In both instances, associations that may identify concluding that a statistical relationship exist!! when it does
causes and effect!! are sought The cas~ontrol method start!! not. This may occur in a case-<:ontrol study when many factors/
with the effect (cases) and searches for host and exposure exposures are evaluated. With multiple test!!, a relationship may
factors, and the cohort method start!! with potential causative be found to be statistically significant but represent!! a false pos-
factors and evaluates the effect The cas~ontrol and cohort itive. Often these false positive relationships have only border-
methods also have been referred to as retrospective or prospec- line significance (pvalues near the statistical threshold of0.05)
tive studies, respectively; both methods, however, can be either with weaker magnitudes of association and lack of biological
retrospective or prospective. These terms indicate the temporal plausibility. The take-home message is not to examine factors
frame of reference for the collection of specific data: in a retro- that are not clinically relevant or biologically plausible, since a
spective study, data are collected after the event has occurred; relationship may be identified purely by performing multiple
in a prospective study, the data are collected as the event occurs. test!! looking at multiple variables (54,57). For other studies not
related to outbreaks, it is best to make an a priori plan in which
Case-Control Study. In a cas~ontrol study, cas~patient!! variables are to be collected and analyzed to prevent this prob-
are compared with (a set ratio usually of 1:2 or 1:3) control- lem. If multiple comparisons are going to be carried out, there
patient!! who do not have the adverse outcome or infection but are ways to "correct" for this including, to increase the thresh-
have had the opportunity for the exposure. The cas~control old that would be considered statically significant (e.g., raising
approach has the advantages of being inexpensive, relatively pfrom <0.05 to .1) (58) .
quick, and easily reproducible. It is used most often in acute Type II error (/3 error) relates to concluding that a factor is
disease investigations, since the epidemiologist usually arrives not significantly associated with becoming a case when it in fact
Chaptt!r 1 • Epidemiology of Healthcare-Associated Infections l l
is related. This error is related to the concept of power. Power

OUTCOME
is 1-/3 error. These concepts are greatly affected by the sample
size in a study. In a planned research protocol, set numbers of Present Absent
cases and controls can be enlisted. In an outbreak situation, the (cases) (controls)
number of cases is obviously limited. The main points are that
HAl outbreaks/studies may be of a smaller scale and that cer- Present
a: (exposed) A B
tain associations may not reach statistical significance; however, 0
trends may still have clinical significance (59).
Another area of controversy is how long variables of in- ~ Absent
(unexposed) c D
terest should be collected in case and control patients. This
needs to be clear for those reviewing charts/medical records.
Relative Rjsk
In one ICU outbreak we investigated, exposure data were col- Risk of disease among exposed = A I (A+B)
lected for the case-patients from SICU admission until the day Risk of disease among unexposed = C/ (C+D)
of diagnosis of their Serratia m.arcescens BSI and for controls
from the date of SICU admission to the median time that the . R" k A I (A+B)
Re Ia t1ve 1s = C 1 (C+D)
case-patients developed theirS. marcescens BSI (7 days) or dis-
charge date from the SICU if the controls' SICU length of stay Odds Ratio
Odds of exposure given disease =A I C
was less than 7 days. The exposure period for case-patients
Odds of exposure given no disease = B I D
and controls should be similar (52). For case-patients only,
exposure until the onset of illness should be collected. For .
D1sease Odds Rat"10 = A/C
BID = AD
BC
example, antimicrobial exposures for acquisition of VRE or
CRE probably should be collected for the proceeding days Relationship between relative risk and odds ratio
or weeks rather than months before onset of colonization. When disease is rare, B»A, and D>>>C
Exposure months before onset of a disease may be present,
Re Iat .1ve R"1sk = C
A/ (A+B) AD Odd t"
but may have no relationship to disease acquisition. Similarly, 1 (C+D) - BC = s ra 10
exposure data should be collected for a preceding biologically
plausible period of time. Control exposures to case-patients Figure 1.2. Example of a two-by-two table and definitions for
measures of effect or association, relative risk and odds ratio (57,60).
should be collected for a similar period, not for the entire
hospitalization. Otherwise, this process could be misleading
to a difference with case-patients that really represents the
allowing for the determination of a dose response. Unlike the
fact that the exposure period in controls (admission to dis-
OR, the RR not only describes that the exposure is associated
charge) is longer than in case-patients (admission until onset
with the outcome but also denotes causation.
of disease).
Disadvantages of the cohort study are that they may be
Case-control studies establish only that case-patients were
costly and time-consuming since patients must be followed in
more likely to have been exposed to potential risk factors than
time until a sufficient number develop the outcome of interest
were controls. In case-control studies, one can calculate an
(which could be a lengthy period of time if the disease course is
odds ratio (abbreviated OR), which estimates the relative risk
slow or the disease is rare). This could lead to loss offollow-up
(RR) and measures the strength of the association between the
of some in the cohort. Some of these limitations are lessened by
condition and the exposure/risk factor (Figure 1.2) (54,60).
performing a cohort study retrospectively because the outcome
has already happened. A variant on the traditional case-control
Cohort Study. In a cohort study, one assesses the entire pop- and cohort design can be helpful in the evaluation of HAis.
ulation (e.g., all ICU patients from June 2000 to December
A case-control study within an identified cohort is sometimes
2001) and evaluates what exposures are more common among
termed a "nested case-control" study. For example, a larger co-
those who develop disease/infection than those who do not.
hort study could look at group of hospitalized patients and fol-
As mentioned earlier, a cohort study may be either prospective
low for who develops C. difftcile infection, including recurrent
or retrospective. This distinction depends on when the study is
infections. A nested case-control could ident:if}' those from the
conducted with regard to when the outcome of interest occurs.
cohort who develop recurrent C. difficile infection and compare
If patients are identified as exposed and unexposed and then
them to a sampling of the patients from the cohort who did not
followed forward in time to determine whether they develop
develop C. diffo;ile infection to look for patient and exposure
the disease, this is a prospective cohort study. If the study is con-
factors associated with recurrent C. dijjicile infection.
ducted after the time of outcome has already occurred, this is a
retrospective cohort study. In either study, subjects are selected
based on their exposure to the variable of interest, and these OTHERANALYTICS EPIDEMIOLOGY METHODS
groups are compared based on the outcome.
Ecologic Stu/lies
The main advantage of the cohort study (vs. the case-control
study) is that if significantly more exposed patients than un- The studies described so far share the characteristic that the
exposed patients develop the outcome, this factor may be not observations made pertain to individuals. Ecologic or aggre-
only associated, but also causally related to the outbreak. In a gate studies conduct research in which the unit of observation
cohort study, one can quantifY the extent to which the exposure is a group of people rather than an individual. The require-
increases the risk of developing the condition in a summary ment is that information on the population studies be avail-
term RR (Figure 1.2) (60). Several cohorts may be followed, able to measure the exposure and disease distributions in each
each representing a different level of exposure to a factor, thus group. Because the data in ecologic studies are measurements
12 S«tionl • General Considerations ofHospital Infections
averaged over individuals, the degree of association between a cross-sectional study may be analyzed as a cohort or case-
exposure and disease need not reflect individual associations. control study.
These data may be more easily obtainable than individual-level
patient data but, as discussed, cannot be extrapolated to an in-
dividual patient. In fact, if done could lead to an ecologic fal- MEASURES OF ASSOCIATION AND
lacy, an error in the interpretation of statistical data, in which RELATED CONCEPTS
inferences about the nature of individuals are based solely on
aggregate statistics collected for the group to which those in- A measure of association provides an index of how strongly
dividuals belong. This fallacy assumes that all members of a two factors under study vary in concert (62) . The more tightly
group exhibit characteristics of the group at large. they are linked, the more evidence exists that they are causally
In healthcare epidemiology, some examples of ecologic related to each other (though not necessarily that one causes
studies are the use of data aggregated for other purposes, such the other, since they might both be caused by a third factor).
as drug dispending data from hospital pharmacies, and the Although this term and "measure of effect" have frequently
antimicrobial susceptibility data from the hospital clinical mi- been used interchangeably, Rothman and Greenland draw the
crobiology laboratory used for antibiograms. A good example following distinction: "associationsw involve comparisons be-
would be hospital data that could show an increase in use of tween groups or populations; "effectsw involve comparisons of
the antimicrobial vancomycin and VRE in enterococcal isolates the same population (hypothetically) observed in two different
or MRSA with reduced susceptibility to vancomycin, but it will conditions; measures of association are typically used to esti-
not be possible to know whether the patients who received van- mate measures of effect (62).
comycin were the patients who acquired VRE or MRSA with In Figure 1.2, a two-by-two table is constructed and the cal-
reduced vancomycin susceptibility. This type of data, however, culation for RR and OR (57,60), the two main measures of as-
may serve as exploratory data on which to base additional sociation that healthcare epidemiologists deal with on a regular
studies. basis, are illustrated. The calculations are not the difficult part;
An interesting use of ecologic data was the CDC's NNIS it is the understanding what these measures elude about the
Intensive Care Antimicrobial Resistance Epidemiology study and the two populations being compared (and what they
(!CARE) project (61). During this 4-year study, a subset of do not mean).
NNIS hospitals (50 ICUs at 20 U.S. hospitals) monitored anti- Depending on the study performed, either an RR or OR usu-
microbial use and MDROs. Participating hospitals reported the ally will be calculated. First, it is worth distinguishing between
grams of select antimicrobial agents administered to patients risk vs. odds. Risk refers to probability and has a numerator
and the antimicrobial susceptibility results of isolates recovered with the event/ occurrence of interest and a denominator with
from clinical specimens from hospitalized patients each month. all possible outcomes including the event of interest. The odds
Microbiologic data were aggregated for each ICU separately, all has the same numerator, but the denominator includes all pos-
non-ICU inpatient wards combined, and all outpatient areas sibilities minus the event/outcome of interest.
combined. Pharmacy data were reported for the same hospital The RR is the ratio of two probabilities of the outcome in
strata except for outpatient areas for which pharmacy data were the exposed over the probability of the outcome in the unex-
not available. Amounts of antimicrobial agents reported were posed (62). The RR can be calculated in cohort studies (and
standardized by conversion to defined daily doses; for paren- RCTs). If there is no difference in the risk of the exposed vs. the
teral vancomycin, a defined daily dose was equal to 2 g. unexposed, then the RR=l.O. RR > 1.0 implies that the exposed
The study found that after data were adjusted for changes group is more likely to have the outcome than those without
in MRSA prevalence, changes in specific prescriber practice at the exposure (no effect) . An RR <1.0 implies that the exposed
ICUs were associated with significant decreases in vancomycin group was less likely to have the outcome than the nonexposed
use (mean decrease-48 defined daily doses per 1,000 patient group (protective) (62) .
days, p < .001). These ICUs also reported significant decreases A study of pyrogenic reactions associated with single daily
in VRE prevalence compared with those not using unit-specific dosing of intravenous gentamicin illustrates the use of RR in a
changes in practice (mean decrease of 7.5% compared with cohort study (63). The authors conducted cohort studies in an
mean increase of5.7%, p <.001). In this study, practice changes inpatient service of a large community hospital in Los Angeles,
that focused on specific ICUs were associated with decreases California, following patients for the occurrence of pyrogenic
in ICU vancomycin use and VRE prevalence. This example il- reactions (i.e., chills, rigors, or shaking chills) within three
lustrates how HAl data may be aggregated for ecologic study, hours after the initiation of gentamicin. During the epidemic
such as the aggregation of defined daily doses and antimicro- period, 22/152 (15%) patients developed documented pyro-
bial resistant pathogen (ARP) prevalence comparisons between genic reactions following receipt of gentamicin. Pyrogenic re-
hospital units and not individual patients. actions were more likely among patients receiving single daily
dosing than multiple daily dosing of gentamicin (20/73 [27%]
vs. 2/79 [3%]; RR was 10.8%). Thus, in simple terms, those
Crass-SectionRI Studies
receiving single daily dosing of gentamicin had a risk of devel-
A cross-sectional study is a survey or sampling of a population oping a pyrogenic reaction that was 10.8 times higher than the
in which the status of the exposure and the outcome are ascer- risk of those who received multiple daily dosing.
tained at the same time. In healthcare epidemiology, this study The OR is less intuitive in its interpretation, but is the mea-
type is frequently used to assess the prevalence of a specific dis- sure that will be available from a case-control study (62). In this
ease, such as amount of antimicrobial resistance. A disadvan- type of study, the subjects are enrolled based on the outcome of
tage to this type of study is that it does not give an idea about interest (comparing a group with the outcome to a group with-
transition of status over time. Depending on the populations, out the outcome) to determine what proportion in each group
Chaptt!r 1 • Epidemiology of Healthcare-Associated Infections 13
has an exposure/risk of interest. An RR cannot be directly cal- clinical relevance (a problem in large database analysis, that
culated, because how common the outcomes/exposures are in is, pooled data such as a nationwide database). On the other
the entire population cannot be measured. Only an OR can be hand, a larger difference may not reach statistical significance
calculated. An OR reflects the odds of exposure with the out- if the sample size is small (a problem in some HAl outbreaks if
come divided by the odds of exposure in study su~ects without small numbers of cases are seen).
the outcome. An OR=l.O implies no effect. In the Serratia outbreak linked to fentanyl contamination
An RR cannot be calculated from a case-control study in described earlier (64), patients with S. marcescens BSI were more
usual situations; however, if a disease is rare, the OR can closely likely to have received fentanyl in the surgical ICU (odds ratio,
approximate the RR that would have been derived from a 31; p < .001). The p.value was actually much smaller <.000001,
cohort study (42,62). The calculations to support this are in thus, there was a less than 1 in 1,000,000 chance that the results
Figure 1.2. seen (that cases were more likely to have received fentanyl in
An outbreak of S. marcescens BSI traced to an infused nar- the surgical ICU than controls) is by chance alone.
cotic by using a case-control study illustrates the interpretation Due to the limitations of the p.value, a 95% confidence in-
of OR (64). To identify risk factors for the BSis, patients with terval for the measures of association (ORs and RRs, depend-
S. marcescens BSis were compared with randomly selected con- ing on the study performed) provides a range within which the
trols. Patients with S. marcescens BSis were more likely to have true magnitude of the association lies with a certain degree of
received fentanyl in the surgical ICU (odds ratio, 31; p < .001) assurance. If the range includes 1.0, the p.value often is nonsig-
and were more likely to have been exposed to two particular re- nificant or close to 0.05. Sample size also affected these confi-
spiratory therapists (odds ratios, 13.1 and 5.1; p < .001 for both dence intervals. Especially since HAl outbreaks may be small,
comparisons). One respiratory therapist had been reported for studies often suffer from wide confidence intervals (42). For
tampering with fentanyl, and his hair sample tested positive for example, in the study described earlier, pyrogenic reactions
it. Cultures of fentanyl infusions from two case-patients yielded were more likely among patients receiving single daily dosing
S. marcescens and E. cloacae. The isolates from the case-patients than there receiving multiple daily dosing gentamicin (20/73
and from the fentanyl infusions had similar patterns on pulsed- [27%] vs. 2/79 [3%]; RR=10.8, p < 0.01 with a 95% confidence
field gel electrophoresis. After removal of the implicated respi- interval of 2.6 to 44.7) ( 63) . Thus, those receiving single daily
ratory therapist, no further cases occurred. To translate some dosing had a risk to develop a pyrogenic reaction that was
of the ORs into understandable statements, for the OR of 31, higher than the risk of those who received multiple daily dos-
13.1, and 5.1 above, cases (patients with Serratia BSI) were ing of gentamicin, but it is not clear whether it was 2.6 times
31 times more likely than controls to have received fentanyl in higher, 44.7 times higher, or somewhere in between.
the surgical ICU, cases were 13.1 times more likely than con-
trols to have been exposed to/received care from respiratory
BIAS AND CONFOUNDING
therapist X, and 5.1 times more likely to have been exposed toI
received care from respiratory therapist Y. Bias is defined as any systematic error in an epidemiologic
study that results in an incorrect estimate of the association be-
tween exposure and risk of disease (65). Evaluating the role
STRENGTH OF ASSOCIATION
of bias as an alternative explanation for an observed associa-
AND CONFIDENCE INTERVALS
tion is necessary in interpreting any study result. Unlike chance
Analysis should begin with simple univariate frequencies fol- and confounding, which can be evaluated quantitatively, the ef-
lowed by two-by-two tables for binary outcomes with bivariate fects of bias are far more difficult to evaluate and may even be
analysis (Fisher's exact or chi-square tests) or appropriate tests impossible to consider in the analysis. There are two general
for continuous variables (parametric t tests or nonparametric classes of bias. Selection bias refers to any error that arises in
tests); (Figure 1.2) (57). A software package, Epi-Info, is avail- the process of identifying the study populations (discussed in
able from the CDC at no cost. This software package is very use- the case-control section regarding appropriate controls). The
ful for acquiring, organizing, and interpreting epidemiologic second general category, observation or information bias, in-
data from questionnaire to final analysis (http:/ /www.cdc.gov/ cludes any systemic error in the measurement of information
epiinfo/). on exposure or outcome (discussed in the case-control section
It is not the intent of this chapter to discuss the background regarding how long to collect exposure information for cases
or derivation of these tests for significance. However, interpret- and controls). The prevention and control of potential biases
ing the results for everyday use in healthcare epidemiology is must be accomplished through careful study design and me-
helpful. The idea of these tests is to assess whether a difference ticulous conduct of the study. Once a potential source of bias
seen between groups compared in the studies is real or could is introduced, it usually is extremely difficult to correct for its
be based on chance alone and to assign a probability that the effects analytically. However, it is necessary to estimate both the
difference is real. By convention, a p.value of <.05 is usually direction and magnitude that the bias would have on the ef-
considered statistically significant (29,30). This suggests that fect, and investigators should discuss all of these issues fully in
there is a <5% chance that the difference between the groups published reports to provide readers the maximum opportu-
is due to chance alone. The 0.05 is the convention but some- nity to judge for themselves whether the bias accounts for the
what arbitrary, and there may be instances where a less strin- observed findings.
gent cut off of 0.1 (e.g., exploratory analyses, criteria for entry Confounding can be thought of as a mix of the effect of the
into multivariate modeling) or more stringent cut off point exposure under study on the disease with that of a third factor
0.01 (e.g., multiple comparisons) is used. The p.value can be (66). This third factor must be associated with the exposure
affected by sample size; with a large enough sample, even small and be independent of that exposure, that is, be a risk factor
differences may be statistically significant but may not have for the disease. Confounding can lead to an overestimate or
14 S«tion I • General Considerations ofHospital Infections
underestimate of the true association between exposure and QUASI-EXPERIMENTAL STUDIES

disease and can even change the direction of the observed (PRE- AND POST-INTERVENTIONS)
effect. A number of methods are available to control con-
founding in the design or analysis of any study. These include Quasi-experimental studies, however, are used in infection con-
trol, particularly when a nonrandomized intervention is put
restriction, matching, or randomization (in clinical trials) in
the design and stratification and multivariate techniques into place, assessments of a baseline are taken before the in-
tervention, and similar data are collected before and after the
in the analysis. No single method can be considered optimal
intervention (42,67) . The advantages of these methods include
in every situation. Each has strengths and limitations, which
allowance for study of an intervention when a RCT is not fea-
must be carefully considered at the beginning of the study. In
sible for a number of reasons including ethics (in an outbreak
most situations, a combination of strategies will provide better
insight into the nature of the data and more efficiently control setting, the first priority is to protect patients and control the
outbreak, withholding treatment/control measures), may be
for confounding than a single approach (66). Common ex-
amples of confounders in HAis are length of stay and severity unethical, logistics (it may be impossible to randomize changes
to different patients/units), cost, and acceptability.
of illness.
One disadvantage of quasi-experimental studies is that it
may be difficult to account for all potential confounding vari-
ables that may have changed over the same/similar time as the
EXPERUMENTALEPIDENITOLOGY intervention that could account for the change in outcome in
part or in full rather than the intervention. Another disadvan-
RANDOMIZED CONTROL TRIALS (RCTS) tage may be a natural change/range in outcomes that may have
The third method of epidemiologic investigation is the experi- happened even without the intervention; thus, it may be dif-
mental method, which is a definitive method of proving or dis- ficult to attribute the change to the intervention. Often also
proving a hypothesis. The experimental method assumes that intervention or control measures in infection control are mul-
risk or protective factors are followed by effects on outcomes tifaceted or applied as bundles. In these situations it may be
and that a deliberate manipulation of these factors is predict- difficult to discern which component of the intervention was
ably followed by an alteration in the outcomes that could rarely successful and to what extent. Some statistical methods may be
be explained by chance. The two groups selected for study are employed to attempt to address some of these issues including
ideally similar in all respects except for the presence of the interrupted time series analysis (taking into consideration tim-
study factor in one group. Either the case-control or the cohort ing of the intervention).
method is used to evaluate the interaction between the cause An example of this type of study is described in relationship
and the effect. to preventing transmission of the multidrug-resistant Mycobacte-
An example of the experimental method is the evaluation rium tuberculosis to patients and HCWs (68). It was a retrospec-
of a new drug as treatment for a disease: A group of patients tive cohort study measuring the proportion of case-patients
with the disease is randomly divided into two subgroups that with healthcare-associated M. tuberculosis and the rate of tuber-
are equal in all respects except that one of the subgroups is culin skin test conversion among HCWs before and after imple-
treated with the experimental drug, and the other subgroup mentation of control measures (from the 1990 CDC guidelines:
(the control group) is given a placebo or another agent prompt isolation and treatment of patients, rapid diagnostic
known to be effective in treating or preventing the disease. If techniques, negative pressure isolation rooms, and molded
there is no other variation between the two groups, any differ- surgical masks for HCWs). The study found that the propor-
ences in the course of the disease may be ascribed to the use tion of patients with multidrug-resistant strains of M. tuberculosis
of the drug. decreased after the intervention (10/70 [14%] compared with
The experimental method has less direct use in the inves- 30/95 [32%] patients before the intervention; RR=0.5, 95% CI,
tigation of HAl outbreaks today than the other analytic meth- 0.2 to 0.9).
ods such as case-control or cohort studies. The experimental
method, however, is useful in assessing general patient-care
practices and in evaluating new methods to control and pre-
CHAIN OF INFECTION
vent disease. Placebo-controlled trials have less use in therapeu-
GENERAL ASPECTS
tic studies because of the needs for informed consent and for
preventing the placement of the patient at an unjustified or Infection results from the interaction between an infectious agent
greater risk in attempting to conduct a specific study. and a susceptible host. This interaction-called trarumission-
Thus, while the healthcare epidemiologist may not perform occurs by means of contact between the agent and the host.
these studies, it is important to have a working knowledge of Three interrelated facto11t-the agent, transmission, and host-
these types of studies as a comparison to the descriptive and represent the chain of infection.
analytic methods described previously so that the strengths The links interrelate with and are affected by the environ-
and weaknesses of these other designs can be acknowledged ment; this relationship is referred to as the ecology of infection,
(since experimental trials such as random control trials pro- that is, the relation of microorganisms to disease as affected by
vide the best support for causality). In addition, healthcare the factors of their environment. In attempting to control and/
epidemiologists play multiple roles at facilities and may be or prevent HAis, an attack on the chain of infection at its weak-
asked to aid in the assessment of new products for which ex- est link is generally the most effective procedure. With defini-
perimental trials may have been performed and should be tion of the links in the chain for each HAl, future trends of
able to read the literature and interpret studies for others at the disease should be predictable, and it should be possible to
the facility. develop effective control and prevention techniques. Defining
the chain of infection leads to specific action in contrast to the Microorganisms may be specific with respect to their range
incorporation of nonspecific actions in an attempt to control a of hosts. Brucella abortus is highly communicable in cattle but
HAl problem. not in humans. Some Salmonella spp. is common to both ani-
Disease causation is multifactorial; that is, disease results mals and humans, but others have a narrow range of specificity.
from the interaction of many factors related to the agent, trans- Infectivity refers to the ability of an organism to spread from
mission, and host. The development of disease reflects the in- a source to a host (1,18). An infected human may be infective
teraction of these factors as they affect a person. Thus, some during the incubation period (e.g., hepatitis A), the clinical
people exposed to an infectious agent develop disease and oth- disease state (e.g., Influenza A), convalescence (e.g., salmonel-
ers do not. losis, shigellosis), or some combination of the three. Addition-
ally, an asymptomatic carrier (or colonized person) who does
not show evidence of clinical disease may be infective. In some
AGENT diseases, such as typhoid fever or hepatitis B, a chronic carrier
state may develop in which the individual may be infective for a
Agent Ch11rll&teristics
long time, possibly years, while showing no symptoms of illness.
The first link in the chain of infection is the microbial agent, However, the microorganisms that most commonly cause HAis,
which may be a bacterium, virus, fungus, or parasite. The ma- such as E. col~ Klebsiella, Enterobacter, and Pseudomonas spp., do
jority of HAis are caused by bacteria and viruses; fungi are as- not demonstrate the same patterns of infectivity or evoke the
suming a greater role and parasites a rare cause. A number of protective immune responses that typhoid fever or hepatitis B
factors help to characterize the agent, including infectiousness, does.
pathogenicity (including virulence and invasiveness), dose, Asymptomatic or subclinical carriers may be the more
specificity, infectivity, and other agent factors (including anti- important source of infection than the clinically infected indi-
microbial resistance) (1,18). vidual. The staphylococcus carrier provides a classic example of
The determination of the number of susceptible individuals the asymptomatic dissemination of infectious organisms; in this
who become infected with an organism to which they are ex- instance, the site of dissemination may be the anterior nares
posed is a measure of the infectiousness of that organism. Host or, at times other areas such as the skin. Similarly, the site of
factors can influence the infectiousness of an organism. asymptomatic streptococcal carriage may be in the pharynx,
The measure of the ability of microorganisms to induce dis- perianal area, or vagina.
ease is referred to as pathogenicity, and it may be assessed by The source of an infection may be an atypical case of a spe-
disease-colonization ratios. An organism with low pathogenic- cific disease whose clinical course has been modified by ther-
ity is alpha-hemolytic streptococcus; it commonly colonizes hu- apy, vaccine (as in measles), or prophylaxis (such as the use
mans but only rarely causes clinical disease. The pathogenicity of immune serum globulin in hepatitis A). Animals also may
of an organism is additionally described by characterizing the provide a source of infection, although this is of less concem in
organism's virulence and invasiveness. the healthcare settings.
Virulence is the measure of the severity of the disease. In Additional characteristics of the agent that may affect their
epidemiologic studies, virulence is defined more specifically by ability to produce disease are the production of virulence
assessing morbidity and mortality rates and the degree of com- factors/enzymes, antigenic shift and drift (such as seen by
municability. The virulence of organisms ranges from slightly Influenza A), and development/acquisition of antimicrobial
to highly virulent. Although some organisms are described as resistance (via plasmid or gene mutation) .
avirulent, it appears that any organism can cause disease under The increase in antimicrobial resistance has had a dramatic
certain circumstances. Some naturally occurring organisms effect on HAis. Changes in antimicrobial sensitivity may make
have been considered avirulent or of low virulence; however, therapy difficult; it can result in an increasing prevalence of
under certain conditions, such as high doses, host immuno- the resistant strain, reduce the necessary infecting or coloniz-
deficiency, or both, disease has resulted from contact with ing doses of the organism in those receiving drugs to which
these organisms. For years, S. marcescens, for example, was con- these strains are resistant, increase the numbers of organisms
sidered to be an avirulent organism; because of this and the disseminated from persons colonized with these strains, and
easily recognizable red pigment produced by certain strains, potentially increase the frequency of HAis due to this more re-
these organisms were used for environmental studies in hos- sistant strain ( 1).
pitals. However, as hospitalized patients became more suscep-
tible to developing infections due to advancing age, comorbid
R.eset"J'oir, Sot~rce, 11nd PortRl of&it
conditions, immunosuppression, and the effects of new di-
agnostic and therapeutic measures, HAis due to S. maTUScens All organisms have a reservoir and a source; these may be the
subsequently became recognized and reported. Invasiveness same or different, and it is important to distinguish between
describes the ability of microorganisms to invade tissues. Some these potentially different sites if control and/or prevention
organisms can penetrate the intact integument whereas other measures are to be directed at this aspect of the chain of infec-
microorganisms can enter only through a break in the skin or tion. The reservoir is the place where the organism maintains
mucous membranes. its presence, metabolizes, and replicates. Vuuses generally sur-
Another important agent factor is dose, that is, the number vive better in human reservoirs; the reservoir of gram-positive
of organisms available to cause infection. The infective dose of bacteria is usually a human, whereas gram-negative bacteria
an agent is that quantity of it necessary to cause infection. The may have either a human, or an animal reservoir (e.g., Salmo-
number of organisms necessary to cause infection varies from nella), or an inanimate reservoir (e.g., Pseudomonas in water) .
organism to organism and from host to host and is influenced The source is the place from which the infectious agent
by the mode of transmission. passes to the host, either by direct or indirect contact, droplet,
airborne, common vehicle, or a vector as the means of trans- Droplet Trsnsmission

mission. Sources also may be animate or inanimate. The source
may become contaminated from the reservoir. For example, a Droplet transmission, theoretically, is a form of contact trans-
reservoir for Pseudmrumas spp. may be the tap water in a hos- mission. However, the mechanism of transfer of the pathogen to
pital; however, the source from which it is transmitted to the the host is quite distinct from either direct- or indirect-contact
patient may be a humidifier that has been filled with contami- transmission. Thus, in the 1996 and subsequent Guidelines for
nated tap water or contaminated respiratory fluid. Isolation Precautions in Hospitals, droplet transmission was
The portal of exit for organisms from humans usually is considered a separate route of transmission (69,70). Droplets
single, although it may be multiple. In general, the m,Yor por- are generated from the source-person primarily during cough-
tals of exit are the respiratory and gastrointestinal tracts and ing, sneezing, talking, and performing certain procedures
the skin and wounds. Blood also may be the portal of exit, as such as suctioning and bronchoscopy. Transmission occurs
in hepatitis B or human immunodeficiency virus (HIV) infec- when droplets (large-particle droplets, >5 pm in size) con-
tions. However, depending on the organism, any bodily secre- taining microorganisms generated from the infected person
tion or excretion can be infectious. are propelled a short distance through the air and deposited
on the host's conjunctivae, nasal mucosa, or mouth. Transmis-
sion via large-particle droplets requires close contact between
TRANSMISSION source- and recipient-persons, because droplets do not remain
Transmission, the second link in the chain of infection, de- suspended in the air and generally travel only short distances,
scribes the movement of organisms from the source to the usually 3 feet or less, through the air. Because droplets do not
host. Spread may occur through one or more of five different remain suspended in the air, special air handling and venti-
routes: contact (either direct or indirect), droplet, airborne, lation are not required to prevent droplet transmission (as
common vehicle, and vector-borne (described later based on opposed to airborne transmission). Examples of pathogens
CDC guidelines for isolation precautions in hospitals) ( 69). An transmitted by the droplet route are Bordetella pertussis and
organism may have a single route of transmission, or it may Neisseria meningitides.
be transmissible by two or more routes. M. tubm;ulosis, for
example, is almost always transmitted by the airborne route; Airborne Trsnsmission
measles is primarily a contact-spread disease but may also be
transmitted through the air; salmonellae may be transmitted Airborne transmission occurs by dissemination of either air-
by contact or by the common-vehicle, airborne, or vector-borne borne droplet nuclei (small-particle residue [:55 pm in size)
routes. Thus, in defining the route of transmission, although of evaporated droplets containing microorganisms that remain
one route may be the obvious one involved in an HAl problem, suspended in the air for long periods of time-hours or possibly
another route also may be operative. Knowledge regarding the days) or dust particles containing the infectious agent Micro-
route of transmission for a specific pathogen can be very help- organisms carried in this manner can be dispersed widely by
ful in the investigation of an HAl problem. Such information air currents and may be inhaled by a susceptible host within
can point to the source and may allow control measures to be the same room or over a longer distance from the source-
introduced more rapidly. patient, depending on environmental factors; therefore, special
air handling and ventilation are required to prevent airborne
transmission. Microorganisms transmitted by airborne transmis-
Contact Trsnnnission sion include M. tuberculosis, rubeola, varicella viruses (including
Contact transmission is the most important and frequent mode disseminated zoster) (69--71), and smallpox if there were ever
of transmission of HAl pathogens. Contact transmission can recurrence of cases. In the last several years, there has been con-
be divided into two subgroups, direct-contact transmission and troversy as to whether other emerging pathogens/diseases (in-
indirect-contact transmission (69,70). Direct-contact transmis- cluding SARS and the 2009 pandemic HINI Influenza A) might
sion involves a direct body surface-to-body surface contact and be transmitted via airborne route (which would have implica-
physical transfer of microorganisms between a susceptible host tions for isolation and personal protective equipment) (72-74).
and an infected or colonized person as occurs when a person The airborne route of transmission is more frequently assumed
turns a patient, bathes a patient, or performs other patient-care to be the route of an infection than is the case (1). Creation of
activities that require direct personal contact. Direct-contact an infectious aerosol is more difficult than is usually recognized.
transmission also can occur between two patients with one
serving as the source of the infectious microorganisms and the
Common-Vehicle Trt:Jnsmission
other as a susceptible host
Indirect-contact transmission involves contact of a suscepti- In common-vehicle-spread infection, a contaminated inanimate
ble host with a contaminated intermediate object, usually inani- vehicle, such as food, water, medications, devices, and equip-
mate, such as contaminated instruments, needles, or dressings, ment, serves as a vector for transmission of the agent to mul-
or contaminated hands that are not washed, and gloves that are tiple persons (69,70). The susceptible host becomes infected
not changed between patients. The intermediate object may after contact with the common vehicle. This transmission may
become contaminated from an animate or inanimate source. be active if the organisms replicate while in the vehicle, such
An example is the transfer to susceptible hosts of enteric organ- as salmonellae in food, or passive if the organisms are passively
isms on an endoscope that initially became contaminated when carried by the vehicle, such as hepatitis A in food. Other types
brought in contact with an infected patient (the index patient). of common vehicles include blood and blood products (hepati-
Examples of organisms that can be transmitted via contact are tis Band HIV), intravenous fluids (gram-negative septicemia),
MDROs, such as VRE, MRSA, CRE, and C. difficile. and medications (gram-negative septicemia, fungal infections)
in which units or batches of a product become contaminated evidence of disease, but when the same organism colonizes a
from a common source and serve as a common vehicle for fresh surgical wound, an SSI may develop.
multiple infections. Recently a multistate outbreak of fungal
meningitis was linked to contamination of injectable steroids Nonspecific sml Specific Defense Mechsnisms
produced at a commercial compounding pharmacy (75,76).
Humans have extensive nonspecific and specific defense mech-
anisms to protect against infection (1). Nonspecific defense
Vector-Borne SpreiUl mechanisms include the skin, mucous membranes, and certain
Vector-borne transmission occurs when vectors such as mos- bodily secretions (tears, mucus, enzymes). The local inflam-
quitoes, flies, rats, and other vermin transmit microorganisms matory response provides another nonspecific host defense
(69,70); this route of transmission is of less important in U.S. mechanism. Other nonspecific protective mechanisms include
hospitals than in other regions of the world. genetic, hormonal, nutritional, behavioral, and personal hy-
giene factors. Age, as influenced by these nonspecific factors,
is associated with decreased resistance at either end of the
HOST
spectrum; the very young and the very old frequently are more
The third link in the chain of infection is the host. Disease does susceptible to infection. Surgery and the presence of chronic
not always follow the transmission of infectious agents to a host. diseases, such as diabetes, blood disorders, certain lymphomas,
As previously discussed, various agent factors play a part; simi- and collagen diseases, alter host resistance.
larly, a variety of host factors must also be surmounted before Specific immunity results from either natural or artificially
infection occurs and disease develops. Host factors that influ- induced (i.e., vaccines, immunoglobulin) events. Over the last
ence the development of infections are the site of deposition several decades, medical therapies for conditions such as can-
of the agent and the host's defense mechanisms, referred to as cers, solid organ/bone marrow transplantation, and HIV have
immunity, either specific or nonspecific. increased the population of hosts with significant immunosup-
pression. These hosts have added to the challenges of HAis.
PortR-l of Entrsnce
Host Response
Sites of deposition include the skin, mucous membranes, and
respiratory, gastrointestinal, and urinary tracts. Staphylococci The spectrum of the host's response to a microorganism may
spp., including community-acquired MRSA strains need a min- range from a subclinical (or inapparent) infection to a clini-
ute breach in the integrity of the skin to gain entrance to the cally apparent illness, the extreme being death. The host may
body. Mechanical transmission may occur through the nor- become a carrier of the organism. The clinical spectrum of dis-
mal skin, as with hepatitis B or HIV viruses on a contaminated ease varies from mild to a typical course (although a disease
needle or in contaminated blood. Abnormal skin, such as a may typically be mild) to severe disease and possible death. The
preexisting wound, may be the site of deposition of organisms degree of host response is determined by both agent and host
such as P. aeruginosa. Mucous membranes may be the site of factors and includes the dose of the infecting organism, its or-
entrance, as the conjunctiva is for adenovirus. gan specificity, the pathogenicity of the infecting organism, its
Another site of deposition is the respiratory tract. The exact virulence and invasiveness, and its portal of entry. Host factors
area of deposition depends on the size of the airborne particle include the quantitative and qualitative level of the specific and
and the aerodynamics at the time of transmission. Generally, nonspecific immunologic factors previously discussed.
particles 2:5/lm in diameter will be deposited in the upper re- The same organism infecting different hosts can result in
spiratory tract, whereas those <5/lm in diameter will be depos- a clinical spectrum of disease that is the same, similar, or dif-
ited in the lower respiratory tract. ferent in various individuals. For example, many cases of what
Infectious agents may gain entrance to the body through the appears to be the outbreak disease may meet the clinical case
intestinal tract by means of ingestion of contaminated foods definition, whereas other cases that epidemiologically are re-
or liquids, contaminated supplemental feedings, and contami- lated to the same epidemic may not meet the same case defini-
nated medications or through contaminated equipment, such tion. They may, in fact, be cases of the outbreak disease but
as endoscopes inserted into the intestinal tract. The urinary with a different clinical spectrum (as can occasionally be dem-
tract may become infected from contaminated foreign objects onstrated by serologic tests). They also may be cases of other
such as catheters or cystoscopes inserted into the urethra or by diseases occurring concurrently with the outbreak.
the retrograde movement of organisms on the external surface
of a catheter inserted into the bladder.
ENVIRONMENT
Organisms may gain entrance into the host via the placenta,
as occurs in rubella and toxoplasmosis. Transplantation is an- Patients at healthcare facilities often are confined to a hospital
other method by which microorganisms enter the host; infec- bed and surrounded by multiple medical devices, equipment,
tion may follow renal transplantation if the donated kidney is and environmental surfaces. Thus, there is concern that the
infected with cytomegalovirus. facility environment may play a role in the chain of infection.
An organism may colonize one site and cause no disease, but The role of the environment is more strongly documented
the same organism at another site may result in clinical disease. in C. difftcile than many other HAis. It is in this setting, en-
E. coli, for example, routinely colonizes the gastrointestinal hanced cleaning protocols, including use ofbleach/sporiocidal
tract and under normal circumstances does not cause disease; agents, have become standard. Studies using ultraviolet (UV)
however, the same organism in the urinary tract may cause in- light or other chemicals to supplement standard cleaning have
fection. S. aureus may colonize the external nares without any shown some promise for the future.
TABLE 1.3 Epidemiological RcK>urccs (with an Emphasis on Hcalthcarc-Assodatcd Infections/

Health Epidemiology)
Type ~aofS~/Coounenu
GENERAL EPIDEMIOLOGY
Gordis L, ed. Epidemiologj. Philadelphia, Text Excellent beginning text on general principals
PA: W.B. Saunders; 2000:140-157. of epidemiology (especially case-control
(54,55,59,60) and cohort studies and odds ratios and
relative risk measures).
Hennekens CH, BuringJE, Mayrent SL, Text Abo an excellent a beginning text on general
eds. Epidemiology in Medicine. Boston, principles of epidemiology (especially bias
MA: Litde, Brown;1987:272-286. (65,66) and confounding).
Rothman KJ, Greenland S, eds. Modem Text An excellent, more advanced text on general
Epidemiolog:J. Philadelphia, PA: principals of epidemiology (especially
Lippincott-Raven;1998:29-46. (40,67) measures of associations, relative risk
measures).
Schoenbach VJ, Rosamond WD. Text (electronic) Online at: http:/I Abo an excellent a beginning text on general
Understanding the Fundamentals of~ www.epidemiolog.net/evolving/ principals of epidemiology with ongoing
o/Qgy: An Evolving Tm. Chapel Hill, NC: TableOfContents.html edits (available for free online)
Department of Epidemiology, School
of Public Health, University ofNorth
Carolina; 2000. (2)
CDC's "EXCITE": Epidemiology in the Step-by~tep discussion steps of an outbreaks
classroom, how to investigate an out- in any setting, including on construction
break, steps of an outbreak investigation. and interpretation of epidemic curves
http:/ /www.cdc.govI excite/classroom/
outbreak/steps.htm. (39)
EPIDEMIOLOGICAL PRINCIPALS SPECIFIC TO HEALmCARE EPIDEMIOLOGY TOPICS

Beck-&gue C,Jarvis WR, Martone WJ. Article Simple discussion of steps and considerations
Outbreak investigations. Infect Control in outbreak investigation of hospital
Hosp Epidemiol. 1997;18(2):138-145. (25) outbreaks
Centers for Disease Control and Prevention, Online at: http:/ /www.cdc.gov/ Includes electronic version of CDC, Infection
Division of Quality Healthcare ncidod/dhqp/healthDis.html Control Guidelines
Promotion. Infection control in
healthcare settings. (4)
Centers for Disease Control and Prevention, Online at: http:/ /www.cdc.gov/ Includes background on NHSN
NHSN-website nhsn/
NHSN, CDC 8c Association of Professional Online at: http:/ /www.cdc.gov/ Includes details of state HAl reporting
in Infection Control and Epidemiology HAl/surveillance/reports/ state-
(APIC) and related resources on specific-hai-sir-luly-dec-2009 .html
mandatory reporting http:/ /www.cdc.gov/nhsn/PDFs/
dataStat/NHSN-Report_201 0-
Data-Summary.pdf
http:/ /www.apic.org/Resource_/
TinyMceFileManager/Advocacy-
PDFs/HALmap.gif
Liutenbach E, Woelge KF, Malani P, et al, Text Variety of healthcare epidemiology topics
eds. Praaia:dH~~
3rd ed. Chicago, IL: University of
Chicago Press; 2010. (42)
Society for Healthcare Epidemiology of Online at: www.shea-online.org Including access to Infection Control Health
America (SHEA) website wwwJournals.uchicago.edu/ICHE EpidemiologyJournal (ICHE)
Association for Professionals in Infection Online at: www.apic.org Including access to American journal of
Control and Epidemiology (APIC) Infection Control (AJIC)
At times, too much emphasis is placed on the role of the that impose unnecessary and ineffective actions on the hospital
environment; for example, it is inappropriate to take environ- staff and a consequent loss of efficiency and effectiveness, and a
mental cultures routinely throughout a hospital. However, in in- wasting of resources such as personnel time and money (1,25).
vestigating HAis, it may be appropriate to obtain environmental Some environmental factors can influence all of the links in
cultures as suggested by the circumstances of the specific prob- the chain of infection, whereas others are more limited in their
lem under investigation (1,25,77). A compromise and a healthy range of action. Humidity, for example, can influence a multi-
respect for the environment are needed with maintenance plicity of factors; it can affect the persistence of an agent at its
that does not deliberately promote the transmission of disease- source, its transmission through the air, and the effectiveness of
causing agents to hosts but without excessive control measures a host's mucous membranes in resisting infection.
Replication of the agent at its reservoir may depend on cer- 15. Wong ES, Ru.pp MF:, Mermel L, et ill. Public dioclooure ofhealthcare-<~~~ociated infectiODI:
the role of the Society for Heillthcare Epidemiology of America. 111/«f Ctmlrol H..p ~
tain substances in the environment. The agent's survival is in- llliol. 2005;26:21{}-212.
fluenced by the temperature, humidity, pH, and radiation at its 16. Medicare program: change• to the holpital inpatient proiJlecti.., payment l)'ltemJ and
reservoir or source. fiocal l"""' 2008 rateo.&d&g. 2007:72;47129-48175.
17. Medicare program: change• to the holpital inpatient proiJlecti..., payment l)'lteml and
The transmission of agents will be affected by environmen- fiocal year 2009 rateo; payment fur graduate m..Ucal education in certain emergency oitua-
tal factors, such as temperature and humidity, as mentioned tions; cbangeo to dioclooure of phYJician ownenhip in hoopitals and phYJician oelf-rd'erral
ruleo, updateo to the long tenn aJI'e proopectm: payment l)'ltem; updateo to certain
earlier. Airborne transmission is influenced by air velocity, hu- IPI'St>ulnded hoopitals; and collection of informatiou regarding fiuaucial relationohipo
midity, and the direction of air movement. The stability and betw<:en hoopitals. Final ruleo. Fetl. &g. 2008;75;4Mll$-49084.
concentration of an aerosol are directly related to environmen- 18. Reiman DA Fallww S. Microbial virulence factoro. In: Mandell GL, Douglao .RG, Bennett
JE, et al, edo. M<m<WI, Dtntf,iu, ....tBmmtt~ l'rimip/cs ....tPnJaiu •fInfraiuw Di.JorMrs. Phila-
tal factors. In winter, people tend to be indoors with closed win- delphia, PA: Churchill Livingltone; 2000:2.
dows and reduced air circulation, and this increases the risk 19. Jarno WR. The epid.cllliology of colonization. bof«t CoRtrul H..p ~ 1996;17:47....52.
of airborne disease; in summer, room air is air conditioned or 20. Jarno WR, Ootrow>kyB. Dinooaun, metlricillin-reoiJtant Staph~ctU ""'""'·and infection
control perooDDel: awvival through tranolating ocience into prcv=tion. brfoa Control H..p
diluted with outside air. In outbreaks associated with common- Epidomiol. 200!1;24:592-596.
vehicle transmission, the temperature of the environment will 21. Muto CA, Jemigan JA, Ootrow>ky BE, et ill. SHEA guideline for preventing noooconrial
tranomiooion ofmultidrug-reaiJtant otraino of Sk>pliJ/t.lciJmu """""and enterococcuo. Injla
influence the level of contamination in the vehicle. Conhul H..p F4JiMrroid. 2005;24:562-!186.
The host's resistance mechanisms are affected by environ- 22. OotrowJky B, Steinberg JT, Farr B, et aL Reality check: ohould we try to detect and iJolate
mental factors; for example, in an excessively dry atmosphere, vancomycin-reaiJtant enterococci patienta? hlfocl CtmJroiH..pEpidomiol. 2001;22:110-119.
2!1. Morgan D, Pineleo L, Shardell M, et al. The effect of contact precaution• on hcillthcare
mucous membranes become dry and are less able to protect worker activity in acute care hoopitals. hlfocl Conll!>l HOIJ> ~ 201S;M:~7S.
against microbial invasion. Also, the host's behavioral patterns 24. Sherertz .RJ, Bailetti S, Bauetti-Wy11 B. "Cloud" health-<:are worken. ~ bifoct DU.
2001;7:241-244.
are influenced by temperature.
25. Beck-Sague C, Jarm WR, Martone ~- Outbreak W...atigationo. Iraft<t ConmJl H..p ~
Ultimately, the reason to discuss the links in the chain of infec- tniol. 1997;18:1SS-145.
tion and their modulators, for example, the environment, in such 26. Kluyt:mauoj,""' BclkwnA, Verbrugh H. Naoal c:arriage of Staphylo<omu fillmll.l: epidemiol-
ogy, underlying mechanism~, and aooociated rukl. Clin MicnJbiol &v. 1997;10:5()!;-520.
detail is that once these factors have been examined, the most ap- 27. Emori TG, Culver DH1 Horan TC, et aL National no1ocomial infections surveillance rys-
propriate methods of control and prevention can be detennined. tem (NNIS): deoaiption ofour...illancemethodo. Aa]Injla Conln>L 1991;19:1~55.
28. Horan TC, Gayneo RP. Sur...illance of nooocomiiil infectiom. In: Mayhall CG, ed. H,.
pikll F.J>iderlliolot mod boftaion Control. Philadelphia, PA: Lippincott Willianu Be Wllkino;
2004:1659-1702.
CONCLUSIONS 29. CDC, National Hcillthcare Safety Network. http:/ /www.cdc.gov/nbon/ about html.
SO. Dudeck M, Horan T, Petenon K, et al. NalitnuJl ~ Saf<tj N - (NHSN) &pun,
Dllt4 Sv.mm4ry for 2010, ~llt«l Modvk Atlanta, GA: CDC. http:// www.cdc.gov/
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Epidomiol. 1999;20:25{}-278.
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references on general epidemiology concepts and specific is- Program c"P"rience, 1980 to 1990. Epidenriology Branch, Hoopital Infecti.ono Program.
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!Ill. Jarno Wit. Hoopital Infecti.ono Program, Centen for DiJeue Control and Pr...,ntiou On-
lite Outbreak ln..,.tigatiom,l990 to 1999. Slflllnjl<l Conlrol. 2001:7$-84.
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2 VIrginia R. Roth and Bryan P. Simmons
The Healthcare Epidetniologist

DEFINITION ROLES AND RBSPONSmiLITIES
A healthcare epidemiologist investigates the rates and determi· Healthcare epidemiologists play a key role in the prevention
nants of adverse outcomes in healthcare with a primary focus and control of adverse healthcare outcomes, with a particu-
on healthcare-aasociated infections (:HA:b). A healthcare epi· lar focus on HAis. 'I1Ws is accomplished through surveillance,
demiologi!t is not solely an investigator. but aho implements outbreak investigation, quality management and patient safety
preventative measures to improve outcomes. initiatives, educational programs, research, and committee
representation (Table 2.1). The healthcare epidemiologist
urually workll alongside one or more infection preventionists
HISTORY (IPs) and may be responsible for administering the infection
prevention and control program. He or she is also responsible
Healthcare epidemiology has been practiced since the for maintaining close communication with personnel involved
mid-1800s; Nightingale, Semmelweis, Lister, and Holmes all in other programs within the healthcare environment as well as
made significant contributions to the field. Modem health· with public health and govemmental agencies. More recently,
care epidemiology began in the 1950s in Great Britain, healthcare epidemiologists have been involved in contingency
when infection control systems were used to address hospi· planning for pandemics and other disasters.
tal outbreaks of staphylococcal infections. In the 1960s, the
American Hospital Association (AHA) formed the Commit-
SURVEILLANCE
tee on Infections within Hospitals, and the Communicable
Disease Center (CDC, now the Centers for Disease Control Surveillance is one of the single most important functions
and Prevention) formed the Hospital Infections Unit. These of the healthcare epidemiologist (5). All more jurisdictions
two organizations supported an organized approach to ad- mandate public disclosure of HAl rates, healthcare epidemi-
dressing HAis in the United States, and the AHA published a ologists are increasingly being called on to design and imple-
manual on prevention of HAis that was used extensively for ment mandatory reporting systems and monitor their results
almost two decades (1). (6) (see Chapter 15). The primary objectives of surveillance
Because of the need to organize and promote the scientific are to identify problems for correction, order priorities, and
basis of hospital infection prevention and control programs, take meaaures to reduce adverse outcomes (see Chapter 4).
and to encourage expansion of such programs, the CDC The healthcare epidemiologist is respousible for setting survei~
convened the first Intemational Conference on Nosocourial lance priorities and overseeing data collection, analysis, inter-
Infections in 1970 (2-4). In 1980, a group of physicians prac- pretation, and reporting. More professional societies outside of
ticing healthcare epidemiology formed the Society for Hospi· infection prevention and control are developing HAl survei~
tal Epidemiology of America (SHEA), now called the Society lance systems (7). These may produce conflicting data within
for Healthcare Epidemiology of America (see Chapter 11). the same healthcare organization when different definitions for
Similar organizations were formed in other countries, many numerator or denominator data or risk. adjuslment are used.
ofwhich are member societies of the International Federation The healthcare epidemiologirt should be prepared to respond
of Infection Control (IFIC). The first hospital epidemiologists to these data, to advocate for surveillance methodology that is
concentrated their efforts on preventing HAis, and the land· consistent with national or international surveillance systems,
mark Study on the Efficacy of Nosocomial Infection Control and to ensure anyone collecting infection surveillance data
(SENIC) project reinforced their efforu by demonstrating that within their organization has the necessary training in infection
a physician specially trained in infection control could reduce surveillance. Surveillance data are most useful when compared
the HAl rate (5). The boundaries of healthcare epidemiology against historical rates within the same facility or against na-
have now expanded beyond infection prevention and control tional benchmarks. The U.S. CDC's National Healthcare Safety
into clinical performance, quality management, and disaster Network (NHSN; formally the National Nosocomial Infections
planning. Furthermore, the settings in which healthcare epide- Surveillance System, or NNIS) demonstrates the value of a na-
miology is practiced have now expanded beyond hospitals into tional surveillance S)'3tem in promoting patient safety (8). It has
long-term care, long-term acute care, continuing care, outpa- been suggested that many HAis are preventable (9), and sev-
tient and ambulatory care, community-based settings, and even eral centers have shown that multifaceted system interventions
home healthcare. can reduce central line--associated bloodstream infections and
21
responsible for providing formal infection prevention training

TABLE 2.1 The Healthcare to infectious diseases residents and other physicians. Finally,
Epidemiologist's Roles the healthcare epidemiologist should support and promote the
• Surveillance development of an infection prevention orientation and train-
• Outbreak investigation ing program for all healthcare personnel.
• Quality management and patient safety initiatives
• Education
• Research RESEARCH
• Committee representation Healthcare epidemiologists have a well-established history of
• Administration of infection prevention and control programs identifying and quantifying infection prevention and control
• Consultation and communication
measures that reduce adverse patient outcomes (32). The in-
• Disaster planning
fection prevention and control literature accounts for many of
the patient safety practices for which there is strong supporting
scientific evidence (33,34). However, many research gaps have
ventilator-associated pneumonia rates to almost zero (10,11). been identified (33,35,36), and healthcare epidemiologists
The healthcare epidemiologist should lead multidisciplinary must play a pivotal role in addressing these gaps (37).
intervention teams to implement the system changes necessary
to reduce HAl rates.
COMMI'TI'EE REPRESENTATION
The healthcare epidemiologist should be an active standing
OUTBREAK INVESTIGATION
member, and may serve as chair, of the infection prevention
The healthcare epidemiologist plays a key role in confirming and control committee. This committee is responsible for
the existence of an outbreak and overseeing data collection, approving infection prevention policies, highlighting infec-
data analysis, and implementation of control measures by the tion prevention and control issues to the medical and senior
outbreak management team. As part of the outbreak investi- administration of the facility, and reviewing infection preven-
gation, the healthcare epidemiologist should determine what tion and control surveillance and outbreak data to develop an
patient and environmental testing is required and assist in inappropriate action plan. In addition to infection prevention
terpreting the results. Additional responsibilities during an out- and control committee membership, the healthcare epidemi-
break include communication with administrators, physicians, ologist provides valuable input to other committees, includ-
the local public health department, and the media. ing occupational health and safety, product evaluation and
standardization, pharmacy and therapeutics (particularly with
respect to antimicrobial selection and use), and sterilization/
QUALITY MANAGEMENT AND PATIENT SAFETY
disinfection. Membership in these committees may be on an ad
Many healthcare epidemiologists have become involved in hoc basis. Finally, healthcare epidemiologists provide valuable
quality management and patient safety initiatives because epi- technical and clinical expertise to national and international
demiology is as useful to these areas as it is to infection preven- committees responsible for developing infection prevention
tion and control (see Chapter 14) (12,13). Continuous quality and patient safety-related guidelines.
improvement (CQI) programs depend on data management
and statistical analysis that can be provided by healthcare epi-
ADMINISTRATION OF AN INFECTION
demiologists (13,14). The tools of CQI can also be applied to
PREVENTION AND CONTROL PROGRAM
infection prevention and control programs to reduce the rate
of endemic infections, which constitute the majority of HAis In some settings, the healthcare epidemiologist is respon-
(15,16) (see Chapter 31). The healthcare epidemiologist can sible for the human and financial resources of the infection
also expand into other areas of quality management, such as prevention and control program. These responsibilities in-
clinical practice guideline development ( 17). The use of such clude developing and implementing the program's goals and
guidelines can minimize unwanted practice variation, improve objectives, recruiting and selecting staff, delegating responsi-
outcomes, and reduce healthcare costs. In particular, health- bilities, developing and controlling the budget, and reporting
care epidemiologists are expected to take a leadership role in to administration. Administrative responsibilities also include
antimicrobial stewardship (18). advocating for additional resources depending on local need
and ensuring an appropriate reporting mechanism to allow
for timely administrative action when infection prevention and
EDUCATION PROGRAMS
control issues are identified.
Good infection prevention practices can reduce both patient
and provider risk of HAis (19,20). Unfortunately, healthcare
COMMUNICATION
providers often fail to follow these basic practices, and compli-
ance among physicians is generally much lower than among The healthcare epidemiologist must maintain close communi-
other providers (21-27). Several studies have shown an alarm- cation with all other members of the infection prevention and
ing lack of infection prevention training and knowledge in this control team. Furthermore, healthcare epidemiology impacts
provider group (28-31). The healthcare epidemiologist is in nearly every area of healthcare delivery, including medical,
a unique position to promote and reinforce proper infection nursing, occupational health, microbiology, pharmacy, house-
prevention measures among physicians and medical trainees. keeping, logistical services, risk management, and patient
In academic settings, healthcare epidemiologists often are relations. Thus, the healthcare epidemiologist must maintain
Chapttr 2 • The Healthcare Epidemiologist 23
good communication with personnel in these areas. Informal as a hobby are unlikely to make the impact necessary for their
communication during clinical rounds or hallway conversa- healthcare systems to compete in the future. Scientific skills
tions often are as effective as formal consultations or meetings. will allow the epidemiologist to prevent infections and other
Thus, the healthcare epidemiologist should be a visible and ap- complications and to seek out and eliminate costly but inef-
proachable member of the infection prevention and control fective infection prevention and control traditions (ritual) and
team. Finally, he or she should ensure good external commu- quality management busywork. These skills should also help
nication on infection prevention and control-related issues in in product evaluation and selection. Most new products cost
conjunction with the public relations department. more than the products that they are designed to replace, but
few are worth the extra cost. Good epidemiology skills also are
needed to present accurate data to the administration and the
DISASTER PLANNING
medical committees in a concise and forceful format. Such
The healthcare epidemiologist should play a lead role in emer- data are difficult to ignore and can drive necessary change and
gency preparedness and response to pandemics, incidents of improvement.
bioterrorism, natural disasters, and other emergencies (38--40).
He or she should be involved in developing the healthcare fa-
LEADERSHIP SKILLS
cility's response plan, providing information and education on
protective measures for staff, stockpiling of medications and The healthcare epidemiologist requires leadership skills to be
supplies, and ensuring that robust surveillance systems are in effective in the complex healthcare environment. Effecting
place for prompt detection of an emerging infectious disease change and implementing policy, sometimes over the objec-
or potential emergency events or bioterrorism attacks. tions of many other physicians and hospital leaders, require
an effective leader. Leadership skills are necessary to develop
a vision and goals for the infection prevention and control
SKILLS AND SUPPORT NEEDED program and to foster team building to achieve these goals.
Healthcare epidemiologists who are responsible for program
The healthcare epidemiologist needs many skills to succeed administration also require time management, budgeting,
(Table 2.2). The discipline of infection prevention and con- planning, and human resource management skills. The health-
trol has increasingly incorporated epidemiologic principles care epidemiologist should consider leadership and manage-
and statistical analyses that are generally not learned in clini- ment training.
cal training. Thus, formal training in healthcare epidemiology
has become important. Few countries have established stan-
INTERPERSONAL SKILLS
dards or certified training programs for healthcare epidemi-
ology, although efforts are underway in Europe (36-41), and It is essential to know how to interact with people to get things
more universities now offer graduate-level training in infection done. The healthcare epidemiologist should be friendly, vis-
prevention and control. In the absence of training standards, ible, approachable, and known. The healthcare epidemiologist
healthcare epidemiologists must have sufficient knowledge and must have the confidence of the medical staff to persuade phy-
training to be viewed locally as credible authorities on infection sicians to change their ways when necessary. Negotiation skills
prevention and control and epidemiology, particularly by physi- are a valuable asset because change must often be negotiated
cians and health administrators. rather than mandated. The healthcare epidemiologist must
also have the confidence of the administration and be able to
negotiate the monetary and other support necessary to imple-
EPIDEMIOWGY SKILLS
ment change. It is important that administration be kept in-
The healthcare epidemiologist's most valuable tool is a thor- formed of the activities, successes, and needs of the infection
ough knowledge of the science of epidemiology and its associ- prevention and control department.
ated statistical tools. Those who treat healthcare epidemiology
CLINICAL SKILLS
TABLE 2.2 What You Need to Succeed A clinical background, although not essential, proves very use-
As a Hospital Epidemiologist ful to the healthcare epidemiologist. It allows for more seam-
Sldlk less integration into the healthcare delivery environment and
• Infection prevention and control knowledge enhances credibility with physicians and other clinical leaders.
• Epidemiology and statistical .skills It also creates opportunities to interact with, and provide im-
• Leadership skills mediate feedback to, other healthcare workers in the clinical
• lnterpe:nonal .skills setting (e.g., during "ward rounds") rather than adopting a
• Clinical skills purely administrative approach.
Support
• Partnership with infection prevention and control
professionals INFRASTRUCTURE REQUIREMENTS
• Effective reporting structure
One of the first management decisions a healthcare epidemi-
• Network of colleagues
ologist should make is to determine what support is needed
• Computer/software support
• Administrative support to do a good job. The healthcare epidemiologist is likely to
• Acontract be most effective when surrounded by a team of IPs and pro-
vided administrative support. He or she should report to both
a senior administrator (e.g., vice president of medical affairs)

and an influential infection prevention and control committee
TABLE 2.3 Future Opportunities for the
( 42). Developing a network of other healthcare epidemiolo- Hcalthc:arc Epidemiologist
gists through professional societies and scientific conferences • Improving quality in the fuce of reduced re&)urces
is another valuable resource. • Control of multidrug-re!istant organimls
Computers and software are essential to the modem infec- • Antimicrobial stewardship
tion prevention and control program (43) (see Chapter 8). • Mandatory healthcare worker immunization programs
Computers allow management of surveillance data to assess • Disaster planning
trends and find solutions to problems. The availability of elec- • Public reporting
tronic health records has eliminated the need for manual chart • Increased outpatient focus
• Clinical performance management and assessment
review. More recently, mobile devices, such as smart phones,
• New product/new technology assessment
have greatly facilitated real-time surveillance and process audits
(e.g., hand hygiene compliance). Pocket cameras can be used
effectively to document problems, such as clutter, and mobilize
teams to address these problems. The healthcare epidemiolo- of an adverse patient outcome. Thus, quality, not cost, may be
gist, in partnership with the IP, needs to select the best elec- the primary incentive for administrators to retain healthcare
tronic solutions for the hospital's needs, and must be familiar epidemiology expertise.
with the potential uses and limitations of the data management
systems within their organization.
THE FUTURE
NETWORKS
There will be many opportunities for healthcare epidemiolo-
Infection prevention and control networks are becoming an gists to apply their skills in the future (Table 2.3) (47,53-55).
invaluable resource for healthcare facilities without access to One of the major challenges will be improving quality in the
a well-trained healthcare epidemiologist, particularly at many face of declining resources. The need for healthcare epidemi-
community hospitals (see Chapter 10). Infection prevention ology expertise is increasing with mandated public reporting
and control networks can favorably impact HAl rates (44). Poli- of HAis, healthcare performance standards, and increased de-
cies, surveillance techniques, data analysis, education, outbreak mands of government regulation and patient advocacy groups.
investigation, and product evaluations are additional aspects of Healthcare epidemiologists have recently taken on more pro-
the infection prevention and control program that can be proactive roles in promoting patient safety through mandatory
vided effectively by a network (45). healthcare influenza vaccination programs (56). Clearly, the
well-trained and experienced epidemiologist will have many
challenges and opportunities ahead.
GETTING PAID
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29. Feather A, Stone SP, Wcssier A, et aL 'Now pleue wash your bands': the bandwuhing 2002;!0:145--152.
behaviour nf final MBBS candidateo.]H..p Infl&l. 2000;45:62-04. 49. Dunagan WC, Murphy DM, Hollenbealt CS, et a!. Making the buoine11 caoe for infection
!10. Allkarian M, Minaci K, Mundy LM, et al. AooCIIlllcDt nf knowledge, attitudeo, lllld prac- control: pitf.ollo and opportunitieo. Afll]Info:t ~ 2002;50:86-92.
tice& regarding ilolation prccautiono among Iranian healthcare worken. hlf«t Comrol H..p 50. Percnce?ich EN, Stone PW, Wright SB, eta!. Railing otandardl whilew.Jtcb:ing the bottom
~ 2005;26:10r....108. line: making a bwiness case for infection control. bif«:t CoMul H..p E;~ 2007;28:
st. Aokarian M, Honarvar B, Tabatabaee HR. et aL Knowledge, practice and attitude towards 1121-1155.
otandard illolation prccau.tiono in Iranian medicalotudentJ.] H..p Infect. 2004;58:292-296. 51. Haley KW. Mana![ing H..pitollnjraion CoMul for ~' A Strrsutr/ for R«l1u;ing
52. Simmono B, Braun BI, Steinberg ]P, et al. ffutory of SHEA.ponoored reocarch: time to Infrt:Mv.s ~-Chicago, n.: American Hoopita!Aooociation Publicationo; 1986.
pau the torch. Infta QmlrDl H..p F1M-iol. 2010;52:1~165. 52. Starling C. Infection control in developing countries. Curropinlnfo:tDU. 2001;14:461-466.
!!. Shqjania KG, Duncan BW, McDonald KM, et al. Making health care oafer: a critical analyoil 55. Wenzel RP. lnotituting health care reform and preoc!"''ing quality: role of the lu>opital ep>-
of patient llllfi:tr pmcticeo. Evii!.R.p :llduwl&,.., (Sum•). 2001;4S:i-x,1-008. dcllriologiot. Clmhlf«tDU. 1995;17:851-834; quiz 8!5-MS.
M. Berwick DM, CalkinJ DR, M<Uumon q, et al. The 100,000 lives Cli!Ilpaign: oetting a goal 54. Simmono BP, Parry MF, William• M, et al. The new era of hoopital epidemiology: what you
lllld a deadline for improving health care qualitr.JAMA· 2006;295:52~27. need to ou.cceed. Clinlnf«tDU. 1996;22:550-55!.
SS. Lynch P,Ja<bon M, SaintS. ReoearchPrioritieol'n!jcct, year 2000: eotabliohlng a direction 55. Ruef C. Proopective evaluation nf a hoopital epidemiologilt'o acti'ritieo at a European
for infe<:tion control and hoopital epidcllriology. Am] Inf«:t ConlroL 2001;29:7~78. tertiary-care medical center. Infta QmlrDIHosp F1M-iol. 1999;20:60~6.
!6. Duchner FD, Cauda R, Crundmann H, et aL Hoopital infe<:tion control in Europe: evalu- 56. 'Illlbot TR, Babcock H, Coplan AL, et al. Reviled SHEA pooition po;per: influenza .accina-
ation ofpreoent practice and future goab. Clin Mimlbiolhlfl&l. 2004;10:26!-266. tion of health care penonnel. hlf«:t CoMul H..p Epid.moioL 2010;51 :987--995.
3
Hand Hygiene
HISTORY OF HAND HYGIENE Guidelines on Hand Hygiene in Healthcare (6) have defined
alcohol·based handrubbing, where available, as the standard
Handwashing with soap and water has been comidered a of care for hand hygiene practices in healthcare settings,
measure of penonal hygiene for centuries (1,2), but the liDk whereas handwashing is reserved for particular situations only
between handwashing and the spread of disease has only been (6) (Table 3.1).
established in the last 200 years. In the mid-1800s, decades
before the discoveries of Pasteur and Lister, studies by Ignaz
Sem.melweis in Viewta and Oliver Wendell Holmes in Boston DEFINITIONS
established that hospital-acquired diaeases were trausmitted via
the hands ofhealthcareworkers (HCWs). In 1847, Semmelweis Hand hygiene is a general term referring to any action of hand
was appointed as a howe officer in one of the two obstetric cleansing. The purpose of performing hand hygiene during
clinics located at the University of Vienna Allgemeine Kranken· routine patient care is to remove microbial contamination ac-
haw (General He»pital). He observed that maternal mortality quired by recent contact with infected or colonized patients
rates, mostly due to puerperal fever, were substantially higher or with environmental sources and, in some cases, to remove
in one clinic compared to the other (16% vs. 7%) (3). He alsG organic matter from the hands. Hand hygiene during health·
noted that physicians and medical students often went directly care delivery can be performed either by handwashing or by
to the delivery suite after performing autopsies and had a handrubbing.
disagreeable odor on their bands, despite handwashing with StMtdartl lulm:lwtuhing with plain soap and water removes
soap and water before entering the clinic. He hypothesized lipid and adhering dirt, soil, and various organic substances
that "cadaverow particles" were transmitted via the bands Df from the bands, but it has minimal antimicrobial activity.
students and physicians and cawed the puerperal fever. & HJgWmie 1uJtrd ~is defined as the treatment of hands
a consequence, Semmelweis recommended that hands be with either an anweptic hand rub or an antimicrobial soap or
scrubbed in a chlorinated lime solution before every patient detergent and water to reduce the traruient microbial flora
contact and particularly after leaving the autopsy room. Fol- without necessarily affecting the resident skin flora (6).
lowing the implementatiGn of this measure, the mortality rate ~ lumd ndls are available as different formulations
dropped dramatically to ~% in the clinic most affected. This (liquid, gels, foams) and bypass the need for an exogenous
intervention represents the first evidence that cleansing heavily source of water and towels or other hand-drying devices. Accord-
contaminated hands with an antiseptic agent can reduce noso- ing to the CDC guidelines (12) and WHO recoDWlendatiows (6),
comial transmission of microorganisms more effectively than when an alcohol-based hand rub is available it should be wed as
handwashing with plain soap and water. Unfortunately, both the preferred means for routine hand hygiene in healthcare.
Holmes and Semmelweis failed to observe a swtained change Indications for performing hand hygiene and for opting
in their colleagues' behavior. for handwashing rather than handrubbing are discussed below
A pre»pective controlled trial conducted in a hospital nUill- and listed in Table !U.
ery ( 4) and investigations conducted during the past 40 years
have confirmed the critical role that contaminated HCWs'
hands play in the tranamission ofbealthcare-associated patho- TRANS:MISSION OF MICROORGANISMS
gens (5,6). The 1980s represented a landmark. in the evo- AND HAND HYGIENE BEHAVIOR
lution of concepts of hand hygiene in healthcare. The tint
national hand hygiene guidelines were published in the A clear understanding of the process of hand-pathogen trans-
United States in the 1980s ('1-9), followed by several others mission is critical to successful education strategies, assess-
in more recent years in different countries. In 1995 and 1996, ment of HCWs' band hygiene performance, and research.
the US Centers for Disease Control and Prevention's (CDC) An evidence-based model of hand transmission was proposed
Healthcare Infection Control Practices Advisory Committee by Pittet et al. and served as a basis for the recently reviewed
(lllCPAC) recommended that either an antimicrobial soap or recommendations on indications for hand hygiene action
a waterless antiseptic agent be used for cleansing hands upon (5,6). According to this model, the transmission ofhealthcare-
leaving the rooms of patient! with multidrug-resistant patho- associated pathogens from one patient to another or within the
gens (10,11). More recently, the CDC/HICPAC guidelines is- same patient from one body site to another via HCWs' hands
sued in 2002 (12) and the World Health Organization (WHO) requires five sequential steps (FigUre 3.1). It is important
26
Indkations for Handwaahing and Hand AntisepsJB
• Wash banda with aoap and water when visibly dirty or contaminated with proteinaceoWI material, or visibly soiled with blood or other body
ftuida, or if expoaure to potential spore-forming orpnisms is strongly su.pected or proven (m), or after uaiDJ the reatroom (D).
• Preferably use an alcohol~ hand Nb for routine band antileplis in all other cliDical siruatiOliB desaibed in itema (a) to (f) lilted below
if banda are not visibly loiled (lA). AlternatiYely, wuh bands with soap and water (m).
• Perform band hygiene:
(a) before and after having direct contact with patients (m);
(b) after remoring giOYes (m);
(c) before handling an invasiYe device for patient care, reprdleas of whether or not gloves are UJed (m);
(d) after contact with body fluids or excretions, mucous membranes, nonintact akin, or wound dreaainga (IA);
(e) if moving from a contaminated body site to a clean body site during patient care (m);
(t) after contact with inanimate objects (including medical equipment) in the immediate vicinitf of the padent (m).
• Wash banda with either pbin or antimicrobial soap and water or rub banda with an alcohol~d formulation before handling medication
or preparing food (m).
• When alcohol-based band rub is already used, do not use antimicrobial aoap concomitantly (D).
Adapted &om the WHO GWWn&rfor Ht#Ul HJP'M in HlllltA c,_ Geneva, Switzerland: World Health Organization; 2009.
F.igure 3.1. The model for hand transmi.nion of microbial pathogem. ~ 1: ~ Jlf'fWIIft OtJ JNriUMt
, . , Ql' tM iMtei-a -wo-mt Both the patient lkin and the inanimate environment harbor large amounts
of organiama including multiresistant bacteria, fungi, and v.iruses. S,. 2: o.p..imtlriiNfor em HCW•' ~tad~.
Hand skin acquires transient Oora by exposure to colonized objects, inanimate surfaces, and patients. Cloves
do not provide complete protection against hand contamination. S,. J: o...,amt ftln1WalMiuwU. Hand
colonization with transient &ora as well as with potential pathogens progrea.sively inaease& during patient
care according to their differing capacitf to survive on skin. S#; 4: Dttjitdiiw 1uJM 1r.J1i- n:nllt.r V.hortd.r
~· 11fa eirtrrlrd, Adequate (appropriate duration and Cull coverage of band surfaces) and timely (when
indicated) hand hygiene technique is essential for the effective removal of contamination and to prevent
permtent colonization. Wearing rings and artificial fingernails increases the frequency of hand contamination
and has been associated with infection outbreab. Step J: Com inatecl "-ds ~ mprAn1u. Failure to
practice hand hygiene between sequential hand-surface exposures re.mlts in HCWa' hands acting as organism
carriers ready to spread potentially harmful pathogens onto another surface. Once deposited on patients, the
cro.u-transmitted organisms may establish either a carrier atate or lead directly to infect.ion.(Adapted from
Pittet D, Allegrami B, Sax H, et al. E.vidence-baled model for hand transmission during patient care and the
role af improved practices. lAtu:IJt lnftJct Dis. 2006;6:641-652.)
28 Sectitml • GmmJl ~ qJHospilallnftc#tms
to recall that in addition to tramfer of pathogens from the

TABLE 3.2 .Main Facton IDfluencing
hospital enviroWllent or patient-to-patient transmiasion,
pathogen tramfer can occur within the 3allle patient from a .Adhaalcc to Hand Hygicue
colonized area to a clean body site or onto an invasive medical Praaic:es
device. Given that most healthcare-associated infections (HAls) INDIVIDUAL LEVEL:
are of endogenoua nature, this latter pathway of transmission • Lack of education or experience
by HCWs' bands is of the utmost etiologic importance. • Being a physician, compared to other healthcare profeaaionals
Recent epidemiologic investigations on HCWs' compliance • Lack of knowledge of guidelinea
with hand hygiene recommendations have revealed key find- • Being a refnu:tory noncomplier
ings. According to the literature, in the absence of hand hy· • Skin irritation by hand hygiene agenta
giene promotion, compliance has been unacceptably poor in CROUP LEVEL:
many countries worldwide with mean baseline rates ranging • Lack of education or Jack of performance feedback
from 5% to89% and an overall average ofabout40% (reviewed • Working in aitical care or in high~ conditiom
in detail in (6) with selected subsequent reference& including • Downsizing or underltafling
(13-1 7)). Very low compliance rates have been reported espe- • Lack of eocouragemeot or role model from key staJf
cially in poorly resourced settings (18-25). The predictors of INSTITUTIONAL LEVEL:
poor adherence to recommended hand hygiene measures dur- • Lack of written guidelinea
ing routine patient care have been identified (6), and include • Lack of suitable hand hygiene agena
• Lack of skin care promotion or agents
professional category (13-15,26,27), hospital ward (14,28,29),
• Lack of aJlture or ttadition of compliance
time of day/week (~.~1), glove use (26,~2-~5), and type and
• Lack of ac:lmmiJttati\oe leadership, 11a11ctions, rewards, or
intensity of patient care, defined either as the number ofoppor· support
tuniti.es for hand hygiene per hour of patient care (Figure ~-2)
COVEilNMEN'L\L LEVEL:
or patient-to-nurse ratio (Table ~-2) (13-14,28). Moreover,
• Lack of awareneaa and commitment repnling the importance
hand hygiene compliance is frequently poorer before patient ofhealthc:are-eaaociated iofection
contact than after (6,14,26,31,36), although this is not always • Lack of apecific regulatiODJ and policiea on prevention of
observed (29). healthcare-usodated infection
Perceived barriers to adherence with hand hygiene guide- • Lack of national guidelinea on band hygiene in healthcare
lines have been assessed or quantified in observational stud· • Lack of promotion of national or regional campaigns to
ies (6). Among others, they include skin initation caused by imprO'Ie hand hygiene in healthcare
hand hygiene agents (34), inaccessible hand hygiene supplies • IDJuJiicient allocation of financial reaourcea for tlUs purpoae
(1~,15), interference with HCW-patient relationships, patient
needs perceived as a priority over hand hygiene, forgetfulness,
Jack of knowledge of guidelines, insufficient time for hand hy- HAND ANTISEPSIS AGENTS
giene (34), and high workload and understaffing (Thble 3.2).
Adherence may be better when patients are under contact Antiseptic agents (both soap and hand rubs) contain an anti-
precautions (15,37). microbial substance, which reduce& or inhibits the growth of
microorganisms on living tissues. The most popular agents are
brielly described below and swnmarized in Table 3.3.
Amongst hand antisepsis agents, alcohols have the broadest
spectrum of antimicrobial activity with excellent in vitro and in
100 vivo activity against gram-positive and gram-negative bacteria
.. (including multidrug-resistant pathogens such as methicillin-
Q)
resistant Staphylococcus aumu [MRSA] and vancomycin-resistant
c Enterococci [VRE]), Mycobaamum tuben:ulosis, and a variety of
Q) 75
-~ fungi (~8-47). Mycobacteria and fungi also are killed by iodo-
..r::
"0
phors, but less effectively by chlorhe:xidine, chloroxylenol, and
c hexachlorophene. Most enveloped (lipophilic) viruses, such as
ro
..r:: 50 herpes simplex virus, l:{[Y, influenza virus, respiratory syncytial
£ virus, and vaccinia virus, are susceptible to alcohols, chlorbexi-
·~
dine, and iodophors (38,48-57). Other enveloped viruses

~
c (hepatitis B virus and probably hepatitis C virus) are somewhat
ro 25 less susceptible to alcohols, but are killed by concentrations as
Ci
E high as 60% to 70% (v/v) (58). In some in vivo studies, alcohols
8 . .. also showed some activity against a number of nonenveloped
viruses (rotavirus, adenovirus, rhinovirus, hepatitis A virus, and
0
enteroviruses) (59-6~). In general, ethanol has greater activity
0 25 50 75 100 against viruses than isopropanol (64). Iodophors, and to ami-
Opportunities for hand hygiene per hour of care nor extent chlorhexidine, also are active against some nonen-
Flpre 3.2-. The relation between the number of opportunities veloped viruses. None of the listed antiseptic agents bas activity
for hand hygiene and compliance. (Reproduced with permission from against bacterial spores or protozoan OOC)I3t3. Iod.ophors are
Pittet D, Mourouga P, Pemeger 1V. Compliance with handwashing only slightly sporicidal, but at higher concentrations than the
in a teaching hospital. Ann ImM«l. 1999; 130:12~180.) ones used in antiseptics (65).
-~%\ :f fi , , . Preparations for Hand Hygiene
Gram-Positive Gram-Negative Enveloped N onenveloped Speed Residual
Agent Bacteria Bacteria Mycobacteria Fungi V11"Wi V11"Wi Spores of Action Activity Use
Alcohols +++ +++ +++ +++ ++ + - Fast No HR
Chlorhexidine +++ ++ + + ++ + - Intermediate Yes HR,HW
Chloroxylenol +++ + + + + +!- - Slow Contradictory HW
Hexachlorophene" +++ + + + ? ? - Slow Yes HW, but not
recommended
Iodophors +++ +++ ++ ++ ++ ++ +J-b Intermediate Contradictory HW
Quaternary ammonium ++ + +!- +!- + ? - Slow No HR, HW; seldom;
compounds' +alcohols
Triclosan 4 +++ ++ +/- +!-' ? ? - Intermediate Yes HW;seldom
HR, handrubbing; HW, handwashing

Activity: + + +, excellent; + +, good, but does not include the entire bacterial spectrum; +, fair; +I-, controversial; -, no activity; ?, insufficient data.
"Bacteriostatic.
bJ:n concentrations wed in antiseptics, iodophors are not sporicidal.
"Bacteriostatic, fungistatic, and microbicidal at high concentrations.
"Mosdy bacteriostatic.
'Activity against Candida spp., but little activity against filamentous fungi.
~
Alcohols are the most frequently used antimicrobial com- activity against Mycobacteria and fungi and greater activity
ponent of hand rubs. Alcohol-based hand rubs are considered against lipophilic viruses.
the most effective antiseptic agents for hand hygiene, and they Triclosan is a nonionic, colorless substance that has antimi-
generally contain either ethanol, isopropanol, or n-propanol, crobial activity at concentrations ranging from 0.2% to 2.0%,
or a combination of two of these products. Alcohol solutions but tends to be bacteriostatic (1). Like chlorhexidine, triclosan
containing 60% to 80% (v/v) alcohol are most effective, has persistent activity on the skin. According to the FDA, the
with both higher and lower concentrations being less potent available data are insufficient to classify it as safe and effective
(39,40,66). Alcohols are more effective than plain soap, and for hand antisepsis (96).
in the vast m,Yority of trials they reduced bacterial counts on Every new formulation for hand antisepsis should be
hands to a greater extent than washing hands with soaps or tested for its antimicrobial efficacy to demonstrate that it
detergents containing hexachlorophene, povidone-iodine, 4% has superior efficacy over normal soap or meets an agreed
chlorhexidine, or triclosan (67,68). Several forms of alcohol- performance standard. The most appropriate method is to
based products are available, including rinses (low-viscosity so- artificially contaminate volunteers' hands with the test or-
lutions), gels, and foams. The efficacy of each product should ganism before applying the test formulation. In Europe, the
be confirmed as this will vary according to its formulation and most commonly used test methods are those of the Euro-
the concentration of its active components (6,69-75). The pean Committee for Standardization (CEN): EN 1499 (98)
WHO-recommended alcohol-based formulations contain ei- for antiseptic soaps and EN 1500 (99) for hand rubs. These
ther ethanol (80% v/v) or isopropyl alcohol (75% v/v), and use a randomized, cross-over design and compare the prod-
can be produced locally to reduce costs (6,21,76). uct with a standardized reference agent. In the United States,
Chlorhexidine gluconate has been incorporated into a antiseptics are regulated by the FDA (96), which refers to the
number of hand hygiene preparations. Aqueous or deter- standards of the American Society for Testing and Materials
gent formulations containing 0.5%, 0.75%, or 1% chlorhexi- (ASTM). The most frequently used method for testing hand-
dine are more effective than plain soap, but are less effective washing and handrubbing agents is the ASTM E-1174 (100).
than antiseptic detergent preparations containing 2% and 4% The shortcomings of current test methods are discussed in
chlorhexidine gluconate (77,78). Chlorhexidine's immediate detail elsewhere (6,73).
antimicrobial activity is slower than that of alcohols, but it has
significant residual activity (77-84). Chlorhexidine resistance
attributable to plasmid-borne qacA/B genes that code for mul- INDICATIONS FOR HAND HYGIENE
tidrug effiux pumps is being increasingly reported, though DURING HEALTHCARE
the impact of this phenomenon on the effectiveness of hand
hygiene products containing chlorhexidine is not well-defined Effective hand hygiene should remove transient flora on
(85--88). HCWs' hands at critical moments during care activity with
Iodophors are composed of elemental iodine, iodide or tri- the clear objective to prevent cross-transmission of potentially
iodide, and a polymer carrier of high molecular weight, such as harmful organisms and infection. A set of indications for hand
polyvinyl pyrrolidone (povidone) and ethoxylated nonionic de- hygiene has been established according to scientific evidence
tergents (poloxamers) (52,89). Their persistent antimicrobial and is congruent with the model of transmission (see above) .
activity is controversial. Most iodophor preparations used for These indications are listed in the most recent international
hand hygiene contain 7.5% to 10% povidone-iodine. guidelines and graded according to supporting evidence
Chloroxylenol has been widely used in antimicrobial soaps (Thble 3.1) (6,101). To support their application at the point
and as a preservative in cosmetics and other products. It has of care, a new concept was developed by WHO on the basis
good in vitro activity against gram-positive organisms and fair of expert advice and scientific evidence that condenses these
activity against gram-negative bacteria, Mycobacteria, and indications into five moments when hand hygiene is required
some viruses (1,90,91); in particular, the activity against Pseur (6,102). This approach proposes a unified vision for HCWs,
domonas aeruginosa is limited. Chloroxylenol is considered to trainers, and observers to minimize interindividual variation
be less rapidly active than chlorhexidine gluconate or iodo- and facilitate training, understanding, monitoring, and report-
phors, and its residual activity is less pronounced than that of ing of hand hygiene indications, and achieving best practices.
chlorhexidine (90,91). According to this concept, HCWs are requested to clean their
Hexachlorophene is a bisphenol contained in emulsions hands (a) before touching a patient; (b) before clean/aseptic
used for hygienic handwashing and for patient bathing. It has procedures; (c) after body fluid exposure/risk; (d) after touch-
residual activity for several hours after use and a cumulative ing a patient; and (e) after touching patient surroundings. This
effect (1,92-94). Because of its high rates of dermal absorp- concept has been integrated into the various WHO tools for
tion and subsequent toxic effects, including neurotoxicity the implementation of the WHO Guidelines (103) and has
(95), the agent is classified by the U.S. Food and Drug Admin- been adopted worldwide, including in national hand hygiene
istration (FDA) as not safe and effective for use as an antisep- guidelines (Figure 3.3).
tic agent for handwashing and has been banned worldwide According to the model of transmission, hand hygiene
(64,96,97). before a patient contact or an invasive procedure is aimed at
Quaternary ammonium compounds belong to a large group; protecting the patient. In contrast, hand hygiene after tasks or
alkyl benzalkonium chlorides have been the most widely used contact with patients and their immediate surroundings serves
antiseptics. They are primarily bacteriostatic and fungistatic, to protect the HCW against colonization and infection and
although microbicidal at high concentrations against some or- to prevent pathogen spread to the environment. As discussed
ganisms (1). They are more active against gram-positive bacte- above, HCWs more often comply with the indications after a
ria than against gram-negative bacilli, and have relatively weak patient contact or after a healthcare task.
My 5 moments for
HAND HYGIENE
I
,, .,.--------------~ ' \
\
' '
'\
\ .... ________ _
Figure 3.3. ~My five moments for hand hygiene." (Reproduced
with permission from Sax H, Allegrami. B, Uclay I, et al. ~My five
'
moments for hand hygiene•: a U!!ei'-centred design approach to
undentand, train, monitor and report hand hygiene.] Hot~p Inftx:t.
2007;67:9-21.)
For practical pwpwes, it is important to recogllize that two decades, :several studies have demonstrated the effectiveness
or more of the listed indications might occur simultaneously of such strategies on improving this process indicator, mostly
during a sequence of care requiring only a single hand hy- based on a multimodal approach (6,21,27,108-126).
giene action. The guidelines also describe optimal techniques It is evident that the most valuable method to demonstrate
for handrubbing and handwashing, and specify that the latter the impact of hand hygiene improvement ill to detect a sig-
be reserved only for situatiom where hands are visibly soiled, nificant reduction of HAI rates in the study-intervention set-
where transmDaion of spores is strongly suspected or proven, ting. Ideally, this key research question should be investigated
and after using the restroom (6) (Table 3.1). through controlled (cluster) randomized studies focusing only
Hand hygiene should be performed after glove removal be- on hand hygiene interventions and adjusting for confounders.
cause wearing gloves does not completely prevent hand con- For several reasons, particularly ethical, most publillhed stud-
tamination (6,26,1~107). Moreover, hand hygiene should be ies on thill topic are observational, before-after intervention
performed when an indication occurs, regardless of whether investigations. Despite this lower quality design, many studie,s
gloves are worn or not (6,12). focusing on hand hygiene as the single new intervention imple-
mented during the study period demonstrated a temporal re-
lation between improved hand hygiene practices and reduced
IMPACT OF HAND HYGIENE infection rates (Table 8.4), and several reported a sustained
PROMOTION effect over a prolonged period of time (1 08-114,127-132).
In addition, over the past decade, an increasing number
The positive effect of hand hygiene promotion, in particular of studies have investigated the temporal association between
through multimodal strategies, is usually demonstrated by an hand hygiene product consumption and HAis, particularly
increase in hand hygiene compliance, which is meant to reflect focusing on alcohoJ,.based hand rub and :MRSA bacteremia
actual HCWs' practices at the point of care. Over the past two (111,112,132-141). Many of these studies demonstrated that
TABLE 3.4 .Assodation between Hand Hygiene lm.pmvcma1t and. Healt~KaJ...:-AIIoc:iatcd Infection
Rata: Hospital-Baaed Stadia, from 1995 to .lOll
Duration of
Year Hospital Setting Follow-Up
1995 Zalar et al. (155) Newborn nunery Control of an MRSA outbreak using a tricloaan 5.5yeara
preparation for hand antiaepsia, in addition
to other infection control meaaurea.
2000 Larson et aL (255) MICU/NICU Significant (85%) relathe reduction ofVRE rate in 8montlu
the intervention hospital; relative reduction in
control hoepital (44%, NS); no aip!ificant change
inMRSA.
(um#nued)
32 S«tion I • General ConsideratWns ofHospital Infections
TABLE 3.4 .Association bc:twccn Hand Hygiene Improvement and Hcalthcarc-.Assoc:iatcd Infection
Rates: Hospital-Based Studies, from 1995 to 2011 (C..ti•Wil)
Duration of
Year Authon Hospital Setting Significant Results Follow-Up
2000 Pittet et al. (127,254) Hospital-wide Significant reduction in the annual overall prevalence 8years
of HAl (41.5%) and MltSA crou-transmi5sion
rates (87%). Active surveillance cultures and con-
tact precautions were implemented during the
same time period. Cost-dfectiveness was demon-
strated in a subsequent analysis after 8 years.
2003 Hilburn et al. (255) Orthopedic surgical unit 36.1% decrease in infection rates (from 8.2% to 5.3 %) •. 10 months
2004 MacDonald et al. (256) Hospital-wide Significant reduction in hospital-acquired MltSA cases 1 year
(from 1.9% to 0.9%).
2004 Swoboda et al. (257) Adult intennediate Reduction in HAl rates (NS). 2.5 months
care unit
2004 Lam et al. (162) NICU Reduction (NS) in HAl rates (from 11.3/ 1,000 6months
patient-days to 6.2/ 1,000 patient-days).
2004 Won et al. (128) NICU Significant reduction in HAl rates (from 15.1/ 1,000 2 years
patient-days to 10.7/ 1,000 patient-days),
in particular for respiratory infections.
2005 Gordin et al. (129) Hospital-wide Significant reduction in nosocomially acquired MltSA 3years
(21 %) and VRE (41 %).
2005 Zerr et al. ( 130) Hospital-wide Significant reduction in hospital-aMociated rotavirus 4years
infections.
2005 Rosenthal et al. (131) AdultiCUs Significant reduction in HAl rates (from 47.5/1,000 21 months
patient-days to 27.9/ 1,000 patient-days).
2005 Johnson et al. (132) Hospital-wide Significantreduction (57%) in MltSA bacteremia. 36months
2007 Le et al. (108) Neurosurgery Reduction (54%, NS) of overall incidence ofSSiwith 2 years
significantly lower incidence in the intervention
ward. Significant reduction of superficial SSI.
2007 Pessoa.Silva et al. (109) Neonatal unit Reduction of overall HAl rates (from 11 to 8.2/ 1,000 27months
patient-days)" and 60% decrease of HAl risk in
very low birth-weight neonates (from 15.5 to
8.8/1,000 patient-days).
2008 Grayson et al. (111) 1) 6 pilot hospitals 1) Significant reduction of MltSA bacteremia (from 1) 2 years
0.05/100 to 0.02/ 100 patient-discharges per
month) and of clinical MRSA isolates.
2) all public hospitals 2) Significant reduction of MltSA bacteremia (from 2) 1 year
in Victoria (Australia) 0.03/100 to 0.01/100 patient-discharges per
month) and of clinical MRSA isolates.
2008 Capretti et al. (258) NICU Significantreduction of HAl incidence (4.1/ 1,000 18 months
patient-days vs. 1.2/ 1,000 patient-days) .
2008 Cromer et al. (259) Hospital-wide Significant reduction in facility-acquired MRSA from 10 months
0.85 to 0.52 per 1,000 patient-days.
2008 Nguyen et al. (18) Urology ward Significant reduction in HAl incidence from 13.1% 6months
to 2.1%.
2009 Lederer et al. (110) Hospital-wide, 7 acute-care Significant reduction of MRSA rates from 0.52 to 3years
facilities 0.24 episodes/1,000 patient-days.
2009 McLaws et al. (115) Hospital-wide in 208 public Significant reduction of 6% of overall MltSA infec- 18 months
hospitals (statewide) tions/10,000 patient-days; reduction of16% in
MRSA infection in nonsterile sites in ICU and of
25% in sterile sites in non-ICU wards.
2010 Helder et al. (116) NICU Significant reduction in the incidence of BSI (from 18 months
44.5% to 36.1 %) and of overall HAl (from 17.3 to
13.5/1,000 patient-days).
2010 Cheng et al. (260) AdultiCU Significant reduction of incidence density of ICU- 3years
onset bacteremic and nonbacteremic MRSA infec-
tion in the intervention units.
Chapter 3 • Hand Hygiem 33
TABLE 3.4 Association betwc:cn Hand Hygiene Improvement and Hcalthcare-.Assodatcd Infcction
Rates: Hospital-Based Studies, &om 1995 to 2011 (Colffi1111M)
Duration of
Year Authors Hospital Setting Signif'ICIID.t Results Follow-Up
2011 Yeung et al. ( 117) 7LTCFs In the intervention LTCFs, significant reduction of 7months
incidence of serious infections (from 1.42 to
0.65 cases/1,000 resident-days) and significant
reduction of mortality due to infection.
2011 Barrera et al. ( 11!I) 6ICUs Significant reduction of CLA-BSI incidence over time lt5years
(-12.7% per year).
2011 Chen etal. (114) Hospital-wide 8.9% decrease in HAis. Significant decrease lt5years
of BSI, UTI, and skin and soft tissue infections.
Every US$1 spent on HH could result in a
US$23.7 benefit.
2011 Garcia-Vazquez ICU Significant HAl reduction from 13.7% to 8.3%. 6months
et al. (118)
2011 Koff et al. (119) ICU Significant reduction ofVAP (from 3.7 to 6.9 12 months
episodes/1,000 ventilation-days).
2011 Grapon et al. (112) Nationwide (521 hospitals) Significant reduction of BSI MRSA (p = 0.008) . 2 years
HAl, healthcare-associated infection; ICU, intensive care unit; NICU, neonatal intensive care unit; MRSA, methicillin-re!istant Staph]lococcus
aurew; MICU, medical intensive care unit; NS, not statistically !ignificant; BSI, bloodstream infections; LTCFs, long-term care facilities.
"Statistics not reported.
an increase in alcohol-based hand rub consumption correlated

significantly with a reduction of MRSA bacteremia or the inci-
TABLE3.5 Strategies for Successful
dence ofMRSA clinical isolates, as shown by Sroka et al. in their Promotion of Hand Hygiene
review and data pooling (142). Although it remains important in Hospitals
to generate additional scientific and causal evidence for the im- Strategy
pact of enhanced adherence with hand hygiene on HAl rates in
healthcare settings, these results strongly suggest that improved 1. System change (113,114,117-119,127,151,
hand hygiene practices reduce the risk of transmission of Make hand hygiene po ssible, 161,162,179,257,261-264)
pathogenic microorganisms. easy, convenient (18,127,128,148,149,151,
Make alcohol-based hand rub 15!1,154,265)
available
2. Education (6,105,116,266--269)
STRATEGIES TO PROMOTE 3. Routine observation (6,105,122,127,152-154,
HAND HYGIENE and feedback 161 ,262,263,270--272)
4. Reminders in the workplace (6,110,273,274)
Understanding the factors influencing HCW behavior and re-
sulting in poor hand hygiene practice is essential to identify 5. Improvement of institutional (6,116,122,182,272,275-277)
the best strategies to achieve improvement. Over the last three safety climate (through active
participation and enhanced
decades, many investigations have explored the optimal ap-
self~fficacy at individual and
proaches to overcome barriers and achieve hand hygiene best institutional levels)
practices. In early studies, improvement was pursued through
6. Avoid overcrowding, (28,127,156,278,279)
the promotion of handwashing with antimicrobial soaps and
understaffing, excessive
water (143-146), mostly through HCW education. Later, many
workload
studies showed a significant increase in hand hygiene compli-
ance after the introduction of hand rubs (28,127,147-164). 7. Administrative sanction/ (6,122,128,171,172,280)
rewarding
However, HCWs' behavioral attitudes toward compliance
with recommended practices are complex and multifactorial 8. Patient education and (6,148,241 ,245--251)
(6,165--170), and, therefore, successful hand hygiene improve- participation
ment strategy programs must be multidisciplinary and multifac- 9. Combine several of the above (6,21 ,27,108,110--124,126,252,
eted, as demonstrated by many studies (Table 3.5). strategies 272,280,281)
Some of these strategic elements may be unnecessary in
"'nly selected references h ave been listed.
certain settings, but may be helpful in others. To establish
Adapted with permission from lW/0 Guidelines fur Hand HygWrie in
whether single factors, such as increased education, individual Hmlth Cmr. Geneva, Switzerland: World Health Organization; 2009.
reinforcement technique, appropriate rewarding, administrative
sanction, enhanced self-participation, active involvement of By contrast, conducting covert observations to avoid this prob-
a larger number of organizational leaders, enhanced percep- lem can create a climate of mistrust among observed HCWs
tion of health threat, self-efficacy, and perceived social pressure and jeopardize the value of performance feedback, essential
(169,171-174), or combinations of these factors actually deter- to multimodal strategies. On the basis of studies conducted at
mine the improvement of HCWs' adherence to hand hygiene the University Hospitals of Geneva (28,127), WHO developed
requires further research. Ultimately, adherence to recom- a standardized method for direct observation and associated
mended hand hygiene practices should become part of a patient tools (184-186). By focusing on the five key hand hygiene indi-
safety culture, where a set of interdependent elements of qual- cations ("My five moments for hand hygiene"), this method is
ity interact to achieve the shared objective (175). On the basis designed to be relatively simple to apply and can be learned with
of published evidence, the WHO developed the Hand Hygiene the support of educational tools and training films (187,188).
Multimodal Improvement Strategy (176), which includes the Collecting data on local hand hygiene performance and pro-
following five key components with the above-mentioned "My viding regular feedback to the concerned HCWs is a very pow-
five moments for hand hygiene" concept at its core (6,102): sys- erful approach to raise awareness about defective practices and
tem change, staff training and education, monitoring of hand achieve improvement.
hygiene indicators and performance feedback, reminders in If monitoring hand hygiene compliance becomes part of
the work place, and improvement of the institutional patient regular activities within an ongoing campaign, the Hawthorne
safety climate (Figure 3.3). Tiris strategy was tested in a broad effect is likely to be neutralized. Many recent reports demon-
range of settings worldwide, and its implementation proved to strate that repeated, regular compliance monitoring is feasible,
be feasible and led to the improvement of hand hygiene in- even at the national level (14,112,177). Hand hygiene perfor-
frastructure, significant increase of hand hygiene compliance, mance is also increasingly used as a quality indicator for exter-
HCWs' knowledge, and perception of the importance of hand nal benchmarking and public reporting (189,190). In addition,
hygiene (6,21). It has also been adopted in many national cam- innovative systems for automatic (electronic or video) monitor-
paigns, in more than 15,000 healthcare settings worldwide as re- ing (191) and web-based data collection and entry applications
ported to the WHO (http://www.who.int/gpsc/en/), and used using mobile devices (112) can facilitate data collection and
in several published studies (111,112,120,121,123,177-180). A minimize the human resources and time required.
guidance document to the application of the strategy and re- Using consumption of hand hygiene products, in particu-
lated technical and implementation principles in outpatient and lar alcohol-based hand rub, as a surrogate marker of compli-
home care and long-term care facilities has been recently issued ance has become very popular, and is part of infection control
byWHO (181). indicators at the national level in some countries. Over time,
Although multimodal strategies are comprehensive and usu- trends can be easily calculated through regularly available data
ally effective in stimulating behavior change and improvement and these have been correlated with MRSA incidence in several
of hand hygiene indicators, their complexity may raise con- studies. Although tracking this indicator provides useful infor-
cerns regarding their long-term sustainability. However, some mation about the implementation of hand hygiene campaigns,
recent studies demonstrated the maintenance of improvement caution should be exercised when using product consumption
and the possibility of overcoming persistent barriers through to replace hand hygiene compliance monitoring (192). Con-
positive deviance and reinforcement (122,178,182). Addition- sumption can be overestimated and may not reflect actual use
ally, WHO recently issued the Hand Hygiene Self-Assessment only by HCWs (or use at the correct time). In particular, this
Framework, a tool that provides a situation analysis of hand surrogate marker does not provide information on actual com-
hygiene and practices within an individual healthcare facility pliance according to real hand hygiene opportunities and re-
(183). This can be used at baseline and repeated regularly to lated actions, and cannot be used to motivate a change in staff
identify key areas for improvement, thus adapting the multi- behavior as it does not reflect their practices.
modal promotion to the local context and monitoring progress
and achievements, including sustainment over time.
EFFICACY OF ALCOHOL-BASED HAND
RUBS AGAINST CWSTRIDIUM DIFFICILE
AND NOROVIR.US
MAIN CONTROVERSIES IN THE FIELD
No hand hygiene agent is reliably sporicidal against Clostridium
OF HAND HYGIENE IN HEALTHCARE spp. or Bacillus spp. at concentrations tolerated by human skin.
For this reason, handwashing with plain soap and water is rec-
CHALLENGES WITH HAND HYGffiNE
ommended if exposure to these organisms is strongly suspected
MONITORING
or proven (Table 3.1) because the mechanical action of friction
Monitoring hand hygiene performance is of crucial importance and rinsing helps eliminate these microorganisms (6). How-
to assess baseline compliance by HCWs, provide feedback to ever, given the preference for alcohol-based hand rubs in most
HCWs, evaluate the impact of promotion interventions, investi- other situations for hand hygiene in healthcare over the last
gate outbreaks, and to answer research questions (6). However, decade, concem has been raised about their potential role in
selecting the most suitable indicators and methods as well as large outbreaks and increasing trends of C. difficile incidence
performing regular monitoring can be challenging. Unobtru- in some countries (193-195). However, in the United States,
sive direct observation of hand hygiene practices by a trained C. diffo;ilM.ssociated disease rates began to rise long before the
observer is considered the gold standard to evaluate compli- large-scale use of alcohol-based hand rubs (196), and it has
ance, although an inherent bias might arise as disclosure of the been acknowledged that the spread has mainly been due to
observer's activity may influence the behavior of those being the emergence of a previously rare and now more lethal strain
observed toward a higher compliance ("Hawthorne effect") . (ribotype 027). Several publications have demonstrated a lack
of correlation between the increased use of alcohol-based care management, and routine use of moisturizing skin care
hand rubs and the incidence of clinical isolates of C. difftcile products.
(133,134,197-199). Furthermore, one large outbreak was suc- Other adverse events that may prompt concerns about
cessfully managed while introducing alcohol-based hand rub the use of alcohol-based hand rubs are ingestion, dermal ab-
for all patients, other than those with C. difftcil6-associated dis- sorption, and inhalation. Accidental or intentional ingestion
ease (200). Finally, during the implementation period of the of alcohol-based hand rubs may lead to acute, and in some
English "Cleanyourhands" national campaign, mainly focused cases severe, alcohol intoxication (6,225--227) . Until recently,
on alcohol-based hand rub availability at the point of care, a de- these notifications have been rare and related to unique con-
crease in C. difficile infection was obseiVed (141). Contact pre- ditions, even in the context of large-scale campaigns, such as
cautions should be emphasized for C. difficile control, especially the one implemented in England and Wales for several years
the systematic use of gloves and gowns, adequate isolation or (228). However, Gormley et al. recently reviewed the US Na-
cohorting of patients affected by C. difftcile-associated disease, tional Poison Data System and found that the number of new
and appropriate environmental control measures. Hand hy- cases per year of intentional alcohol-based hand rub ingestion
giene (in this case, handwashing) also plays an important role, significantly increased between 2005 and 2009, although the
but the preferred use of alcohol-based hand rub for all other vast moyority of cases had a favorable outcome (229). While an
instances should be maintained. awareness of this risk and appropriate security measures are
Similar questions have been raised regarding the limited ef- needed (6), especially in pediatric, psychiatric, and some geri-
ficacy of alcohol-based hand rubs against noroviruses (201), al- atric wards, this should not jeopardize the efforts to introduce
though these concerns maybe overstated (202). In vitro studies the widespread use of alcohol-based hand rubs in healthcare.
demonstrate that 70% alcohol-based formulations, particularly Another issue of potential concern is the absorption or inha-
ethanol (203), and the WHO-recommended formulation I lation of alcohol following dermal application of alcohol-based
based on 80% ethanol (204) possess virucidal activity against hand rub. According to available studies, either undetectable
norovirus surrogates. In addition, norovirus outbreaks have or negligible blood concentrations of alcohols were detected
been controlled using alcohol-based hand rubs in the context and no symptoms were noted (230-238). The fire hazard is-
of multiple inteiVentions (205,206). sue has been addressed previously (6,239) and no longer rep-
resents a real barrier for the implementation of alcohol-based
ADVERSE EVENTS ASSOCIATED hand rubs.
WITH ALCOHOL-BASED HAND RUB USE
PATIENT PARTICIPATION IN HAND HYGIENE
The tolerability of hand hygiene products is a major factor
that influences acceptance and ultimate usage by HCWs and Patient participation in hand hygiene improvement has been
is a key determinant to the success of hand hygiene promo- proposed as a potentially effective means to increase HCW
tion (6,207,208). The frequent performance of hand hygiene hand hygiene compliance and promote an institutional safety
actions may lead to two moyor types of skin reactions-irritant climate (6,18,110,240-251). Specific approaches vary, but com-
contact and allergic contact dermatitis. The former is the most mon themes include patient education regarding the rationale
common and has especially been reported with iodophors and technique for hand hygiene in healthcare, recommenda-
(209) and less frequently with chlorhexidine, chloroxylenol, tions regarding patient hand hygiene while in hospital, and
triclosan, and alcohol-based products. The latter is rare and an invitation to remind HCWs to perform hand hygiene when
results from an allergy to an ingredient in the hand hygiene omitted. In this way, patients can play an active role in their
product, most commonly fragrances and preservatives, with own care. While the available evidence suggests that patient
emulsifiers being less common triggers (210-213). Liquid participation could be an important component to be included
soaps, hand lotion, ointments, or creams used by HCWs may in multimodal hand hygiene improvement programs, risks and
contain ingredients causing contact allergies (211,212). barriers need to be carefully addressed. Such barriers include
Frequent glove use and the donning of gloves on wet hands the relative vulnerability and limited capacity of many patients
can increase the risk of skin irritation. Skin that is damaged to play such a proactive role in the hospital environment and
by repeated exposure to detergents may be more susceptible the possibility of perturbing the patient-HCW relationship.
to irritation by all types of hand antiseptic formulations (214). Patient participation should probably be implemented only at
Routinely washing hands with soap and water immediately be- a more advanced stage of hand hygiene promotion, after care-
fore or after using an alcohol-based formulation is not only un- ful consideration of the local context and in close collaboration
necessary, but may also lead to dermatitis. Antimicrobial soaps with all stakeholders, especially HCWs.
may cause irritation because of the antimicrobial agent or other
ingredients of the formulation. Conversely, several studies have
demonstrated that alcohol-based preparations are better toler- GLOBAL PERSPECTIVE
ated and associated with better skin condition when compared AND RESEARCH AGENDA
with either plain or antiseptic hand products (6,215--218).
Allergic contact dermatitis due to alcohol-based hand rubs is Poor compliance with hand hygiene affects facilities at any level
very uncommon, and may represent true allergy to the alco- of country development Improvement relies not only on in-
hol, allergy to an impurity or aldehyde metabolite, or allergy dividual HCW awareness and knowledge, but also on involve-
to another product constituent (207,210,219-224). There are ment at imtitutional and governmental levels, thus implying
three primary strategies to minimize hand hygiene-related the need for system and policy changes. In a global perspective,
irritant contact dermatitis among HCWs: selection of less irri- hand hygiene promotion may imply different approaches de-
tating hand hygiene products, education regarding proper skin pending on where the inteiVention is conducted. In developed
countries or where implementation is more advanced, the issue 8. Gamer JS, Favero MS. CDC guideliue for handwaohing and hoopital en>imnmental con-
trol, 1985./rifrcl Control. 1986;7:!31-!45.
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..,nti.ng the •pread ofoancomycin reoiltance. InfoctCmomnHOIJ>Epidfttiol. 1995;16:10!>-113.
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in ~ wardo acrooo Europe and hncl: a multicenter obocrvationalotud7. ,A,.]bofra
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mission and the ultimate outcomes of HAis, the spread of an- organization hand h}'llic:ue improvement otrategy ill a referral hospital in Mali, Africa.
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ACKNOWLEDGMENTS toring cmnpliance with Momenu 1 and 4 of the WHO "My 5 Momeuu for Hand H}'lliene"
methodology. BMClnf<cl.Di&. 2011;11:151.
5!. Girou E. Chai SH, Oppein F, et a!. Mmue of gioveo: the foundation for poor compliance
The authors thank Rosemary Sudan for outstanding editorial with hand hygiene and potential for microbialll'llil>mi3oion?JHOIJ>InJ.a. 2004;57:162-169.
support. 33. Katheraoon SG, Naiug L, Jaalam K, et al. Hand decontamination practice> and the ap-
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M. Al-Wazzan B, Sahneen Y, Al-Amiri E, et a!. Hand hygiene practice> liiilong nuning otalf ill
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266. Mathai E, AI1egranzi B, Seto WH, et al. Educating healthcare worken to optimal hand 280. Chou T, Kcnidge J, Kull<ami M, etal. Changing the culture of hand hygiene compliance
hygiene practiceo: addreNing the need. Info:Jion. 2010;!18:!14!HI56. uaing a bundle that include• a violation letter. A•JInfra ConmJI. 2010;!18:575-578.
267. Moni&trol 0, Calbo E, Riera M, et al. Impact of a hand hygiene educational programme 281. HelmoB,DorvalS,Laurentl'S,etalimpraringhandbygienecampiiance: amultidilciplinary
on ho'J'ital-acquired infectiono in medical wardo. ClinMirnJIJiol btflti ~012;18:1212-1218. approach. hr<JInfrct Coniml. 2010;!18:572-574.
4 David T. Kuhar, Elise M. Beltrami, and Elizabeth A. Bolyard
Occupational Health Services

Healthcare personnel (HCP) are at r:iak of exposure to infec- The organization of an occupational health service can be
tious pathogeru in both the workplace and the community. If influenced by the size of the institution, the number of HCP,
they develop an infection, they may pose a r:iak for transmission and the services offered. 1b enmre that contractual HCP who
of that infectious pathogen to patients, other HCP, members of are not paid by the healthcare facility receive appropriate oc·
their houaeholda, or other community contacts. In this chapter, cupational health services, contractual agreements with their
the term HCP refers to all paid and unpaid persons working employers should contain provisions consistent with the poli-
in healthcare settings who have the potential for expoaure to cies of the facility that uses thoae HCP. Experts with specialized
infectious materials, including body mbstances, contaminated training and qualifications in occupational health can facilitate
medical supplies or equipment, contaminated environmental the provision of effective services.
surfaces, or contaminated air. HCP include, but are not limited
to, physicians, nUI'3e&, nursing assistants, therapists, technicians,
COORDINATION WITH OTHER DE.PAB.T.MBNTS
emergency medical personnel, dental persowtel, pharmacistJJ,
students and trainees, contractual personnel, home healthcare For infection prevention (IP) objectives to be achieved, the ac-
personnel, and persons not directly involved in patient care tivities of the occupational health service must be coordinated
(e.g., clerical, dietary, house·keeping, laundry, security, main· with IP and other appropriate departmental staff. This coordi·
tenance, billing, chaplains, and volunteers) but potentially ex- nation will help ensure adequate surveillance of infections in
posed to infectious agents that can be trarumitted to and from HCP and provision of appropriate preventive services. Coordi-
HCP and patients. Healthcare settings include, but are not lim- nation of activities also will help to ensure that investigations of
ited to, acute-c:are hospitals; long-term care facilities, such u expomres and outbreaks are conducted efficiently and preven-
nursing homes and skilled nursing facilities; physicians' offices; tive measures implemented promptly.
urgent-care centers; outpatient clinics; and home healthcare. In
general, HCP inside or outside hospitals who have contact with
PREPLA.CBMBNT MEDICAL IWALUATIONS
patients, body fluida, or specimens have a higher risk of acquir-
ing or transmitting pathogens than do other HCP who have only Medical evaluations before placement can help ensure that
brief casual contact with patients and their environment (e.g., HCP are not placed in jobs that would pose undue risk of in·
beds, furniture, bathrooms, food trays, or medical equipment). fection to them, other HCP, patients, or visitors. An important
This chapter outlines the infection control elements of an component of the preplacement evaluation is a health inven-
occupational health service and discu&ses important aspects tory. This includes determining immunization status and ob-
of selected traii&DW..ible diseues excluding hepatitis B virus taining histories of any conditions that could predispose HCP
(HBV) infection, hepatitis C virus (HCV) infection, and hu- to acquiring or t:ransmitting infectious diseases.
man immunodeficiency virus (HIV) infection, which are dis- A physical examination can be used to screen HCP for con-
cussed in Chapter 42. ditions that could increase the risk of t:ransmitting pathogens or
acquiring work-related diseases, and can serve as a baseline for
determining whether future diseases are work-related. However,
INFECTION CONTROL ELEMENTS OF the cost-effectiveness of routine physical examinations, includ-
ANOCCUPKOONAL~THSHR~CE ing routine laboratory testing (e.g., complete blood cell counts,
urinalysis, and chest radiographs) and screening for enteric or
Whether perfonned •in house" or contracted out, certain el- other pathogens for IP purposes, has not been demonstrated.
ements are necessary for the appropriate functioning of an Conversely, serologic screening for some vaccine-preventable
occupational health service: (a) coordination with other depart- diseases, such u HBV, measles, mumps, rubella, or varicella,
ments, (b) preplacement medical evaluations, (c) health and may be cost-effective. In general, the health inventory can be
safety education, (d) immunization programs, (e) management used to guide decisions regarding physical examinations or
of job-related illnesses and exposures to infectious pathogens, laboratory tests. However, some local public health ordinances
including policies for work restrictions for infected or exposed may mandate use of certain screening procedures. Periodic
personnel, (f) counseling services for persowtel on infection evaluations may be done u indicated for job reusignment, for
risks related to employment or special conditions, and (g) main· ongoing programs (e.g., tuberculosis [TB] screening), or for
tenance and confidentiality of individual health records. evaluation of work-related problems.
41
HEALTH AND SAFETY EDUCATION employed an influenza immunization strategy that includes one
or more of the following components: education about influenza,
HCP are more likely to comply with an IP program if they un-
easy access to vaccine, incentives to encourage immunization, or-
derstand its rationale. Thus, education is an important element ganized campaigns, institution of declination policies, and legisla-
of an effective IP program for HCP. Clearly written policies,
tive and regulatory efforts (e.g., vaccination requirements) (2-9).
guidelines, and procedures ensure uniformity, efficiency, and
National guidelines for immunization of and postexposure
effective coordination of activities. However, because the risk
prophylaxis (PEP) for HCP are provided by the U.S. Public
of infection varies by job category, IP education should be tai-
Health Service's Advisory Committee on Immunization Prac-
lored accordingly. HCP in some jobs may need specialized edu-
tices (ACIP) (9--31).
cation on infection risks related to their employment and on
Screening tests are available to determine evidence of immu-
preventive measures that will reduce those risks. Furthermore, nity to certain vaccin~preventable diseases (e.g., HBV, measles,
educational materials need to be appropriate in content and
mumps, rubella, and varicella). Such screening programs should
vocabulary to the educational level, literacy, and language of be combined with tracking systems to ensure accurate main~
the employee. The training should comply with existing fed-
nance of HCP immunization records. Accurate immunization
eral, state, and local regulations regarding requirements for records ensure that susceptible personnel are promptly identified
employee education and training. All HCP need to be edu-
and appropriately vaccinated. For more details about vaccinations
cated about the organization's IP policies and procedures.
for HCP, see Vaccinations in Patients and Healthcare Workers.
IMMUNIZATION PROGRAMS MANAGEMENT OF JOB-RELATED ILLNESSES

AND EXPOSURES
Ensuring that HCP have evidence of immunity to selected
vaccin~preventable diseases is an essential part of successful oc- Primary functions of the occupational health service are to ar-
cupational health programs. Optimal use of vaccines can help range for prompt diagnosis and management of job-related
prevent transmission ofvaccin~reventable diseases and limit the illnesses and to provide appropriate PEP after job-related ex-
need to apply work restrictions. Prevention of illness among HCP posures. The healthcare organization is responsible for impl~
through comprehensive occupational immunization programs is menting measures to prevent further transmission of pathogens,
fur more cost-effective than case management and outbreak con- which sometimes warrants exclusion of personnel from work
trol. In particular, interventions to increase influenza vaccination or patient contact (32). Decisions about work restrictions are
ofHCP have been shown to be effective (1). Hospitals and other based on the mode of transmission and the epidemiology of
healthcare organizations in the United States traditionally have the disease (Table 4.1). The term "exclude from duty" in this
TABLE 4.1 Summary of Suggested Work Restrictions for Healthcare Personnel Exposed to or
Infected with Infectious Discasc:s of Importance in Hcalthcare Settings, in the Absence
of State and Local :&gulations
Disease/Problem Work Restriction Duration
Conjunctivitis Restrict from patient contact and contact Until discharge cea&es
with the patient's environment
Cytomegalo'Yirm infections No restriction
Diarrheal diseues
Acute stage (diarrhea with other Restrict from patient contact, contact with Until at least 48 hours after resolution of symptoiilll
symptoiilll) the patient's environment, or food consistent with norovirus infection
handling
Convalescent stage, Salmunello. spp. Restrict from care of high-rillk patient. Until symptom.. resolve; consult with local and state health
authorities regarding need for negative stool culturo
Group A streptococcal infections Restrict from patient care, contact with the Until24 hours after adequate treatment started
patienu environment, or food handling
Hepatitis A Restrict from patient contact, contact Until 7 days after onset ofjaundice
with patient's environment, and food
handling
Herpes simplex hands Restrict from patient contact and contact Until lesions have crusted
(herpetic whitlow) with the patient's environment
Measles active Exclude from duty Until4 days after the r.uh appears
Postexposure (HCP without Exclude from duty From the 5th day after the 1st exposure through the
evidence of immunity) 21st day after last exposure
Meningococcal infections Exclude from duty Until24 hours after start of effective therapy
Mumps active Exclude from duty Until5 days after onset of parotitis
Postexposure (HCP without Exclude from duty From 12th day after bt exposure through until25 days af
evidence of immunity) ter last exposure or until5 days after owet of parotitis
Pertussu active Exclude from duty From beginning of catanhal stage through 3rd week
after onset of paroxysms or until 5 days after start of
effective antimicrobial therapy
Chapttr 4 • Occupational Health Servius 43
TABLE 4.1 Summary of Suggested Work Ratrictions for Hcalthcarc Personnel Bxposcd to or
Infec:tcd with Infectious Diseases of Importance in Hcalthcare Settings, in the Absence
of State and Local Regulations (Omrinwtl)
Disease/Problem Work Restriction Duration
Postexposure (asymptomatic No restriction from duty; on antimicrobial
personnel-HCP likely to prophylactic therapy
expose a patient at risk for
severe pel'tUMi.s)
Postexposure (asymptomatic No restriction, can receive PEP or be
personnel~ther HCP) monitored for 21 days after exposure
Postexposure (symptomatic Exclude from duty Until5 days after start of effective antimicrobial
personnel) therapy
Rubella Active Exclude from duty Until 7 days after rash appears
Postexposure (HCP without Exclude from duty From 7th day after 1st exposure through 2lJrd day after
evidence of immunity) last exposure
~ aureru infec:tion
Acute, active, draining skin lesions Restrict from contact with patients and Until lesions have resolved
patient's environment or food handling
Chronic, draining skin lesions Restrict from contact with patients and Until lesions have resolved, though considerations for ear-
patient's environment or food handling lier return to work could include the location of the
provider's infection, if the lesi.on can be completely
covered, the hand hygiene and infection prevention
practices of the individual provider, and others.
Tuberculo.is
Active di&ease Exclude from duty Until proved noninfectious
TST or IGRA converter No restriction
Varicella active Exclude from duty Until all lesions dry and crusL If only lesions that do
not crust (i.e., macules or papules), until no new
lesions appear within a 24-hour period.
Postexposure (HCP without Exclude from duty until receipt of the From 8th day after 1st exposure through 21st day (28th
evidence of immunity) second dose of varicella vaccine within day ifVariZIG given) after last exposure; if varicella
!1-5 days of exposure occurs, until all lesions dry and crust or, if only
lesions that do not crust (i.e., macules or papules),
until no new lesions appear within a 24-hour period
Viral respiratory infections, acute Exclude from duty Until afebrile for greater than 24 hours (without
febrile the use of fever-reducing medications, such as
acetaminophen)
Consider for temporary reassignment or exclusion from
work for 7 days from symptom onset or until the res-
olution of symptoms, whichever is longer, if return-
ing to care for patients in a protective environment,
such as hematopoetic stem cell transplant patients.
Zoster
Localized, in immunocompetent Cover lesions; restrict from care of high-risk Until all lesions dry and crust
HCP patients (pregnant women, neonates,
and immunocompromised patients of
any age)
Disseminated or localized in Exclude from duty Until all lesions dry and crust
immunosuppressed HCP
Postexposure (HCP without Exclude from duty unless receipt of the From 8th day after 1st exposure through 21st day (28th
evidence of immunit}'dissem second dose of varicella vaccine within day ifVariZIG given) after last exposure or, if vari-
inated zoster or localized !1-5 days after exposure cella occurs, until all lesions dry and crust or if only
zoster with uncontained/ lesions that do not crust (i.e., macules and papules),
uncovered lesions) until no new lesions appear within a 24-hour period
Postexposure (HCP without For HCP with at least one dose of varicella From 8th day after 1st exposure through 21st day
evidence of immunit}'J.ocalized vaccine, no work restrictions. For HCP (28th day ifVariZIG given) after last exposure or,
zoster with contained/covered with no doses of varicella vaccine, re- if varicella occurs, until all lesions dry and crust
lesions) strict from patient contact or if only lesions that do not crust (i.e., macules
and papules), until no new lesions appear within a
24-hour period
Modified from Bolyard EA, Tablan OC, Williams WW, et al. Guideline for infection control in health care personnel, 1998. Infect Control Hasp
Epidemiol. 1998;19:407-463.
chapter should be interpreted as exclusion from the healthcare EPIDEMIOWGY AND CONTROL OF
facility and from healthcare activities outside the facility. HCP SELECTED INFECTIONS TRANSMITfED
who are excluded should avoid contact with susceptible persons AMONG HCP AND PATIENTS
both in the facility and in the community. Exclusion policies
should include a statement of authority defining who may ex- The following section provides more detail about selected in-
clude HCP. The policies also need to be designed to encourage fectious pathogens and conditions that can be transmitted in
personnel to report their illnesses or exposures, not to penalize the healthcare setting. Bloodbome pathogens, including HBV,
them with loss of wages, benefits, or job status. While workers' HCV, and HIV, are not included here but are discussed in
compensation laws cover occupationally acquired infections, Chapter43.
they do not cover exclusion from duty based solely on expo-
sures to infectious diseases; therefore, policies should include
a method for providing wages during the period that HCP are CONJUNCTIVITIS
not permitted to work. In addition, exclusion policies must be Although conjunctivitis can be caused by a variety of bacte-
enforceable, and all HCP, especially department heads, supervi- ria and viruses, adenovirus has been the primary cause of
sors, and nurse managers, should know which infections and healthcare-associated outbreaks of conjunctivitis. Healthcare-
exposures warrant exclusion and where to report the illnesses associated outbreaks of conjunctivitis caused by adenovirus
24 hours a day, 7 days a week. HCP who have contact with in- have primarily occurred in eye clinics or offices, but also have
fectious persons outside the healthcare setting also need to be been reported in neonatal intensive care units and long-term
included in a postexposure program and encouraged to report care facilities (36-40). The incubation period ranges from
any suspected or known exposures promptly. 2 to 12 days, and shedding of virus occurs from late in the
incubation period to as long as 14 days after onset of disease
HEALTH COUNSELING (37,41). Adenovirus survives for long periods on environmen-
tal surfaces; ophthalmologic instruments and equipment can
Access to adequate health counseling for HCP is another cru- become contaminated and be a source of transmission. Con-
cial element of an effective occupational health service. Health taminated hands also are a major source of person-to-person
counseling allows HCP to receive individually targeted informa- transmission of adenovirus, both from patients to HCP and
tion regarding (a) the risk and prevention of occupationally from HCP to patients. Hand hygiene, glove use, and disinfec-
acquired infections, (b) the risk of illness or other adverse out- tion of instruments can prevent the transmission of adenovirus
come after exposure, (c) management of exposure, including (36,37). Infected personnel should not provide patient care for
the risks and benefits of PEP regimens, and (d) the potential the duration of symptoms after onset of purulent conjunctivitis
consequences of exposure or communicable disease for family caused by adenovirus or other pathogens (37,38).
members, patients, or other persons, both inside and outside
the healthcare facility.
CYTOMEGALOVIRUS
There are two principal reservoirs of cytomegalovirus (CMV)
MAINTENANCE OF RECORDS, DATA
in healthcare institutions: (a) infants and young children in-
MANAGEMENT, AND CONFIDENTIALITY
fected with CMV and (b) immunocompromised patients; for
Maintenance of records related to medical evaluations, evi- example, those undergoing solid-organ or bone-marrow trans-
dence of immunity, immunizations, exposures, PEP, and plantation or those with acquired immunodeficiency syndrome
screening tests in a retrievable, preferably computerized, da- (AIDS) (42,43). However, HCP who provide care to such high-
tabase allows efficient monitoring of the health status of HCP. risk patients have a rate of primary CMV infection that is no
Such record keeping also helps to ensure that the organization higher than that among personnel without such patient con-
will provide consistent and appropriate services to HCP. tact (3% vs. 2%) (44-48).
Individual records for all HCP should be maintained in ac- CMV transmission appears to occur directly either through
cordance with the Occupational Safety and Health Adminis- close, intimate contact with a person excreting CMV or through
tration (OSHA) medical records standard, which requires the contact with contaminated secretions or excretions, especially
employer to retain records, maintain employee confidential- saliva or urine (47,49,50). Transmission by the hands of HCP
ity, and provide records to employees when they ask to review or infected persons also has been suggested (43,51). The incu-
them (33). In addition, the OSHA "Occupational Exposure to bation period for person-to-person transmission is not known.
Bloodbome Pathogens; Final Rule" (34) requires employers, Although CMV can survive on environmental surfaces and
including healthcare facilities, to establish and maintain an other objects for short periods (52,53), there is no evidence
accurate, confidential record for each employee with occupa- that the environment plays a role in the transmission of this
tional exposure to bloodbome pathogens. The standard also pathogen (43) .
requires that each employer ensures that he or she maintains Because infection with CMV during pregnancy may have ad-
employee medical records for at least the duration of the work- verse effects on the fetus, women of childbearing age need to be
er's employment plus 30 years. counseled regarding the risks and prevention of transmission
Occupational health departments need to protect and safe- of CMV in both nonoccupational and occupational settings
guard protected health information as defined by the Health In- (54). No studies clearly indicate that seronegative HCP can be
surance Portability and Accountability Act of 1996 (HIPAA) and protected from infection by transfer to areas with less contact
the American Disabilities Act (ADA) (35). Disclosure of such in- with patients likely to be reservoirs for CMV (42-44,48) . Work-
formation to public health authorities is permitted for the pur- place reassignment should not be routinely used as a method
pose of preventing or controlling disease, injury, or disability. to reduce CMV exposures among seronegative pregnant HCP.
Serologic or virologic screening programs to identify risk for severe disease (e.g., neonates, elderly persons, and im-
CMV-infected patients or seronegative female personnel of munocompromised patients). The initial evaluation of HCP
childbearing age are impractical and costly because (a) virus with gastroenteritis needs to include a thorough history, physi-
shedding can be intennittent (55), and thw repeated screen- cal exam, and determination of the need for specific laboratory
ing tests could be needed to identify shedders, (b) seropositivity tests (69,79,82-85).
for CMV does not offer complete protection against maternal Restriction from patient care and the patient's environment
re-infection or reactivation and subsequent fetal infection (42), or from food handling is indicated for HCP with diarrhea or
and (c) no currently available vaccines or prophylactic therapy acute gastrointestinal symptoms regardless of the causative
for HCP can provide protection against primary infection. agent (56,79) . Work exclusion for a minimum of 48 hours af-
Work restrictions for personnel who contract CMV illnesses ter resolution of symptoms for HCP with symptoms consistent
are not necessary. The risk of transmission of CMV can be re- with norovirus infection has been recommended (85). Some
duced by careful adherence to hand hygiene and standard pre- local and state agencies have regulations that require work ex-
cautions (42,56). dwion for HCP, food handlers, or both who have gastrointesti-
nal infections caused by specified organisms (e.g. Salmonella or
Sh~lla spp.). These regulations may require such personnel to
DIPHTHERIA
be restricted from duty until results of at least two consecutive
Healthcare-associated transmission of diphtheria among stool cultures obtained at least 24 hours apart are negative.
patients and HCP has been reported (57-59). HCP are not at
substantially higher risk than the general adult population for
HEPATITIS A VIRUS
acquiring diphtheria.
Prevention of diphtheria is best accomplished by maintain- Healthcare-associated hepatitis A virus (HAV) infections oc-
ing high levels of diphtheria immunity among children and cur infrequently, and transmission to HCP usually occurs when
adults (21,60,61). Immunization with tetanw and diphtheria the source-patient has unrecognized hepatitis and is fecally
toxoid (Td) is recommended every 10 years for all adults who incontinent or has diarrhea (86-93). Other risk factors for
have completed the primary immunization series (9,21). Per- HAV transmission to HCP include activities that increase the
sons without documentation of having received Td vaccination risk of fecal-oral contamination such as (a) eating or drinking
should receive a series of three vaccinations with Td-containing in patient-care areas (86,88,90,94), (b) not perfonning hand
vaccine. Preferably, the first dose of this series should be admin- hygiene after caring for an infected infant (88,94,95), and
istered as Tetanus, diphtheria, and acellular pertussis (Tdap) (c) sharing food, beverages, or cigarettes with patients, their
vaccine (see Pertussis). HCP directly exposed to oral secretions families, or other staff members (86,88) .
of patients infected with Corynebacterium diphthmru should be HAVis transmitted primarily by the fecal-oral route. The
evaluated in consultation with local public health authorities. incubation period for HAV is 15 to 50 days. Fecal excretion of
HAV is greatest during the incubation period of disease before
the onset ofjaundice. Once disease is clinically obvious, the risk
GASTROENTERITIS
of pathogen transmission is decreased. However, some patients
Gastrointestinal infections may be cawed by a variety of agents, admitted to the hospital with HAV, particularly premature in-
including bacteria, viruses, and protozoa. However, only a few fants or immunocompromised patients, can still shed virus be-
agents have been documented in healthcare-associated trans- cawe of prolonged or relapsing disease, and such patients are
mission, such as Salmonella typhimurium, Yminia enterocolitica, potentially infectious (87). Fecal shedding of HAV, formerly
Eschmchia coli, and norovirus (62-75) . Few episodes of health- believed to continue only as long as 2 weeks after onset of dark
care-associated Clostridium difftcik infection (CDI) among urine, has been shown to occur as late as 6 months after diag-
HCP have been reported (76), and increased risk of CDI nosis of infection in premature infants (86) . Anicteric infection
among HCP has not been dearly demonstrated. Healthcare- is typical in young children and infants (96).
associated transmission of agents that cawe gastrointestinal in- HCP can protect themselves and others from infection with
fections wually results from contact with infected individuals HAV by adhering to standard precautions (56).
(62,68,77), from consumption of contaminated food, water, or Three inactivated HAV vaccines are now available and pro-
other beverages (62,77,78), or from exposure to contaminated vide long-term preexposure protection against clinical infec-
objects or environmental surfaces (63,79). Inadequate HCP tion with >94% efficacy (96). Routine administration of HAV
hand hygiene (80) and inadequate sterilization or disinfection vaccine in HCP is not recommended because HCP have not
of patient-care equipment and environmental surfaces increase been demonstrated to be at increased risk for HAV infection
the likelihood of transmission of agents that cawe gastrointesti- due to occupational exposure. However, vaccine may be use-
nal infections. Generally, adherence to proper hand hygiene by ful for HCP working or living in areas where HAV is highly
HCP before and after all contacts with patients and food, and endemic and is indicated for individuals who handle HAY-
to either standard or contact precautions (56) will minimize infected primates or are exposed to HAV in a research labo-
the risk of transmitting enteric pathogens (70,81). ratory. The role of HAV vaccine in controlling outbreaks has
HCP who acquire an acute infectious gastrointestinal illness not been adequately investigated (96). Immune globulin given
(defined as vomiting, diarrhea, or both, with or without asso- within 2 weeks after an HAV exposure is 80% to 90% effective
ciated symptoms such as fever, nawea, and abdominal pain) in preventing HAV infection and may be advisable in some
are likely to have high concentrations of the infecting agent in outbreak situations (96).
their feces (bacteria, viruses, and parasites) or vomitus (viruses Restriction from patient-care areas or food handling is indi-
and parasites). Determining the etiology of gastrointestinal ill- cated for HCP with HAV infection. They may return to regular
ness is important in affected HCP who care for patients at high duties 1 week after onset of the illness.
46 SectWn I • General Considerations ofHospital Infections
HERPES SIMPLEX VIRUS Measles is transmitted both by large droplets during close
contact between infected and susceptible persons and by the
Healthcare-associated transmission of herpes simplex virus airborne route ( 117). Measles is highly transmissible and fre-
(HSV) is rare. It has been reported in nurseries (97-99) and
quently misdiagnos ed during the prodromal stage. The incu-
intensive care units (100,101) where high-risk patients (e.g., bation period for measles is 7 to 21 days. Immunoco mpetent
neonates, patients with severe malnutritio n, patients with se-
persons with measles shed the ~rus from the nasoph~x,
vere burns or eczema, and immunoco mpromised patients) are beginning with the prodrome until 4 days after rash onset; •m-
located. Healthcare-associated transmission of HSV occurs pri- munocomp romised persons with measles could shed virus for
marily through contact either with primary or recurrent lesions
extended periods (118).
or with virus-containing secretions, such as saliva, vaginal secre-
Strategies to prevent healthcare-associated transmission
tions, or amniotic fluid (98,100,102). Exposed areas of skin are of measles include (a) documenta tion of evidence of measles
the most likely sites of infection, particularly when minor cuts, immunity in HCP, (b) prompt identificati on and isolation of
abrasions, or other skin lesions are present (101). The incuba- persons with fever and rash, and (c) adherence to airborne pre-
tion period ofHSV is 2 to 14 days (10~) . The duration ofviral cautions for suspected and proven patients with measles (56).
shedding has not been well defined (104). Documenta tion of evidence of measles immunity is essen-
HCP can acquire a herpetic infection of the fmgers (her- tial for all HCP, regardless of their length of employme nt or
petic whitlow or paronychia ) from exposure to contamina ted
whether they are involved in patient care. Presumptive evi-
oral secretions (101,102). Such exposures are a distinct hazard dence of immunity to measles for persons who work in health-
for nurses, anesthesiologists, dentists, respiratory care person- care facilities includes those (a) with written documenta tion of
nel, and other personnel who have ungloved direct (usually
vaccination with two doses of live measles or Measles-Mumps-
hand) contact with either oral lesions or respiratory secretions Rubella (MMR) vaccine administer ed at least 28 days apart,
from patients (101) . Less frequently, HCP may acquire muco- (b) with laboratory evidence of immunity ("equivocal" results
cutaneous infection on other body sites from contact with in- should be considered nonimmun e), (c) laboratory confirma-
fectious body secretions (105). tion of disease, or (d) born before 1957.Altho ugh persons born
HCP with active HSV infection of the hands (herpetic whit-
before 1957 are generally considered to be immune to measles,
low) can potentially transmit the pathogen to patients with serologic studies indicate that 2% to 9% of HCP born before
whom they have contact (102). Transmission ofHSVfrom HCP 1957 may not be immune (9,119,120) . During 2001 to 2008, a
with orofacial HSV infection to patients also has been infre- total o£12.5% (1 of 8) measles cases reported to the Centers for
quently documente d (97); however, the magnitude of this risk Disease Control and Prevention (CDC) among HCP occurred
is unknown (99,106) . Although asymptomatic HSV-infected in persons born before 1957 (9). For unvaccinat ed personnel
persons can shed the virus, they are less infectious than persons
born before 1957 who lack laboratory evidence of measles im-
with active lesions (104,107). munity or laboratory confirmatio n of disease, healthcare facili-
HCP can protect themselves from acquiring HSV by adher-
ties should consider vaccinating personnel with two doses of
ing to standard precaution s (56). The risk of trans~ission of the MMR vaccine at the appropriat e interval, absent a measles
HSV from personnel with orofacial infections to patients can outbreak. During an outbreak of measles, two doses of the
be reduced by performing hand hygiene before all patient care MMR vaccine are recommen ded for these personnel (9) .
and by the use of appropriat e barriers (e.g., a mask or gauze
Work restrictions are necessary for HCP who acquire mea-
dressing) to prevent band contact with the lesions. . . sles; they need to be excluded from duty for 4 days after the
Because HCP with orofacialle sions could touch the•r les10ns rash appears. Likewise, HCP without presumptiv e evidence
and potentially transmit HSV, they should be evaluated to deter-
of immunity to measles need to be excluded from duty from
mine their potential for transmitting HSV to patients at high ris~ 5 days after the first exposure through 21 days after the last
for serious disease (e.g., neonates, patients with severe malnutri-
exposure to measles.
tion, patients with severe burns or eczema, and immuno~om
promi.sed patients) and excluded from the care of such patients
as indicated. The evaluation also should consider the extent of MENINGO COCCAL DISEASE
the lesion and the severity of illness in the patient population Healthcare-associated transmission of Neisseria meningitidis is
that personnel will contact. HCP with HSV infections of the rare. When proper precaution s were not used, N. meningitidis
fingers or hands can more easily transmit HSV and therefore
has been transmitted from patient to personnel through con-
need to be excluded from patient care until their lesions have
tact with the respiratory secretions of patients with meningoco c-
crusted. In addition, herpetic lesions can be secondarily infected cal disease or through handling laboratory specimens (121) .
by Staphylococcus or Streptococcus spp., and HCP with such infec-
N. meningitidis infection usually is transmitted by close con-
tions should be evaluated to determine whether they need to be tact with aerosols or secretions from the human nasophar-
excluded from patient contact until the secondary infection has
ynx; the incubation period is from 2 to 10 days, and patients
resolved. There have been no reports that HCP with genital HSV infected with N. meningitidis are rendered noninfectio us by
infections have transmitted HSV to patients; therefore, work re-
24 hours of receiving therapy effective in eradicating carriage.
strictions for HCP with genital herpes are not indicated. HCP who care for patients with suspected N. meningitidis infec-
tion can decrease their risk of infection by adhering to droplet
precaution s (56).
MEASLES
PEP is advised for persons who have had close, unprotecte d
Healthcare-associated transmission of measles virus has been contact (i.e., without wearing a mask) with infected patients
well described (10S-115) and responding to measles exposures (e.g., mouth-to-m outh resuscitation, endotrache al intubation,
in hospital settings can be very costly and disruptive (116) . endotrache al tube manageme nt, or close examinatio n of the
oropharynx of patients) (15). Antimicrobial prophylaxis can disease, healthcare facilities should consider vaccinating per-
eradicate carriage of N meningitidis and prevent infections in sonnel with two doses of MMR vaccine at the appropriate in-
HCP who have unprotected exposure to patients with menin- terval. For unvaccinated personnel born before 1957, who lack
gococcal infections (122). laboratory evidence of mumps immunity or laboratory confirma-
Because secondary episodes of N meningitidis occur rap- tion of disease, healthcare facilities should recommend two doses
idly (within the first week) after exposure to persons with of MMR vaccine during an outbreak of mumps (9).
meningococcal disease ( 123), it is important to begin pro- Work restrictions are necessary for HCP who acquire
phylactic therapy immediately after an intensive, unprotected mumps; such restrictions should be imposed for 5 days after
exposure, often before results of antimicrobial testing are the onset of parotitis. Otherwise, HCP without presumptive
available. Rifampin (600 mg orally every 12 hours for 2 days) evidence of immunit}' who are exposed to mumps need to be
is effective in eradicating nasopharyngeal carriage of N 'IJU'Il-- excluded from duty from the 12th day after the first exposure
ingitidis (122). Ciprofloxacin (500 mg orally) and ceftriaxone through 25 days after the last exposure (9,131).
(250 mg intramuscularly) in single-dose regimens also are ef-
fective in reducing nasopharyngeal carriage of N meningitidis
PAR.VOVIR.US
and are reasonable alternatives to the multidose rifampin regi-
men (15). These antimicrobials may be useful when infections Transmission of human parvovirus B19 (B19), the cause of
are caused by rifampin-resistant meningococci or rifampin is erythema infectiosum (fifth disease), to HCP from infected
contraindicated. Rifampin and ciprofloxacin are not recom- patients appears to be rare but has been reported (132-136).
mended for pregnant women (102,124,125). HCP have acquired infection while working in laboratories or
The quadrivalent A, C, Y, W-135 polysaccharide vaccine has during the care of patients with B19-associated sickle-cell aplas-
been used successfully to control communit}' outbreaks caused tic crises (133-139).
by serogroup C (15,124), but its use is not recommended for Bl9 can be transmitted through contact with infected per-
PEP in healthcare settings (15). Preexposure vaccination is sons, fomites, or large droplets (140). The incubation period
recommended for laboratory personnel who routinely handle varies, depending on the clinical manifestation of disease, and
soluble preparations of N meningitidis (9,15,121). ranges from 6 to 10 days ( 141). The period of infectivit}' also
In the absence of exposures to patients with N meningitidis varies, depending on the clinical presentation or stage of dis-
infection, personnel who are asymptomatic carriers of ease. Persons with erythema infectiosum are infectious before
N meningitidis need not be identified, treated, or removed the appearance of the rash-those with infection and aplastic
from patient-care activities. However, HCPwith meningococcal crises for as long as 7 days after the onset of illness, and persons
infection need to be excluded from duty until 24 hours after with chronic infection for years.
the start of effective therapy. Pregnant HCP are at no greater risk of acquiring B19 in-
fection than are nonpregnant HCP; however, if a woman does
acquire Bl9 infection during the first half of pregnancy, the
MUMPS
risk of fetal death is increased. Female HCP of childbearing age
Mumps transmission has occurred in healthcare facilities should be counseled regarding the risk of transmission of B19
housing neonates, adolescents, and young adults (126-128). and appropriate infection control precautions (56).
Most episodes of mumps in HCP have been community-ac- Most patients with erythema infectiosum are past their pe-
quired. Mumps is transmitted by contact with virus-containing riod of infectiousness at the time of clinical illness (139). How-
respiratory secretions, including saliva; the portals of entry are ever, patients in aplastic crisis from Bl9 or patients with chronic
the nose and mouth. The incubation period varies from 12 to B19 infection can transmit the virus to susceptible HCP or
25 days and usually is 16 to 18 days. The virus can be present in other patients; therefore, patients with preexisting anemia who
saliva for 7 days before parotitis and transmission is most likely are admitted to the hospital with febrile illness and transient
to occur up to 5 days after onset of disease. Exposed HCP aplastic crises should remain on droplet precautions for 7 days,
may be infectious for 12 to 25 days after their exposure, and and patients with known or suspected chronic infection with
many infected persons remain asymptomatic (129). Droplet B19 should be placed on droplet precautions on admission and
precautions are recommended for patients with mumps; such for the duration of hospitalization (56,134). Work restrictions
precautions should be continued for 5 days after the onset of are not necessary for HCP exposed to B19.
parotitis (56).
An effective vaccination program is the best approach to
PERTUSSIS
the prevention of healthcare-associated mumps transmission
(9,12). Vaccination with mumps virus vaccine, available as part Healthcare-associated transmission of B~ll!J pertussis has in-
of the MMR vaccine, is recommended, unless otherwise contra- volved both patients and HCP; nonimmunized children are at
indicated, for all those who are susceptible to mumps (12,130). greatest risk (142-146). B. pertussis transmission occurs by con-
Presumptive evidence of immunit}' to mumps for persons who tact with respiratory secretions or large aerosol droplets from
work in healthcare facilities includes those (a) with written docu- the respiratory tracts of infected persons. The incubation pe-
mentation of vaccination with two doses of live mumps or MMR riod usually is 7 to 10 days, but can be up to 21 days. The period
vaccine administered at least 28 days apart, (b) with laboratory of communicability starts at the onset of the catarrhal stage,
evidence of immunit}' ("equivocal" results should be considered manifest by mild cough and upper respiratory symptoms, and
nonimmune), (c) laboratory confirmation of disease, or (d) born extends into the paroxysmal stage, manifest by classic coughing
before 1957. Although likely to have been infected naturally, for fits, up to 3 weeks after onset of symptoms. Pertussis is highly
unvaccinated personnel born before 1957, who lack laboratory communicable in the catarrhal stage, when the symptoms are
evidence of mumps immunity or laboratory confirmation of nonspecific.
Prevention of transmission of B. pertussis in healthcare set- United States due to the low risk of OPV-associated paralytic
tings involves (a) early diagnosis and treatment of patients with poliomyelitis. IPV should be used when adult immunization is
clinical infection, (b) implementation of droplet precautions warranted, including immunization of pregnant or immuno-
for infectious patients (56), (c) exclusion of infectious HCP compromised HCP and HCP who may have contact with im-
from work, and (d) appropriate management ofHCP exposed munocompromised patients (9,25,26,150).
to infectious patients (9). Patients with suspected or confirmed HCP who have contact with patients who could be excret-
pertussis who are admitted to the hospital need to be placed on ing wild virus (e.g., imported poliomyelitis patient) and labo-
droplet precautions until they have clinical improvement and ratory personnel handling specimens containing poliovirus or
have received antimicrobial therapy for at least 5 days. performing cultures to amplify virus should receive a complete
HCP may play an important role in transmitting B. pertussis series of polio vaccine; if previously vaccinated, they could re-
in healthcare settings. Regardless of age, HCP should receive a ceive a booster dose ofiPV (9,26).
single dose ofTdap as soon as feasible, preferably before place-
ment, if they have not previously received Tdap and regard-
RABIES
less of the time since their most recent Td vaccination (9,23).
Acellular pertussis vaccine is immunogenic in adults and car- Human rabies episodes occur primarily from exposure to ra-
ries a lower risk of adverse events than does whole-<:ell vaccine bid animals. Laboratory and animal care personnel who are
(146,147). The duration of protection afforded by Tdap is exposed to infected animals, their tissues, or their excretions
unknown. are at risk for the disease. Also, rabies transmission to labora-
Data on the need for PEP in Tdap-vaccinated HCP are incon- tory personnel has been reported in vaccine production and
clusive. Certain vaccinated HCP are still at risk for B. pertussis, research facilities after exposure to high-titered infectious aero-
and Tdap might not preclude the need for PEP. PEP is indicated sols (152,153). Theoretically, rabies can be transmitted to HCP
for exposed HCP, regardless of receipt ofTdap vaccination, who from exposures to saliva from infected patients, but no epi-
are likely to expose a patient at risk for severe pertussis (e.g., sodes have been documented after bite or nonbite exposures
hospitalized neonates and pregnant women). A course of either (154,155).
azithromycin (one 500 mg single dose on day 1, then 250 mg per It is also possible for rabies to be transmitted when other po-
day on days 2 to 5), erythromycin (2 g per day in four divided tentially infectious material (e.g., brain tissue or transplanted
doses for 14 days), clarithromycin (1 g per day in two divided tissue) comes into contact with nonintact skin or mucous mem-
doses for 7 days), or trimethoprim-sulfamethoxazole (1 tablet branes (30,154). Bites that penetrate the skin, especially bites
twice daily for 14 days) has been used for this purpose (23,148). to the face and hands, pose the greatest risk of transmission of
Other HCP should either receive PEP or be monitored daily for rabies virus from animals to human beings (30). The incuba-
21 days after pertussis exposure and treated at the onset of signs tion period for rabies usually is 1 to 3 months, but longer peri-
and symptoms of pertussis (9). ods have been reported.
Restriction from duty is indicated for HCP with pertussis Exposures inflicted by infected humans could theoretically
from the beginning of the catarrhal stage through the third transmit rabies, but no laboratory-diagnosed instances occur-
week after onset of paroxysms, or until 5 days after the start of ring under such situations have been documented, except for
effective antimicrobial therapy. Exposed HCP do not need to solid organ transplants (30). Two nonlaboratory-<:onfirmed epi-
be excluded from duty. sodes of human-to-human rabies transmission in Ethiopia have
been described (30). The reported route of exposure in both
instances was direct salivary contact from another human (a
POLIOMYELITIS
bite and a kiss). Routine delivery of healthcare to a patient with
As the Americas were certified to be free of indigenous wild- rabies is not an indication for PEP unless exposure of mucous
type poliovirus in 1994 (149), with complete transition from membranes or nonintact skin to potentially infectious body flu-
the use of oral poliovirus vaccine (OPV) to inactivated polio- ids has occurred. Such exposures and provision of PEP to HCP
virus vaccine (IPV) in 2000, the risk of exposure to any live have been reported in healthcare settings (29,156).
poliovirus in the United States is limited. However, global eradi- Exposures to rabies virus can be minimized by adhering to
cation of poliomyelitis has not yet occurred, so reintroductions standard precautions when caring for persons with suspected
of poliovirus into the United States are still possible. or confirmed rabies (56) and by using proper biosafety precau-
Poliovirus is transmitted through contact with feces or tions in laboratories (157). Preexposure vaccination has been
urine of infected persons, but can be spread by contact with recommended for all personnel who (a) work with rabies virus
respiratory secretions and, in rare instances, through items or infected animals or (b) engage in diagnostic, production,
contaminated with feces. The incubation period for nonpara- or research activities with rabies virus (30,155,157). Consider-
lytic poliomyelitis is 3 to 6 days, but usually is 7 to 21 days for ation can also be given to providing preexposure vaccination
paralytic polio (150). Communicability is greatest immediately to animal handlers when research animals are obtained from
before and after the onset of symptoms when the virus is in the the wild rather than from a known supplier that breeds the
throat and excreted in high concentration in feces. The virus animals.
can be recovered from the throat for 1 week and from feces for
several weeks to months after onset of symptoms.
RUBELLA
Poliomyelitis associated with the OPV can occur in the recip-
ient (7 to 21 days after vaccine administration) or susceptible Healthcare-associated transm1ssmn of rubella has occurred
contacts of the vaccine recipient (20 to 29 days after vaccine from HCP to other susceptible HCP and patients, and from
administration) (151). Although OPV is still used in other patients to susceptible HCP and other patients (158,159).
countries, it is no longer recommended for routine use in the Rubella is transmitted by contact with nasopharyngeal droplets
from infected persons. The incubation period is variable, but of transmission to HCP (56,162). Routine cleaning of the en-
can range from 12 to 23 days; most persons have the rash an vironment of patients with typical scabies, especially bed linens
average of 14 to 17 days after exposure. The disease is most and upholstered furniture, will aid in eliminating the mites.
contagious when the rash is erupting, but virus may be shed Additional environmental cleaning procedures could be war-
from 1 week before to 7 days after the onset of the rash (160). ranted for crusted scabies (161,162,166,167).
Rubella in adults is usually a mild disease, lasting only a few There are no controlled evaluations of the efficacy of pro-
days; in 25% to 50% of infected adults, the infection may be phylactic scabicide therapy among HCP. Most infested HCP
subclinical or inapparent. have typical scabies with low mite loads (165); a single cor-
Droplet precautions are used to prevent transmission of rect application of a scabicide is adequate and immediately
rubella. Infants with congenital rubella can excrete virus for decreases the risk of transmission (168). Several lotions are
months to years; when caring for such patients, it is advisable to available to treat scabies. The treatment of choice is the topical
use contact precautions for the first year of life unless nasopha- use ofpermethrin (5%). Ivermectin is an alternative drug; it is
ryngeal and urine culture results are negative for rubella virus taken orally and is effective when used alone for treating scabies
after 3 months of age (56). or when used in combination with permethrin cream for the
Ensuring immunity among all HCP (male and female) is the treatment of crusted scabies in immunocompromised persons
most effective way to eliminate healthcare-associated transmis- (168). Some experts recommend two applications of scabicide
sion of rubella (9,31). Presumptive evidence of immunity to for all infested HCP (169,170). IfHCP continue to have symp-
rubella for persons who work in healthcare facilities includes toms after initial treatment, another application of scabicide
those (a) with written documentation ofvaccination with one could be needed. Persistent symptoms likely represent newly
dose of live rubella or MMR vaccine, (b) with laboratory evi- hatched mites rather than new infestation; however, pruritus
dence of immunity ("equivocal" results should be considered after scabies infestation and treatment can persist for as long as
nonimmune), (c) laboratory confirmation of rubella infection 2 weeks, even without infestation (168). In outbreak situations
or disease, or (d) born before 1957 (except women of child- in which transmission continues to occur, prophylaxis can be
bearing potential who could become pregnant, although preg- warranted for both patients and exposed HCP (162,169).
nancy in this age group would be exceedingly rare). Because Restrictions from patient care are indicated for HCP in-
many health departments mandate rubella immunity for HCP, fested with scabies until after they receive initial treatment and
personnel health programs should consult with their local or have been medically evaluated and determined to be free of
state health departments before establishing policies for their infestation. They should be advised to report for further evalu-
facilities. ation if symptoms do not subside.
Work restrictions are necessary for HCP who acquire ru-
bella; ill HCP need to be excluded from duty for 7 days after
Pediculosis
the rash appears. Likewise, HCP without presumptive evidence
of immunity to rubella require exclusion from duty from the Pediculosis is caused by infestation with any of three species
7th day after the first exposure through the 23rd day after the of lice: Pediculus humanus capitis (human head louse), Pediculus
last exposure (9). humanus corporis (human body louse), or Phthirus pubis (pubic
or crab louse). Head lice are transmitted by head-to-head con-
tact or by contact with infested fomites such as hats, combs,
SCABIES AND PEDICULOSIS or brushes. Healthcare-associated transmission, although not
common, has occurred (161).
&IJbies
The recommended treatment of pediculosis includes per-
Scabies is caused by infestation with the mite Sarcoptes scabiei. methrin cream 1%, pyrethrins with piperonyl butoxide, mala-
The typical clinical presentation of scabies includes intense thion 0.5%, or ivermectin (168). Resistance to various drugs has
pruritus and cutaneous tracks where mites have burrowed into been reported. HCP exposed to patients with pediculosis do
the skin. Crusted or "Norwegian" scabies can develop among not require treatment unless they show evidence of infestation.
immunocompromised and elderly individuals in which their Restriction from patient care is indicated for personnel with
skin may become hyperkeratotic; pruritus may not be present. pediculosis until after they receive initial treatment and are
In conventional scabies, 10 to 15 mites are present; in crusted found to be free of adult and immature lice. If symptoms do
scabies, thousands of mites are harbored in the skin, increasing not subside after initial treatment, personnel should be advised
the potential for transmission (161,162). to report for further evaluation.
Healthcare-associated outbreaks of scabies have occurred in
a variety of healthcare settings. Healthcare-associated transmis-
STAPHYLOCOCCAL INFECTION OR CARRIAGE,
sion of scabies occurs primarily through prolonged skin-to-skin
INCLUDING METIDCILLIN-RESISTANT
contact with an infested person who has conventional scabies
STAPHTLOCOCCUSAUREUS
(161,163). Shorter periods of skin-to-skin contact with persons
who have crusted scabies can result in transmission. HCP have Staphylococcal spp. infection and carriage occur frequently
acquired scabies while performing patient care duties such as in human beings. In healthcare settings, the most important
sponge bathing, lifting, or applying body lotions (161,162,164). sources of S. aumtS are infected or colonized patients. Methicillin-
Transmission by casual contact (e.g., by holding hands) or resistant S. aureus (MRSA) has accounted for approximately
through inanimate objects, such as infested bedding, clothes, 56% of all S. aureus isolates associated with episodes of device-
or other fomites, has been reported infrequently (165). associated healthcare-associated infection and 49% of S. aureus
The use of contact precautions when taking care of infested isolates associated with surgical site infections reported to the
patients before application of scabicides can decrease the risk CDC's National Healthcare Safety Network (NHSN) (171) .
The modes of transmission of MRSA do not appear to GROUP A STREPTOCOCCUS INFECTIONS

differ from that of methicillin-susceptible S. au11!1W. Health-
Group A Streptococcus (GAS) has been transmitted from in-
care-associated transmission of S. au11!1W can be prevented
by adherence to standard precautions and other forms of fected patients to HCP after contact with infected secretions
(195-197), and the infected HCP have subsequently devel-
transmission-based precautions as needed (56) . Healthcare-
oped a variety of GAS-related illnesses (e.g., toxic shock-like
associated transmission of S. au11!1W occurs primarily via the
syndrome, cellulitis, lymphangitis, and pharyngitis). GAS car-
hands of HCP, which can become contaminated by contact
riage among HCP has infrequently been linked to sporadic
with the colonized or infected body sites of patients or their
outbreaks of surgical site, postpartum, or burn wound infec-
surrounding contaminated environment (172,173). HCP who
tions (198-203). The incubation period is variable for GAS
are infected or colonized with S. aUfliUS also can serve as res-
infections (204).
ervoirs and disseminators of S. au11!1W (174-177). The role
Culture surveys to detect GAS carriage among HCP are not
of contaminated environmental surfaces in transmission of
S. au11!1W has not been well quantified (178,179) and may not warranted unless HCP are epidemiologically linked to episodes
of healthcare-associated infection (205). When a thorough
be a dominant mode of transmission, although heavy contami-
nation of fomites could facilitate transmission to patients by epidemiologic investigation has linked a provider to GAS case-
patients, cultures should be obtained from skin lesions, the
the hands of HCP (172). The incubation period for S. au:11!1W
pharynx, rectum, and vagina; GAS isolates obtained from HCP
infections varies by type of disease (180).
and patients should be compared by use of the same typing
Carriage of S. aum.u is most common in the anterior na-
method(s) (e.g., pulsed-field gel electrophoresis [PFGE], sera-
res, but other sites, such as the hands, axilla, perineum, naso-
typing, etc.) to determine strain relatedness. Although related
pharynx, or oropharynx, also can be involved (172,181,182).
strains of GAS between HCP and patients could be either from
Carriage of S. au:11!1W in the nares has been shown to correspond
to hand carriage (183), and persons with skin lesions caused by the same source or simply representative of the currently circu-
lating GAS serotype in the community, eradication of carriage
it are more likely than asymptomatic nasal carriers to dissemi-
nate the organism. is recommended for HCP colonized with an outbreak strain
of GAS. Because eradication of GAS is more difficult than ef-
Screening HCP for asymptomatic carriage can detect carri-
ers of S. aun~US, but does not indicate which carriers are likely fective treatment of mild GAS infections (e.g., pharyngitis and
impetigo), a limited number of antibiotic regimens are recom-
to disseminate organisms nor which HCP are likely to serve as
mended for the treatment of carriers (e.g., benzathine peni-
persistent reservoirs of S. aureus vs. only transiently colonized
cillin G plus rifampin, clindamycin, or azithromycin) (205).
(184,185). Thus, such screening is not cost-effective and can
Contact is the major mode of transmission of GAS in health-
subject HCP with positive culture results to unnecessary treat-
care settings. Healthcare-associated transmission of GAS to
ment and removal from duty. Screening HCP for asymptomatic
HCP can be prevented by adherence to standard precautions
carriage could be indicated if, after a thorough epidemiologic
or other transmission-based precautions as needed (56).
investigation, HCP are linked to infections. Such implicated
Restriction from patient care activities and food handling
HCP can then be removed from clinical duties until carriage
has been eradicated (172,174,186-189). is indicated for HCP with GAS infections until 24 hours after
they have received appropriate therapy. However, no work re-
Antimicrobial treatment to eradicate carriage should be
limited to HCP who are carriers epidemiologically linked to strictions are necessary for HCP colonized with GAS unless they
have been epidemiologically linked to transmission of infection
disease transmission. Several antimicrobial regimens have been
within the facility.
used successfully to eradicate staphylococcal carriage in HCP
(190,191). Current regimens for decolonization of patients
typically include a topical antimicrobial agent (e.g., mupi-
TUBERCUWSIS
rocin) alone or in combination with topical antiseptics (e.g.,
chlorhexidine or diluted bleach baths). Oral antimicrobials Healthcare-associated transmission of Mycobacterium tuberculosis
are not routinely used to eliminate carriage. If employed, oral (MTB) is well documented, but such transmission in the
antimicrobial regimens may consist of a rifampin-based com- United States is generally low. However, the risk can be
bination (e.g., with trimethoprim-sulfamethoxazole or doxycy- increased in healthcare facilities located in communities with
cline) and may be used with a topical antiseptic (192). Resistant (a) high rates of HIY, (b) high numbers of persons from
S. au:reus strains have emerged after the use of these oral or TB-endemic countries, and (c) a high prevalence of TB
topical antimicrobial agents for the eradication of colonization infection (206,207). During the TB resurgence of the
(190,191,193,194). early 1990s, some areas in the United States experienced an
Restriction from patient<are activities or food handling is increase in the incidence and prevalence of multidrug-resistant
indicated for HCP who have draining S. au11!1W skin lesions until M. tuberculosis (MD R-TB), which included healthcare-associated
they have received appropriate therapy and the infection has MDR-TB outbreaks (208-216). In response, US government
resolved. In the case of a chronic draining S. aUfliUS skin lesion, agencies, state and local health departments, healthcare-
considerations for earlier return to work could include the lo- related professional associations and societies, and other part-
cation of the provider's infection (e.g., on areas that should not ners developed and implemented effective TB infection control
come into contact with patients, such as the legs), if the lesion and prevention measures (217,218). By the late 1990s, the
can be completely and continuously covered, the hand hygiene prevalence of MDR-TB had decreased by 50% and no further
and IP practices of the individual provider, and others. No work healthcare-associated outbreaks were being reported (219).
restrictions are necessary for HCP colonized with S. aun!US un- Transmission of MTB can be minimized by developing
less they have been epidemiologically implicated in S. au11!1W and implementing an effective TB control program that is
transmission within the facility. based on a hierarchy of controls: (a) administrative controls,
(b) engineering controls, and (c) respiratory protection until the scab has separated from the skin (2 to 21 days after vac-
(207,209,220-22g). cination); thus, susceptible persons could acquire vaccinia from
A TB screening program for personnel is an integral part of a recently vaccinated person (226-229). Covering the vaccina-
a healthcare facility's comprehensive TB control program. Either tion site and washing hands after contact with the vaccination
tuberculin skin test (TST) testing or interferon gamma release as- site (including bandages) will prevent transmission.
say (IGRA) testing may be used without preference among HCP Smallpox vaccination (every 10 years) is indicated for per-
for baseline (e.g., during placement evaluations) or subsequent sonnel who work directly with orthopox viruses (e.g., monkey-
TB screening to identify those who have been infected (224). pox, vaccinia, variola) or in animal care areas where orthopox
Routine testing with both a TST and an IGRA is generally not viruses are studied. In selected instances, vaccination should be
recommended. For personnel with a history ofBacille Calmette- considered for HCP who provide care to recipients of recom-
Guerin (BCG) vaccination, use of an IGRA test is preferred over binant vaccinia vaccine (20). HCP who receive the vaccine may
TST for TB testing to increase diagnostic specificity (224). continue to have contact with patients if the vaccination site is
For baseline testing, a two-step TST procedure for person- covered and hand hygiene is strictly observed (20). Vaccine is
nel without a TST in the past 12 months should be used to not recommended for HCP with immunosuppression, eczema,
minimize the likelihood of confusing reactivity from an old a heart condition, three or more known major cardiac risk
infection (boosting) with reactivity from a recent infection factors, or for HCP who are pregnant or breast-feeding.
(conversion). Two-step testing is not required for IGRAs be-
cause IGRA testing does not boost subsequent test results.
VARICELLA
Criteria used for interpretation of a TST reaction can vary
depending on (a) the purpose (diagnostic or epidemiologic) Healthcare-associated transmission of varicella-zoster virus (VZV)
of the test, (b) the prevalence of TB in the population being is well recognized (230-234). Sources for healthcare exposures
tested, and (c) the immune status of the host. At a minimum, have included patients, HCP, and visitors (including the children
annual TST or IGRA testing is indicated for personnel with the of HCP) with either varicella or herpes zoster (HZ).
potential for exposure to TB. The incubation period for varicella is usually 14 to 16 days
Obtaining an initial chest radiograph for HCP with positive but can be from 10 to 21 days after exposure, although the in-
TST reactions or IGRA tests, documented TST or IGRA conver- cubation period can be shorter in immunocompromised per-
sions, or symptoms suggestive of TB is important. In addition, sons (235). In persons who receive postexposure VZV immune
HCP who have positive TST reactions or positive IGRA tests globulin, the incubation period can be as long as 28 days after
but also received adequate preventive treatment do not need exposure. Transmission of infection may occur from 2 days be-
repeat chest films unless they have symptoms suggestive of TB. fore rash onset until crusting of all lesions, typically 4 to 7 days
Administering TSTs to personnel as soon as possible after after rash onset (2g5)
MTB exposures is recognized as important. Such immediate VZV is transmitted by contact with infected lesions and, in
TST testing establishes a baseline with which subsequent TSTs hospitals, airborne transmission has occurred from patients
can be compared. A TST performed 8 to 10 weeks after the last with varicella or HZ to susceptible persons who had no direct
exposure will indicate whether infection has occurred. Persons contact with the infected patient (2g6-240). Adherence to air-
already known to have reactive TSTs need not be retested. HCP borne and contact precautions when caring for patients with
with evidence of new infection (i.e., TST conversions) need to known or suspected VZV infection can reduce the risk of trans-
be evaluated for active TB. If active TB is not diagnosed, pre- mission to HCP (56) .
ventive therapy should be initiated (207). It is generally advisable to allow only HCP who have evidence
For HCP with positive TST or IGRA results who were prob- of varicella immunity to take care of patients with VZV. Because
ably exposed to drug-susceptible MTB, preventive therapy with of the possibility of transmission to and development of severe
isoniazid is indicated unless there are contraindications to such illness in high-risk patients (e .g., pregnant women, premature
therapy (207). Alternative preventive regimens have been pro- infants born to susceptible mothers, infants born at <28 weeks'
posed for persons who have positive TB-test results after expo- gestation who weigh ~1,000 g regardless of maternal immune
sure to drug-resistant MTB (22g,225). status, and immunocompromised persons of all ages, includ-
HCP with active pulmonary or laryngeal TB can be highly ining persons who are undergoing immunosuppressive therapy,
fectious; exclusion from duty is indicated until they are nonin- have malignant disease, or are immunodeficient), HCP with
fectious. Work restrictions are not necessary for HCP receiving localized HZ should not take care of such patients until all le-
preventive treatment for latent TB (i.e., positive TST or IGRA sions are dry and crusted (13,240) . HCP with localized HZ are
result without active disease) or for HCP with latent TB who do not likely to transmit infection to immunocompetent patients if
not accept preventive therapy. However, these HCP should be their lesions can be covered. However, some institutions may ex-
instructed to seek evaluation promptly if symptoms suggestive clude HCP with HZ from work until their lesions dry and crust.
of TB develop. Administration of varicella vaccine is recommended for all
HCP without evidence of varicella immunity. Evidence of pre-
existing immunity includes (a) written documentation ofvac-
VACCINIA
cination with two doses of varicella vaccine, (b) laboratory
Through aggressive surveillance for smallpox combined with evidence of immunity or confinnation of disease, (c) diagnosis
the effective use of smallpox vaccine (vaccinia virus vaccine), the or verification of a history of varicella by a healthcare provider,
World Health Organization was able to declare the world free or (d) diagnosis or verification of a history of HZ by a health-
of smallpox in 1980. The smallpox vaccine licensed for use in care provider (9,13) . HCP without evidence of immunity to
the United States is derived from infectious vaccinia virus. Mter varicella should receive two doses of varicella vaccine adminis-
vaccination, the virus can be cultured from the vaccination site tered 4 to 8 weeks apart. If >8 weeks elapse after the first dose,
the second dose may be administered without restarting the identified case-patient because of the risk for severe disease in
schedule. Recently vaccinated HCP do not require any restric- these groups. If the VZV exposure was to localized HZ with cov-
tion in their work activities; however, HCP who develop a vac- ered lesions, no work restrictions are needed if the exposed
cine-related rash after vaccination should avoid contact with HCP had previously received at least one dose of vaccine or
persons without evidence of immunity to varicella who are at received the first dose within 3 to 5 days postexposure. A sec-
risk for severe disease and complications until all lesions re- ond dose should be administered at the appropriate interval.
solve (i.e., are crusted over) or, if they develop lesions that do HCP should be monitored daily during days 8 to 21 after expo-
not crust (macules and papules only), until no new lesions ap- sure for fever, skin lesions, and systemic symptoms suggestive of
pear within a 24-hour period (9). Persistence of immunity to varicella and excluded from a work facility if symptoms occur.
VZV after vaccination of HCP has been demonstrated up to If at least one dose was not received, restriction from patient
8.4 years (241). contact is recommended (9).
Transmission of the vaccine virus is rare and has been docu-
mented in immunocompetent persons by polymerase chain re-
VIRAL RESPIRATORY INFECTIONS, INCLUDING
action (PCR) analysis from only eight persons, resulting in nine
INFLUENZA AND RESPIRATORY SYNCYTIAL
secondary infections, since implementation of the varicella vac-
VIRUSES
cination program. All episodes resulted in mild disease without
complications (242). No transmissions have been documented Healthcare-associated respiratory infections can be caused by
from vaccinated HCP. a number of viruses, including adenoviruses, influenza virus,
HCP who have received two doses of vaccine and who are parainfluenza viruses, respiratory syncytial virus (RSV), rhinovi-
exposed to VZV (varicella, disseminated HZ, and uncovered ruses, or coronavirus (i.e., SARS) (243). This section focuses on
lesions of a localized HZ) should be monitored daily during prevention of influenza and RSV.
8 to 21 days after exposure for fever, skin lesions, and systemic
symptoms suggestive of varicella. HCP can be monitored di-
rectly by occupational health program or infection-control
practitioners or instructed to report fever, headache, or other Healthcare-associated transmission of influenza has been re-
constitutional symptoms and any atypical skin lesions immedi- ported in acute and long-term care facilities (244-247), and
ately. HCP should be excluded from a work facility immediately can occur in any healthcare setting. Transmission has occurred
if symptoms occur. HCP who have received one dose of vac- from patients to HCP (245,246), from HCP to patients (248),
cine and who are exposed to VZV (varicella, disseminated HZ, and among HCP (247,249-251).
and uncovered lesions of a localized HZ) (in the community or Traditionally, influenza viruses have been thought to spread
healthcare setting/workplace) should receive the second dose from person to person by large-particle respiratory droplet
within 3 to 5 days after exposure to rash (provided 4 weeks transmission. Transmission via large-particle droplets requires
have elapsed after the first dose) . After vaccination, manage- close contact between source and recipient persons, because
ment is similar to that of two-dose vaccine recipients. Those droplets generally travel only short distances (approximately
who did not receive a second dose or who received the second 6 ft or less) through the air. Indirect contact transmission via
dose >5 days after exposure should be excluded from work for hand transfer of influenza from virus-contaminated surfaces
8 to 21 days after exposure (9). or objects and airborne transmission via small-particle aero-
Unvaccinated HCP who have no other evidence of immu- sols in the vicinity of the infectious individual may also occur.
nity who are exposed to VZV (varicella, disseminated HZ, and Airborne transmission over long distances, such as from one
uncovered lesions of a localized HZ) are potentially infective patient room to another, has not been documented and is
from days 8 to 21 after exposure and should be furloughed dur- thought not to occur (252).
ing this period. They should receive postexposure vaccination The incubation period of influenza usually is 1 to 5 days,
as soon as possible. Vaccination within 3 to 5 days of exposure and the period of greatest communicability is during the first
to rash might modifY the disease if infection occurred. Vaccina- 3 days of illness. However, virus can be shed before the onset
tion >5 days postexposure is still indicated because it induces of symptoms and as long as 7 days after illness onset and can
protection against subsequent exposures (if the current expo- be prolonged in young children and immunocompromised
sure did not cause infection). persons (253,254). Adherence to droplet and standard precau-
For HCP at risk for severe disease for whom varicella vac- tions can prevent healthcare-associated transmission of influ-
cination is contraindicated (e.g., pregnant or immunocompro- enza (56,252).
sed HCP), varicella-zoster immune globulin after exposure is Facilities are strongly encouraged to provide vaccine to HCP
recommended. The varicella-zoster immune globulin prod- by using approaches that maximize vaccination (1,252,255) .
uct currently used in the United States, VariZIG (Cangene During institutional influenza outbreaks, prophylactic an-
Corporation, Winnipeg, Canada), is available under an Inves- tiviral agents (e.g., neuraminidase inhibitors) can be used in
tigational New Drug Application Expanded Access protocol; a conjunction with influenza vaccine to reduce the severity and
sample release form is available at http://www.fda.gov/down- duration of illness among unvaccinated HCP. Oseltamivir or
loads/BiologicsBloodVaccines/SafetyAvailability/U CM176031. zanamivir may be administered for 2 weeks after HCP vacci-
pdf. Varicella-zoster immune globulin might prolong the in- nation or, in unvaccinated HCP, for the duration of influenza
cubation period by a week, thus extending the time during activity in the community (256). Prophylactic antiviral medica-
which personnel should not work from 21 to 28 days. In an tions can be offered to unvaccinated HCP who provide care to
outbreak, HCP without evidence of immunity who have con- persons at high risk or to all HCP regardless of their vaccina-
traindications to vaccination should be excluded from the tion status if the outbreak is suspected to be caused by a strain
outbreak setting through 21 days after rash onset of the last of influenza virus that is not well matched to the vaccine.
RMpiratory Syncytitzl Virus 11. Watoon JC, Hadler SC, Dykewicz CA, ct al. Meaoleo, mumpo, and rubella---va<:cine we and
strategies for climioa.ti.ou of mcule1, rubella, and amgt:nital rubella lfDdrome and con-
trol of mumpo: recommendation• of the Advioory Committee on Immunization Practice•
Healthcar~sociated transmission of RSV is greatest during the
(ACIP) • .MMMH!.am"" &p. 1998;47:1-57.
early winter when community RSV outbreaks occur; patients, vis- 12. Centenfur Diaeaoe Control and Prevention. Notice to readen: updated recmnmendations
itors, and HCP can transmit the virus in the healthcare setting. of the Advisory Committee on lmmmrization Practices (ACIP) for the coutrol and elimina-
tion of mumpo. MMWR Mm!> .M..W "!my Rip. 2006;55:~50.
RSV infection is most common among infants and children, who 15. Marin M, Gwu D, Sandra S, et al. P"""""tion of varicella: recommendation• of the Advi-
are likely to experience more severe disease. Healthc~soci oory Committee on Immunization Practiceo (AClP). MMWR ~ &p. 2007;56:1--40.
14. Centers for Dileue Control and Prevention. FDA approval of an extended period for ad-
ated transmission has been reported most frequently among
ministering VarlZIG fur pootexpooure prophylaxio of varicella. MMWR MoriJ M..W ~
newborn and pediatric patients (257,258), but outbreaks associ- Rip. 2012;61:212.
ated with substantial morbidity and mortality have been reported 15. Bilukha 00, Rooenotein N, et al. Pre.=tion and control of meningoroa:al dileaoe. Rec-
ommendation~ of the Advilory Committee on Immunization Practiceo (ACIP). MMWR
among adults in bone-marrow transplant centers (259), inten- &com... &p. 2005;54:1-21.
sive care units (260), and long-term care facilities (261,262). 16. Centen for Dileue Control and Prerention. Updated recommendation from the Adrioory
RSV is present in large numbers in the respiratory secretions Committee on Immunization Practia:o (ACIP) for n:vat:cination of peroono at prolonged
increased risk for meningocoa:al dileaoe. MMWRMoriJMnrtal ~ &p. 2009;58:1042--100.
of persons symptomatically infected with the virus and can be 17. Ceu.ten for Di1eue Control and Pn:veu.tion. Updated recommeudatiom for use of me-
transmitted directly through large droplets during close con- ningococcal conjugate vaccineo----Advioory Committee on Immunization Practiceo (ACIP),
tact with such persons or indirectly by hands or fomites that are 2010. MMWR Mml> Mortal twy &p. 2011;60:72-76.
18. Flore AE, Uyeki TM, Broder K. et al. Prevention and control of Wfluenza with vaccineo:
contaminated with RSV. Hands can become contaminated by re00111111endation1 of the Advilory Committee on Immunization Practice> (ACIP), 2010.
handling infected persons' respiratory secretions or contami- MMWR~Rip. 2010;59:1~ .
19. Rotz LD, Dotoon DA, Damon IK, ct aL Vaccinia (llllallpox) vaccine: recommendations of
nated fomites and can transmit RSV by touching the eyes or the Advilory Committee on Immunization Practiceo (ACIP), 2001. MMWR &com• &p.
nose (243). The incubation period ranges from 2 to 8 days; 2001;50:1-25, quiz CEl-7.
4 to 6 days is most common. In general, infected persons shed 20. Wharton M, Stribt RA, Haipaz R, et al. Recommendations for uoing om.allpox vaccine in
a prcx:vent vaccination prognun. Suppl.elllental recommendation~ of the Adrioory Com-
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long as 3 to 4 weeks. Adherence to contact precautions effec- Adrioory Committee (HICPAC). MMWR &cooooo Rip. 200!;52:1-16.
21. Kretoinger It, Broder KR, Corteoe MM, et al. Preventing tetanuo, diphtheria, and pertuooil
tively prevents healthcare-associated transmission.
among adulu: we of tetanw tmroid, redw:ed diphtheria toxoid and acellular pertuooil
vaccine recommendation• of the Advilory Committee on Immunization Practice• (ACIP)
and re00111111endation of ACIP, aupported by the Healthcare Infection Control Practice•
Work &strictions Adrioory Committee (HICPAC), fur we of Tdap among health-<:are penonnel. MMWR
.n-.. &p. 2006;55:1-57.
Because large numbers of HCP can have viral respiratory ill- 22. Centers for Dilleaoe Control and Pn:.=tion. Updated recommendations for use of tetanU>
tomid, reduced diphtheria tomid and acellular pertwllil (Tdap) vaccine from the Adrioory
nesses during the winter, it might not be possible to restrict Committee on Immunization Practice•, 2010. MMWRMorl> Mortal HW)Rip. 2011;60:15-15.
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Rip. 2005;54:1-16.
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care for patients in a protective environment, such as hemato- of the Adrioory Committee on hmnunbation Practice• (AClP) Part II: illlmunbation of
adulto. MMWR&comm &p. 2006;55:1--ll!, quiz CE1-4.
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27. Centers for Diaease Control and Prevention and Adrioory Committee on Immuniza-
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191. Kluytmam JA, Wertheim HF. N:ual camag., of SIGplo'}IMJccw ""'""'and prevention of 225. Centers for Dioeaae Control and Prevention. Manag=ent of peroono exposed to multi-
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192. Liu C, Bayer A, Coogrove SE, et al. Clinical practice guideline• by the Infectiouo Dioeaoeo 226. Lane JM, Ruben FL, NeffJM, et al. Complicatiom of omallpox vaccination, 1968: results
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inkctiono in adulto and cbildren. Clin bifoct Di.J. 2011;52:elS.....55. 227. Centers for Dioeaae Control and Prevention. Contact opread of vaccinia frOJil a recently
195. Peru-Fontm M, Rooaleo M, Rodrfguu{)annonaA, etal. Mupirocin relliltance after long- vaccinated Marine-Louiaiana. MMWR Mmi! Mortal M!:I&Jl. 1984;!15:~7-!8.
~ we for SIGplofi"<JJccw ..,......, coloni<ation in patiento undergoing chrome periloneal 228. Centers for Dioeaae Control and Prevention. Contact opread of vaccirrla from a National
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194. Fa1aga> ME, Bliziotio lA, Fn!Joulia KN. Oral rifiunpin for eradication of SIGplo'}IMJccvs av- 229. Gentero for Di•eaae Control and Prevention. Vaccinia outbreak-Newfowullaud. MMWR
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197. Weber DJ, Rulola WA, Denny FW Jr. Management of bealthcare workero with pharyngitio virus. bofrcl ~ 1986;7:!12-316.
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198. Mastro TD, Farley TA, Elliott JA, et al. An outbreak of mrgical...aund inkctiono due to tion control practitioner. A•1 Infoct CtmlrDl. 1987;15:207-211.
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201. Bert.elman RL, Martin D, Gillham DR, et al. Streptococcal wound infection• caused by a di=t contact with an indicator zooter ca.oe and il! prevention by a live vaccine. BibnJ
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202. SehaffnerW,Lefkowitz LBJr, GoodmanJS, et al. Hoopital outbreakofinfectiom with group 237. Sawyer MH, Chamberlin q, Wu YN, et al. Detection ofwricella-woter virus DNA in air
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205. Centers for Dioeue Control and Prevention. Nooocomial group A otreptococcal infec- 238. Leclair JM, Zai.a JA, Lev.in MJ, et a1. Airborne traDmliloion of chickenpox in a hoopital.
tions aaoociated with aaymptomatic bealt!H:are ""rken-Maryland and Califomi.a, 1997. N ER«<J M.d. 1980;S02:450-453.
MMWRMm6 Martal M'1 &p. 1999;48:16!1-166. 239. Gwtafoon TL, Lavely GB, Brawner ERJr, et al. An outbreak of airbome nosocomial wri-
204. American Academy ofPediatrico. Summarie1 of infectious diaeaoeo: group A streptococcal cella.l'IIUotrics. 198.2;70:55~556.
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tion ofinvuivc group A streptococcal diaeaae among household contactl of cue patiento after vaccination of healtbcare ""rken. Infld C<mlrol Hwp ~ 2001;22:279-28S.
and among pootpartulll and poouurgical patient!: recommendation• frOJil the Centers 242. Gerohon A, Tabb..hi M, Seward]. Varicella vaccine. In: Plotkin S, Orenstein W, Oflit P,
for Dioeaae Control and Prevention. ClinlnfoctlJi.J. 2002;!15(8):95<HI59. edo. Vaccitw. Pbiladelpbia, PA: W.B. Saunders; In preoo.
206. Bameo PF, Bloch AB, Davidson PT, et al. Thben:ul.oois in patiento with human immunodt>- 243. Tablan OC, Andenon LJ, Beoaer R, et al. Guideliueo for prevcntiug bealth-<:are-<lllooci-
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207. Jcnoen PA, Nardcll E, Volcbenkov G. Guidelines for prevcntiug the tranllllliaai.ou of 1\f;l,.,. Practices Advioory Committee. MMWRR.Amm&p. 2004;53:1--!16.
b..a.riuoolvbomUolis in health-care aettingo, 2005. MMWR RIAmm &p. 2005;54:1-141. 244. Evano ME, Hall RL, Berry SE. Influenza control in acute care hoopitalo. A,.1bifoct ~
208. Edlin BR, Thkan Jl, Grieco MH, et al. An outbreak. of multidrug-reoistant tuberculollil 1997;25:357-362.
among hospitalized patienl! with the acquired immunodeficiency oyndrome. N FAtg!1 245. Kapila R, Lintz DI, Tecoon FI', et a1. A nosocomial outbreak of influenz.a A Chm.
M«l.1992;526:1514-1521. 197'1;71(5):576-5?'9.
209. Stroud LA, Tokanjl, Grieco MH, et a1. Evaluation of infection control meaoureo in pre- 246. Van Varia LP, Belohe RB, ShafferJL. Nosocomial influenza B virus infection in the elderly.
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New York City hoopital. Infoct Cont7ol H..p EJ>id-it>L 1995;16:141-147. 247. Pachucki CT, Pappu SA, Fuller GF, et al. Influenz.aAamong hoopital personnel and patients.
210. Beclt-Sague C, Dooley SW, Hutton MD, et a1. Hoopital outbreak of multidrug..-elliltant Implication• for recognition, prevention, and control Anlllnlcm MMl. 1989;149:77-M.
My~ lvbomUoJis inkctiono. Factors in tranuniaai.on to otaff and HIV-infected pa- 248. Centers for Diocue Control and Prevention. Suopected nooocomial influenza caoeo in an
tiento. .fi4MA.1992;268:128~1286. intenme care uniL MMWR Mmi! Martal M'1 &p. 1988;S7:H, 9.
211. Wenger PN, Ottenj, Breeden A, et al. Control of nooocomial tranomiooion of mullidrug- 249. Centero for Diocue Control and Prevention. Outbreak of influenza A in a nuroing
relliltant 1\f;l~ lvbomUoJis among healthcare workers and HIV-infected patiento. home-New York, December 1991-JanuaiY 1992. MMWR Mmi! Martal W1l!:l &p. 1992;41:
Ltmat. 1995;345:2!1>-240. 129-131.
212. Dooley SW, Villarino ME, Lawrence M, et a1. Noaocomial tranomiooion oftuberculooio in 250. Grooo PA, Rodotein M, LaMontagne JR, et al. Epidemiology of acute reopiratory illneaa
a boopital urrlt for HIV.mfi:cted patiento. fAMA. 1992;267:26!2-2634. during an influenza outbreak. in a nuroing borne. A prospective otudy. An-h l11t11m M.d.
215. Pearoon ML,JerebJA, Frieden TR. etal. Nooocomial tranllllialion ofmultidrug-relliltant 1988;148:559-561.
My~ lvbm:ulo.riJ. A riok to patienl! and health care workers. Ann lnllrm Mod. 251. Cartter ML, Rcuzullo PO, Hclgenon SD, et al. Inflw:w:a outhrealu in nuning homes:
1992;117:191-196. how effective io influenza nccine in the inotitutionalized elderly? bifoct Ctmlrol Hwp
214. CU:vclandJL, Kentj, Gooch BF, et al. Multidrug-reoiotant M~""' tubm:ulasit in an EJ>it1-ia1. 1990;11 :4 7H78.
H1V dental clinic.Infoct ContnJIHwpEp~ 1995;16:7-11. 252. Centers for Dioeaae Control and Prevention. Prevention •trategieo for oeuonal influenza
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nodeficiency virus and suboequent tranomiooion of multidrug-reoiotant tuben:ul.oois in a .cdc.guv/flu/profnlionalo/infectioncontrol/healthcareoettingo.htm.
bealtbcare worker. Infoct CrmbrJIHospEpitlnrtiol. 1997;18:422-42!. 25S. Hall CB, Douglas RGJr. Nooocomial influenza infection as a cause of intercurrent revcn
216. JerebJA, Klevcno RM, PrivcttTD,etal. Thberculooio inheallhcare,.,.kero at ahoopital with an in inhnl!. ~ 1975;55:67!h'l77.
outbreak of mu!Jidrug..-coiotant ~ tuiJomlloriJ. AnA lnlcm M<rL 1995;155:854-&9. 254. Noble GR. Epidemiological and clinical aspects of influewa. ID: Beare AS, ed. App&rl
217. Centers for Dioeue Control and Prevention. National action plan to combat multidrug- lnjlvmi.G ~ FL: CRC Pre11; 1982:11-49.
relliltant tuberculooia. MMWRRM:mlta&p. 1992;41:5-48. 255. Adal KA, Flowen RH, Anglim AM, et al. Prevention of nosocomial influenza. bl{fcl Comrol
218. Centers for Dileaoe Control and Prevention. Guldelineo for prevenling the tranuniaai.on HwpEp~ 1996;17:641~48.
of M~,...lvbm:ulo.riJin healt!H:are facilitieo, 1994. Centero for Diaeaae Control and 256. Fiore AE, Fry A, Shay D, et a1. Antiviral agento for the treatment and chemoprop~•
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219. Centen for Dioeaae Control and Prevention. RlporVdlvbm:ulo.riJ in tho lhlilcs S14W, 2010. (ACIP). MMWR&cmram &p. 2011;60:1-24.
Atlanta, GA: CDC, U.S. Department of Health and Hwnan Semceo. 257. Hall CB. Reopiratory oyncytial virus: il! tranllllialion in the hoopital environment. Yak J
220. Pugliese G, lipper ML. Thberculooia control in health care.Infoct Comro!Hwp EpidmWJI. Bioi Mid. 1982;55:21~225.
1996;17:81-27. 258. Suydman DR, Greer C, Meilloucr HC, et a1. Prevention of nooocomial trauomiaai.on of
221. Menzies D, Fanning A, Yuan L, et al. Thberculolio among health care worken. N ER«<J reiJ>iratory oyncytial virus in a newborn nuroery. Irifrc1 C<mlrol Hosp EpillnWJI. 1988;9:
M<rL 1995;!152:92-98. 105-108.
222. Janio WR. Nooocomial trannniuion of multidrug..-elliltant ~ tubm:ulasit. Am] 259. Harrington RD, Hooton TM, Hackman RC, et al. An outbreak of relpiratory oyncytial
Infect Cmtlrol. 1995;2!:146-151. virus in a bone manvw tranoplant center. 1 Infra Dis. 1992;165:987--995.
225. Maloney SA, Peanon ML, Gordon MT, et al. Efficacy of control meaaureo in preventing 260. Guidry GG, Bla.ct-Payne CA, Payne DK, et al. Reopiratory oyncytial virus infection among
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workers. Ann Illlml Mid. 1995;122:90-95. 261. Faloey AR. Noninfluenza reopiratory virus infection in long-term care facilities. Infocl
224. Mazurek GH, Jereb J, Vernon A, et al. Updated guidelines for using wterlcron Gamma Contrul Hwp EpidnnWL 1991 ;12:602~8.
Releaoe Aooayo to detect My~ luiJemMoJiJ infection- United Stateo, 2{)10. MMWR 262. Sonillo PJ, Huie SF, Struoburg MA, et al. An outbrea). of respiratory oyncytial virus
&cmrta&p. 2{)10;59:1-25. pneumorrla in a nuniug home for the elderly. 1Infect. 1984;9:252-256.
5 Hilary M. Babcock and Keith F. Woeltje
The Developntent of Infection

Surveillance and Prevention Prograrr1s
INTRODUCTION in medical and nursing care, but also in healthcare epidemiol·
ogy. More recently, the IP field baa appreciated the importance
The goal of an infection surveillance, prevention, and control of business and management skills aa well. From a financial per-
program is to prevent healthcare-associated infections (HAls) spective, IP departments are viewed aa nonrevenue-generating
in patients, employees and visiton, and to achieve that preven- department! because there ill no charge to the patient or payor.
tion in a cost-effective manner (1). Therefore, evexy infection H careful demonstration of the value to the organization ill not
prevention (IP} (previously called infection control [IC]) pro- documented and shared with key leaders, including those who
gram should formally evaluate the impact of prevention efforts bold the purse strings, IP may find its financial resources lim-
and their cost-effectiveness (2,3). More recently, IP programs ited or diminished. To garner resources for the program and its
have embraced the concept of interventional epidemiology, mission of preventing H.Als, an IP program must adopt the new
which emphasizes the importance of viewing the activities and approach of"interventional epidemiology" and "give sufficient
decillions made by IP from a business perspective, including weight to the economic impact of any project or activity undei~
global systems thinlcing ( 4). taking" ( 4). IP program personnel must incorporate effective-
The term epidemiology in the context of an IP program re- ness evaluations into routine pr<!iect and program planning so
fen to the study of the enumeration, distribution, and control that they can demonstrate the value of IP and control to the
of infectious diseases (IDs) in its target healthcare population healthcare organization.
(e.g., patients, visiton, and employees). Individuals charged
with directing an IP program must be knowledgeable in the
science of epidemiology, including surveillance methodology, COMPONENTS OF AN INFECTION
study design, statistical methods, infectious agents, and many CONTROL PROGRAM
other competencies (5). It is no surprise that these sJtills are
the 3allle set used by public health professionals, because IP An IC program baa many facets; however, the central com·
was born out of public health in the late 1950s when there wu ponents to be addressed when developing a program are
mounting concern regarding the transmission of infectious governance, personnel, and the IP plan, including the sur-
agents within hospital settings. veillance plan. Also critical to an effective program are the in-
In 1958, outbreaks of Staphylococcvs aumuinfections in hos- ternal and external collaborations, compliance activities, and
pitals prompted the American Hospital .Anociation to recom- interventions.
mend that hospitals set up IP programs (6). A few years later,
in the early 1960s, the Centen for Dilleue Control (now the
GOVERNANCE
Centers for Disease Control and Prevention [CDC]) organized
an investigations section that would assist hospitals in investigat- A successful IP program must have both medical and admin-
ing outbreaks. As the 1960s progressed, medical care became istrative support and participation to accomplish its goals.
increaaing complex.. Antibiotic-resistant organums and oppor- Often this is accompllished through a formalized IP commit-
tunist pathogens presented increaaing challenges to the IP and tee that makes decisions and recommends policies for the
control efforts within the hospital setting (4,'1). Nationwide facilities' IP program (11). The IP committee repom to a
adoption of hospital IC programs did not occur until the early governing body within the hospital, such aa a medical execu-
1970s when the CDC and the Joint Commission on Accredita- tive group or the hospital's administrative board. 1'hill body
tion of Hospitals (now simply the Joint Commission) recom- reviews and acts on the committee's recommendations. The
mended that hospitals have IP progranu (6,8). The landmark governing body may, in tum, request a review of a current
Study of the Efficacy of Nosocomial Infection Control (SENIC) topic in the community or a hospital-specific policy, practice,
project demonstrated that an active IP program that included or issue brought forward from another hospital forum such
surveillance with feedback of infection rates, administered by a aa a surgical committee. Although the joint Commission no
physician and nurse with IC knowledge, resulted in a reduction longer requires an IP committee per se, the IP standards do
ofHAis (9,10). call for the demonstration of collaboration between medical
Because the historical development of IP programs bad epi- staff, administraton, multiple hospital specialties, and IP to
demiologic roots, personnel charged with I'UDI1ing the IP pro- develop and aasess the IP program (12). It ill necessary for a
gram traditionally were expected to have strong skills not only hospital to demonstrate that IP occurs in all aapects of services
57
rendered throughout the institution and that all employees to focus on surveillance, prevention, and control activities.
understand their job-specific IP actions. In addition, some Secretarial support for scheduling meetings; typing minutes,
states require that hospitals have a formal IP committee as policies, correspondence, and other documents; and maintain-
part of the hospital licensing rules. ing general paperwork can greatly enhance a program's ef-
fectiveness. Additional services for forms creation, data entry,
and data management should be available to the IP program
DepR-rtmentlll Reporting Struaure
(1). The size of the facility and the complexity of the IP pro-
Like the governance of IP, no single departmental report- gram will determine whether these are dedicated or shared
ing structure fits every healthcare facility. Across the country, personnel resources. Some facilities have found that sharing
there are many examples of effective programs that report to secretarial, chart abstraction, data entry, or database manage-
different roles or departments, such as nursing, quality, pa- ment personnel between departments such as IP, quality, and
tient safety, or medical services. Regardless of the chain of regulatory proves cost effective.
command, the critical components are the support of the
program during routine operations, and an appreciation of
THE INFECTION PREVENTION PLAN
critical issues that require immediate attention and added
resources, such as sentinel events, outbreaks, or community The annual IP plan is an essential roadmap for the activities
emergencies. that the IP program will undertake. The annual plan is devel-
oped based on the IP program's strategic or long-term goals
and the institution's mission and strategic objectives. Strategic
PERSONNEL
planning should encompass traditional business strategies,
Personnel needs are established based on the size, complex- entrepreneurial thinking, and futurist exercises (16). Institu-
ity, services, and the needs of the facility and the community. tional initiatives, new laws and regulatory requirements, and
A hospital epidemiologist and at least one infection preven- newly published methods for preventing infections should
tion specialist (IPS, also called infection preventionists) are be incorporated. Components of the plan include the over-
the minimum personnel needed for an IP program. The hos- all mission and goals of the program, the goals for the year,
pital epidemiologist may be a physician and in many instances and the scope of the IP department, including the depart-
is an ID physician. The expert knowledge of an ID physician ment staffing, hours and mechanisms for providing 24-hour
is very useful; however, it is also necessary for the hospital coverage.
epidemiologist to have specialized training in epidemiology Another foundational component of the annual IP plan
and IP. The Society for Healthcare Epidemiology of America is the surveillance plan. This plan should include the spe-
(SHEA) in conjunction with the CDC, some medical schools, cific indicators to be followed during the year (e.g., intensive
and other professional organizations offer specific training. care unit (ICU) central line-associated bloodstream infec-
The hospital epidemiologist often serves as the chair for the tion (CLA-BSI) rates and surgical site infection (SSI) rates in
IP committee and is involved in the planning and implemen- cardiac surgery), the rationale for choosing those indicators,
tation of the program. The position of hospital epidemiolo- case-finding methods, definitions, and data management
gist is typically not a full-time position or a hospital employee; strategies including report distribution. Evaluation of the his-
the physician contracts with the hospital for epidemiology torical data and a review of services and populations served
services (13). by the institution will guide the development of the IP sur-
The IPS usually is a registered nurse or a medical tech- veillance plan ( 17) . The surveillance plan is only a part of the
nologist. Specialized training programs for IPS are offered IP plan. Not only is the IP program a surveillance program,
by the Association for Professionals in Infection Control and but it should also incorporate activities directly aimed at im-
Epidemiology (APIC), the Community and Hospital Infection proving endemic rates. Although IP is charged with protect-
Control Association-Canada (CHICA), other international ing against and investigating outbreaks, only approximately
societies, and other organizations including state hospital as- 5% to 10% of all HAis are associated with outbreaks. The
sociations and health departments. Professional and practice other 90% to 95% of HAis are due to endemic or common
standards define the required competencies and professional causes; therefore, the majority of prevention efforts should
accountabilities of the IPS (5) . After 2 years ofiP practice and be focused on reducing endemic HAis and mitigating HAl
passing a voluntary, standardized examination to demonstrate risks (18-20).
proficiency in basic IP and control knowledge (14), physicians, A plan for IP-related educational activities is an important
technologists, and nurses are eligible to become Certified in component of the IP plan. In addition to routine require-
Infection Control (CIC) by APIC (other international organiza- ments, such as new employee and annual education, a review
tions may have other criteria). of the questions and concerns posed by employees in the past
Historically, one IPS for every 250 beds was recommended will provide a foundation for new programs or highlights for
based on the SENIC study (9). Advances in medicine, changes the year. It may be helpful for the IPS to log calls received to
in healthcare delivery, and increasing regulatory and compli- examine for common educational themes.
ance requirements have outdated this figure (1). A Delphi A schedule for periodic reviews of policies and procedures
project sponsored by APIC noted that staffing decisions should should be included in the IP plan as well. Although this review
consider the facility's size, needs, complexity, and patient popu- is often seen as a tedious administrative task, it can be turned
lation. In general, it recommended a ratio of 0.8 to 1.0 IPS for into a productive activity if it is accompanied by a review of any
every 100 occupied acute care beds (15). new literature or guidelines and a departmental walk-through
In addition to the hospital epidemiologist and at least one that assesses the current environment and practices for their
IPS, support personnel are needed to allow the trained IP staff impact on patient and employee HAl risk.
Chapter 5 • The Deu~lopment of InfectUm Surveillance and Prevmt:Um Programs 59
The IP plan should also outline any special studies and in- Predetermined protocols for the treatment of exposures serve
tervention projects. These ventures should be directly related to provide rapid responses and management, which is critical
to the missions and goals. for the prevention of bloodborne pathogen transmission, espe-
Incorporating routine activities, such as consultation to vari- cially HIV (23) (see Chapter 43). Some exposure episodes are
ous committees, product evaluation, and community involve- less straightforward than can be managed with a written proto-
ment, into the IP plan is critical because these activities account col. In these instances, the hospital epidemiologist often serves
for considerable amounts of time. Painting a clear picture of as the consultant for the management of unusual occupational
the time and resources necessary for all IP activities should be exposures. The prevention of sharps injuries necessitates an
an objective of the plan. However, unexpected circumstances epidemiologic approach to exposure incidence, including sub-
arise, and the plan should have enough flexibility to accommo- analyses within specific groups of HCWs (e.g., nurses, operat-
date unplanned events, such as outbreaks in the institution or ing room personnel, physicians, housekeepers, etc.), specific
community and unexpected regulatory mandates. devices, activities, and work areas. Formal evaluative reports
In summary, the IP plan includes the mission, goals, and presented to the IP committee or other governing body, in ad-
program scope; surveillance plan; education plan; policy and dition to on-going feedback to the departments where injuries
procedure review plan; and special studies. are occurring, provide the mechanism for leadership input and
resource allocation.
Depending on the community prevalence, tuberculosis pre-
~RNALCO~ORATIONS
vention and control may account for only a fraction of program
Collaborations are critical to the success of the IP program. time or a significant amount of energy for both the occupa-
Although largely immeasurable, the relationships that the IPS tional health and IP departments. This is an excellent example
develop will positively contribute to the program's mission. No of why personnel staffing needs are facility-specific and why IP
amount of policies or education will substitute for the trusting and occupational health departments must be closely linked,
relationships that healthcare workers (HCWs) develop with either formally through the internal chain of command or
the IP staff. Hospital personnel need to feel that they can be informally through collaboration and the IP committee (or
candid about concerns without fear of retribution or shame. similar function).
Bear in mind that relationships and trust are between individu-
als, not departments or functions. Therefore, when developing
P11-tient S.fety
an IP program, the IP staff should concentrate on meeting all
department heads and key department leaders including front- Another critical internal collaboration is between IP and
line staff. IP employees should focus on understanding the de- patient safety. Although IP is rightly viewed as the first formal
partment's issues and attempt to resolve concerns even if they effort to protect patients in healthcare settings, the discipline
may not have a significant impact on HAl rates. When nuisance of patient safety gained prominence after the 1999 publication
problems are resolved, individuals are much more likely to of Th Err Is Human by the Institute of Medicine (24,25). Now
have the time, energy, and trust to work on the more challeng- The Joint Commission has incorporated IP into its National
ing issues. Although it may seem elementary, the demonstra- Patient Safety Goals by requiring evidence of compliance with
tion of trust and cooperation is the first and foremost critical the CDC's hand-hygiene recommendations and the reporting
step in the development of an effective IP program. of infection-related adverse or sentinel events (26). Hospitals
Departmental partnerships are as extensive as the number are now called on to investigate every death caused by an
of departments within a facility because the IP program is an HAl using the specific model of root cause analysis (RCA).
entity-wide function. Each and every department should work Although RCA may be an appropriate tool for rare IP occur-
with the IP program to incorporate IP activities into their own rences, such as group A streptococcus surgical infections or
work. They should recognize that IP is everyone's job, not just an episode of aspergillous HAl, its value has yet to be demon-
the IP's. The affiliations that are paramount and closely aligned strated for infectious deaths due to common cause or endemic
with the IP program will be discussed in detail. HAis. Nevertheless, the RCA process can be a useful tool to un-
cover many suboptimal process issues that contribute to high
endemic rates. For example, a death caused by Clostridium dif
jicile is likely to be rooted in the on-going, common causes of
The Joint Commission and some state regulations mandate the horizontal transmission related to suboptimal hand hygiene
occupational health department's relationship with IP. Even and isolation precaution compliance, prolonged antibiotic ex-
if not required, the overlap of preventing HCWs and patients posure, inadequate environmental cleaning, and specific host
from sustaining infectious pathogen exposures is an obvious factors rather than a single "root cause." Since the Joint Com-
link between the two departments. IP and occupational health mission mandates RCA for many healthcare facilities, IP per-
must work together on the development of the requirements sonnel must collaborate with their partners in patient safety
for HCW immunizations, prevention of ID pathogen expo- to perform these analyses. Because the Joint Commission sur-
sures, and postexposure prophylaxis and secondary exposure veys approximately 82% of acute care hospitals that account
prevention, including HCWwork restrictions (21,22). for 96% of the hospital beds in the United States (Peter B.
The more frequent occupational occurrences necessitate Angood, MD, Personal communication, May 24, 2006), most
clear and on-going coordination between IP and occupational IP personnel will likely participate in RCA procedures. IP per-
health. Specifically, the treatment and prevention of sharps sonnel can partner with patient safety peers to assist in the epi-
injuries and other body substance exposures through policy demiologic investigations of process and outcome measures
and engineering controls is necessary and mandated by the such as falls, venous thrombus embolic events, and medication
Occupational Safety and Health Administration (OSHA). safety events.
CliniMI CIJre Arem

The quality department and IP are also closely aligned because IP must collaborate with personnel from all clinical areas to
both departments are charged with improving patient out- ensure that patient care is provided with the utmost attention
comes. Many quality departments are authorized by the hos- to IP. Established procedures for IP must be implemented
pital to measure quality indicators and report those results to in routine practice. The clinical care areas must be alert for
organizations such as the Institute for Healthcare Improvement problems that would not be detected by routine surveillance
(IHI} (100,000 lives and impact campaigns} and the Centers for methods such as gastroenteritis or rashes among patients and
Medicare and Medicaid Services (CMS). At 56 hospitals partici- employees, insects and varmints, humidity and temperature ab-
pating in a collaborative compliance with the CMS IP indicators normalities, or product defects. Areas with high-risk patients,
in the Surgical Care hnprovement Project (SCIP) resulted in a high-risk procedures, and high volumes should command
27% mean reduction ofSSI rates (27,28). Often the quality mea- special attention from IP. Examples of such areas include the
sures are based on prior IP and healthcare epidemiology studies operating room, ICUs, emergency departments, interventional
that demonstrated the effectiveness of the individual interven- radiology, and cardiac procedure areas.
tions combined into quality project bundles, such as timely and IP must collaborate with many other critical departments,
appropriate surgical prophylactic antibiotics (29-35). such as environmental safety, education, emergency prepared-
In addition to having overlapping indicator interest with ness, and pharmacy. An appreciation of the literature and the
IP, quality personnel often are well-versed in models of im- standards of practice put forth by each professional discipline
provement, such as Continuous Quality Improvement (CQI), will aid in the development of IP approaches.
Plan-Do-Check-Act (PDCA), Six Sigma, Toyota Production
System, Positive Deviance, and Lean. IP frequently uses the epi-
demiologic methods for improving endemic and epidemic HAl EXTERNAL PARTNERSHIPS
rates; however, these additional quality tools can broaden IP's IP has a direct partnership with the community public health
problem-solving armamentarium. IPs can lean on the quality department At most facilities, the IP department is charged
professionals who often are proficient in leading and facilitat- with notification of reportable diseases. In community out-
ing teams for direct assistance or guidance. breaks or disasters, public health and IP work sid~by-side to
protect the public's health. Depending on the facility's mission,
the IP department may be directly involved and collaborate
Risk M11nagement
with the public health department for community outreach
Another hospital department with which IP routinely joins programs, such as health fairs or educational campaigns.
forces is risk management Every HAl-related death or perma- Bioterrorism or emergency preparedness collaborations and
nent disability should be reported to the patient safety depart- mandatory reporting of selected HAl rates have been strength-
ment and to the risk management department IP should also ened more recently at state and local levels. Relationships with
report outbreaks and other potentially litigious situations to other hospitals, surgical centers, long-term care facilities, and
risk management to protect the institution and its HCWs. In other service providers within the community provide two-way
addition to reporting duties, risk management relies on IP de- feedback regarding patients' HAl acquisition.
partments to implement standards of care that prevent HAis
and thereby reduce liability. Risk management may also request
that IP departments review the medical records of patients who COMPLIANCE ISSUES
have filed or threatened lawsuits that may have IP implications. The IP department must evaluate many compliance standards
Policies and procedures from years ago may need to be r~ or regulations. They may be mandatory, such as the OSHA
viewed to validate that the standard of care for the time period bloodbome pathogen standard, or not legally required but rec-
was being followed. ommended for good practice, such as the CDC's IP guidelines.
Even when not specifically mandated, guidelines such as the
CDC's recommendations are often held as a standard of care
Microbiology
and therefore should be carefully evaluated. Failure to adopt
A high-quality microbiology department is a true asset to the IP d~ recommended practices may place the institution at risk if
partment Skilled microbiologists and technicians understand the adverse events occur and are legally pursued. However, differ-
importance of specific clinical specimens, and those individuals ent agencies may have conflicting recommendations, or some
will alert IP. Microbiology policies for alerting the IP department recommendations may not be based on sound epidemiologic
should be developed to leave no ambiguity regarding notification or medical principles (i.e., evidence based). When these situ-
of common yet significant pathogens, such as methicillin-resistant ations occur, IP personnel should evaluate the literature and
S. aureus, C. difftcile, or more unusual findings such as acid-fast studies cited for the recommendations and propose the best
bacilli in respiratory specimens or gram-negative diplococci on a practices for their patients and employees through its gover-
stain of cerebral spinal fluid. Due to the stringent requirements nance (such as the IP committee). Professional organizations
for laboratory certification, most U.S. facilities have reliable meth- that have standards for the prevention of HAis include APIC and
ods to identifY microbiologic pathogens. External laboratories SHEA in the United States, and CHICA in Canada, as well as the
may be used particularly for specialty tests that require specialized Infection Control Nurses Association in the United Kingdom,
equipment, media, or reagents. During outbreaks, the micro- and the Asia Pacific Society for Infection Control. Additionally,
biology staff can advise regarding environmental sampling and specialty care organizations such as the Association of Operating
planning for additional specimen processing, such as with the Room Nurses, American Society for Gastrointestinal Endos-
heightened screening of a population. copy, Society of Gastroenterology Nurses and Associates, the
Chapter 5 • The Deu~lopment of InfectUm Surveillance and Prevmt:Um Programs 61
Association for Vascular Access, and the Intravenous Nurses Once the project has been selected, IP and the process
Society also have standards or guidelines on preventing infec- owners should use an improvement model that is consistent
tion. Governmental and nongovernmental regulatory agencies with its organizational model. Different improvement method-
that promote recommendations include the Joint Commis- ologies have advantages and disadvantages; however, ensuring
sion, CDC, OSHA, CMS, the Food and Drug Administration, that team members understand the tools and use a systematic
the Agency for Healthcare Research and Quality, the National method for evaluating the problem and implementing a solu-
Quality Forum, and state and local governments including tion is more important than the superiority of the model. At a
health departments. minimum, the model should call for the multidisciplinary team
In the past decade, agency requirements for demonstrating to establish a goal and a target for success and determine the
the implementation of evidence-based practices and measures measurement component that will demonstrate the project's
that prevent harm have proliferated. Although these require- effectiveness.
ments may have imposed a considerably increased data burden
on hospitals that do not use electronic records systems, the
EVALUATION OF INTERVENTIONS
requirements have forced the deployment of improved pro-
cesses that are expected to result in improved care or health An intervention and its evaluation should be designed concur-
outcomes. For example, before the CMS requirement of col- rently. The evaluation should include whether the project was
lecting and reporting appropriate timing of surgical prophy- successful as determined by the original goal and target estab-
laxis, appropriate prophylaxis was only occurring at rate of 56% lished by the team. It should also include a cost analysis that
(36). Despite the fact that the literature to support this practice compares the cost of the intervention with the savings associ-
is more than 15 years old (29), it took regulatory mandates to ated with avoided HAis. Intervention costs should include the
improve compliance. time of the intervention team members, the development of
the education program, the time of staff required to complete
any education, and engineering control such as products and
M11ndatory &porting
equipment retrofitting.
Since 2002, an increasing number of states have required re- When an improvement project implements multiple inter-
porting of HAis for quality and transparency reasons. Begin- ventions at the same time, the interventions cannot be indi-
ning in 2011, CMS has required reporting of selected HAis vidually assessed for effectiveness. However, this should not
(initially CLA-BSI in the ICU, extended in 2012 to include preclude the evaluation of the intervention as a package (most
catheter-associated urinary tract infections (CAUTI) in the HAl prevention interventions are multifactorial, often called
ICU, as well as SSis for abdominal hysterectomy and colon bundles). Often improvements are seen initially, but the suc-
procedures) (37). CMS chose to use the CDC's National cess begins to fade over time because the intervention change
Healthcare Safety Network (NHSN) as a reporting vehicle, so was not firmly rooted in a new manner of performance. In
that well-established, standardized definitions for HAl are be- other words, there was a regression to the old processes (39).
ing used. With a trend toward increased demands for trans- Therefore, continued assessment of the intervention should be
parency in healthcare, undoubtedly more measures will be incorporated.
required to be reported in the future. IP programs will require The define-measure-analyze-improve-control (DMAIC) im-
additional resources to conduct the necessary surveillance for provement model of Six Sigma recognizes the need for a formal
these reporting programs. Clear record keeping will be as process for monitoring the improvement and for developing
important as ever, since hospitals will be susceptible to audits, a response plan if the improvement deteriorates. In most in-
so there will need to be a clear rationale for why a particu- tervention projects, IP should continue to track the HAl rates
lar case was or was not deemed to have met the surveillance (outcome measure), while the clinical areas quantify the pro-
definitions. cess measures. For example, IP should monitor CLA-BSI rates
while the ICU staff monitors the percentage of femoral lines or
the percentage of central venous catheters (CVCs) placed using
INTERVENTION IMPLEMENTATION
maximal barrier precautions. When the process measures are
The goal of preventing HAis is accomplished by implementing carefully chosen, their monitoring is critical because they have
appropriate interventions. The area targeted for improvement a direct relationship with the desired outcome (.W) . In most in-
should be chosen (38) using surveillance data; reviewing high- stances, the process measures worsen before the outcome mea-
risk, high-volume, problem-prone procedures and processes; sure is affected. By tracking the process, the healthcare team can
and evaluating current regulatory and practice standards. Pro- intervene before an adverse HAl outcome occurs.
cess owners and collaborators should be objectively evaluated
for readiness to change current practices. According to the
principles of change leadership, people will not make needed CONCLUSION
sacrifices, but will hold onto the status quo and resist new strat-
egies in the absence of a sense of urgency or need to change The components of a successful IP program include clearly
(39}. When leaders of areas that need improvement are satis- defined governance, knowledgeable personnel, and a strate-
fied with the current performance, the IP team should seek gic plan for improving HAl rates and IP practices. A predeter-
change by first creating an uncomfortable feeling with the sta- mined plan guides activities and facilitates keeping the IP team
tus quo. Dissatisfaction with the present condition is essential focused on goals without getting unnecessarily sidetracked to
to instill the motivation for change. Alternatively, IP personnel other projects or "flavor of the month" campaigns. Positive re-
should find a project that demonstrates the need for improved lationships with hospital personnel and external agency repre-
practices or outcomes to partners and key leaders. sentatives will directly influence IP's ability to meet its mission
to prevent HAis in patients, employees, and visitors, and to 19. Gayneoll.P. S~ance of nowconUal infectiono: a fundamental ingredient for quality.
.br.ftt:t Contml Hrup EJM-ioL 1997;18:475-4 78.
achieve that prevention in a cost-effective manner. 20. Stamm WE, Weiuoteio RA, Dm,n ll.E, Comparioon of endemic and epidemic nooocomial
infcctiono. A01] Mrd. 1981;70:393-1197.
21. CDC. Immunization of health-<:are worken: recommendaliono of the Adviaory Committee
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6 Mary Andrus, Teresa C. Horan, and Robert P. Gaynes
Surveillance of Healthcare-Associated
Infections
DEFINITION OF SURVEILLANCE Semmelweis' rigorous approach to the collection, analysis, and
use of surveillance data. In contrast, the concurrent work of
Surveillance is "the ongoing, systematic collection, analy:sis, and Dr. Oliver Wendell Holmes ou the same subject in the United
interpretation of health data essential to the planning, imple- States was based primarily on the traditional anecdotal case-
mentation, and evaluation of public health practice, closely study approach of clinical medicine.
integrated with the timely dissemination of these data to those Semmelweis' investigation constitutes an amazingly con-
who need to mow" (1 ). A healthcare-associated infection (HAI) temporary example of the effective use of surveillance in ad-
surveillance system may be sentinel event-based, population- dressing a widespread HAl problem. When he assumed the
based, or both. A sentinel infection is one that dearly indicatet directorship of the obstetric service at the Vienna Lying-in
a failure in the hospital's efforts to prevent HAh and, in theory, Hospital in 184'7, Semmelweis noted that the apparent risk of
requires individual investigation (2,3). For example, gastroen- maternal mortality had been at high levels for >20 years. The
teritis caused by Salmtmella spp. iu a patient hospitalized for eminent clinicians of the day, in fact, considered the risks to
> 3 days should always prompt investigation because it clearly be no more than the expected endemic occurrence that could
indicates a failure of the hospital's safeguards. Denominator not be influenced. Semmelweis first undertook a retrospective
data usually are not collected in sentinel event-based surveil- investigation of maternal mortality and set up a prospective sur-
lance. Sentinel event-based surveillance will identify ouly the veillance system to monitor the problem and, later. the effects
most serious problems and should not be the only surveillance of control measures. The initial re!ults of his retrospective study
system in the hospital. Population-based surveillance (i.e., SUI'- of annual hospital mortality showed dearly that the maternal
veillance of patients with similar risks) requires both a numera· mortality level, which he measured by calculating yearly mortal·
tor (i.e., HAl) and denominator (i.e., number of patients or ity rates, had increased 10-fold following the introduction in
days of exposure to the risk.). An HAl surveillance program the 1820s of the new anatomic school of pathology, which used
should be accurate, timely, useful, consistent, and practical. autopsy as its primary teaching tool. On the basis of the use of
ward-specific mortality, Semmelweis calculated that the risk of
death on the ward used for teaching medical students was at
HISTORICAL PERSPECTIVE least four times higher than that on the ward used for teaching
midwifery student:J. After the septic death of his mentor sug-
Since the first edition of this book, there has been a great deal gested the presence of a transmissible agent, Semmelweis used
of cii.scuuion and debate among professionals over the desi'f'- the findings from his retrospective surveillance study to impli·
ability of continuing routine surveillance, argued by some to be cate the practices of the medical students. After observing their
too pemmuel-time-intensive in an era of constrained hospital daily routines, he surmised that students might be transferring
budget:J. .As this discun:ion continues, an account of the devel- "cadaver particl.es" from cadavera to the parturient women and
opment of concepts and techniques of surveillance should be that washing hands with a chlorine solution might prevent this
considered. Many of these techniques were developed to meet transmission. Subsequently, his prospective surveillance data
emerging problems, and the basic concept of surveillance has documented a dramatic reduction in maternal mortality im-
been found effective in reducing HAl risk. Knowledge of the mediately following the institution of mandatory handwa.shing
historical reasons for these developments may help improve before entering the labor room.
the efficiency and effectiveness of surveillance without discard- Apparently, due to his abrasive manner, lack of diplomacy,
ing the well-conceived approaches that remain effective. and inability to organize his statistical data into a concise and
The use of surveillance methods to control HAis dates back convincing repon, Semmelweis failed to win over his clinical
at least to the classic work. of Dr. Ignaz Semmelweis in Vienna in colleagues to his discovery. Within 2 years, he was dismissed
the 1840s (4). Although the Sem.melweis story is best remem- from the staff of the hospital, and his successor gradually al-
bered as the first demonstration of person-to-person spread of lowed the strict handwashing measures to decline. In the
puerperal sepsis and of the effectiveness of handwash:ing with absence of continuing surveillance, the epidemic promptly re-
an antiseptic solution, an equally important achievement was sumed and lasted well into the early part of the 20th century, ita
'Ibe findlDgs and conclulion1 in th1J chapter have not been formally dlaemlnated by the Centen for Dileate Conttol and Prevention and mould not be COIUUUed
to represent any agency determ1o.atioo. or poll.cy.
63
severity and means of prevention apparently unappreciated by Several fuctors have influenced contemporary practices fa-
several more generations of clinicians. voring robust surveillance activities in infection prevention and
This story illustrates one of the main impediment:~ to in- control progranll!. First, the result:l of the Study on the Efficacy
fection prevention and control today: in the absence of of Nosocomial Infection Control (SENIC) project strongly sub-
carefully collected epidemiologic data and a diplomatic pre- stantiated the importance of surveillance along with prevention
sentation, clinicians, who are oriented almost entirely toward and control measures to reduce HAl rates and provided the sci-
the treatment of individual patient:l, often fail to appreciate entific basis for surveillance ofHAis (8). The conclusion was that
the severity of the HAl pathogen-transmission problem and hospitals that are effective in reducing their HAl rates have an
sometimes resist control measures. It also point:l out the util- organized, routine, hospital-wide surveillance system. Second,
ity of surveillance in identifying problems and developing and the requirement:~ of the Joint Commission on Accreditation of
applying control measures. From a methodologic viewpoint, Healthcare Organizations (1JC, formerly JCAHO) have legiti-
Semmelweis' effom encompassed almost all aspect:l of the mized the need for personnel to perform surveillance (9,10).
modem surveillance approach: retrospective collection of data Third, the surveillance practices developed in infection control
to confirm the presence of a problem; analysis of the data to have begun to influence other aspect:l of the hospital's quality
localize the risks in time, place, and person; controlled com- monitoring and improvement activities ( 11). The strategies of
parisons of high- and low-risk groups to identify risk fuctors; targeting surveillance to reduce specific endemic problems and
formulation and application of control measures; and prospec- monitoring to assess the intervention's effectiveness were incor-
tive surveillance to monitor the problem, evaluate the imple- porated into TJC's 1994 infection control standards for accredi-
mented control measures, and detect future recurrences. The tation and were applied to hospital quality-assurance programs
main shortcoming of his approach was in not diplomatically to reduce noninfectious complications (12) .
educating his powerful colleagues with a careful report of his The increasing pressure to continually improve quality has
findings. broadened the use of surveillance to aid in the prevention of
Despite Semmelweis' historical model, the modem era of HAis (13). The Institute of Medicine's Report, 'IbErr is Human,
HAl surveillance grew more from mid-20th century experi- in 2000 helped to focus public attention on the problem of
ence. The importance of surveillance for disease control in medical errors, including discussions on HAis as preventable
general arose in the effort to control tropical diseases among harms (14). Since that report, consumer advocacy groups, legis-
troops stationed in the Pacific Theater in World War II. At the lative bodies, and accreditation organizations have increasingly
end of the war, most of the epidemiologist:~ of the "Malaria demanded public reporting of HAis. These groups argued
Control in War Areas Unit" were transferred to a civilian fa- that heightened transparency of HAl rates would improve the
cility to apply their surveillance and control strategies to the quality of care largely by increasing competition to stimulate
control of malaria in the southern United States. Located in hospitals to reduce infections.
Atlanta, near the endemic areas, the unit was first named the
Communicable Diseases Center and later became the Centers
for Disease Control and then the Centers for Disease Control GOALS OF SURVEILLANCE
and Prevention (CDC). Since the large number of repom of
malaria indicated the disease to be widespread, a surveillance A hospital should have dear goals for doing surveillance. These
system was immediately set up to define the extent of the prob- goals must be reviewed and updated frequently to address new
lem. However, as investigators examined each reported case, HAl risks in changing patient populations, such as the intro-
they found virtually all of the reports had errors in diagnosis. duction of new high-risk medical interventions, changing
Thus, the mere activity of surveillance "eradicated" the malaria pathogens and their resistance to antibiotics, and other emerg-
epidemic in the United States. ing problems. The collection and analysis of surveillance data
Because of this and similar successes, when the pandemic must be performed in conjunction with prevention strategies.
of staphylococcal infections swept the nation's hospitals in the It is vital to identify and state the objectives of surveillance be.frm
mid-1950s, CDC staff members were quick to apply the con- designing a surveillance program and starting it (15,16).
cept:l of surveillance to the problem (5). When asked to as-
sist in investigating a staphylococcal epidemic in a particular
REDUCING HAl RISK WITlllN A HOSPITAL
hospital, these early investigators often met strong resistance
from clinicians, and hospital administrators convinced that no The most important goal of surveillance is to reduce the risks of
unusual infection problems were present in their hospitals. In acquiring HAis. To achieve this goal, specific objectives for sur-
instances when CDC staff members were able to continue the veillance must be defined on the basis of how the data are to be
investigations, the collection and reporting of surveillance data used and the availability of financial and personnel resources
regularly changed those attitudes to strong concern over the for surveillance (15-17). The objectives for surveillance can be
documented problems and eagerness to apply control mea- either outcome- or process-oriented. Outcome objectives are
sures. These initial investigations thus confirmed a nationwide aimed at reducing HAl risk and their associated cost:l ( 17). By
staphylococcal epidemic and led the CDC to sponsor several using comparative HAl data and providing feedback to patient-
national conferences to discuss the problem. care personnel, outcome data are useful in demonstrating
By the early 1980s, some critics were questioning the effec- where gaps in HAl prevention activities exist. Process objectives
tiveness and cost-benefit of routine HAl surveillance although a help to identify the delivery of care problems that can have an
growing number of hospitals were increasing their surveillance effect on patient outcomes. Examples of process measures are
effom rather than cutting them back (6). Surveillance was, and observing and evaluating patient-care practices, monitoring
remains, a time-consuming activity, requiring about 40% to equipment and the environment, and providing education.
50% of the time of an infection preventionist (IP) (7). However, these activities are of limited value without clearly
Chapter 6 • Surveillance of Healthca.Associated Infections 65
stating the outcome objectives. While HAl surveillance has surveillance is needed to ensure that the problem is under
other legitimate pwposes, the ultimate goal is to use process control. By continual monitoring, some control measures that
objectives to achieve the outcome objectives: decreases in HAl seemed rational can be shown to be ineffective. For example,
rates, morbidity, mortality, and cost. the use of daily meatal care to prevent healthcare-associated
urinary tract infections (UTis) seemed appropriate but did not
control infection (20). Even after the initial success of control
ESTABLISIDNG ENDEMIC RATES
measures, breakdowns in applying them can occur, requiring
Surveillance data should be used to quantify the baseline rates of a constant vigil including the continued collection of surveil-
endemic HAis. This measurement provides hospitals with knowl- lance data.
edge of the ongoing HAl risk in hospitalized patients. Most
HAis, perhaps 90% to 95%, are endemic (i.e., not part of recog-
SATISFYING ACCREDITING AND REGULATORY
nized outbreaks) (18). Thus, the main purpose of surveillance
AGENCY SURVEYORS
activities should be to lower the endemic HAl rate rather than
identify outbreaks, and many hospital IPs report that their pres- Satisfying the requirements of accrediting organizations,
ence on the wards may be sufficient to influence HAl rates (19). such as 1JC, is a very common use of HAl surveillance data
However, the mere act of collecting data does not usually influ- but one of the least justifiable. The collecting of surveillance
ence HAl risk appreciably unless it is linked with a prevention data merely to satisfY a surveyor who visits a hospital once every
strategy. Otherwise, surveillance is no more than "bean count- 3 years (or occasionally more often) is a largely unproductive
ing," an expensive exercise without focus that today's hospitals use of resources. 1JC also changed its requirements to avoid
can ill afford and that IPs will ultimately find dissatisfying. this task-oriented process of collecting data when it altered
its standards in 1990. Hospitals are now required to use HAl
surveillance in a directed manner to initiate specific interven-
IDENTIFYING OUTBREAKS
tions designed to lower the risk ofHAis in patients (10).1JC's
Once endemic HAl rates have been established, IPs and hos- Agenda for Change has motivated hospitals to use HAl surveil-
pital epidemiologists may be able to recognize deviations from lance for its originally intended purpose: to change the out-
the baseline that sometimes indicate infection outbreaks (see come of patient care by reducing HAl risk. More recently, the
Chapter 8). This surveillance benefit must be balanced with US Congress has passed legislation that sanctions the Centers
the relatively time-consuming task of ongoing data collection for Medicare and Medicaid Services (CMS) to financially incen-
because only a small proportion of HAis, perhaps 5% to 10%, tivize hospitals if potentially preventable HAis are reduced (21)
occur in outbreaks (17). Moreover, HAl outbreaks often are (see Chapter 13).
brought to the attention of IPs by astute clinicians or laboratory
personnel much more quickly than by the analysis of routine
DEFENDING MALPRACfiCE CLAIMS
HAl surveillance data. This lack of timeliness often limits the
use of routine HAl surveillance in identifying outbreaks in a One concern about the collection of HAl surveillance data has
hospital, although the use of data-mining software may address been that it would create a record that could be used against
this issue (see Chapter 10). the hospital in a malpractice claim related to an HAl. A strong
surveillance component in an infection prevention and control
program will demonstrate, however, that a hospital is attempt-
CONVINCING HOSPITAL PERSONNEL
ing to detect problems rather than conceal them. Additionally,
Convincing hospital personnel to adopt the recommended the records of infection control committees are considered
preventive practices is one of the most difficult tasks of an in- privileged in most states and may not be discoverable in civil
fection prevention and control program. Familiarity with the court proceedings. Therefore, surveillance is often helpful in
scientific literature on hospital epidemiology and infection pre- defending against malpractice claims, and it is rarely, if ever, a
vention and control is effective in influencing behavior only if hindrance.
the hospital personnel believe the information is relevant to
the specific situation in question. Studies in the literature may
COMPARING HOSPITALS' HAl RATES
not address the many varied situations encountered in a par-
ticular hospital. Using information on one's own hospital to in- Traditionally, HAl surveillance has been recommended solely
fluence personnel is one of the most effective means to address for gaining an understanding of and reducing HAl rates
a problem and apply the recommended techniques to prevent within individual hospitals. The idea of comparing HAl rates
HAis. If surveillance data are analyzed appropriately and pre- among hospitals, though often suggested by administrators
sented routinely in a skillful manner, hospital personnel usu- and quality-assurance supervisors, has generally been discour-
ally come to rely on them for guidance. The feedback of such aged by IPs and hospital epidemiologists. They argue that the
information is often quite effective in influencing the behavior mix of intrinsic HAl risk of the patients in different hospitals
of healthcare workers to adopt the recommended preventive renders differences among the hospital rates virtually uninter-
practices (8). A team approach with IPs working with clinicians pretable. Studies performed by CDC, however, have suggested
from a variety of disciplines is particularly effective (15). that interhospital comparisons can be useful in reducing HAl
risk (22), if the rates are specific to a particular site of HAl
(e.g., UTI) and control for variations in the distributions of the
EVALUATING CONTROL MEASURES
major risk factor(s) for that type of infection (e.g., duration of
After a problem has been identified through surveillance indwelling urinary catheterization). Conversely, using a single
data and control measures have been instituted, continued number to express a hospital's overall HAl rate falls short as
a valid measure largely because suitable overall risk adjusters sufficiently correlated with HAis to provide useful informa-
for infections of all types are lacking (2g....26). Therefore, a tion about the actual institutional HAl rate (43). For example,
hospital's overall HAl rate should not be used for interhospital the SSI rates following coronary artery bypass graft, Cesarean
comparisons. section, or breast surgery appear to correlate closely with the
proportion of patients who receive extended courses of inpa-
tient antibiotics and are useful indicators of a hospital's SSI out-
PUBLIC REPORTING OF HAl DATA
comes for those procedures (44) .
Many state and national initiatives to mandate or induce
healthcare organizations to publicly disclose information re-
garding institutional and physician performance are underway METHODS OF SURVEILLANCE
(see Chapter 47). Mandatory public reporting of healthcare
performance is intended to enable stakeholders, including PLANNING FOR SURVEILLANCE
consumers, to make more informed decisions about health-
Once the goals of surveillance have been identified, the hospi-
care choices, and has taken several forms such as report cards
tal should develop a formal, written surveillance plan, detailing
and honor rolls. In an effort to provide guidance and to estab-
how these goals will be met. The plan should include the out-
lish more uniformity, the CDC, through the Healthcare Infec-
comes and/or care processes to be surveyed; the frequency and
tion Control Practices Advisory Committee (HICPAC), issued
duration of the monitoring; methods of surveillance to be un-
a guidance document on public reporting of HAis in 2005,
dertaken, including definitions; metrics and their calculations;
which included both outcome and process measures (27). As of
and dissemination strategies (15). Most acute care facilities
January 2012, 32 states in the United States require hospitals to
(e.g., hospitals, long-term acute care facilities) in the United
publicly report their HAl rates (28,29). Most states (28) and the
States perform prospective incidence surveillance of endemic
District of Columbia use or will use the CDC's National Health-
infections. Depending on the goals, as well as the size of the
care Safety Network (NHSN) for HAl reporting mandates. In
facility, complexity of the patients, and resources available for
addition, CMS' Hospital Inpatient Quality Reporting Program
surveillance, a combination of targeted and facility-wide surveil-
requires the use of NHSN for hospitals in that program to re-
lance will be included in the surveillance plan. The methods
port central line-associated bloodstream infections (CLA-BSI),
will focus on a combination of outcome and process measures
catheter-associated urinary tract infections (CA-UTI), and sur-
and will include active case finding.
gical site infections (SSI) for two operative procedure catego-
ries (30). These data are or will be publicly reported on CMS'
Hospital Compare website (31). PROSPECTIVE INCIDENCE SURVEILLANCE
The accuracy of data reported via mandate has been ques-
Prospective surveillance is the monitoring of patients during
tioned by several attempts at validating these data (32-36).
their stay in the hospital and for a limited period after discharge
The problems in accuracy were sometimes based on inac-
(see "Postdischarge Follow-Up" section). This method can be
curate denominator data but most often were due to under-
contrasted with retrospective surveillance, in which monitoring
reporting of infections, largely because of the variability and
is done by medical record review at a time distant from the
subjectivity in applying surveillance definitions. Efforts to cre-
patient's actual stay. Incirlence surveillance seeks the number of
ate accurate objective measures of HAl, including electronic
new episodes of disease that occurs in a defined population dur-
algorithms [37--4()] that will be most useful for public reporting
ing a specified time period. This method can be compared to
of HAl data, should ensure that such measures of HAl evaluate
the same event, no matter where the care is delivered or who
prevalence surveillance, in which the number of episodes of the
disease found to be active within a defined population either
collects the information. In addition, ideally, every hospital,
during a specified period (period prevalence) or at a specified
healthcare provider, or payer should be able to implement the
measures relevant to the care provided or compensated.
Presently, the evidence on the merits and limitations of us- Patient 1
ing an HAl public reporting system as a means to reduce HAis Patient 2
is insufficient. The CDC/HICPAC guidance was intended to as- -t!i Patient 3
·;;:
sist policymakers, program planners, consumer advocacy orga- 1li Patient 4
nizations, and others tasked with designing and implementing
-~ Patient 5
HAl public reporting systems. The challenges for meaningful 1li Patient 6
interpretation of publicly reported HAl data include accuracy ~Patient 7
in identifying HAis, risk adjustment to account for the varying ~ Patient 8
degrees of risk among the sampled patient population, and the Patient 9
method of expression of the HAl data. Some investigators have Patient 10
recommended that efforts should be directed instead to creat-
ing acceptably accurate, objective measures of quality of care,
such as process and/or surrogate measures that all healthcare
facilities can use (41). Process measures can be useful when Time A TimeB
their link to beneficial or adverse outcomes is well established. Figure 6.1. The incidence of infection is 3 during either time A or B
For example, the appropriate delivery of perioperative antimi- (three new cases were added during each time period). The prevalence
crobial prophylaxis is a case in point of a process measure that of infection during time A is 4 and during B is 6 (four and six cases
emerged from decades of research (42). Surrogate measures respectively, occurred in each period of time). The point prevalence of
are o~ective indicators of readily ascertained events that are infection at time C is 3 (at that point in time, three cases existed).
point in time (point prevalence) is sought (Figure 6.1). The pro- hand hygiene, use of maximal sterile barriers, and adherence
spective incidence method is preferred for HAl surveillance be- to active surveillance testing for the target organisms in the
cause it focuses on identifying new episodes of infection in a same location), the transmission of these organisms can be in-
timely manner, which alloW!! for rapid implementation of pre- terrupted, contact precautions can be promptly initiated, and
vention and control measures as needed. For more information MDRO and CDI rates can be reduced (52) .
on prevalence and its role in HAl surveillance, see Chapter 7.
Procedure-Specific Suneil/R,nce ofInfections
TARGETED SURVEILLANCE and Surgicii-1-0ire Processes
Since the mid-1980s, the trend has been away from continu- Surveillance of SSis following operative procedures is an impor-
ously monitoring all patients for all HAis in all parts of a hos- tant part of an HAl prevention program. For SSI surveillance,
pital ("hospital-wide" or "comprehensive" surveillance) in favor all patients undergoing operations are enrolled in a surveil-
of an approach that targets specific patient-care areas, infection lance registry at the time of the operation, and information on
sites, infections with certain organisms, infections that follow several key risk factors are recorded at that time. General risk
surgery, and the patient-care processes associated with infec- factors most likely to be useful in the analysis are the wound
tious outcomes. When the level of effort is matched with the classification, type and duration of the operation, and a mea-
seriousness of the HAl problem, the method has been called sure of the severity of the patient's underlying disease, such as
"surveillance by objective" (16). Although such targeting was the number of underlying diagnoses or the physical status clas-
initially motivated by the need to reduce the amount of person- sification of the American Society of Anesthesiologists (ASA)
nel time devoted to surveillance in hospitals with inadequately score (53-56). Attempts should be made to follow up all, or a
staffed programs, this approach has proven beneficial in re- subset, of the patients for SSis occurring after discharge (see
ducing HAl rates in certain high-risk patients (45-47). For ex- "Postdischarge Follow-Up" section) (57,58).
ample, in one hospital, the HAl rate in the intensive care unit
(ICU) was three times higher than in general medical-surgical
patients ( 48). ICUs tend to house patients who are most sus- HOSPITAL-WIDE SURVEILLANCE
ceptible to HAis-that is, the patients most likely to have sup- Examples of hospital-wide surveillance that continue to be use-
pressed immune systems, to be undergoing invasive diagnostic ful are those that can be done by tapping into existing elec-
or therapeutic procedures, or to be receiving intensive nursing tronic databases, such as NHSN's MDRO/CDI LabiD event
and medical care with the attendant risk of person-to-person surveillance (51). This method uses only positive laboratory
pathogen spread. Focusing scarce resources on specific infec- results to define the infection (called a LabiD event), which
tions in a few relatively small units has the advantages of greatly minimizes surveillance effort and misclassification since com-
simplifying the surveillance effort and of preventing HAis in plicated infection case definitions do not need to be applied.
the patients with the highest risks and greatest likelihood of Another of NHSN's modules also derives its data directly
sustaining severe and life-threatening HAis. from source databases in the hospital. In the Antimicrobial
Use and Resistance (AUR) Module, antimicrobial use data are
De71ice-.AssociR:tt:d SuneiliR-nce of Infections obtained from the pharmacy database and antimicrobial re-
t~-nd
Patient-C.re Processes sistance data from the laboratory database and imported into
the NHSN application. The objectives of this surveillance are
Many hospitals have sought to maximize the use of personnel to facilitate risk-adjusted intra- and interhospital comparison of
time by directing surveillance toward device-associated HAis in antimicrobial use and resistance data, as well as evaluate trends
patient-care areas with the highest HAl risk (e.g., CIA-BSis in of usage and resistance over time locally and nationally (59).
ICUs). The CDC's NHSN uses this approach in its Patient Safety
Component Device-associated Module (49). In that module, the
hospital chooses each month which device-associated HAis and/ COLLECTING THE DATA
or patient-care processes in which patient-care areas to monitor.
Definition of E11ent:s to Be Suneyed
For example, a hospital's surveillance plan could call for moni-
toring CIA-BSI and central line insertion practices (CLIP) in Carefully defining those events to be surveyed is important as
the surgical ICU each month of the year. By focusing attention an initial step in developing an HAl surveillance system. Ap-
on both the process and outcome measures, important insight plying accepted definitions systematically in the data-collection
into what works for infection prevention can be gained (50). process is another key step. In attempting to understand the re-
lationship between UTI and urinary catheterization, for exam-
ple, it is necessary first to define or establish criteria to decide
Loe~Jtion-Specific SuneiliR-nce
ofSigni.ficll,nt Organism
what will be called a UTI and what will be considered urinary
Infections and Patient-Oire Processes
catheterization. Once the event to be surveyed has been de-
Another way to maximize surveillance resources is to target fined and the criteria for determining its occurrence have been
specific organisms by either monitoring only for HAis caused established, then these definitions and criteria are applied sys-
by those organisms or monitoring positive laboratory results tematically and uniformly henceforth. Ideally, all members of
that identify those organisms occurring in specific patient-care the population at risk for the infection would be systematically
areas (locations). In NHSN, this is the focus of the Multidrug- monitored for the presence or absence of the criteria elements
Resistant Organism and Clostridium diffo;ile Infection (MDRO/ that define the infection being surveyed.
CD!) Module (51). When such surveillance is performed at the The CDC has published definitions for determining the
location level (and is combined with monitoring adherence to presence and classification ofHAis (60), and these have been
modified for use in CDC's NHSN (61). These are not rigorous or a particular ward or service (19,26). Another denominator
definitions of disease, but serve as practical, operational HAl used was patient-days, which are derived by summing the num-
surveillance definitions for most hospitals regardless of their ber of days that all patients stayed in the hospital during the
size or medical sophistication. The infection control commit- surveillance period. Since the patient-day denominator in-
tee, hospital administration, and affected clinical staff need to cludes length of stay, the resulting HAl rates are at least par-
understand the definitions being used for HAl surveillance, and tially adjusted for differences among patients' lengths of stay, a
that when the HAl under surveillance is covered by a reporting proxy for severity of illness. These data can be obtained either
mandate, no deviations are allowed. Such widespread advance electronically or in a written monthly report from the hospi-
agreement is necessary to avoid later having the results of tal medical records department or business office. However,
surveillance discounted by disagreements over the definitions. these denominators fail to take into account other differences
in patient risks for HAis, such as exposures to certain invasive
devices. The calculation of overall rates using these denomina-
RoleoftheiP
tors is not recommended (23), except in limited circumstances
In the United States, most hospitals employ an IP, whose compe- such as for a facility-wide CDI LabiD event rate (see "Hospital-
tencies include designing the surveillance system, ability to ap- Wide Surveillancew section) (51).
ply surveillance definitions accurately, collecting and compiling The method commonly used in SSI surveillance is to col-
the data, and interpreting and presenting surveillance results. lect a record on every patient undergoing those operative pro-
Additional details of the qualifications, functions, and responsi- cedures being monitored for SSI. In this method, the record
bilities of the IP are described elsewhere (see Chapter 5). The contains the risk factors associated with SSI and, should an
IP works directly with the infection control committee chair- SSI develop, that record is linked to the patient's procedure
person or the hospital epidemiologist, and reports prevention record (63). While collecting data on all surgical procedures
and surveillance information to hospital administrators, boards selected for monitoring is more time-consuming than other
of directors, as well as to the infection control committee. In methods, this method offers IPs more flexibility in the types
addition to HAl surveillance in the hospital, the IP must often of SSI analyses that can be generated by making available any
conduct HAl surveillance in other settings (e.g., skilled nurs- combination of risk factors. This alternative is made even more
ing, behavioral health, and outpatient areas). IPs must set pri- attractive when detailed operative records can be downloaded
orities for the use of their time in ways that will maximize their periodically from the operating room database.
impact on infection risks in those settings for which they are For device-associated HAl surveillance, it is important to
responsible (62). account for the exposure to the risk factor (i.e ., the device).
The denominator typically used is the number of device-days.
Device-days are determined by a daily count of the number
Minimum DR.UJ to Collect IJbout Infections
of patients with a specific device (e.g., central line, indwell-
The precise information collected in conjunction with each ing urinary catheter, or ventilator) in the patient-care location
HAl depends on the surveillance objective and may vary ac- during a time period. At the end of the time period, the sum
cording to the institution, service, site of infection, or causative of the daily counts is the number of device-days used in the
agent. Certain essential identifYing data, however, can be rec- denominator ( 49).
ommended: the patient's date of birth, gender, hospital identi-
fi.cation number, ward or location within the hospital, service,
Identifying Sot~rces of Infection DR-tll
and date of admission; the date of onset of the infection; the
site of infection; the organism(s) isolated in culture studies To ensure the most complete enumeration of HAis, IPs seek a
or by laboratory tests; and the antimicrobial susceptibility pat- variety of infection information sources from both within and
tern of the organisms isolated. Additional information should outside the hospital (19). These active techniques of case find-
be collected only if it will be analyzed and used by the hospi- ing are used in almost all hospitals and are strongly preferred to
tal. Some institutions may wish to include the patient's name, passive techniques. The active techniques allow more complete
primary diagnoses, an assessment of the severity of underly- detection of HAis and provide for the IP to visit the patient-
ing illness(es), the name(s) of the attending physician(s) or care areas regularly, interact with and provide consultation
other staff who attended the patient, whether the patient was to the medical and nursing staffs, and gain first-hand aware-
exposed (before the onset of the HAl) to therapies that may ness of HAl problems. Passive techniques include asking physi-
predispose to infection (e.g., antimicrobials, steroids, or immu- cians or staff nurses to fill out infection report forms or relying
nosuppressive therapy), antimicrobial agents used to treat the solely on reviews of computerized microbiology reports for all
infection, and some assessment of mortality related to the HAl. types of infection. The usefulness of passive techniques is lim-
It is important to record the presence or absence of particu- ited by their inaccuracy in routine detection ofHAis. Hospitals
lar risk factors (e.g., surgery, the use of invasive devices such relying on passive techniques typically find extremely low HAl
as urinary catheters for UTis, ventilators for pneumonias, and rates, but these usually are due to underreporting rather than
central intravascular catheters for primary bacteremia). good patient-care practice (19). While the use of administrative
data (e.g., billing codes) can be a useful tool to identify patient
charts for review, this approach also has ml!ior shortcomings
DenominR-tors
as a singular methodology for identifying infections (64-66).
The methods for collecting the denominators for HAl data The actual collection of HAl data is typically accomplished by a
have been the most labor-intensive aspects of surveillance ( 43). combination of manual and electronic surveillance techniques.
Historically, the most commonly used denominator was the The IP often has electronic access to demographic informa-
number of patients admitted to or discharged from the hospital tion, microbiology and pharmacy reports, nursing graphics
(e.g., temperature, blood pressure), and radiology dictation SSI rates in the SENIC project used length of stay as a covariate
summaries. Many of the data elements used to satisfy the crite- in multiple regression analyses (8); others have suggested using
ria for HA!s, however, are fonnd in the patient chart or by con- the incidence density (i.e., patient-days in the denominator of
sultation with physicians, nursing, or respiratory therapy staff. the SSI rates) (73).
The choice of postdischarge surveillance method is contro-
versial and problematic. Minimally, surgical patient readmis-
Role ofthe Microbiology LRhor11tory
sions should be reviewed for evidence of SSI. Many IPs follow
Of all case-finding methods, one of the most useful is the up with postcard inquiries or telephone calls to the surgeon
periodic (usually daily) review of microbiology laboratory re- 21 to 30 days after the date of the operation to determine
ports. Data-mining computer applications also may be used to whether an SSI occurred (69-71). More recently, e-mails have
identify microorganisms of special significance to the patient become widely used. Though this creates additional work for
population requiring specific infection prevention measures. the surveillance staff, the amount of work may be commen-
A review of microbiology results may be performed each mom- surate with the gain in completeness and accuracy of the SSI
ing before patient-care area rounds, so any new or potential rates. Patients themselves are rarely contacted and questioned
HAis can be identified at that time. Such review requires that about signs and symptoms of SSI because the reliability of this
the IP recognize epidemiologically significant organisms for information is questionable. Postdischarge antibiotic exposure
immediate review and investigation; such knowledge might be also may be a resource-efficient adjnnct for surveillance of SSis
achieved through an infection prevention and control course after discharge (44).
and should be reinforced by periodic continuing education.
However, generally speaking, a review of microbiology labo-
CONSOLIDATING AND TABULATING DATA
ratory reports alone is not sufficient for the identification of
all types of HAis because (a) cultures are not obtained for all Consolidating the HAl data in ways that make them more un-
infections or may be handled incorrectly, (b) some infectious derstandable helps users identify potentially important rela-
agents (e.g., viruses) will not be identified in many hospital tionships or patterns of infection. The most effective analyses
laboratories, and (c) for some types of infections (e.g., SSI and of surveillance data may take many forms depending on the
pneumonia), the identification of a potential pathogen from a objective being addressed by the surveillance. As a first step,
culture specimen does not mean that infection is present and IPs should analyze HAl data in single-variable frequency tables
such infections require clinical detection and verification (see (e.g., number ofHAis by hospital location, body site, or patho-
Chapter 11). Also, positive blood culture results do not neces- gen) and two-way cross-tabulations (e.g., a line listing with
sarily indicate the presence of a primary bloodstream infection; the number of HAis by body site and by pathogen for each
rather they could indicate contamination or secondary seeding patient-care nnit), and tally antimicrobial susceptibility patterns
of the blood from another primary site of infection, such as the for each pathogen by HAl site (74). However, more thorough
gastrointestinal tract. analyses also should be done, including three-way rate tables
(e.g., pathogen by site by patient-care area), four-way rate ta-
bles (e.g., susceptibility patterns by pathogen by site by patient-
P11tien~C.re Aru Rounds
care area), and more complex cross-tabulations. Usually, these
Periodic (preferably daily) patient-care area rounds should be tabulations are performed for subsets of the patients, such as
included as an integral part of an effective HAl surveillance those on a particular service or the patients of a specific sur-
program. The purposes of such rounds are to identify new HAis geon. Statistical and other software are widely available for such
and to follow up previously identified HAis. New HAis may be analyses (see Chapters 9 and 10).
identified outright by physicians or nurses working in the area The basic purpose of tabulating the HAis is to gain a new
visited or by review of patient records, temperature records, understanding of when, where, and in whom the HAis are oc-
patients having high-risk procedures (e.g., surgery, central line curring. One of the most frequent mistakes made when the
insertion, intubation and mechanical ventilation, indwelling raw data are organized is to make initial tabulations hastily and
urinary catheters), and patients in isolation or receiving anti- proceed with calculating the rates without pausing to examine
microbial therapy. Visiting the patient-care area may also allow the data. It often is useful to read over the original listings and
direct assessment of the patient and documentation of visible the simple tabulations for an initial synthesis of the data that
HAis. The added value of patient-care rounds is the opportu- can suggest the need for additional tabulations, graphs, and
nity for the IP to interact directly with patient-care staff and listings. This process of exploration of the data has no rigid
initiate measures that could prevent HAis in the future. rules; what is right is that which works!
The analysis of the denominator data alone can be extremely
revealing. For example, if an IP determines that a hospital's uti-
PosttlischtJr.!Je Follow-Up
lization of central lines in ICUs is high compared with that in
With the progressive reduction in the average length of patient other hospitals' ICUs of the same type (see hospital nnit A in
stay in US hospitals, an increasing percentage of some HAis, the middle panel of Figure 6.2), a review of appropriateness
most notably SSis, become manifest after hospital discharge. of device use may be needed. Also, after the SSI rates have
The percentage of SSis that becomes apparent after discharge been assessed, useful information can be obtained by further
ranges from 20% to 60% (67-71). Since the average postopera- exploring the distribution of risk factors in each of the surgical
tive length of stay of surgical patients influences the probability categories. For example, while a surgeon with more than the
that SSis will be recognized while the patient is in the hospital, expected number of herniorrhaphy operations in higher-risk
this variable must be taken into acconnt when analyzing and groupings may be operating on more high-risk patients, he or
evaluating a hospital's SSI rates (72). Multihospital analyses of she may also be consistently exceeding the 75th percentile for
26
24
en 22
""c:::J 20
iii 18
~ 16
en 14
0
J::
12
0 10
G;
.l:l 8
E 6
::J
z 4
2
0
0.5 4 4.5 5 5.5 6 6.5
Number of central line-associated BSis per 100 patients
26.----------------------------------------------------------------------------.
24+----------------------------------------------------------------------1
~ 221-------------------------------------------------------------------------------~
c: 201-------------------------------------------------------------------------------~
::J
18+-------------------------------------------------------------------------1
it 161-------------------------------------------------------------------------------~
~ 14+-----------------------------------------------------------------1
J:: 121-------------------------------------------------------------------------------~
~ 10 +------------------
.! 8 + - - - -
§ 61---------
z
0.65 0. 7 0. 75 0.8 0.85

Number of central line-days/number of patient days
26.-------------------------------------------------------------------------,
24+----------------------------------------------------------------------1
~ 221-------------------------------------------------------------------------------~
"E 201-------------------------------------------------------------------------------~
i·a 161----------------------------------------------------------------------------1
181-------------------------------------------------------------------------------~
20 121----------------------------------------------------------------------------1
141-------------------------------------------------------------------------------~
~ 10~------------------------------------------------------------------------------~
~ 8
§ 6
z 4
2
0
0 24 25
Number of central line-associated BSis per 100 central line days
FJ&ure 6.2. Comparison of the distribution ofbloodstream infection (BSI) rates (patient-based and central line-
days-based) and central line utilization in combined hospital intensive care units. (Adapted from Jarvis WR, Edwards]R,
Culver DH, et al. Nosocomial infections in adult and pediatric intensive care units in the United States 1986-90. Am]Med.
1991;91(suppl3B):185S-191S, with permission.)
the duration of surgery for the herniorrhaphy procedure, thus indication of where HAl problems might be occurring. Since
increasing the patients' risk of SSI. The question must be asked, these initial analyses are based solely on separate examinations
"Are patients unnecessarily being placed at risk of an HAl?" of the characteristics ofHAis (numerator data) and denomina-
Because the examination of appropriateness of medical care tor data, further analysis involving the calculation of rates or
and device use is of major interest to performance improve- ratios is necessary to develop stronger evidence.
ment personnel (24,75-77), IPs may find areas for collabora-
tion with their performance improvement colleagues.
Definition ofRAte
A rate is an expression of the probability of occurrence of some
CALCULATIONS
particular event, and it has the form (-x:/y)k. The numerator,
After the initial tabulations of the HAis have been com- -x:, equals the number of times an event has occurred during
pleted, IPs and hospital epidemiologists should have a strong a specific time interval, and is divided by y, the denominator,
which equals a population at risk during the same time inter- as the denominator, was nearly five times higher than the me-
val, and is multiplied by k, a constant, to yield a whole number dian. However, the middle histogram shows that hospital unit
(100; 1,000; 10,000; and so on). The constant used depends A had the highest central line-utilization ratio; that is, >80%
on the magnitude of x/y, and it is selected to pennit the rate of patient-days were also central line-days. Using central line-
to be expressed as a convenient whole number. For example, days as the denominator of the rate helps to take into account
if five HAis were found among 100 patients in a given month, this high utilization of central lines. Hospital unit A's ClA-BSI
the value of x/y would be 0.05 HAis per patient per month; to rate was slightly lower than the median (bottom histogram).
express the rate as a convenient whole number, x/y would be Although hospital unit A was no longer an outlier, its high cen-
multiplied by the constant 100, giving 5 HAis per 100 patients tral line use may need to be reviewed for appropriateness. On
per month. If 50 HAis were found among 10,000 patients in a the other hand, for hospital unit B, the ClA-BSI rate (top his-
month, the constant 1,000 would be used to express the rate as togram) was near the median, and its central line use (middle
5 HAis per 1,000 patients per month. It is important to empha- histogram) was low. When its rate was calculated using central
size that in determining a rate, both the time interval and the line-days as the denominator, the rate was quite high, suggest-
population must be specified, and these must apply to both the ing the need to review central line-placement and mainte-
numerator (x) and the denominator (y) of the rate expression. nance practices (79).
An attack rate is a special kind of incidence rate. It is usually
expressed as a percentage (i.e., k = 100 in the rate expression),
Types of Imitlence R.Jt.tes
and it is used almost exclusively for describing outbreaks where
Incidence rates are the fundamental metrics of HAl surveil- particular populations are exposed for limited periods of time
lance. An incidence rate is obtained by dividing the number of (e.g., in common-source outbreaks). Since the duration of an
new HAis (numerator) by the population at risk (denominator) outbreak is reasonably short, the period of time to which the
during the specified time period. One denominator is the num- rate refers is not stated explicitly but is assumed. This is what
ber of patients (which technically makes it an infection ratio). In distinguishes an attack rate from an incidence rate for which
Figure 6.1, which portrays the infection status oflO hospitalized the period of time is always stated. If 100 infants in a newborn
patients, the incidence of infection during either time period nursery, for example, were exposed to a contaminated lot of
A or B, for example, would be 3, since three new infections be- infant formula over a 3-week period, and if 14 of the infants
gan among the 10 patients in each time period. Assuming that developed a characteristic illness believed to be caused by the
period A was 1 month and period B was 3 months, the incidence contaminated formula, the attack rate for those infants ex-
rates would be 3 infections per 10 patients at risk (30%) per posed to the formula would be 14%. Note that the incidence
month in period A and 10% per month in period B (i.e., exactly rate would be 14 cases per 100 infants per 3 weeks, preferably
equivalent to 30% per 3 months). expressed as 4.67 cases per 100 infants per week.
Another incidence rate denominator is the number of
days at risk during the period of surveillance. An example is
Dwice Utilizlltion R.Jt.tio (DUR)
a patient-day denominator, which is the sum of all days spent
by all patients in the specified area during the time period The DUR is a calculation that measures the proportion of pa-
covered. Another example is a device-day denominator, which tients within a population that have a device in place during the
is the sum of all days in which a specified device was used in specified period. The formula for DURis as follows:
patients in the specified area during the time period covered
(78). This type of rate is referred to as the incidence density. The Number of deuicH:lays
incidence density is useful primarily in two situations: (a) when Number ofpatient-days
the infection rate is a linear function of the length of time a
patient is exposed to a risk factor (e.g., indwelling urinary or No constant is used as a multiplier for this measure and the
intravascular catheter) and (b) when the duration of follow-up resulting value is always <1. For example, if an ICU has 100
will influence the measured infection rate (e.g., SSI rates when central line-days and 400 patient-days during a month, then
no postdischarge surveillance is done). the DUR would be 0.25 (100/400). This means that 25% of
The denominator should reflect the appropriate popula- the patient-days in the ICU are also central line-days. This mea-
tion at risk as precisely as possible. In determining the inci- sure can be a useful tool in making decisions about whether
dence density rate of CA-UTI in an ICU, for example, only a device is being used more or less than in previous months
those ICU patients who have an indwelling urinary catheter or compared to a standard population. If incidence rates are
should be included in the denominator. In the CDC's NHSN, increasing and the DUR also is increasing, the IP may want to
device-days (e.g., central line-days, urinary catheter-days, or consider that the increased use of the device is a possible rea-
ventilator-days) are used as the denominator data for ClA-BSI, son for the increased incidence of the HAl.
CA-UTI, and VAP rates (49), respectively, because the choice
of denominator is critical for purposes of interhospital com-
Smndardized Infection R.Jt.tio (SIR)
parison. This is more fully illustrated by the distribution of sev-
eral rates for hospital ICUs (Figure 6.2). The top histogram of The SIR is a summary measure used to track HAis at a national,
this figure shows the number of ClA-BSis per 100 patients, the state, or local level over time. The SIR adjusts for patients of
middle histogram shows the number of central line--days di- varying risk within each facility. In HAl data analysis, the SIR
vided by patient-days (i.e., central line-utilization ratio, further compares the actual number of HAis reported to a standard
defined in the next section), and the bottom histogram shows population's experience (e.g., NHSN aggregate data), adjust-
ClA-BSis per 1,000 central line-days. For hospital unit A, the ing for several risk factors that have been found to be signifi-
rate on the top histogram, which uses the number of patients cantly associated with differences in infection incidence.
The SIR is calculated by dividing the number of observed patient-care area or population to determine whether signifi-
infections by the number of expected infections. For devic~ cant changes have occurred over time. Current rates and those
associated HA!s, the number of expected infections is cal- of preceding periods can be visually inspected in tabular form,
culated using the rates from a standard population during a or the rates can be plotted on a graph to detect changes of
baseline time period. For SSis, the expected number of infec- potential importance. Potentially important deviations from
tions is derived from a logistic regression model of predictive baseline rates should then be tested for statistical significance
risk factors obtained during a baseline time period. The SIR (see Chapter 9), and further investigation should be under-
can be expressed by the formula below: taken if indicated (see Chapter 8). Although it is convenient to
compare the rates each month, caution is needed when the d~
Observed (0) HAis nominator of a rate is small. This may be particularly true when
Expected (E) HAis examining SSI rates or SIRs. Tests of significance must often be
performed when the estimate of a surgeon's SSI rate or SIR is
Using the SIR metric for devic~ociated infections allows unstable due to a small number of procedures performed.
the IP to summarize the data by more than a single patient-care
location, adjusting for differences in the incidence of infection
Interpreting the Ruulu
among the location types. Additionally, the SIR may be an eas-
ier measure to discuss among internal and external stakehold- Many consider the interpretation of the data to be the final
ers. If the SIR is > 1, it indicates that the observed number of step in analysis; it is the intellectual process by which meaning
infections is greater than the standard population's experience is ascribed to the tabulated and analyzed body of information.
(i.e., past rate). If the SIR is <1, then the observed number of The interpretation may vary from no significant change in the
HAis is less than what was expected (80). HAl rates to the detection of a serious endemic problem or
outbreak in the hospital. Often, however, more information,
particularly that obtained through further investigation di-
Compa.ring P11tient Groups
rected at problem areas identified by the analysis of the surveil-
Analysis implies careful examination of the body of tabulated lance data, will be necessary for the final interpretation of the
data in an attempt to determine the nature and relationship of data. Additional uses of other information collected through
its component partll. This includes comparing current HAl met- surveillance, such as the time of onset of HAl, are described in
rics to determine whether significant differences exist among Chapters 8 and 9.
different groups of patients. Suppose, for instance, that both
the gynecology and general surgery wards had two CA-UTis REPORTING THE DATA
during a given month; however, during the same month, the
gynecology ward counted 350 indwelling urinary catheter-days Tabulated data, or at least their analyses and interpretations,
and the surgical ward had 100 indwelling urinary catheter-days. should come to the attention of those people in the hospital
Thus, the incidence density rates for gynecology and general who can take appropriate actions. A periodic report containing
surgery wards are 5.71 and 20 CA-UTis per 1,000 indwelling the tabulated data and the analytic results and their interpre-
urinary catheter-days respectively. Determining whether the tations should routinely be submitted to the infection control
difference observed between these infection rates is significant committee and maintained on record in the hospital. Weekly
(i.e., higher than what we would expect by random or chance or even daily reports may be necessary during an outbreak or
occurrence alone, or if indeed no real difference exists) r~ unusual situations. When the analysis yields tables that contain
quires the use of a statistical process known as significance testing. insufficient data to justifY inclusion in the report, the tables
Several tests of significance (e.g., the chi.,quare test, Fisher's should be retained and a summary table released whenever suf-
exact test for cross-tables, or Student's t-test for comparison of ficient data have accumulated.
sample means) should be familiar to hospital epidemiologists The data should be displayed in graphical form to provide
and IPs (see Chapter 9). Currently available software packages clinicians and/or administrators with visual evidence of the
for computers make even the most sophisticated statistical test- existence of a problem and the need to take action. Simple,
ing procedures very accessible to all infection prevention depart- creative graphics such as dashboards are particularly effective.
ments ( 41,73). In the preceding example, the difference between The IP should not assume that those individuals have the time
the observed infection rates (5.71 vs. 20.0) is highly significant at or epidemiologic expertise to interpret the data without clearly
p < 0.03, according to a binomial exact test. This means that a presented graphics and narratives. When possible, it may be
difference as large as or larger than that observed would be ex- beneficial to have the IP or hospital epidemiologist personally
pected to occur by chance alone fewer than three times in 100. review these data with those individuals in the hospital who
Thus, it is very likely that there is a real difference between the can facilitate interventions that may be indicated (e.g., hospi-
infection rates on the two wards, and further investigation is in- tal administrators, clinical leaders, boards of directors) . In the
dicated to explain why such a difference exists. If the IP wants to reporting phase and throughout the surveillance process, mea-
compare the hospital HAl metrics to that of other hospitals, such sures should be taken to ensure the privacy of the information
comparisons can be made only when other hospitals' data have collected on patients and hospital staff members. For example,
been collected using the same definitions and methods (23). the IP should keep all surveillance forms that list patients by
name under very tight security, including password protection
for computerized records or a locked filing cabinet or other
Comp11ring R.sltes OPer Time
secure storage for paper records. Reports should not mention
Another type of analysis involves the comparison of cur- patients or staff members by name unless there is a good rea-
rent HAl incidence rates with previous rates within the same son for doing so, and the distribution of the reports should
be limited to those who need to know. The infection control 24. Chaaain MR, Kosccoff J, Park RE, et al. Doco inappropriate uac cxpl:tiu geographic
oariationo in the uae of health care aenicea? A atudy of three procedure~. ]11MA.
committee should establish a policy on information privacy, 1987;258:253!-25!7.
including specific procedures for handling records or reports 25. Haley RW.JCAHO infection control indicaton, pam 1 and 2. Infocl ComrolH..pEpiMmiol.
that identify patients or staff members (e.g., surgeon-11pecific 1990;11:545-648.
26. Lanon E. A comparioon of method> for ourvcillauce of nooocomial. infccti.om. In.focl
SSI rates or SIR!! or laboratory data implicating an employee as Conlrol. 1980;1:577-!81.
a human disseminator of an outbreak organism). 27. McKibben L, Horan TC, Tobn Jl, et al. Guidance on public reporti.ug of healthcar.,.
811ocia.tcd infct:tiom: rcconuncudatiom of the Hcalthcare IDfection Control Practice•
HAis have a substantial impact on patient outcomes in the Adriaory Committee. .U.J I,.fl&l Ctmln>L 2005;!5:217-226.
hospital setting. With trends in healthcare toward shorter hos- 28. HAl IU:porti.ug La... and Lcgillation. Available at hnp:/ / www.apic.org/lle>ource.../
pital stays, increasing the use of invasive devices, increasing the TinyMceFileManager/ Adrocacy-PD.FI/HAI__map.gif. Acce11edjune 50, 2012.
29. CDC Stat<>-ba>Cd HAl Tmckiug. Available at hnp://www.cdc.gov/ HAI/ atat<>-bucd/indc:x.
rates of antimicrobial resistance, and rising public and payer html. Acceoacdjune 50, 2012.
(including governments) interest in decreasing HAl-related 50. Centera fur Dileaae Control and Prevention. Uoiug NHSN fur CMS' Holjrital Iupati.cut Qual-
morbidity and mortality, surveillance activities will require ity Reporting Program Requin:mcn... Awililble at htq>://WIIW.cdc.gov/ nhan/ cmo-welcome.
htllll. Accc11edjuuc 50,2012.
more time and expertise than in the past. Resources for HAl 51. Ho~pital Compare wcbllitc:. Available athnp:/ / www.hoapitalonmpare.hha.gov/ otaticpagea/
surveillance and prevention have not increased proportionally leam/importaucc_quality.aapx?measurecd= HAI. AcccucdJunc 50, 20U.
52. Nicdner MF. The harder you look, the more you find: cathctcr-aaaociatcd bloodstream
with these demands (81,82). Maintaining successful features infection aurveillance variability. Am]lrofr<t Omtrol. 2010; 38:585-595.
of traditional surveillance systems, adopting novel surveillance !5. HautER, PronovootPJ. Surveillance hia.o in outcomeareporting..Jil.MA. 2011;305:2462-246!.
strategies, such as using surrogates for HAis, and employing M. LiD MY, Hota B, Khan YM, ct al. Quality of traditionalouncillaw:e fur public reporting of
nooocomial. bloodotrcam i.ufecti.on rateo. ]11MA. 2010;!04:20!5-2041.
new approaches to collecting and using information with new 35. Backman LA, Melchreit R, Rodriquez K- Validation of the aurveillance and reporting of
technologies will make healthcare surveillance an even better ccntralliue<UIOciatcd bloodotrcam i.ufecti.on data to a otate health department. AmJ Infl&l
Conlrol. 2010;38:852--858.
tool for prevention.
!6. Oh JY, Cunningham MC, Beldava W, et al. Statewide validation of hoopital-reportcd cen-
tral liue-usociated bloodnream infections: Oregon, 2009. Infocl Conlrol HIU[i E{1idniWI.
2012; !5:439-445.
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22. Gaynca R, Richard> C, EdwanisJ, ct aL Feeding back rurveillauce data to prevent hoapital- aenaus paper on the ourveillance of rurgi.cal """nd infecti.ona. Iro.focl C""""' H..p E{1idniWI.
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2!. National Nosocomial Infection• Survcillauce Syotcm. Nosocomial infection ratco fur in- 59. National Healthcare Safety Network- Pati.cut Safety Component Mcdication-Auociatcd
tctboapital compariwn: lillli.tatiom and poaaibk aolutiom. hrjila Conlrol H..p E{1idniWI. Module Autiluicrobial Uac and Ri:oi•taucc (AUR) Option. Availabk: at hnp:/ /www.cdc.
1991;12:~21. gov/uhon/PDI'a/ pocManual/llpacAlJRcurnnt.pdf. AcceoacdJune 29,2012.
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Art~]Info<~ Oml>ol. 2008;ll6:11()9....3!2. 72. Petherick ES, DaltonJE, Moore PJ, et al. Methodo fur identifying ourgical wound infection
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improve detection of ourgU:al lite illfectiono IollowiDg hip arthroplao~J; lwec arthroplaoty, ControlHw[IEpidntiol. 1990;11:117-121.
and v;ueular ourgery. bo.{.a CtmlmlHOI[>Epidntiol. 201!;!!:40-49. 77. McGeer A, Crede W, Hierholzer WJ Jr. Surveillance for quality u oeument: II. Sur..:illance
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NHSN criteria, are poor indi.caton of healthcan><U~<Jciated infecti001. Am]bo.f.a GmtroL '1'9. Janio WK. Edwardo JR, Culver DH, et al. NoiOCOJilial infection• in adult and pediatric
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69. WeigeltJA, DIJ"'" D, Haley RW. The neceoaity and efficiency of wound IUn'eillance after fectiona. 2007. Anilable at httpo:/ /www.premierinc.com/oafety/ topico/ guidelineo/
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7 Bruno P. Coignard
The Use of Prevalence Surveys

for Healthcare-Associated Infection
Surveillance
INTRODUCTION Although other countries also replicated the NNIS model
(7,8), they also have been using hospital-wide point·preva·
A point-prevalence survey often is the first step to be imple- lence surveys as a tool for HAl surveillance for a long time.
mented for healthcare-associated infection (HAI) surveillance From the first HAl point-prevalence survey implemented
in healthcare facilities. Its objectives are to give an estimate of in the 1970s in Sweden (9) to the most recent one coordi-
the total burden of HAis, to describe patients' characteristics nated by the European Center for Disease Prevention and
(i.e., specialties, risk. factors including exposure to invasive Control (ECDC) among 30 countries in 2011 and 20I2 (IO),
devices or procedures), illfections (i.e., sites, microorgauisnu numerous point-prevalence surveys on HAis and/ or antimi·
including markers of antimicrobial resistance), and/or antimicrobial use and resistant pathogens were conducted in Eu·
crobial treatments they are exposed to. rope (Table 7.I) or elsewhere in the world (Table 7.2), with
Point-prevalence surveys have been extensively used a prevalence of patients with one or more HAis ranging &:om
at local, regional, or national levels since the early 1960s. 3.5% to I6.8%. Some surveys also were targeted on specific
Among the first published surveys were those conducted infection sites, pathogens, or specialty populations, providing
in the United States at Boston City Hospital &:om 1964 to a quick and useful focus on undocumented HAis of public
1973, which documented at ~year intervals the prevalence health importance, such as methicillin-resistant St4ph:Jiococcw
of HAis and of antimicrobial use, of 12.0% and 33.0% in aunus (MRSA.), Clostridium di.ffi<:i/8 infections, HAis in neona·
1970, respectively (1,2). From 1969 to 1973, the Centers for tal or pediatric patients or in long-term care facility residents
Disease Control and Prevention (CDC) also conducted sur- (Thble 7.3).
veillance in 8 hospitals in the Comprehensive Hospital Infec-
tion Project (CHIP), which was based on prevalence studies
performed every 4 months (3). The Study of the Efficacy of THE PROS AND CONS
Nosocomial Infection Control (SENIC) Project (from 1974 OF PREVALENCE SURVEYS
to 1983) and the National Nosocomial Infections Surveil-
lance (NNIS) System (from 1970 to 2004) then advocated for Point-prevalence surveys have numerous advantages over inci·
continuous, prospective incidence surveillance components dence surveys. They are unique in their ability to quickly get
(4). In an effort to allow for interhospital comparison of rates an overall picture of the magnitude and scope of all HAis.
and benchmarking of healthcare facilities, targeted, risk-ad- Hospital-wide point-prevalence surveys not only describe the
justed surveillance components, now incorporated into the full spectrum of infection sites and pathogens affecting hospi-
National Healthcare Safety Network (NHSN, from 2005 till talized patients, but first and foremost their main characteris-
present), were developed and have produced estimates of se- tics, risk factors, invasive devices, procedures, or antimicrobial
lected HAis for many years (5). However. hospital-wide sur- treatments they are exposed to. In France in 2006, the median
veillance, which was mandated in the early days of the NNIS age of the patients was 69 years, 1 out of 10 patients was im-
system, was discontinued in 1996, and incidence surveillance munosuppressed, I out of 3 had an ultimately or rapidly fatal
was focused on intensive care unit (ICU), high-risk nursery, disease (McCabe score I or 2), 1 out of 5 had surgery within
or surgical patients. Reinforced with U.S. state-mandated HAl the past 30 days, 1 out of 4 had a vascular catheter, and I out
reporting, this long-lasting trend narrowed the focus of HAl of 10 had a urinary catheter; 5.0% had one or more HAls (uri-
surveillance, limiting its ability to identify emerging infec- nary tract, lower respiratory tract, and surgical site infections
tions or even estimate the true magnitude of hospital-wide accounting for 60% of infections) and I5.5% received an anti-
HAis and leading CDC to recently reconsider the value of microbial therapy (11). Such point-prevalence surveys provide
HAl prevalence surveys (6). a sound basis for identifying and setting-up future priorities for
75
'I
0\ TABLE 7.1 Selected Point-Prevalence Surveys in Europe, from 1975 to 2012
Prev. of lnfectioDII Prev. of
Patients with Documented Patients with
Year of Hospitals Patientll 'I)'pe of Types of CDC def. for 2:1 HAl I of by Microbiology Antimicrobials
Country Survey (No) (No) Care Type of Wards InfectioDS HAl HAl(%) (%) (%) Ref.
Sweden 1975 5 4,246 AC,LTC All All sites N -/17.0 9.
Norway 1979 15 7,833 AC All All sites N -/9.0 38.
United 1980 43 18,1~ AC All All sites N (HIS) -/9.2 39.
Kingdom
Italy 1983 130 34,577 AC All All sites N 6.8/- 35.5 40.
Belgium 1984 106 8,723 AC All UTI,SSI, N 9.3/- 41.
BSI
Czechoslovakia 1984 23 12,260 AC All All sites N -/6.1 42.
Spain 1990 123 38,489 AC All All sites y 8.5/9.9 33.8 43.
France 1990 39 11,599 AC All UTI,SSI, y 6.7/7.4 81.2 29.5 44.
LRTI,
BSI, CAT
Norway 1991 76 14,977 AC All All sites N -/6.3 45.
UK& 1993-1994 157 37,111 AC All All sites N (HIS) -/9.0 46.
Republic
of Ireland
Germany 1994 72 14,996 AC All All sites y 3.5/3.6 56.5 36.
Switzerland 1996 4 1,349 AC All All sites y 11.6/13.0 65.0 47.
France 1996 830 236,334 AC,LTC, All All sites Y, mod. 6.7+1.3a/7.6 48.
RH, PSY (+McGeer)
Greece 1999 14 3,925 AC All All sites y 8.6/9.3 51.5 51.4 49.
France 2001 1,533 305,656 AC,LTC, All All sites Y,mod. 6.9/7.5 72.0 15.9 50.
RH,PSY (+McGeer)
Italy 2001 15 2,165 AC All but S14 yo All sites y 7.5/8.3 51.
Slovenia 2001 19 6,695 AC All All sites y 4.6/5.0 55.8 52.
Latvia 2001 2 1,291 AC All All sites N (HIS) 5.1/5.7 29.0 22.0 53.
Italy 2002-2004 51 9,609 AC All but S14 yo All sites y 6.1/6.7 68.4 45.3 54.
Albania 2003 1 968 AC All All sites Y,mod. 16.8/19.1 71.4 46.9 55.
Finland 2005 30 8,234 AC All All sites y 8.5/9.1 53.0 39.0 35.
Scotland 2005 45 11,608 AC All but S16 yo All sites Y,mod. 9.5/10.7 56.
France 2006 2,337 358,353 AC, LTC, All All sites Y,mod. 5.0/5.4 70.0 15.5 11.
RH,PSY ( + McGeer)
UK& 2006 270 75,694 AC All but All sites y 7.6 33.1 57.
Republic children
of Ireland
Belgium 2007 63 17,343 AC All All sites y 6.2/7.1 58.
The 2007-2008 41 26,937 AC All All sites Y,mod. 6.2/7.2 30.9 59.
Netherlands
Lithuania 2007 30 6,288 AC All All sites y 3.4 28.6 32.1 60.
Scotland 2011 52 11,902 AC All All sites N (ECDC) 4.9/5.2 61.
"'nly HAl acquired in the reporting facility were described; 1.3% of patients had a HAl at their admission
HAl, healthcare-usociated infection; AC, acute care; LTC, long-term care; RH, rehabilitation; PSY, psychiatries; UTI, urinary tract infection; SSI, surgical site infection; LRTI, lower
respiratory tract infection; BSI, bloodstream infection; CAT, catheter-aasnciated infection; Y, yes; mod, modified; illS, Hospital Infection Society; ECDC, European Centre for Disease
Prevention and Control; yo, year-<~ld
TABLE 7.2 Selected Point-Prevalence Surveys in the World Outside the United States or Europe, from 1984 to 2008
Prev. of Patients Infections Prev. of Patients
Year of Hospitals Patients Type of Type of Types of CDCdef. with <:!:l HAl/ Documented by with Antimicrobillls
Country Survey (No) (No) Care Wards Infections for HAl of HAl(%) Microbiology(%) (%) Ref.
Australia 1984 28,643 AC All All sites 6.3/8.1 62.
Hong-Kong 1987 10 9,848 8.6/- 63.
Lebanon 1997 14 834 AC All All sites y 6.8/8.5 39.4 64.
Indonesia 2001-2002 2 2,222 AC All Ul'l, SSI, Y,mod. -/6.9 42.3 65.
PHL, SEP
Canada 2002 25 5,750 AC Adult only All sites Y,mod. 10.5/11.6 36.3 66.
Cuba 2004 33 4,240 AC All All sites y 6.7/7.3 30.2 67.
South 2005 6 AC All UI'I, SSI, y 9.7/- 68.
Africa LRTI, BSI
Iran 2004-2005 8 2,667 AC All Ul'l, SSI, BSI y 8.8/8.8 69.
Thailand 2006 20 9,865 AC All All sites y -/6.5 70.8 47.0 70.
Vietnam 2008 36 7,571 AC All All sites y 7.3/7.8 18.4 71.
Argentina 2008 39 4,249 AC All All sites y 11.3/14.2 45.3 72.
China 2007-2008 13 20,350 AC All All sites Y,mod. 3.9/4.1 35.3 50.8 73.
(Hubei
Province)
HAl, healthcare-associated infection; AC, acute care; UI'I, urinary tract infection; SSI, surgical site infection; PHL,
phlebitis; SEP, septicemia; LRTI, lower respiratory tract infection; BSI, bloodstream infection; Y, yes; mod, modified
~
'I
00
TABLE 7.3 Selected Point-Prevalence Surveys Targeting Specific Populations or Pathogens from 2002 to 20ll
Prev. of Infections Prev. of
patients with documented by patients with
Year of Hospitals Patients Type Types of CDCdef. ~1 HAl/ of microbiology antimicrobials
Country survey (No) (No) of care Type of wards mfectioos for HAl HAl(%) (%) (%) Ref.
United States 2006 1,237 187,058 AC All MRSA y 2.4/- 100.0 74.
United States 2008 648 110,550 AC All CDI y 0.9/- 100.0 75.
United States 2010 590 67,412 AC All MRSA y 1.3/- 100.0 76.
Canada 2002 19 997 AC Pediatrics LKI'I, UTI, Y, mod. 8.0/9.1 38.6 77.
BSI, SSI,
CDI, VRI,
NE,VGE
Canada 2009 30 1,353 AC Pediatrics LKI'I, UTI, Y, mod. 8.7/9.2 92.7 40.1 78.
BSI, SSI,
CDI, VRI,
NE,VGE
Russia 2006 1 472 AC Pediatrics All sites Y, mod. 15.2/17.0 39.0 79.
Europe (13 2009 117 14,491 LTC Elderly All sites N [McGeer, 5.0/- 5.4 24.
countries) mod.]
The Nether- 2009 24 1,772 LTC BSI, LKI'I, Y, mod. 7.6/- 6.6 80.
lands B,C,GE,
UTI
The Nether- 2010 10 1,429 LTC Elderly All sites N [McGeer 2.8/- 3.5 81.
lands mod.]
Republic 2011 108 5,922 LTC Elderly All sites N [McGeer 4.1/- 10.1 82.
of Ireland mod.]
HAI, healthcare-associated infection; AC, acute care; LTC, long-term care; MRSA, methicillin-resistant Staphylococcus aureus; CDI, Clostridium dif.ficile infection; LKI'I, lower respiratory tract
infection; UTI, urinary tract infection; BSI, bloodstream infection; SSI, surgical site infection; VRI, viral respiratory infection; NE, necrotizing enterocolitis; VGE, viral gastr~nteritis;
GE, gastr~teritis; B, bronchitis/bronchiolitis; C, conjunctivitis; Y, yes; mod, modified
Chapter 7 • The Use ofPrevalence Surveys for Htalthcare-Associated Infectiun Surveillance 79
infection surveillance and control, including incidence surveys The simplicity of point-prevalence surveys also resides in their
and targeted prevention programs in identified high-risk pa- methods, which facilitates their implementation on the field as
tients or areas. They also can provide more detailed data on they are easier to understand and reduce the need for training
patients and their exposures than can usually be collected in of local staff and investigators. Generally conducted over one
on-going incidence surveillance systems. single day, they are based on short questionnaires (Figure 7.1)
Less difficult to implement than incidence-based surveil- filled in for each included patient, and infection-related variables
lance, point-prevalence surveys also are relatively inexpensive only apply to a minority (5% to 10%) of included patients-
and less time-consuming. For healthcare facilities or countries those infected. Such surveys also are potentially more accurate
that do not have the necessary financial or personnel resources, as they easily incorporate a bedside examination of the patient,
administrative support, or will to conduct HAl incidence sur- and therefore include relevant clinical information, whereas in-
veillance, point-prevalence surveys can help build a minimal cidence studies/surveillance usually use retrospective data col-
HAl surveillance program, by identifying the hospital areas or lection from medical records and notes (and seldom include
HAl sites to focus prevention efforts. In addition, such surveys examination of the infected patient themselves) (13). The aver-
facilitate assessment of the burden of HAis and quickly raise age time needed for data collection and entry during a point-
awareness and skills of hospital staff for infection surveillance prevalence survey was estimated at about 19 minutes per patient
and control. AB HAis are a public health problem ofincreasing (32 hours per 100 patients) in a pilot phase of the ECDC proto-
interest worldwide, they help answer questions from patients, col, performed in 2010 in 66 hospitals from 23 countries (10). In
politicians, the media, and the general public (12,13). The addition, data from point-prevalence surveys do not require so-
measured outcome, as a proportion of patients with a HAl, is phisticated analysis tools or skills and can potentially be managed
very simple and understandable for all audiences and facilitates locally in participating hospitals, therefore increasing the timeli-
this communication. For example, the burden of MRSA or ness and usefulness of local feedback. The use of a dedicated
C. difficile in ICUs or hospital-wide can be determined, whereas software or web site for data entry, validation, and immediate
with incidence surveillance such hospital-wide data collection is feedback to participating facilities can greatly enhance participa-
too resource intensive and seldom collected. tion in prevalence surveys, such as in 2006 in France where 2,337
ECDC prevalence survey of healthcare-assoclated Infections and antimicrobial use
Form A -
Patient based data (standard protocol) ., 5'
!!: )S!
II,.
Plllll!l11 data (to collect for all patienlll)
---+
Antimicrobial (geMric or brand n1111111) i !l -~II 0
Hospital code I I ,.0 iii" 5'
Ward name (abbrevia1Bd)/Unit ID I I

I I
__ ,__ ,____
Ward specialty
(~~
Survey date:
Patl..,t counter:
Age in years: _ _ years; age if < 2 years old: ___ months Route: P: parenteral, 0: oral, R: rectal, 1: lnhalaUon. lncl.._lon: 01-1..1 -HI: traatmentlntentlon lor
oommunlty-acqulrad (CI), long.llntllnn&dla.,..lllnn """'"""''ulrad (LI), or IICUI& hospiiBI·IlOqulrad lnlaollon
Sex:M F (HI); surgical prophylaxis: SP1: single dOH, SP2: one day, SP3: >ana day; MP: m11dlcal prophyllllds;
0: other; Ul: unknown indicalion. Dlagnoela: ae& ailllliat, only for lrlllltm&nt int&ntion.
Dllm or ha.pltel admission: _ I _ I ___ (dO'Innv)lm) - n Inn-: YIN.
Consultant/patient epeclalty:
I I HAI1 HAI2 HAI3
Surgery alnce edmleelon:
...... c... definition code
0 No surgery 0 Minimal invasivelnon·NHSN surgery R...vant Nvto. In sHu OYe<s ONo OYe<s ONo OYe<s ONo
0 NHSN surgery OUnknown before o_,.Pl 0 Unknown 0 Unknown 0 Unknown
McCIIbe acora: Preaent at lldmlalon OYes ONo OYee ONo OYIIII ONo
0 Non·fatal disease 0 Ultlmamly fatal disease Date of on~~at~•l _ ,_, __ _ ,_, __ _,_, __
0 Rapidly fatal disease OUnknown
0 currant hospital 0 currant hospital 0 currant hospital
Cenlntl vnculer catheter: ONo OYes OUnk Origin of infection 0 other hospital 0 other hospital 0 other hospital
0 other originlunk 0 other originlunk 0 other originlunk
Periphenl wacular catheter: ONo OYes OUnk
If BSI: sourceOO
Urinary catheter: ONo OYes OUnk
Intubation; ONo OYes OUnk Rl'l
MOcode Rl"l MOcoda Rl"l MOcode
Patient receives anllmlcroblel(e)!1l: ONo OYes OUnk
-IF YES
Mlcroorgenlam 1
Patient has active HAJI2l: ONo OYes OUnk
Mlcroorgenlem 2
(t) N. the uma ol the aurvey, except lor surgical prophytaxla 24 houra belora 8 a.m. on the Microorganiam 3
day o1.tha. survey; Wyes, ftllln
. llllllmlc:roblal
. """data; (2) Pnlactlon
. with onset:.: Day 3, OR
SSI Cfit&r1a met (surgery m p~Wioua 30 days/1 year), OR diSCharg&d lrom acute core hoap1ta1 (3) Relevenlclevlc<il u. (lntubaUon lor PN, CVCIPVC lor BSI, urinery . - r lor UTI) within 411 houra belora
< 411 houra ago, OR CDI and dlechargedlrom aculll care hollpltal < 2ll da)'!l ago OR on$~ < onset ollnleollon (tMin lntennlllllnt usa), """"n da)'!l lor UTI. (4) Only lor lnlacllons not p111HnllllC!Ive at
Day 3 allllr Invasive diiVIcwprooedu111 on D1 or 021 AND [HAl """"criteria mat on survey admilllion (ddlrnmfyyyy). (5) CCVC, c-PVC, S.PUL. S.UTI, S.DIG, S.SSI, 5-{;ST, S.Oll-1, UO, UNK. (II) AMR
day OR paUentiS raoeMng (eny) traetmenllor HAl AND CQe Criteria are mel betwllen 01 of
marker 0, 1, 2 or 9, 811& table.
lrealmant and survey dayJ; II yes, ftll In HAl data.
Figure 7.1. Questionnaire used in the ECDC point-prevalence survey (standard, patient-based protocol). (With pennission from European
Centre for Disease Prevention and ControL Point prevalence survey ofhealthcare-associated infectiom and antimicrobial use in European acute
care hospitals-protocol version 4.3. Stockholm: ECDC; 2012. http://www.ecdc.europa.eu/en/activities/surveillance/HAI/about_HAI-Net/Pages/
PPS.a&px.)
healthcare facilities accounting for 94% of all French hospital healthcare records used, and screening criteria) for identify-
beds were included ( 11) . ing and classifying HAis (6). The laboratory capacity and types
Repeated point-prevalence surveys also have been used of tests used (e.g., culture w. Polymerase Chain Reaction) at
to get more comprehensive data and evaluate the global im- participating hospitals also can vary, affecting the way HAis
pact of infection control strategies, policies, or programs at are diagnosed/detected, as illustrated by the proportion of
various levels. In a Hong Kong hospital, single-day HAl point- HAis with microbiologic confirmation/ documentation, rang-
prevalence surveys were conducted in the 1980s to assess the ing from 29.0% to 81.2% among surveys {Tables 7.2 and 7.3) .
impact of the introduction of an infection control policy. The A recent review from the ECDC also underlined important
prevalence of HAis fell from 10.5% to 5.6%, and a significant differences in European point-prevalence survey protocols:
decrease in the prevalence of urinary tract infections was at- variations in the list of included infection sites, exclusion of in-
tributed to a catheter-care infection control policy (14). At the fections acquired in other hospitals in some surveys, use of var-
national level, a comparison of the results of two national point- ious case definitions, and different ways in the application of
prevalence surveys in France, adjusted for patient risk factors their criteria (Table 7.4) (19). Indeed, minor differences can
for HAl, demonstrated a 12% decrease in the prevalence of affect results, such as the period in which data are collected,
patients with an HAl from 2001 to 2006 and a 40% decrease in especially if pending microbiologic results at the time of the
the prevalence of patients with a MRSA infection, contributing survey are later incorporated in the dataset {13). The day of
to the assessment of a national infection control program (11). the week selected for data collection also has been identified
Point-prevalence surveys, however, have several limitations. as a variation factor by a Spanish study, with a higher preva-
First, they cannot measure the true risk of infection, that is, they lence of patients with HAis for the period of Saturday-Monday
include in the numerator not only the number of newly but also ("week-end effect") (20) .
already infected patients. The calculated rates are higher and For all these reasons, there is a need for standardizing point-
cannot be compared to incidence rates, especially as prevalence prevalence survey protocols at the intemationallevel, in order
surveys are more likely to capture HAis of longer duration and to facilitate direct comparisons and meaningful results (13),
patients with a longer length of stay, more comorbidities, and a but to date such initiatives are rare. The European Prevalence
greater risk of being infected. Some authors have tried to calcu- oflnfection in Intensive Care (EPIC) study in 1995 was the first
late incidence rates derived from prevalence data using the for-
mula of Rhame and Sudderth for all HAis or only bloodstream
infections (15-17). Such extrapolations of incidence rates from TABLE 7.4 Methodological Differences
prevalence rates/studies should be done with great caution. In in 17 European Prevalence
addition, point-prevalence surveys lack adequate denomina-
Survey Protocols (19)
tor data relevant to specific, device-associated infections (e.g.,
ventilator-days for pneumonia or catheter-days for bloodstream Countries
Methodological DiffereDC:e8
infections). Although they can capture the exposure to invasive % Nama"
devices, such as a urinary or intravascular catheter, they cannot
Cue definitioDS
ascertain if these devices are a cause or a consequence of the
• Diagnostic related groups 11.8 LV,SE
infection because of their croS~H~ectional design. • CDC, modified 11.8 FR,NL
More importantly, comparison of prevalence rates between • CDC, unmodified 76.5 Other countries
healthcare facilities or countries is not easy. At the individual Imported HCAI Included& 47.1 DK, ES, FI, FR, IE,
hospital level, the calculated outcome lacks precision because NL,SE, UK
of the small average sample size {e.g., based on a 7.5% preva- Included infectioDS
lence rate, only 15 patients with a HAl would be identified in a • All infections 52.9 BE, GR, IT, LT, LV,
200-bed hospital). Moreover, the numerator usually combines NL, PT, SE, SI
• Only main infection types 11.8 NO,DK
all types of HAis, and the overall prevalence rate is not a risk- UK, IE, FI, DE
• Exclusion ofsecondary 23.5
adjusted measure such as 1 bloodstream infection per 1,000 bloodstream infections
catheter-days. Prevalence survey data should, therefore, not • Exclusion of asymptomatic 11.8 ES,FR
be used as a measure of quality of care and to compare hospi- bacteriuria
tals (18). Some surveys have tried to compare prevalence rates Data collection type/ workload
across regions in a country. In 2006 in France, the prevalence • Aggregated numerator and 11.8 NO,DK
of patients with an HAl varied from 2.66% in Corsica to 5.75% denominator
• Patient-based numerator and 11.8 SE,LV
in Rhone-Alpes, but categories of enrolled healthcare facilities
aggregated denominator
and patients' case-mix also varied from one region to the other, • Patient-based numerator and 76.5 Other
limiting the interpretation of the results ( 11). denominator
The same applies when trying to compare prevalence sur- Exclusion of specific patients 17.6 FR,NL,FI
veys among countries, which is even more difficult because or specialties
published surveys (Tables 7.1-7.3) used different study designs
and definitions of HAl. Facilities were included on a voluntary "BE, Belgium; DE, Germany; DK, Denmark; ES, Spain; FI, Finland;
basis in most studies, therefore limiting their representative- FR, France; GR, Greece; IE, Ireland; IT, Italy; LT, Lithuania; LV,
Latvia; NL, Netherlands, NO, Norway; PT, Portugal; SE, Sweden;
ness, and patients with a higher case-mix {e.g., acute care wards
SI, Slovenia; UK, United Kingdom; References; http:/ / ecdc
only) were sometimes selected. In addition, investigators with
.europa.eu/, except Belgian PPS: http:/ / www.kce.fgov. be/
various degrees of qualification or training were used to collect ~otalways included in main HCAI prevalence results; UK, ll.;
data (questioning the way standard definitions for infection only if re-admission from same hospital.
were applied), or applied different methods (i.e., definitions,
international mrvey for mearuring the prevalence of HAis in a the time of the survey (26). As patients can have more than one
standardized manner in ICUs (21). In 2009, the EPIC II study infection, authors also report the outcome as a xatio of active
was conducted among 1,265 ICUs in 75 countries and four infectiom divided by the total number of patients screened.
continents and enrolled 13,'796 patients, 51% of whom were The "prevalence of infection" is sometimes used to name both
infected (22). Other, similar initiatives were launched for HAl indicators in publications, but they are different.
surveillance in the Mediterranean region (23), or in Europe The HAl definitions should be as simple as possible in order
with the Healthcare-usociated Infections and Antimicrobial to be applied consistently by different investigators. Most of the
U.se in European Long-Term Care Facilities (HALT) (24) or the published surveys used CDC definitions (27), although some
European Surveillance of Antimicrobial Consumption (ESAC) were modified (19). Additionally, the impact of their translation
(25) projects. In 2010, the pilot ECDC point-prevalence survey into other languages cannot be ascertained. In Europe, case
for HAl and antimicrobial use (10) is the most recent initia· definitions for HAis were developed by Hospital in Europe Unk
tive, which led to finalization of a common protocol and then for Infection Control through Surveillance (HEUCS) or other
enrollment of !0 countries in such a survey from 2011 to 2012; European projects and consolidated into a single set in order to
results will be published in 2013 (http:/ /www.ecdc.europa. prepare countries for a European point-prevalence SUIVey (10);
eu/). Many of the challenges in standardizing point-prevalence those definitions were published in 2012 by the European Com-
survey methodologies also apply to incidence surveillance, pail> mission (28). For long-term care facilities, McGeer definitions
ticularly when large numbers of hospitals and different people have been used (29,W).
are collecting the data and applying and interpreting the HAl Case-finding approaches also should be defined. The pres-
de&nitiom. ence of fever (temperature 2: 38"C), the administration of an
antimicrobial treatment, or the presence of an invasive device
have been used as screening criteria in a survey, systematically
METHODSOFPREVALENCHSURVEYS detecting the most common HAis (i.e., bloodstream, surgical
site, lower respiratory tract, and urinary tract infections) while
A point-prevalence rurvey provides data about hospitalized pa- requiring rurveillance ofonly 62% of patients (31). Similarly, an-
tients in a given ICU, or ward, or facility at one point in time other survey found that only 6% of patients with an HAl would
(26), acting as an instant snapshot of the patients and their have been miased by using either microbiology reports or an-
infection(s), if any. In contrast, incidence surveys act as a mo- timicrobial treatment as a screening criteria (sensitivity of this
tion picture over a given period of observation, recording the approach: 94%); however, the sensitivity was< 80% in some ha&-
number of new episodes of infection that occur per unit popu- pitals, underlining the need for a careful evaluation oflocal prac-
lation at risk (incidence de:ruity), or the proportion of exposed tices before applying such criteria (32). More recently, a CDC
patients who become infected over the entire period of expo- survey performed in nine acute care hospitals in Florida used
sure or duration of hospitalization (cumulative incidence or three proxy indicators (i.e., abnonnal white blood cell count,
attack rate) (26). A theoretical example of calculation is pro- abnormal temperature, or receipt of antimicrobial therapy) for
vided to illustrate these differences (Figure 7.2). detecting infections. Antimicrobial therapy was the most sensi-
Point-prevalence surveys are usually conducted during tive proxy indicator, identifying 95.5% of patients with HAis, but
1 day, although larger hospitals might need several da)'3 to sur- was very frequent (46%) in the surveyed population (33). In all
vey all their patients. In general, only those infectiomjudged to instances, a clear. well-defined algorithm for case-finding, such
be clinic:ally active at the time of screening are recorded. The as the one used in the European survey (Figure 7.3), should be
outcome is recorded as a proportion of all patients screened given to all investigators for a consistent approach, also specifY-
who are infected, that is, who had at least one active infection at ing the types ofhealthcare records to be used.
Patients - - - - Patient stay - Patient Infected
i- ------ ------- ~------- ----f)--------------1------+------+----+-----h I

A
B
! i : I
c
!' : :
D
l It j'
E
.......
co 01 02 03 04 L ~.! ce D7 os D9 010 011 012
Fipre 7.Z. Prevalence versus incidence
rate: a theoretical eumple. Daya
Introduce yourself to ward manager.

Collect ward specialty type, number
~
Surveillance team arrives on ward. of beds.
Record start date and time Request patient list.
I Exclude patients from further data
collection if admitted after 8 a.m.
~
Collect denominator data on all Walk around ward.
patients in hospital before 8 a.m. For each patient, observe for
I invasive devices (UC, PVC, CVC,
ventilation)
Collect ONE set of patient notes (medical, nursing,

observation, drug, wound, pressure, stool charts, etc.)
HAIIICCOrdlng to .tandard
On antimicrobials?
daflnltlons?
If notes are If notes are unclear,

unclear, ask for ask for clarification of
treatment signs and
indication from symptoms only
medical, pharmacy, from nursing/medical
or nursing teams. team
Complete data collection for all patients.

Once complete, thank ward manager and leave.
Record end time on forms
Pass on data forms to

local coordinator or data
entry facilitator.
UC =urinary catheter; PVC= peripheral vascular catheter; CVC =central vascular catheter
Figure 7.3. Recommended Clll!e-finding algorithm for the ECDC point-prevalence survey. (With per-
mission from European Centre for Disease Prevention and Control. Point prevalence survey ofhealthcare-
associated infections and antimicrobial use in European acute care hospitals-protocol version 4.3.
Stockholm: ECDC; 2012. http:/ /www.ecdc.europa.eu/en/activities/surveillance/HAl/about_HAI-Net/
Pages/PPS.aspx.)
Questionnaires used in prevalence surveys should be kept as this approach is very costly. In 1998, a German survey used
as simple as possible. An example of such a questionnaire is four physicians traveling to 72 hospitals; their inter-rater reli-
provided (Figure 7.1). They usually collect a minimal dataset ability (IRR) was checked before the survey using case studies
on patients (i.e., basic demographics: age, gender; hospital ad- designed by the study supervisors (37). However, considering
mission date; specialty), their exposure to invasive procedures that prevalence surveys should mobilize hospital staff in order
(surgery), devices (urinary catheter, vascular catheter, intuba- to raise awareness, the French prevalence surveys always used
tion), or antimicrobial treatments. Some surveys also have col- local infection control personnel; they were already acquainted
lected proxies for comorbidities or severity of illness, such as with and knowledgeable about HAl surveillance and specifically
the McCabe score (34) in the French (11) and Finish surveys trained for the point-prevalence survey objectives and methods
(35), which is highly correlated with the HAl prevalence and by regional infection control coordinating centers ( 11) . Other
now is incorporated into the ECDC protocol ( 10). Additionally, surveys used personnel with less training such as nurses, phar-
simpler protocols collecting aggregated denominator data at macists, or medical students (6) .
the ward or hospital level can be used (10,36).
Last, as point-prevalence surveys often encompass all infec-
tion sites, the background of investigators and their training, CONCLUSION
especially for applying case definitions for HAl, is important,
and a source of considerable variation in the methods and Point-prevalence surveys are relatively easy to perform, require
results among published surveys. Only a few point-prevalence fewer resources, and can mobilize many healthcare facilities in
surveys used external investigators visiting multiple hospitals a country within a short period of time. They are, and should
Chapter 7 • The Use ofPrevalence Surveys for Htalthcare-Associated Infectiun Surveillance 83
1!. Humphrey~ H, Smyth ETM. Pn:nlence IIU'Ve)'l of healthcan>-auociated infectiono: what

remain, simple surveys in order to facilitate data analysis and
do they tell uo, if anything? Clm MicrobiDI.hofoa. 2006;12:2--4.
increase feedback timeliness. Although they have limitations 14, French GL, Cheng A, Farrington M, 'Repeated prevalence ourveyo for monitoring effective.
when compared to risk-adjusted incidence surveys, they are ne11 of hotpillll infection control. Llm<fi.1989;2:1021-102S.
a first step in infection surveillance and control that should 15. G9.tmeicr P, Briuer H, Sobr D, et al. Converting incidence and prevalence data of noooco-
mial infection~: results from eight hoopitalo. Infoct Conlrol Hasp Ep~ !001;2!:!1--M.
be implemented everywhere, in order to identify priority for 16. Graveo N, Nichollo TM, Wong 00, eta!. The prevalence and eotimateo of the cumulative
healthcare quality improvement. They serve as a quick method incidence of hoopital..cquired infection• among patients admitted to Aw:klaud District
Health Board Hoopitalo iu New Zealand. Inj«l Ctmlrol Hosf>Epidnniol. 20011;24:56-01.
for determining the hospital-wide distribution of HAis, device 17. Ghaguidi Haore H, Muller A, Talon D, et al. Eotimation of the cumulative incidence of
exposures, or antimicrobial exposures, which is much more hoopillll-<ll:<Juired bactereiDia from prevalence data: a fonnula. Injrt:t Conlrol Hasp F?UJ-iol.
challenging to determine using incidence surveillance. 2005;26:415--417.
18. Stow: PW, Horan TC, Shih HC, ct al. Comparilom ofbealthcan:-;uaociated infectin111 iden-
Depending on the available resources, their implementation tifu:arion wing two mecharum!a for public reporting. Am]Injocl Conb'ol. 2007;!5:14!>-149.
offers many possibilities in order to adjust the balance from 19. Sw:ti!DS C, Anunou A, Weiot K, ct al.IU:riew of mcthodo ofuatinnal pn:nleuce •urveyo of
healthcare-uoociated infectiono in 17 European countrieo. In: Proceedingo from the 19th
a carefully designed survey, possibly using a sampling frame
Europeau Congren of Clini<:al Microbiology aDd Wfectinw Dioeueo; 16-19 May, 2009.
and external investigators, to other, simpler ones, offering to Hellinki, Pmland. Abatract 624.
all hospitals and countries practical tools in order to increase 20. Rouell6-Urge11J, Vaqu6-RafartJ, Annadano-Gil LL, etal. The importance of the day of the
week and duration of data collection in prevalence l urYC}" ofnooocomial infectiono.J Hasp
awareness for infection control. Injra. 2004;57:152--138.
In order to facilitate comparisons between published surveys 21. VlllCentJL, Bihari DJ, Su""' PM, et al. The prevalence of nooocomial infection in inti!Diive
in the future, efforts should be pursued to disseminate interna- care units in Europe. IU:sulbl of the European Prevalence of Wfection in Intemi.ve Care
(EPIC) Study.JL\!A-1995;274:~.
tionally recognized definitions of infections, such as the ones 22. VlllCent]I. RelloJ, Manhali.J, et al.lntematinnalotudyofthe prevalence and outcome• of
from CDC, ECDC, or McGeer, and standardized prevalence infection in intenoive care units. JAMA. 2009;!102:2!2~21129.
211. Amazian K,lloolello J, Caotella A, et al. Prevalence of nooocOJnial infection• in 27 hoapitall
protocols, such as the one initiated in Europe by the ECDC.
in the Mediterranean region. Eall M..ulorr HIIJ/thj. 2010;16:107()...1078.
Standardized protocols for conduct of HAl point-prevalence 24. Latour K,Jano B, the HAli management team. Healthcareaoociated infectiono in long-tenn
surveys are essential if periodic assessments are to be conducted carelacilitiea. Ralullo ofthe pilotpointpr-.olencc 1\l""'l' N""""'her2009. htlp:/ /halt.wiY-ilp.he/
25. Anoari F, Emtell M, Goouen1 H, ct a!. The European a"""illance of antimicrobial con-
and compared at the individual hospital, region, country, or swnption (ESAC) point-prevalence ·~of antibacterial uoc in 20 European hoopillll• in
within a group of countries. Given their ease of conduct, con- 2006. Clminfoctl.>iJ. 2009;49:1496-1504.
sideration should be given to including such point-prevalence 26. Freeman J, McGowan JE. Methodologic isruco iu hoopital epidemiology. I. Rateo, CIK>-
fiuding, aDd inteipretation. &v!nftct J.>U.1981;!:658-007.
surveys in the armamentarium of infection preventionists in 27. Horan TC, Andruo M, Duded MA. CDC/NHSN ourveillance definition of healthcare-
their assessments of the extent and type of HAis. Uiociated infection aDd criteria for opecific typeo of infection• in the acute care aetting.
AmJ Infect Ctmlrol. 2008;56:509-.!!32.
28. European Commisaion. Comrnillion Implementing DeciJion of 8 Augwt 2012 amending
Decioion2002/255/EC laying down caoe definitinno for reporting communicable di.oeaoeo
ACKNOWLEDGMENTS to the Community network under Decioion No 2119/98/EC of the European Parliament
lWd of the Council (notified under docutuent C (2012) 5558). http:/ /cur-U:x.europa.eu/
LcxUriServ/LexU riServ.do?uri=OJ :L:2012:262:0001:01:EN:HTML.
The author thanks Dr. Carl Suetens for shared materials and 29. McGcer A, Campbell B, Emori TG, et aL Definition• of infection for ouneillance in long-
tenn care focilitieo. Am] Injocl Conb'ol. 1991;19:1--7.
fruitful discussions when preparing the ECDC point-prevalence !10. Stone ND, Alhnf MS, Calder J, et al. Society for Healthcore Epidemiology Long-Tel'lll
survey on HAl and antimicrobial use, and Dr. William R.Jarvis Care Special Intereot Group. Surveillance definitiono of infection a in long-term care focili-
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Netherlando, 2007-2008: ""ulto ofdle lint four national otudieo.]H..plry'io:l. 2010;75:168-172. 77. Gravel D, Matlow A. Ofner-Agcotioi M, et a1. A point prevalence ouney of healthcare-
60. Valinteliene R, Gailiene G, Berzan&ltyte A Prevalence of healthcare<UIOciated infectiOIU auociated infection• in pediatric population• in major Canadian acute care hoapitab. Aa
in Lithuania. J Htnp 1Afoet. 2012;80:2!>--30. 1brfot:t Conln>l. 2007;55:157-162.
61. Rcill.y J, Caimo S, fleming S, et a1. Result> from the oecond Scouiah national prevalence 78. Rutledge-Taylor K. Mallow A. Gravel D, et al. A point prevalence •urver of healthcare-
ouney. the changing epidemiology of healthcare-a110ciated infection in Scotland. I H..p """ciated infection• in Canadian pediatric inpatient>. Am]Infoa Conln>l. 2012;40:491-496.
mf.a. 2012;82:17(}...174. 79. Hajdu A. Samodcmo OV, Carlooon TR, et a1. A point pre'931ence aurveyofhoopital-acquired
62. McLaw. ML, GoldJ, King K, et al. The prevalence of nooocomial and community4cquired infections and antimicrobial we in a paediatric hoopilal in north-western 1W»ia. J H..p
infections in Australian hoopitab. Mid] Awt. 1988;149(11,12):582-590. l#.fo<t. 2007;66:378-584.
63. Kam KM, Mak WP. 'ICrritory-wide '"""'Y of hoopital infection in Hong Kong.] H..p Infect. 80. Eikch:nboom-Bo•kalllp A, Cox-Ciaeueno JH, Boom-Poelo PG, et al. Thn:c>-year prevalence
1993;23:14!-151. ofhealthcare<uoociated infection• in Dutch nursing homeo.J Htnp lnfta. 2011;78:59-62.
64. Azzam R, Dramaix M. A onc-<lay prevalence ouney of hoopital;u:quired infectiOIU in 81. Ei1en R., Veldman-Ariesen I\q, Haencn A, et al. Prevalence and d.etenninaob u•oci-
Lebanon. I Hr»p lnftcl. 2001;49(1) :74-78. ated with health~ted infection• in long-term care facilitieo (HALl") in the
65. Duerink DO, Roe1hadi D, Wahjono H, et a1. Surveillance of healthcaro<UOOciated infec- Netherlando, May to June 2010. Evm Sunoill. 2012;17(54):pii=20252.
tion• in lndoneoian hoopitab.] Htnp Infta. 2006;6.2:21 ~229. 82. Health Protection Surveillance Centre (HPSC). !i«tmdN.aitmal~Surot!y OfJJUaltA-
66. Gravel D, Taylor G, Ofner M, etal. Point pn:val.ence IU""'Yfor healthc""'""""ciated infec- """~ hlf«limu f.IJill Antibioti< wc mIrish l.moc-'Ifm< Canr FIJcilitW. Dublin, lreland:
tion• within Canadian adult acute-<we hoopitab.J Htnp 1Afoet. 2007;66:24~248. HPSC.
8 William R. Jarvis
Investigating Endemic and Epidemic

Healthcare-Associated Infections
Although healthcare facility infection control (IC) programs Most endemic HAis result from breaks in aseptic tech·
have been shown to be effective in reducing the healthcare- nique, most commonly from person-to-person transmis-
wociated infection (HAl) rate, endemic and/or epidemic in· sion via transient HCW band carriage of the colonizing or
fectiom associated with the delivexy of healthcare continue to infecting pathogen. Numerous studies have documented
occur (1). It bas been estimated that approximately only one- that HCWs often fail to perfonn hand hygiene before and
third of all HAis are preventable (2}. However, IC programs between contacts with patients or their contaminated envi·
at U.S. hospitals prevent only -6% of these HAis because of ronment (6). Nevertheless, investigating endemic HAis trans-
incomplete implementation of the recommended control mea· mitted in this way focuses the attention on the importance
.sures (2,3}. The goal.s of any healthcare facility IC program of general IC recommendations (including identifYing and
.should be to educate healthcare workers (HCWs) on the rec- isolating infectious patients, HCW hand hygiene, environ-
ommended measures to prevent and control HAis; conduct mental cleaning and disinfection, and existing guidelines to
active, pro.spective HAl mrveillance; analyze HAl swveillance prevent these infections) and can be associated with a reduc-
data to identifY endemic or epidemic HAl problems warranting tion in the rate of these infections. Because many endemic
further investigation; conduct epidemiologic investigations to infections are preventable, investigation of such problems by
identify the .source of these problems; and implement control the infection preventionist (IP) or ho.spital epidemiologist
measures and assess their efficacy in preventing and control- may be warranted if the rate of endemic HAl is gradually
ling these problems. The purpose of this chapter is to de.scribe increasing at the institution or the rate of these infections
the epidemiology of endemic or epidemic HAis, discuss the is higher than the institutional goal, that which is expected,
criteria for determining whether to investigate endemic or than reported in the literature, or than reported from other
epidemic HAis, and outline the systematic approach to such similar institutions.
investigations. Epidemic HAis are defined as the occurrence of infection
at a rate statistically significantly higher than the background
rate of such infections; recognized infection clusters often
DEFINING ENDEMIC OR. are unexpected, and involve either an unusual pathogen or a
EPIDEMIC HAIS pathogen with an unusual antimicrobial susceptibility pattern
(see Chapters 9,15). The recognition of clusters of common
Endemic HAls are defined as sporadic infections that con· organisms with common antimicrobial susceptibility patterns
stitute the background rate of HAls at the healthcare facility; may be difficult because they merge with the existing endemic
the rate of such HAis usually :fluctuates from month to month, infections. Often, IC personnel attempt to detennine whether
but overall it is not .statistically significantly different from the a cluster represents an outbreak on the basis of numerator data
background rate of these infections (see Chapters 6,30). Of all only. In such a situation, it is difficult, if not impossible, to de-
HAis, endemic HAis account for the majority of infections, and termine whether a detected cluster represents an outbreak un-
are the focus of most IC activities. The predominant pathogens less it involves either a very rare organism (e.g., Vtbrio cho'Urrae
and sites of endemic infection are somewhat similar at different diarrlula) or a common organiam with an unusual antimicrobial
types of healthcare facilities, but do differ on the basis of the susceptibility pattern (e.g., vancomycin-resistant Staphylocot:C'IJ.!
cue-mix of patients (including underlying diseases and sever- aumu).
ity of illne.ss) and types of procedures performed and device.s The determination of an outbreak should not be based on
used (see Chapter 30) (Thbles 8.1, 8.2A, 8.2B) (4,5). (http:/I numerator data alone. Although one episode of healthcare-
www.cdc.gov/nbsn/PDFs/dataStat/NHSN-R.eport_201 O.Data· associated malaria or cholera in a U.S. hospital repre.tenta an
Summary.pdf). Endemic infections can change in type (patho- epidemic, one cannot determine whether a cluster ofhealthcare-
gen, site, or both} and/or rate as the re.sult ofa variety offactors, associated S. aumu bloodstream infections (BSis) represents an
including opening or moving to a new facility, introducing a new outbreak unless one can calculate and compare the S. aumu BSI
or expanding existing clinical services or specialties (e.g., bone rate.s in the time periods during and before the cluster. Because
marrow or organ transplant, neonatal intensive care unit (ICU), of the abrupt nature of epidemics and the feeling that moat such
surgical or medical subspecialty), introducing new diagnostic outbreaks are preventable, in most situations epidemics warrant
methods (e.g., laboratoxy or radiology), and so on. investigation.
85
TABLE 8.1 Distribution and Rank Order of Selected Pathogens Associated with Cases
ofHealthcare-Assoclated Infection (HAl) Reported to the National Healthcare
Safety Network, January 2006 to October 2007, by Type of HAl
CLABSI CAUTI VAP SSI
No.(%) of No.(%) of No.(%) of No.( % ) tf No. (%) of
Prlthopic PaiiJogerric Pathogmic Palhoptie l'alhogmic
Pathogen lmliJtn Rllfll bol.ata Rllfll baltJta BmW lmliJtn BmW IIOliJtn RBfll
CoNS 5,178 (15.!1) 1 !1,900 (!14.1) 1 2!14 (2.5) 7 79 (1.3) 9 965 (1!1.7) 2
Staphylococcus 4,91!1 (14.5) 2 1,127 (9.9) 4 208 (2.2) 8 1,456 (24.4) 1 2,108 (!10.0) 1
aureus
Enterococcus !I 2 3 10 3
species
E. jfJifUliis 1,177 (!1.5) 627 (5.5) !135 (!1.6) 21 (0.4) 194 (2.8)
E.faecium 1,888 (5.6) 942 (8.2) 562 (6.0) 38 (0.6) !145 (4.9)
NOS 1,028 (3.0) 265 (2.3) 496 (5.!1) 18 (0.3) 249 (3.5)
Candida species 4 !I 2 7 8
C. albicans 2,295 (6.8) 67!1 (5.9) 1,361 (14.5) 140 (2.4) 115 (1.6)
Other
Candidaspp.
or NOS
1,!1!13 (!1.9) 669 (5.9) 613 (6.5) 20 (0.3) !10 (0 .4)
Esclurichia coli 3,264 (9.6) 5 !110 (2.7) 8 2,009 (21.4) 1 271 (4.6) 6 671 (9.6) 4
p~ 2,664 (7.9) 6 357 (3.1) 7 938 (10.0) 4 972 (16.3) 2 390 (5.6) 5
aeruginosa
Kkbsiella 1,956 (5.8) 7 56!1 (4.9) 5 722 (7.7) 5 446 (7.5) 5 21!1 (3.0) 7
/JMUfiiO'IIiae
Enterobacter 1,624 (4.8) 8 443 (!1.9) 6 !184 (4.1) 6 498 (8.4) !I 293 (4.2) 6
species
Acinerobacter 902 (2.7) 9 252 (2.2) 9 109 (1.2) 9 498 (8.4) !I 42 (0 .6) 9
baumannii
Kkbsiella cn~JIOM 359 (1.1) 10 99 (0.9) 10 85 (0.9) 10 128 (2.2) 8 47 (0.7) 9
Other 5,267 (15.6) 1,201 ( 10.5) 1,!121 (14.1) 1,375 (23.1 ) 1,363 (19.4)
Total 33,848 (100) 11,428 (100) 9,377 (100) 5,960 ( 100) 7,025 (100)
"The overall total includes data for 58 pathogens associated with postprocedure pneumonia (not shown); the overall no.(%) of pathogenic
isolates is dependent on the relative amount of data submitted for each type of HAl.
Of the 28,502 ca.!les of HAl reported, 4,671 (16.4%) were polymicrobial. CAUTI, catheter-associated urinary tract infection; CLABSI, central
line-associated bloodstream infection; CoNS, coagulase-negative staphylococci; NOS, not otherwise specified; SSI, surgical site infection; VAP,
ventilator-associated pneumonia.
Centers for Disease Control and Pre1rention (CDC). NHSN annual update: antimicrobial.resistant pathogens a.!I.!IOciated with healthcare-associ-
ated infections: annual summary of data reported to the National Healthcare Safety Network at CDC, 2006-2007. Infect Control H osp Epidemiol.
2008;29:996-1011.
TABLE 8.2A Distribution of Device-Associated Healthcare-Assoclated Infections (HAIS) Reported to

the National Healthcare Safety Network, January 2006 to October 2007, Stratified by
Type of Patient Care Area (PCA)
No. of Unit No.(%) ofHAh
Reporting
TypeofPCA (n= 1.040'? Owrall CLABSI CAUII VAP
BumiCU 18 690 (!1.0) 271 (2.7) 206 (2.4) 213 (4.7)

Medical cardiac 84 1,135(4.9) 429 (4.3) 548 (6.4) 158 (!1.5)
ICU
Cardiothoracic 76 1,299(5.6) 44!1 (4.4) 469 (5.5) !187 (8.6)
surgical ICU
MICUb 116 2,961(12.8) 1,204 (12.0) 1,252 (14.6) 505 ( 11.2)
Medical.,.urgical 268 5,260 (22. 7) 1,918 (19.0) 2,208 (25.7) 1,1!14 (25.1)
ICU
Medical-surgical 31 1,116(4.8) 288 (2.9) 827 (9.6) 1 (0.02)
ward
NICU• 127 2,421(10.5) 2,076 (20.6) 0 (0.00) !145 (7.6)
Neurosurgical ICU !11 867(3.7) 268 (2.7) !198 (4.6) 201 (4.4)
Chapter 8 • Investigrlting Endemic and Epidemic Healthcare-Associated Infections 87
TABLE 8.2A Distribution of Device-Associated Hcalthcarc-Assoclated Infections (HAIS) hportcd to

the National Hcalthcarc Safety Network, January 2006 to October 2007, Stratified by
Type of Patient Care Area (PCA) (Co•ri•wtl)
No. of Unit No.(%) ofHAis
Reporting
TypeofPCA (n = 1.0405) o-ull CLABSI CAU71 YAP
PICU4 65 958(4.1) 621 (6.2) 197 (2.3) 140 (3.1)

SCA' 25 6lH(2.7) 552 (5.5) 65 (0.8) 14 (0.3)
SICU 100 2,730(11.8) 1,031 (10.2) 1,005 (11.7) 694 (15.3)
TraumaiCU 27 1,520(6.6) 448 (4.4) 495 (5.8) 577 (12.8)
Impatient ward! 37 900(3.9) 312 (lU) 579 (6.7) 9 (0.2)
Other location 35 679(2.9) 203 (2.0) 330 (3.9) 146 (3.2)
Total 23,167(100) 10,064 (100) 8,579 (100) 4,524 (100)
"Data were collected from 1,428 PCA.s overall, but only from 1,040 PCA.s for device-urociated HAis.
bJ:ncludes prenatal and neurology ICUs.
'Level II-III and level III NICUs.
4All types.
'Bone marrow transplant, inpatient acute dialysis, hematology and oncology, pediatric hematology and oncology, long-term acute care, solid
organ transplant, and pediatric solid organ transplant.
.lbther than SCAli and inpatient medical-surgical wards.
CAUTI, catheter-associated urinary tract infection; CLABSI, central line-associated bloochtream infection; ICU, inten!ive care unit; MICU,
medical ICU; NICU, neonatal ICU; PICU, pediatric ICU; SCA, specialty care area; SICU, surgical ICU; VAP, ventilator-aasociated pneumonia.
Centers for Disease Control and Prevention (CDC). NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated
infectioru: annual summary of data reported to the National Healthcare Safety Network at CDC, 2006-2007. Infect Control Hosp EpidemioL
2008;29:996-1011.
TABLE 8.2B Device-Associated Infection Rates by Hospital Unit or Ward, Centers for Disease Control
and Prevention's National Hcalthcarc Safety Network, 2010
Central Line-Associated Catheter-Associated Urinary Vendlator-Associated
Critical Care Units Bloodstream Infection Ratea 'lract Infection Ratea Pneumonia Ratea
Bum 3.5 4.7 5.8
Medical (teaching) 1.8 2.4 1.4
Medical (all other) 1.3 1.9 1.0
Medical cardiac 1.3 1.9 1.ll
Medical-surgical (teaching) 1.4 2.2 1.8
Medical-surgical (all other, <15 beds) 1.1 1.ll 1.2
Medical-surgical (all other, >15 beds) 1.0 1.ll 1.1
Neurologic 1.2 3.0 4.8
Neurosurgical 1.3 4.0 3.1
Pediatric cardiothoracic 2.1 2.3 0.7
Pediatric medical 1.9 3.9 1.1
Pediatric medical~urgical 1.8 2.2 1.2
Surgical (teaching) 1.4 3.0 3.5
Surgical (all others) 1.0 1.5 2.5
Surgical cardiothoracic 0.9 1.6 1.6
Trauma 1.9 3.2 6.0
Specialty areas
Bone marrow transplant 3.0 1.6
Hematology-oncology 2.0 2.0
Pediatric hematolog)"<lncology 2.8 0.0
INPATIENT WARDS
Acute stroke 0.1 0.2
Antenatal 0.0
Behavioral health/ psychiatric 1.2 1.9
Bum 2.5
Genitourinary 0.7 1.2
Gerontology 1.2
Gynecology 0.7 0.6
Jail 2.8
(continued)
TABLE 8.2B Device-Associated Infection Rates by Hospital Unit or Ward, Centers for Disease Control
and Prevention's National Hcalthcare Safety Network, 2010 (Ctmtl11wtl)
Central Line-Associated Catheter-AIIsoc:iated Urinary Ventilator-Aaoc:iated
Critical Care Units Bloodstream Infection Rate" Tract Infection Rate" Pneumonia Rate 13
Labor and delivery 0.0 0.5
Labor, delivery, recovery, po5tpartum suite 0.6 0.7
Medical 1.1 1.6 0.2
Medical-,surgical 0.9 1.5 0.4
Neurologic 0.8 2.0
Orthopedic 0.6 U5
Orthopedic trauma 1.6 0.7
Pediatric medical 1.2 1.5 0.0
Pediatric medical-,surgical 1.5 1.4 0.7
Pediatric orthopedic 1.6
Pediatric rehabilitation 2.8
Pediatric surgery 1.3
Postpartum 0.0 0.4
Pulmonary 1.0 1.3 1.8
Rehabilitation 0.5 3.2
Surgery 1.0 1.6
Telemetry 1.0 0.5
Va..cular surgery 0.8 2.5
Well baby nursery 0.0 0.0
tJRate per 1,000 device days.

Adapted from http:/ /www.cdc.gov/nhsn/PDFs/ dataStat/NHSN-Report_201 0-Data-Summary.pdf.
RECOGNIZING ENDEMIC OR and calculation of infection rates in the area are part of an on-
EPIDEMIC HAIS going, validated process. Once the cluster is identified, the in-
vestigator next determines whether the problem is endemic or
Surveillance is the cornerstone for the rapid recognition of en- epidemic in nature.
demic or epidemic HAis (see Chapter 5). In order to detect Differentiating endemic from epidemic HAis requires
either endemic or epidemic HAis, one must have a surveillance review of how the numerator and denominator are collected,
program in place to detect such infections. Because the ma- validation of the accuracy of these data, and assessment of
jority of HAis arise in severely ill patients exposed to invasive whether factors exist that might influence either the numera-
devices (e.g., patients in ICUs or those with invasive devices) tor or denominator data (i.e., surveillance artifact, change in
or those undergoing surgical invasive procedures, surveillance definitions, introduction of new diagnostic technologies or
for infections in these populations is most important. If no sys- patient populations or procedures, etc.) (Table 8.3) . Care must
tematic surveillance system is in place, many clusters may not be taken to ensure that surveillance artifact is not leading to
be recognized, and if they are recognized, it is impossible to dean erroneous conclusion that either the number of HAis or
termine whether the cluster identified is endemic or epidemic the HAl rate is increasing. A wide variety of factors that can in-
unless appropriate denominator data are obtained and rates flate or deflate the numerator or denominator data can lead
are calculated and compared. to surveillance artifact; they include changes in the definitions
If active prospective surveillance using standardized defi- used to ascertain HA!s, HAl detection methods--including sur-
nitions and methodologies, such as those published by the veillance or laboratory methods-changes in the populations of
CDC's National Healthcare Safety Network (NHSN) (http:/1 patients served, devices used, or procedures performed.
www.cdc.gov/nhsn/TOC_manual.html), is not conducted, it
may be necessary to carry out a specific retrospective study to TABLE 8.3 Selected Conditions that
determine the background rate of infection before one can can Result in Surveillance
determine whether the HAl problem detected or recognized
Artifact
is endemic or epidemic (7-17). In institutions in which active
prospective surveillance is not being conducted in the area, • Introduction of new infection definitions.
when a cluster is detected, a retrospective study must be un- • New infection control practitioner(s).
dertaken to attempt to reconstruct the current and past rates • Initiation of surveillance in a new area or population
of such infections in the area. Only then can one differentiate of patients.
between an endemic and epidemic problem. A simple defini- • Introduction of new laboratory tests.
tion of epidemic is a rate of HAl significantly higher than the • Introduction of new population of patients.
• Increased or decrealled frequency of culturing/ testing
background rate.
of patients.
The early detection of infection clusters and the determina- • Introduction of new medical procedure (e.g., endoscopy,
tion of whether the cluster identified is endemic or epidemic cardiac surgery).
are most readily done if active surveillance for such infections
Because surveillance artifact influencing either the nu- HAl rates during the suspected epidemic and preepidemic pe-
merator or the denominator data can pr~udice HAl rate riods. Care should be taken when comparing the HAl rate at
comparisons, it is important that the accuracy of these data be one's own institution with that reported either in the literature
detennined before rate comparisons are made. Although it is or from other institutions. Unless the surveillance methods
tempting to quickly begin comparative epidemiologic studies used (including HAl definitions and case-ascertainment meth-
to ascertain the source and risk factors for infection, it is imper- ods), the populations served, the types and number of invasive
ative that sufficient time be taken before embarking on such device used, and the types and number of surgical procedures
analyses to ensure the accuracy of the numerator and denomi- performed are similar and the type of denominator data used
nator data used to demonstrate that the HAl rate is increasing. for rate calculations are the same, it may be misleading to com-
Otherwise, one will be misled and devote precious personnel pare one institution's HAl rate with that of another institution.
resources to conducting an investigation of a less urgent, non- Benchmarking, such as comparing to state-reported HAl rates
emerging, or nonimportant problem. or CDC NHSN rates, may give one a general sense of the overall
Often, numerator data are the first finding that leads to a be- HAl rate. However, because of the large number of confound-
lief that there is an epidemic. Thus, confirmation of the validity ing variables that can influence the numerator, denominator,
and accuracy of the numerator data is an important first step. or HAl rate, one often is safest comparing HAl rates over time
To be consistent, the numerator data should be obtained using at one's own institution. However, even then, one must be cau-
the same standardized definition over the time periods being tious in making such comparisons, ensuring that the compari-
compared. For instance, if the IP has changed the HAl defini- sons include both similar numerator and similar denominator
tions used, it may appear that the HAl rate also has changed data.
when it did not; case ascertainment has altered, and reclassifi- For example, comparison of healthcare-associated central
cation of the HAis using the "old" surveillance definitions may line-associated BSI (CLA-BSI) rates in an ICU to which only
show no change in the number of HAis or the HAl rate. Even medical patients are admitted with rates in another unit at that
if the same surveillance definitions are used, for some sites of same institution to which both medical and surgical patients
infection, it may still be necessary to validate the accuracy of the are admitted or comparison of healthcare-associated CLA-BSI,
surveillance data. catheter-associated urinary tract infections (CA-UTI), SSI, or
For instance, ifBSis are being classified by the IP as primary ventilator-associated pneumonia (VAP) or event (VAE) rates
or secondary on the basis of microbiology data, but data con- among patients in a medical ICU to the rates in patients in sur-
cerning the presence of a catheter in patients with BSis are gical ICUs maybe misleading. Because both the mix of patients
not being collected, there may be misclassification of BSis. If and the devices used can influence HAl rates, controlling for
a review of the surveillance definitions used for case ascertain- these factors by making comparisons with similar populations
ment suggests that the sensitivity and/ or specificity of the defi- and controlling for the duration of patients' stays and devices
nitions used is low or allows for considerable subjectivity, it may used is necessary if valid rate comparisons are to be made.
be necessary to validate the accuracy of the case-ascertainment These factors are most easily controlled for by making HAl rate
method by having several members of the IC team review each comparisons in a particular unit or population within an insti-
"case" independently and ensure its accuracy. tution over time.
Because the existence of an outbreak usually cannot be de-
tennined by the evaluation of the numerator data alone, one
DIFFERENTIATING ENDEMIC FROM EPIDEMIC
needs to be equally precise in ensuring the validity and accuracy
INFECTIONS
of the denominator data that will be used to calculate the HAl
rates in the epidemic and preepidemic periods. The selection No one definition can be used in all situations to differentiate
of the denominator to use in calculating HAl rates is critically endemic from epidemic infections or define epidemic infec-
important. Previous studies have shown that for ICU patients, tions. Depending on the severity of the problem and the ad-
the duration of a patient's ICU stay, device (e.g., central line or ministrative and other pressures present, one may be able to
urinary catheters or mechanical ventilation) exposure and the precisely and accurately define the numerator and denomina-
duration of that exposure, and severity of illness all contribute tor data or need to perform a "quick and dirty" analysis to de-
to the patient's HAl risk (10-13). termine whether an epidemic is present and an investigation
Thus, these important confounding variables must be con- must be initiated. Once one is confident of the validity and ac-
trolled for by using ICU-specific, device-specific denominator curacy of these data, one is in a position to compare the rate of
data (e.g., the number of urinary catheter days for the surgical the HAis or other adverse events recognized in the cluster to
ICU) rather than using either patients or patient-days as the the background rate of such events and determine whether the
denominator if valid HAl rate comparisons are to be made (8). cluster is an epidemic or endemic occurrence. If one can con-
Similarly, the use of a surgical patient risk index that attempts firm the accuracy of the numerator data but not the denomina-
to control for some of the most important factors determining tor data, one may be forced to use a less accurate denominator
a surgical patient's infection risk, such as the type and duration (e.g., the number of patients or the number of patient-days) to
of the surgical procedure, severity of illness, and wound class, is calculate the "rate."
essential if valid HAl rate comparisons are to be made in surgi- It must be realized that depending on the variation in the
cal patients (14,15). In addition, other important factors such possible confounding variables, the findings of the compari-
as body mass index, diabetes mellitus, reoperation, and history son of the "epidemic" to "preepidemic" rates (i.e., statistically
of smoking all of which have repeatedly been shown to increase significantly higher, lower, or unchanged) may be misleading.
the surgical site infection (SSI) risk should be controlled for. Furthermore, it may sometimes be difficult, even given the
In most instances, one can determine whether a perceived appropriate numerator and denominator data, to determine
problem is endemic or epidemic only by the comparison of whether a cluster of infections is endemic or epidemic. For
instance, if an endemic rate of infection continues to rise, at If a decision is made within the hospital that an investigation
some point it may be considered epidemic in nature if recent is warranted, the necessary staff should be mobilized and the
experience is compared with suitable remote baseline data. In investigation initiated. If the staff's availability or expertise is in-
other situations, the lack of background rate data (e.g., no sur- sufficient to conduct the investigation, hospital personnel can
veillance conducted, new patient population or new diagnos- request assistance from a private consultant, the local or state
tic test introduced at the facility) may preclude the possibility health departments, or the CDC. Regardless of the outside
of making rate comparisons. However, in most situations, it is source, the exact nature and scope of the investigation desired
possible to either determine or estimate the background rate by the hospital personnel and what the outside consultant or
and to decide whether the detected cluster of HAis represents organization is offering to do should be well-defined and out-
an epidemic or endemic problem. The recent development of lined before a request for assistance is extended. In addition,
a variety of computer statistical software packages has simpli- because of the changing epidemiology of HAis and the pos-
fied the calculation and comparison of HAl rates; however, the sible complexity of an investigation, combined epidemiologic
ease with which it is possible to make such comparisons has and laboratory investigations may be indicated, and the capa-
further highlighted the importance of ensuring the accuracy bility to perform these investigations should be documented
and validity of the numerator and denominator data used (see before an invitation is initiated or as soon as the need for such
Chapter 10). expertise is realized.
Some researchers have suggested conducting prospective At the Federal level (i.e., Division ofHealthcare Quality Pro-
surveillance and using threshold programs to determine when motion, CDC), the decision to initiate an epidemiologic inves-
the HAl rate increases above a certain level that warrants fur- tigation at a healthcare facility is based on the public health
ther investigation. Such programs were used in the 1970s in the importance of the problem, whether the cluster may represent
CDC's National Nosocomial Infections Surveillance (NNIS) sys- a nationwide problem (e.g., intrinsic product contamination or
tem and were found to be unreliable because of normal varia- a serious problem related to a newly introduced medical de-
tions in the HAl rate at most institutions. Although it may be vice), the morbidity and mortality associated with the cluster,
easy to establish a high HAl rate above which further investiga- the extent to which the investigation may advance knowledge of
tion is indicated, the sensitivity of such a system would be low. healthcare epidemiology and IC, and staff availability (16,17).
To date, it has been impossible to design a sensitive and specific Moreover, because combined epidemiologic and laboratory
threshold program that would not only identify all epidemics investigations are frequently most useful, the ability to obtain
when they occur, but also highlight other nonoutbreaks as clus- and genetically type the colonizing or infecting isolates associ-
ters requiring investigation. It has been equally difficult to de- ated with the cluster may influence the decision to initiate the
velop a sufficiently sensitive and specific threshold program for investigation. Because the CDC is a nonregulatory agency, its
the detection of clusters requiring further investigation. collaboration in the investigation requires the approval of and
More recently, data have been published from national sur- invitation from both the healthcare facility's IC department
veillance and other studies providing HAl rate distributions for and administration and the local and/or state health depart-
a variety of groups of patients (8-15). These data can be used ment. State health departments often have the legislative au-
to compare the HAl rate at one's own institution and assist in thority to enter a facility and conduct an investigation, but even
determining whether the endemic HAl rate is too high and at the state level such an action usually requires that the facility
should be investigated or whether the HAl rate documented at initiate the invitation.
the institution is significantly higher than at one's own institu- Clusters of infection caused by very unusual organisms, those
tion in the past and significantly higher than national averages. associated with great morbidity or mortality, and those of epide-
These national benchmark data are most useful for evaluating miologic importance (introduction of a new multidrug-resistant
one's endemic HAl rate rather than for determining whether pathogen) may warrant initiating an investigation without care-
an epidemic is in progress. Despite these data, there are many fully comparing HAl rates in the epidemic and preepidemic pe-
populations for which there are no published benchmark HAl riods. These clusters include infections caused by very unusual
rates. Furthermore, some of the published benchmark rates or never previously reported pathogens (i.e., vancomycin-resis-
have not carefully controlled for intrinsic or extrinsic risk fac- tant S. aum.u, Rlwdococcus or Nocardia spp. infections in surgery
tors. Thus, one often is forced to decide whether to further patients), two or more infections caused by organisms usually
investigate an epidemic or endemic problem on the basis of the indicative ofa carrier (e.g., Group A streptococcus), and isolated
limited data one has at the institutional level. infections caused by a multidrug-resistant HAl pathogen (e.g.,
vancomycin-resistantS. aum.u, multidrug-resistant Mycobacterium
tuberculosis, carbapenem-resistant Enterobacteriaceae), which, if
DECIDING WHEN TO CONDUCT not controlled, could become endemic or dissemination of a
AN INVESTIGATION clonal organism, which often suggests an eradicable common
source (16-26) .
Making the decision to conduct an epidemiologic investigation Once a cluster is identified and the decision is made to con-
and determining the extent of that investigation depend on duct an investigation, the extent of the investigation must be
a number of factors. These factors differ at the institutional, determined. If the cluster is associated with little morbidity and
local health departmental, state health departmental, Federal mortality and involves only colonization or infection of a small
governmental (CDC), and private consultant levels. In all situ- num her of patients, a brief investigation may be performed. In
ations, the factors that influence the decision to initiate the in- such circumstances, the possible case-patients' medical records
vestigation include whether the cluster is endemic or epidemic are reviewed, a line-listing may be generated, a mode of trans-
in nature, the morbidity and mortality associated with the HAl mission is hypothesized, and interventions are implemented. If
cluster, and staff availability and expertise. a full-acale investigation is to be initiated, a systematic approach
should be taken (discussed later). In general, it is recom- CONDUCTING AN EPIDEMIOLOGIC

mended that cultures of HCWs, products, solutions, or envi- INVESTIGATION
ronmental sources be directed by the epidemiologic data.
Documentation of an epidemiologic association between SAVING CRITICAL MATERIALS
the outbreak and a product, device, or HCW, with subsequent
culture confirmation is preferred to widespread culturing of The first step in any investigation is to ensure that critically im-
HCWs, solutions, or equipment with the hope that the source portant isolates and/or materials that maybe associated with
will be identified. Widespread culturing of animate or inani- the outbreak are saved. At the first sign of an outbreak, the IC
mate objects with the object of serendipitously identifying the staff should get in touch with the director of the microbiology
source is wasteful of the time ofboth IC and laboratory person- laboratory and request that any of the infecting organisms from
nel (see Chapters 11,19). On the other hand, if one cannot current and past possible "cases" be saved. Laboratory person-
preserve the area in which the outbreak is taking place and the nel also should be alerted to keep any subsequent isolates of
inanimate environment is going to be cleaned or the product the outbreak strain that may be recovered during the investi-
reprocessed, selected cultures should be obtained before the gation. If this is not done, laboratory confirmation of the sub-
scene of the outbreak is altered. In addition, it may be important sequent epidemiologic findings in the form of isolate typing
to inunediately interview HCWs in the area where the outbreak will be impossible. In addition, if there is the possibility that an
has occurred because practices may change or recall bias may be intrinsically or extrinsically contaminated product device may
introduced if these persons are interviewed days or weeks later. be the source of the outbreak, such solution or devices should
Lastly, careful consideration should be given to whether be immediately quarantined.
the unit/ward/ area should be closed or surgery or other pro- For example, if there is an unusual cluster of BSis with the
cedures discontinued. If a large number of deaths are associ- same organism(s) in one unit over a short period of time (1
ated with the outbreak in one area, closing the area may be to 5 days), a contaminated product should be seriously consid-
warranted. However, if such a decision is made, IC personnel ered; it may be prudent to collect all medications, multidose vi-
should realize the seriousness of the message being sent. Be- als, or solutions from the involved area and immediately move
fore closing the area, there should be discussion, and a consen- them to an area where they can be preserved and protected. If
sus should be developed concerning what criteria must be met extrinsic contamination of a product or solution is suspected, it
before reopening the area. The decisions to close and reopen may be useful to have personnel save the products or solutions
an area can be made only at the institutional level. Regardless used in the area as the epidemiologic investigation is being
of whether the unit is closed, IC and administrative personnel conducted so that these solutions/products can be cultured
should ensure that all potentially relevant materials (i.e., de- or studied if epidemiologic studies establish an association be-
vices, medications, solutions, etc.) are saved and quarantined tween them and the adverse outcome.
for future evaluation.
If there is serious morbidity or a large number of deaths or
THE SOURCE, THE PATHOGEN, THE HOST,
if many patients are affected, serious consideration should be
AND THE MODE OF TRANSMISSION
given to identifying a spokesperson, best coordinated through
IC and public relations staff, who will regularly update both Epidemiologic investigations have similarities and differences.
appropriate institutional (e.g., staff and patients) and exter- The approach is similar, although the risk factors assessed may
nal (e.g., regulatory, governmental, or media) personnel. The be different. For this reason, standardized forms are usually not
spokesperson should present enough information to assure used in such investigations; instead, the data collected during
others that an appropriate institutional investigation is being each epidemiologic investigation is individualized depending
conducted, but should not prematurely reveal preliminary in- on the data available on the pathogen, the host, and the known
formation. All public inquiries should be directed to the identi- or suspected mode(s) of transmission. Although the approach
fied spokesperson to ensure that one voice is being heard and may differ slightly for each investigation initiated, in general,
conflicting stories do not emerge. Open and honest communi- epidemiologists use a fairly standard system (Table 8.4). Four
cation with the local or national media is preferable to dissemi- major areas assessed in any epidemiologic investigation in-
nating misinformation or refusing to speak to them. clude the source(s), the pathogen(s), the host, and the mode
It should be remembered that state and Federal laws re- of transmission. Factors in these four areas contribute to the
quire that healthcare facilities notify public health authorities outbreak, and modification of one or more of these elements
of selected adverse events (see chapter 47). Because laws dif- usually can terminate the outbreak. For infection to occur, suf-
fer in each state, IC personnel should consult the law in the ficient organisms must be present, the host must be susceptible
state where their healthcare facility is located. Any outbreaks to the organism, and opportunity must exist for the host to
that may have a public health impact at the county, state, or have contact with the organism. The goal of the epidemiologic
national level should be reported to local, state, or Federal investigation is to determine which of these factors is the most
health officials. Any outbreaks associated with intrinsically con- important in causing the outbreak and which can most easily
taminated or defective products (including solutions, blood or be modified to interrupt transmission.
blood products, or devices) should be reported to the Food It is important to understand the pathogen and the ecologic
and Drug Administration (FDA) through the Med-Watch niche the organism prefers. For instance, Sternotrophomonas
Program (1-800-FDA-1088). If such an outbreak involves many maltaphilia or Burkholderia cepacia are increasingly common HAl
healthcare facilities in more than one state, Federal public pathogens that often can be traced to water sources (22-24).
health agencies are responsible for coordinating the investiga- Malassezia sp. are lipid-loving organisms that usually infect pa-
tions, often in close collaboration with state and local health tients receiving intralipid. A nosocomial Malassezia pachydermitis
departments. outbreak among neonates in a neonatal ICU was traced to
air (27,28). Acinetobacter or Serratia spp. emerge in situations

TABLE 8.4 General Approach to an
of high antitnicrobial pressure, and the latter organisms have
Outbreak Investigation been traced to intrinsic or extrinsic contamination of antisep-
The Preliminary Investigation: Quick and Dirty tics (29,30). Legionella spp. are typically associated with water
Rcriewexbtingunonnation sources and primarily infect inununocomprotnised hosts (31).
Surveillance records Some salmonella and most Group A streptococcus infections
Interviews with clinical/laboratory staff are traced to personnel carriers (32,33).
Microbiology records
In general, molecular typing of the infecting pathogen can
Patients' records
VerifY the diagnosis provide valuable information (34) (see Chapter 11). If the in-
Develop tentative case definition (may be broad, i.e., fairly fecting organisms are identical (i.e., clonal), the chances are
sensitive but not too specific) great that there is a common source (e.g., a solution, device,
Microbiologic or HCW) and that an epidemiologic investigation can iden-
Other clinical laboratory tifY the source, the source can be removed, and the outbreak
Hematology can be terminated. On the other hand, if molecular typing of
Chemistry
Other (e.g., toxicology)
the infecting organisms shows that they are not identical (i.e.,
Radiologic nonclonal), the organism is most likely being introduced from
Pathologic multiple sources and/or transmitted from person to person
Clinical signs/symptoms via HCWs' hands. An epidemiologic investigation may pin-
Other (e.g., skin testing) point the factors increasing the risk ofinfection (i.e., failure to
Combinations of these areas rapidly identify colonized/infected patients and isolate them,
Ascertain cases
failure of HCWs to perform hand hygiene, etc.), but the em-
Descriptive epidemiology
Establish the nature of the problem (e.g., SSI), population at piric reinforcement of such practices as isolation of patients
risk, location, severity of illness, and time frame and hand hygiene may terminate the outbreak without a more
Construct the epidemic curve complete investigation. Thus, reviewing the microbiology of
Time the infecting pathogen can provide valuable clues to the likely
Place source of an infection and facilitate the generation of hypoth-
Person
eses about that source.
Establish existence of an outbreak
Compare rates Next, the host factors need to be evaluated. For the host
Exclude surveillance artifact or pseudoepidemic to become infected, there must be sufficient numbers of
Assess adequacy of control measures organisms, and the patient must be susceptible to infec-
Enforce existing control measures tion. In some instances, host susceptibility is related to age
Supplement with additional control measures or immunosuppression that is condition-specific (e.g., low-
Decide on a course of observation vs. defmitive investigation,
birthweight neonates), disease-specific (e.g., HIV-infected
taking into account
patients), or condition- or medication-induced (patients
Severity of illness
Colonization vs. disease with hematologic malignancy, or bone marrow or organ-
Morbidity vs. mortality transplant patients). In other instances, the host has be-
Effectiveness of control measures come susceptible to colonization or infection because of
The comprehensive investigation exposure to medical devices, surgical or invasive procedures,
Refine the case definition (e.g., increasing specificity) antimicrobial exposures, or exposures to a contaminated
Ascertain additional cases
inanimate source.
Record reviews
Surveys The next factor to be considered is the mode of transmis-
Microbiologic sion. HAl pathogens may be transmitted by contact (direct,
Other (e.g., skin testing, antibody testing) indirect, droplet) or a common source, or it may be airborne
Refme descriptive epidemiology (droplet nuclei, skin squamae) or vector-home (see Chap-
Refme evaluation, establishing the existence of an outbreak ter 1). Although HAl pathogens can be transmitted by the air-
Develop hypotheses
borne route (e.g., Aspergillus spp., M. tuberculosis, measles, or
Test hypothese&-analytical epidemiology
Case control V5. cohort studies varicella-zoster viruses), the m.gority are passed by contact, usu-
Retrospective vs. prospective studies ally necessitating the transfer of the organisms from an infected
Control selection or colonized patient to a susceptible patient via transient HCW
Reevaluate control measures hand colonization (18,21,26,29,35) or by droplet (<3ft) spread
Implement additional measures if warranted (e.g., respiratory syncytial viruses [RSV] or adenoviruses).
Ask whether additional epidemiologic/laboratory studies
With most organisms transmitted by contact, the infected or
are needed
Draw conclusions and formalize recommendations for control colonized patient is the source; for some organisms, such as
Continue surveillance for new cases Clostridium difficile, vancomycin-resistant enterococci (VRE),
Evaluate the effectiveness of implemented control measures RSV, norovirus, and rotavirus, the environment plays an impor-
Write and Distribute a Comprehensive Report tant role in infection transmission.
SSI, surgical site infection The predominant site of HAl also can help the epidemiol-
ogist focus the investigation on the most likely route of trans-
mission. For instance, a cluster of BSis is most likely related
colonization of the hands of HCWs via colonization of the to an intrinsically contaminated common vehicle or extrin-
ears of their pet dogs (25,26). Aspergillus spp. usually infect sically contaminated solution or device {including transduc-
immunocompromised patients, and can be found in soil and ers) or to lapses in aseptic technique on the part of HCWs
during intravascular catheter device manipulation (36). the HCWs who took part in the surgery, and exposures specific
Healthcare-associated events or pneumonia are often traced to the surgical procedure, including the type and timing of
to contamination of respiratory therapy equipment or per- administration of prophylactic antimicrobials.
son-to-person transmission of infecting pathogens via HCWs' For BSI outbreaks, the types of catheters, their dates of in-
hands (37). Healthcare-associated UTis are typically attrib- sertion, and the duration of intravascular catheterization, and
uted to contamination during urinary tract manipulation, the types of intravenous fluids, medications, and monitors
open urinary drainage systems, or the insertion or main- should be documented. The epidemiologist or IPs should col-
tenance of a urinary catheter (38). SSis are often traced to lect adequate information to characterize the population at
preoperative colonization, sources in the operating room risk sufficiently so that the type of outbreak (i.e., colonization
(16,18,32,39,40,41) or, more rarely, to the postoperative ICU or disease), population (i.e., patients affected), place (i.e., spe-
(42) or the preoperative ward. cific wards, ICUs, or surgical areas), and estimated outbreak
When initiating an investigation, a review of the source, period can be defined. Sufficient detail should be collected to
pathogen, host, and mode of transmission can help guide the establish a case definition, taking care to avoid generating an
direction of the epidemiologic investigation. The more that is enormous amount of useless information. The primary purpose
known about these areas, the more focused the investigation of this review is to try to identify the common characteristics
can be. In contrast, the less that is known about these areas (for among the patients so that one can describe the time period
instance, the first healthcare-associated outbreak of Rkodococcus of the outbreak, the group of patients at greatest risk, and the
bronchialis among surgery patients), the broader the scope of affected area(s) of the healthcare facility. In the course of this
the investigation must be at the beginning (18). review, investigators should ensure that the HAis are real and
that neither surveillance nor diagnostic artifact has resulted in
the "appearance" of an outbreak.
INITIAL "CASE" REVIEW
Regardless of whether a brief or detailed epidemiologic study CASE DEFINITION
is being carried out, one of the first steps in the investigation of
a possible epidemic or outbreak is to review some or all of the The next step in the investigation of an outbreak is the de-
medical records of possible ~case-patients." The purpose of this velopment of a case definition. Initially, unless the disease is
review is to characterize the population at risk by time, place, known or the time or place of exposure is well-defined, the
and person so that a "case" definition can be developed. If pos- case definition should be broad. This tentative case definition
sible, this review should encompass all known possible "case- can be further refined as more information is obtained during
patients." If the number of possible "case-patients" is large, one the conduct of the investigation. Each case definition should
may select a sample of them; if either a random or convenience specify the estimated time period of the outbreak, the place or
sample is chosen, the reviewer should be aware that bias may places in the healthcare facility where the outbreak is taking
thus be introduced and lead to erroneous conclusions. place, and the types of persons who are becoming case-patients.
For HAis that have a long incubation period, meaning that In outbreaks of a pathogen-specific disease, development of the
the majority of patients experience the onset of symptoms af- case definition may be relatively simple, for instance, all neo-
ter hospital discharge-such as with SSis, review of the medi- natal ICU patients from June 2 to August 30, 2013, with blood
cal records of only those who are still hospitalized may lead to cultures positive forM. pachydermitis (26). For syndromes for
an underestimation of the extent of the outbreak and may not which a direct association with a specific infectious agent can-
describe the affected population accurately. Examples of such not be established from the information available (e.g., initial
outbreaks include many insidious postoperative SSis (caused investigations of toxic shock, Legionnaires disease, or toxic
by, e.g., nontuberculous Mycobacteria, Nocardiaspp., Rkodococcus exposures), development of the case definition can be more
spp.), S. aureus infections among newborns, and infections with challenging. In these instances, the case definition should
long incubation periods (18,42-44). In outbreaks with long include all of the signs and symptoms common to all of the
incubation periods, after the case definition is developed, an "tentative cases" reviewed.
extensive case-ascertainment is necessary. In addition, the case definition may include combinations
of signs and/or symptoms common to the majority of the cases
reviewed. One such case definition might be any patient in
LINE-LISTING
the surgical ICU from january 5 to March 19, 2013, who had a
During the initial case review, a detailed line-listing should temperature >102•F and a >20-mm drop in systolic blood pres-
be developed for each patient (Table 8.5). The data collected sure together with any one or more of the following signs: a
should include demographic and clinical data, the date of white blood cell count of >25,000 cells/mm!l, a platelet count
hospital admission, wards/units admitted to and the dates of of <20,000 cells/mm!l, a bilirubin level of>5 mg/dL, or spleno-
admission to and discharge from each ward/unit, underlying megaly. When formulating a case definition, a balance must be
diseases, the date of onset of infection and/or colonization, drawn between sensitivity and specificity. It may be preferable
and, if the outbreak involves infection, whether colonization to have a case definition that is very specific rather than overly
with the infecting pathogen preceded the onset of infection sensitive; in this way, one can be more certain that each "case"
and at what site the infection was noted. Additional information identified is a true case. Furthermore, in subsequent analytic
is collected specific to the site of the infection/colonization. epidemiologic studies, missed ~case-patients" may be included
For example, with SS!s, information is collected on the pre-, in the control or noncase group and create bias toward not
intra-, and postoperative courses of the case-patients; these data finding differences between the case and control or non-case-
should include whether a patient was admitted to an ICU be- patients; thus, any significant differences identified are prob-
fore the surgery, the date and type of each surgical procedure, ably even more significant. Alternatively, one may wish to
~
Parenteral Duration Fever after Date of Culture

Type of Date of Operating Antibiotic of Surgery Wound Surgery Wound
Cue Age Sex Ward Surgery Surgery Room Propbyluis (min) Drain (hr)a Inflammation Datll Site~
1 TAH,BSO 4/2!1 A No 100 4/30 Wound

2 77 M 3C Cholecystectomy cho- 5/02 F No 150 5/06 Wound
ledocholithectomy
3 47 M 5SW Laminectomy 5/06 G No 120 Yes 24 5/09 5/09 Wound
5/08 Blood
5/10 Blood
4 3!1 F 3C Lobar resection and 5/08 D No 120 Yes 17 5/12 5/16 Wound
pleural stripping
5 84 F 2SE Pyelolithotomy 5/14 c No 60 Yes !16 5/19 5/21 Wound
5/21 Blood
5/24 Blood
6 55 M 3C Sigmoid resection 5/20 F No 105 Yes 48 5/2!1 5/23 Wound
7 22 F 5SW ORlFankle 7/06 A No 150 No 20 7/07 7/08 Wound
8 65 F 5SW Bunionectomy 7/21 F No 45 No 18 7/2!1 7/23 Wound
9 40 F 4SW Melanoma resection 7/21 A No 145 Yes 99 7/25 7/25 Wound
with !kin graft
10 !17 F 5NW TAH,BSO 7/30 A No 105 No !12 8/01 8/04 Wound
"''emperature ~101"F.
TAH, total abdominal hysterectomy; BSO, bilateral salpingo-oophorectomy; ORlF, open reduction internal fixation.
identify "definite," "probable," or "possible" case-patients; this The shape of the epi curve can suggest the possible mode
approach helps ensure that controls do not include possible of transmission. If there is an abrupt increase in the number
or probable case-patients and that case-patients are only those of adverse events over a short time period, the curve suggests
patients most likely to be cases for case-control comparisons. a single exposure to a point-source of contamination, such
as a contaminated product (Figure S.lA). In contrast, when
the epi curve depicts patients over a more prolonged time
CASEASCERLAUNMENT
course, it is most suggestive of a person-to-person transmission
Having established a case definition, the next step is to conduct (Figure 8.1B). In some situations, there may be more than one
an extensive case ascertainment. In this process, the IC staff try to mode of transmission operating either sequentially or simul-
identify all of the cases that may have arisen. All potential sources taneously (Figure 8.1C). Additional epi curves depicting the
of information should be examined for possible case-identifying dates of culture or possible exposure may also be informative-
information. If the case definition is microorganism-based, usu- particularly when the incubation period is long. It may also be
ally a careful review of the existing microbiology records is all useful to draw epi curves with different time intervals (i.e., day,
that is needed to identify the case-patients. Reviewing microbiol- week, month) on the horizontal axis.
ogy methods may be necessary to exclude the possibility that the
organism might not be identified or that specimens are referred GEOGRAPIDC ASSESSMENT (PLACE)
to an outside laboratory.
It is useful to closely examine the place of the outbreak to
Thus, case ascertainment in organism-based outbreaks of
determine whether there is geographic clustering. Use of
BSis, UTis, or most SSis is simplified. Nevertheless, one must
spot maps may facilitate the recognition of clustering of
be aware of the possibility of changes in culturing frequency
case-patients that is not otherwise obvious. Do all of the case-
upon case detection (44). However, depending on the site of
patients come from one ward or unit? If all the case-patients
infection, outbreaks where culturing bias (i.e., clinicians are
are from one ward/unit, one can plot graphically the dates of
less likely to document the infection by culture) may exist; for
admission and discharge from that unit (or multiple units) for
example, healthcare-associated pneumonia (for which a review
each case-patient and ask whether there is continuous overlap
of radiology reports in addition to microbiology records may
among the patients. If so, this finding would suggest a person-
be necessary) or SSis caused by multiple pathogens (when it
to-person transmission from one colonized or infected patient
may be necessary to review the records of all patients undergo-
to the next. If all the case-patients have an infection that can be
ing the procedure to identify those with signs or symptoms of
transmitted via the airborne route, is plotting the patients by
SSis from whom cultures were not taken), may require more
room location consistent with the ventilation system airflow dia-
extensive and rigorous case ascertainment. During the case-
grams or direction of airflow demonstrated by smoke tube? If
ascertainment process, all computerized and noncomputerized
the case-patients are located in several different wards or units,
data sources (including microbiology, radiology, IC, pharmacy,
have they all had common exposure to medications, solutions,
operating room, surgery, outpatient or ambulatory surgery,
devices, procedures, or rooms where a procedure may have
hemodialysis, other invasive procedures, nursing, or patients'
been performed? If the outbreak is at one surgical site, have all
medical records) that may facilitate case ascertainment should
procedures been performed in one operating room, on 1 day
be considered. At the same time that case ascertainment is
of the week or as the first procedure of the day, or in the outpa-
being conducted, one should review an arbitrarily defined
tient surgical suite? Geographically plotting the case-patients by
preoutbreak period (usually 6 months to 2 years) for the occur-
a variety of dates, including those of the time of culture, onset
rence of the outbreak adverse event. In this way, one can define
of illness, possible exposures, and so forth, may all be useful.
the background number of such events. This information will
be used to calculate the preepidemic rate of the adverse event HOST FACTORS (PERSON)
that will be compared to the epidemic period rate to determine
whether an outbreak has occurred or is occurring. Further review of the characteristics of the case-patients is then
undertaken to try to define the most likely risk factors of in-
fection. What role are specific underlying host factors playing
THE EPIDEMIC CURVE (TIME)
in the outbreak? For instance, are all neonatal ICU patients at
Using the information obtained from case definition and case risk or only those whose weight is <1,500 g? Are all surgical pa-
ascertainment, an epidemiologic curve (epi curve) should be tients at risk or only those undergoing cardiac surgery? Are all
drawn. This curve depicts the number of case-patients on the hematology-oncology patients at risk or only those who have
vertical axis or y-axis, and time on the horizontal axis, or »-aXis prolonged neutropenia? Each of the case-patients' host char-
(Figures 8.1 A-C). The line-listing information and epi curve acteristics should be reviewed to determine whether there are
can provide data to facilitate the generation of hypotheses common features among these patients.
about the mode of transmission. The time scale used should The factors to assess include those intrinsic to the host (i.e.,
be shorter than the presumed incubation period of the ad- age, gender, race, underlying disease(s), and nutritional status)
verse event because otherwise a person-to-person transmission and those extrinsic to the host (e.g., receipt of medications or
may appear to be a common-source transmission. By plotting solutions or environmental exposures-admission to an ICU
the time course of the adverse event during the epidemic and or procedure room; HCW exposures; exposure to therapeutic
preepidemic periods, one can compare the occurrence of the measures that might alter host susceptibility, e.g., receipt of an-
adverse event during the epidemic and background periods, timicrobials or steroid injections; or exposure to invasive pro-
identify clusters of the event, and, on the basis of the shape cedures or to invasive devices, e.g., central venous or urinary
of the epi curve, generate hypotheses about the mode of catheters, mechanical ventilation, epidural injections, or arte-
transmission. rial pressure monitoring).
96 S«titm I • GmmJl ~ofHospital Infu:tioru
Fip.re 8.1. Example of E 8 r-

tO
epidemic c:unoes. A: Distribution CD
of patientJ with BSI.a a.uociated
::: <Ul
liiC 6 r-
with a coocamioated common-
.11ource medication. B: Disttibu-
_g
~0
4 .---
Ill '-
tion of patienu with S. mmw skin a-=
infection• as.ociated with penon- 0
2 -
z
t'O-peiiOD tnll.lmisai.ODI. I I I I I I I I
C: DiJttibution of patients with 2 3 4 5 6 7 8 9 10
gutroenteritU UIIOCiated with
a common contaminated food June 1998
80urce followed by patient-to- (a)
patient tran51lliuioo.
8
~ ~
~ 0
::l+=
6 r-
C1l () r--
Cl)~ 4 r- f--
-..!:
0 c:
o:i2 2 r- I II I
Z<ll I I
1 II
I I I I I I I I I I I I
J F M A M J J A S 0 N D
1998
(b)
-
<I>
·c:
$ 14
c:
~ 12
16 r--
t--
7;)
~
(!) 10
$:j
-~ 8
j!l
c:
C3) 6 r--
:=
{'G r-
~ 4
0
0 2 r:=J
z __r::::]_ r---1
I I l I I I I I I I
2 3 4 5 6 7 8 9 10 11 12 13 14 15
(c)
BEFINBMENT OF THE CASE DEFINITION AND likelihood of finding an association between an exposure and
REASSESSMENT OF THE NEED FOR. FURTHER. the case-patients. In contrast, an overly inclusive case defini-
INVESTIGATION tion will result in the inclusion of non<ase-patients in the case-
patient group and may obscure possible associations. In most
At this point, the basic elements of the $imple epidemiologic circumstances, it u preferable to begin the investigation by be-
investigation are complete. IC should refine the case defini-
ing overly inclwive and become more restrictive as the investi-
tion on the baaia of the data accumulated. Only the euential
gation proceeds. In some investigations, it may not be possible
elements reflecting the time, place, and persons who have
to divide all the patients into case-patient and non<ase-patient
experienced the adverse erent should be included. For exam-
or control populatiow. If it has not already been done, one
ple, if the line-liating shoWB that all (or nearly all) of the caae-
may at this point need to define the possible and/or probable
patients weigh <1,500 g and have stayed in the neonatal ICU for
case-patients and then perform further analyses including and
a median of 5 days, the case definition might be modified from
then acluding these patient& in the case-patient group.
that of all neonatal ICU patientll to those who weigh <1,500 g
Occasionally, the review of the case-patients' medical and
who stayed in the unit for ~ d.aya. Careful addition of patients
microbiology records suggests that there is a cluster of positive
or deletion of those initially thought to be case-patient& who
cultures but that the patients do not have clinical illness (16).
do not fit the case definition should take place. It is imperative
Such findings should alert one to the possibility ofa pseudoepi·
that the refined case definition be as precise and accurate as
demic, that is, an apparent cluster of positive cultures that may
possible because the remits of subsequent epidemiologic stud-
be false positives or contaminants. In the 1960s and 1970s, auch
ies are contingent on this case definition.
outbreaks most often were associated with crosH:ontamination
If the case definition is in error, it may lead to erroneous
in the laboratory during manual processing of cultures. In the
conclwions. & mentioned previously, an overly restrictive case
1980s and 1990s, clwtera of po.sitive cultures have increasingly
definition will exclude true ca5e-patients and diminish the
been associated with cross-contamination via automated sys- interest in healthcare epidemiology, private consultant epide-
tems (16,17). Pseudoepidemics have been traced to a variety miologists, or the CDC. State and local health departments may
of sources, including intrinsically or extrinsically contaminated be able to assist in arranging epidemiologic and/or laboratory
antiseptics or culture media, cross-contamination of cultures support. The healthcare facility administrative and IC person-
during manual or automated processing, or intrinsically or nel or personnel at the state health department can request
extrinsically contaminated blood<ollection tubes. Whenever CDC assistance. In CDC<onducted on-site investigations, both
there is an unusual cluster of positive cultures, particularly if epidemiologic and laboratory support is provided at no cost to
it is an uncommon or environmental organism and the case- the healthcare facility.
patients do not have clinical signs or symptoms indicating HAl, Regardless of the outside source of assistance, the investi-
evaluation of the specimen collection and processing methods gation should be considered and conducted as a collaborative
to exclude a pseudoepidemic should be initiated. effort with the healthcare facility personnel. Without the assis-
At this point in the investigation, IC personnel may have tance of healthcare facility personnel, a comprehensive inves-
arrived at the most likely source and mode of transmission of tigation cannot be efficiently conducted, and it will be these
the outbreak. Because of personnel, time, or other constraints, personnel who will need to implement the recommended con-
it may be decided to introduce a number of IC interventions trol measures. Furthermore, local personnel are likely to be
thought likely to reduce or interrupt transmission and then dis- much more knowledgeable about the available data sources, lo-
continue the investigation. If the outbreak is similar to others cal IC and other policies and practices, HCW changes, and the
previously reported, it may be possible to simply implement the particular control measures that can realistically be successfully
previously documented successful IC measures. If this is done, implemented at their institution.
it is imperative that surveillance be maintained for the adverse
event so that one can document the effectiveness of the imple-
THE COMPREHENSIVE INVESTIGATION
mented interventions. If the interventions do not reduce (to
acceptable levels) or interrupt transmission, it may be necessary The first step in conducting the comprehensive investigation
to initiate a more comprehensive comparative investigation. is to review the basic investigation's line-listing, case definition,
and case-ascertainment methods to ensure that no shortcuts
were taken that may influence the comparative studies. Was
IS OUTSIDE ASSISTANCE NEEDED~
the case definition based on a review of all possible cases or
If it is decided that a more comprehensive epidemiologic in- just a sample? If sampling was used, was it random sampling,
vestigation is warranted because the outbreak (a) has not been which may be representative of all case-patients, or conve-
terminated by the introduced control measures; (b) is unusual, nience sampling (i.e., those medical records that were read-
complex, or associated with substantial morbidity or mortal- ily available)? Could the case review sampling have biased the
ity; (c) is of m,Yor public health importance; or (d) represents case definition? Except in very large outbreaks, it is preferable
an opportunity to advance our knowledge and/or understand- to review the medical records of all potential case-patients.
ing of healthcare epidemiology, one should reevaluate whether Occasionally, it is the small number (often one or two) of
the personnel, time, and/or expertise are sufficient to conduct patients who are otherwise very similar to the case-patients but
the required comprehensive studies. Such investigations may who did not have the adverse condition to provide insight into
demand a substantial investment in IC, laboratory, and statistical/ the possible cause of the outbreak. Was the case ascertainment
computer resources. The comprehensive investigation may complete? If not, it should be extended and repeated. Does the
involve an exhaustive evaluation of potential risk factors; a series case ascertainment need to be broadened to a review (and/
of several case-control and/or cohort studies; complex analytic or contacting) of patients who have been discharged from the
techniques, including multivariate analyses and modeling to con- hospital or to communicating with IC personnel at nearby hos-
trol for confounding variables; HCW questionnaires, interviews, pitals or home care? Was the line-listing extensive enough, or
or observational studies; epidemiologically directed environmen- is further review of the case-patient medical records necessary
tal, product, device, and/or HCW cultures; genetic typing of to obtain information on additional exposures or clinical find-
isolates; and implementation of interventions and evaluation of ings? Was the denominator used to calculate the rate of the
the effectiveness of these interventions. adverse event and to compare the rates of these events in the
If the adverse event is serious enough to consider a compre- epidemic and preepidemic periods the correct denominator?
hensive investigation, sufficient resources should be dedicated If the denominator was not correct, is there a way to obtain the
to the investigation to permit the rapid initiation of the study, correct denominator, or must one estimate the denominator?
identification of the source, and introduction of control mea- For example, if the outbreak involves BSis in the medical
sures. If healthcare facility IC personnel add the conduct of ICU but in the initial investigation one had to use either the
such an investigation to their ongoing responsibilities, it may number of medical ICU patients or the number of patient-days
mean that the comparative studies will be conducted over sev- as the denominator, can one obtain the more appropriate de-
eral months. By the time the probable source of the outbreak nominator, that is, the number of days medical ICU patients
is identified, it is possible either that the device, solution, or had central lines? If these data are not available or have not
source will have been reprocessed or discarded or that the epi- been collected, it may be unrealistic to try to derive them by
demiologically implicated HCW will no longer be colonized reviewing the medical records of all medical ICU patients (as-
with the infecting strain. suming that the central line insertion, presence, and removal
If outside advice or assistance is desired, a variety of experts dates are well-documented in the medical records).
are available, including the personnel at the local or state However, it would be possible to estimate these denomina-
health departments, colleagues at other healthcare facilities tor data. One could randomly sample time periods during the
in the same area, experts at nearby academic centers with an preepidemic and epidemic time periods and, for several days
or a week in the preepidemic and epidemic periods, determine problems. However, if the case-control study data are insuffi-
for all patients in the medical ICU how many had central lines cient to determine the cause of the outbreak and/or the case-
and what proportion of the ICU days those patients had such control study has narrowed the population at risk, carrying out
catheters. Then, one can determine a "central line use factor" a prospective cohort study may be useful.
(i.e., the proportion of patient-days spent with central lines
times the number of patients in the unit) for each time period.
CASE-CONTROL STUDY
In this way, one can estimate the number of central line days in
the unit during the epidemic and preepidemic periods. Such In contrast, in a case-control study, the case-patients are
estimation may be necessary when either the necessary data are compared with a similar population without the adverse con-
not available or the review of records containing the needed dition. In a case-control study, the selection of the controls is
data would be excessively laborious and/or time-consuming. critical. Unless it cannot be avoided, historical controls (i.e., pa-
tients present in the unit but in the time period before the out-
break) should not be used. Such patients may not have had the
COMPARATIVE EPIDE.MIOWGIC same opportunity for exposure and may not be similar to the
STUDmS population affected. Random selection of patients in the same
unit at the same time as the case-patients is preferred. If one
Once one has defined the case-patient, performed compre- is concerned that there could be differences in one or more
hensive case ascertainment, developed an extensive line-listing, factors influencing the types of exposures of case-patients and
and drafted epidemic curves, one is ready to develop and test controls, a small, focused case-control study focusing on these
the hypothesized risk factors and modes of transmission. This factors can be done before the comprehensive case-control
can be done through either a case-control or a cohort study study. For instance, if by examination of the line-listing, one
(see Chapters 1,9). In a case-control study, all or some of the becomes concerned that birthweight (e.g., <1,500 g) and dura-
case-patients are compared with a group of patients who did tion of neonatal ICU stay (i.e., >5 days) influenced the types of
not experience the adverse event (controls) for exposure to exposure of the patients, one can first evaluate these two fac-
the potential risk factors. In contrast, in a cohort study, such tors. If they are found to be significantly different between case-
exposures are compared among all the patients in the involved and control-patients, selection of controls could be limited only
area or who underwent the same procedure during the speci- to those neonates who weighed <1 ,500 g and who stayed in the
fied period. neonatal ICU for >5 days.
Numerous factors influence the decision to conduct a case- There are several other methods to control for such con-
control or cohort study, including statistical and practical confounding variables (matching, stratification, or multivariate
siderations. In a cohort study, one can calculate the relative risk analyses). In matching, one selects the controls by matching
(RR) or a quantitative measure of the strength of the associa- one or more factors (e.g., birthweight, duration of stay, severity
tion between the exposure and the risk of developing the ad- of illness, underlying disease) with the case-patients. It must be
verse condition (see Chapter 9). In contrast, in a case-control realized that such matching factors cannot be evaluated as po-
study, one can estimate the strength of the association between tential risk factors. Furthermore, the more factors one wishes
the exposure and the adverse condition only by calculating an to match between case- and control-patients, the more difficult
odds ratio (OR); one can only determine that case-patients it is to identify controls without reviewing all of their records
were more likely to be exposed to the factor than were controls. looking for these factors. It is preferable to randomly select the
Adverse conditions with a high attack rate lend themselves to controls and evaluate the factors under consideration for their
cohort studies, whereas conditions with low attack rates are bet- strength of association with the adverse condition. Then, if they
ter evaluated through a case-control study. If the duration of are found to be statistically significant, they can be controlled
the outbreak is short and the number of patients in the unit for through stratified or multivariate analyses. In contrast, in
during the outbreak is small, it may be feasible to conduct a matched analyses, it is assumed that these factors are not sig-
cohort study. On the other hand, if the duration of the out- nificant without assessing whether the assumption is true.
break is long (months or years) and the number of patients Several important decisions must be made when conduct-
in the involved unit(s) is large (e.g., >100), it may be impracti- ing a case-control study. The first is whether to include all or a
cal to conduct a cohort study, and a case-control study may be sample of the case-patients. In general, it is best to include all
more realistic. Depending on the duration of the outbreak, the case-patients to increase the power of the study and to avoid
size of the population at risk, and the extent of the data being introduction of bias. Second, one must decide how to select the
obtained from the medical records, a case-control study may controls. To enhance the likelihood of determining the source
take days to weeks, whereas a cohort study may require weeks of the outbreak, the controls should have similar opportunity
to months. for exposure to the potential risk factors as the case-patients. In
other words, they should be selected from the same population
(same ward or unit or undergoing the same procedure) as the
COHORT STUDY
case-patients and be hospitalized during the same period as the
In a cohort study, all patients in the unit or units of interest or case-patients. Third, once the population of potential controls
undergoing the particular procedure of interest are evaluated is identified, one must decide how many controls to select for
for exposures to the variable(s) of interest. Such a study can each case-patient.
be conducted either prospectively or retrospectively. Because The number of controls selected is based on statistical
case-control studies are easier to perform, take less time, and power and practical considerations. If the attack rate is high
tend to be more powerful, retrospective cohort studies are less and the number of case-patients is large, one control per case-
frequently undertaken to evaluate HAl endemic or epidemic patient may be sufficient. If the number of case-patients is small
Chapter 8 • Investigrlting Endemic and Epidemic Heallhc~&sociated Infections 99
(e.g., <20), one should select two to three controls per cas~ the close cooperation of the epidemiologist and the statistician
patient The proportional increase in power associated with the for the appropriate conduct and interpretation.
selection of more than three controls per case declines mark-
edly, and the proportional increase in power by selecting more OBSERVATIONAL STUDms
than four to five controls usually does not justify the increased
volume of work. Last, one must decide how the controls are Often, outbreaks associated with healthcare facilities are the re-
going to be selected. There are at least two selection methods: sult of failure by HCWs to fully comply with current recommen-
random and stratified or proportional sampling. dations or policies. Therefore, IC personnel should observe
The random selection of controls is the easiest and most HCWs performing the procedures in question to document
widely used method. With this method, all potential con- the adequacy of their understanding and compliance with IC
trols are listed and then selected using a random numbers recommendations. Observational studies can help generate
table. Random numbers tables can be found in most statistics hypotheses about the cause of the outbreak, or they can con-
books, and may be generated by numerous statistical soft- firm the findings of the epidemiologic studies. For instance, if
ware packages. If one has 500 potential controls and wishes the comparative analyses have linked the transmission of the
to select 50, one just lists the controls in numerical order etiologic agent to a particular product and HCW, observation
from 0 to 500 and then generates 50 random numbers be- of this person preparing or manipulating the product may
tween 1 and 500. Alternative random selection methods in- identify how the product was contaminated.
clude choosing every "nth" control from the list of controls IC personnel should review all written policies associated
or selecting the patient who came before and/ or after the ad- with the practices in question, interview supervisory staff, and
mission or surgery of the case-patient. The random numbers identify any changes in the procedures in question before, dur-
method is preferred because the other methods may intro- ing, and after the outbreak. IC personnel should observe the
duce bias-all patients are not admitted to a unit randomly, implicated procedures and/ or HCWs and directly question the
and in outbreaks associated with surgery, patients at risk may personnel who are performing the implicated procedures. It
not undergo surgery at night or on weekends. may be useful to observe HCWs on all shifts and to distribute a
If one is concerned about the distribution of some factor questionnaire asking the HCWs about their particular practices.
among the cas~patients, such as admission to one of several For instance, in questionnaires distributed to them, HCWs of-
ICUs or an SSI that affects patients who have undergone a vari- ten claim to perform hand hygiene before and between con-
ety of surgical procedures, one may wish to select the controls tacts with patients, but observational studies usually document
using the proportional or stratified method. The more factors that such hand hygiene occurs -30% to 40% of the time (6).
one is concerned about, the more difficult and tedious it will be
to match these factors. To identify a match, one needs to review CULTURE SURVEYS
the characteristics in the control-patients' medical records; this
process requires review and discarding of large numbers of Cultures of the environment and/ or HCWs should not be
controls until the desired factors are identified. In contrast, us- performed before the comparative epidemiologic studies are
ing the stratified or proportional method, controls are placed completed. Cultures of the environment may identify the caus-
into categories on the basis of the variables of concern (e.g., ative agent, but this may represent secondary contamination
type of surgery, admission into ICU), and then the proportion rather than the source of contamination. Many common HAl
of controls desired is randomly selected from each category. pathogens, such as gram-negative organisms and fungi, can be
For example, if in an SSI outbreak 10% of cas~patients had isolated from the environment even in the absence of an out-
cardiac surgery, 20% had neurosurgery, 30% had orthopedic break. Similarly, a positive culture from an HCW can represent
surgery, and 40% had general surgery, the controls would be the source of the outbreak but may also represent secondary
distributed into categories by the type of surgery they had un- contamination from the environment, colonized or infected
dergone. Then they would be selected from each surgical cat- patients, transient carriage, or carriage of the organism ind~
egory in the same proportion as the case-patients. pendent of the outbreak. Because the identification of an HCW
Once the cas~ and control-patients are selected, one can carrier may require his or her removal from work, conclusive
compare the exposures of interest. These exposures should epidemiologic data identifying a person as associated with
be compared statistically using one of the available statistical transmission in the outbreak is needed to warrant such an ac-
software packages (see Chapter 10). If only one risk factor is tion. Random culture surveys of products, the environment, or
statistically significantly different between cas~ and control- personnel are costly both in materials and time.
patients, no further epidemiologic analytic studies are neces- Once the comparative epidemiologic studies have been com-
sary. If there are significant differences in two to three risk pleted, cultures should be obtained from the epidemiologically
factors, further analysis using stratification may demonstrate implicated sources (products or personnel) . At the same time,
which of these factors is the most important. In addition, if several other cultures should be carried out on HCWs or prod-
case- and control-patients differ significantly in two or more ucts representing controls to avoid the risk of identifying the
factors, multivariate analyses can be performed to identify the product or HCW before the investigation is completed and ap-
independent importance of these factors. For many HAl out- propriate recommendations can be made. The performance of
break investigations, numerous risk factors are identified as cultures of only those products or HCWs who are epidemiologi-
significant. Because some of these variables are confounding cally implicated reduces the number of cultures to be obtained,
factors, they are highly correlated with the causative risk fac- the personnel resources needed to conduct the cultures (they
tors. Multivariate techniques can be used to try to identify the should not be performed by the implicated HCW), and the bur-
independent importance of the factors found to have signifi- den on the laboratory. Cultures ofnonsterile areas (e.g., floors,
cance in univariate analyses. Multivariate techniques require sinks, walls) and other animate or inanimate objects that do not
l 00 Section I • General ConsideratiOfiS of Hospital Infectiuns
have plausible connections to the outbreak are a waste of valu- ~GRECOMMffiNDATIONSAND

able resources and may generate uninterpretable data. EVALUATING THE EFFICACY OF THE
If the epidemiologic data identify a source yet the cultures of RECOMMENDATIONS
the person or product do not disclose the causative agent, one
should not abandon the hypothesis. The epidemiologic data Once the epidemiologic and laboratory studies have been
should always supersede the laboratory data. When low-level completed, one can assess the results and make appropriate
contamination of a product occurs, it may require cultures of recommendations to terminate the outbreak and prevent fur-
large numbers of the product to pinpoint the contamination. ther transmission. Often, these recommendations are based
Furthermore, the cultures of the implicated HCW may give on existing guidelines. Several outbreak investigations have
negative results if the colonized site is not cultured, or if the documented that transmission often stems from failure to fully
HCW shows positive results only intermittently, or has treated implement IC guideline recommendations, not that the guide-
himself or herself and is no longer culture positive. IC person- line recommendations are inadequate (50-52) . Occasionally,
nel should never vindicate a source that has been identified the outbreak investigation identifies a practice that needs revi-
by a well-designed epidemiologic study even in the absence of sion or a contaminated product that should be removed. More
culture confirmation. often, the investigation finds lapses in aseptic technique that re-
Because the appropriate method of culturing inanimate and quire further HCW education. Thus, it is imperative that once
animate objects varies, IC personnel should consult with the the recommendations are made, follow-up studies be initiated
microbiologist before such culturing is initiated. For cultures of to ensure that there is compliance with the recommendations
HCWs' hands, the broth hand-wash method is preferred (45). and that the transmission is terminated.
For water or dialysate used in hemodialysis, the pour-plate or Furthermore, during the investigation, one has the oppor-
millipore ffiter method is preferred (46). For cultures of the tunity to improve general IC measures throughout the hospital
environment when low numbers of organisms are anticipated, (even if the outbreak is taking place in only one unit) and to
the use of premoistened swabs and inoculation into nutrient improve methods of documentation of information that would
broth may facilitate the recovery of the organism. When inves- have made the investigation easier. For instance, if, during an
tigating outbreaks associated with possible airborne transmis- investigation of BSis in ICU patients, it is impossible to deter-
sion, the use of settle plates or air samplers may expedite the mine the dates of central line insertion and removal, the pro-
recovery of the implicated pathogen (19,20,28,47-52). spective collection of such data in a standardized manner by
ICU staff should be included in the recommendations.
To ensure that the outbreak investigation is conducted ef-
TYPING OF THE OUTBREAK STRAIN
ficiently and that hospital HCWs fully implement the recom-
When the outbreak strains are available from the case-patients mendations, hospital administrative personnel should be
and the environment or implicated HCW (s) or products, it is es- actively involved in the investigation and follow-up. IC person-
sential that they be saved for potential future studies. Although nel should alert hospital administrative staff as soon as the out-
outbreaks can be clonal (caused by one strain) or nonclonal break is detected. IC personnel should update administrative
(caused by multiple strains of one species); typing the outbreak staff during the course of the investigation and then review
strains can be a vital addition to the epidemiologic study. A wide with them the investigation findings and recommendations.
variety of nonmolecular and molecular typing methods are Follow-up meetings with administrative staff should review the
available for many of the pathogens associated with outbreaks adequacy of implementation of the recommendations and de-
in healthcare facilities (see Chapters 10,16) (34). The finding termine whether the outbreak has been terminated.
of clonality among isolates increases the likelihood that the out- For complex outbreaks that involve a variety of services or
break is caused by a contaminated product or colonized HCW, are causing significant morbidity or mortality, a task force,
whereas the finding of a nonclonal outbreak increases the which should include administrative staff, should be formed
likelihood that the pathogen is being transmitted via HCWs' at the beginning of the investigation, and this group should
hands from one source (patient or environment) to another be responsible for monitoring the adequacy of implementa-
patient. For this reason, it may be useful to type some outbreak tion of the recommendations and evaluation of their efficacy.
strains, particularly those that are common to the environment, The successful conclusion of any investigation of an endemic
water, or HCW. Such typing may influence the direction of the or epidemic problem is the documentation through follow-up
comparative studies. data that the problem has been controlled or terminated by
Typing methods include biotyping, antimicrobial susceptibil- the implemented control measures. Any successful investiga-
ity testing, multilocus enzyme electrophoresis, serotyping, phage tion requires the close cooperation of a wide variety of people
typing, and a variety of molecular methods, such as plasmid from many hospital departments. It becomes the responsibility
analysis, restriction endonuclease analysis, chromosomal analy- of these people to translate the recommendations into action.
sis, ribotyping, restriction fragment length polymorphism, If the investigation is conducted in dose collaboration with
polymerase chain reaction-based methods, or pulsed-field gel staff members of other departments, they will in tum help with
electrophoresis. In general, the molecular methods-in particu- the implementation and monitoring of the recommendations in
lar, pulsed-field gel electrophoresis-have become the most use- their departments. To educate and inform those associated with
ful for epidemiologic typing (34). However, the field of molecular the outbreak or the investigation, it is important that a report be
typing is evolving rapidly, and polymerase chain reaction-based written at the conclusion of the investigation summarizing the
pulsed-field gel electrophoresis typing and other methods are methods used, the results, and the recommendations. This re-
proving useful for organisms for which previous nonmolecular port should be circulated to all of those assisting with the study,
or molecular typing methods have been deemed inadequate. all service chiefs or heads of departments where the outbreak
Chapter 8 • Investigating Endemic and Epidemic Healthcare-Associated Infections l 0 l
took place, and the administrative, risk management, and hos- 22. Villarino Ml':, Stevena L, Sehable B, et aL F:p:idemic XanthaoRona.r ffUIIIopllilitJ infeetiono and
eolonization in an intenllive care unit Jnfta ConbolHospEpidntiol. 199!;lli:!Ol-206.
pital public relations departments. In this way, all necessary per- 2l!. Thblan OC, Martone WJ, Doenbuk CF, et al. Colonization of the reop:iratory tract with
sonnel are informed about the findings and recommendations ~ t»j>4t:ia of patiento with cyotic fibroaia: rill< facton and outcomeo. Ch4Jt.
of the investigative team. Feedback of follow-up data to these 1987;91:527--5llll.

24. Mangram A, Jarv.i• WJ. No&OCOillial Bvrillloldma upai!i& outbreab and poeudO<rutbreal<o.
departmental staff members will help them improve conditions Infta ConmJI Hosp EpidntiDL 1996;17:713-720.
and practices in their departments. Investigations of endemic 25. Weibel SF, McNeil M, Promanilt A, eta!. Nooocomial Mtlla.u...., paciiJtlmnW bloodltreaw
infeetiono in a neonatal intenoive care unit Porliatr brfoaDisJ. 1994;13:104-109.
or epidemic problems should be viewed as collaborative efforts 26. Chang H, Miller H, Watkiru N, eta!. An epidemic of MalG.ma'4 ~in intenoive
between the IC personnel and other departments. With the care nunery UIOCiated with healthcare worken' dofP. N Ef11J] of AW. 1996;llll:706-711.
cooperation of other departments, a successful outcome is en- 27. Riehet HM, McNeil MM, Dav.io BJ, et al. ~ ~ oterual wound infection in
patiento und"'lf"ing open-heart 'WJ!"'Y· Am]Epidm<Wl. 1992;lll5:48-58.
hanced; without it, success is unlikely. Publication of the results 28. Buffington J, Reporter 'K, McNeil MM, et al. An outbreak of invaoive aopergillollis among
of the investigation either in the peer-reviewed literature (53) hematology awl bone Illlii'IUW tranoplant patiento at a Los Angele• hoopital. JPrtliolr I'!fod
or online in the Outbreak Database, the worldwide database for Dis. 1994;1S:ll86-ll9ll.
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HAl outbreaks (http://www.outbreak-database.com), may be ....,.,.;in five in""""" care unitl. A•J Epidntiol. 1990;132:72ll-7ll3.
useful to other facilities and help them avoid similar outbreaks. 50. Archibald LK, Manning ML, Bell LM, et aL Patient denoity, nune-to-patient ratio and
nOIOCOillial infection rilk in a pediatric cardiac intenaive care unit. Podialr lnft<t Dis J.
1997;16:104!>--1048.
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with shower uoe: poollible role of amoebae. fAMA. 1990;26ll:924.
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4. Jarv.io WR, Manone WJ. Predominant pathogen• in hoopital infectiono.JA~ a.mwtMr. 57. Thblan OC, Andenon LJ, lleloer R, eta!. Guidelineo for prevention ofhealthcare-aoooci-
1991;28:15-19. ated pneumonia, 2003. MMWR &o:o- Rip. 2004;53(RR-II) ~-ll6.
5. Cen"'n for Dileaoe Control and Preoention (CDC). NHSN annual updat.>: antimicrobial- !16. Wong ED, HootonTM. G..idllim for l'mJmlion 11/ ~-Auot!iGIId Urinary ThJ&Ilnfraioru.
rellistant pathogen• aiSOciated with healthClll'C<IIoociated infectiono: annual oummary of Atlanta, GA: Centen for Dileaoe Control and Prevention; 1981.
data reponed to the National Healthcare Safety Network at CDC, 2006-2007. In/Itt Conbol 59. Beritelwan RL, Martin D, Gralwn DR, et a!. Streptococcal wound infectiono cauoed by a
HwpEpidnML 2008;29:996-1011. vaginal earrier.JAMA. 1982;247(19) :2681}-2682.
6. Janis Wll. HandwaJhlng: the SemmelweiJ le11on forgotten? LiJAaJL 1994;!144:lllll-UU. 40. Mangram AJ, Horan TC, Peanon ML, eta!. Guideline for prevention ofmrgic:alllite infec.
7. Garner J,Jarv.io WR, Emori G, et aL The Centen for Dileaoe Control dcfinitiom for n<»<>- lion, 1999. Hoopital Infection Control Practice• Adv.ioory Conunittee. lnft<t CimtnJl H..p
comial infectiono, 1988. AM]lnft<t c.m..L 1968;16:12&--140. Epi. 1999;20:247-278.
8. National NooocoDiial Infcctiono Smvcillance (NNIS) Sy>tem. NooocoDiial infection rate• 41. Lowry PW, Blankenohlp RJ, Gridley' W, et a!. A dwter of kginnella 1temal-wound infee-
for interhoop:ital cmnparilon: limitatiom and poooible oolutiono.lnft<t Conbol H..p~ tiono due to pootoperaU..: topical expooure to conllmlinated tap water. N Eng! j MML
1991;U:609-021. 1991;324:109.
9. Emori TC, Cui= DH, Horan TC, et aL National Nooocmniallnkctkml Surveillance Syotem 42. Safranek TJ, Janis WR, Caroon LA. et aL ~ clultlnuwound infectiono after plat-
(NNlS): deocription of methodology awl 1mvcillance component!. A• J Iflj<a c.m..L tic 'WJ!"IY emp!uying contaminated gentian violet Uin marking lolution. N Eng!J M«l.
1991;19:1!1-l16. 1987;317:197-201.
10. Janis WR, Edwards JR. Culver DH, et aL Noooc0111ial infection~ in adult and pediat- 45. Nabohima AK, Allen JR. Martone WJ, et aL Epidemic bullou1 impetigo in a nunery due
ric in""""" care unill in the United Stateo. National NooOCOillial Infection• Surveillance to a naoal carrier of St4p/1Jiowccw - . role of epidemiology and control meaoureo. I'!fod
System. Am]MMl. 1991;91:185S-191S. Gonhul.l984;5(7):326-lllll.
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eare unito in the United State~. National NooocOillial IDfectiono Suncillance l)'ltem. Cril in US hoopitals through increued we of diagno•tic te1to, 19'ro-1976. Aa J EpillnUnL
ea.. AW. 1999;27:887--892. 1985;121 (2):168-181.
12. Richards MJ, EdwardsJR. Culver DH, eta!. N010e01llial infectiono in pediatric intenoive eare 45. Petenen NJ, Collino DE, ManhallJH. A lllicrobinlogical"'""l' technique for hand>. Hmlth
unito in the United Stateo. National NOIOCOillial Infectiono Surveillance 1)'111!m. l'odialrieJ. Lab Soi. 1973;10:13-22.
1999;105:ell9. 46. Franlon MAH, ed. Slandanl ~ for EztNnioullion of - and w - . 16th ed.
1!1. Gayw:s RP, Martone WJ, Culver DH, et aL Comparioon of~ ofnooocomial infection• in Waohington, DC: American Public Health Aooociation; 1985.
neonatalintenoive care unito in the United Sweo. Natioual NooocOillial Infectiono Surveil- 47. Bect-Sague CM, Dooley SW, Hutton MD, eta!. Outbrealc. ofmultidrug-reoiltant tuben:u-
lance Syotem. Am]Mrd. 1991;91:192S-197S. lollis among peroom with HIV infection in an urban hoop:ital: tr.uumiooion to 1taff and
14. ~r DH, Horan TC, Gayw:s RP, eta!. Surgical wound infection rateo by wound daoo, patiento awl control weaoureo. Am] MML 1992;268:1281}-1!86.
operati.v.: procedure, and patient ri.Jk. index. National N010comial1Dfecti.om Surveillance 48. F:dlin B'K, Tokan Jl, Grieoo MH, et a!. An outbrealc. of multidrug-relliotant tuberculollis
System. Am]MMl. 1991;91:152S-157S. awong hoopitalized patiento with the acquired illlmunodeficiency oyndrome: epide-
15. Haley RW, ~r DH, Mo'l!"" WM, et a!. Identifying patiento at high riak of •urgieal miologic 1tudieo awl re1triction fuoglllent length polylllorphillll ana!yoi>. N Engi J Mrd.
wound infection: a 1imple multivariate index ofpatientouoceptibility and wound contami- 1992;326:1514-1522.
nation. AmJEpidaUDI. 1985;121 :206-215. 49. Peanon ML,JerebJA, Frieden TR, eta!. N010comial tran..m..ion ofmultidrug-rellistant
16. Janis WR. N010oomial outbreab: the Centen for Dileaoe Control'> Hoopital Infection• MJcoboctmlmo tukmllorit: a rill< to hotpitalized patiento and health-are woriten. AMlftUrn
ProgralD experience, 1961}-1990. Epidemiology lhanch, Hoopitallnfectiono Prognm. AR] M«l. 1992;117:191-196.
M«l.l991;9(SB):101S-106S. 50. Maloney SM, Peanon M, Gordon M, eta!. Efficacy of eontrol meaoureo in preRnting tran•
17. Janis WR. Hoopital Infectiono Prognun, Centen for Dileaoe Control and Prevention million of multidrug-rellistant tubereulotis to patient! and healthcare worken. .A,,.,. lftUm
On-oite Outbreak Invatigationo, 1900--1999. S...illlnft<t c.m..L 2001;1:74--84. M«l. 1995;122:91}-95,
18. Richet HM, Craven PC, Brown JM, et aL RMd«ouw (Gordona) lmmclli4lis aterual wound 51. Wenger P, Otten J, Breeden A, et al. Control of nooocolllial tnuwnillion of multidrug-
infectiono following ooronary artery bypuo graft ourgery. N EnctfM«l. 1991 ;ll24:1 04-109. rellistant My<d~Gaori""' lvbmulosiJ among healthcare worken and HIV-infeeted patientl.
19. EdlinBR, Tokan]l,GriecoMH,etal.Anoutbreakofmulticirug.-eliJtanttubereulomawong Lanat. 1995;!145:235--240.
hoopitalhed patient> with the acquired immunodeficiency oyndrowe: ep:idenrlologic otudieo 52. Stroud LA, Thkan JI, Grieco MH, et aL F:oaluation of infection control meaoureo in pre-
and reotrietion .fraglllent length polymorphllw analyllis. N EtlgljMML 1992;ll26:1514-1522. venting the nooocomial tranlllliloion of multidru~trellistant ~ ~ in a
20. Jarv.io WR. Nooocomial tr.uwninion of multidrug-reoiotant Myc~ lvbemclmi.s. JUs New York Cityhotpital I'!fod ConlYrJl H..pEpillnUnl 1995;16:141-147.
MiaobitJl. 1993;144:117-122. 5ll. Archibald LK, Jarv.io WR. Health care;wociated infection outbrealc. inveo~tion1 by the
21. Shay D'K, Maloney SM, Montecalvo M, et aL F:pidemiology and mortality of"""comycin- Cen..,..forDileaae Control and Prevention, 1946-2005. AM]Epidloooiol.2011;174(oupplll):
reliatant enterococcal bloodatream infectiono.] Inf«t!Jis. 1995;172:99ll-1000. S47--S64.
9 Jennifer H. Han and Ebbing Lautenbach
Epidetniologic Methods for Investigating

Infections in the Healthcare Setting
INTRODUCTION factor of interest). The most commonly used measures of dis-
ease frequency are prevalence and incidence.
A sound understanding of the principles and approaches of
epidemiology is critical to the study of infectious diseases in PREVALENCE
the healthcare setting. The urgency of comprehending and ap-
plying epidemiological principles ilJ supported by the fact that Prevalence is defined as the proportion of people with disease
the incidence and impact of healthcare-asaociated infectioWI at a given point in time (e.g., the proportion of hospitalized
(HAis) and antimicrobial resistance have increased markedly patient! who have an HAl). This may also be referred to as the
since the last edition of this textbook. In addition, the appli· "point prevalence."
cability of techniques traditionally reserved for bealthcare
.......__, Number of diseased individuals
epidemiology has been recognized as uniquely suited to other .u~cuence = -------------....=..
emerging issues (e.g., patient safety, bioteiTorism, drug use Total population
management, quality asaenment, teclmology assessment, prod·
Prevalence, which is a proportion and has no units, depends
uct evaluation, and risk management) (1,2).
on both the incidence (i.e., the number of new episodes that
The value of epidemiological methods in the study ofHAh
develop) and the disease duration (i.e., how long a disease lasts
has been recognized for some time now (S..6). The ability to
once it has developed). The greater the incidence and dura·
accurately quantify new patterns of HAis, design and carry
tion of disease, the higher the resultant prevalence. Prevalence
out rigorous studies to identify the factors associated with dis-
is useful for measuring the burden of disease (i.e., the overall
ease, and devise and evaluate interventions to address emerg-
proportion of persons affected by the disease). Because all pop-
ing issues are vital to the study of HAis. Indeed, during the
ulations are dynamic, the prevalence may vary depending on
past decade, there has been a renewed interest and vitality
when it is measured. H a dynamic population is at steady state
in efforts to explore previously unstudied aspects of epide-
(i.e., cases leaving are equal to cases entering), the prevalence
miological methods in the study of HAis and antimicrobial
will be constant over time. Surveillance systems in Westem
resistance (S..7).
European countries have more commonly measured the prev-
There are two primary goals of this chapter. The first goal
alence rather than the incidence of HAis at the country and
is to review the basic epidemiologic principles relevant to the
hospital levels (see Chapter 6).
study of HAls, including (a) measures of disease frequency,
(b) study design, (c) measures of effect, (d) bias, and (e) con·
founding. The second goal is to discuss in more detail specific INCIDENCE
current epidemiologic issues in the study of FIA:b, including
Incidence is defined as the number of new episodes of W.
(a) quasi-experimental study design, (b) case-crossover study
ease occUlTing in a specified period of time. Incidence may
design, (c) control group selection in studies of antimicrobial
be described in several ways. Cumulative incidence is defined
resistance, (d) definitions ofantibiotic exposure, and (e) assess-
as the number of new episodes of disease in a particular time
ment of mortality as an outcome of infection. The oveiTiding
period divided by the total number of disease-free individu-
focus of thilJ chapter is discussion of epidemiologic methods
alsat~of~~aseat~be~ingof~~~~
applicable to the study of HAis and antimicrobial re.tistance.
(e.g., the proportion of patient! who develop an HAl during
The reader is also directed to numerous published textbooks
hospitalization).
solely dedicated to general epidemiology, infectious diseases
epidemiology, or statistical analysis (8-14). Number of new cases of
Cumulative incidence = disease between t0 and t1
Total disease free individuals
MEASURES OF DISEASE FREQUENCY at risk of disease at t0
Accurately quantifying the frequency of disease is important for The cumulative incidence, like prevalence, is a proportion
measuring the scope of the problem (i.e., bow many people are and thus has no units. To calculate the cumulative incidence,
affected by the disease) and for allowing comparison between one must have a complete follow-up on all individuals so that
different groups (i.e., those with and without a particular risk their final disposition with regard to the outcome is known.
102
Chapter 9 • Epidemiologic Methodsfor ln'llestigating Infections in the Healthcrm Setting l 03
Although this measure describes the total proportion of new CASE REPORT/CASE SERIES
episodes occurring in a time period, it does not describe when
A case report is the clinical description of a single patient
in the time period they occurred. For the cumulative incidence
of HAis, the period implied is the beginning of hospitalization (e.g., a single episode of a patient with a bloodstream infec-
tion due to fluoroquinolone-resistant Escherichia coli [FQREC]).
until a first event or until discharge. However, patients do not
stay in the hospital and remain at risk for exactly the same pe- A case series is a report of more than one patient with the
disease of interest. In addition to serving as a clinical or thera-
riod of time. Thus, comparing the cumulative incidence of HAl
peutic example, a case report/series can function to generate
among patient groups with differing lengths of stay may be very
hypotheses that may then be tested in future analytic stud-
misleading.
ies. The primary limitation of a case report/series is that it
The incidence rate (or incidence density) is defined as the
number of new episodes of disease in a specified quantity of describes at most a few patients and may not be generalizable.
In addition, because a case report/series does not include a
person-time of observation among individuals at risk (e.g., the
number ofHAis per 1,000 hospital days). comparison group, one cannot determine which characteristics
in the description of the patient(s) are unique to the illness.
Number of new episodes of disease

ECOLOGIC STUDY
.d during given period
I na ence = ----------~~--~-----------
In an ecologic study, one compares geographic and/or time
Total person - time of a observation
among individuals at risk trends of an illness to trends in risk factors (i.e., a comparison
of annual hospital-wide use offluoroquinolones [FQs] with an-
nual prevalence of FQREC). Ecologic studies often use aggre-
The value of this measure can be seen when comparing
gate data that are routinely collected for other purposes (e.g.,
infection rates in groups that differ in their time at risk (e.g.,
antimicrobial susceptibility pattems from a hospital's clinical
short-stay patients vs. long-stay patients). When the time at
microbiology laboratory). As a result, one advantage of the
risk in one group is much longer than in another, the inci-
ecologic study is that it is often relatively quick and easy to do.
dence rate is the most convenient way to correct for time.
This allows one to separate the effect of time (duration of Thus, such a study may provide early support for or against a
hypothesis. However, one cannot distinguish between various
exposure) from the effect of daily risk. Incidence rate is usu-
ally restricted to first events (e.g., the first episode of HAl). It hypotheses that might be consistent with the data. Perhaps
most important, ecologic studies do not incorporate patient-
is standard to consider only first events because second events
are not statistically independent from first events in the same level data. With such a study, one knows only that there is a
correlation between annual hospital-wide use ofFQ;i and yearly
individuals.
prevalence of FQREC, not that the actual patients infected
Unlike cumulative incidence, the incidence rate does not
with FQREC received FQs. Thus, these data may be true but
assume a complete follow-up of subjects. However, even when
unrelated.
the follow-up is complete (and thus cumulative incidence
could be calculated), reporting the incidence rate may still
be preferable. Cumulative incidence reports only the overall CROSS-SECTIONAL STUDY
number of new episodes occurring during the period (regard- A cross-sectional study assesses the status of subjects with regard
less of whether they occur early or late in the time period). By to the risk factor and disease at the same point in time. A cross-
comparison, the incidence rate, by incorporating the time at sectional study to investigate FQREC might assess all patients
risk, accounts for potential difference in time to occurrence currently hospitalized and whether they have an FQREC infec-
of the event. tion and whether they are receiving FQs. A cross-sectional study
The assumption in the incidence rate is that all time at risk is relatively easy to carry out because all subjects are assessed at
is equal (e.g., the likelihood of developing an HAl in the first only one point in time. As such, this type of study may provide
3 days after hospital admission is the same as the likelihood of early evidence for or against a hypothesis. A m,Y or disadvantage
developing an infection during days four through six of hos- of a cross-sectional study is that it does not capture the concept
pitalization). If all time periods are not equivalent, the inci- of elapsed time (i.e., it is not possible to determine whether the
dence rate may be misleading. The Centers for Disease Control risk factor or the outcome came first). Furthermore, a cross-
and Prevention's (CDC's) National Healthcare Safety Network sectional study does not provide information about the transi-
(NHSN) predominantly uses incidence rate calculations rather tion between health states.
than prevalence rates (see Chapter 5).
CASE-CONTROL STUDY
STUDY DESIGN To compare the various types of analytic studies (e.g., case-
control, cohort, experimental-randomized controlled trial), it
Various study designs may be chosen when seeking to address is useful to consider the traditional 2 X 2 table (Figure 9.1).
a clinical question. These study designs, in order of increasing While all three study designs seek to investigate the association
methodologic rigor, include case report, case series, ecologic between a risk factor (or exposure) and an outcome of inter-
study, cross-sectional study, case-control study, cohort study, est, they differ fundamentally in how patients are enrolled in
and randomized controlled trial. Randomized controlled tri- the study. In a case-control study, patients are entered into the
als, case-control studies, and cohort studies are considered as study on the basis of the presence or absence of the outcome
analytic studies, whereas the other designs are considered as (or disease) of interest. These two groups (i.e., those with the
descriptive studies. disease and those without the disease) are then compared to
104 St!Ctionl • GeMral~ofHospiUJllnfo;tiqns
controls must be chosen in a manner independent of their sta-

tua with regard to an exposure of interest and should not be
fiJ selected because they have characteristics similar to the cases.
w The selection of controls in case-control studies of antimicro-
0 DISEASE
bial resistance will be discussed in more detail in a later section
~
..J
Present Absent
(cases) (controls) of this chapter.
~
w 00 Pffi~nt A 8 COHORX STUDY
::E (exposed)
~
I-
w
Q.
Absent c D Unlike a case-control study, patients are entered into a cohort
study on the basis of the presence or absence of an exposure
~ (unexposed)
(or risk factor) of interest (Figure 9.1). These two groups (i.e.,
Figure 9.1. Study de.sigm. those with the exposure and those without the exposure) are
(Adapted from Lautenbach E. Epldemlo1ogic:al methodl in infection controL then compared to determine whether they differ with regard
ID: Lautenbach E, Woel~e K, eda. .Prru:tWIH~for H«<lttlt:an~ to the development of the outcome of interest. A cohort study
'Iborofue, NJ: Slack; 2004:66.) may be either prospective or retrospective, which depends on
when it is conducted with regard to when the outcome of inter-
est occurs. If the patients are identified as exposed or unex-
determine if they differ with regard to their presence of riak posed and then followed forward in time to determine whether
factors of interest. they develop the outcome, it is a prospective cohon study. If the
A case-control study design, which is always retrospective, is study is conducted after all outcomes bave already occurred, it
parti.cularly attractive when the outcome being studied is rare is a retrospective cohort study. As an example, one might iden-
because one may enroll all patients with the outcome of inter- tify all the patients who receive an FQ in the hospital (i.e., the
est. As such, this study design is much more efficient than the exposed) and compare them to a randomly selected group of
comparable cohort study in which a group of patients with and patients who do not receive an FQ (i.e., the unexposed). These
without an exposure of interest would need to be followed for groups could then be followed forward to determine what pro-
a period of time to determine who develops the outcome of in· portion of patients in each group develops the outcome of in-
terest. Another advantage of the case-control study is that one terest (i.e., FQR.EC HAl).
may study a number of risk factors for the outcome of interest. An advantage of a cohort study ill that one may study mul-
One limitation of a case-control study ilJ that only one outcome tiple outcomes from a single risk factor or exposure. Also, this
may be studied. Another disadvantage of this approach is that study design allows the investigator to calculate an incidence
one cannot directly calculate the incidence or relative risk be. and a relative risk in comparing the two groups. Potential limi-
cause the investigator fixes the number of cases and controls tations of a cohort study include substantial time and cost re-
to be studied. quirements due to an often prolonged follow-:up of subjects. In
Of great importance in a case-control study is the process addition, if the outcome is rare, a luge number of subjects will
by which the cases and controls are selected. The cases may be need to be followed to ensure an adequate sample size. Fmally,
restricted to any group of diseased individuals. However, they the longer the study duration, the more likely the sutnects will
must arise from a theoretical source population so that a dis- be lost to follow-up, potentially biasing the study results. Some
eased person not selected is presumed to have arisen from a of these limitations are mitigated in a retrospective cohort study
different source population. For example, in studying risk fac- because the outcomes have already occurred and the patients
tors for healthcare-associated FQREC infection, the theoretical do not need to be followed prospectively.
source population could be considered to be the population
of patients hospitalized at the institution who did not have
llANDOMIZED CONTROLLED TRW..
community-acquired FQR.EC infections at the time of admis-
sion. Thus, a patient at that institution with a clinical FQREC The randomized controlled trial is very similar to the cohon
isolate recovered after admission would be included as a case. study (Ftgure 9.1). However, in a cohort study, patients are
However. a patient with FQREC infection at a different hospi- enrolled already with or without the exposure of interest. In
tal would not be included. The cases also must be chosen in a a randomized controlled trial, the investigator assigns the ex-
manner independent of their status with regard to an exposure posure randomly. This study design, if well designed, provides
of interest. the most convincing demonstration of causality because the
Careful attention is also required when selecting the con- patients in both groups should (provided randomization has
trols. The controls should be representative of the theoretical worked appropriately) be equal with regard to all important
source population that gave rise to the cases. Thus, if a con- variables except the one variable (exposure) manipulated by
trol were to have developed the disease of interest, the person the investigator. While randomized controlled trials may pro-
would have been selected as a case. In the preceding example, vide the strongest mpport for or against an association ofintel'-
the controls may be randomly selected from among all non- est, they are costly studies, and there may be ethical issues that
FQREC-infected patients in the hospital. In investigating the preclude their conduct. For example, in studying the associa-
possible association between prior FQ use and FQ,R.EC infection between FQ use and FQREC HAI, one could not ethically
tion, these two groups (i.e., patients with FQREC infection and assign patients to receive FQ if they did not require the drug.
a random sample of all other hospitalized patients) could be One alternative to the randomized controlled trial is the quasi-
compared to determine what proportion of patients in each experimental study design, which will be discussed in a later
group had experienced recent FQ exposure. Finally, like cases, section of this chapter.
ChafMr 9 • EpidemW/Qgic Mtlth«b for lnvutigtmng lnftaitwu in the Ht~Q/Uu;(m Setting 105
MEASURES OF EFFECT is the OR. which is defined as the odds of exposure in rubjecu
with the outcome divided by the odds of exposure in rubjects
RBLATIVE RISK. (lUl) without the outcome (Figure 9.2). An OR of 1.0 is called the
value of no effect, or the null value.
The relative risk. (RR. also called the risk ratio) is the ratio of two As noted, one cannot calculate an RR from a case-contl'Ol
probabilities: the probability of the outcome among the exposed study because this type of study offers no insights into the abso-
divided by the probability of the outcome in the unexposed lute rates or proportions of disease among the rubjects. However,
(Ftgru:e 9.2). An RR can be calculated from a cohort study or a in situations in which the disease under study is rare ( <1 0%), the
randomized controlled trial becauae from the.se study de.sigw, one OR derived from a case-contl'Ol study closely approximates the
can derive population-based rates or proportions. An RR. of 1.0 is RR that would have been derived from the comparable cohort
called the value of no effect, or the null value. An RR of2.0 means study. Figure 9.2 shows how the case-control formula approaches
that the exposed subjects were twice as likely to have the outcome the formula for RR when the rare-outcome criterion is met
of interest as the unexposed subjects. An RR of O.S mearu that
the exposed were half as likely to experience the outcome as the
MEASURES OF STK.ENGTH OF ASSOCIATION
unexposed, indicatiDg a protective effect of the exposure.
PVIIIMe
ODDS RATIO (OR.) The chi-square test for comparison of two binomial proportions
In a case-control study, rubjecu are enrolled on the basis of the is the most common method of measuring the strength of asso-
outcome of interest. One then compares these two groups (ie., ciation in a 2 X 2 table. This calculation is identical for all 2 X 2
those with the outcome and those without it) to determine tables whether or not the data were derived from a cohort or
what proportion of subjects in each group demonstrates a risk case-conttol study. When the chi-1quare value has been calcu-
factor of interest. Unlike the cohort study, one cannot directly lated, the associated probability that the observed difference be-
calculate an R.lt What one can calculate in a case-conttol study tween binomial proportions could have arisen by chance alone
can be looked up. A Pvalue of <.05 indicates that an effect at
OUTCOME
least as extreme as that observed in the study is unlikely to have
occurred by chance alone because there is tl'uly no relationship
between the exposure and the disease. Although this is the con-
ventional interpretation, there is nothing particularly unique
~~:::~::)
(.) ----1--
about the 0.05 cutoff for statistical significance. One limitation of
the Pvafue is that it reflects both the magnitude of the difference
~ Absent C between the groups and the sample size. Consequently, even a
(not exposed)
small difference between groups (if the sample size is large) may
be statistically significant even if it is not clinically important.
Conversely, a larger effect that would be clinically important may
not be statistically significant if the sample size is small
Relative Risk 95% Omjillente lnterP11l

Risk of disease among exposed = A I (A+B)
Risk of disease among unexposed = Cl (C+D) Because of the limitations of the P value just noted, it is pref-
erable to report the 95% confidence interval (CI) for a given
Relative Risk= A I CA+B) RR or OR. The 95% CI provides a range within which the true
C I (C+D) magnitude of the effect (i.e., the RR or the OR) lies with a
certain degree of assurance. Observing whether the 95% CI
crosses 1.0 (i.e., the value of null effect) provides the aame in-
Odds Ratio formation as the Pvalue. If the 95% CI crOllles 1.0, the Pvalue
Odds of exposure given disease =A I C will almost never be <.05. The impact of the sample size can be
Odds of exposure given no disease= B I D ascertained from the width of the CI. The narrower the CI, the
less variability present in the estimate of the effect, reflecting
Disease Odds Ratio =
NC AD a larger sample size. The wider the Cl, the smaller the sample
BI D BC size. When interpreting results that are not statistically signifi-
cant, the width of the CI may be helpful. A narrow CI implies
that there is most likely no real effect, whereas a wide interval
Relationshi p between relative risk and odds ratio ruggests that the data also are compatible with a tl'Ue effect and
When disease is rare, B>>A, and D>>>C that the sample size was simply inadequate.
Relative Risk = A I CA+B) - AD = Odds ratio BIAS

C I (G+D) BC
Bias is the systematic error in the collection or interpretation of
Figure 9.2. Relative risk and odds ratio.
data. The types of bias include information bias (i.e., distortion
(Adapted from Lautenbach E. Epldemlologl.cal methodl in infection con1r0L
Ill: Lautenbach E, Woelge K, eda. ~H~for H«<lttlt:an~ in the estimate of effect due to measurement error or misclas-
'Iborofue, NJ: Slack; 2004:66.) sification of subjects on one or more variables) and selection
bias (i.e., distortion in the estimate of effect resulting from the more likely to develop FQREC HAl. In addition, more severe
manner in which the subjects are selected for the study). For illness also is more likely to result in mortality. Thus, because it
example, a common type of information bias in case-control is associated with both the exposure and outcome of interest,
studies is recall bias. One may compare the patients with an severity of illness is a potential confounding variable. Unlike
FQREC HAl to a random sample of noninfected controls in bias, a confounding variable may be controlled for in the study
an effort to identify the risk factors for FQREC HAl. If the pa- analysis. However, to do this, data regarding the presence or
tients with an FQREC HAl are aware of their diagnosis, they absence of the confounder must be collected during the study.
may be more likely to try to identify the possible reasons for Thus, it is also important to consider the potential for con-
experiencing a resistant infection. If this group is more likely founding variables in the design of the study.
to remember recent antibiotic use than are controls, the asso-
ciation between recent antibiotic use and FQREC HAl will be
spuriously strengthened. SPECIAL ISSUES IN HEALTHCARE
The potential for bias must be addressed when the study is EPIDEMIOLOGY METHODS
designed because it cannot be corrected during the analysis of
the study. Indeed, blinding in randomized controlled trials is a QUASI-EXPERIMENTAL STUDY DESIGN
commonly used method to minimize the potential for bias in
such studies. In addition to evaluating whether a bias may exist, In addition to the study designs reviewed previously, the quasi-
one must also consider the likely impact of the bias on the study experimental study is a design frequently employed in health-
results. The bias may be nondifferential (i.e., biasing toward care epidemiology investigations (15). This design is also
the null hypothesis and making the two groups being com- frequently referred to as a "before-after" or "pre-post interven-
pared look artificially similar) or differential (i.e., biasing away tion" study (16,17). The goal of a quasi-experimental study is
from the null hypothesis and making the two groups being typically to evaluate an intervention without using randomiza-
compared look artificially dissimilar). tion. The most basic type of quasi-experimental study involves
the collection of baseline data, the implementation of an inter-
vention, and the collection of the same data following the inter-
CONFOUNDING vention. For example, the baseline prevalence of FQREC HAl
in a hospital would be calculated, an intervention to improve
Confounding occurs when the association observed between FQ use would then be instituted, and the prevalence of FQREC
an exposure and outcome is due, in part, to the effect of some HAl again would be measured after a prespecified time period.
other variable. To be a confounder, a variable must be associated Many different variations of quasi-experimental studies exist,
with both the exposure and outcome of interest but cannot be and include (a) institution of multiple pretests (i.e., collection
a result of the exposure. Confounding can result in an over- or of baseline data on more than one occasion), (b) repeated in-
underestimate of the effect of the exposure of interest. For ex- terventions (i.e., instituting and removing the intervention se-
ample, in assessing the association between an FQREC HAl and quentially), and (c) inclusion of a control group (i.e., a group
mortality, one must consider the underlying severity of illness on which baseline and subsequent data are collected but on
as a potential confounder. Patients with more severe illness are which no intervention is implemented) (Table 9.1) (15,18,19).
A. Quasi-Experimental Designs without Control Groups

1. One-group pretest-posttest design 01 X 02
2. One-group pretest-posttest design using a double pretest 0102 X 03
3. One-group pretest-posttest design using a nonequiwlent dependent variable (Ola, Olb) X (02a, 0 2b)
4. Removed-tteaonent design 01 X 02 03 remove X 04
5. Repeated-treaonent design 01 X 02 remove X 03 X 04
B. Quasi-Experimental Designs That Use Control Groups

1. Posttest~nly design with nonequiwlent groups X 01
X 02
2. Untreated control group design with dependent pretest and posttest samples 01a 02a
Olb02b
3. Untreated control group design with dependent pretest and posttest samples and a 01a 02a X Olla
double pretest Olb 02b 03b
4. Untreated control group design with dependent pretest and posttest samples and 01a X 02b Olla
switching replications 01a 02b X 03b
0, observational measurement; X, intervention under study, and time moves from left to right.
In general, studies in category B are of higher study design quality than those in category A. Also, as one moves d own within each category, the
studies become ofhigher quality, for example, study 5 in category A is of higher study design quality than study 4, and so on.
Adapted from Harris AD, Lautenbach E, Perencevich E. A systematic review of quasi-i:xperimental study designs in the fields of infection
control and antibiotic resistance. Clin InfedDis. 2005;41:77~2.
Although often employed in the evaluations of HAl interven- a more comprehensive assessment of the possible regression
tions, critical evaluation of the advantages and disadvantages of to the mean. Second, changes in the outcome of interest may
quasi-experimental studies has only recently been conducted be measured at a control site (e.g., another institution) during
( 15,18,19). Indeed, a recent systematic review offourinfectious the same time period. Finally, the use of segmented regression
diseases jownals found that during a 2-year period, 73 articles analysis may assist in addressing the possible regression to the
focusing on infection control and/ or antimicrobial resistance mean in that the immediate change in prevalence coincident
used a quasi-experimental study design ( 15). Of these articles, with the intervention will be assessed as will the change in slope
only 12 (16%) used a control group, 3 (4%) provided justifica- over time (20-23).
tion for the use of the quasi-experimental study design, and Uncontrolled confounding, another potential limitation
17 (23%) mentioned at least one of the potential limitations of in quasi-experimental studies, is most likely to occur when
such a design (15). More attention has recently been focused variables other than the intervention change over time or dif-
on increasing the quality of the quasi-experimental study defer when comparing the pre- and postintervention periods
sign and conduct to enhance the validity of conclusions drawn (16,17). This limitation can be addressed by measuring the
regarding the effectiveness of interventions in the areas of in- known confounders (e.g., hospital census, number of admis-
fection control and antibiotic resistance (15,18). sions) and controlling for them in analyses. However, not all
The quasi-experimental study design offers several advan- confounders are known or easily measured (e.g., quality of
tages. The study designs available when one wishes to study medical and nursing care). To address this, one may assess a
the impact of an intervention are limited. In general, a well- nonequivalent dependent variable to evaluate the possibility
designed and adequately powered randomized controlled trial that factors other than the intervention influenced the out-
may provide the strongest evidence for or against the efficacy come (15,18,19) . A nonequivalent dependent variable should
of an intervention. However, there are several reasons why a have similar potential causal and confounding variables as the
randomized controlled trial may not be feasible in the study primary dependent variable except for the effect of the inter-
of infection control interventions. Randomizing individual pa- vention. For example, in assessing the impact of an interven-
tients to an intervention of infection control often is not a rea- tion to limit FQ use on FQREC HAl prevalence, one might
sonable approach given the person-to-person transmission of consider the incidence of catheter-associated bloodstream in-
resistant pathogens. One might consider randomizing specific fections as a nonequivalent dependent variable. While FQREC
units or floors within one institution to receive the interven- HAl prevalence and catheter-associated bloodstream infection
tion. However, these units are not self-contained, and patients might both be affected by such factors as patient census, it is
and healthcare workers frequently move from unit to unit. unlikely that FQ use specifically would affect the incidence of
Thus, any effect on the reduced transmission/acquisition of catheter-associated bloodstream infections.
new resistant infections noted in the intervention units is also Maturation effects are related to natural changes that the
likely to result in some reduction in resistant infections in non- patients experience with the passage of time (16,17). In addi-
intervention areas (i.e., contamination). This would bias the tion, cyclical trends (e.g., seasonal variation) may be a threat
results toward the null hypothesis (i.e., no effect of the inter- to the validity of attributing an observed outcome to an inter-
vention). Similarly, if only certain areas in an institution were vention. This potential limitation may be addressed through
randomized to the intervention, enhanced attention to infec- approaches noted earlier, including the assessment of a pro-
tion control that might be part of an intervention would likely longed baseline period, use of control sites, implementation of
be evident to nonintervention floors, given that many health- interventions at different time periods at different sites, and
care workers (e.g., physicians, nurses) work in multiple areas. assessment of a nonequivalent dependent variable.
This might result in enhanced infection control practices on
nonintervention floors, which would bias the results toward the
CASE-CROSSOVER STUDY DESIGN
null. In such a situation, a well-designed quasi-experimental
study offers a compelling alternative approach. In addition, this The case-crossover study design also has been increasingly rec-
study design is frequently used when it is not ethical to conduct ognized as a useful approach when addressing issues in health-
a randomized controlled trial. In addition, when an interven- care epidemiology (24). In this design, each case serves as his
tion must be instituted rapidly in response to an emerging issue or her own control (i.e., self-matching). For each su~ect, the
(e.g., an outbreak), the first priority is to address and resolve exposure status is measured in the "case" time period occurring
the issue. In this instance, it would be unethical to randomize shortly before the outcome. Then this is compared to the expo-
an intervention across patient groups. sure status in one or more earlier "control" time periods. Then,
Several primary limitations exist in quasi-experimental RR are estimated by comparing the frequency of exposure im-
studies including regression to the mean, uncontrolled con- mediately before the case event (the case period) vs. the earlier
founding, and maturation effects. The implementation of period (i.e., control period).
an intervention is often triggered in response to a rise in the This study design offers several advantages. Because cases
rate above the norm (20). The principle of regression to the serve as their own controls, the design adjusts for many of the
mean predicts that these elevated rates will tend to decline differences between cases and controls that might confound
even without intervention. This may serve to bias the results a traditional case-control study. Also, this study design is less
of a quasi-experimental study because it may be falsely con- susceptible to confounding by indication (25). All retrospec-
cluded that an effect is due to the intervention (16,17). Sev- tive studies relying on patient recollection of exposure data
eral approaches may be employed to address this potential may suffer from recall bias. Another potential advantage of the
limitation. First, incorporating a prolonged baseline period case-crossover study is that the same person is recalling data
before the intervention permits an evaluation of the natural from both the control and case time periods since each person
fluctuation in the rates of the outcome over time and permits serves as his or her own control (25,26).
Several disadvantages of the case-crossover design also exist. the explanation for this finding has been postulated as follows:
An underlying assumption in this design is that the confound- If the controls are represented by patients with FQSEC HAis, it
ers are not changing over time in a systematic way; otherwise, is very unlikely that these patients would have recently received
this may be a source of confounding (25). In addition, bias FQs (i.e., the risk fuctor of interest) because exposure to FQs
could result from temporal changes in the exposure of interest may have eradicated FQSEC colonization. Thus, the association
or through the selection of the control time window (25). between FQ use and FQREC HAl would be overestimated (38).
The case-crossover study design is ideally suited to studying A limitation of using the first type of approach (i.e., using pa-
brief exposures with immediate and transient effect and acute tients without infection as controls) is that in addition to identi-
outcomes with abrupt onset (e.g., motor vehicle accidents, in- fying risk factors for resistance, this approach also identifies the
jury) (27,28). Also, exposures must vary over time within an risk factors for infection with that organism in general (regard-
individual; otherwise, there would be no ability to compare ex- less of whether the infection is resistant or susceptible). Thus,
posed and unexposed periods within the individual. However, there is no way to distinguish the degree to which a risk factor is
it has been suggested that with lengthened exposure assess- associated with the resistance phenotype vs. associated with the
ment windows for both the case and control time periods, case- infecting organism in general (34).
crossover methods may also be useful for studying exposures One concern with using the first type of control group
with prolonged effects and outcomes with insidious onsets (i.e., selecting from all hospitalized patients) is the potential for
(29-31). This may be particularly relevant for studying the ad- misdassification bias. Specifically, the subjects selected as con-
verse effects of prolonged drug exposures (e.g., antimicrobials) trols who have never had a clinical culture obtained may in fact
given the concerns regarding the control selection bias and harbor unrecognized colonization with the resistant organism
confounding inherent in traditional case<ontrol studies of under study (33). Because it is probable that the patients colo-
adverse effects (29). nized with the resistant organism would likely have had greater
With regard to healthcare epidemiology specifically, this prior antimicrobial exposure than the subjects who are not col-
design has been used successfully to study sharps injuries in onized, this misclassification would likely result in a bias toward
healthcare workers (26). In this study, the case-crossover design the null (i.e., the cases and controls would appear falsely similar
was well-«uited to assess the relationship between brief, tran- with regard to prior antimicrobial use). Another concern with
sient exposures, such as fatigue or rushing, and the acute event using the first type of control group and identifying the patients
of a sharps injury. Another recent study used a case-crossover who have never had a clinical culture as controls is that the dif-
approach to study the association between wet, humid weather ferences between cases and controls may reflect the fact that
and the incidence of legionellosis (32). This approach was use- clinical cultures were performed for case-patients but not for
ful in controlling for seasonal factors that might confound the controls. Because procurement of cultures is not a random pro-
relationship between weather and disease occurrence to facili- cess and is based on clinical characteristics, it is possible that the
tate the identification of acute weather patterns associated with severity of illness or antibiotic exposure may be greater among
LegicmeUa spp. infection ( 32). the cases regardless of the presence of an antibiotic-resistant
infection (3). One potential approach would be to limit the eli-
gible controls to those patients for whom at least one clinical
CONTROL GROUP SELECTION IN STUDIES
culture has been performed and does not reveal the resistant
OF ANTIMICROBIAL RESISTANCE
organism of interest. Such a negative culture would suggest that
Many studies have focused on identifying the risk fuctors for an- the patient is likely not colonized with the resistant organism.
timicrobial resistance. The majority of these studies have been However, recent work has demonstrated that using clinical cul-
case-control-designed studies. & noted previously, how con- tures to identify the eligible controls leads to the selection of a
trols are selected in case-control studies is critical in ensuring control group with a higher comorbidity score and greater ex-
the validity of the study results. Recent work has highlighted posure to antibiotics compared with a control group for which
this issue of control group selection specifically for studies of clinical cultures were not performed (33).
antibiotic resistance (3,33-37). One proposed approach to addressing the difficulties in
Historically, two types of control groups have been used in control group selection in studies of antimicrobial resistance
studies of antimicrobial-resistant organisms (3). The first type is the case-case-control study design (34,39-41). In this design,
of control group is selected from patients who do not harbor two case<ontrol studies effectively are performed. In the first
the resistant pathogen. The second type of control group is study, cases are defined as those patients harboring the resis-
selected from among su~ects with a susceptible form of the tant organism, whereas controls are those patients without the
infection. For example, in a study of risk fuctors for HAl with pathogen of interest. In the second study, cases are instead
FQREC in hospitalized patients, the first type of control group defined as those patients harboring the susceptible bacteria,
would be selected from among the general hospitalized patient whereas controls, similar to those in the first approach, are
population, whereas the second control group would be se- those patients without the pathogen of interest (34). These
lected from among those patients with an FQ-susceptible E. coli two separate studies are then carried out with risk fuctors
(FQSEC) HAl. The choice of control group should be based from the two studies compared qualitatively. This approach
primarily on the clinical question being asked. While the use of allows for the comparison of risk factors identified from the
this second type of control group has historically been a more two studies to indicate the relative contribution of the resistant
common approach, it has recently been demonstrated that the infection over and above simply having the susceptible infec-
use of this type of control group (e.g., patients infected with tion. A potential limitation in this approach is the difficulty in
the susceptible form of the organism) may result in an overes- matching for potential confounders because of the use of only
timate of the association between antimicrobial exposure and one control group (34). Because there are two different case
resistant infection (35,36). Using the example ofFQREC HAl, groups, case variables (e.g., duration of hospitalization, patient
location) cannot be used for matching. In addition, the quali- Another issue regarding defining prior antimicrobial use
tative comparison of results from the two studies in this design centers around how specific agents are grouped. For example,
leaves open the question as to how much of a difference in antibiotic use could be classified by agent (e.g., cefazolin),
results is meaningful. class (e.g., cephalosporins), or spectrum ofactivity (e.g., gram-
negative). Antibiotics are frequently grouped together in classes
even though individual agents within the class may differ sig-
DEFINITIONS OF ANTIBIOTIC EXPOSURE
nificantly (48), and such categorizations may mask important
Many studies have sought to uncover the risk factors for infec- associations. It is unknown whether using different categoriza-
tion or colonization with resistant organisms (6,42). Elucidat- tion schemes results in different conclusions regarding the as-
ing such risk factors is essential to inform the interventions sociation between antibiotic use and resistance. A recent study
designed to curb further emergence of resistance. Past stud- explored these issues, focusing on ESBL-EK as a model (49).
ies have particularly focused on antimicrobial use as a risk fac- In a systematic review, 20 studies of risk factors for ESBL-EK
tor because it can be modified in the clinical setting (43,44). that met inclusion criteria revealed tremendous variability in
However, the approaches used to define prior antibiotic ex- how prior antibiotic use was categorized. The categorization of
posure vary considerably across studies (3). More important, prior antibiotic use was defined in terms of the specific agents,
only recently have attempts been made to identify the impact drug class, and often a combination of both. No study justified
of differences in these approaches on the study conclusions. its choice of categorization method. There was also marked
A recent study investigated the methods used in past studies variability across studies with regard to which specific antibiot-
to describe the extent ofprior antibiotic use (e.g., exposure yes/ ics or antibiotic classes were assessed. As expected, a majority of
no vs. duration of exposure) and the impact of using different the studies ( n = 16) specifically investigated the use of}-lactam
methods on the study conclusions (45). A systematic review of antibiotics as risk factors for ESBL-EK. A variable number of
all studies investigating the risk factors for extended-spectrum studies also examined the association between the use of other
P-lactamase-producing E. coli and Klebsiella sp. (ESBL-EK) was antibiotics and ESBL-EK infection: aminoglycosides (9 stud-
conducted. Among the 25 included studies, prior antibiotic use ies), FQs ( 10 studies) , and trimethoprim-sulfamethoxazole
was defined as a categorical variable in 18 studies, four stud- (7 studies). In a reanalysis of data from a prior study of risk
ies defined prior antibiotic exposure as a continuous variable, factors for ESBL-EK (46), two separate multivariable models of
and three studies included both a categorical and a continuous risk factors for ESBL-EK were constructed, one with prior anti-
variable to describe prior antibiotic exposure. Only one paper biotic use categorized by class and the other with prior antibi-
provided an explicitjustification for its choice of variable to de- otic use categorized by spectrum of activity (49). The results of
scribe prior antibiotic exposure. The authors then reanalyzed a these multivariable models differed substantially. Recent work
dataset from a prior ESBL-EK risk factor study (46), developing has reported similar findings when focusing on risk factors for
two separate multivariable models, one in which prior antibi- carbapenem-resistant Pseudomonas aeruginosa (50).
otic use was described as a categorical variable (e.g., exposure Another final important issue is how remote antibiotic use is
yes/no) and one in which antibiotic use was described as a con- assessed. A recent systematic review of studies investigating the
tinuous variable (e.g., antibiotic days). The results of the two risk factors for ESBL-EK (noted earlier) (45) found that the
multivariable models using different methodologic approaches time window during which antibiotic use was reviewed ranged
differed substantially. Specifically, third-generation cephalospo- from 48 hours to 1 year before the resistant infection. Further-
rin use was a risk factor for ESBL-EK when antibiotic use was more, studies often did not explicitly state how far back in time
described as a continuous variable, but not when antibiotic use prior antibiotic use was assessed (45).
was described as a categorical variable (45).
These results suggest that describing prior antibiotic use as a
ASSESSMENT OF MORTALITY AS AN OUTCOME
categorical variable may mask significant associations between
OF INFECTION
prior antibiotic use and resistance. For example, when the cat-
egorical variable is used, a subject who received only 1 day of Studies have increasingly focused on more clearly identifying
an antibiotic would be considered identical to a subject who the impact of HAis and antimicrobial resistance (51). These
received 30 days of the same antibiotic. However, the risk of studies seek to identify the risk factors for negative outcomes
resistance is almost certainly not the same in these two indi- such as mortality, increased cost, and prolonged length of hos-
viduals. Describing prior antibiotic use as a continuous variable pital stay. Increasing attention has recently been paid to poten-
allows for a more detailed characterization of the association tial methodologic issues in assessing the relationship between
between the length of exposure and resistance. Recent work an antimicrobial-resistant infection and mortality (3,51). One
in the medical statistics literature emphasizes that the use of important issue is the need to control for severity of illness.
cut points can result in misinterpretation of data and that di- An oft-noted risk factor for resistant infection is the greater
chotomizing continuous variables reduces the analytic power underlying severity of illness. However, severity of illness also
and makes it impossible to detect nonlinear relationships (4 7). is a predictor of mortality. These characteristics suggest that
Indeed, the relationship between prior antimicrobial use and severity of illness is likely to be an important confounder in
resistance may not be linear (i.e., the risk of resistance may not the association between resistant infection and mortality (i.e.,
increase at a constant rate with increasing antimicrobial expo- severity of illness is associated with both the exposure and out-
sure). It is possible that the risk of resistance does not increase come of interest). Several measures assess the severity of illness
substantially until a certain amount of antimicrobial exposure including the Acute Physiology and Chronic Health Evaluation
has been attained (e.g., a "lower threshold"). A more precise (APACHE) II score (52) and the McCabe-Jackson score (53).
characterization of this "lower threshold" would serve to better It is important to note that no severity of illness score has been
inform the antibiotic use strategies. developed or validated specifically to predict the outcome in
ll 0 Section I • General ConsideratiOfiS of Hospital Infectiuns
patients with infection. Regardless of the measure used, it is A final issue with regard to assessment of mortality as an
critical to assess the score and control for it in studies assessing outcome is how mortality is defined. Crude in-hospital mortality
the impact of resistant infection on mortality. has been the most common measure of mortality, likely
It is important to carefully consider when severity of illness because it is the least subjective in its assessment. However,
is assessed (54,55). The vast majority of studies have assessed se- this definition of mortality fuil.s to distinguish those patients in
verity of illness at the time the infection is diagnosed (i.e., when whom infection clearly resulted in death as opposed to those in
the culture is initially drawn). However, the culture is generally whom infection occurred but was likely unrelated to mortality
obtained because of a clinical suspicion of infection, suggesting (e.g., infection occurs several weeks before death). Some stud-
that the infection has already progressed at some time point ies have proposed approaches to categorizing the outcome of
before the culture was obtained. Because the infection will also mortality relative to how likely it is to have been a result of infec-
typically lead to a more severe illness, it is likely that the severity tion. One approach would be to assign an arbitrary time period
of illness measured on the day the culture is obtained is more after the infection (e.g., 1 week) beyond which the occurrence
accurately an intermediate variable (e.g., infection leads to a of mortality would be assumed to be independent of the in-
more severe illness, which then ultimately leads to death). Con- fection. Another approach has proposed categories designed
trolling for an intermediate variable in this way usually causes to assess attributable mortality as an outcome (46,60-62).
an underestimate of the effect of the exposure of interest on the In this definition, the possible outcomes are classified as fol-
outcome (56). To avoid this issue, it has been suggested that the lows: (a) mortality directly attributable to infection: death dur-
severity of illness be assessed at least 48 hours before the date ing hospitalization in the setting of clinical evidence of active
the culture was obtained to provide a more reasonable assess- infection and a positive culture result, (b) mortality indirectly
ment of the patient's underlying severity of illness rather than attributable to infection: failure or further compromise of an
the severity of illness caused by the infection itself (54). Inter- organ system due to infection and death occurring during
preting the results of studies that control for severity of illness hospitalization as a result of organ failure, (c) mortality unre-
on the day the culture is obtained should be interpreted with lated to infection: death occurring during hospitalization after
caution because they may represent an underestimate of the an episode of infection but due to causes independent of the
true association between resistant infection and mortality (54). infectious process, and (d) survival: patient discharged alive
Furthermore, the timing of the measurement of severity of ill- from the hospital. The proportion of deaths directly and indi-
ness may significantly impact the magnitude of the association rectly attributable to infection define the attributable mortality.
between receipt of appropriate antimicrobial therapy and mor- While this approach may more appropriately designate mortal-
tality when adjusting for severity of illness as a confounder (55). ity as attributable to infection, many of the criteria remain quite
The length of stay in the hospital before the infection is also subjective. Of note, recent studies using both this approach and
an important potential confounder in the association between crude in-hospital mortality as outcomes found no substantive
resistance and mortality. An increased length of stay is a risk differences in the final study results (63,64,65).
factor for resistant infection and for negative clinical outcomes
(3). A recent study assessing the mortality associated with E. coli
bacteremia first compared patients with E. coli bacteremia to CONCLUSIONS
unmatched controls without the bacteremia and then com-
pared them to patients without E. coli bacteremia but matched To best respond to the increasingly complicated field of HAis
by the prior length of hospital stay (57). The authors found and antimicrobial resistance, a strong understanding of epide-
similar associations between E. coli bacteremia and mortality miologic principles and approaches is essential. This chapter
regardless of whether matching was used (57). Although these has reviewed the basic principles of epidemiology and a num-
results suggest little impact of controlling (through matching) ber of more specific topics, with particular relevance to HAis
for the length of stay, the results should be interpreted with and antimicrobial resistance. While a resurgence in the study
caution because the prior length of stay in the patient groups of epidemiologic methodology in HAis has occurred in recent
was relatively short (median of 6 days) (3). years, this field of inquiry must continue to expand in the fu-
Similar to the preceding discussion, the choice of control ture. Only by providing the most rigorously derived evidence
group also is relevant in studies of outcomes (54). Of note, be- can we hope to devise and implement successful strategies to
cause studies addressing the outcomes related to infection are limit future infections in the healthcare setting.
primarily cohort studies, "controls" in these studies are more
appropriately referred to as the "unexposed" or "reference"
group. As in case-control studies of antibiotic resistance, there
are effectively two choices for a reference group. In the first,
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higher estimate of the impact of resistance on mortality (58,59). Dis. 2008;47(supp11):S21-S31.
Chapter 9 • Epidemiologic Methodsfor ln'llestigating Infections in the Healthcrm Setting lll
8. Tho!IWI JC, Weber DJ. ~/ogi< M6lhod.s for tlw SludJ ofIrifoctWw .Di.r«J.m. Oxford, UX: 59. Kaye KS, HaniJ AD, GoW H, et al.ll.iok fl.ctoro for recovery ofampicillin-.ulbactam-reoiotant
Ol<ford UDivenityPreoo; 2001. Esdimt;/,;g coli in hoopitalized palients. A1llilllicnJ!>Agma a..-Jwr. 2000;44:1004-1009.
9. Hoomer DW, Lemeoho SL. Appli«l LQgillic ~ 2nd ed. New York, NY: Wlley lnter- 40. HaniJ AD, Perencerich E, Roghmann M.C, eta!. ll.iU facton for piperacillin-tazohactam-
ocience; 2000. reoiotant Puudomonas ~among holpitalized patieuu. Alllilllierob Agma CNmotlwr.
10. Agreoti A. CIJtiK!>ricalDaraAIIGlyru. N""' Yori, NY: Wlley lnterocience; 2002. 2002;46:8!i4-&8.
11. Hennekem CH, Buring ]E, Mayrent SL. Ep~ ;, MMi<iM. Philadelpbia, PA: 41. HaniJ AD, Smith D, Johnson JA, et a!. ll.iU fl.cto!'l for imipenem...eoiotant P.rludooaonar
Lippincott Wlilliunt & Wllkino; 1987. '"""Ci"""' among hoopitalized patienu. a;,. bsft<tDiJ. 2002;34:34B-ll45.
12. Kleinbaum DG, Kupper LL, Morgenatern H. Epidmi~ &s-.h: ~ 4114 ~ 42. Livermore D. Can better preocribing tum the tide of reliatance? N<U &v Mim>bioL
liw Mtflwdl. New York, NY: V:w Nootnwd RciuhoW; 1982. 2004;2:~78.
13. Neloon KE, Wlilliunt CM, Graham NMH.lnftcMw~Ep~: n.or, 4114~ 45. Patteroon JE. Antibiotic utilizalion: io there an effect on anWDicrobial reliatance 1 CMsl.
New York, NY: Aopen Publi>hcro; 2000. 2001;119:426S-430S.
14. Rothman lij, GreeDI.and S. Modml EpidmiDillf:J, New York, NY: Lippincott Williama & 44. Safdar N, Maki DG. The commonality of rilk .factoro for nooocomial colonization and in-
Willwu;l998. fection with 811tililicrobial-retilta.Dt Staph'lowa;us avmu1 eutcroooca.u, grarn-ucga.ti'Yt: ba-
15. HaniJAD, Lautenbach E, Perencevicb E.AI}'Item3lic reri.ewofquaoi""'P"rimentalotudyde- cilli, C/rulridi...,. riiffo;ilo, and CIJ'nd;da. Ann bst.m MMl. !002;136:8~H44.
sigos in the field.o ofinfection control and antibi.otU: remtance. amln{<aDis. 2005;41:77-82. 45. Hyle EP, Bilker WB, Gaoink LB, et a!. Impact of different method.o for deocribing the ex-
16. Shadi.th WR, Cook m, CampbellDT. ~ a1Ul ~Doligrufor a.-- tent of prior anlibio tU: e>:paoure on the aooocialion betw<oeu anlibiolic uoe and anlibiotic-
a&.d CGusalbJfrmlu. Bootou, MA: Houghton MiHiiD CO!Ilpany; 2002. reoiotant infeclion. bJftct C<mtrol HOI[> Epid<miol. 2007;28:647-654.
17. Cook ID, Campbell DT. Qu<JJ>&opori,.,.,.,;, Dni&n a1Ul AI!Glyru lmuJ for FWtl Sollmgl. 46. Lautenbach E, Patel JB, Bilker WB, et al. Extended..pectrwn beta-lactamaoe-producing
ChU:ago, IL: Raud McNally Publiohlng; 1979. Esdoerichia coli and KllinUlJtr, ~ riak filctor> for infection and impact of remtance
18. Shardell M, HaniJ AD, El-Kamary SS, et aL Statialical analyoio and applicalion of quaoi e>:- on outcomeo. Clinl11foc1Di&. 2001 ;52:1162-1171.
periments to anWDicrobial reoiotanceilltcrvenlion otudieo. amirif«tDi&. 2007;45:901-907. 47. Royoton P, Alt:Dian DG, Sanerbrei W. Dichotmnizing continuouo predicton in multiple
19. HaniJ AD, Bradham DD, Baumgarten M, et aL The uoe and interpretaCion of quaoi- regreooion: a bad idea. Stat Mal. 2006;25:127-141.
e>:perimeutal atudieo in infectiouo dioeaoeo. am Irife:l Di&. 2004;!18: 1586-1591. 48. Donokey q. The role of the inteotinal tmct ao a reoervoir and oource for tran:mWoion of
20. Mor1on V, Torgenon DJ. ~ of regre11ion to the mean on deci>ion m;oking in health nOIOCOIIlial pathogeno. Cli11 bsft<tDiJ. 2004;59:219-226.
care. BJ1.f1. 200S;326:108~1084. 49. MacAdam H, ZaoutiJ TE, Gaoink LB, eta!. ln...,.tigating the aooocialion between antibiotic
21. Ramoay CR, Matowe L, Grilli R, et a!. Intnrupml time oeriel deoigna in health teehnology UJC and anlibiotU: reoiotance: impact of different method.o of cat.ogoriling prior anlibiotU:
......ment: le11ono from two l)'ltematU: reriewo of behav.ior change otrategi.eo. 11111 Th:lmol noe. lnt1 Allli111icrob Apats. 2006;28:52!>-!lll!.
A.mu H...W. ear., 2005;19:61~3. 50. GaoinkLB, ZaoutiJ TE, BilkerWB, etal The ~ri>alion ofprioranlibiolic UJC: impact
22. Wagner AK, Soumerai SB, Zhang F, et al. Segmented regreoaion analyliJ of interrupted on the identification of riok factor> for drug reliatance in cue control otudieo. A"' j I'!{e:l
time oerieo otudieo in medicalion UJC reoean:h. 1 Clin 1'luoniO 7M: 2002;27:299--309. Conlrol. 2007;ll5:6l!IH;42.
23. Matowe LK, Leioter CA, Cmera C, et a!. Interrupted time &erieo analyoil in clinical re- 51. Coogrore SE. The relalionohlp between antimicrobial reoiotance and patient outcomeo:
oean:h. A=~ 2003;!!7:111B-1116. mortality, length of hospital otay, and health care coots. am bsJ«< Dis. 2006;42(•upp12):
24. Maclure M. The ciii<XI'OIIIIorer deoign: a method for otudying tranoieut effects on the riok S82-S89.
of acute events. A,,.JEpidntiol.l991;133:144-153. 52. Knauo WA, Draper EA, Wagner DP, e t al. APACHE II: a oc:vcrity of dioeaoe cluaificalion
25. Schneeweioo S, Stunner T, Maclure M. Caoei:!tlll09erand caoe-time-control designo u altema- oyotem. Crit C.. Mal. 1985;1~:811H!29.
livea in phannacoepidemiologi<: reoean:h. ~~ Sof. 1997;6(mppl ~):51-59. 53. McCabe WR,Jacbon GG. Gram..oegative bacteremia. An:lt bstlm Mrtl. 1962;110:847-S55.
26. Filman DN, Harrio AD, Soroct GS, et al. Sharp...-elated injurieo in health care worken: a 54. Coogrore SE, Carmeli Y. The impact of antimicrobial reoiotance on health and economic
Clii<X:rollover otudy. Am1 Mal. 2003;114:688-094. outcomeo. Clinbsf.aDi&. 2003;!16:145~1437.
27. Sorod GS, Lombardi DA, Hauer RB, et aL A caoe-crouover otudy of occupalioual trau- 55. Thom KA, Shardell MD, Ooih RB, eta!. Controlling for aeverity ofillneoo in outcome otud-
matU: hand injury: method• and iWiial findingo.Am1 Ind.Mtrl. 2001;59:171-179. iel involvillg infcctiow diJ.eues: impact of measurement at dilfen:nt time points. Infoa
28. Redelmeier DA, Tibohirani li.J. Aooocialion betw<oen cellular-{elephone callo and motor ve- Co1llrol H..p Epidntiol. 2008;29:104&-1055.
hicle collioiono. N Ezw!1MMl. 1997;~36:45~8. 56. Robina J. The control of confounding by illtermediate variableo. Stat Mtrl. 1989;8:
29. Wang PS, Schneeweioa S, Glynn li.J, et aL Uoe of the cue-croooover deoign to otudy pro- 67<}.-701.
louged drug e1pooureo and insi.diouo outcome>. A,,.,. Epidntiol. 2004;14:296-305. 57. BlotS, De Bacquer D, Hoste E, et al. Influence of matching for exposure time on estimate•
30. Dixon KE. A comparioon of cue-cmooover and caoe-control deoigno in a otudy of riok fiu;- of attributable mortality cawed by noooconrial bacteremia in critically ill patients. Irife:l
toro for hemorrllagi.c f.,..,.. with renal oyndrome. ~ 1997;8:2~246. Co1llrol H..p Epidntiol. 2005;26:552-356.
~1. Suiooa S. The caoe-time-eontrol deoign. ~· 1995;6:248-253. 58. Engemann.IJ, Carmeli Y, Coogrove SE, eta!. Adveroe clinical and economic outcomea at-
52. Filman DN, Lim S, WelleDiw GA, et aL It'o not the heat, it'a the humidity: wet weather tributable to methicillin reoi&tance among patients with ~ ........, ourgical lite
increaoeo Legionellooio riok in the grnter Phlladelpbia metropolitan area. 1 111foct IN. infeclion. CAA bJftct DiJ. 2005;56:592-598.
2005;192:2066-2075. 59. Kaye KS, Engemann.IJ, Mozafl'ariE, et aL Reference group choice and antibiotU: reaiotance
!Ill. HaniJ AD, Carmeli Y, Samore MH, et a!. Impact of oeverity of illneoo biao and control outcome&. Ewwrg InfoaDi&. 2004;10:1125-1128.
group mioclaollification biao in caoe-control otudieo of antimicrobial-reoiotant organiamo. 60. No1kin GA, Petenon Lll., Warrenjll. E'"""""""'..fac<iumand EnllrocD«Wjiu<alishacu.re-
I11foct C.U.IH...pEpidntiol. 2005;26:542-545. mia: acquioilion and outcome. Cliwln{<a Di&. 1995;20:296-301.
M. Kaye KS, HaniJ AD, Samore M, et aL The caoe<aae-<:ontrol otudy deoign: addre11ing the 61. Lautenbach E, Schuoter MG, Bilker WB, et aL The role of chloramphenicol in the treat"
lilnitationo of riok filctor atudieo for antinW:robial reoiotance. bsf«t C<mtrol H...p Epide!RioL IDent of blood.otn:am illfectinn due to vancomycil>-remtant Enterococcw. Cim bJftct Di&.
2005;26:!146-551. 1998;27:1259-1265.
35. HaniJ AD, Karchmer TB, Canneli Y, et aL Method.ologi.cal principleo of caoe-control otud- 62. Weinotein MP, Mmphy JR, Rcller LB, eta!. The clirucaloignificance of pooitift: blood cul-
ieo that analyzed riok .factoro for antibiotU: reliltance: a l)'ltematU: reri.ew. am ln{<a IN. ture!: a compreh..W.., analysil of 500 epilodeo of bacteremia and fungemia in adulto. II.
2001;32:105.'>-1061. CliDical oboenatiom, with apecial reference to !acton iDfluencing prognooio. Rill InJ.aDi&.
36. HaniJ AD, Samore MH, Upoitch M, et aL Control'1!J'OUp &eleclion importance in otudieo 1985;5:54-70.
of antimicrobial reoiotance: =pi•• applied to ~~a, Enterococc~ and 6!. Lautenbach E, Metlay JP, Bilker WB, et al. Association between fluoroquinolone roistance
&Wridli4CIJU. Cliwln{<aDiJ. 2002;li4:155S-1563. and mortality in ~ coli and KllinUlJtr. ~""infecliono: the role ofinadequab:
57. Rafailidio PI, Blizioti.o IA, Falaglu ME. Caoe-controlotudieo reporting on riak filctoro for empirical antinW:robial therapy. aminJraDi&. 2005;41:92~929.
emergence of anWDicrohlal reoiotance: biao aooociated with the oeleclion of the control 64. Hyle EP, Lipworth AD, Zaoutia TE, eta!. Impact of inadequate iWiial anWDicrobial therapy
group. Mimlb Drug &rut. 2010;16:30!-.!108. on mortality in infectiono due to extended..pectrum beta-lactamaoe-producing enterobac-
38. Carmeli Y, Samore MH, Huokino C. The aooocialion between anb:cedent.,.,.comycin treat- teriaceae: variability by lite ofinfeclion. Anlllfllml Mid. 2005;165:lll75-1380.
ment au.d ho1pital-acquin:d vaw:om.yriu-n:Uta.ut enterococci: a Jbc:ta-illlillylia. .AnA Iflkm. 65. Laut..nbach E. Epi.demiolo!JicaliDCihod.oiD infection control. In: Lautenbach E, Woelgc K,
Mid. 1999;159:2461-2468. ed.o.l'nulicalHillldJJoolcforHrallh<,..~. Thorofilre, NJ: Slack; 2004.
10 Keith F. Woeltje
Use of Contputerized Systents

in Healthcare Epidellliology
INTRODUCTION used as simple databases, such as a line-llisting for an outbreak
investigation. Spreadsheet software can also make graphs for
Computers have become ubiquitous in modem society, and vim.alization of data, such as run charts of infection rates over
computer power has increased steadily. It takes about the same time. These graphs then can be imported into a word process-
amount of computing to answer one Google Search query as ing document or slide presentation for distribution to others.
all the computing done-in Oight and on the ground-for Such graphs are easy to make, and by helping staff visualize the
the entire Apollo apace program (1). The "Meaningful Use" data, make for far more compelling discussions.
program mandated by the U.S. government has spurred much Desktop relational database software (e.g., MicrosoftAcceu,
more rapid adoption of electronic medical records in hospi- LibreOffice Base) is not included in many basic editions of of.
tals, with a concomitant increase in data that are, at least poten- fice suite software, but may be available in more extended or
tially, available electronically. While the use of computers has "professional" editions. Although in some respects more diffi-
become ubiquitous in hospitals, the degree of use continues to cult to use than other desktop computer productivity software,
vary widely. database software can offer healthcare epidemiologists aiguifi-
cant advantages over other methods of storing data, such as
using spreadsheet software. For example, if blood culture data
are being stored as part of a study, if a given blood culture has
BASIC COMPUTER. SUPPORT > 1 organism, then in a spreadsheet, either a number of col-
umns need to be included (e.g., "organism_!," "organisms_2")
PERSONAL COMPUTERS
if data from a given culture are all to be included on one row,
Personal computers (PCs) started as machines built by geek:y or a number of separate rows need to be used to record the
enthusiasts in the 1970s, but became widely commercially avail- information from a single culture. Both alternatives may intro-
able in the 1980s. In the first years of the 21st century, com- duce difficulties in subsequent data retrieval and analysis. Are-
puters have become commodity items. PC prices have fallen lational database, however, would allow tbe information to be
steadily while computing power has increased exponentially. structured in a manner that avoids these inues.
Until a few years ago, considerable thought had to be given to Because most office productivity software can be used at a
buying a PC in balancing price, capability, and upgradeabillty. bui.c level without any special training, the benefits of formal
Now, even the moat inexpensive PCs and laptops available at training are frequently under-appreciated. Various levels of
large electronics stores or online can readily handle basic com- training classes may be offered by larger organizations or may
puter needs. be available at local community colleges. Ollline training or
A computer and its operating system alone would not be structured textbooks provide additional alternatives. The time
able to accomplish very much. Additional software is needed to and expense spent on training will be returned many times
perform basic tasks, such as word processing. Although stand- in productivity gains. In particular, database software requires
alone programs of productivity software are available, they are some training to use it appropriately. An excellent introduction
typically obtained in suites with all components somewhat inte- to databases at a conceptual level (not tied to any particular
grated, allowing consistency of use across programs. Microsoft program) is Database Design for Mere Mortals (2).
Office has become the most commonly used office suite, but
a variety of competitors exist, including the free, open~ource,
NBTWOllKED COMPUTERS
LibreOffice (www.libreo:ffice.org). Most institution.s prefer to
have all employees use the same program for ease of exchang- Although a stand-alone PC can bring a huge productivity boost
ing information, but most of these programs can convert be- to a healthcare epidemiology department, the potential utility
tween the moat common formats. Online "cloud" versions of of the computer increases significantly when it is networked
these applications are also available-they are discussed below. to other computers. The PC then is no longer limited to data
Spreadsheet software (e.g., Microsoft Excel, LibreOffice that have been entered by hand or files brought to it on some
Calc) is designed primarily to manipulate numbers, not text. form of solid media. Instead, the PC can now share information
Spreadsheets are extremely useful to healthcare epidemiolo- with other computers at high speeds. Euentially, all hospitals
gists for calculating rates and doing basic statistics. The col- now have networks that connect the computers in their various
umn and row structure of spreadsheets also allows them to be departtnents together. These networb, in turn, are typically
112
Chapter 10 • Use of Computerized Systems in Healthcrm EpidemWlof!J 113
connected to the Internet, providing an electronic connection E-MAIL

between the hospital and the rest of the world.
Electronic mail, or e-mail, is probably even more popular than
the World Wide Web in terms of total number of users. Send-
INTERNET AND THE WORLD WIDE WEB ing files as attachments in an e-mail has become a preferred
method of sending data from one person to another. In addi-
The Internet is really a network of computer networks (3),
tion, e-mail can serve as a means to alert healthcare epidemiolo-
Precursors to the Internet began as a research project in the
gists to significant issues in a timely fashion. Organizations (e.g.,
late 1960s sponsored by the U.S. Department of Defense's Ad-
SHEA and APIC) send e-mail alerts to their members when war-
vanced Research ~ect Agency (DARPA). The Internet as we
ranted. Healthcare professionals also can sign up for alerts and
know it started on January 1, 1983 (4), and has grown exponen-
tially in the intervening decades. updates on terrorism and emergency response from the CDC at
emergency.cdc.govI coca/subscribe.asp. In addition, the CDC's
For many people, the World Wide Web ("the Web") is syn-
onymous with the Internet. The World Wide Web started in Division of Healthcare Quality Promotion has a Rapid Notifica-
tion System for Healthcare Professionals that sends out e-mail
1990 as a research project at the European Organization for
Nuclear Research (CERN) (5). The purpose of the Web is to alerts related to outbreaks and product recalls. The sign-up page
is at www2a.cdc.gov/ncidod/hip/rns/hip_rns_subscribe.html.
provide access to online documents (Web pages), including an
E-mail "list-serv" software allows e-mail to be sent to many
easy mechanism for one page to refer to another. These pages
persons by sending an e-mail to a particular e-mail address.
can be viewed with software called Web browsers. Since its in-
This facilitates group discussions via e-mail. Popular e-mail
ception, the Web has grown beyond simple text to include im-
groups for healthcare epidemiologists include ProMED-mail
ages and multimedia presentations and allow downloads of files
(sign up at www.promedmail.org), which is sponsored by the
of various types.
For healthcare epidemiologists, the Web provides a wealth of International Infectious Diseases Society, and the Emerging
Infections Network (request sign-up information from ein@
resources. Many professional organizations have Web sites that
provide news, guidelines, and links to other resources for both uiowa.edu), which is sponsored by the Infectious Diseases
Society of America (IDSA) and the CDC. Because of the rise
members and nonmembers. Examples include the Society for
of unsolicited commercial e-mails (termed "spam"), many in-
Healthcare Epidemiology of America (SHEA, www.shea-online
stitutions have "spam filters" in place to reduce the influx of
.org), the Association of Professionals in Infection Control and
these nuisance messages. Unfortunately, these filters may filter
Epidemiology, Inc. (APIC, www.apic.org), the Community and
out legitimate e-mail. List-serve-mails, in particular, may be fil-
Hospital Infection Control Association-Canada (CHICA-
tered out as "bulk e-mail." Local information systems person-
Canada, www.chica.org), the Hospital Infection Society (HIS,
nel should be consulted to determine what steps are needed to
www.his.org.uk), and the International Federation of Infection
ensure that desired e-mail reaches the recipient.
Control (IFIC, www.theific.org). Government organizations such
as the Centers for Disease Control and Prevention (CDC, www
.cdc.gov) provide a wealth of resources including guidelines,
information on specific diseases and outbreaks, and reference ONLINE SOFTWARE SERVICES
materials. State and local health departments may also have
Web sites that provide valuable information on local issues. The An increasing variety of software is available to use online. This
Web also provides easy access to information from companies re- includes general productivity software (e.g., Google Docs,
garding their products. Literature searches of the U.S. National Microsoft Office 365), e-mail (e.g., GMail, Yahoo! Mail), and
Library of Medicine's MEDLINE database can also be conducted others. These often are termed cloud applications because they
on the Web using the PubMed system (www.pubmed.gov). live in the "data cloud" of the Internet. Advantages include
One of the most exciting developments of the Web is the access from any computer with Internet access and reliable
explosion of educational opportunities. Many universities offer backups. A major disadvantage is the requirement for Internet
online classes, and it is possible to earn an advanced degree from access (although this is often overcome by local software that
a respectable institution through web-based learning. There is can sync-up with the cloud service once Internet access is again
also an abundance of noncredit, but free educational sites. One available). A more significant concern in the healthcare set-
example is the Supercourse, a Web-based set of >5,000 lectures ting is data security. The same ease of access that makes these
in epidemiology (available at www.pitt.edu/-superl/) hosted services convenient makes them potentially insecure. Hospitals
by the University of Pittsburgh. Other universities are making and universities typically have strong guidelines regarding data
their classroom materials available online for noncredit use, security. This is, in part, to ensure compliance with Federal reg-
for example Coursera (coursera.org) sponsored by Stanford, ulations, such as the Healthcare Insurance Portability and Pri-
and edX (www.edX.org) sponsored by Massachusetts Institute vacy Act (HIPAA) privacy and security rules. Guidance should
of technology (MIT) and Harvard. Besides universities, other be sought before using online services for any data that might
start-up companies offer similar classes, bringing in some of the be sensitive.
best university professors from around the world to do indi-
vidual courses (e.g., Udacity [www.udacity.com]).
GENERAL STATISTICAL SOFfWARE
Some hospitals and other organizations block or severely
limit access of employees to the Web. Healthcare epidemiol- For more extensive analysis than can be done with a spread-
ogy and infection prevention programs can make a strong ar- sheet, a healthcare epidemiologist could use general-purpose
gument for having relatively unfettered Web access to do their statistical software. A wide range of programs exists, from
jobs correctly. This typically requires going through a formal basic statistical packages included with some statistics texts
request process. to expensive, very complex programs that can perform even
114 Section I • General ConsideratiOfiS of Hospital Infectiuns
the most esoteric analysis. Widely used statistics packages in- quite sophisticated systems for healthcare epidemiology-data
clude SAS, SPSS, and Stata. Many other very capable com- gathering and analysis.
mercial programs are available. R (www.r-project.org) is an
open-source general-purpose statistical package. EpiTools
EpiDstll
(available from cran.r-project.org/web/packages/epitools/
index.html) is a set of tools for use with the R statistical EpiData (www.epidata.dk) started as a Windows-friendly data
package designed to add functions of use to epidemiolo- entry program for the older MS-DOS versions of Epi Info. This
gists. Although some of these programs allow for some form program has now become EpiData Entry. It enables the user
of direct data entry, they really are designed to import data to design data entry screens and then enter and manage data.
that was entered using another program (e.g., a database or EpiData Entry supports double data entry. Once entered, the
spreadsheet). Thus, using these programs for routine health- data can be exported in a variety of formats for additional anal-
care epidemiology use takes some effort. A user who is facile ysis. This includes export into SAS, SPSS, and Stata formats. As
with a given program may choose to do basic analyses in that such, Epillata Entry is a good companion program to a general
program. For the most part, these statistical programs are statistical package to provide the data entry and management
overkill for most healthcare epidemiology programs and are functions the statistical programs lack.
used primarily in research settings or by facilities that have EpiData Analysis is a newer program released in the fall
dedicated statistical analysts. of 2005. It provides additional data management functions
beyond those offered by EpiData Entry. It also provides some
basic descriptive statistical analysis and graphical functions, in-
GENERAL EPIDEMIOWGY SOFIWARE
cluding statistical process control (SPC) charts. Although on-
Some programs occupy a middle ground between the general going active development was not apparent as of mid-2012, it
statistical software packages and more fully developed surveil- remains a solid option for some users.
lance programs. They provide more support for data entry and
management than general-purpose statistical programs, while
Other Softwsre sntl Resources
providing more flexible statistical analysis than most specialty in-
fection prevention/healthcare-epidemiology software packages. Sometimes an epidemiologist just needs to do a quick calcula-
The primary downside is the considerable work that would be tion, such as a 2 X 2 table or a sample size calculation. Such a
necessary to set up specific functionality that comes "ready-made• simple task can actually be tedious to do in a full-fledged statis-
with healthcare epidemiology specific software. The benefit is the tical package. For this purpose, Epi Info has a StatCalc module
ability to design in the specific functionality the user desires. that is designed for such quick calculations. A similar program
is EpiCalc 2000, written by Mark Myatt (www.brixtonhealth
.com; this Web site also contains links to a wide variety of other
Bpi Info
programs that may be of use to healthcare epidemiologists).
Epi Info (www.cdc.gov/epiinfo/) is a program designed and For those with ready access to the Internet, the OpenEpi
distributed free by the CDC. Early versions of the program project (www.openepi.com) provides a wealth of epidemiology
were designed to run on Microsoft MS-DOS to assist CDC analysis tools available in any Web browser.
Epidemiologic Intelligence Service (EIS) Officers in inves- Many more software packages that are of use to healthcare
tigating outbreaks. It was steadily upgraded, and in the late epidemiologists exist than can be described here. Many of the
1990s, a version for Microsoft Windows was finally released. Web pages mentioned provide links to additional resources.
Initially named "Epi Info 2000; to distinguish it from the A source of many links for statistical analysis is statpages.org.
MS-DOS version, the name has subsequently been simplified A quick search using an Internet search engine can yield a wide
to "Epi Info" again. Development has made this an increas- variety of additional options.
ingly sophisticated product.
Epi Info does not generate specific reports or graphs de--
Commercisl Infection Prnention Softwsre
signed for healthcare epidemiologists. Rather, it is a collection
of tools that can be used in a wide variety of ways, including col- A number of software packages have been designed specifically
lecting and analyzing epidemiologic data. Functions are avail- for healthcare epidemiology programs. Such software is avail-
able to design data entry screens. Once designed, data can be able from a number of vendors. These software packages allow
entered, stored, and retrieved using the program. Internal data the user to enter surveillance data (both denominator and nu-
are stored in a relational database, which alloW!I for sophisti- merator data) or gather data directly from electronic sources.
cated data storage, if that is needed. Double data entry (see later They will then generate reports and graphs on rates; some of
"Data Entry" section) for ensuring data integrity is supported. these programs include the ability to compare a facility's rates
Epi Info provides an extensive range of statistical analysis with benchmarks from the CDC's National Healthcare Safety
tools. Analysis is not limited to data entered and stored using Network (NHSN) , and increasingly they have the ability to sub-
the software. The program can import and analyze data that mit data to NHSN as well.
have been stored in a number of database and spreadsheet for- The advantage of these specialized infection control (IC)/
mats. Results can also be displayed in a variety of graphical forhealthcare epidemiology software packages is that they are de--
mats. Advanced statistical analysis, including logistic regression signed with the needs of an infection preventionist (IP)/health-
and Kaplan-Meier survival analysis, is available. care epidemiologist in mind. Although they are somewhat
In addition to statistical analysis, Epi Info contains a module configurable, they require minimal setup to generate useful
for mapping of data using geographic information system (GIS) information. This narrow specialization is also their downside;
standards. Overall, Epi Info provides a framework for developing if a user needs a specific functionality that is not included in the
package, the user must use other software. Vendors are eager is preferred to a second internal drive so that an internal com-
to hear what features their users would like to see, but a feature ponent failure (e.g., a short circuit in the power supply) does
is typically added only if there is substantial interest A wide va- not damage both drives simultaneously. For networked comput-
riety of options are available, and the features offered by each ers, storage space maybe available on their local network; this
program continually increase. Each program may have features provides a good alternative to an external hard drive. Online
not offered by any of the others, and are increasingly being inte- ("cloud") backup services are also available. Before using one of
grated into suites of other programs, such as patient safety sur- these services, however, guidance should be sought from infor-
veillance software. Facilities interested in such software should mation technology (IT) or the hospital's compliance office to
determine what features they require, request information from ensure that the storage meets security standards (e.g., HIPAA).
each vendor, and do a careful cost-benefit analysis. Although All backup systems are useless if not used. Users should
currently these programs are independent of electronic medi- remember to take backups regularly, or even better, should
cal records (EMRs), a logical future step would be the integra- have software in place that automates the process. Copies of
tion of at least some of this functionality into EMR systems. data should be stored in a secure place; for the highest level
of security, this could mean an off-site location. Data stored on
network drives managed by the institutional IT department are
DATA ENTRY AND INTEGRITY
typically backed up on a daily basis.
In order to use computers for any form of data analysis, the
data must first be entered in a form that the computer can ac-
cess. For a stand-alone computer, this is typically done through ELECTRO~CSURVE~CE
keyboard entry. If entering a large amount of data (e.g., tran- FOR HEALTHCARE-ASSOCIATED
scribing information from paper data collection forms), double INFECTIONS (HAIS)
data entry can provide a higher level of assurance that the data
have been entered correctly. This entails entering every form Computers were first introduced into most hospitals in the form
into two separate copies of the same database (often done by of large mainframe computers used for financial systems; com-
two different people) and then comparing the results to ensure puters were out of reach of most healthcare epidemiologists.
that they are identical. Any discrepancies are resolved by refer- When PCs became available, they were quickly adopted for
ring back to the original data form. Not all software is capable use in healthcare epidemiology. Schifman reported in 1985 on
of allowing for double data entry, but it is a nice feature to use the use of custom software at the Tucson Veterans Administra-
to provide the highest level of data integrity. The EpiData Web tion Medical Center; microbiology data were entered by hand
site (www.epidata.dk/documentation.php) has links to a variety to generate positive culture rates by ward by site (e.g., sputum
of publications that describe additional good practices for data blood, urine), and the results for each month were compared
management to the previous 12-month average (14). The landmark Study of
With the increasing use of computers in healthcare facilities, the Efficacy oflnfection Control (SENIC) project (15) demon-
more and more data needed by the healthcare epidemiologist strated the value of surveillance in healthcare epidemiology. In
already is available in electronic form. Patient demographics addition, 1985 was the year that the first precursor program to
may be available from the admissions office, information on Epi Info was released. This convergence of the demonstrated
surgical procedures maybe available from the operating room need to do surveillance for HAis and the increased availability of
scheduling system, and so on. As noted previously, depending relatively inexpensive computers and software to assist the pro-
on what software is being used, data may need to be converted cess led to the steady integration of computers into healthcare
into a specific format to be imported. A variety of de facto stan- epidemiology programs. Because of the increasing availability
dards exist (e.g., many programs can export and import data in of PCs in most IC departments and the enormous variability of
Microsoft Excel format). If data are not already available in a mainframe computers in hospitals, the CDC's National Noso-
format that can be used directly, frequently the hospital's infor- comial Infections Surveillance (NNIS) system (now NHSN)
mation systems department can write a program to convert the developed PC-based HAl data entry and analysis software for
information into a useable format. As EMRs (6) become more PCs in the early 1980s. The CDC NNIS/NHSN software systems
commonly used (7), even more information may be available to have evolved as the capability of PCs has expanded with the
the healthcare epidemiologist. It will be essential to work with need for additional HAl surveillance data. Most of the PC/
the appropriate committees as an EMR is being implemented at software use has been to assist traditional methods of health-
an institution to ensure that important data (e.g., presence of a care epidemiology; this can be termed "electronically-assisted
central venous catheter on a given day) are being captured in a surveillance." With the increasing availability of comprehen-
manner that allows for easy data querying and aggregation (8,9). sive electronic clinical data, along with increases in computer
For items that are not available electronically, a variety of power, fully automated electronic surveillance is beginning to
methods beyond simple paper notes have been used to colbe implemented. This does not require the intervention of an
lect the information. As technology has progressed, these have IP or healthcare epidemiologist to determine whether a patient
ranged from scanned in forms (10) to small personal digital meets an HAl surveillance definition.
assistants (PDAs) (11,12), to tablet computers (13).
Once data have been entered by whatever means, provisions
ELECTRONICALLY-ASSISTED SURVEILLANCE
must be made to prevent data loss. An external means ofbacking
up data should be considered essential. A variety of options are For most healthcare facilities, PCs are used to perform retro-
available, including external hard drives, external tape drives spective analysis on data that have been entered. Some amount
(less common as hard drive prices have fallen), and recordable of data may be pulled from a variety of electronic sources, but
CDs or DVDs. If using a second hard drive, an external drive typically, all of this information constitutes "denominator data"
for analysis. "Numerator data" (i.e., which patients actually benefits from having access to electronic data on central line
have HAis) are typically determined by manual surveillance use, and so is able to evaluate for CLA-BSis. The system can
performed by IPs. Computers may aid their data entry, but exclude 68% of positive blood cultures of ICU patients from
much of the work of detection and recording is still manual. review, with a negative predictive value of 99.2%. Thus, the IPs
Although this remains largely true today, efforts continue to can focus on a much smaller number of patients to determine
shift more of this work onto computers. Such shifts require that whether they meet NHSN criteria for a CLA-BSI (32).
a substantial amount of data be readily available electronically. Efforts have been made to automate a significant portion
At the most basic level, computers can provide surveillance of the effort required for surveillance of other HAis besides
assistance that is relatively simple but can provide considerable CLA-BSI. Surveillance systems with a high negative predictive
time savings. One such basic assistance is simple aggregation of value for catheter-associated urinary tract infections (CA-UTis)
microbiology data (16). Many hospitals provide such reports have been studied (3g,34). Studies in Boston evaluated the use
to their healthcare epidemiology departments; these reports of hospital discharge diagnoses combined with inpatient antibi-
are generated by the hospital's laboratory systems and either otic administration data to detect surgical site infections (SSis)
printed or sent electronically. after cesarean section (35). A combination of this information
Some hospitals have been able to provide even more com- had a positive predictive value of94% with a sensitivity of 59%.
puter assistance. The Latter Day Saints (LDS) hospital in Salt This method was later validated for coronary artery bypass graft
Lake City, Utah, developed the Health Evaluation through Log- (CABG) surgery at hospitals in Boston and Israel (36) and at a
ical Processing (HELP) system, a ground-breaking computer number of US hospitals for CABG, breast, and cesarean section
support system for clinicians. By applying a variety of rules to surgeries (37). Overall sensitivities in the latter study ranged
available information (e.g., microbiology data, patient date of from 93% to 97%, but positive predictive values were only 20%
admission), the HELP system could detect patients likely to to 42%. Predictive value was particularly sensitive to antibiotic
have an HAl (17-19). At Bames Hospital (now Barnes-Jewish prescribing practices at the various hospitals. As with some of
Hospital) in St. Louis, Missouri, the GermWatcher system was the BSI approaches mentioned, such methods may still be very
developed in the early 1990s (20-22). Positive microbiology valuable by allowing IPs to narrow their focus to the patients
cultures are evaluated by an expert system that ranks them as most likely to really have an SSI, thus making surveillance more
likely contaminants or not and prioritizes cultures for IPs (e.g., efficient. The Boston investigators also have reported using
a sputum culture growing an acid fast bacteria is higher priority similar surveillance methods to detect SSis in patients after hos-
than a urine culture with E. colt) . This assistance allows the IPs pital discharge by evaluating health maintenance organization
to focus on patients most likely to have significant HAis and (HMO) data (38). Given the difficulty of post-discharge surveil-
not have to spend time scrutinizing all positive cultures. A data lance, such methods hold some promise, but may be limited
warehouse developed in Chicago that included data from by the availability of records. Another approach to assist (but
Cook County Hospital and two smaller hospitals was recently not fully automate), SSI surveillance was instituted in a Paris
described (2g). One goal in developing this system was to facili- hospital where computer surveillance for positive cultures from
tate similar computer-assisted surveillance. Other facilities have surgical patients was used as a screen (39).
developed similar systems (24,25). In addition to HAl surveillance, hospital computers can assist
In addition to the systems that have been developed at large with other healthcare epidemiology tasks. Many hospitals have
academic medical centers as described, similar capabilities are systems in place in which patients who are known to be carriers
now available to hospitals that do not have the expertise to of antimicrobial-resistant organisms, such as methicillin resis-
build their own systems. Some commercial healthcare epidemi- tant Staphylococcus aumus (MRSA) , can be flagged in a hospital
ology software has components that offer similar surveillance computer system. This flag then triggers automatic placement
assistance (26-29). into appropriate isolation precautions if the patient is readmit-
Beyond simple assisted surveillance, efforts have been ted. Typically, turning such flags on and off is itself a manual
made to fully automate surveillance for HAis. Because of the task. However, some automated systems (e.g., GermWatcher
requirement for a clear signal (in this case, a positive culture) and others) can highlight patients who have positive cultures
healthcare-associated bloodstream infections (BSis) have been with such organisms, making it less likely that they will be
a good target for early investigation. A retrospective evalu- missed and hence not flagged. Implementation of such a sys-
ation of blood cultures from six hospitals in the Boston area tem in Geneva, Switzerland, resulted in significantly more pa-
suggested that a simple system of rules applied to microbiol- tients being isolated at the time of admission (40). An even
ogy data alone had a sensitivity of 64% and a specificity of98% more automated system for ensuring that patients are placed in
(30), A similar study using data from neonatal intensive care appropriate isolation was described at Columbia-Presbyterian
units (ICUs) in six New York City hospitals reported a sensi- Medical Center. Automated computer protocols evaluated
tivity of 79% and a specificity of 96% (31), In both instances, chest radiograph reports using a natural-language processor.
the negative predictive value was much better than the positive The automated system also evaluated patients for evidence of
predictive value. Both studies were also limited in that they in- immunocompromised status by evaluating laboratory data for
cluded all BSis, notjust central line-associated BSis (CLA-BSis). evidence of human immunodeficiency virus (HIV) infection
However, these studies suggested the possibility that although and pharmacy data for use of medications used only to treat
neither system would be capable of fully automated BSI sur- HIV. This automated system was able to identify patients who
veillance, both could eliminate patients not likely to have true should have been on isolation, but were not ( 41) .
BSis, thus aiding IPs in selecting patients whose charts should Not all attempts to use computers to assist or automate HAl
be reviewed. At Barnes-jewish Hospital, a rule-based surveil- surveillance have been successful. In particular, the use of elec-
lance system has been put into place that focuses on having a tronic hospital claims data alone has been shown to correlate
high negative predictive value for true infection. This system poorly with true HAis (42-44) .
FULLY ELECTRONIC SURVEILLANCE 6. Did RS, Steen EB, Detmer DE, edl. 2M ~Ba.Jed l'riiWnt Record: "" EmnMl 'll<lmo~
ot:J for Hltlltl> c-. Rev. ed. W31hlngton, DC: National Academy Prell; 1997.
7. The Oflice of the National Coordinator for Health Information Thchnology (ONC). cy>dafl
Beyond simple assisted surveillance, efforts have been made
on/NMopti<m ofHitllti>In.{onltlmon 1ielanolot:! GM.J.U/4UdE/fartii<IFGdlil<l#INEIII<hmi< U11
to fully automate surveillance for HAis. Because of the re- GM.~ ofHltlltl> Infor-titm. A &port to Ctmgms. Acce11edjanuary 2012. Available at:
quirement for a clear signal (in this case, a positive culture) http:/ /healthiLhh&.gov/portal/oerver.pt/gatcway/PTARGS_0_0_4585_1259_15610_45/
http%11B/wcipubcontcnt/pub1Uh/onc/public_communilieo/p_t/reoourceo_and__public_
healthcare-associated BSis have been a good target for early offain/reporu/ reporu_ponlet/files/january201Lupdate_on__hit_adoption....report_to_
investigation. Some early efforts were discussed above (30,31). congrcli!l.pdf
A study in two Chicago hospitals evaluated a variety of rule-based 8. Cla11en DC, Burke JP. The oompute!'bued patient record: the role of the hoopital epide-
miologi.ot. Inftt:t Ctmtrol Hasp .ey,utm.iol. 1995;16:'729-756.
approaches to BSI, compared with IP review, compared with 9. Wright MO, Filher A. john M, et a!. The electronic medical record u a tool for infec-
"gold standard" review by physician investigators ( 45). The best lion surveillance: IIUCCcaaful automation of d.cYicoxlap. A"' ] brftt:t GmlnJl. 2009;~7:
564--370.
computer algorithm had a sensitivity of 81% and a specificity of 10. Thompson IM. Automated entry of no1ocomial infection sUI'l'eillao.ce data: we of an opti.-
72%. However, the temporal trends of the computer algorithm calocanrrlng't'f't=l. JHasplnfts;t.1999;45(ouppl) :S275-S278.
over time tended to track well with the reference standard. This 11. Farley JE, Srinivasan A. Richard• A. et a!. Hlwdheld cmnputcr rurveilhwce: ahoc-kather
epidemiology in the "palm" of your hand. A•JInfra Conml. 2005;311:444-449.
suggests that although the automated method may not give a 12. Mwphy DM. From c:xpcrt data collector> to intcn<:ntioni.ots: chaugiojJ the focus for infec-
"true~ rate, it may be possible to follow trends over time without lion control profeollional.t. A•J Infod Cont>ol. 2002;30:1W-1ll2.
any active surveillance by an IP. If rates become unexpectedly 13. Wllcox AB, Gallagher KD, Boden-Aibala B, et a!. Rac:an:h data colli:ctiou method>: from
paper to tablet cmnputen. Morl c- 2012;50(auppl) :S6lj...{i73.
high, a specific investigation could be launched. The Chicago 14. Schifman RB, Palmer RA. Surveillance of nooocomial. infection• by computer malylia of
study was also limited by lack of access to electronically available pooitive cult>= rata.I am Mictof1ioL 1985;21 :49.!1-495.
15. Haley KW, Culver DH, White JW, et aL The eflicacy of infection ourveillance and con-
central line information. Work done in St. Louis did have access
trol program• in preventing noiiOCOIIIw infectiom in US hoopitalo. A"' ] ~
to such central line use data electronically. A rule-based surveil- 1985;121 :182-205.
lance system designed to evaluate for CLA-BSI outside of the 16. Burken MI, Zaman M, Smith Jl]. Semi-tomatcd infection controlourveillaru;e in a Veter-
an•' AdminiJtration medical center. Inftet Conhul HOJP ~ 1990;11:4Ja-.12.
ICU (since NHSH surveillance was already in place within the 17. Evam KS, Gardner RM, Buoh AR, et a!. Development of a computcriud in!ectiOUJ di.oeaae
ICUs) was evaluated. The best-performing rule set had an over- monitor (CIDM). eo...pvtBimMtliW. 1985;18:10~115.
all sensitivity of 95.2%, specificity of 97.5%, positive predictive 18. E-.am KS, Lancn RA, Burke JP, eta!. Computer mrveilhwce ofhoopital"""juired iufectiona
and antibiotic use.]AMA. 1986;256:1007-1011.
value of90%, and negative predictive value of99.2% compared 19. Burke JP, Claucn DC, Pcatotnik SL, eta!. The HELP 't'f'lcltl311d its application to infection
with intensive manual surveillance (46). Like the Chicago study, control.] Hasp Infoct. 1991;18(ouppl A) :424-451.
20. Kahn MG, Steib SA, Fraser~. et a!. An c:xpcrt 't'f'tcltl for cultun>bued infection control
the system showed a good correlation with manual surveillance
omveilhwce. ln: Proceedinga from the Annual Sympooium on Computer Applicationa in
rates over time. This system, subsequently named NICER (for Medical Can:; 1993;171-175.
Non-ICU CLA-BSI Electronic Rates), has been implemented 21. Kahn MG, Steib SA, Duoaga.n WC, et al. Monitoring expert 't'f'lem performance uaing
continuous user feedbadr.. JAaMrtlinforaA.uoc. 1996;3:216-225.
for surveillance in all BJC HealthCare hospitals. 22. Kahn MG, Bailey TC, Steib SA, et al. Statio tical pmceoo control methodo for expert 't'f'lem
One concern with fully electronic surveillance is that a performance monitoring.] A"' Md.Inj'rna&.oc. 1996;~:256-269.
trained healthcare epidemiologist or IP does not evaluate each 2ll. W'wriew.l<i MF, KieozkowU.i P, ZagorU.i BM, et a!. Development of a clinical data ware-
howe for hospital iufection control. JAm Mm lnj'rna&.oc. 2003;10:454-462.
patient to determine whether there may be another etiology 24. Pokorny L, Itoma A. Martin-Baranera M, et aL Automatic detcc1ion of patiena with nooo-
(i.e., whether the blood culture is secondary to another infec- comial infection by a computer-bued rurveilhwce l)'ltcm: a validation amdy in a general
hotpital Inftet Conhul Hrnp ~L 2006;27:500-503.
tion). While this is a limitation, the advantage is a considerable 25. Leth RA. Moller JK. Surveillance ofhoopital-acquired infection• hued on electronic hoapi-
increase in consistency in the application of the definitions tal regi.ttriet.J Hasp Infra. 2006;62:71-79.
(47). This may be a distinct advantage in an era of increased 26. Bl'OIIette SE, Sprague AP, Hardin JM, et aL Asaociation ruleo and data mirrlng in ho•
pita! infcclion control and public health ourveillance.] Aa M.J InjiJm A..... 1998;5:
public reporting of HAis. 37~381.
27. Hymel PA, Brouettc SE. Dam mining-eDhanced infection control ouncillance: ocn>i.ti"'
ity and opecificity. In: Abotract from the Society for Healthcare Epidemiology of America
(SHEA) Annual Meeting; Thronto, Canada; 2001.
CONCLUSIONS 28. Wright MO, Perenceoi.ch EN, Novak C, et aL Preliminary a11ewnent of an auto-
mated mrvcillance 't'f'tcltl for infection control. Inftet Cantrol Hasp ~ 2004;25:
Computers are ubiquitous in modem life, including in health- 112!>-532.
29. Stcinzor N, PickettS. APIC invcotigatco rurvcillance tcclwology. APICN<ws. 2005;24:12-19.
care epidemiology. As computers become more powerful and 50. Yokoe DS, Andenonj, Chamben R, et al. Simplified rurveillance for no&ocomial blood-
as more information becomes available electronically, health- stream infectioDS. lnftt:t Cantrol HOJP ~ 1998;19:657-660.
51. Graham PL m, San Gabriel P, Lutwick S, et aL Validation of a multicenter computer-hued
care epidemiologists can anticipate an even greater use of auto- aurvcillaucc l)'ltcnJ. for hompital-acquired blo odatreaib. infcctio lD in neonatal intenllive ~:arc
mated tools. Still, computers are only tools. At their best, they department>. Am]brftt:t Ctmlrol. 2004;li2:232-2M.
can perform the tedious portions of surveillance and calcula- 52. Woel!je KF, Butler AM, Gorlo AJ, et a!. Automated ourveillance for central line-
aooociated bloodotream iufection in intenoive care unia. Info<t Control Hasp ~
tions for us, but it will still take a person to interpret the data 2008;29:842-a46.
and use it to improve patient care. 55. Gori.o AJ, Nihill DM, Ruhland MJ, eta!. Automated rurvcillance for cathetcr-uoociated uri-
nary tract infectiona. ln: Proceedingo from the fifth DecennDllntemational Conference
on Healthcare Aooociated Infecliona2010; Mareh, 2010; Atlanta, GA.
M. ChoudhuriJA, Pergamit RF, ChanJD, eta!. An electronic catheter~uociated urinary tract
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ll Michael A. P£aller and Daniel J. Diekema
The Role of the Laboratory in Prevention

of Healthcare-Associated Infections
The work required of the clinical microbiology laboratory and to prevent and control HAis effectively (10,11). Given con·
of the hospital infection prevention program (IPP) bas become tinuow changes in HAl pathogens, antimicrobial resistance,
increasingly complex, demanding, and intertwined as we enter medical care, and healthcare delivery, staff members from the
the second decade of the new century. To do their jobs effec- laboratory and from the IPP must work to ensure collabora-
tively and efficiently, these two groups must work as a team, us- tion and open communication. The relationship between the
ing the expertise from each discipline to improve patient care microbiology laboratory, the IPP, and increasingly the antibi·
and safety. A:s alwaf3, the microbiology laboratory must be able otic stewardship program (12-15), is critical to the ruccess of
to detect and identify microorganisDU and determine their an- these important efforts to improve patient care, control costs,
1imicrobialsu.sceptibility profiles so that clinicians can diagnose and preserve options for effective antimicrobial therapy. In this
and treat established infections and the IPP can monitor and chapter, we discuss the microbiology laboratory's role in this
prevent infections and exporures in bealthcare settings. essential collaboration.
The ever-increasing complexity and sophistication of mod-
em medical care pose& challenges for the IPP. The need for
accurate and rapid diagnosis, identification, and antimicrobial PARTICIPATION IN HOSPITAL-WIDE
resistance detection is more important than ever. New technoJ..
ogy, developed to detect and characterize microorganisms, not
INFECTION PREVENTION ACTIVITIES
only significantly improves the laboratory's ability to keep up
RELATIONSHIP OF THE LABORATORY TO
with the ever-changing array of bealtbcare-associated infec-
THE INFECI'ION P.REVENTION COMMI'ITBE
tion (HAl) pathogens, but also challenge& laboratory and IPP
personnel to we this technology in the most appropriate and The clinical microbiologist (or microbiology supervisor in an
cost-effective manner (1-6). In particular, molecular and pro- institution that does not have a doctoral-level microbiologist) is
teomic technologies have enhanced the speed, accuracy, and an integral part of the IPP and thus mwt be an active member
sensitivity of detection methods and have allowed the labora· of the infection prevention committee. Becawe the infection
tory to identify organisDU that were previowly unknown or prevention committee frequently bases its decisions on the re-
"cryptic" as well as those that do not grow readily in culture sults of microbiological testa, the clinical microbiologist must
(S,5,6). Molecular and proteomic techniques also enable the guide the committee in integrating culture results and select-
microbiologist to identify antimicrobial resistance genes and to ing appropriate microbiologic approaches to solve specific
perform strain typing of hospital organisms, thereby facilitating problems. The microbiology laboratory can benefit if the IPP
studies of HAl pathogen transmission (7-9). staff understand the routine processes in microbiology (e.g.,
In addition to performing their traditional role& in the clini- timelines for the processing of blood, wound, or urine cultures
cal diagnostic laboratory, laboratory personnel must perform and related techniques) (16). Specimen processing timelines
additional tasks that are critically important in supporting in· enable IPP staff to set expectations of turnaround time& for spe-
fection prevention activities: (a) participate in hospital-wide IPP cific results and time constraints of microbiology test services,
activities, (b) recover and accurately identify responsible organ· thus minimizing premature phone calls to the laboratory re-
isms to the extent that is needed in an outbreak investigation, questing culture information. Conversely, while serving on the
(c) determine the antimicrobial susceptibility profile of HAl committee, the microbiologist will learn about the problems
pathogens, (d) report in a timely fashion laboratory data rel- confronting the IPP and thw will be better able to organize the
evant to infection surveillance and prevention, (e) provide ad· laboratory's response to such problems.
ditional studies, as needed, to establish the genetic relatedness The microbiologist must educate the committee about sev-
of organisms, (f) provide, on occasion, microbiologic studies eral important issues. Becawe most IPP personnel have not
of the hospital environment and personnel, and (g) teach IPP worked in laboratories, the microbiologist should ensure that
personnel how to use laboratory resources appropriately during these individuals understand basic microbiology principles and
surveillance of HAis and during epidemiologic inve&tigations. techniques. The microbiologist must also explain the advan-
The clinical microbiologist (doctoral-level microbiologist, tages and limitations, the scope and accuracy (i.e., sensitivity
pathologist, microbiology supervisor, or designated laboratory and specificity), and the costs of microbiologic methods wed
personnel), hospital epidemiologist (or infectiow disease eli· to detect, identify, and assess the antimicrobial susceptibility of
nician) and infection preventionist (lP) mwt work as a team HAl pathogens.
119
In addition, the microbiologist should inform the commit- the clinical microbiology laboratory as an integral component
tee about changes in methods, reagents, or instrumentation of the IPP may help healthcare administrators understand the
that may substantially affect the laboratory's ability to detect importance of adequate funding for the clinical microbiology
and characterize HAl pathogens. These include changes in laboratory, particularly as the laboratory's activities increase to
the sensitivity and specificity of diagnostic methods, changes meet infection prevention priorities. Effective prevention saves
in antimicrobial susceptibility testing interpretive criteria, and not only lives but money, and these savings are rarely credited to
taxonomic changes that may create confusion. An example of the clinical microbiology laboratory (21).
changes in testing and reporting criteria that directly affect
infection prevention efforts is the recent change in the inter-
pretive breakpoints for the Enterobacteriaceae and cepha- ACCURATE IDENTIFICATION
losporins and carbapenems enacted by both the Clinical and AND SUSCEPTIBILITY TESTING
Laboratory Standards Institute (CLSI) (17) and the European OF ORGANISMS INVOLVED IN
Committee on Antimicrobial Susceptibility Testing (EUCAST) HEALTHCARE-ASSOCIATED
(18). The new (lower) breakpoints are intended to obviate the INFECfiON
need for extended-spectrum P.lactamase (ESBL) confirmatory
testing or modified Hodge testing (confirmation of carbapen- In many instances, the results of routine cultures are the first
emase) for clinical use. The result of this change in testing and indication that patients have an HAl. For most epidemiologic
interpretive criteria has been the loss of epidemiologic data for investigations, the routine procedures performed in the mi-
some IPPs that have come to rely on these confirmatory tests crobiology laboratory are satisfactory. In selected instances,
to guide prevention activities (19), and also has led to an in- however, certain laboratory services and expertise that extend
crease in the number of isolates characterized as resistant to beyond routine practice and knowledge may be necessary.
cephalosporins and carbapenems, and therefore potentially Regardless of which tests are performed, the laboratory must
multidrug-resistant (MDR), with major implications for infec- perform the tests quickly, accurately, and reproducibly to
tion prevention (20-23). One institution recently reported ensure that the IPP can identify and assess HAis properly.
that this change resulted in a 35% increase in the number of The spectrum of organisms causing HAis is ever-changing
MDR-Gram-negative rods (GNR) identified and a concomitant and varies from region to region and even from hospital to
increase in the hospitals' use of contact precautions (20). hospital (Table 11.1). From the 1970s through 2000, the spec-
Members of the IPP must communicate with each other to trum of HAl pathogens shifted from GNR to Gram-positive or-
accomplish their goals. Communication may be enhanced if ganisms and Candida emerged as a major problem (25,26). The
the IPP staff regularly round in the laboratory to ask questions, incidence of HAis caused by staphylococci and enterococci in-
review microbiologic and molecular testing results, and discuss creased, as these organisms became progressively more resistant
current problems and views. Likewise, the microbiology staff to antimicrobial agents, and IPP efforts focused on methicillin-
should attend conferences at which IPP personnel discuss epi- resistant Staphylococcus aumt.S (MRSA) and vancomycin-resistant
demiologic principles and contemporary topics. Unfortunately, enterococci (VRE) (27,28). Notably, infections due to Candida
several ongoing trends challenge these valuable personal in- spp. steadily increased during this time (29) and were found
teractions between the micro biology and IPP personnel (21) . to exceed those due to MRSA and VRE among intensive care
Consolidation of clinical microbiology laboratory services, off- unit (ICU) patients in the Extended Prevalence of Infection in
site moves of microbiology laboratories, and total reliance on Intensive Care (EPIC II) survey in 2007 (Table 11.1) (25,30).
the electronic medical records to the exclusion of first-hand The improvement in methods to detect and identifY viruses also
observation (e.g., review of culture plates or Gram stains) too highlighted these organisms as frequent HAl agents (31) .
often keep clinicians and infection prevention personnel out of More recently, MDR-GNRs have become increasingly
the microbiology laboratory and keep microbiologists confined prevalent in many hospitals (13,14,32-37). These include
to the laboratory. ESBL- and carbapenemase-producing Enterobacteriaceae
and multiple-or pan-drug-resistant nonfermenters such as
P. aeruginosa, A. baumanni~ and Stenotroplwmonas maltophilia
BUDGETARY CONSIDERATIONS
(Table 11.2) (13,33,36). The data from the EPIC II study show
Given that most laboratories have limited financial and staff that the mcyority (62.2%) of infections in ICU patients were due
resources, the microbiologist must help the IPP staff and the com- to Gram-negative organisms in 2007 with 40% to 48% of all in-
mittee understand the costs and appropriate indications for the fections in Eastern European, Latin American, and Asian ICUs
microbiologic tests most commonly used to support epidemio- caused by P. aeruginosa and Acinetobacter spp. alone (Table 11.1) .
logic investigations, so that these limited resources are used effec- The ESKAPE pathogens (E. faecium, S. aureus, K ~'11UY11-iae,
tively. Costs for laboratory procedures that are not related directly A. baumannii, P. aeruginosa, and Enterobacter spp.) are respon-
to the care of patients (e.g., bacteriologic sampling of personnel sible for most HAis in the modem hospital (Table 11.2) (36).
or the environment) should be borne by a budget separate from The data from the EPIC II study indicate that the ESKAPE
the laboratory. To facilitate all of the microbiologic activities n~ pathogens are involved in >70% of infections in ICUs
cessitated by an outbreak, the laboratory (or the hospital epidemi- (Table 11.1) (25). This group of organisms is at the heart of the
ologist or the infection prevention committee, depending on the global antimicrobial resistance problem, the members of which
hospitals' organizational structure) should have a contingency are often MDR by virtue of multiple acquired and transmissible
fund to enable personnel, materials, and space to be temporarily resistance factors (Table 11.2).
assigned to support the outbreak investigation (11,24). An investi- Rapid and accurate identification of these key HAl patho-
gation of an outbreak should not be financed by charging individ- gens, including their resistance mechanisms, is a key issue in
ual patients for cultures taken during the investigation. Viewing both optimal patient care and in prevention efforts (7,38) .
Chapter 11 • Thl Roll of 1M Laboratory in .Pnroention of Healthcare-Associated Infections 121
TABLE ll.l Types of Bacteria and Fungi in Culture-Positive Infccted ICU Patients According
to Geographical hgion: Epic D, 2007¥
No.(%) by Geographic regionc
OrJrmi- All WEU EEU LAM NAM oc AFR AM

Total isolates 4947 (100.0) 2678 (100.0) 357 (100.0) 719 (100.0) 457 (100.0) 204 (100.0) 54 (100.0) 478 (100.0)
GRAM-POSITIVE 2315 (46.8) 1311 (49.0) 185 (51.8) 273 (38.0) 252 (55.1) 104 (51.0 ) 27 (50.0) 163 (34.1)
s. lm1!1W" 1012 (20.5) 525 (19.6) 77 (21.6) 138 (19.2) 123 (26.9) 56 (27.5) 16 (29.6) 77 (16.1)
MRSA 507 (10.2) 233 (8.7) 37 (10.4) 79 (11.0) 80 (17.5) 19 (9 .3 ) 11 (20A) 48 (10.0)
s. epiderrnidis 535 (10.8) 301 (11.2) 43 (12.0) 67 (9.3) 56 (12.3) 17 (8.3) 8 (14.8) 43 (9.0)
s. jm#u"rTW"niae 203 (4.1) 127 (4.7) 16 (4.5) 24 (3.3) 20 (4.4) 5 (2.5 ) 3 (5.6) 8 (1. 7)
VSE 352 (7.1) 250 (9.3) 35 (9.8) 17 (2.4) 24 (5.3) 9 (4 .4) 0 17 (3.6)
VRE 186 (3.8) 113 (4.2) 16 (4.5) 15 (2.1) 22 (4.8) 10 (4 .9) 0 10 (2.1)
Other 319 (6.4) 184 (6.9) 15 (4.2) 29 (4.0) 48 (10.5) 19 (9 .3) 4 (7.4) 20 (4.2)
GRAM-NEGATIVE 3077 (62.2) 1573 (58.7) 258 (72.3) 510 (70.9) 228 (49.9) 122 (59.8) 31 (57.4) 355 (74.3)
E. coli 792 (16.0) 458 (17.1) 53 (14.8) 103 (14.3) 65 (14.2) 27 (13.2) 6 (11.1 ) 80 (16.7)
Enterobacter 345 (7.0) 184 (6.9) 29 (8.1) 62 (8.6) 37 (8.1) 7 (3.4) 4 (7.4) 22 (4.6)
KleiJsiel/4 627 (12.7) 261 (9.7) 76 (21.3) 116 (16.1) 41 (9.0) 24 (11.8) 10 (18.5) 99 (20.7)
Pseud<mwnas 984 (19.9) 458 (17.1) 103 (28.9) 189 (26.3) 59 (12.9) 30 (14.7) 8 (14.8) 137 (28.7)
Acinetobacter 435 (8.8) 149 (5.6) 61 (17.1) 99 (13.8) 17 (3.7) 9 (4.4) 8 (14.8) 92 (19.2)
Other 840 (17.0) 487 (18.2) 54 (15.1) 121 (16.8) 52 (11.4) 42 (20.6) 11 (2o.4) 73 (15.3)
ESBL 93 (1.8) 47 (1.8) 7 (2.0) 21 (2.9) 1 (0.2) 0 1 (1.9) 16 (3.3)
Anaerobes 222 (4.5) 142 (5.3) 12 (3.4) 10 (1.4) 36 (7.9) 7 (3.4) 1 (1.9) 14 (2.9)
Other bacteria 76 (1.5) 33 (1.2) 7 (2.0) 14 (1.9) 4 (0.9) 4 (2.0) 3 (5.6) 11 (2.3)
FUNGI 963 (19.5) 561 (20.9) 72 (20.2) 104 (14.5) 105 (23.0) :n (15 .2 ) 6 (11.1 ) 84 (17.6)
Candida 843 (17.0) 495 (18.5) 66 (18.5) 92 (12.8) 83 (18.2) 26 (12.7) 6 (11.1 ) 75 (15.7)
Aspergillus 70 (1.4) 44 (1.6) 1 (0.3) 5 (0.7) 12 (2.6) 3 (1.5) 0 5 (1.0)
Other 50 (1.0) 22 (0.8) 5 (1.4) 7 (1.0) 10 (2.2) 2 (1.0) 0 4 (0.8)
Parasites 34 (0.7) 18 (0.7) 2 (0.6) 6 (0.8) 3 (0.7) 2 (1.0) 0 3 (0.6)
Other organisms 192 (3.9) 122 (4.6) 9 (2.5) 15 (2.1) 22 (4.8) 8 (3.9 ) 2 (3.7) 14 (2.9)
"Data compiled from VmcentJL, Relloj, Marshall], et al. International study of the prevalence and outco mes of infection in intensive care
units. ]AMA. 2009;302:2323--2329.
6Abbreviations; AFR, Africa; EEU, Eastern Europe; EPIC II, Extended Prevalence of Infection in Intensive Care; ESBL, extended-spectrum
~-lactaiii.iUes; ICU, intensive care unit; LAM, Latin America; MRSA, methicillin-resistantS. aul"llWj NAM, North America; OC, O ceania;
VRE, vancomycin-resistant enterococci; VSE, vancomycin-auaceptible enterococci; WEU, Western Europe.
'Percentages do not necessarily equal 100, because patients may have had more than 1 type of infection or microorganism.
Whereas semi-automated and automated identification and understanding of the phylogenetic relationships among these
susceptibility testing systems are well-established in most clini- organisms and is the new standard for bacterial and fungal iden-
cal microbiology laboratories, recent improvements in some tification (3). Another excellent technique for microorganism
automated instruments have involved the expansion of their identification relies on the protein composition of a bacterial or
databases and the use of advanced technologies to decrease fungal cell using matrix-assisted laser desorption ionization-time-
time to detection, greatly improving their clinical utility. Fur- of-flight (MALDI-TOF) mass spectrometry (MS) (1,6).
thermore, a few commercial platforms have created novel
decision support software that integrates identification and
COLLECTION AND TRANSPORT OF SPECIMENS
susceptibility test results with surveillance strategies for antimi-
crobial resistance and guidelines for therapy (39). Specimen collection, transport, and handling must be of suf-
In an effort to supplement the information supplied by Gram- ficient high quality to provide valid data (42-44). Specimens
stain of cultures and clinical material, novel culture-independent that are not collected or transported properly may give inac-
technologies have emerged to reduce the time required for curate results, even when handled as well as possible once they
identification of microorganisms, including peptide nucleic acid reach the laboratory. In turn, these inaccurate results may lead
(PNA), fluorescence in situ hybridization (F1SH), polymerase to improper clinical decisions by physicians, unnecessary la-
chain reaction (PCR), and rRNA probe matrices (40,41). Nu- bor by laboratory and IPP personnel, and unnecessary patient
cleic acid-based platforms now have been incorporated into the charges. Many tests may have very specific requirements for
routine clinical laboratory to identify microorganisms by DNA specimen type, collection, and transport to the laboratory. This
target sequencing, to detect a pathogen by real-time amplifica- is especially true for most molecular tests (45).
tion techniques, or to simultaneously detect multiple pathogens Many HAl pathogens (e.g., coagulase-negative staphy-
by arrays (2) (Tables 11.3 and 11.4). Nucleic acid sequence lococci, Candida) also commonly colonize patients' skin or
analysis of bacterial and fungal rRNA genes has expanded our mucous membranes and can easily contaminate cultures if
TABLE 11.2 Antimicrobial Rmstancc Problems Associated with the ESKAPB Pathogens•
Pathogen Anthnicrobial Agent Resistance Mechanisms
Enterococcw faecium Ampicillin Mutation in Pbp5
Aminoglycosides Enzymatic modification
Vancomycin Altered peptidoglycan cros!l-link target
Staphyf«occus auJeUS Aminoglycosides Enzymatic modification
Fluoroquinolones Mutation in gyrA leading to reduced binding to active site; effiux.
Linezolid Mutation in rRNA leading to reduced binding to active site.
Penicillin P-lactamase
Oxacillin Altered PBP (PBP2a)
Sulfonamides Mutation or recombination of genes encoding DHPS
Tetracyclines Efllux
Trimethoprim Mutations in gene encoding DHFR
Vancomycin Altered peptidoglycan cros!l-link target
P-lactams Amp C enzymes
ESBL
Altered/decreased porins
Efllux
Carbapenems Metall~lactamases
KPC-type p..lactamases
Altered/ decreased porins
Fluoroquinolones Altered target, protection from DNA binding, eftlux
Acinetobacter baumannii Aminoglycosides Enzymatic modification
p..lactams Numerous ~lactamases
OXA carbapenemases
Porin alteration
Fluoroquinolones Altered target
Aminoglycosides Changes in outer membrane permeability, effiux, enzymatic
modification
~lactams Chromosomal cephalosporinase
Efllux
Enterobacter spp. ~lactams AmpC ~lactamase
Efllux
"Abbreviations: DHFR, dihydrofolate reductase; DHPS, dihydropteroate synthetase; ESBL, extended-spectrum P-lactamase;
PBP, penicillin binding protein.
specimens are not collected or handled properly. If contami- of specimen collection, delay in transporting specimens to the
nants are considered to be infecting organisms and result in a laboratory, or delay in culturing them.
patient meeting the HAl definition, HAl rates may be inflated Specimen collection and handling should be assessed regu-
through misclassification (16,46). larly to detect and correct such problems; the frequency with
The laboratory must monitor specimen quality carefully and which probable contaminants are isolated from clinical speci-
also work closely with inpatient and ambulatory care units to mens can be a measure of the quality of specimen collection
develop and enforce strict criteria for acceptable collection in a specific hospital area. Addressing these issues is another
and handling of clinical specimens. This is necessary to ensure area where laboratory and IPP personnel can work together to
that the laboratory information presented to the clinician and improve results. Bringing such data to a multidisciplinary level
the IPP reflects organisms that are actually associated with the by involving IPP personnel has the potential to decrease con-
patients' site of culture rather than contaminants. tamination rates (17). For example, determining the frequency
Certain laboratory findings suggest specific handling er- of urine specimens with characteristics suggestive of contami-
rors (47). For example, a persistentfuilure to isolate organisms nation can identify patient care units that may require further
from patient specimens with pathogens seen on Gram-stain evaluation and, if necessary, in-service education programs
suggests inadequate transport media, delay or inappropriate re- conducted by laboratory or IPP personnel.
frigeration of specimens in transit, errors in staining, contami- Many hospitals also monitor specimen transport time and
nated reagents, or inadequate culture techniques. Likewise, the use this information to avoid culturing of old, inadequate speci-
frequent recovery of 2:3 different organisms in dean-voided, mens. Evaluation of test turnaround time has become an im-
midstream urine specimens suggests unsatisfactory methods portant element of laboratory quality assurance (48).
Chapter 11 • Thl Roll of 1M Laboratory in .Pnroention ofHealthcare-Associated Infections 123
TABLE 11.3 FDA-Cleared or-Approved .Molecular Diagnostic Tests for Infectious Diseases.,.
Orgauisnw Detected in Clinical Material or ldentif'red from Culture
Idnaijied
bONA HCV
HIV
HC Chlamydiatrachumatis
Neisseria grmcmhoeae
CMV
HPV
HDA HSVl and 2
HPA c. traclumultis Mycobacteria spp. (6 species)
N. grmcmhoeae Blastomyces derrnatitidi.s
Group A Streptococci Coccidioides immitislposadasii
Group B Streptococci Cryptococcus 'fUKJjimnans
West Nile virus (blood donation) Culture confirmation of 9 different bacteria
Invade!® Chemistry HPV

Loop amplification technology Clostridium dij]icile
Group B Streptococci
NASBA MRSAscreen
CMV
Enterovirus
PCR Bacillus anthf'acis MRSA
&mJetella pertussis Culture confirmation of> 1,000 different
species
Chlamydophila pneumonia~~
c. diffo:ile
Co~lla bumetii
c. traclumultis
Framisella tukJrmsis
Leishmania
MRSA
M tubemllosis
Enterococcus vanA
Adenovirus
Avian F1u
Enterovirus
HBV
HCV
HIV
HBVI HCVI mv (for blood and tissue
donation)
HSVl and 2
Human Metapneumovirus
HPV
Influenza V1I1LS Panel
Influenza VJ.l'll&-HlNl
Respiratory V1I1LS Panel
West Nile Virus (blood donations)
PNA-FISH M. tubemdosis Candida spp. (5 species from blood cultures)
Enterowccus faecalis
Escherichia coli
Klebsiella pneumonia~~
Pseudomonas aeroginosa
StfJPhylococcus aum~S
Other Enterococci
Other Staphylococci
SDA c. trachomatis
N.grm~
HSV 1 and 2
TC C. trachomatis
N. grmcmhoeae
(continued)
TABLE ll.3 FDA-Ckarcd or-Approval Molecular Diagnostic Tests for Infectious Diseases"'• (OmtiJJt~etl)
Organimls Detected in Clinical Material or Identified from Culture
Idmdfi«l
HBV/HCV/HIV (blood and tissue
donations)
HPV
TMA c. tradunnatis
N. grmqrrlweae
Mycob<u:terium tuberculo.ris
71ichomonas vaginali.s
HCV
HPV
Multiplex gold nanoparticle Influenza Virus Panel MRSA
probes Respiratory VJ.I11& Panel (7 viruses) Culture confirmation of 9 different
West Nile Virus (blood donations) species of Gram-positive cocci, m«:A,
van.A, vanB
"Modified from http://www.amp.org accessed 1 July 2012

6Abbreviations: bDNA, branched chain DNA Signal Amplification; CMV, cytomegalovirus; HBV, hepatitis B virus; HC, hybrid capture;
HCV, hepatitis C Virus; HDA, Helicase-Dependent Assay; InV, human immunodeficiency virus; HPA, Hybridization Protection Assay;
HPV, human papillomavirus; HSV, herpes simplex virus; MRSA, methicillin-resistant S. aw-m.r, NASBA, Nucleic Acid Sequence-Based
Amplification; PCR, polymerase chain reaction (includes real-time PCR, multiplex PCR, and RT-PCR); PNA-FISH, peptide nucleic
acid-fluorescent in situ hybridization; SDA, Strand Displacement Amplification; TC, Target Capture; TMA, Transcription Mediated
Amplification.
INITIAL EVALUATION OF SPECIMENS examination of clinical material. Unfortunately, microscopy

is inherently insensitive and nonspecific and so a number of
Assessing the quality of specimens at the time that they are re- different rapid culture-independent methods have been de-
ceived in the laboratory is one of the best ways to evaluate their
veloped that employ immunologic, molecular, or proteomic
suitability for further microbiologic work up. Microscopic re- methods in order to enhance the laboratory's ability to diag-
view of Gram-stain of sputum specimens is a proven means for
nose and identifY HAl pathogens (1-6,51-55) .
determining the adequacy of these specimens (42,49); speci-
Although no formal definition of "rapid" exists for describ-
mens identified as inadequate (multiple squamous epithelial
ing the time required for results to be generated, most clini-
cells, no neutrophils) are not processed further and do not
cians and microbiologists consider rapid results to be available
confuse either clinician or epidemiologist. Scoring systems
within 2 to 4 hours (4,39). Presently, immunologic methods for
for use in determining acceptable wound, vaginal, cervical,
rapid diagnosis directly from clinical material are used to de-
or other specimens have also been described (42,50). Appli- tect a variety of viruses, S. pneumoniae, N meningitidis, Group B
cation of such criteria ensures that the information gener-
streptococcus, L. pneumophila, C. difficile toxin, Aspergillus,
ated from the specimens that are processed completely will Candida, C. neoformans, P. jirouecii, Giardia, Oryptosporidium, and
more likely correlate with true infecting organisms and will
E. histolytica, to name a few (51).
reduce unnecessary laboratory costs. Repeat specimen collec- Although long considered to be of great potential for en-
tion should be requested for inadequate specimens, and fur-
hancing the ability of the micro biology laboratory to rapidly
ther processing of organisms isolated from poor specimens
detect and identify infectious agents (4), the use of molec-
(e.g., species identification, susceptibility testing) should be
ular methods in infectious disease diagnosis has increased
delayed or eliminated. The culture report should alert the
substantially only in the past 5 to 10 years. The growth in
clinician regarding the questionable value of the specimen the number of commercially available test kits and analyte-
so that results will be used cautiously, if at all, for guidance
specific reagents (ASRs) has facilitated the use of this tech-
in diagnosis and therapy. Efforts such as these substantially nology in the clinical laboratory (Tables 11.3 and 11.4) (56) .
improve the quality of the microbiologic results provided and
Technological advances in real-time PCR techniques, auto-
reduce errors in the diagnosis and use of unnecessary antimi- mation, nucleic acid sequencing, multiplex analysis, and MS
crobial therapy.
have pushed the field forward and created new opportuni-
ties for growth.
Although the literature is replete with reports of "laboratory
RAPID TESTS FOR ORGANISM DETECTION
designed" or "homebrew" methods that are directly applicable
AND IDENTIFICATION
to the needs of infection prevention (2,56), most commercial
Arguably, the most rapid and cost-effective test performed molecular diagnostic tests are of limited or no use for infec-
in the clinical microbiology laboratory is direct microscopic tion prevention purposes (Tables 11.3 and 11.4) . Among the
• @C :f 5:f f, . Commercial Molecular Assays for Diagnosis of Sepsis -.•

Detection Limit Turnaround
Assay Manufactul'er Method Detectable Pathogens (cfu/ mL) Time (hr)
PERFORMED ON POSITIVE BLOOD CULTURE BOTI'LES

BDGeneOhm BD Diagnostics, Real-time PCR S. aurew, MRSA, MSSA NA
Staph SR Sparks, MD
XpertMRSA/ Cepheid, Real-time PCR S. aurew, MRSA, MSSA NA
SABC Sunnyvale, CA
PNA-FISH AdvanDX, Fluorescence-based Identification of 7 bacteria NA
Woburn,MA hybridization with and 5 Candida species
PNAprobes
Hyplex BAG, Lich, Multiplex PCR with 10 different pathogens NA
BloodScreen Germany hybridization on an and metA gene
ELISA plate
Prove-it Sepsis Mobidiag, Multiplex PCR with 50 different pathogens NA
Helinski, hybridization on a and metA
Finland microarray
Verigene Gram- Nanosphere, Inc. Multiplex gold 11 different pathogens NA
Positive Blood Northbrook, IL nanoparticle probes and met:A., vanA, vanB
Culture Test genes
PERFORMED DIRECTLY ON WHOLE BLOOD

SepsiTest Molzym, Breman, Broad-range PCR with >300 different pathogens 20-40 for 8-12
Germany sequencing S. aurew
Vyoo SIRS-Lab, Jena, Multiplex PCR with gel >40 different pathogens !1-10 8
Germany electrophore.sis and met:A., vanA, vanB,
vanC and blasHV genes
LightCycler Roche Molecular Multiplex real-time 25 different pathogens !1-30 6
SeptiFast Test Systems, PCR
Branchburg, NJ
"Adapted in part from Mancini N, Carletti S, Ghidali N, et al. The era of molecular and other non-culture-based methods in diagnosis of
sepsis. Clin Microbiol Rev. 2010;23:235-251.
6Abbreviations: ELISA, enzyme linked immunosorbent assay; MRSA, methicillin-resistant S. aumu; MSSA, methicillin-iusceptible S. aumu; NA,
not available; PCR, polymerase chain reaction; PNA-FISH, peptide nucleic acid-fluorescent in situ hybridization.
FDA-cleared or approved tests listed in Table 11.3, the most with either a full or partial16S rRNA (D2large-subunit rRNA
useful for infection prevention purposes include rapid iden- for fungi) sequence from over 1,000 type strains by using the
tification of ESKAPE pathogens by PNA-FISH and molecular MicroSeq analysis software (63). The software analysis provides
detection of MRSA, M. tuberculosis, C. difficik, enterovirus, influ- percent base pair differences between the unknown agent and
enza, and other respiratory viruses. the 20 most closely related organisms, alignment tools to show
PNA-FISH probes have been used for identification of differences between the related sequences, and phylogenetic
S. aurew, E. col~ P aeruginosa, and C. albicans directly from posi- tree tools to verifY that the unknown organism clusters with the
tive blood culture bottles (Table 11.4) (57-59) and direct detec- 20 closest organisms in the database. Continual refinements in
tion of M. tuberculosis in smear-positive sputum specimens (60). methods and software, and decreases in cost, should lead to
PNA-FlSH probes for rapid (-3 hours), direct identification of more widespread use of sequence-based approaches to micro-
S. aurew, coagulase-negative staphylococci, E. Jaecalis, E. coli, bial identification.
K pneumoniae, P aeruginosa, C. albicans, C. glabrata, C. tropicalis, As seen in Table 11 .4, two additional kits that use PCR and
C. pampsilosis, and C. krusei from positive blood culture bottles sequence-based identification of organisms from positive blood
and S. agalactiae from Lim broth cultures are available from cultures are commercially available in Europe: the Hyplex
AdvanDx (Woburn, MA) (Table 11.3) (59,61,62). Whereas BloodScreen (BAG, Lich, Germany) and the Prove-it Sepsis kit
the use of PNA-FISH probes can provide identification within (Mobidiag, Helsinki, Finland) . Both methods use multiplex
3 hours, the requirement for prior amplification in culture PCR with subsequent hybridization to identify between 10 and
lessens the impact of this technology. 50 pathogens plus the mecA gene. The turnaround time for
PCR coupled with nucleic acid sequencing has proven to both assays is 3 hours and they both claim sensitivities of 94%
be an excellent means of rapidly ident:if}'ing bacteria and fungi to 100% and specificities of 92% to 100% (54). The Hyplex
from blood culture or other cultural materials, and this ap- assay also is available in formats to allow the detection of other
proach can be considered the new standard for bacterial and resistance markers, such as van genes and several ft-lactamase
fungal identification (56). Applied Biosystems (Foster City, CA) genes. The Verigene Gram-Positive Blood Culture Test has
has developed ribosomal gene sequencing kits for bacteria and recently been cleared by the FDA for the identification of 11
fungi. A sequence from an unknown organism is compared different Gram-positive bacteria and 3 resistance genes from
126 Section I • General Considerations ofHospital InfectWns
positive blood cultures. This assay uses PCR plus nanotechnol- of antimicrobial resistance, such as SHV P.lactamase genes, the
ogy to provide rapid, accurate result!!. Again, the clinical useful- mecA gene, and vanA and vanB genes. Among the three, the
ness of these assays is limited by their use only for positive blood LightCycler SeptiFast Test has received the most attention and
cultures and not directly fur blood samples. has shown promising performance as an adjunct to blood cul-
The most recent approach to the rapid identification of ture in a variety of patient groups (54,55,70,71) . A recent study
bacteria and fungi from culture is the use of proteomics facili- by Mauro and colleagues (55) found that the SeptiFast Test,
tated by MALDI-TOF MS (1,6). MALDI-TOF systems use mass combined with blood cultures, improves microbiologic data in
measurement!! of nucleic acids or proteins of bacteria or fungi immunocompromised patient!!, especially in instances of previ-
and have emerged as robust, rapid and inexpensive methods ous antibiotic therapy and invasive fungal infection. The cur-
to detect and characterize a wide range of organisms including rent limitations of the SeptiFast Test include it!! high cost and
anaerobes, nonfermenting GNR, staphylococci, Candida, and the lack of any information on antimicrobial susceptibility. The
AspergiUusspp. (64). The use ofMALDI-TOF MS to identify bac- rapid detection of a pathogen may allow better fine-tuning of
teria has been shown to be highly accurate relative to 168 rRNA empirical therapy with possible economic savings; however, the
sequencing and capable of delivering an identification of a pre- absence of a specific susceptibility profile with MDR pathogens
cultured organism in 6 minutes at a cost that is one-quarter of may limit the clinical role of molecular methods.
that of conventional identification (1). Some methods for the Although most clinicians and microbiologists enthusiasti-
processing of positive blood culture samples have been pub- cally welcome the introduction of rapid molecular and immu-
lished, but direct testing of other samples, such as urine, will nologic tests for diagnosing infectious diseases, the high cost
require additional development (6,64,65). Novel applications of these tests is a concern (2,4,~,54,56,72). One advantage
for this technology are being developed and include microbial of rapid molecular and immunologic testing is that these tests
strain typing, antimicrobial susceptibility testing, and the study may be performed quickly if there are adequate laboratory re-
of virulence profiles (6). sources. However, it is challenging to perform such testing with
Rapid methods for detecting important antimicrobial resis- rapid turnaround times because of the financial advantages of
tances have been developed, with most of the current focus batch testing and the difficulty of staffing the laboratory for
being on rapid detection ofMRSA (38,66,67) and VRE (5,38). frequent testing. It is often stated that rapid results obtained
A positive result from any of these test!! allows clinicians to by molecular testing are associated with improved patient out-
implement appropriate isolation precautions quickly in order comes, reduced length of hospital stay and duration of anti-
to prevent the spread of resistant organisms. Whereas PCR- microbial administration, as well as substantial cost savings
based methods have been developed that allow rapid charac- (38,73-75). It must be understood, however, that much of the
terization of common and emerging resistance mechanisms, justification for expenditures on molecular testing is specula-
including a variety of P.lactamases and carbapenemases in tive (76) and rapid microbiologic testing does not always have
key HAI pathogens (Table 11.4), for the most part, they are demonstrable patient care or financial benefit (77). In order
not yet readily available outside of the research or reference to realize these potential benefits of rapid testing, such tests
laboratory setting (8). must be available 24 hours per day 7 days per week. As a con-
Whereas blood cultures remain the current gold standard sequence, their availability may not only increase costs and
for the diagnosis of bloodstream infection (BSI), the require- require dedicated personnel, but will also modify greatly the
ment fur bacterial or fungal growth to optimize detection and organization of the laboratory. Conversely, if the testing hours
identification makes this key diagnostic test of litde use in the are restricted, rapid reporting of results will be compromised
rapid diagnosis of infection (54). An ideal test fur both diag- and the clinical impact, as well as cost savings to the institution
nostic and infection prevention purposes would be one that gained by a shorter length of patient stay or reductions in un-
could be applied direcdy to a sample of the patients' blood necessary treatments, will not be fully realized (2,54).
(or other clinical material) and that would detect the presence The rapid turnaround times of the newer molecular and
and identity of the etiologic agent within 2 to 4 hours or at immunologic assays may increase clinical acceptance and lead
least on the same day that the specimen is processed (3,5,54). to significant increases in their use. As for any laboratory test,
Many such assays using nucleic acid-based technologies have there is a potential for overuse-if clinicians order the test in-
been developed in the research setting (54,63,68,69); however, discriminately or the laboratory has poor quality control, rapid
aside from application in virology (52,56), commercial devel- diagnostic tests can lead to errors, including falsely positive
opment of kits for use in routine microbiology has been quite tests that lead to inappropriate treatment and isolation of pa-
slow (4,54) . Presendy, three assays for detecting and identifica- tients. Erroneous results may also cause the IPP to waste time
tion of pathogens direcdy in blood samples are available com- investigating a pseudo-outbreak (78-80). One such pseudo-
mercially in Europe (Table 11.4): one broad-range (SepsiTest, outbreak occurred in a neonatal intensive care unit (NICU),
Molzym, Bremen, Germany) and two multiplex (Vyoo, SIRS- where a false-positive antigen detection test for adenovirus was
Lab, Jena, Germany; LightCycler SeptiFast Test, Roche Mo- seen in 28 of 56 infunts (79). These false-positive test results
lecular Systems, Branchburg, NJ) PCR assays. These methods precipitated an extensive investigation where the entire NICU
use DNA extraction directly from blood followed by PCR with was placed on contact precautions and considerable laboratory
subsequent characterization of the amplification product by se- and IPP resources were expended in the investigation of the
quencing, electrophoresis, or melting profile analysis to allow pseudo-Qutbreak.
the detection of the pathogen and its identification to the genus The clinical microbiologist, in consultation with appropri-
or species level. These assays are potentially capable of detect- ate clinicians and members of the IPP team, should determine
ing and identifying between 25 and >300 different pathogens what rapid microbiological test!! should be offered and provide
with reported turnaround times of6 to 12 hours (Table 11.4). the necessary restrictions and guidelines for their use. The
In addition, the Vyoo assay is also capable of detecting markers group should base their decisions on data in the literature, data
Chapter 11 • Thl Roll of 1M LalxJratory in .Pnroention ofHealthcare-.Associated Infections 127
generated by their laboratory (if possible), and data on their identification of organisms may obscure real problems and
target patient population. Ideally, these assays should be used make retrospective epidemiologic investigation impossible. For
as part of a well-designed and carefully planned strategy for the example, a report of "Klebsiella/Enterobacter group" tails to dis-
reduction of HAl and antimicrobial resistance in the health- tinguish between two genera (Klebsiella and Enterobacter) that
care setting. Given the added expense of such testing, the have different epidemiologic patterns of infection within the
group should try to determine whether the test would improve hospital.
patient care substantially. More expensive testing procedures Unusual microorganisms or common microorganisms with
may be justified if they reduce the use of less sensitive and less atypical phenotypic properties often cannot be reliably identi-
specific tests and eliminate unnecessary diagnostic procedures fied by commercial systems and may require the use of molecu-
and ineffective therapies (4) . lar or proteomic methods to obtain an accurate identification
(39,56). As pathogens continue to evolve and taxonomic clas-
sifications are revised, microbiologists must pay attention to
AUTOMATED IDENTIFICATION
the manufacturers' communications about products, such as
AND SUSCEPTmiLITY TESTING
letters, notices or test exclusions regarding the accuracy of the
Modem clinical microbiology laboratories continue to rely test methods, as well as the published literature describing the
largely on the so-called system-dependent approach to the potential problems encountered by others using these identi-
identification of microorganisms (39). This approach relies on fication systems. Prompt notification of IPP personnel of such
a set of substrates that are carefully selected for their positive issues will avoid confusion on that front as well.
and negative reactions. The pattern of reactions creates meta- Commercial AST systems were introduced into clinical mi-
bolic profiles for each genus and species that are compared crobiology laboratories during the 1980s and have been used
with established databases. In order to overcome the problem in the majority oflaboratories since the 1990s (82,83). Manual
with slow generation times for most organisms, and to speed up and semiautomated broth microdilution (BMD) systems are
the time to identification, most manufacturers of identification used in laboratories with small volumes of susceptibility testing,
systems use novel substrates with which preformed enzymes, while larger laboratories often chose an automated BMD sys-
produced by the organisms to be tested, may react to elicit re- tem. Most AST systems also perform organism identification.
sponses detectable within 2 to 4 hours. The biochemical indica- The AST systems generally include data management software
tors employed singly or in combination include (a) pH changes that may be interfaced with a laboratory information system
resulting from utilization of the substrate, (b) enzymatic reac- (US) and offer various levels of expert system and epidemio-
tions that allow the release of a chromogenic or fluorogenic logic analysis.
compound, (c) tetrazolium-based indicators of metabolic activ- A laboratory may choose to use an automated AST system
ity in the presence of a variety of carbon sources, (d) detection for reasons that include labor savings, test reproducibility, data
of volatile or nonvolatile acids, and (e) recognition of visible management with expert system analysis, and the opportunity
growth. At the present time, all commercially available antimi- to generate results more rapidly. The provision of AST results
crobial susceptibility testing (AST) systems rely on microbial 1 day sooner than that provided by most manual AST meth-
growth, with the semi-automated and automated systems moni- ods seems a logical advance in patient care. Three studies have
toring growth and growth inhibition using various optical ap- demonstrated both the clinical and economic benefits from
proaches (81,82). the use of rapid AST and reporting (84-86), while one study
The clinical microbiology laboratory's ability to identify has not shown such a benefit (87).
HAl pathogens accurately is challenged continuously by the New antimicrobial resistances continue to emerge, and exist-
expanding spectrum of organisms that colonize and infect seri- ing resistances are increasing in frequency. The most important
ously ill patients. Whereas the more common ESKAPE patho- resistances emerging in HAl pathogens include ESBLs (includ-
gens are readily identified by the available semi-automated and ing carbapenemases} among Enterobacteriaceae (13,33-37),
automated systems, many nonfermentative GNR and other glycopeptide resistance among enterococci (27), and staphylo-
less common or fastidious organisms that cause HAis can be cocci (88,89), MRSA (90), and multiple- or pan-drug resistance
much more difficult to identify. Current examples include among nonfermenters such as P. aeruginosa, Acinetobacter, and
bacteria such as Acinetohacter spp., Burkholderia cepacia, and S. maltophilia (91} (Table 11.2} .
Stenotrophomonas maltophilia; fungi such as non-albicans species A previously cited shortcoming of rapid AST methods was
of Candida, Aspergillus spp., and Fusarium spp.; viruses such as the failure to detect some inducible or subtle resistance mecha-
respiratory syncytial virus, H1N1 influenza A, rotavirus, and nisms (92-95). However, the instruments most notorious for
cytomegalovirus; and parasites such as Cryptosporidium and 1bxo- such problems are no longer marketed, and the manufactur-
plasma. Consequently, the laboratory must frequently update ers of the remaining instruments have made substantial efforts
the methods used to identify and characterize HAl pathogens. to correct earlier problems (96-98} or to extend testing to
The degree to which organism identification routinely is include fastidious organisms (99). Current problems with the
conducted can be very important to HAl control efforts. Infec- automated systems include detection of linezolid resistance in
tion prevention personnel frequently seek evidence that a com- enterococci and staphylococci (100,101), penicillin resistance
mon organism has spread from patient to patient (21,24). The in staphylococci (102), false-positive oxacillin resistance in
ability to detect such an event is enhanced by identifying the coagulase-negative staphylococci (103), reduced glycopeptide
organism at least to the level of species. Laboratories that iden- susceptibility in staphylococci ( 17,88), ESBL and carbapen-
tify HAl pathogens to the species level may find outbreaks that emase resistance in Enterobacteriacae (104-106), and multiple
would otherwise have gone undetected because clusters of un- ,8-lactamases and P. aeruginosa (107,108). Whereas the new
usual organisms or unusual clusters of common organisms may CLSI breakpoints for ,8-lactamase and ESBL-producing GNR
be clues to outbreaks. Furthermore, incomplete or incorrect were intended to improve the detection of ESBL-producing
strains and eliminate the need for confirmatory testing (17), created by intense antimicrobial exposure favors the selection
false-positive results have been reported for several automated and expression of antimicrobial resistance genes (34,111).
systems (82). It should be noted that confinnatory ESBL tests Even among species that are usually susceptible, the strains
that measure the inhibitory effect of clavulanate together with causing HAis are often resistant to agents in > 1 antimicrobial
ceftazidime or cefotaxime are available for all of the automated class (33,112). Thus, the IPP team must track not only MRSA
systems (82). and VRE, but also resistance to P..Iactams and carbapenems
In order to guard against significant AST errors for some in Enterobacteriaceae, MDR in Acinetobacter and Pseudmnonas
organism-antimicrobial combinations, laboratories must spp., and azole and echinocandin resistance in Candida spp.
supplement automated systems with additional methods. For (13,32,34,35,111} . In some instances, Gram-negative bacteria
example, failure of automated systems to recognize carbape- with "extreme drug resistance" have been noted in which the or-
nem resistance among K pneumoniae and A. baumannii isolates ganisms (most often A. baumannii, P. ruroginosa or S. maltophilia)
on the one hand (82,105) and false resistance among Entero- express complete resistance to first-line agents used to treat
bacteriaceae and P. aeruginosa on the other (109) led to the Gram-negative infections (i.e., amikacin, tobramycin, cefepime,
recommendation to use the modified Hodge test or another ceftazidime, imipenem, meropenem, piperacillin-tazobactam,
AST method to confirm carbapenem susceptibility and resis- ciprofloxacin, and levofloxacin} plus second-line drugs, such as
tance, respectively ( 17,109). If the laboratory uses methods tigecycline and polymyxin (34,113) . This resistance burden is
that do not accurately identify organisms or particular resis- further compounded by the discovery of new resistance factors
tance patterns, the IPP may not identify serious problems or such as the New Delhi metallo-P,.Iactamase, a broad-spectrum
even outbreaks. Conversely, IPP personnel may investigate carbapenemase capable of disseminating rapidly via plasmid
spurious problems, thereby diverting and wasting precious transmission among normal human Gram-negative intestinal
resources. flora (114}.
Every IPP must implement control measures to pre- The microbiology laboratory's role in monitoring resistance
vent the spread of multidrug-resistant organisms (MDROs) is extremely important to the success of the infection preven-
(13,14,21,24,32,34,35). However, the success of any program tion effort. Laboratory personnel must notify IPP staff imme-
to control MDROs depends upon the ability of the laboratory diately when key resistant organisms are identified and when
to detect these organisms. Laboratory directors must keep cur- new or unusual phenotypic resistance patterns are detected
rent with the literature regarding automated systems' ability to so that appropriate isolation precaution can be instituted
detect emerging resistances and they must implement, if neces- (21,32,34,38,115).
sary, additional methods to detect or confirm particular resis- Infections due to MRSA continue to be a great cause for
tance patterns. Increasingly, such confirmatory testing will be concern: 65% of S. aureus infections in North America ICUs
performed using molecular methods (8). were due to MRSA according to EPIC II (Table 11.1) (25) .
Reports of community-associated MRSA (CA-MRSA) began
to appear in the late 1990s and in some locations CA-MRSA
EMERGING PATHOGENS
have emerged as the predominant cause of skin and soft tis-
AND ANTIMICROBIAL RESISTANCE
sue infections ( 116} . These strains are usually susceptible to
During the 1990s, much of the effort in infection prevention ciprofloxacin, dindamycin, gentamicin, and trimethoprim/
was spent trying to contain the spread of MRSA and VRE: these sulfamethoxazole and possess exotoxin genes (e.g., Panton-
pathogens were declared the two antimicrobial-resistant patho- Valentine leukocidin genes} ( 117). Initially thought to be dis-
gens that were "most out of control" in U.S. hospitals (110). tinct from hospital-acquired strains, recent reports indicate
Whereas these two Gram-positive pathogens remain prominent that these strains are now common causes of HAl and may also
causes of HAl, Gram-negative bacterial infections now out- show decreased susceptibility to vancomycin (118).
number Gram-positive infections in ICU patients worldwide Transposon-mediated vancomycin resistance in E. faecium
(Table 11.1). Gram-negative bacteria accounted for 62% ofiCU has been well characterized (119,120). Understanding the
infections in the EPIC II study conducted in 2007, compared mechanisms of vancomycin resistance encoded by the vanA
to just 39.1% of infections when the study was first conducted and vanB operons has informed the development of newer-
in 1995 (25). Similar to Gram-negative infections, fungal infec- generation antibiotics that retain activity against vancomycin-
tions (predominately Candida) also increased from a preva- resistant strains. Resistance in E. faecium to aminoglycosides,
lence of 17% in 1995 to 19% in 2007 (25). Within the group erythromycin, fluoroquinolones, clindamycin, and linezolid
of Gram-negative pathogens of current interest, the great- has also been well characterized (Table 11.2) .
est concern surrounds the emergence of multidrug-resistant Resistance concerns with K pneumoniae have generally fo-
(MDR; nonsusceptibility to 2::1 antimicrobials in 2::3 antimicro- cused on the various ESBLs (13). Carbapenems were con-
bial classes) strains of K pneumoniae, P, aeruginosa, A. baumanni~ sidered to be the agents of choice for treating infections due
and Enterobacter spp. (13,14,33,36). Notably in EPIC II, infection to ESBL-producing strains (121); however, the emergence
with MDR organisms such as Acinetobacterand Pseudomonas spe- of new ESBLs during the past decade has further restricted
cies and fungal pathogens was statistically correlated with excess treatment options. Some K pneumoniae strains now express
mortality rates (25). carbapenem-hydrolyzing P,.Iactamases: the K. pneumoniae car-
One of the most alarming trends has been the increasing bapenemase (KPC) class in the U.S.; elsewhere, most com-
frequency with which resistant pathogens are causing HAl monly metallo-enzymes (Table 11.2) (122). Irrespective of
(13,28,34). The widespread use of multiple classes of antibacte- whether resistance is attributable to metallo-enzymes or KPCs,
rial and antifungal agents within the ICU setting makes critical resistance to extended-spectrum cephalosporins, inhibitor
care areas the epicenter for the acquisition and dissemination combinations, and aztreonam accompanies expression of the
of resistance in bacteria and fungi alike. Selection pressure enzymes. Carbapenemase-expressing strains are often resistant
to aminoglycosides, trimethoprim-sulfamethoxazole, and fluo- United States have demonstrated the emergence of co-resistance
roquinolones ( 123), leaving only the peptide antibiotic colistin to both azoles and echinocandins in clinical isolates of C. glalnata
and the newer glycylcycline tigecycline as treatment options. (111,112). The mechanisms of resistance involve drug effiux
Emergence of resistance to colistin and tigecycline has been (azoles) and point mutations in the FKS gene encoding glucan
reported as well. Notably, studies by the Centers for Disease synthase (echinocandins) (112). These findings emphasize the
Control and Prevention's (CDC) National Healthcare Safety importance of rapid identification of BSI isolates of Candida to
Network (NHSN) surveillance system found that MDR strains of species level, as well as antifungal susceptibility testing, especially
K. pneumoniae were reported from 50% of U.S. states reporting in patients with recurrent Candida infection who are receiving or
in the survey (33). were previously exposed to antifungal treatment (112).
A. baumannii was considered a relatively minor, albeit intrin- Molecular methods can rapidly detect antimicrobial resis-
sically MDR, environmental bacteria until outbreaks with MDR tance in clinical settings and have contributed greatly to our
strains occurred in different parts of the world (124). Some of understanding of the spread and genetics of resistance (8,9 ,56).
this intrinsic resistance can be attributed to decreased outer Conventional broth-and agar-based AST methods provide a
membrane permeability (125): A. baumannii also has at least two phenotypic profile of the response of a given microbe to an
different MDR effiux pumps that confer levels of resistance to a array of agents. Although useful for selecting potentially active
variety of agents. Resistance to P.lactam antibiotics is the result therapeutic agents, conventional methods are slow and fraught
of the production of one or more P.lactamases, including a chro- with problems (Table 11.5). One of the more common failings
mosomal cephalosporinase and a variety of acquired enzymes is in the detection of methicillin resistance in staphylococci
(Th.ble 11.2). Resistance to carbapenems in A. baumannii is of- (Th.ble 11.5), which may be expressed in a very heterogeneous
ten attributed to production of enzymes of the OXA class ( 124). fashion, making phenotypic characterization of resistance dif-
A. baumannii strains resistant to virtually all commonly used anti- ficult (81,82). Currently, molecular detection of the resistance
biotics are being reported with increasing frequency (126,127), gene, mecA, is the standard against which phenotypic methods
necessitating the use of second-line agents with questionable for detection of methicillin resistance are judged (8).
efficacy, such as colistin and tigecycline. Resistance to these Molecular methods may be used to detect specific antimi-
agents may emerge during receipt of therapy, resulting in truly crobial resistance genes (resistance genotyping) in many or-
pan-resistant strains (36,127). In the EPIC II survey, infection ganisms (Table 11.2) (8). Detection of specific point mutations
with Acinetobacterwas associated with an increased risk of hospi- associated with resistance to antiviral agents is also increasingly
tal death (25) . Given the high level of resistance of Acinetobacter important (56). Screening for mutations in an amplified prod-
to many antimicrobial agents, including carbapenems, and the uct may be facilitated by the use of high-density probe arrays,
high associated mortality (128), this pathogen presents a con- proteomics, or pyrosequencing (8,56).
tinuing challenge in the critical care setting. Despite its many potential advantages, genotyping will not
Despite being the focus for new antibacterial drug devel- likely replace phenotypic methods for detecting antimicrobial
opment for many years, P. aeruginosa persists as a major cause resistance in the clinical laboratory in the near future. Molecu-
of HAl with increasing numbers of MDR strains being re- lar methods for resistance detection may be applied directly to
ported (129). Resistance to fluoroquinolones is now common the clinical specimen, providing simultaneous detection and
due to a variety of effiux pumps coupled with topoisomerase identification of the pathogen plus resistance characteriza-
mutations (Table 11.2) (129). The P. aeruginosa chromosomal tion (3,5,8). Likewise, they are useful in detecting resistance
cephalosporinase results in P.lactam resistance and when com- in viruses, slow-growing or nonviable organisms, or organisms
bined with reductions in outer membrane protein D2 may with resistance mechanisms that are not reliably detected by
lead to resistance to imipenem (130). P. aeruginosa can also phenotypic methods (5,56) . However, because of their high
express several varieties of plasmid-mediated P.lactamases, specificity, molecular methods will not detect newly emerging
aminoglycoside-modifying enzymes, and effiux mechanisms resistance mechanisms and are unlikely to be useful in detect-
(Table 11.2). Pan-resistant strains of P. aeruginosa, susceptible ing resistance genes in species where the gene has not been
only to colistin, are now being reported (131). observed previously (8). Furthermore, the presence of a resis-
AmpC cephalosporinases are chromosomally encoded tance gene does not mean that the gene will be expressed, and
P.lactamases that are common in species of Enterobacter (132). the absence of a known resistance gene does not exclude the
The AmpC P.lactamase is not normally produced at high possibility of resistance from another mechanism. Phenotypic
concentrations, but production can be induced when the or- AST methods allow laboratories to test many organisms and de-
ganisms are exposed to extended-spectrum cephalosporins, tect newly emerging as well as established resistance patterns.
resulting in stably derepressed MDR strains (132). The AmpC
enzymes also have been mobilized onto transmissible plasmids
ANTIMICROBIAL STEWARDSHIP
and can be transmitted to other GNR that are lacking or poorly
expressing the chromosomal enzyme (133). Every hospital in the United States must now have an antimicro-
Data from EPIC II clearly document the importance of bial stewardship program (ASP), guidelines for which have been
Candida as a cause of infection in ICUs (Table 11.1) (25,30). published by the Infections Disease Society of America (IDSA)
Among the common species of Candida, the only one that ap- and the Society for Healthcare Epidemiology ofAmerica (SHEA)
pears to be emerging as a resistant pathogen is C. glalnata (137). Antimicrobial stewardship efforts are directly dependent
(111,112,134-136). In the United States, both the frequency on reports from the clinical microbiology laboratory, so good
of C. glabrata as a cause of BSI and in vitro resistance to flucon- communication between the laboratory, pharmacy, IPP, and a
azole has increased steadily since 1992 (135). Furthermore, case stewardship team is essential. For guiding empirical antimicro-
reports and case series suggest the emergence of MDR in this bial therapy, unit-specific and tailored antibiograms should be
species. Recent data from multicenter surveys conducted in the updated on a regular basis and provided to clinicians for use at
TABLE ll.S Potential Problems with Dcm:tion of Antimicrobial ~istancc Phenotypes

by Automated Susceptibility Testing Systems"
Resistance Phenotype Comment
Vancomycin resistance in enterococci Problems with detection of low-level vancomycin resistance ( vanB and va71C) have been
demonstrated with Vitek, Phoenix, and MicroScan. Suggest conf"trmation with alternative
method for E. casselijlavw and E. grdlinarom.
High-level aminoglycoside resistance Detection of HLAR improved by changes in growth medium and extended incubation.
(HLAR) in enterococci
Linezolid resistance in enterococci and Trailing endpoints complicate MIC endpoint reading. Low prevalence oflinezolid re!istance limits
staphylococci ability to optimize detection. Categorical agreements with CLSI BMD results range from 89.6%
(Phoenix) to 96.0% (MicroScan).
Penicillin resistance in staphylococci Generally requires an induced }-lactamase test. Prevalence of penicillin~usceptible staphylococci is
low and J-lactamase production may not be detected by phenotypic methods. Confirmation by
molecular methods recommended to ensure penicillin susceptibility.
Oxacillin re!istance in staphylococci Automated systems have demonstrated excellent sensitivity and specificity for detecting MRSA. New
CLSI breakpoint may result in fahe-re!istance among coagulase-negative staphylococci (CoNS).
Reduced glycopeptide susceptibility Systems may incorrectly categorize S. aul'llUS and CoNS as vancomycin-resistant. CLSI encourages
in staphylococci laboratories to confirm nonswceptible vancomycin results with a second method.
Inducible clindamycin resistance Recently FDA-deared tests for inducible clindamycin resistance in staphylococci have become
available for all automated ll)'lltems (Phoenix, Vitek 2, Micro Scan WalkAway, Sensititre ARIS 2x) _
ESBL-producing En~ Implementation ofrevised (2010) cephalosporin and aztreonam CLSI breakpoints for
Enterobacteriaceae makes ESBL testing unnecessary. Confinnatory ESBL tests that typically
measure the inhibitory effect of clavulanate on ceftazidime are available for all of the
automated systems. Both false-positive and false-negative results continue to occur.
Carbapenem re!istance Failure of automated systems to recognize carbapenem resistance among K pneumoniae and
A baumannii isolates has been reported. False resistance has also occurred with En~
and P. aerugi'IWSa. Use of a second AST method to confinn nonsusceptible carbapenem results.
CLSI recommends using the modified Hodge test to confirm carbapenemase production in
isolates with elevated carbapenem MICs.
Other resistance in GNR Elevated error rates have been reported for .B-lactams and P. aeruginosa with all automated ll)'lltems.
,. Data compiled from Richter SS, Ferraro MJ. Susceptibility testing instrumentation and computerized expert systems for data analy!is and
interpretation. In; Versalovic J, Carroll KC, Funke G, et al, eds. Manual ofClinical Microbiology. 1Oth ed. Washington, DC: American Society for
Microbiology; 2011:1144--1154.
the bedside. Such antibiogram data can also be used for evalu- LABORATORY INFORMATION SYSTEMS (LIS)
ation of trends in important antimicrobial resistance rates and AND REPORTING OF DATA
for education of clinicians regarding optimal antimicrobial use.
An LIS that can do prospective data mining and interface with
Directed antimicrobial therapy requires patient-specific culture
and susceptibility data. This allows for a prospective audit of other parts of the electronic medical record could help IPP
staff perform surveillance, monitor patient-to-patient spread
antimicrobial use with feedback to the prescriber.
A major challenge to effective stewardship is the ability to of pathogens, and provide earlier detection of outbreaks
(138--140). Thus, individuals selecting an LIS must consult
obtain antimicrobial susceptibility data from the laboratory
with both laboratory and IPP personnel before purchasing the
in a timely and efficient manner. Efforts to reduce the analyti-
optimal system for the hospital.
cal turnaround time are helpful; however, the data must then
Culture and antimicrobial susceptibility results are an im-
be incorporated rapidly into antimicrobial management. The
portant data source for the IPP and usually are reviewed daily
task of the ASP is made considerably more difficult if laborious
by IPs. Thus, routine microbiology results should be easily ac-
chart re\iews are required for each patient on antimicrobial
therapy. The use of a computer decision-support system can cessible to IPP personnel. In most instances, results are stored
in a computer database, facilitating retrieval and analysis. The
streamline this process by automatically alerting the steward-
ship team when restricted drugs are ordered, indicating where laboratory should store the following information: specimen
type, date of collection, patient name, hospital number, hospi-
the patient resides, other medications the patient is receiving,
and pertinent microbiology laboratory results (15,138). Other tal service, and the results of any specialized testing performed
(e.g., strain typing). Both clinicians and the IPP benefit from
alerts may include notification if a patient was receiving dou-
periodic summaries of selected microbiologic data, such as an
ble antimicrobial coverage or no antimicrobial coverage for
antibiogram specifically for HAl pathogens. These results can
an identified pathogen and identification of potential candi-
be presented in a tabular format that includes the antibiograms
dates for a switch from intravenous (IV) to oral therapy or for
of the most common HAl pathogens by anatomical site and hos-
discontinuation of therapy when cultures fail to detect a poten-
pital service location and also includes antimicrobial dosing and
tial pathogen (15). One ASP projected that a decision-support
system saved the institution over $600,000 annually compared cost information. This information will help clinicians select em-
piric antimicrobial therapy for patients with HAis. The CLSI has
to the ASP without the decision-support system (15).
developed guidelines for the preparation of antibiograms ( 141).
The laboratory should report all results as quickly as pos- some states, pay-for-performance, and public reporting of HAl
sible. In most situations, routine reporting on the hospitals' rates) (16,21).
LIS will be adequate for clinical and epidemiologic purposes. Given that the results of routine cultures submitted to the
However, the detection of certain epidemiologically important microbiology laboratory for the diagnosis of HAl constitute
pathogens requires immediate notification ofiPP personnel so the most common means of HAl surveillance, the laboratory
that transmission prevention measures can be initiated imme- often serves as an "early warning" system (10) by identifying
diately (including, if applicable, notification of public health clusters of organisms with unique phenotypic characteristics
authorities). Examples of organisms for which urgent notifi- and communicating the observations promptly to IPP per-
cation should occur include M. tuberculosis, N. meningitidis, sonnel. Whereas this mode of surveillance may be sufficient
Legionella, enteric pathogens such as SalmoneUa or Shigella, to detect true instances of infection, it is unlikely to detect
and MDROs such as MRSA, glycopeptide-intermediate and those patients who may be colonized with a MDRO and who
-resistant S. aurew, VRE, and ESBL-producing Enterobacte- may serve as a reservoir for MDRO transmission (32,35,115).
riaceae. In addition, new or unusual pathogens, or potential Therefore, during outbreaks, when new MDROs are emerg-
agents of bioterrorism (e.g., B. anthmcis, Y. pestis, and ortho- ing, or if transmission of an MDRO continues despite the
poxviruses) should be reported immediately to the IPP. The use of standard infection prevention practices, "active sur-
list of organisms for immediate notification may vary from one veillance" testing may be used to identify patients colonized
institution to another. For example, an MDRO may have be- (but not clinically infected) with an MDRO (144). In addition,
come endemic in one hospital, to the point that the IPP no some states (as well as the VA healthcare system) have man-
longer requires immediate notification, while another hospital dated the routine use of active surveillance testing for MRSA,
has not yet had introduction of the MDRO and needs such and thus many hospitals have adopted this approach for con-
notification (21). trol ofMRSA (16,115,145).
In addition to providing electronic, printed, and verbal re- In contrast to the extensive experience with MRSA active
ports, laboratory staff should meet regularly with IPP staff to surveillance testing, we know far less about how to apply ac-
ensure that their communication is direct and clear. They can tive surveillance testing to prevent transmission ofMDR-GNRs
discuss areas of mutual concern, such as the status of epidemio- (21,32,35). MDR-GNRs are vastly different from MRSA in
logic and microbiologic investigation of clusters or outbreaks. terms of the diversity of species and resistance mechanisms,
Together, they can determine whether supplementary studies, optimal screening methods for the myriad of MDR-GNRs are
such as molecular typing or environmental cultures, will be still being developed, and several important questions about
necessary. If special studies are necessary, they can determine MDR-GNR transmission remain to be answered before the util-
exactly what needs to be done, who will do these procedures, ity of active surveillance testing can be established for these
and when they will be performed. organisms (21,32). Thus, the optimal means of detecting and
preventing infection/colonization due to MDR-GNRs, and
the role of active surveillance testing for MDR-GNRs, remains
ROLE OF THE MICROBIOWGY unclear (35).
LABORATORY IN SURVEILLANCE A m~or reason for careful consideration before launching
AND OUTBREAK INVESTIGATION into large-scale active surveillance testing efforts is the fact that
such measures are complex and resource intensive (21,115). In
addition to the cost of the screening test itself, there are costs
SURVEILLANCE
associated with sample acquisition and transport, laboratory
Review of the clinical microbiology laboratory records is the validation and reporting, process and outcome monitoring,
most common method for case finding in HAl surveillance: it personal protective equipment, bed management, and patient/
is estimated that more than 80% of HAis may be identified by family education (145). Indeed, the prospect of performing ac-
a review of positive cultures from the laboratory ( 16,24). Thus, tive surveillance testing for a large number of diverse MDROs
the most important role of the microbiology laboratory is to (which requires that test samples be obtained from several dif-
promptly and accurately detect HAl pathogens and their an- ferent anatomic sites of each patient) threatens to overwhelm
timicrobial resistance patterns. The laboratory must also work and divert the resources of microbiology laboratories, IPPs and
with the IPP and the hospitals' information technology depart- hospital units (35). Broader application of active surveillance
ment to determine how microbiology data are delivered and testing will require the development of molecular or other
linked to other surveillance data to streamline this process. novel approaches to identify multiple MDROs simultaneously
Computer programs have been developed to identify clustering and at low cost in patient samples.
of infections with the same organisms that occur at the same In the meantime, active surveillance testing for MDROs
time in the same patient care area (142,143). Such programs should be limited to new introduction of problematic
have permitted identification of outbreaks; whether they pro- pathogens (e.g., carbapenem-resistant Enterobacteriaceae),
vide such information in rapid enough fashion to permit the continued transmission of a problematic MDRO despite im-
effective use of control measures remains open to question. plementation of standard and enhanced infection prevention
M~or surveillance challenges facing the clinical microbiol- practices, or outbreak settings (144). Furthermore, the use of
ogy laboratory include the continued emergence of novel inactive surveillance testing should always be seen as an adjunct,
fectious agents, novel antimicrobial-resistant pathogens (e.g., and shouldn't draw attention away from those well-established
MDR Acinetobacter, carbapenem-resistant Enterobacteriaceae), practices for infection prevention that are applied to all at-risk
and new governmental and public health mandates that place patient populations and are designed to prevent infections due
more pressure on the laboratory to provide more robust sur- to all pathogens (e.g., hand hygiene and bundled practices for
veillance support (e.g., mandated active surveillance testing in prevention of device-associated infection) (21,35,145).
OUTBREAK DETECTION AND MANAGEMENT money, materials, space, or special tests) would be required to
investigate a "typical" outbreak. Laboratory staff also should an-
When confronted with a cluster or outbreak of HAis, the IPP
ticipate the extra costs associated with outbreak investigations
must act quickly to characterize and define the extent of the out- so that they can work with hospital administration to include
break, to identify possible causes, and to design and implement
funds for those efforts in annual budgets.
effective control measures (Table 1 1.6). The clinical microbiol-
Outbreaks are often detected retrospectively, either after
ogy laboratory has important roles to play in any potential out-
they have resolved or when they are already beginning to wane.
break situation, including early recognition of possible clusters
Therefore, a maJor challenge to the clinical microbiology labo-
and outbreaks, rapid notification and collaboration with the
ratory is in detecting outbreaks early enough to allow effective
IPP staff, additional case finding, and provision of molecular
intervention and impact morbidity and mortality. Effective and
typing for determination of relatedness, which requires main- regular communication between laboratory personnel and the
tenance of an organism bank. The laboratory should also act
IPP staff is essential to this effort. Given the stress inherent in
in a consultative capacity with the IPP staff to help determine an outbreak investigation and the speed with which important
whether an outbreak is "realw or a potential pseudo-outbreak
decisions must be made, the IPP team, including laboratory
due to fulse-positive rapid diagnostic or screening tests or con- personnel, might need to meet daily to discuss new findings
tamination of specimens outside or within the laboratory. In
and make decisions. In the future, efforts at early detection will
addition, the laboratory can help generate hypotheses as to the
likely be facilitated by real-time data-mining programs that can
potential source of an outbreak, its reservoir, and its mode of
raise flags based upon subtle changes in rates of test ordering
spread, through molecular typing of the suspected organisms
or of positive test results.
and through testing of the environment and/ or personnel as
Staff members in both the IPP and the laboratory have im-
necessary.
portant unique responsibilities during outbreak investigations
Outbreak investigations can be facilitated if the IPP team (Table 11.6). One of the laboratory's critical responsibilities is
prepares in advance. One step in this process is to identify the
to save all potentially relevant organisms in case further analysis
most common types of outbreaks that have occurred in the hos- is needed. Regardless of their ability to perform special tests
pital (e.g., S. aun:us wound infections in the surgical ICU or
to characterize the organisms, all microbiology laboratories
legionellosis on the renal service). Laboratory and IPP person- should save isolates during outbreaks. If the laboratory cannot
nel can then determine what resources (e.g., personnel, time,
TABLE 11.6 Steps in a Nosocomial Outbreak Investigation and the Role of the Laboratory
at Bach Step•
Investigative Step Laboratory Participation
IDENTIFY THE PROBLEM Laboratory surveillance

Form Calle definition Communication (early warning)
Confirm CalleS Microbiological confirmation
Look for additional cases Identification
Calculate rates Susceptibility testing
Archive data on occurrences
Store isolates for subsequent studies
CHARACTERIZE mE OUTBREAK Characterize outbreak-related isolates

Who Strain typing of isolates
Where Phenotype
When Genotype
What Assess the number and distribution (clustering) of strains
CONSIDER. POSSmLE CAUSES Conduct supplementary studies

Define the mode of transmission Obtain cultures of specimens from personnel,
Identify potential reservoirs patients and environment
Identify potential vectors Select isolates from these cultures on basis of phenotypic characteristics
Perform a Clllle-<:ontrol or cohort study Perform strain typing of phenotypically identical isolates to determine whether
they match the outbreak strain
CONTROL OR TERMINATE THE OUfBREAK Adjust laboratory procedures to support control activities
Define and implement control measures Continue laboratory surveillance
Evaluate the efficacy of control measures Store isolates
Continue surveillance for new cases Maintain communication
Compiled from McGowan]EJr, Metchock BG. Basic microbiologic support for hospital e~idemiology. Infect ~HospE~l..
11
.
1996·17:298--:i03· Pfaller MA Herwaldt lAThe clinical microbiology laboratory and infection control; emergmg pathogem, antimicrobtal
resis~ce, and n~ technol~gy. Clin Infect Dis. 1997;25:858--870; and Diekema DJ, Pfuller MA. Infection control epidemiology. and d~ical
microbiology. In; Versalovic J, Carroll KC, Funke G, et al., eds. Manual of Clinical Microbiology. lOth ed. Washington, DC; Amencan Soc1ety for
Microbiology; 2011:7~.
perform the necessary tests, the isolates can be sent to a refer- for carriage of epidemiologically significant organisms. The
ence laboratory. Similarly, the laboratory should save all organ- most common organisms for which screening is performed
islllll that might be remotely related to the outbreak, because are the MDROs (i.e., MRSA, VRE, and MDR-GNRs), often as
organisms can be discarded if they are not needed but cannot one aspect of an enhanced program for MDRO control (21,24,
be retrieved once they have been thrown away. 32-35,38,66,115). Screening for other organisms (e.g., Group
In a broader sense, the microbiology laboratory should plan A streptococci) may be performed as part of a HAl or outbreak
ahead and save all epidemiologically important isolates from investigation. Finally, hand cultures may be performed as part
routine cultures. Laboratory and IPP personnel should decide of educational efforts in support of a hand hygiene campaign
which isolates should be banked and how long they should be or to confirm the mechanism of cross-infection during an
stored based upon their epidemiologic importance and the outbreak investigation ( 146).
available resources. We recommend that all isolates from nor- For some organisms (e.g., MRSA, VRE), screening meth-
mally sterile sites (e.g., blood and cerebrospinal fluid), impor- ods are standardized and well established, while for others
tant MDROs (MRSA, VRE, and ESBL-producing GNRs) from (e.g., MDR-GNRs), such methods are evolving and will con-
any site and other epidemiologically important pathogens (e.g., tinue to evolve as more complex resistance phenotypes emerge
M. tuberr;ulosis, Legionella) be saved for a period of 3 to 5 years. (32,35,147). Table 11.7 outlines current approaches to screening
patients and HCWs for organislllll of epidemiologic significance.
When performing screening cultures of personnel and the
SUPPLEMENTARY CULTURES
environment, special culture media might improve the labora-
The clinical microbiology laboratory is often called upon to de- tory's ability to identify the reservoir and the pathogens of inter-
tect potential HAl pathogens that may be colonizers of patients, est. For example, selective media (i.e., which inhibits the growth
healthcare workers (HCWs), and the hospital environment. For ofspecies other than that ofinterest) or differential media (i.e.,
example, patients and HCWs are increasingly being screened which reveals distinctive morphological features [pigmentation,
TABLE 11.7 Screening Patients and Healthcare Workers for Asymptomatic Carriage of Organisms
of Epidemiologic Significan~•
Turnaround
Organimn(s) Diagnostic Procedures Time (h) Optimum Specimens
S. aum.~.S, including MRSA Aerobic culture and AST 48--96• Nares,4 throat, perirectal, skin, wounds
Chromogenic agar medium 18--48' Nares, throat, perirectal, skin, wounds
Real-time PCR 1-4 Nares!
VRE Aerobic culture and AST 48--72 Perirectal or stool swab

Real-time PCR 1--41 Perirectal or stool swab
Multiresistant GNR (P. aeruginosa, Aerobic culture using selective 48--72 Perirectal or stool swab, endotracheal
Acinetobaaer spp., S. moitqphilia, media and AST-' or sputum sample, sites of prior
ESBL-and carbapenemase- infection or colonization'.
producing organisms)
Group A Streptococci Aerobic culture 24-48 Rectal, vaginal, skin, throat
Various organisms carried on hands Aerobic cultures with selective 48--96 Hand cultures
medium, contact agar plates, Direct imprint on agar plate
broth-based glovejuice
Culture ofbroth after 1 min of hand
technique
immersion with agitation of broth
"Adapted from DiekemaDJ, Pfaller MA. Infection control epidemiology and clinical microbiology. In: Versalovicj, Carroll KC, Funke G, et al,
eds. Manual of Clinical MK:robioW10. lOth ed. Washington, DC: American Society for Microbiology; 2011:73--84.
6 Such cultures should only be done for the following reasons: (1) as part of an outbreak investigation, to seek carriage of an organism among
patients or healthcare workers who are epidemiologically linked to cases; (2) to seek carriers of MOROs as part of enhanced MDRO control
strategies; (3) to identify S. aum.~.S carriers in order to proceed with a decolonization strategy to decrease risk for acquisition of S. aum.~.S
infection during a period of vulnerability (e.g., perioperative).
'The "gold standard" method includes overnight broth enrichment and confirmation of species identification and antimicrobial susceptibility,
which can increase turnaround time to 96 hours. Most conventional agar-based screens (e.g.• mannitol salt agar with or without oxacillin),
without broth enrichment, provide a turnaround time of approximately 48 hours.
4The nares provides the best sensitivity and specificity of any single site for detection of S. aum.~.S (including MRSA). However, several studies
have shown that sampling of additional sites, including oropharynx and perirectal sites, may increase yield by 10% to 40%.
"Positive results for chromogenic agar medium can be reported at 18 to24 hours, but negative results require 48 hours.
/Currently available real-time PCR assays are FDA approved only for nares samples but have been used in some studies for oropharyngeal, skin,
and perirectal samples.
CNo real-time PCR assay for VRE detection is FDA approved at this time.
4Several modifications of culture methods may enhance recovery by increasing medium selectivity for MOROs (e.g., addition of ceftazidime for
ESBL-producing E1itero~Jacteria levofloxacin for fluoroquinolone-resistant E. coli).
'Sample site choice should be guided by likely reservoirs, gastrointestinal (e.g., E. col1) and respiratory (e.g., Acinetobacter, P. aeruginosa).
colony type] that differentiate the species of interest from other hospital environment serves as an important source of potential
species), or both, might allow the laboratory staff to process HAl pathogens (147) , and there are specific circumstances in
specimens quickly and efficiently. In addition, enrichment cul- which environmental sampling for quality assurance (QA) or for
tures might be necessary to optimize the laboratory's ability to the detection of potential pathogens is required. Routine sam-
detect specific HAl pathogens (e.g., Candida (148) or MRSA pling for QA should be limited to biologic monitoring of steril-
(149)) present in low numbers (Table 11. 7). ization processes and monthly cultures of water and dialysate for
Laboratory and IPP should weigh two important factors be- hemodialysis. On rare occasions, it may be helpful to perform
fore deciding to culture hospital personnel during an outbreak a short-term evaluation of the effectiveness of hospital cleaning
investigation: (a) finding the outbreak strain on the hands disinfection (e.g., sampling surfaces for VRE or C. di.fficik after
or in the nares of a HCW does not establish the direction of terminal room cleaning, to evaluate the effectiveness of cleaning
transmission or definitively implicate a HCW as the source or practices). Similarly, sampling the hospital potable water supply
reservoir for the outbreak, (b) culturing hospital personnel infor Legionella spp. is indicated after diagnosis of nosocomial le-
discriminately can lead to confusing results and can generate gionellosis or as part of a comprehensive program to decrease
ill will toward the IPP. In general, only HCWs epidemiologically risk ofnosocomiallegionellosis (150,152,153). Air sampling for
linked to cases should be cultured. With these caveats in mind, mould spores can also be an important step in determining the
we recommend that IPPs obtain cultures of hospital personnel source of invasive fungal infection in highly immunocompro-
only after consulting with a hospital epidemiologist experi- mised patients. On very rare occasions, sampling of other inani-
enced in outbreak investigation (11,24). mate objects or surfaces may be indicated and then only when
At one time, the hospital environment was considered to be a careful epidemiologic investigation suggests that a particular
the major source of HAl pathogens. More recently, it has been object or surface may be implicated in pathogen transmission.
recognized that patients most often acquire infection from their Table 11.8 outlines current approaches to screening the hospital
own endogenous (colonizing) flora (150,151). Nonetheless, the environment for organisms of epidemiologic significance.
TABLE ll.S Miaobiologic Studies of the Hospital Environment (Air, Water, and Surfaces)
for Organisms of Epidemiological Significan~•
Soun:e and Organism (s) Procedure (s) Turnaro1md Time Optimum Specimen
AIR
Fungi (moulds) Fungal culture on selective 48 houn--7 days Air processed with large-volume air sampler'
medium
Bacteriad Routine aerobic cultures 48--72 hours Air processed with large-volume air sampler
WATER
Legimlella spp. Culture on selective media' 5-10 days 500 ml.-1 L water samples/Swabs of internal
surfaces of faucets, shower heads, and aeraton/
Fungil Fungal culture on selective 48--96 houn 500 ml-1 L water samples/Swabs ofintemal
medium surfaces of faucets, shower heads, and aeraton/
Bacteria Routine aerobic cultures 48--72 houn Water and dialysate samples as outlined by AAMI.A
SURFACES
Aerobic bacteria Aerobic cultures wing selective 48--72 houn Surface swab or sponge, contact agar plate (Rodac) i
(including MDROs) and non-selective media
c. dif.ficile Anaerobic cultures 48--72 houn Surface swab or sponge, contact agar plate (Rodac)i
VRE Selective aerobic cultures 48-72 hours Surface swab or sponge, contact agar plate (Rodac)
"Adapted from Diekema DJ, Pfaller MA. Infection control epidemiology and clinical microbiology. In: Venalovic J, Carroll KC, Funke G, et al.,
eds. Manual ofClmicalMil;ro/Mlogy. lOth ed. Washington, DC: American Society for Microbiology; 2011:7!J-84.
~~With the exception of water and dialysate cultures for monitoring of hemodialysis, and potable water cultures for Legitml:llaspp., environmental
cultures should be performed only when an epidemiologic investigation suggests the environment may be involved in pathogen transmission.
'Large-volume air samples are preferred for air sampling for mould spores: settle plates should not be used for this purpose.
11There are no standards for acceptable leveL. of bacteria in air samples, nor is there any evidence correlating bacterial burden to infection
risk. Air sampling for bacteria should be performed only rarely, either as part of an outbreak inve5tigation or a research protocol.
•Legionella spp. will not grow on routine aerobic culture media. Buffered charcoal yeast extract agar in a C02~nriched atmosphere is required
for isolation of LegUmella.
.frhe larger volume (1 L) is preferred. H the water source is chlorinated, 0.5 mL of 0.1 N sodium thiosulfate should be added to each liter
sample to neutralize the chlorine. Water samples are filter concentrated. Swabs should be immersed in 3 to 5 mL of water taken during
sampling of the same site, to prevent drying.
IThe role of waterborne fungi in infection transmission in the hospital environment remains poorly described, but cultures may be indicated
as part of a search for environmental sources during an outbreak of invasive fungal infections in an immunocompromised patient population.
fiAAMI, Association for the Advancement of Medical Instrumentation, whose standards govern microbiological monitoring of hemodialysis.
iThe sterile swab or sponge should be moistened (e.g., with nuoient broth or sterile saline) before sample collection.
iFor C. difficile, the contact agar plate should be optimized for anaerobic recovery (selective, prereduced media, prompdy placed in an
anaerobic environment).
In general, routine undirected cultures of HCWs or the AST, biochemical profiles, and bacteriophage susceptibility
hospital environment should be discouraged. Both IPP and patterns), which discriminate poorly among isolates (154,155).
laboratory staff member8 must under8tand that such cultures Molecular strain typing employs a broad range of tech-
are labor intensive and nonstandardized, and they rarely niques ranging from simple plasmid profiling to whole-genome
provide useful information (150). With few exceptions (see sequencing (Table 11.9) (154). Strain typing is performed in
above), such sampling should only be performed as part of an order to determine whether various isolates yield the same or
epidemiologic investigation in consultation with the hospital different profile using one or more molecular tests. If isolates
epidemiologist. When such an investigation reveals a common from different patients yield the same result or "fingerprint,"
organism in patient, HCW, and/or environmental samples, the the isolates probably originated from a single clone and were
laboratory should also provide access to epidemiologic strain transmitted from patient-to-patient from a common source or
typing methods. by a common mechanism (155,156). In some instances, the use
of traditional typing protocols, such as pulsed-field gel electro-
phoresis (PFGE), may not be sensitive enough to allow fine epi-
MOLECULAR TYPING TO SUPPORT INFECTION
demiologic discrimination of closely related bacterial isolates.
PREVENTION ACTIVITIES
In such a setting, Ben Zakour and colleagues (156) have dem-
The laboratory characterization of HAl pathogens to provide onstrated the importance of rapid, high-resolution genetic
evidence regarding their biological and genetic relatedness fre- analysis using whole-genome sequencing in performing a
quently is useful to epidemiologists as an aid in the investigation fine-scale epidemiologic investigation of a cluster of puerperal
of HAis. In many situations, species identification and AST re- sepsis due to Streptococcus pyogenes. Whereas isolates of S. pyogenes
sults may provide strong evidence for an epidemiological link. from four different patients were judged to be the same strain
However, if a cluster of HAis is caused by an organism such as by PFGE and emm sequence typing, whole-genome sequencing
E. coli, S. epidermidis, or P aeruginosa that is a frequent or uni- revealed the outbreak to be polyclonal with two isolates from
ver8al member of the normal microbial flora or environment, different hospitals shown to be unrelated, while isolates from
additional tests may be required to determine whether the iso- two patients from the same hospital were indistinguishable,
lates are related or not. In this setting, genotypic or DNA-based suggesting patient-to-patient transmission or infection from a
typing methods have replaced phenotypic typing methods (e.g., common source (156).
Genotypic Methods for Epidemiological Stram 'IYPing of Nosocomial Pathoge~•

'l)'ping Method Comments
Plasmid profiling Simple, low-cost method that u useful as a supplement to other typing methods. Only useful if organism has
plasmids. Restriction endonuclease analysis of plasmid DNA enhances discriminatory power of the method.
Ribotyping Complex, labor-intensive method. Manual ribotyping of hutorical interest. Automated ribotyping may serve as
a first-level (expensive) screening method.
PFGE A complex, labor-intensive method with excellent dUcriminatory power. Generally considered the gold
standard for highly discriminatory bacterial subtyping. Useful in outbreak surveillance and for the
development oflarge-scale library subtyping databases.
RAPD Poorly reproducible method that u best used to answer specific limited epidemiological questions. May be
useful in small-..cale outbreak investigations.
rep-PCR Poorly reproducible method with limited applicability. A semi-automated method (DiversiLab System,
bioMerieux, Marcy l'Etoile, France) may be used for local surveillance.
PCR-ribotyping A simple, low-c03t approach that is the first-line method for subtyping of C di.lfo;ik
AFLP Moderately complex method suitable for local library subtyping and outbreak surveillance. Excellent
discriminatory power.
MLST One of the first DNA sequence-bated typing methods. Limited discriminatory power, 100% typability and high
reproducibility. Best used for phylogenetic studies.
MLVA MLST approach using virulence-associated genes to improve discriminatory power. Moderately labor-intensive
with excellent discriminatory power. May be used in outbreak surveillance and large-..cale library subtyping
if standardized.
Gene sequencing Depending on gene selected may offer excellent discriminatory power. Useful in outbreak surveillance,
large-scale library subtyping and phylogenetic studies.
SNP Developed at a means of simplifying MLST schemes. Offer the same phylogenetic information at MLST
schemes but with less discrimination. Generally not suitable for laboratory-based surveillance focusing on
cluster detection.
Whole-genome sequencing Complex, expensive, and labor-intensive approach with excellent ducriminatory power. Potentially useful in
outbreak investigation and large-5cale library subtyping but not currendy feasible for large-5cale studies
involving prokaryotes and eukaryotes.
"Compiled from Gerner-Smidt P, Hyytia-Thees E, Rota PA. Molecular epidemiology. In: VersalovicJ, Carroll KC, Funke G, et al, eds. Man'UDI of
Cliniwl Miuvbiolog,. lOth ed. Wa.thington, DC: American Society for Microbiology; 2011:100-123.
bAbbreviations; AFLP, amplified fragment length polymorphi..m; MLST, multilocus sequence typing; MLVA, multi-virulence locus sequence
typing; PFGE, pulsed-field gel electrophoresis; RAPD, random amplification of polymorphic DNA; rep-PCR, repetitive-i:lement PCR; SNP,
single-nucleotide polymorphi..ms.
Genotypic typing methods provide meaningful data and are 16. 11arenfanger J, Bente J, Ha.ener G. Optimal performance for clinical microbiologiatl and
their interaction with infection control otalf. Clift Mimlbio/ N<Wl. 2009;!11:9--15.
cost-effective only when they are used for well-defined epidemi- 17. Clinical and Laboratory Standard& lllatitute. ~ ~ftJr A~Swupf>
ologic objectives. These objectives include (a) determining the bility ~ 20tlllnjrmnali<mal ~t Wa}'DC, PA; CLSI; 2010.
source and extent of an outbreak; (b) determining the mode 18. Leclercq It, Canton R, Brown DF, et al. EUCASI' e"P"rt ruleo in antimicrobial IUieeptibil-
itr telling. ainMimlbiollnfrt:t. 2013;19(2) :1469--0691.
of transmission of a HAl pathogen; (c) evaluating the efficacy 19. Livermore DM, Andrew> JM, Hawkey PM, et a!. Are ouaceptibilitr teots enough, or
of preventative measures; and (d) monitoring transmission of lhould laboratorieo •till oeek ESBLo and carbapenetnuea directly?1 A~ CliiJMilNr.
2012;67:15W-1577.
pathogens in high-risk areas (e.g., ICUs), where cross-infection 20. Cooington I.E, Nurallab H, Bebta M, et al. New CLSI recommendation&: practical im-
is a recognized hazard. plication• of eliminating ESBL teating and impletnenting new MIC breakpoints for En-
The ideal genotypic typing system should be standardized terobacteriaceae at a major teaching hoapital. ID: Proceedings from the Annual Scientific
Meeting; April I to 4, 2011; Dallu, TX. Abatr.u:t 632. http:/ / ohea.confex.com/ lhea/2011/
reproducible, stable, sensitive, broadly applicable, and inex- webprogram/Paper4!35.html
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2011;49:557-560.
previous epidemiologic investigations. Further discussion of
22. Pohfula S, Bloembcrg- GV, Giger J, et aL Compari.oon of European Committee on Antimi-
the relative advantages and disadvantages of the many available crobial Swceptibility Teating (EUCAST) and Cl.'>I IICl'eening parameteno for the detection
typing systems is beyond the scope of this chapter and has been of extended..pectrum ~lactamue prodw:tion in clinical Enterobacteriaceae i.oolateo.1An-
summarized in several reviews (154-159) and in Chapter 8 of Ami"""' ChMollvr. 2012;67:159--166.

2!. Rodriguez-Bono J, Picon E, Navarro MD, et al. Impact of change> ill CLSI and EUCAST
this book. breakpoints for IUiceptibility in bloodatream infection> due to extende<kpectrum
~producing&dutricAU.wli. Cli"Micrnbiolbifld. 2012;18(9):894--900.
24. Diekema DJ, P13ller MA. Infection control epidemiology and clinical microbk>J.osy. lD:
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12 August J. Valenti
The Practice of Epidentiology

in Conununity Hospitals
The methods of epidemiology and infection control are see it. These demandll impact all hospitals, but the challenges
broadly applicable regardle,s of the size, location, or affiliation for rural and smaller community hospitals may not be the same
of a healthcare facility. The day-to-day practice of infection pre- as for larger institutions.
vention in most community hospitals is normally more a mat· Until recently, surprisingly little bad been published on in·
ter of developing and implementing policies, educating staff, fection control practices in the community despite the fact that
applying appropriate isolation precautions, conducting surveil- community hospitals provide more of the healthcare in the
lance, and re..ponding to regulatory and accrediting agencies' United States than larger. tertiary care centers (2). Evidence
requirements than engaging in the kind of science common of increasing interest in the state of infection control in com·
to larger academic centen. The ruccess of infection preven· munity hospitals is reflected by a growing literature examining
tionists (IPs) in any hospital depends not only on the training bow these infection control programs are configured and how
and dedication of those managing infection control and the they are responding to the challenges of resource availability,
resources allocated to their efforts, but also on the strength drug-resistant organisms, SSis, Clcstridium dijJidk infection,
of their own interpenonnel skills, their antibiotic stewardship and antibiotic stewardship (3).
programs, their clinical microbiology laboratories, the avail- The most cwrent available data reveals that nongtJYe'llUllent,
ability of healthcare quality expertise, and their access to the not-for-profit community hospitals accounted for 58% of the
decision-making apparatus of their institutions. 4,973 acute care hospitals in the United States (4). A3 hospitals'
The patient safety movement appropriately regards bed numbers decrease, the percentage of those hospitals cla..
healthcare-associated infections (HAis) as preventable adverse sified as rural markedly increases. Overall, 40% of the 4,973
events. The "culture" of patient safety compels healthcare fac:ili. hospitals were classified as rural and roughly 60% as urban.
ties, regardless ofsize, to improve their collection, analysis, and Most of the rural hospitals had S99 beds. The types of services
feedback of HAl data. Regulatory agencies, such as the Depart· offered by rural hospitals vary significantly by bed size, with
ment of Health and Human Service's Centen for Medicare and more services offered by hospitals with the greater number of
Medicaid Service, (CMS) and accrediting bodies (particularly bedll (5).
the Joint Commin:i.on ['IJC] (1), have re,ponded to pre,sures There is a paucity of data from these hospitals in the area
to reduce errors and adverse outcomes in hospitals by giving of studies of infectious disease&, HAl prevention and con·
greater attention to process and quality indicators as well as trot, as well as patient safety (7-10). Fortunately, the National
outcome measures related to HAis. Increasingly, CMS reim· Nosocomial Infections Surveillance (NNIS) system of the CDC
bursement is tied to certain HAis, with hospitals being denied always included a number of such community hospitals, but
payment for hospitaJ..acquired catheter-associated urinary tract before 2006, > 2,300 hospitals with < 100 bedll could not partic-
infections (CA-UTis), central line--associated bloodstream in· ipate in NNIS. The NN1S was merged into the National Health-
fections (CLA.-BSh), and certain surgical site infections (SSis). care Safety Network (NHSN) in january 2006. This Web-based
Such measures are expanding. system is making access to data entry and analysis for all hospi-
The appetite for healthcare quality data should motivate tals more accessible and useful.
hospital leadership to pay greater attention to their HAl rates A collaborative set of evidence-based recommendations
and to seek appropriate benchmarks for comparisons. Along published in February 1998 (11) remains useful for target-
with these changes, there has been a growing tendency toward ing some key discussion points. In March 2006, the authors of
transparency in disclosing hospital-associated adverse events. the previous edition of this chapter conducted a survey at the
Naturally, this requires data gathering and graphic display in Society for Healthcare Epidemiology of America (SHEA) in
ways that are accessible and understandable to consumers as Chicago inviting colleagues in hospital epidemiology to share
well as providers. The electromc medical health record and their top :issues and key frustrations with WI. A similar survey was
data-mining programs often come with the promise of reduc- conducted at the May 2006 statewide Wisconsin Association of
ing the work of surveillance and improving compliance, but Professionals in Infection Control and Epidemiology (APIC)
tailoring these systems to the particular needs of an institution meeting. For over 5 years, the Maine Infection Prevention Col-
(or healthcare system) takes time, money, and expertise. Un- laborative (a consortium consisting of the Maine Hospital A!!-
fortunately, there are as many ways to report and display data sociation, the Maine CDC, the Northeast Health Care Quality
as there are groups within and outside of hospitals who wish to Foundation, hospital epidemiologists, IPs, and administrators
139
representing every hospital in the State) a.l:!o conducted surveys levels of infection control staffing below the level of one IP
and gap analyses (see an example of a gap analysis survey in per 100 occupied beds. Only one hospital reported data entry
Appendix 1) for all participating hospital:! in Maine that echo and analytic support within the infection control department.
the concerns of IPs and hospital epidemiologists expressed in The results of the process observations showed variability in
other "convenience sample" surveys. compliance with evidence-based strategies for preventing
To be sure, more extensive data and gap analyses in infec- HAis. Sustained compliance with best practices frequently
tion prevention programs are needed, but the consistency requires repeated educational interventions, and one can
of concerns expressed in these surveys by IPs and hospital expect varying degrees of availability of trained IPs perform-
epidemiologists should encourage 1JC in its efforts to fos- ing these interventions to impact results. As Christenson et al.
ter a culture of safety, which must include a team of experts note, the size of the study imposes limitations on the con-
in HAl prevention and control, an absolute requirement and clusions one can draw, but it is hoped that such studies will
responsibility of the hospital administration and leadership encourage broader examinations of infection control prac-
(Table 12.1). Lack of time, an increasing scope of work, a fre- tices and contribute to evidence-based practices aimed at bet-
quent lack of administration-provided resources, and sense of ter control of HAis globally. Clearly, more study is needed to
value highlight the results. A few quotes from the Wisconsin examine whether there is a correlation between staffing and
data are relevant. A common thread in the era of pandemic compliance with evidence-based practices and, ultimately,
influenza and bioterrorism preparedness concerns the lack of outcomes.
time (hours, staff, or both): "I have the desire to be proactive Even with data, it remains to be seen whether hospital infec-
rather than always reactive, but there is not enough time ... : tion prevention programs will receive adequate resources. In
The frustration with lack of administration support is articu- October 2006, Wright et al. surveyed the SHEA membership in
lated best from two quite different hospitals. From a 600-bed an attempt to develop data on the responsibilities, resources,
hospital: "The Infection Control Department is perceived as a and compensation for members and their departments. Their
thorn in their (administration's) side instead of an important conclusions suggest that resources for healthcare epidemiol-
component ofhealthcare," and from a 100-bed facility: "Infec- ogy and infection control were below those recommended
tion control has always been seen as a (cost center) rather than in older as well as newer studies, surveys, and expert panels
an income-producing department." published in the literature. They conclude that "The quickly
Our informal surveys underscore some of the findings pub- evolving external mandates that have arisen since our survey
lished in a formal survey conducted among Volunteer Hos- have placed additional strain and expectations on our already
pitals of America (VHA) hospitals in various regions of the resource-acarce departments." (13) . Furthermore, the effects
country by Christenson et al. (12). These authors conducted a that the changing financial landscape of healthcare as well as
demographic survey of 31 hospitals ranging in size from <50 the increasing interest of government (local and federal) in ex-
beds to >500 beds to assess the staffing, structure, and func- ercising control over HAis will have on infection prevention
tions of infection control departments in participating hospi- programs are uncertain.
tals. Participants were asked to conduct observational studies The sundry internal and external forces facing infection
of compliance with process measures, such as hand hygiene control (IC) programs in community hospitals prompted
practices, and ventilator-associated pneumonia (VAP), CIA- Anderson and Sexton to comment forcefully on the chal-
BSI, and CA-UTI rates. One-third of the participants reported lenges facing the programs in community hospitals and their
TABLE 12.1 The Top Issues and Frustrations of InKction Prevention and Control Team Members
in2006
Top Iuuea Top Frustrati01111
1. Collecting, interpreting, and using HAl infection surveillance data 1. Need to find enough time to do multiple tasks and the ability to
uaefully and appropriately prioritize those tasks. Dealing with the
ever-increasing scope of work
2. Getting HCWs, especially nurses and doctors, to consutently 2. Lack of adminutrative understanding, support, and buy-in of the
use evidence-based guidelines, especially for uolation and central role of HAl prevention and control as the paradigm for
hand hygiene patient safety
ll. Having the problem of MOROs and the need for appropriate ll. The ability and willingness of the HCWs, including both doctors
antibiotic use and surgical prophylaxis and nurses, to use policies correctly and understand the benefits
of those policies for their patients
4. Trying to use and keep up with new evidence and guidelines
to create uaeful and up-to-date policies, procedures, and care
measures that the HCWs will understand and use
5. Addressing the increasing need for both old and new d~ease
reporting, planning for new crues, and potential outbreaks and
still doing the preceding 1-4
&um~: 94 responses from hospital epidemiologi..ts and infection control professionals at the March 2006 SHEA meeting and the May 2006
Wisconsin APIC Chapters Meeting.
Chapter 12 • The Practice ofEpidemiology in Community Hospitals 141
survival (14). On the basis of research within their network of • Accomplish these two goals in a cost-effective manner,
39 hospitals affiliated with the Duke Infection Control Out- whenever possible.
reach Network (DICON), they cite the following as three of
They also note both the value and necessity of measuring
the most important factors facing IC programs in community
the effectiveness of the procedures, policies, and programs put
hospitals:
in place to accomplish the three goals. Most hospital epidemi-
• Deficits in administrative leadership ologists agree that, as with medications, conducting prospec-
• IC a low priority tive, controlled trials of a current procedure compared with a
• Frequent leadership changes that "stall" the progress newer procedure is optimal. The outcome of most interest, of
of IC programs when hospital infrastructure changes course, is the HAl rate targeted by the procedure. Rarely can
• Lack of specialization studies like the medication studies using a double-blind con-
• Reliance on volunteer services of busy physicians trolled method be done. And in small hospitals, small denomi-
• Inadequate expertise nators make this especially difficult. Complicating HAl studies
• Even among ID physicians who may not be trained further is that outbreak situations and endemic situations may
in hospital epidemiology not show the same results in separate studies because the un-
• Lack of reimbursement for hospital epidemiologists derlying issues may be different. At times, these realities lead to
• Limited numbers of personnel despite the rise in the a conflict in recommendations (19-21).
type and severity of problems facing IPs We recommend a careful review of this article by our epi-
• Do not meet minimum standards of staffing demiologist and IP colleagues in community hospitals (11).
• Having duties outside of IC more common among Our review of the article indicates that the discussion and the
ICPs in community hospitals as compared with those 23 recommendations are still useful. Since the publication of
in tertiary hospitals this paper in 1998, additional studies have supported and in-
• Lack of support staff creased the evidence supporting these recommendations.
• Lack of resources for continuing education
Good surveillance and infection control activities reduce KEY ISSUES IN COMMUNITY
multidrug-resistant organism (MDRO) rates in acute care HOSPITALS
hospitals, yet two surveys of Canadian hospitals (where MDROs
are less a problem than in the United States, but are, none- ADEQUATE HAl PREVENTION
theless, on the rise) revealed that effective surveillance and AND CONTROL TEAM
control activities are not in place in many Canadian hospi-
tals (15-17). In 2000, a survey of 72% of Canadian hospitals Who, Haw Much Time, and How Many. The 1999 Institute of
with >80 acute care beds revealed that there was <1 IP per Medicine report Th Err Is Human (22) brought the concept of
250 beds in 42% of hospitals, and only 60% ofinfection control patient safety, or lack of it, to the forefront of public discourse.
programs had physicians or doctoral professionals with infec- Lost in this report, however, was the long-11tanding paradigm of
tion control training. SSI rates were provided to surgeons in HAl prevention; it was barely mentioned. A subsequent paper
only 37% of hospitals. A follow-up study indicated that surveil- showed the value of infection control in the safety push (23).
lance and control activities in acute care hospitals in Canada As our colleagues indicate, lack of time, expanding responsibili-
are being performed in roughly two-thirds of the 120 hospitals ties, and support are their principal challenges. As Cook et al.
responding to a survey. point out, the IP, physician epidemiologist (if available), a data
It should be readily apparent from the preceding discussion analyst, and an administrative assistant are the core elements of
that the reasons that infection control programs in many com- the infection prevention team (18).
munity hospitals are struggling to implement best practices are IPs are usually nurses (but not exclusively) with special train-
complex and certainly worthy of further study. We propose a ing and certification, preferably by APIC. They are primarily re-
number of recommendations that we hope will be useful to sponsible for the day-to-day functioning of the infection control
small hospitals facing these challenges. program in most hospitals. They are especially important where
Most of the top issues in Table 12.1 are discussed in detail there is no trained physician epidemiologist. They should have
in other chapters of this book. Scheckler et al. have articu- managerial and information technology skills as well as a good
lated the principal goals for infection control and epidemiol- working knowledge of microbiology, infectious diseases epide-
ogy (11). More recently, Cook, Marchaim, and Kaye published miology, and quality improvement. In small hospitals, they may
widely applicable and sound guidance for developing a success- play a role in employee health, quality, and safety.
ful infection prevention program, which hospitals of any size or According to one study by Stone et al. (24), IPs spend
scope will find helpful (18). They emphasize the importance of only 13% to 15% of their time in fJmlentative roles, such as
a written mission statement, establishing and documenting a teaching, isolation, and preparing policies. The majority of the
vision (future goals) and core values (the day-to-day operation IPs' time (44.5%) is spent on surveillance activities. Because
of the program). The following goals, adapted from Sheckler of the surveillance, data entry, and analysis responsibilities of
et al., are helpful when developing these three essential com- IPs, it is now more common for infection control activities to
ponents of a program: be decentralized, with surveyors on nursing units or in clinical
departments acting either independently or as liaisons of the
• Protect patients. infection control program.
• Protect healthcare workers (HCWs), visitors, and others Another important study on staffing using the Delphi method
in the healthcare environment. reported similar results with respect to the predominance of
surveillance activities (39% ofiPs' time) (25). The Delphi proj- on a survey by reporting lack of administrative support, which
ect's expert panel recommended that there be 0.8 to 1.0 IPs might rebound to the detriment their programs. Finally, the
per 100 occupied beds. It was also pointed out that more than lack of business expertise on the part of infection prevention
just bed numbers should influence decisions about staffing. personnel may hinder their efforts to effectively communicate
Smaller hospitals may not have a physician epidemiologist their needs to business-oriented administrators.
(usually a specialist in infectious diseases with epidemiological
training) available on site. As the Delphi project demonstrates,
the complexity of modem healthcare has made simple calcula-
tions of the full-time equivalent (FTE) size of the HAl preven- 1. Every acute care hospital must have in place a budget plan
tion and control team difficult. Scheclder et al. did not use a for HAl prevention and control. This plan should include
number. The literature has no recommendations correlating the IP and hospital epidemiologist positions and time re-
bed size or discharges with hours needed for a physician hospi- quired per our four recommendations noted in the pre-
tal epidemiologist. ceding section.
Our recommendations, which follow, are based on our own 2. TJC must articulate and enforce its new requirement con-
extensive experience, our review of the literature. The reality cerning hospital administrative responsibility in the area of
of increased reporting requirements and responsibilities such HAl prevention and control as an integral part of patient
as reviewing renovation and new building projects or planning safety.
for natural or man<aused disasters were considered in our 3. Patient safety activities and quality-improvement initiatives
recommendations. in a hospital must complement the necessary roles of IPs
and hospital epidemiologists. The decades of experience
in HAl prevention and control and the science base de-
veloped should be used by those responsible for oversee-
ing quality and safety in our hospitals. Similarly, IPs and
1. For every 100 staffed beds in an acute care hospital, there
hospital epidemiologists also should recognize the value of
should be at least one FTE trained IP and at least 4 hours
well-trained quality professionals in improving safety and
of a paid physician hospital epidemiologist.
outcomes.
2. The smallest hospital should have the services of an IP for
at least 8 hours a week (20% time), which should include
some time-at least 3 days a week-at the hospital. Likewise, CHANGING HUMAN BEHAVIOR-AN ESSENTIAL
a physician hospital epidemiologist should be accessible to COMPONENT OF INFECTION PREVENTION
even the smallest institution by e-mail and telephone, and
There is not enough data to say with certainty that smaller hos-
should be paid for the time spent consulting.
pitals have an easier time getting employees and medical staff
3. Adequate information technology (IT) support, Internet
to accept appropriate vaccinations, postexposure follow-up rec-
access, and time for continuing education are essential for
ommendations, proper use of personal protective equipment
the IPs no matter what the size of the hospitaL
(PPE), and the rationale for policies and procedures related to
4. With acute care hospitals of .<!:200 staffed beds, one FTE
infection prevention and control. However, there is universal
of staff support---secretarial and/ or medical record
agreement that hand hygiene remains a problem in healthcare
specialist-must be available. This person would function
facilities of any size.
as an administrative assistant in facilitating the role of the
Hand hygiene is essential before and after contact with a
IPs and physician epidemiologist.
patient or his or her immediate environment whether using
These recommendations are barebone essentials. Ample evi- gloves or not. One hospital used the "Clean In, Clean Outn
dence indicates that a proactive HAl prevention team can sub- sign in every patient room. However, multiple studies since the
stantially help reduce adverse events in the patients the hospital CDC's Healthcare Infection Control Practices Advisory Com-
serves. The critical issue is making a convincing business case for a mittee (HICPAC) Hand Hygiene Guidelines was released (27)
program's needs. SHEA has published valuable guidelines (25) for have shown only modest compliance with this intervention,
developing a cogent business argument for IGrelated proposals. which has proven effective since the time ofSemmelweis. HCWs
Cook et al. have summarized these and other useful suggestions seem better at hand hygiene after rather than before seeing a
from the literature for making a strong business case (18). These patient. Nurses tend to be much better than doctors. And, most
exercises are of particular value to small hospitals with limited re- surprisingly, nonsurgical primary care physicians and intensiv-
sources. They emphasize the importance of soliciting feedback ists are better than their surgical colleagues (28).
and garnering support from administrators, key stakeholders, and Another long-standing concern of IPs and hospital epide-
institutional business leaders prior to framing a proposal. miologists is the attitude of some nurses and physicians toward
Admininrative Understanding and Support. 1JC attempted in isolation precautions. The apparent lack of understanding
its 2006 requirements for HAl prevention and control and pa- regarding the rationale for careful hand hygiene and the use
tient safety to require that the administrative authorities of the of PPE by those involved in direct patient care continues to
hospital-chief executive officers (CEO) and board---support frustrate the infection control community. The severe acute re-
the staff and resources to do the job. The fact that these respiratory syndrome (SARS) outbreak, the appearance of a new
quirements appear to have made little impact in our surveys SARS-Iike corona virus infection from the Middle East (MERS-
and our experience with many hospitals suggest that they are CoV), the emergence of highly resistant bacteria, and novel-
either too new to be effective or that they are low on TJC's sur- strain influenza viruses should be adequate incentive enough
veyors' priority list. There may also be reluctance on the part of for all HCWs to consistently practice the appropriate use of
IPs and physician epidemiologists to risk getting marked down PPE and hand hygiene. Moreover, the increased scrutiny of the
public on how HCWs manage these threats should heighten a quality)-and are an increasing reality in today's consumer-
sense of professional responsibility. driven patient safety movement.
With the identification of vancomycin-resistant S. aunw
(VRSA), CO-MRSA, more virulent strains of C. difficile, extended-
Recomnu:notions
spectrum beta-lactamase (ESBL)-resistant organisms,
1. One effective way to measure the success of hand hygiene carbapenem-resistant Enterobacteriaceae (CRE), fungal resis-
implementation is by direct observation of the hospital tance, multidrug-resistant Mycobacterium tuberculosis, and other
medical and nursing staff's use of the CDC HICPAC Hand emerging organisms, it is imperative that community hospitals
Hygiene Guidelines with direct feedback to the units have a complete understanding of the resistance patterns in
and types of staff on their percentage use of appropriate their institutions, their affiliates, and their region. Similarly,
hand hygiene. they must keep up with developing recommendations for
2. Select an alcohol-based hand rub (foam or gel) that is most controlling these pathogens, even if such pathogens have not
acceptable to staff in nials. yet affected them.
3. Authorize all HCWs to ask for a "time-<>ut" to review missed While antibiotic resistance is a daunting problem, a substan-
opportunities for the proper use ofPPE in patient isolation tial body of literature demonstrates that these organisms can
situations. be successfully controlled with multidisciplinary efforts that
4. Enable the admitting and/or supervising nurse on a unit include active surveillance testing, contact or barrier precau-
to put a new patient in isolation if the patient's admitting tions, careful environmental cleaning, effective antimicrobial
diagnosis or condition warrants. stewardship, and strict compliance with evidence-based hand
5. Whenever possible, use a ~forcing function" or engineer- hygiene practices. The degree to which control measures
ing control rather than human behavioral change to im- should be adopted universally, particularly in regions with low
plement a new policy. prevalence rates of resistance, is one of the issues surrounding
6. Establish a culture of accountability for clinicians on the debate among experts over developing guidelines for man-
all units/wards. It is the responsibility of clinicians and aging resistance. This can confuse and deter smaller hospitals
chiefs/directors of wards/units, rather than only infec- that are attempting to determine and implement best practices
tion control, to ensure compliance with infection control for the identification and control of these organisms.
recommendations.
RECOMMENDATIONS
CONTROL OF RESISTANT ORGANISMS
In 2003, SHEA published an extensive review of the litera-
No matter what the setting or size of a hospital, the problem of ture and guidelines for the control of MRSA and vancomycin-
MDRO infection is a major preoccupation for !CPs and has led resistant enterococcus (VRE) (15). It is widely known that the
to calls for action from many quarters. Data comparing percent- publication of this guideline during the simultaneous develop-
ages of healthcare-associated Staphylococcus aunus infections ment of draft guidelines by HICPAC sparked a vigorous debate
with methicillin-resistant Staphylococcus aunus (MRSA) in NNIS among experts as to how to interpret and apply the best science
hospitals with <200 beds to those with >200 beds between 1992 to control these organisms. Most hospitals must decide what
and 2002 demonstrates that smaller hospitals, formerly behind they will take from each of the guidelines to develop strategies
larger hospitals in their percentage of MRSA-HAis, have caught for preventing the dissemination of resistance. Both guidelines
up with larger hospitals (29). There is a need for more study should be studied carefully. The CDC HICPAC MDRO Guide-
of MDRO rates in the community healthcare setting; however, line recommends that if a hospital's rate of infection with these
most studies of the epidemiology and control of MDROs have pathogens is not decreasing, it should implement more aggres-
come from large, academic centers. Diekema et al. conducted sive measures, including active surveillance testing. We pres-
a survey of >400 US hospitals and found that antimicrobial re- ent an approach to managing MRSA and VRE adopted by the
sistance rates were strongly associated with the size, geographic MaineHealth® Infection Control Consortium in Appendix 2.
location, and academic affiliation of hospitals (30). The most salient difference between the two guidelines
Hospitals, especially those with intensive care units (ICUs), is the screen and isolate or ~search and destroy" practice (20).
and long-term care facilities are important epicenters and re- The SHEA guidelines recommend aggressive use of active sur-
positories of MDROs. Increasing rates of community-onset veillance testing to identify patients colonized with these or-
MRSA (CO-MRSA) also are having an impact on hospitals as ganisms (because routine clinical cultures do not detect the
CO-MRSA strains are recognized as causes of HAl infections colonized reservoir) and placing those patients on contact
as well (31). Unfortunately, many centers, discouraged by the precautions. The HICPAC guidelines favor a graduated, two-
increase in MRSA and the cost of control, relaxed previously tiered approach with increased intensity of control activities
recommended infection control practices in the recent past. In in settings where baseline measures fail to decrease transmis-
contrast, some northern European countries adopted national, sion rates. A m~or argument used by those who find the SHEA
comprehensive programs resulting in impressive control of re- document too rigorous is that many studies used multiple in-
sistant organisms. terventions and are unable to weigh the strength of any single
Cost and safety issues surround these infections-increased intervention or combination of interventions (an argument
morbidity and mortality, more expensive and limited treat- never made with any of the other CDC HICPAC guidelines,
ment options, longer hospital stays, patient dissatisfaction, the although this is also true of them). However, Muto et al. vigor-
cost and inconvenience of precautions, litigation, and adverse ously defend the SHEA approach of active surveillance testing
publicity for healthcare facilities (especially where drug resis- and contact isolation (also called active detection and isolation
tance is publicly reported and/or considered a measure of or ADI), citing the success of northern European counnies and
Western Australia in controlling these infections. They contrast neither guideline currently considers how resources should be
this with the failure of standard precautions and failure to allocated for control programs-an issue of great importance
control these organisms in other areas of Europe and Austra- to community hospitals without research dollars to divert to
lia where a less aggressive approach is used (32,33). In Euro- such endeavors. Consumer pressure is being brought to bear
pean countries, the delivery of medical care may differ from on community hospitals through legislative efforts to control
that in US healthcare facilities, the intended target for these MRSA. It would seem that collaboration of hospitals and their
guidelines. In countries and institutions where an aggressive experts can influence these efforts by explaining the science at
approach, such as that recommended in the SHEA guidelines, hearings that can often be emotionally charged (36).
has been adopted, however, impressive control of MRSA and Reliltant Grom-Negative Organimts. The size, location, and
VRE have been achieved. services of a hospital also can conceivably impact the risk for
Translating the science coming out oflarger academic cen- acquisition of these organisms. Extended-spectrum and AmpC
ters into practice at the level of smaller, nonteaching hospitals beta-lactamase-producing bacteria are important causes of
is complicated by a lack of understanding of which interven- HAis, and Pseudomonas aeurignosa resistance to quinolones,
tions are most effective and an imprecise understanding of imipenem, and third-generation cephalosporins; Enterobacter
the epidemiology of these organisms outside of large hospi- resistance to third-generation cephalosporins; and multidrug-
tals. Some experts argue that it is better to direct efforts and resistant Acinetobacterare on the rise worldwide (37).
resources at reducing SSis and device-related HAis as a means Even more concerning is the emergence of CRE. In early
to control resistance rather than to implement the type of 2013, the CDC published an alarming report indicating a qua-
"search and destroy" strategies that have been successful in drupling of CRE infections between 2001 through 2011 (38).
Europe. Indeed, the former approach is gaining momentum Carbapenem antibiotics have been regarded as drugs of choice
as a result of national quality efforts toward implementing for the management of infections due to ESBL-producing
proven methods of reducing such infections by encouraging gram-negative bacteria. However, over the last decade, reports
the utilization of "bundles" of evidence-based best practices of CRE have been increasing. Infections with these organisms
for prevention (20). However, it is far from clear that this are associated with high mortality. CRE strains have been de-
will be an adequate national strategy for decreasing the rates tected in all regions of the United States and in community
of MRSA and VRE in the United States and in community hospitals of all sizes, including those with < 100 beds.
hospitals. The Clinical and Laboratory Standards Institute (CLSI, for-
West et al. have published a paper on the effect of targeted merly the National Committee for Clinical Laboratory Stan-
surveillance cultures of high-risk populations for control of dards [NCCLS]) issues guidelines to help laboratories identify
MRSA in a community hospital system (34). They acknowl- ESBL-producing Enterobacteriaceae (and CRE). Despite cur-
edged the workload and expense associated with universal rent recommendations, not all clinical microbiology labora-
surveillance cultures and the reluctance of administrations to tories routinely identify ESBL-producing organisms. Surveys
accept such efforts. They used the SHEA guidelines for isola- looking at the ability of clinical laboratories to detect ESBLs
tion of patients colonized or infected with MRSA and achieved identified a serious gap in this regard (40,41). Community hos-
reductions in MRSA in a cost-effective manner. Patients in- pital outbreaks are well-described (42,43).
fected with MRSA had been placed in isolation since 1988, Risk fuctors for acquiring these organisms are similar to
but infection rates remained stable despite the additional those for the acquisition of other gram-negative bacterial HAis:
measure of screening nares specimens from patients in the indwelling catheters, increased severity of illness, urgent ab-
ICU, a practice initiated in 2001. Only after active surveillance dominal surgery, ventilator use, and prolonged hospital stay.
cultures targeted high-risk patients throughout the hospital Lautenbach et al. found that patients infected with pathogens
was a significant reduction in MRSA infection rates realized. with ESBLs had a greater cumulative antibiotic exposure than
However, Huang et al. have documented the impact of routine did controls; total antibiotic exposure was the only indepen-
screening cultures and isolating colonized patients in ICUs on dent predictor of infections with these organisms (44). Their
hospital-wide MRSA bacteremia. They achieved a 40% reduc- study suggested that curbing the use of all classes of antibiotics
tion in MRSA-BSis in non-ICU patients and a 67% reduction used against gram-negative organisms may be important. Con-
hospital-wide. Using interrupted time--series design for their trol measures should focus on limiting contact transmission of
analysis of 9 years of data, they determined that the statistically resistant isolates and controlling antibiotic use. Although more
significant factor in bringing about these reductions was active study is needed, some have suggested implementing infection
surveillance cultures with subsequent placement of patients on control measures for ESBL-producing pathogens (and CRE)
contact precautions in the ICU. Typical multiple interventions, similar to those used to control MRSA and VRE (15). How-
such as the introduction of alcohol-based hand gels, a hand- ever, it is unclear that active surveillance testing for multidrug-
washing campaign, and maximal sterile barrier precautions for resistant (MDR)-gram-negative bacteria will be as useful as it has
insertion of central lines, did not have significant impact on been for MRSA. A concise review of strategies for the control of
the rates (35). MDROs has been published by He bert et al. ( 45) . They discuss
That vigorous debate over the best approach to controlling various strategies and their limitations. Just as with MRSA, the
MRSA locally, regionally, and nationally persists is evidenced strength of the evidence for recommended measures can be
in a recent review by Kavanagh et al. (36). Other chapters in challenged, as studies are adversely affected by design, setting,
this book discuss these issues more thoroughly, but the implica- poor adherence to interventions by HCWs, lack of and/or de-
tions of these and other guidelines for community hospitals are lays in getting antimicrobial resistance information in a timely
significant. As Strausbaugh et al. (20) note, neither the SHEA manner ( 45).
nor the CDC HICPAC guidelines address in a more compre- Our recommendations for the control of ESBL-producing
hensive sense the goal of these control efforts. In addition, and other MDR-gram-negative organisms of epidemiologic
importance follow. We prefer an aggressive approach to con- colonization; and limiting the use of certain agents should be
trol these organisms until scientific evidence suggests that part of an overall strategy to reduce resistance in all hospitals
less aggressive measures are adequate. Harris et al. have pub- (51). A concurrent review of antimicrobial use by specialists
lished an excellent summary and analysis of the data on ac- along with computer-assisted antimicrobial decision support
tive surveillance cultures to identify colonized patients and can be extremely helpful in controlling the spread of resis-
whether they should be placed on contact precautions (37). tance (52). Such programs require a substantial commitment
They provide a framework for decision making and recom- of resources by a hospital, but can result in cultural changes,
mendations for future investigations. Hospital epidemiolo- reduced costs, and lower rates of bacterial resistance (53) . Pro-
gists must determine what is best in their institutions. The moting infection control and antimicrobial stewardship in all
following recommendations have been adapted from Paterson hospitals should be priorities in a national strategy to combat
and Yu for pathogens producing ESBLs; however, some of resistance.
these recommendations also could be applied to control The community hospital must be considered in the con-
other highly MDR-gram-negative organisms of epidemiologic text of its "trade routes," which provide opportunities for the
importance (46). dissemination of resistance (Figure 12.1). Antimicrobial resis-
tance is commonly a regional problem, involving > 1 facility in
1. Laboratories should follow CLSI guidelines for detecting a geographic area, and regional approaches to controlling the
ESBL-producing organisms and CRE. spread of MDROs, such as CRE, is currently recommended by
2. Proper hand hygiene, gloves, and gowns should be em- the CDC (54). Regional approaches that incorporate coopera-
ployed when caring for infected or colonized patients. tion with local public health authorities will be essential for
3. Clinical and laboratory staff, patients, and their visitors monitoring and thwarting the spread of highly resistant organ-
should be educated about these organisms. (The CDC isms within the conununity.
Web site is an excellent source of information about these A study of the epidemiology of MRSA and VRE among hos-
pathogens for healthcare providers and lay persons.) pitals in Iowa (ranging from approximately 86 to >858 beds in
4. Affected patients should be isolated or cohorted, and diverse geographic regions of the state) uncovered differences
HCW staffing assigrunents should minimize the potential in the epidemiology of these two organisms; these findings have
for cross-transmission. important implications for their control (55). For instance,
5. Antimicrobial controls, especially of extended-spectrum they found that VRE and MRSA shared some risk factors for
cephalosporins and carbapenems, should be instituted. acquisition as well as some significant differences in that MRSA
6. Consider periodic rectal and urine cultures of patients in was endemic in rural hospitals (rural location and hospital size
ICUs to identify carriers. In some institutions, active sur- of <200 beds were significant risk factors for MRSA infection),
veillance cultures are used only in outbreak situations (37). whereas hospitalization at a smaller hospital had a negative cor-
7. Inform receiving units or other facilities of infected or col- relation with VRE infection. The authors present compelling
onized patients. evidence of the importance of understanding the regional epi-
8. Because carriage can persist, previously colonized or in- demiology of resistance and identifying the reservoirs of these
fected patients should be regarded as colonized until organisms.
proven otherwise and medical records should be flagged Thinking regionally has been of benefit in control-
to indicate status at readmission. ling VRE and MRSA within a geographic area. A landmark
9. Colonized or infected patients may be admitted to nursing
homes where they should be placed in single rooms with
private bathrooms. The use of common areas by colonized
patients should be considered on an individual basis. Local residents,
outpatient Other
Although competent antimicrobial stewardship and infec- facilities,

long-term care,
tion control programs are of demonstrable efficacy in reduc-
rehabilitation
ing the spread of resistance, overall use of antimicrobials,
and cost, such expertise may not be available to the smaller
conununity hospital owing to lack of monetary or human re-
sources (47,48). In many hospitals, antimicrobial stewardship
is a shared responsibility of infection control, the pharmacy
and therapeutics committee, and clinicians. The proportional
influence of infection control compared with optimization of
antimicrobial use on the reduction of HAis due to MDROs
seems to depend, to some extent, on the organism and mode
of transmission (49,50). Horizontally transmitted organisms,
such as MRSA, VRE, or C. difficile, seem more amenable to
infection control measures, whereas resistance arising from
the endogenous flora of patients receiving antibiotics, such as
ESBL-producing organisms, requires more emphasis on anti-
microbial controls. Choosing the most appropriate antimicro-
bial, dose, and duration of therapy on the basis of the proper
collection and interpretation of cultures; using an up-to-date Figure 12.1. Relationships among divene healthcare facilities in
clinical microbiology laboratory; treating infection rather than the community setting-routes for the spread of antibiotic resistance.
investigation in 32 healthcare facilities in the Siouxland interdependence as new challenges unfold even as this book is
region of South Dakota, Iowa, and Nebraska reported by published.
Ostrowsky et al. demonstrated that control of VRE could be
accomplished in a regional healthcare system by performing
active surveillance cultures to detect colonization in high-risk REQUIREMENTS FOR INFRASTRUCTURE AND
patients and using contact precautions for colonized and in- ESSENTIAL ACTIVITIES OF INFECTION CONTROL
fected patients (56). This study demonstrates the efficacy of AND EPIDEMIOLOGY IN HOSPITALS (10)
using evidence-based guidelines in all healthcare facilities in The recommendations of the "essentials" are so relevant to
a region. this chapter that we repeat them here with permission. When
Cooperative partnerships that share data and resources possible, the panel used an evidence-based approach. Recom-
among centers can improve efforts at controlling MDROs mendations, therefore, are categorized in Table 12.2, using a
and other important HAis. Kaye et al. reported on the work modification of the scheme developed by the Clinical Affairs
of DICON (57). They used a standardized approach to surveil- Committee of the Infectious Diseases Society of America and
lance, provided frequent feedback, and followed uniform poli- the CDC HICPAC classification scheme.
cies using CDC guidelines at 12 hospitals in their network. They
achieved a reduction in bloodstream infections, healthcare- Functions
associated MRSA infections, VAP, and blood-borne pathogen
exposures among employees. Kaye et al. estimated remarkable Managing Critical Data and Information
economic benefits. As of this writing, DICON continues to re- Recommendation 1: Surveillance of HAis must be per-
port reductions in these areas and in CA-UTis on their Web
formed (Category I). The surveillance process should
site (www.dicon.mc.duke.edu/). There are other examples of incorporate at least the following elements:
successful regional approaches to MDROs (58). A more re-
cent publication from this group confirms that hospitals with • Identification and description of the problem or event
long-term participation in their infection control network ex- to be studied.
perienced significant reductions in HAis (50%), mortality, and • Definition of the population at risk.
costs (59). • Selection of the appropriate methods of measure-
Our own experience is with a 13-fucility infection control ment, including statistical tools and risk stratifications.
consortium sponsored by MaineHealth® that is modeled on • Identification and description of data sources and
the successful outcomes of the Barnes-Jewish Hospital In- data collection personnel and methods.
fection Control and Hospital Epidemiology Consortium in • Definition of numerators and denominators.
the St. Louis area, from which we received valuable support • Preparation and distribution of reports to appropriate
in developing our group (60). The increased cooperation groups.
among the MaineHealth® Infection Control Consortium par- • Selection of specific events to be monitored, which
ticipants, which include very small rural hospitals and larger should be guided by validated, nationally available
hospitals (200 to 600 beds), home care agencies, long-term benchmarks appropriately adjusted for patient risks so
care facilities, a rehabilitation hospital, and so on has been a that meaningful comparisons can be made.
positive and productive experience to date. The group is shar-
ing expertise, data, and policies on the control of MDROs
and providing member institutions with evidence-based algo- Jla:om.m.cndation Categories
rithms and standard approaches to regional problems such as I. Strongly recommended Strongly recommended for
C. dif.ficilB-associated disease (CDAD), VRE, MRSA, and vaccina- implementation based on
tion strategies. Clinicians and others can link to a single Web • Evidence from at least one
site for updated guidelines, policies, and patient educational properly randomized, con-
resources. Regional standardization of policies and shared edu- trolled trial.
• Evidence from at least one
cational documents contribute to the confidence of clinicians,
well-designed clinical trial
administrators, and patients.
without randomization.
• Evidence from cohort or
BURDENS OF EXPANDED WORK case-control analytical studies
(preferably from more than
Planning for a bioterrorism event, dealing with the possibil- one center).
ity of the admission of a patient with a novel coronavirus from • Evidence from multiple time-
overseas, and having to plan for the next pandemic of influ- series studies.
enza have added work to already stressed infection control pro- n. Recommended Recommended for implementation
grams. It is not the function of this chapter to replicate what based on
is well-covered in other parts of this book. Suffice it to say that • Published clinical experience
these issues are an important part of the field ofhealthcare epi- or descriptive studies.
demiology in community hospitals. They also require dose col- • Reports of expert committees.
• Opinions of respected
laboration with local and state public health authorities. The
authorities.
need for an expanded review of the infection control issues and
risks in hospital renovation and building projects has also taken m. Recommended when
on a new urgency in recent years. More work means more time required by government
rules or regulations
needed. These issues illustrate in a profound way the reality of
Recommendation 2: Surveillance data must be analyzed employee health program that relate to the transmis-
appropriately and used to monitor and improve infection sion of infections in the hospital.
control and healthcare outcomes (Category I). • Infection control personnel should be available to the
Recommendation 3: Clinical performance and assessment employee health program for consultation regarding
indicators used to support external comparative mea- infectious disease concerns.
surements should meet the criteria delineated by SHEA Recommendation 10: At the time of employment, all
and APIC (Category II). facility personnel should be evaluated by the employee
Specifically, these indicators and their analyses must health program for conditions relating to communi-
address the following parameters: cable diseases (Categories II and III) .
• Relation to outcome or process. The evaluation should include the following:
• Ability to measure variation in quality. • Medical history, including immunization status and
• Definition of numerators and denominators. assessment for conditions that may predispose per-
• Reliability, completeness, and feasibility of data sonnel to acquiring or transmitting communicable
collection. diseases.
• Appropriate risk adjustment. • Tuberculin skin testing or QuantiFeron Gold testing.
• Comparability of populations; severity and case-mix • Serologic screening for vaccine-preventable diseases
adjustments for external comparison. if indicated.
• Training required for indicator implementation. • Medical examinations that are indicated by the
• Applicable benchmarks of standards of care. preceding evaluation.
Recommendation 11: Appropriate employees or other
HCWs should have periodic medical evaluations to as-
Setting and Recommending Policies and Procedures sess for new conditions related to infectious diseases that
Recommendation 4: Written infection prevention and may have an impact on patient care, the employee, or
control policies and procedures must be established, other HCWs, which should include review of immuniza-
implemented, maintained, and updated periodically tion and tuberculin skin test or QuantiFeron Gold status
(Categories ll and III). if appropriate (Categories II and ill).
• The policies and procedures should be scientifically • All facilities should maintain confidential medical
valid. records on all HCWs.
• The policies and procedures should be reviewed for • The employee health program should have the capa-
practicality and cost. bility to track employee immunization and tuberculin
• The policies and procedures should lead to improved skin test or QuantiFeron test status.
prevention or improved patient outcomes. Recommendation U: Employees must be offered
Recommendation 5: Policies and procedures should be appropriate immunizations for communicable
monitored periodically for performance (Categories II diseases (Categories I and ill).
and III). • Immunizations should be based on regulatory
requirements and recommendations of an advisory
committee on immunization practices for HCWs.
Compliance with Regulations, Guidelines,
Recommendation 13: The employee health program
and Accreditation Requirements
should develop policies and procedures for evaluat-
Recommendation 6: Healthcare facilities should use ing ill employees, including the assessment of disease
infection control personnel to assist in maintaining communicability, indications for work restrictions, and
compliance with relevant regulatory and accreditation management of employees who have been exposed to
requirements (Category II). infectious diseases, including postexposure prophylaxis
Recommendation 7: Infection control personnel should and work restrictions (Category I).
have appropriate access to medical or other relevant
records and to staff members who can provide informa-
tion on the adequacy of the institution's compliance
Interoening Directly to Prevent Thmsmisrion
with regard to regulations, standards, and guidelines
ofInfectiow Diseases
(Category II). Recommendation 14: All healthcare facilities must have
Recommendation 8: The infection control program should the capacity to identify the occurrence of outbreaks
collaborate with and provide liaison to appropriate local or clusters of infectious diseases (Category I) .
and state health departments for reporting communi- • Infection control personnel should review microbiol-
cable diseases and related conditions and to assist with ogy records regularly to identify unusual clusters or
control of infectious diseases (Categories ll and III). a greater-than-usual incidence of certain species or
strains of microorganisms.
• In patient areas of the healthcare facility in which
Employee Health
active prospective surveillance is not conducted, infec-
Recommendation 9: Infection control program personnel tion control programs should maintain regular contact
should work collaboratively with the facility's employee with clinical, medical, and nursing staff to ascertain
health program personnel (Category II). the occurrence of disease clusters or outbreaks, to
• The infection control program should review and assist in maintaining and monitoring infection control
approve all policies and procedures developed in the procedures, and to provide consultation as required.
Recommendation 15: All healthcare facilities must have will be under increased pressure generated by the consumer-
access to the services of personnel who are trained and driven movement toward public reporting of HAis-a move-
experienced in conducting outbreak investigations ment that is not always grounded in good science. The modern
(Category II). infection control program must maintain its standards in an
Recommendation 16: When an outbreak occurs, the infec- environment of cost-cutting and competition for resources with
tion control team must have adequate resources and diverse quality initiatives. Some IPs are leading these efforts,
authority to ensure a comprehensive and timely investi- but others are struggling to find a place at the table.
gation and the implementation of appropriate control Community hospitals, particularly rural facilities, are not al-
measures (Category II). ways able to attract professionals with infection control exper-
tise or interest, and, even when these professionals are available,
Education and 'I'raining ofHealthcare Workers hospital administrators may be unable or reluctant to provide
appropriate support for them so they can accomplish their
Recommendation 17: Healthcare facilities must provide on- traditional responsibilities in addition to investigating process
going educational programs in infection prevention and breakdowns or working on the cultural changes necessary for
control to HCWs (Categories II and III). the adoption of evidence-based practices. It could be argued
• Infection control personnel with knowledge of that cultural and policy changes are more easily brought about
epidemiology and infectious diseases should be in smaller institutions, but a number of factors other than size
active participants in planning and implementing influence these processes in our experience. The wise epide-
the educational programs. miologist weighs systems problems against ignorance or more
Recommendation 18: Educational programs should be culpable explanations for resistance to adopting practices of
evaluated periodically for effectiveness, and attendance proven efficacy such as hand hygiene.
should be monitored (Categories II and III). How, then, is the institution to find creative solutions to
• Educational programs should meet the needs of the the challenges of infection control in the community? Part-
group or department to which they are given and nering with other institutions to form regional infection con-
must provide learning experiences for people with trol and quality consortia gives small hospitals an opportunity
a wide range of educational backgrounds and work to share resources and expertise with larger hospitals in ad-
responsibilities. dition to providing academicians with new opportunities for
scientific study. In return, academic hospital epidemiologists
Resources should consider how they can support their community-based
(1) Persrnmel colleagues in developing scientific studies that will lead to
Recommendation 19: The personnel and supporting re- the development of evidence-based practices suitable to the
sources, including secretarial services, available to the populations they serve.
hospital epidemiology and infection control program Working with public health authorities in identifYing and
should be proportional to the size, complexity, andes- managing outbreaks or controlling regional infectious prob-
timated risk of the population served by the institution lems can benefit both the private and the public sectors. In-
(Category II). fection control working groups, which bring public health and
Recommendation 20: All hospitals should have the continu- private professionals together for regular discussion of com-
ing services of trained hospital epidemiologist(s) and mon concerns, afford another opportunity to share expertise
IP(s) (Category I). and resources. A number of states have found such coopera-
Recommendation 21: IPs should be encouraged to obtain tion gratifYing and effective.
certification in infection control (Category II). Community-based infection control professionals must take
(2) Nonpersonnel a greater role in educating their colleagues, administrators,
Recommendation 22: Each healthcare facility should pro- government, and the public about the importance, causes,
vide or make available in a timely fashion sufficient and metrics of HAis. IPs must convey the validity and utility of
office space and equipment, statistical and computer sound epidemiologic methodology to those involved in devel-
support, and clinical microbiology and pathology oping the public reporting of HAis. It is increasingly important
laboratory services to support the HAl surveillance, to the well-being of patients that those who manage community
prevention, and control program of the institution hospitals appreciate the efficacy of infection control programs.
(Category II). If community-based IPs and hospital epidemiologists wish to
Recommendation 23: Resources should be provided continue their leading role as patient safety advocates, they
for continuing professional education of hospital must be willing to educate a wider audience on the evolution,
epidemiologist(s) and IP(s) (Category II). methodology, and value of healthcare epidemiology. They must
also be ready to discuss the impact of their recommendations
on the resources of their facilities and the community at large.
CONCLUSIONS There is hope that the recent surge of interest in reduc-
ing the number of HAis-part of the overall focus on patient
Despite the historical primacy of infection control among safety-will lead to increased resources to control HAis, imple-
hospital quality and safety initiatives-and its documented mentation of evidence-based practices, improved monitoring
efficacy-today's infection control programs that are still try- of outcomes, and a better understanding of how to address the
ing to manage the traditional duties of surveillance, outbreak global issue of antibiotic resistance. It is our hope that these ef-
management, and education are now asked to include an in- forts will benefit the large number of patients in US community
creasing number of responsibilities. Moreover, they are or soon hospitals and elsewhere.
APPENDIX I the members of the Maine Infection Prevention Collaborative

with the help of the Maine CDC and the Northeast Health Care
The following is an example of an infection prevention gap Quality Foundation. The references at the bottom of the fonn
analysis survey fonn that was developed, approved, and used by provided the basis for this analysis.
•Policy exists for Measurement Performance Intervention to Instructions: Following the arrow, move from Left to
facility-wide use process exists data reviewed improve practice Right and place a check [..J ] in each box that applies.
X X X X Hand Hygiene and Environmental Cleaning Practices

Ensure easy access to soap and water/alcohol-based
hand gels.
Observation of practices-particularly with high-risk
procedures (before and after contact with colonized or
infected patients).
Feedback-•Just in time" feedback if fuilure w perform hand
hygiene is observed.
Prioritize room cleaning of patients on Contact Precautions.
Focw on cleaning and disinfecting frequently wuched surfuces
and equipment in the immediate vicinity of the patient.
Conduct environmental rounds.
X X X X Contact Precautions
Ensure availability of supplies (e.g., gown, gloves, etc.).
Use of gown and gloves for patient care.
Don equipment prior w room entry.
Remove prior to room exit.
Single room or cohorting for MDRO colonized/infected
patients.
Use of dedicated, nonessential items (blood pressure cuffi,
stethoscopes, IV poles/pumps).
X X X X Recognizing Previously Colonized/Infected Patients

Plan for ID of these patients.
These patients are subjected w "timely" intervention
(defined by hospital).
X X X X Laboratory Reporting and Surveillance

Mechanism w "rapidly" (within 1 hour oflab ID) report
MDRO results from laborawry w clinical area (list of MOROs
for notification) .
Rapid institution of interventions on newly identified MDRO
patients (within 2 hours of lab ID).
Moniwr trends in the incidence of target MOROs in the
facility over time.
X X X X Education for Staff and Patients

To improve adherence w hand hygiene.
To improve adherence w interventions (e.g., Contact
Precautions, Environmental cleaning).
To better understand the significance of the MDRO problem.
Patients who acquire MDRO during their hospital stay are
informed of this.
Patients and their families receive discharge instructions
regarding how to prevent MDRO transmission at home.
continued...
*Policy exists for Meuuremeot Performance Intervention to InstruclioWI: Following the arrow, move from Left to
facility-wide use process exists data reviewed improve practice Right and place a check [..J ] in each box that applies.
Goahfor MDB.O Program Gftd ~: Ct~TW ~
X X X X Strategies to Prevent Device- and Procedure-Associated

Infections Hospital-Wide
Centralline-118.!1ociated bloodstream infection ("bundle"
compliance)
Surgical site infections
CatheteroQSSOciated urinary ttact infections (avoid catheters,
timely removal)
Ventilator-associated pneumonia
X X X X Antibiotic Stewardship Program
The facility has an antibiotic stewardship program in place
addressing MDROs.
An antibiogram report u produced annually.
X X X X Administrative Measures
All MDRO HAls are reviewed via root cause analysu.
CEO and Board of Directors regularly review the facility
MDRO program and data.
CEO and Board of Directors regularly review progress
toward targets: processes (hand hygiene, gown and glove
use, environmental cleaning); outcomes (MRSA HAl rates
including CA-UTI, CIA-BSI, YAP, and SSI rates).
There is a progressive enforcement process wed for HCW
lapses in infection control practice: failure to perform hand
hygiene, failure to employ gown and glove use.
The progressive enforcement process for infection control
practice applies in equal measure to employed staff and
medical staff.
["*" Policy can include other supportive documentation]
APPENDIX2 cultures. Early identification of colonized patients and prompt

institution of precautions is necessary to decrease transmission.
The description of what constitutes "contact precautions" re-
MAINEHEALTff® INFECTION CONTROL mains gray in the literature as draft recommendations from the
CONSORTIUM GUIDELINES FOR THE CDC appear to recommend mandatory gloving and gowning
MANAGEMENT OF MRSA AND VRE for entry into the room. The previously published CDC guide-
lines call for anticipation of the likelihood of contact with the
Consistent use of standard precautions remains the basis for patient or his or her environment and the decision of whether
preventing the spread of infection in all facilities. In addition PPE is needed. We have chosen to include both at this time, as
to standard precautions, transmission-based precautions for some institutions are following the older guidelines and oth-
"organisms of epidemiological significance" remain important ers are following the recently released CDC MDRO guidelines
once an organism has been identified. This document seeks (which are similar to the SHEA guidelines with regard to man-
to lay the foundation for the basics of care. In certain circum- datory gowns and gloves).
stances, it may be necessary to exceed the basic guidelines, and There is a lack of information in the literature regarding
that decision is the prerogative of any individual institution. In the discontinuation of precautions and "clearance" of MDROs.
addition, as new guidelines and information are published, it A number of studies examined the duration of colonization
will be necessary to alter or update this document after review and found it could persist for months to years. Several articles
and approval by the Consortium DRO Committee. reported varying degrees of success with decolonization proto-
Prevention is the first principle in the management of drug- cols. Some Maine institutions have adopted a "once an MDRO,
resistant organisms (DROs). A DRO prevention and control always an MDRO" policy. Others require several screening cul-
strategy incorporates evidence-based infection control prac- tures from various sites for clearance. The subgroup felt that in
tices, antibiotic stewardship, laboratory support, and active consideration of the risk factors for MDRO, acquisition was the
surveillance. Active surveillance cultures are believed to be es- place to start deciding which patients were likely to remain pos-
sential to the identification of the pool of colonized patients itive and decrease unnecessary expense and the emotional im-
that may be missed by only monitoring the results of clinical pact of active surveillance cultures. After an extensive review, we
have proposed a set of exclusion criteria and then standardized transmission. Consideration may be given to a
the sites and number of cultures required to ~prove" culture- program that includes testing for both C. difftcile
negative status. Standardizing the criteria for clearance cultur- and VRE in patients with diarrhea.
ing and the sites/method of culturing will benefit all patients 5. Pooling of specimens decreases the sensitivity of MRSA
but especially those patients that move between institutions. detection compared with processing each swab sepa-
We also researched the utilization of precaution gowns and rately; therefore, pooling is not recommended.
gloves for visitors. We found varying requirements in the litera- D. Patients Who Are Culture-Positive or Have a History of a
ture. After careful review, we believe that the chain of transmis- Positive Culture
sion falls primarily on the actions of HCWs as they move from 1. Place patient on Contact Precautions* upon every admis-
patient to patient, not on the actions of visitors, who are there sion or at identification of positive culture.
only to see their loved one. We currently do not support the 2. Utilize contact precautions.
requirement of the routine use of gowns and gloves for visi- a. Gloves-wear upon entry into room.
tors; rather, we would emphasize the need for family education b. Gowns-wear upon entry into room as recommended
regarding hand hygiene with the caveat that if the family mem- by the draft 2004 CDC Guidelines. Current SHEA and
bers are likely to soil their clothing because of participation in previous CDC guidelines recommend utilization if in
nursing-type care of the patient, gowning and/ or gloving may contact with the patient or environment.
be appropriate. c. Masks--wear only when transmission by droplets
After review and discussion, the following guidelines are is suspected or according to Standard Precautions
presented as current "best practice." based on the nature of patient-care activity.
3. Decolonization-no recommendation is made to rou-
tinely attempt to decolonize. Decision to attempt decolo-
RECOMMENDATIONS FOR ACUTE nization should be made within a facility in consultation
CARE MANAGEMENT OF MRSA with the infection control department.
ANDVRE 4. Patients should be placed in a private room or may be co-
horted with another/other patient(s) who has/have the
A Standard Precautions same organism in any location on the body (i.e., VRE with
1. Standard Precautions will be the basic practice for all VRE or MRSA with MRSA or MRSA/VRE with another
patients before or after diagnosis of colonization or patient with MRSA/VRE) and no other active infection.
infection with an MDRO. 5. Family and visitors to patients on Contact Precautions
2. Institution of contact or MDRO precautions is addressed need to be instructed in the importance of hand hygiene
later in this document. upon entering and leaving the patient's room. Addition-
B. Active Surveillance Cultures of Patients with Known History ally, they should be instructed to refrain from visiting
ofDROs other patients or entering patient-care locations (i.e.,
1. Patients with a known history of MRSA should not be on-unit kitchenettes, solariums). Visitors who may be
screened for MRSA. at risk of clothing or skin contamination from blood or
2. Patients with a known history of VRE should not be body fluids due to type of activity they may be providing
screened for VRE. should be instructed in the use of gowns and gloves. Visi-
C. Active Surveillance Cultures of Patients with Unknown His- tors without this type of exposure do not routinely need
tory ofDROs to wear gowns or gloves.
1. Culture high-risk populations (to be defined by each E. Discontinuation of Precautions for Patients with MDROs of
facility). MRSA or VRE Across the Healthcare Continuum
a. Groups that may be considered "high risk" include 1. Although patients may test negative, multiple studies in-
patients from long-term care or physical rehabilita- dicate that it is likely that colonization is only temporarily
tion units, dialysis patients, transfers with extended undetectable and recolonization is expected.
stays in acute care facilities, and patients with chronic 2. The routine testing of previously positive patients for dis-
conditions. continuation of precautions should be discouraged. In
2. Obtain culture within 48 hours of admission. the unlikely case that the patient passes all of the follow-
3. Repeat active surveillance cultures once a week at a ing exclusion criteria, screening may be indicated:
predetermined day/time identified by each unit/facility. a. Not hospitalized (defined as 8-hour or longer stay in
Repeat screening of known positives is not necessary. an acute care facility) within the last 6 months.
4. Cultures are to be of the following: b. Not treated with antibiotic therapy, including intrana-
a. MRSA sal mupirocin, within the last 6 months.
i. Nares-one swab used to culture both nostrils. c. Not admitted to or treated at a long-term care or re-
ii. Groin-one swab used to culture the fold of the habilitation facility in the last 6 months.
skin on each side (an alternative site may be indi- d. Currently has no indwelling lines, which include but
cated in certain healthcare settings). is not limited to PICC, tunneled, peripheral, central,
w. Open wounds--culture any open area such as a arterial, or dialysis-type devices.
pressure ulcer, diabetic foot ulcer, etc.
b. VRE
i. Perirectal culture using one swab. •The CDC HICPAC MDRO Guideline recommends "enhanced contact pre-
cautions" for drug-resilltant organisms. Some facilities have elected to cre-
ii. Some studies suggest that patients being screened
ate a category of precautions to address this that includes Enhanced Contact
for Clostridium difficile who also are VRE-positive Precautions, Contact Precautions Plus, or MDRO Precautions. Regardless of the
contribute to environmental contamination and nomenclature, the basic precaution requirementl remain the same.
e. Has not undergone any invasive procedure within the 18. Cook E, Marchaim D, Kaye KS. Building a oucceoofol infection prevention progr.un: key
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3. Screen as follows. standard of care? All<]Infocl Conbol. 2004;32:504--511.
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1. Obtain three sets of screening cultures from the 21. Muto CA. Why are antibioti.c.....U.tantnooocomialillfectiono opiralingout ofcontrol? lnfrct
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22. Kohn LT, Corrigan JM, Donaldoon MS, edo. 7b E'fTv H - = Building a Safrr Hmlth ~
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26. Pcn:nccvidl EN, Stone PW, Wright SB, et al. Society for healthcarc epidemiology of
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n. Obtain cultures three times, no closer than 28. Edmanno T, BeooertJ, Behnke M, et al. Compliance with antioeptic band rub uoe in inten-
72 hours (Could say daily-there ll'm 7W data from sive care units: the Hawthorne effect mftcl ConlmlHtnp~ 2006;2'1:951--934.
29. Cenlei1 for DiJeae Control and Prevention. National Nooocomial Infection> Surcveil-
CDC shOOJing the advantage of any approach. Three on lance (NNIS) System Repon, data mmmary fromJaniWY 1992 through june 2003, iuued
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Ho.pqidMiol. 2006;27:102!>--1031.
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Slaplrj/ocoa;w aumu bacten:mia. Cliw.l11foct Dis. 2006;43:971-978.
36. Kavanagh K, Abutalem S, Saman DM. A per1pective on the evidence ,..,garding methicillin-
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Ctmlrol H..p Epitlmoid. 1999:20:202-205. ing hoopital. hiftt:t Omtrol Htnp ~iol. 2006;27:181-184.
59. Anderoon DJ, Miller RA. Chen LF, et al The network approach for pren:ntion of !K. Shlaeo DM, Gerding DN, John JF, et al. Society for healthcare epideuriology of america
healthc....,.....ociated infectiono: long-term effect of participation in the Dub: Infection and infection diseues IOciety of America joint committee on the preft:nti.on of aDtimi-
Control Outreach Network.lnft<t OmtrolH..p Epid#lrlid. 2011;32:315--522. crobial reoiatance: guidelineo for the prevention of antimicrobial reoiotance in holj>itah.
60. Mwphy DM. From expert data collector> to inten=tioW.t>: chauging the focuo for infec- hr{oa OmiTDIH..pEfJitkmioL 1997;18:275--291.
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64. Arnold MS, Dempoey JM, Fiohman M, et al. The beot holj>ital praeticeo for controlling (MRSA) patientexpooure byinl\:ction controlrneuureo.Ann CtJllSurg&gt 2005;87:123-125.
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2001;25:69-76. Sttlplajlotcou........, (MRSA) in Denmark: a nationwide atlldy in a country with low preva-
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Eflidewliol. 2005:858--Ml. to reduce opread of MRSA in intenoivcxare unita: proopective two center otlldy. lAnl:d.
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programme for methicilJin.reoiltantSI4p/ly/Qcoccw""""' (MRSA) catrlenat holj>ital admit- MRSA control InjD;l Conlrol H..pEpitlmoid. 2006;27:191-194.
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71. Khoury J, Joneo M, Grim A, et al. Eradication of methicillin-reoiltant Stoph:Jlocoaw avmu of methicillin-reoiltant Slof>TrJlococcw ........, carrier otatul in healthcare worker>. J Htnp
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72. Eveillard M, Lancien 11, Barnaud G, et al. lmpact of ocreeni~J& for MRSA carriero at ho• Sto{JhjltJ&occvs .......,.. straino among individual patiento over Cl<tended periods of time. Eur
pita! admiooion on nu-<l<ljuoted indicaton according to the imported MRSA colonir.ation ] C/m Mil:robiDI Infta Dis. 1995;14:282--290.
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What the nephrologiot needo to know. N4plwo/llfJ Nltl»IJIUIS. 2004;18:63-04. OmiT!Jl H..p ~ 2005;26:662~7.
74. LucetJC, GrenetK, Annand-Lefevn: L, et al High prevalence of carriage ofMRSA at ho• 107. Yale diocontinuation of contact precauliona IC policy (www.med.yale.edu/ynhh/
pita! admiJoion in elderly patient>: implication for infection control&trategie&. Inf«l Con#ol infection/guidelines/MKSA/discontinue.html).
HtnpEpitlmoid. 2005;26:121-126. 108. Brigham and Women'• Holj>ital. A program to remove patiento from unneceuary con-
75. Lee TA, Hacek DM, Stroupe Kr, et al. Three IIUI'Veillance otrategieo for '03DCOIIlJ"=intact precaution. A'Oailable at http://w.tllmet'White.com/pdf/jcom_oct02_contacLpdf
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76. Fllruno JP, Ranis AD, Wript MO, et al. Prediction rules to identify patient> with MRSA 110. Australian Infection Control Aawciation. Multi-reoiltant organism• ocreetting lllld clear-
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78. Axon KN, Engemann lJ, ButcherJ, et al Control of nooocomialacquisition ofWll<:OibJ"=in- 113. Sanford MD, Widmer AF, Bale !ofj', et al. Eflicient detection lllld long-term pern.tence of
remtant enterococci through acti..: ourv<:illance of hemodialyoio patient>. hif«:: ConJtul the carriage ofmethicillin-remtantSIGphJlococcwoumu. CJmhr{raDis.1994;19:1123-1U8.
Hwp EpitlmoiDl. 2004;25:436-458. 114. Gould JM. The clinical oignificance of methicillin..-emtant SIIJf>hJiotc!u ovmu. J H..p [,..
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bloodstream Olltbreak among patient> with hematologic ~ancy. hif«l Ctmlrol H..p 115. Rampf G. What ohould be done with nasal SIGphJloaJa:ru"""""' carrier>? J Hasp blflti
Eflidewliol. 2004;25:!91---'194. 2005;6135!1-61354.
80. Pcrcnveich EN, Fiunan DN, Lipaitcb M, ct al. Projca:tcd beucfib of active aunrcillau.cc for 116. Harbarth S, Liauine N, Dharan S, et ai.Ri>k factor> for pc:r>iltent carriage of methicillin-
vancomycin..Wtantenterococci in intenoivecare unit>. CJmlnftaDis. 2004;58:11Ds-1115. reoiltant SlafJ!t:Jloccou aumu. CJmlnfoaDis. 2000;31:1ll80-1385.
81. Ranis AD, Nemoy L,JohnoonJA, et al. CcH:aniage rateo ofVRE andli:SBL producing bac- 117. Johns Hopkins Divilion of Infectiou1 Dileaseo Antibiotic Guide. Reailtance in S. "'"'""
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program. Infl&l Con#ol H..p EpitlmoiDl. 2004;25:10!>-108. 118. Romance L, Nicolle L,.RouJ, et aLAn outbreak ofmethicillin"<Coiitaut~ """"'in
82. JerniganJA, Clemence MA, StottGA, et al. Control ofmethicilJin.reoiltant Slaphylococcw ,_ a pediatric holj>ital-how it got away and how we caught it Can] bifra OmlroL 1991;6:11-13.
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83. Dall'Antonia M, Coen PG, Wllkio M, et al Competition between methicillin.,enoitive and riage amongpatienllafter hoopital dilcharge. l'nfld Ctmtn>IH..p~ 2005;25:629-0511.
reoiatant SlopfrJiotctU ovmu in the anterior DMCO.]Htnplnfret. 2005;61:~7. 120. Sandri AM, Dalarooa MG, DeAicanwa LR, et al. Reduction in incidence of n010comial
84. Aaenoin A, Guerrero A, Qw:n:da C, et al Colonization and infection with MRSA aJaOciated m.cthicilliD-n:li:~tant SfallhJlomccw GUm~~ (MRSA) infct:ti.ou in aD illtellli'R: «:arc Wlit role
factor> and eradication. Infoct CmsJroiH..pEpitlmoid. 1996;17:2G-28. of treatment with mupirocin ointment and chlorahexidine bathJ for nasal carrier> of
85. Pan A, Carnevale G, Colomhini P, et al Trends in methiciliinreoisitant SIIJf>hylococcw rAtmU MRSA- lnfoct CmsJroiHosj>Epitlmoid. 2006;27:18!>-187.
(MKSA) bloodstream infectiono: effect of the MRSA "oearch and ioolate" otrategy in a ho• 121. Humphrey H. Implementing guidelines for the control and pre..:ntion of methicillin-
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86. Farr BM. Pre..:ntion and control of methicillin"£emtant Slap/>Jloeo<<US """"' infectiono. national comparilono ofmcceu? J Htnplnfret. 2006;62:153--135.
Ourr opin Inftt:tDU. 2004;17:317--322. 122. Univeroity ofVupua Health Syotem. 'I7ul prob1ma palllopt ponr.enhip (www.healthsystem.
87. LucetJC, Paoletti X, Lolom I, etal. Succeo&fullongterm program !or controlling methicillin- virginia-edn/internet/PPP).
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88. Weinotein KA. Antihioitic remtance in hooprtalo and intenoive care unit>: the problem and cuo""""" (MKSA) among houoehold contact of individnal with nooocomially acquired
potential oolutiono. Sntin!Wpir Orili em. Mill. 2003;24:113-120. MRSA- lnfoct CmsJroiHosj>Epitlmoid. 2003;24:422-426.
13 M. Sotile, Karen K. Hoffmann, and Tammy S. Lundstrom
The Role of Professional, GoverllDlental,

and Regulatory Organizations in
Infection Prevention and Control
INTRODUCTION The conference resulted in published guidelines on isolation
techniques fur hospitals (5) and guidance for nurses who
The modem era of infection prevention and control (IPC) were filling the new role of infection control nurse (6). A pi-
began in the late 1950s and early 1960s when a new, virulent lot study of HAis in community he»pitals conducted in 1985
antibiotic-resistant strain of Stopkyltx:~Jccw aumc.s led to an epi· evolved into the National Nosocomial Infections Surveillance
demic that swept through U.S. he»pitals. The epidemic quickly (NNIS) Sy:stem (today the National Healthcare Safety Net·
created a dramatic increase in the number of infections in new- work [NHSN] )-the only national HAl database in the United
borns and obstetrical and surgical patients. Up to 25% of new- States (7-9). The CDC remains the primary governmental pub-
hom infants developed superficial pyodermas or more serious lic health partner fur infection preventionisl:! (IPs) and hospi-
deep infections, and approximately 1% of healthy postpartum tal epidemiologists.
mothers died of S. aumc.ssepsis (1). In the late 1950s and early 1960s, the AHA recognized the
These severe infections-with their associated morbidity need to disseminate recommendations for controlling HAis to
and mortality-highlighted the deficiencies in care practices its member he»pitals (3,10,11). The AHA recommended that
fur patients at that time and fucused the attention ofhealthcare hospitals establish a committee on HAis; create an HAl sur-
providers on healthcar~ociated infections (HAis) (2). '!Wo veillance and reporting system; use strict aseptic practices dur·
influential national agencies, the Centers for Disease Control ing surgeries, in delivery rooms, and in nurseries; minimize
and the American He»pital Association (AHA), came forward the use of antibiotics; and identify infections that occurred in
to assist hospitais with the epidemic and with their efforts to the hospital and in the community. These recommendations
prevent HAh (~).The collaboration between healthcare pro- served as early guidelines for all hospital-based IPC programs.
fessionals, public health agencies, governmental agencies, and Subsequent reports and technical briefings addressed evolv-
later professional organizations established ties that shaped the ing IPC issues, such as mvI AIDS and hepatitis B virus (HBV)
early evolution of IPC programs and forged relationships that (12,13). Today, the AHA continues to advocate for IPC issues
continue to the present day. nationally and through its state hospital associations.
This chapter describes the role and innuence of profes- The CDC, the AHA, and other similar organizations helped
sional, governmental, and regulatory entities on the practice of drive the agenda during the early years ofiPC. By the late 1970s,
IPC and hospital epidemiology and on patient outcomes. The almost 90% of hospitals were performing HAl surveillance and
chapter also presents a case study that illustrates the interplay had an IPC committee, and almost half had an infection con·
among those entities using the development and implementa· trol nurse at least part-time (14). Interestingly, regulations or
tion of influenza immunization practices in healthcare as an standarda for IPC did not exist at that time, so early IPC efforts
example. occUITed voluntarily in hospitals (6).
As questions arose about the effectiveness and value of IPC,
the CDC conducted a l().year nationwide study. The Study on
EARLY IllSTORY the Efficacy of Nosocomial Infection Control (SENIC) project
produced strong evidence that effective IPC programs with
The Centers for Disease Control (now the Centers for Dis- specific surveillance, reporting, and staffing components could
ease Control and Prevention [CDC]) and the AHA were the demonstnlte a decrease in HAia (15). Today, the CDC proac-
first entities to partner with healthcare organizations and tively leads IPC initiatives in collaboration with professional so-
professionals engaged in IPC. The CDC created a small unit of cieties and other governmental agencies (Table 13.1), and the
epidemiologists to provide assistance to hospitals struggling to AHA keeps the prevention ofHAis on their list of priorities by
understand and to contain the staphylococcal epidemic in the sponsoring studies, educational initiatives, advocacy programs,
1950s to 1960s, and in 1958, the CDC hosted the first national and evidence-based guidelines to assist the field of IPC define
conference on preventing S. aumc.s infections (the National the epidemiology of HAis and use scientific practices to reduce
Conference on He»pitai-Acquired Staphylococcal disease) (4). HAl risk.
154
Chapter 13 • The Role of Professional, Governmental, and Regulatory Organizations in Infection Prevention and Control 155
TABLE 13.1 Selected World Health Organization (WHO) Programs for Hcalthcare-.Assodatcd
Infec:t:ions (HAl)
Main HAl Prevention
Program and Control Topic Selected Guidelines/Documents
Blood transfusion safety1 Prevention of O'an.rl'usion-transmissible • Blood transfusion safety: information sheet
infections (including HIV, hepatitis B, • Prevention of healthcare-associated HN infection: flyer
hepatitis C, syphilis, and bacterial contami- • WHO resource materials on blood safety; CD-ROM
nation of blood and blood products)
Clean Care is Safer Care! HAl prevention and control, in particular sur- • Guidelines on hand hygiene in healthcare
veillance and prevention of the endemic • Guide to implementation of the WHO multimodal hand
burden of HAl, with special focus on hand hygiene improvement strategy
hygiene • Hand Hygiene Implementation Toolkit (32 tools):
• Tools for system change
• Tools for institutional safety climate
• Hand hygiene self-aMe55ment framework
• "Hand Hygiene Moment I -Global Observation
Survey": summary report
• Save Livo: Clean Your Hands: promotional video
• Occupational health: a manual for primary healthcare
Health worker occupational Prevention of HAl among healthcare workers
worken
health5
• Protecting healthcare worken: preventing needlestick
injuries toolkit
• Joint WHO/ ll.O guidelines on postexporure prophylaxis
to prevent HIV infection
Infection prevention and HAl prevention and control, in particular • Prevention of hospital-acquired infections
control in healthcare4 prevention and preparedne55 and response • Practical guidelines for infection control in healthcare
to epidemics that can be associated with or facilities
amplified by healthcare • Infection prevention and control of epidemic- and
pandemic-prone acute respiratory diseases in healthcare;
WHO interim guidelines and an accompanying set of im-
plementation tools for community and hospital healthcare
• Core components for infection prevention and control
programs and an accompanying set of implementation
tools for national and local programs
Injection safety' Prevention of blood-borne pathogen transmis- • First, do no harm: introducing auto-disable syringes and
sion through unsafe injection practices ensuring injection safety in immunization systems of de-
veloping countries
• WHO best practices for injections and related procedures
toolkit
• Revised injection safety assessment tool
Safe Surgery Saves Lives6 Reduction of complications due to surgery, • WHO surgical safety checklist
including surgical .site infections • Checklist implementation manual
Water, sanitation, hygiene, Promotion of environmental health in health- • Safe healthcare waste management: policy paper
and health7 care settings, in particular safe healthcare • WHO core principles for achieving safe and sustainable
waste management management of healthcare waste
• Management of solid healthcare wallte at primary health-
care centen: a decision-making guide
Web.sites for Programs

Note: These documents are all available in pdf on the above-mentioned website pages related to the corresponding WHO program.
lhttp://www.who.int/bloodsafety/en/
2http://www.who.int/gpsc/en/
Shttp://www.who.int/occupational_health/topics/hcworken/en/index.html
4http://www.who.int/ csr/bioriskreduction/infection_control/en/index.html
5http://www.who.int/injection_safetyI en/
~ttp://www.who.int/patientsafety/safesurgeryI en/index.html
7http://www.who.int/water_sanitation...health/hygiene/en/
Adapted from Allegranzi B, Pessoa,Silva CL, Pittet D. The World Health Organization approach to Healthcare Associated Infection prevention
and control. In: Soule B, Memish Z, Preeti M, eds. Best Practices in Inftction Conlfol: An International Perspeaive. 2nd ed. Oak Brook, IL: Joint
Commission International; 2012:11-18.
INTERNATIONAL INFECTION EXTERNAL EVALUATION PROCESSES

PREVENTION AND CONTROL FOR STANDARDS AND PERFORMANCE
ORGANIZATIONS
Three key steps characterize the external standards evaluation
Various organizations around the world actively engage in infec- process (31). First, formal standards are created and adopted
tion prevention efforts. One example is the Gulf Cooperation to define a set of performance expectations for organizations
Council (GCC), which is composed of seven counuies in the that will use the standards. Second, standards are audited exter-
Middle East. This organization has produced IPC guidelines, nally to determine the degree of compliance by these organiza-
reporting mechanisms, surveillance methods, and prevention tions. Cruse recognized the positive effects of external auditing
strategies that can be used by all member counuies (16). Latin when he assessed surgical site infections (SSis) using external
America also is very active in IPC. The Pan American Health observers (an IP and a physician) and the positive effects of
Organization (PAHO) is an international public health agency providing incidence data and trends on SSI rates to surgeons
with more than 100 years of experience in working to improve (32). Accreditation and regulatory agencies also perform
the health and living standards of counuies throughout the auditing by conducting scheduled and unannounced surveys
Americas (17). PAHO specializes in the health of the Inter- to monitor compliance with their standards and to respond
American System and serves as the World Health Organiza- to complaints. Third, rewards are conferred or sanctions are
tion (WHO) Regional Office for the Americas. Since 2008, this imposed on organizations depending on the degree of compli-
organization has published and updated guidelines, manuals, ance with standards. Examples include awarding, withholding,
and educational materials for Latin American IPs on such top- or revoking accreditation or licensure or issuing citations or
ics as surveillance strategies (18) and sterilization (19) as well as fines and recommendations for improving the care the organi-
created assessment tools for IPC programs (20). zation provides.
Many standards-setting organizations influence IPC prac-
tices. Although it is not possible to discuss all these organi-
WORLD HEALTH ORGANIZATION
zations in detail, a number of organizations that have been
WHO has played a pivotal role in preventing infections in the particularly influential are covered in this chapter, and a
international community. In 2007, the Fift}"-Fifth World Health summary of these and other organizations is provided in
Assembly Resolution (WHA 55.18) recognized the importance Table 13.2.
of promoting patient safety, including IPC programs (21). At
that time, the WHO's ability to enforce IPC practices was so-
lidified by the revised International Health Regulations--an VOLUNTARY AND REGULATORY
international legally and binding instrument applicable to 194 STANDARDS-SETTING
WHO Member States across the globe (22). Because of its role ORGANIZATIONS: INFLUENCE
in international health, WHO is in a unique position to support ON INFECTION PREVENTION
HAl prevention and control through regional and national of- AND CONTROL
fices, WHO Collaborating Centers, Ministries of Health, and
other agencies. Key WHO initiatives for IPC include providing External evaluation and control of health services involves set-
comprehensive tools for improvement strategies on the WHO ting standards against which organizational operations and
website (23); the Safe Injection Global Network (launched programs can be measured. During the Crimean War in the
in 1999) to ensure the safe and appropriate use of injections mid-1800s, Florence Nightingale developed early standards for
around the world (24); and the Clean Care is Safer Care cam- IPC in her efforts to control the patient's environment, to im-
paign (began in 2009), which focuses on hand hygiene and has prove sanitation, and to reduce infections in the sick wards in
the formal support of more than 124 governments around the the field hospital (33).
world (25). In 2011, WHO released a policy package to com- Today, some IPC standards in the United States, such as
bat antimicrobial resistance (26) and launched the Global In- those from the National Quality Forum (NQF) (34) and the
fection Prevention and Control Network (27). A list of major Agency for Healthcare Research and Quality (AHRQ) (35),
WHO IPC initiatives and websites is featured in Table 13.2. are voluntary and are developed by consensus. These standards
are used by organizations for professional self-examination and
to determine competence in IPC program activities and out-
THE INTERNATIONAL NOSOCOMIAL INFECTION
comes. In the international community, organizations such as
CONTROL CONSORTIUM
the Health Information and Quality Authority in Ireland (36)
The International Nosocomial Infection Control Consortium and the Canadian Standards Association (37) set voluntary
(INICC) evolved in the 1990s, and for the past 11 years has de- standards to drive continuous improvement in IPC practices.
veloped programs to perform process and outcome surveillance Other standards are used to improve patient safety and to de-
to detect risk factors for infection in Latin American healthcare termine reimbursement for care. Those standards developed
facilities and has worked to evaluate the cost-effectiveness of by The Joint Commission (1JC) (38) and the American Osteo-
IPC (28). Staff in many hospitals around the globe have been pathic Association (AOA) (39) are voluntary, whereas those
involved in creating and maintaining the surveillance pro- from the Centers for Medicare & Medicaid Services (CMS)
grams, and, as of 2012, more than 1,000 investigators from ( 40) are mandatory and required for healthcare licensure
approximatelyl,OOO healthcare centers in 200 cities and 39 and/or payment.
countries throughout Africa, Asia, Europe, and Latin America Regulatory standards also have been developed by such
actively participate and report their surveillance data (29,30). Federal agencies as the U.S. Occupational Safety and Health
-~(;C:f§:lfJ. Selected Organization Rd"crcnas and Websitcs

Organization Type Website Deac:ription
QUALITY
Agency for Healthcare Research and Quality http:/lwww.ahrq.gov Quality and patient safety guidelines and
(AHRQ) literature
The American Health Quality Association http:/lwww.ahqa.org/publinside Reference documents for quality
American Society for Quality (ASQ) http:/lasq.org Reference documents for quality
CDC Division ofHealthcare Quality http:/lwww.cdc.govI ncezidldhqpl Guidelines and associated recommended
Promotion (DHQP) index.html measures
Hospital Compare http:/lhospitalcompare.hhs.govI Public comparison of mortality rates for various
conditions abstracted from administrative
data sets
Institute for Healthcare Improvement (IHI) http:/lwww.ihi.org Guidance documents for implementing
evidence-based practices
Institute of Medicine (10M) http:/lwww.iom.edu Healthcare-~"elated publications, including
medical errors and national quality progress
The Leapfrog Group http:/lwww.leapfroggroup.org Publicly reported quality and patient safety measures
National Association for Healthcare http:/lwww.nahq.org Reference documents for quality
Quality (NAHQ)
National Committee for Quality http:/lwww.ncqa.org Quality standards for health plans
Assurance (NCQA)
National Initiative for Children's Healthcare http:/lwww.nichq.org Quality measures specific to children
Quality (NICHQ)
National Quality Forum (NQF) http:/lwww.qualityforum.org National voluntary consensus measures for a
variety of conditions, including HAis
INFECTION PREVENTION AND CONTROL

Association for Professionals in Infection Control http:/lwww.apic.org Resources for infection prevention and control
and Epidemiology, Inc. (APIC) (IPC) and healthcare epidemiology (HE),
including guidelines
Center for Infectious Disease Research http:/lwww.cidrap.umn.edu Resources for IPC and HE, including guidelines
8c Policy-University of Minnesota
Centers for Disease Control and http:/lwww.cdc.gov Resources for IPC and HE, including guidelines
Prevention (CDC)
Infectious Diseases Society of America (IDSA) http:/lwww.idsociety.org Resources for IPC and HE, including guidelines
National Foundation for Infectious http:/lwww.nfid.org Resources for infectious diseases
Diseases (NFID)
The Society for Healthcare Epidemiology http:/lwww.shea-online.org Resources for IPC and HE, including guidelines
of America (SHEA)
World Health Organization (WHO) http:/lwww.who.intlen Resources for IPC and HE and current data on
outbreaks
PATIENT SAFE1Y
Agency for Healthcare Research http:/lwww.ahrq.gov Quality and patient safety information; patient
and Quality (AHRQ) safety network
American Hospital Association (AHA) http:/lwww.aha.org Resources for hospitals
American Society for Healthcare Risk http:/lwww.ashrm.org Resources for risk management
Management (ASH RM)
American Society of Health-System http:/lwww.ashp.orglpatient-afetyl Resources for patient safety related to
Pharmacists (ASHP) index.cfm medication
Anesthesia Patient Safety Foundation (APSF) http:/lwww.apsf.org/ Resources for patient safety related to anesthesia
ECRI Institute (formerly the Emergency Care http:/lwww.ecri.org Resources for patient safety
Research Institute)
Emergency Medicine Patient Safety http:/lwww.empsf.org Resources related to emergency medicine
Foundation (EMPSF)
National Institutes of Health; U.S. National http:/lwww.nlm.nih.gov PubMed, MeSH, ClinicalTrials.gov, MedLine
Library of Medicine Plus, and other sites for patient safety
literature
National Patient Safety Agency (NPSA), http:/lwww.npsa.nhs.uk International resources for patient safety
United Kingdom
National Patient Safety Foundation (NPSF) http:/lwww.npsf.org Resources for patient safety
National Quality Forum (NQF) http:/lwww.qualityforum.org/ National voluntary measures for a variety
Measures_LisLaspx of medical conditions
Partnership for Patient Safety http:/lwww.p4ps.org Resources for patient safety
Patient Safety Institute http:/lwww.ptsafety.org Resources for patient safety
Premier Safety Institute http:/lwww.premierinc.comlsafetyl Resources on patient and healthcare worker
safety topics
(continued)
• . §C :) 6j fJ. Sdcctal Organization Rrfcrcnccs and Wcbsitcs (Cosrisweil)

Organization Type Webllite Dacription
U.S. Department of Defense Patient Safety http:/ /health.mil/dodpatientsafety/ Resources for patient safety
Program ProductsandServi.ces/Toolkits
.aspx
Veterans Administration National Center http:/ /www.patientsafety.gov Resources for patient safety
for Patient Safety (NCPS)
REGULATORY
Centers for Medicare &: Medicaid Services (CMS) http:/ /www.cms.gov Conditions of Participation for inclusion in Medi-
care and Medicaid programs; website publicly
displap quality comparative data for hospitals
National Fire Protection Association (NFPA) http:/ /www.nfpa.org/index.asp Sets codes/ regulations to reduce fire hazards
The CDC's National Institute for Occupational http:/ /www.cdc.gov/niosh Conducts research and makes recommendations
Safety and Health (NIOSH) regarding prevention of healthcare personnel
injuries
U.S. Occupational Safety&: Health http:/ /www.osha.gov Regulates the health of healthcare personnel,
Administration (OSHA) including blood-borne pathogens and respi-
rator use
U.S. Department of Transportation http:/ /www.dot.gov Regulates transportation in the United States,
including medical waste
U.S. Environmental Protection Agency (EPA) http:/ /www.epa.gov Regulates air and water discharges and disinfec-
tants used on surfaces
U.S. Food and Dmg Administration (FDA) http:/ /www.fda.gov Regulates single-use medical devices, antiseptics,
and disinfectants used on medical devices
U.S. Government Accountability Office (GAO) http:/ /www.gao.gov Investigates how the US government spends
money
U.S. Nuclear Regulatory Commission http:/ /www.nrc.gov Regulates nuclear devices and materials used in
laboratories and patient testing
U.S. Regulations http:/ /www.regulations.gov Searchable site of all US regulations
ACCREDITATION
American Osteopathic Association (AOA) http:/ /www.osteopathic.org Professional organization for osteopathic phpi-
cians; alternative to The Joint Commission for
deemed status
Det Norske Veritas (DNV) Healthcare http:/ /www.dnvusa.com/ Standards based on the International Organiza-
tion for Standardization
The Joint Commission http:/ /wwwJointcommission.org Standards for hospitals, critical access hospitals,
long-term care, ambulatory care, behavioral
healthcare, home care, laboratories, office-
based surgery, and other settings
Joint Commission International http:/ /jointcommissionintema- Standards for international organizations,
tional.org including hospitals, ambulatory care, care
continuum, clinical laboratories, home care,
long-term care, medical transport, primary
care centers
CONSUMER
Americans Mad and Angry http:/ /www.americansmadandangry Consumer stories regarding medical errors,
.org including HAh
Committee to Reduce Infection Deaths (RID) http:/ /www.hospitalinfection.org Consumer stories regarding HAis
Consumers Advancing Patient Safety (CAPS) http:/ /patientsafety.org Tips for consumers
Consumers Union http:/ /www.consumersunion.org Campaign to require public reporting of HAis
Federation of State Medical Boards http:/ /www.docinfo.org Quality information on doctors
Healthgrades http:/ /www.healthgrades.com Ratings for doctors, dentists, hospitals
Public Citizen http:/ /www.citizen.org/Page. Information on phpician accountability; drugs,
aspx?pid=524 devices, and supplements; and healthcare
delivery
OrnER RESOURCES
Library of Congress http:/ /www.loc.gov Research arm of Congress; largest library in the
world, including US legislation
U.S. Government Printing Office Federal http:/ /www.gpo.gov/ Searchable site of agency regulations
Register fdsp/browse/ collection.
action?collectionCod=FR
Administration (OSHA) (41), the U.S. Food and Drug Admin- by 2020 (which is based on a goal established by the U.S.
istration (FDA) (42), and the U.S. Environmental Protection Department of Health & Human Services [HHS] Action Plan
Agency (EPA) (43). These agencies were established to protect to Prevent Healthcare-Associated Infections) (52). The cur-
human health and the environment by writing and enforcing rent edition of the IC standards became effective January 1,
regulations based on laws passed by Congress that delegated 2013 (38), and these are reviewed and revised periodically.
standards setting, interpretation, and oversight to a specific 1JC works closely with CMS to ensure that most of the 1JC IC
federal or state agency. For example, the U.S. Pharmacopeia! standards align with the CoPs and Conditions for Coverage
Convention (USP) is a scientific nonprofit organization that (CfCs), thus making it easier for healthcare organizations to
sets standards for the identity, strength, quality, and purity of meet the requirements of both organizations. 1JC also devel-
medicines, food ingredients, and dietary supplements manu- ops National Patient Safety Goals (NPSGs). NPSG 7 focuses on
factured, distributed, and consumed worldwide. USP drug stan- reducing HAis, and the 2013 NPSGs address hand hygiene,
dards incorporated into federal law are enforced in the United multidrug-resistant organisms, central line-associated blood-
States by the FDA "FDAF'. D, and these standards are developed stream infections ( CI.A-BSI), SSis, and catheter-associated
and used by more than 130 countries (44). IPs and others rely urinary tract infections (CA-UTis). Surveyed organizations
on USP Chapter 797, which pertains to the safe preparation, are required to meet the NPSGs to be accredited. In addition,
storage, and handling of compounded sterile preparations up Joint Commission International Q"CI) promulgates standards
to the point before administration to patients (45). In 2012, and International Patient Safety Goals (IPSG .5) for the pre-
CMS issued a memorandum based on USP 797 to define the vention and control of infections that apply to organizations
requirements under which repackaging of single-dose vials for accredited in the international community (53).
multiple patients would meet compliance with CMS Conditions
of Participation (CoPs) for all health care settings (46).
AMERICAN OSTEOP.ATIDC ASSOCIATION
THE JOINT COMMISSION AND JOINT The AOA was founded in 1897 to advance the tenets of os-
COMMISSION INTERNATIONAL teopathic medicine and to provide support for doctors of
osteopathy medicine (54). The AOA serves more than 78,000
1JC is a voluntary, nongovernmental not-for-profit organiza- osteopathic medical physician members in the United States,
tion created through a coalition of several m.gor healthcare promotes public health and academic scientific research, pro-
organizations. TJC's standards originated from the American vides education, and offers guidance on providing cost-effective
College of Surgeons' (ACS) Minimum Standards for Hospitals, and ethical medical care. The AOA is the primary accrediting
which in turn were based on Ernest A. Godman's outcome- agency for all osteopathic medical colleges and healthcare facil-
based monitoring system (47). Godman's system involved ities using a voluntary process. And as of 1966, HHS recognized
tracking each patient to determine whether treatments were the AOA as the official body to accredit osteopathic hospitals
effective, and, if they were not, to determine the reasons so under Medicare (55) . In addition, under their Healthcare
subsequent patients could be treated more effectively. The Facilities Accreditation Program, CMS has awarded the AOA
ACS began conducting on-site hospital inspections using these deeming status to accredit other healthcare organizations,
standards in 1918, and in 1953, 1JC (known as the Joint Com- including, most recently, ambulatory surgical centers (56).
mission for the Accreditation of Healthcare Organizations
ijCAHO] at that time) took over these surveys. In 1965, Con-
gress passed the Social Security Amendments with a provision DET NORSKE VERITAS
that TJC-accredited hospitals were "deemed" to be in compli-
ance with the Medicare CoPs and could receive Medicare and Det Norske Veritas (DNV) was created in 1864 in Oslo, Norway.
Medicaid funds (48). Today, TJC continues to "deem" organi- Its headquarters is located in Geneva, Switzerland, and it has
zations across the care continuum through its survey and ac- offices in more than 100 countries, including the United States.
creditation process. DNV Healthcare uses International Organization for Standard-
1JC published its first standards for IPC in 1976 (49). When ization (ISO) standards (a universally accepted international
these standards were published, some professionals noted the quality management system) as the framework to certify and
lack of a substantive body of scientific information to indicate accredit healthcare organizations. In September 2008, CMS
whether following these would reduce HAis (3). A recent study approved DNV Healthcare as a deeming authority for hospi-
demonstrated that accredited hospitals score significantly tals and more recently, for critical access hospitals. The DNV
higher than nonaccredited hospitals on 13 of 16 quality mea- Healthcare accreditation process combines CMS CoPs with ISO
sures, including several measures related to the prevention of 9001 standards for certification. DNV's Managing Infection
pneumonia (50). More recent IPC standards have added re- Risk (MIR) Standard addresses the need for systemic prepared-
quirements for risk assessment, evaluation of goals and strate- ness and provides a framework to help organizations improve
gies, assessment ofiPC data, and improving performance and their management of infection risk. The MIR Standard is com-
sustaining improvement (38). In 2012, 1JC added a standard patible with WHO and CDC guidelines (57).
to encourage organizations to improve influenza immuniza-
tion rates among healthcare personnel (HCP) (Infection Con-
CENTERS FOR MEDICARE AND MEDICAID
trol [IC] Standard IC.02.04.01) (51). This standard requires
SERVICES (CMS)
organizations to establish an annual influenza vaccination
program for licensed independent practitioners and staff and Acute and critical access Medicare-participating hospitals and
to establish goals to incrementally increase immunizations ambulatory surgical centers that are not accredited by 1JC,
among staff to achieve a 90% immunization rate or better AOA. or DNV must undergo state surveys from state health
departments to initially determine (and periodically reaffirm) 40% in the United States, thus preventing 1.8 million injuries
their eligibility for Medicare and Medicaid reimbursement. and averting 60,000 deaths of hospital inpatients by the end
CMS maintains IPC standards under its CoPs and CfCs for of 2013, and is targeting a 20% reduction in hospital readmis-
critical access hospitals and acute care hospitals, ambulatory sions, thus eliminating 1.6 million unnecessary rehospitaliza-
surgical centers, skilled nursing facilities and nursing homes, tions (63). Achieving these targets could save up to $35 billion
dialysis centers, hospices, and home healthcare agencies (58). across the US healthcare system over 3 years, including up to
Compliance with CMS standards is mandatory for participation $10 billion for Medicare alone (63) .
in and reimbursement from Medicare and Medicaid. The regu-
lations require healthcare providers, such as hospitals, nursing
OCCUPATIONAL HEALTH AND SAFETY
homes, dialysis centers, and home health facilities, to develop,
ADMINISTRATION (OSHA)
implement, and maintain an IPC program to prevent, control,
and investigate HAis (59). 1JC standards and CMS CoPs for OSHA is a governmental agency organized under the U.S.
IPC are similar but not identical in most cases. Because 1JC, Department of Labor ( 41). Its mission is to ensure the safety
AOA, and DNV have had their hospital standards approved by and health of U.S. workers by setting and enforcing stan-
CMS, compliance with these accrediting organizations' standards; providing training, outreach, and education; establish-
dards is deemed by CMS to be equivalent to compliance with ing partnerships; and encouraging continual improvement in
federal standards. workplace safety and health (41). In 1991, OSHA issued the
With the passage of the Deficit Reduction Act of 2005 (DRA), Bloodborne Pathogens Standard (BBP) to protect HCP from
the U.S. Congress took steps to revise the way Medicare pays exposures and subsequent infections (65). Under the Gen-
hospitals. As of October 1, 2008, hospitals no longer receive eral Duty Clause of the BBP Standard, employers are required
reimbursement for patients who develop certain preventable to provide a work environment that is "free from recognized
hospital-acquired conditions (HACs) during, or after their hazards that are causing or are likely to cause death or seri-
hospital stay (60). By 2013, 6 of the 11 HACs chosen by CMS ous physical harm to his/her employees" (64, Section 5). The
were HAis. The HAl-related preventable conditions that CMS BBP Standard has been well integrated into IPC programs
identified first in the final regulation implementing subsection and healthcare organizations using policies, education and
5001 (c) of the DRA were urinary tract infections caused by cath- training, administrative controls, and safe practices. In Janu-
eters, infections caused by vascular catheters, and mediastinitis ary 2001, OSHA revised the BBP Standard to conform to the
following coronary artery bypass graft surgery. Other HAis that requirements of the U.S. Needlestick Safety and Prevention
have been added from 2009 to 2013 include: SSI following bar- Act of 2000 (66), which required healthcare organizations
iatric surgery for obesity (i.e., laparoscopic gastric bypass or gas- to redefine engineering controls to include safer medical
tric restrictive surgery, gastroenterostomy); SSI following certain devices and systems and to involve frontline HCP in device
orthopedic procedures (i.e., spine, neck, shoulder, elbow); and evaluation and selection. One study conducted in a hospital
SSI following cardiac implantable electronic device (CIED) (61). to examine the effects of incorporating safety-engineered
In addition, as of January 1, 2011, hospitals electing to devices on percutaneous injuries involving blood-borne
participate in the CMS Hospital Inpatient Quality Reporting pathogen exposure indicated significant decreases in sharps
(IQR) program must use the NHSN to report their HAl rates injuries (67). The OSHA standard and act have helped re-
for specific infectious outcomes. Eligible hospitals that do not duce infections among HCP in the United States. Some states
participate in the Hospital IQR program will receive an annual have retained authority for occupational safety standards.
market basket update with a 2.0 percentage point reduction. These states, called state-plan states, can exceed but not lower
The Hospital IQR program stipulates that hospitals must re- protections required by OSHA. During the H1N1 influenza
port CLA-BSI data from their adult and pediatric intensive care outbreak in the United States, OSHA actively participated in
units (ICUs) and neonatal ICUs via the NHSN, and these data the debate with the CDC and other organizations regarding
are shared with CMS. CA-UTI and SSI (i.e., abdominal hyster- the use of respirators vs. surgical masks for protection ofHCP.
ectomy and colon surgery) reporting started with calendar year OSHA currently publishes useful documents and fact sheets
2012 for FY2014 annual payment updates (62). In 2013, CMS for IPC topics, such as HCP precautions during the seasonal
has added MRSA bacteremia, Clostridium difftcile, and health- influenza season (68) and using respirators vs. surgical masks
care provider influenza vaccination (63). In addition, each for IPC purposes (69).
hospital's data will be included in CMS's Hospital Compare
website, which publicly reports hospital performance. In the
U.S. DEPARTMENT OF HEALTH & HUMAN
future, CMS will continue to add HAis that must be reported to
SERVICES (DHHS)
NHSN for participation in the Hospital IQR program.
In April 2011, the CMS Center for Medicare and Medicaid The DHHS recognizes that HAis are an important public
Innovation launched the Partnership for Patients, a nation- health and patient safety issue. As a result, DHHS convened the
wide public-private partnership to offer support to physicians, Federal Steering Committee for the Prevention of Healthcare-
nurses, and other clinicians working in hospitals and other Associated Infections in 2009 and charged the committee with
healthcare facilities to help them make patient care safer and the task of coordinating and maximizing the efficiency of IPC
to support effective transitions of patients from hospitals to efforts across the U.S. Government. The membership of the
other settings. The Partnership for Patients has identified nine Steering Committee is broad and staffed with clinicians, scien-
areas of focus, four of which are HAl-related: CA-UTis, CLA- tists, and representatives from a wide array of public health or-
BSis, SSis, and ventilator-associated pneumonia (VAP) (64). ganizations, including the National Institutes of Health (NIH);
The Partnership for Patients has set a goal to reduce prevent- the National Vaccine Program; the CDC; CMS; AHRQ; and the
able ~ (including CLA-BSis, CA-UTis, SSis, and VAP) by U.S. Departments of Labor, Defense, and Veteran's Affairs.
In 2009, the .Assistmt Secretary for Health created the Office AMERICAN SOCIETY OF HEATING,
of Healthcare Quality (OHQ) to operationalize the mandate to REFRIGERATING, AND AIR CONDffiONING
prevent and eliminate HAis to improve healthcare quality (70). ENGINEERS
OHQ's approach has been very collaborative, using public and
The American Society of Heating, Refrigerating, and Air Con-
private partnerships to look at new ways to reduce HAis. The
ditioning Engineers (ASHRAE) was founded in 1894 as a build-
OHQ was instrumental in developing the National Action Plan
ing technology society. Today, it has more than 50,000 members
to Prevent Healthcare-Associated Infections: Roadmap to Elimi-
worldwide. The society develops guidelines and stmdards to
nation (52). The plan has three defined phases and uses a vari-
promote indoor air quality and energy efficiency, including
ety of incentives, such as linking payment to quality of care and
green technology and stmdards for ventilation in healthcare
enhancing regulatory oversight of hospitals, to support efforts to
facilities (77).
reduce HAis. The first phase of the plan addresses HAis in acute
care hospitals. Phase two focuses on ambulatory surgical centers,
end-stage renal disease facilities, and increasing influenza vacci- AMERICAN SOCIETY FORHEALTIICARE
nation among HCP. And phase 3 will address HAis in long-term ENGINEERING
care facilities. The HAl action plan includes 5-year goals and met-
rics for nine specific measures of improvement in HAl preven- The American Society for Healthcare Engineering is an as-
tion to address devic~related infections and specific pathogens sociation with 11,000 members dedicated to optimizing the
(71). & of2011, six of the nine goals were on pace to meet the healthcare physical environment. The organization develops a
targets for 2012. The plan has received a great deal of attention number of tools and guides to assist organizations meet CMS
from healthcare providers and the U.S. government, and if suc- and ASHRAE stmdards. Examples of tools include sprinkler
cessful, should make a significant contribution to HAl reduction. and generator checklists, occupancy and move checklists, an
Infection Control Risk Assessment Matrix of Precautions for
Construction and Renovation (78), and disaster recovery
OTHER STANDARDS-SETTING ORGANIZATIONS checklists for healthcare facilities (79).
Many other organizations publish stmdards that affect IPC (see

Table 13-1). These organizations include the EPA, which hasstm- ASSOCIATION FOR THE ADVANCEMENT
dards governing the disposal and transportation of medical waste OF MEDICAL INSTRUMENTATION
and a registry of liquid chemical products used for surface disin- The Association for the Advancement of Medical Instrumen-
fection and sterilization in hospitals (72). Another government tation (AAMI) is a nonprofit organization founded in 1967,
agency is the IDA, which regulates antiseptics and medical ~ which unites 7,000 healthcare technology professionals to
vices (through the Safe Medical Devices Act), the reuse ofsingl~ guide the healthcare community in the development, manag~
use devices, the safety of the blood supply, and most food safety ment, and use of safe and effective medical technology (80). In
(73). Yet another agency is The Government Accountability Of- addition to developing stmdards for medical equipment and
fice (GAO), which has published stmdards regarding the mini- sterilization, AAMI also provides a forum for benchmarking
mum elements of an IPC program, and these focus on economic within sterile processing areas.
issues (74). In addition, the National Fire Protection Association
(NFPA) participated with IPs and other healthcare personnel in
a lengthy debate about the placement of alcohol-based hand hy- INFECTION PREVENTION AND
giene products in egress corridors of hospitals (75). CONTROL HEALTH POLICY: THE ROLE
OF SCffiNCE AND POLIDCS
FACILITY GUIDELINES INSTITUTE
The public health policy process is complex. It reflects the het-
The not-for-profit Facility Guidelines Institute (FGI) was erogeneity of participants, their plurnlistic interests, and the
founded in 1998 to provide continuity in the facility guid~ policy process itself. Policy formulation and adoption do not
lines revision process, to function as a contractual coordinating occur in a vacuum, nor do they occur in an orderly manner
entity, and to enhance the content and format of guidelines (81). The public, interest groups, governmental agencies, and
publications to encourage and improve their application policy makers bring to bear their personal, political, ideologi-
and use. The FGI Guidelines for Design and Construction of cal, and culturnl values when they determine which policies
Health Care Facilities recommend minimum program, space, they will consider, support, or oppose (82). Not all HAl issues
and equipment needs for clinical and support areas of hos- become candidates for public policy. The subject must gener-
pitals, ambulatory care facilities, rehabilitation facilities, and ate anxiety or dissatisfaction or be perceived as a problem by
nursing and other residential care facilities (76). Many of the the public or by policy makers (83). Issues that involve personal
recommendations are geared toward IPC in general health- fear, urgency, or threats are more likely to reach the policy
care environments as well as clinical settings. For example, the agenda. Some issues describe actual risks, while others escalate
guidelines specify the environmental requirements for endos- public fear through sensationalism or misperceptions based on
copy suites, surgical suites, food preparation areas, and other a lack of scientific knowledge. Often, the public policy process
settings in hospitals and ambulatory care. The guidelines also reflects a combination of these elements.
address minimum engineering design criteria for plumbing; In the 1980s, HIVI AIDS first became a policy issue owing
electrical; and heating, ventilation, and air conditioning sys- to public fear and uncertainty regarding its transmission, the
tems that can help prevent transmission of infections if they are identity of the individuals affected, and the lack of adequate in-
implemented correctly (76). formation (84,85). One example is that medical waste disposal
became an important policy issue. Medical waste had rarely collaboratives with numerous organizations, such as TJC. One
been demonstrated to pose a disease risk to humans if man- collaborative example is the consensus measurement of hand
aged in a reasonable manner (86); however, the advent of AIDS hygiene project in which TJC reached out to major leader-
intensified the fear about transmission of HIV from medical ship organizations in the United States and abroad to identify
equipment, devices, and supplies used in hospitals, clinics, or best practices for measuring compliance with hand hygiene
other healthcare organizations and raised these issues to discus- guidelines in healthcare organizations. Participating organiza-
sion at the policy level (83). The potential for an avian influenza tions included WHO, IHI, the Association for Professionals in
pandemic also found a place on the policy agenda because of Infection Control and Epidemiology, Inc. (APIC), the CDC,
the anxiety, scientific uncertainty, and alarm it generated about the Society for Healthcare Epidemiology of America (SHEA),
potential patient morbidity and mortality. On the other hand, and the World Alliance for Patient Safety. The hand hygiene
significant IPC issues (e.g., increasing antimicrobial resistance, project published a free educational monograph in 2008 that
lack of immunizations, and device-related infections) until re- recommends best practices for measuring hand hygiene com-
cently have been managed largely by healthcare professionals pliance (9 1).
without becoming politically charged health policy issues. In recent years, numerous collaboratives, partnerships, and
Health issues must be articulated to attract the attention of consensus papers have been promoted at the local, state, and
policy makers. However, some problems are difficult to quantify national levels. Using American Recovery and Reinvestment
because of their "invisible" nature (82) . One strategy to bring Act funds, the CDC supported the hiring and training of HAl
attention to these issues is to collect and share data that commu- coordinators who would be embedded in state public health
nicate the magnitude of a problem; another is to publicize un- departments to work collaboratively with all types of healthcare
fortunate events. Infections among the homeless, immigrants, providers in their state. In 2008, SHEA, the Infectious Diseases
or other politically underpowered populations are largely left Society of America (IDSA), the AHA, and APIC formed a
to healthcare professionals to manage. However, the increas- partnership to jointly publish science-based practical recom-
ing availability of HAl data has amplified visibility and resulted mendations for acute care hospitals for the prevention of com-
in increased public awareness and concem. Consumer groups mon HAis in Infection Control & Hospital Epidemiology. The
have successfully articulated the need for mandatory public re- Compendium of Strategies to Prevent Healthcare-Associated
porting of HAl data and have lobbied state legislatures to enact Infections in Acute Care Hospitals (92) synthesized the best
HAl reporting statutes (see Table 13.2 for more information available evidence for preventing HAis into consensus guide-
about these groups). IPC societies, governmental agencies, and lines for CA-UTis, ClA-BSis, C. difficik, methicillin-resistant
other organizations have joined this conversation, and the me- Staphylococcus aurew (MRSA), SSis, and VAP. The CDC has also
dia has kept these issues at the forefront of public awareness. used a collaborative module that encourages state to learn from
Science and politics both contribute to health policy formu- another and share their experiences to promote tools to public
lation. Science is essential, but often, not sufficient. It contrib- health agencies and multiple types of healthcare organizations,
utes a relatively impartial and rational aspect to policy making, including dialysis, long-term care, acute care, and ambulatory
but political factors, such as economics, social values, and public care settings (93).
perception, may be more powerful in determining policy (81). Many present-day public-private collaboratives to reduce
For example, the 2005 update of the CDC tuberculosis (TB) HAis are making a difference. One notable pr~ect is the
guidelines involved extensive negotiations and lobbying from Michigan Keystone Intensive Care Unit Project, a partnership
IPs and such agencies as the CDC and its National Institute for between the Michigan Health & Hospital Association andJohns
Occupational Safety and Health (NIOSH) to focus on the sci- Hopkins University (94). The project addressed complex orga-
ence to determine respiratory policies for TB protection (87). nizational change across the state of Michigan by creating a so-
Similar discussions were held during the H1Nl epidemic. And cial network among ICUs in hospitals across Michigan to share
the revised guidelines for isolation (88) and disinfection and best practices to reduce ClA-BSis, developing a checklist for
sterilization (89) were in development for several years while clinicians when they inserted central catheters, and instituting
professionals debated the science, politics, and costs of manag- surveillance practices to monitor ClA-BSI rates. The pr~ect
ing MDROs in healthcare organizations and the issues of vari- was so successful that participating hospitals saw a 66% reduc-
ous disinfecting agents (90). The balance between the forces tion in CIA-BSis, which translated to 1,500 lives saved and cost
that determine the IPC agenda is a continuing challenge. savings of $200 million in the fmt 18 months of the project.
These successes attracted the attention of the President of the
United States and the U.S. Secretary of Health & Human Ser-
THE ERA OF PARTNERSHIPS: vices, who increased the visibility of IPC by making it a greater
CONSENSUS AND COLLABORATION priority in the United States (95) .
One of the major changes in IPC in the past two decades has
been efforts by professional, governmental, and regulatory PATIENT SAFETY AND QUALITY
agencies and organizations to work together in a collabora-
ORGANIZATIONS
tive fashion. This effort began in earnest in 1991 when the
U.S. Secretary of Health & Human Services began to invite
INSTITUTE OF MEDICINE
experts in IPC to help the CDC create and revise HAl guide-
lines, and formed the Healthcare Infection Control Practices In 1999, the landmark Institute of Medicine (10M) report
Advisory Committee (HICPAC). That same year, the Insti- TO Err Is Human: Building a Safety Health System generated in-
tute for Healthcare Improvement (IHI) was founded and be- tense media, policy, and healthcare provider discussion about
gan to initiate and participate in a number of safety and IPC the safety of healthcare in the United States and its impact on
patient morbidity and mortality and the cost of medical errors taxonomy, and incorporates evidence-based recommendations
(96). A subsequent 10M report published in 2001, Crossing the (34). Among the IPC-related measures endorsed by NQF are
Quality Chasm: A New Health System for the 21st Century, discussed measures for SSI prophylaxis, immunizations for selected con-
the necessary redesign of the healthcare system to improve pa- ditions, and device-associated HAis. In addition, in November
tient safety (97) . Finally, a third 10M report, Leadership by Exam- 2011, the NQF named a steering team that developed national
ple: Coordinating Guvemment Roles in Improving Healthcare Quality, voluntary consensus standards for reporting HAis (34). The
published in 2003, not only discussed immunization but also consensus process resulted in seven national voluntary consen-
estimated that more than 40,000 lives could be saved annually sus standards for reporting HAl data and eight recommenda-
through wider implementation of CDC guidelines (98). tions for infection measure development and research ( 102).
Reports such as these have helped lead to the development Many NQF measures subsequently have been adopted by CMS
of numerous patient safety and quality organizations, and have and 'IJC as hospital performance, pa)"for-reporting, or value-
helped spur the development of various pay-for-performance based purchasing measures. There are also approximately 13 ad-
quality programs and large state and national collaboratives de- ditional NQF-endorsed HAl measures in other measure sets, such
signed to improve healthcare quality and prevent HAis. As with as the nursing-sensitive care measures and patient safety measures.
regulatory agencies, it is not possible to discuss all patient safety
and quality organizations; therefore, several will be highlighted
THE INSTITUTE FOR HEALTHCARE
in the following sections.
IMPROVEMENT (IHI)
IHI is a not-for-profit organization founded in 1991 with the
THE AGENCY FOR HEALTHCARE RESEARCH
goal of improving the quality of healthcare delivered to pa-
AND QUALITY (AHRQ)
tients around the world (103). In January 2005, IHI initiated
Previously known as the Agency for Health Care Policy and Re- a nationwide voluntary collaborative-the Save 100,000 lives
search, AHRQ arose out of the Healthcare Research and Qual- Campaign-with the goal of reducing healthcare-related deaths
ity Act of 1999 and is organized under the U.S. Department of by 100,000 in 18 months and every year thereafter (102). Three
Health 8c: Hwnan Services (35). AHRQis the leading U.S. agency of six campaign initiatives involved reducing HAis, including
on quality-of-care research, with the responsibility of coordinat- SSis, VAP, and CLA-BSis. VAP and CLA-BSI initiatives involved
ing all quality improvement efforts and health services research the implementation of central line "bundles" (groups of evi-
in the United States. Through its 12 evidence-based practice dence-based practices that when implemented together result
centers, it supports scientific quality research and maintains the in better outcomes than when implemented individually) ( 104).
National Guidelines Clearinghouse, a website devoted to collect- This campaign grew in 2006 with the Save 5 Million lives Cam-
ing and organizing various evidence-based practice guidelines paign, the goal of which was to prevent 5 million incidents of
developed by external agencies and professional societies (99). medical harm over a 2-year period-HAl-related components
The AHRQ website provides inpatient quality indicators that including reducing MRSA infections and surgical complications
can be abstracted from administrative data to assist hospitals ( 105) . These campaigns allowed participating hospitals to share
identifY problem areas that need further improvement (35). best practices, participate in frequent conference calls, and track
In addition, AHRQ's patient safety indicators include postop- progress on the IHI website countdown (102,104). In addition
erative sepsis, wound dehiscence, and selected infections (35). to campaign materials, the IHI website provides many resources
The AHRQ website also contains nwnerous free resources that designed to improve the quality of patient care. For example,
can be used for improvement efforts, including information for the Partnership for Patients referred to earlier has identified
consumers. In 2006, AHRQ published a compendiwn of quality nine areas of focus, including four that are HAl-related, and
recommendations in which 28% of the recommendations were IHI has developed Improvement Maps for each of these areas.
IPCrelated, and 5 of 11 "clear opportunities for improvement" Another important IHI project is the Global Trigger Tool,
recommendations were IPCrelated, including the use of full which was originally designed by IHI to detect and measure drug-
barriers for central venous catheter insertion and appropriate related adverse events. Today, it provides an easy-to-use method
use ofsurgical prophylaxis (100). In addition, the AHRQfunds to accurately identifY any type of adverse event (or harm) and
a wide array of research projects to identify strategies to prevent to measure the rate of adverse events over time (106). The goal
HAis. During 2011, some of these projects included the Compre- of using this tool is to help hospitals have a more effective way
hensive Unit-based Safety Program (CUSP) for Ventilator-Associ- to identifY events that cause harm to patients to quantifY the de-
ated Pnewnonia Prevention, Electronic Surveillance for Wound gree and severity of harm and to select and test strategies to re-
Infection After Ambulatory Pediatric Surgery, and An Environ- duce harm (105). This tool can also be used in HAl-prevention
mental Disinfection Intervention to Control C. difficile (101). efforts (e.g., device-related HAis, C. difficile, and MDROs).
NATIONAL QUALITY FORUM (NQF)

EVIDENCE-BASED PRACTICES
NQF is a public-private, not-for-profit partnership composed
of approximately 170 organizations established in 1999 as part Evidence-based practices are defined as practices that are sup-
of the President's Advisory Commission on Consumer Protec- ported by some level of scientific review, which can range from
tion and Quality in the Health Care Industry (34). NQF's goal scales using a weighted scheme (e.g., the CDC methodology
is to standardize healthcare performance measures, so they that gives the greatest weight to randomized, controlled clini-
can be used to compare healthcare across the United States. cal trials) to expert consensus. The AHRQ National Guideline
NQF builds consensus around voluntary measures for inpa- Clearinghouse provides descriptions of different evidence
tient and outpatient settings, helps standardize a patient safety rating systems (107).
THE HBALTHCARE INFECTION CONTROL have been selected by DHHS to provide guidance to DHHS and
PRACTICES ADVISORY COMMITTEE (HICPAC) the Director, CDC on the control of vaccine-preventable dis-
eases (112). The committee also contains eight ex officio mem-
The most widely used evidence-based guidelines in IPC origi- bers representing other US agencies and nonvoting liaisons
nate from the CDC's lllCPAC (108) (Table 13.3), APIC (109),
representing other professional organizations with expertise in
and SHEA (110), which all use a weighted scale to rate evidence.
the field of IPC. ACIP develops written recommendations for
HICPAC is a US Federal Advisory Committee composed of 14
the administration of vaccines, including age, dosing intervals,
experts in IPC. Members provide advice and guidance to the CDC
precautions, and contraindications. The process for developing
and the U.S. Secretary of & Human Services on IPC practices and
ACIP recommendations follows that ofHICPAC.
strategies to reduce HAis (107). The committee promulgates
evidence-based guidelines for IPC that are widely distributed and
used in the United States and many countries throughout the
world. Additional reviews of these guidelines and position papers THE INFLUENCE OF PROFESSIONAL
are provided by a large number of ex officio members from gov- ORG~ONSONINFECTION
ernmental agencies (such as CMS, AHRQ, and the NIH) and by PREVENTION AND CONTROL AND
liaisons representing APIC, SHEA, IDSA, the Association for peri- HrnALTHCAREEPIDEN.UOLOGY
Operative Registered Nurses (AORN), 1JC, the AHA, and other PRACTICE
professional organizations and accrediting bodies.
Recent IDCPAC IPC guidelines are shown in Table 13.3. All ASSOCIATION FOR PROFESSIONALS IN
HICPAC meetings are open to the public, and draft guidelines are INFEGI'ION CONTROL AND EPIDEMIOLOGY
published in the Federal Register to solicit additional broad input
(111). The last step before guidelines are finalized is peer review The Association for Professionals in Infection Control and Epi-
through the US Office of Management and Budget {OMB). demiology, Inc. (APIC) was founded in 1972 as the first profes-
Guidelines produced by professional societie!!----!!uch as SHEA, sional organization for IPs in the United States dedicated to
APIC, and IDSA-also use evidence-based studies. These guide- reducing HAis. APIC is the largest professional association for
lines are developed by expert committees with deep experience IPs, with more than 14,000 members worldwide (113). APIC's
in IPC and healthcare epidemiology and are approved by their mission is to create a safer world through the prevention of
respective boards of directors. IPC collaboratives have also devel- infection. This goal is achieved by the provision of better care
oped strong, successful IPC strategies, such as bundles, and other to promote better health at a lower cost ( 114). As early as 1978,
innovative approaches that are being implemented by organiza- APIC emphasized the need for trained IPs (115) and encour-
tions in the United States as well as globally (93). A selection of aged professionals to use epidemiologic principles and meth-
consensus documents is displayed in Table 13.4. ods to address infection, quality, and risk issues {116), and
more recently, added patient safety strategies. To support the
ADVISORY COMMITTEE ON IMMUNIZATION professional development of IPs, APIC published a compre-
PRACTICES (ACIP) hensive text that guides practice ( 117), and recently published
a new competency modelfor IPs (118).
Similar to lllCPAC, the Advisory Committee on Immunization The Certification Board of Infection Control and Epidemi-
Practices (ACIP) is a U.S. Federal Advisory Committee consist- ology (CBIC), established by APIC in 1980, is a voluntary, au-
ing of 15 experts in fields associated with immunization who tonomous, multidisciplinary board that directs and administers
TABLE 13.3 Centers for Disease Control and Prevention Healthcare Infection Control Practices
Advisory Committee (HICPAC) Guidelines, Guidance, and Recommendations
(http://www.cdc.govjhicpac/pubs.html)
Year Document
2011 Guideline for the Prevention and Control ofNorovirw Gastroenteritis Outbreaks in Healthcare Setting~~
2011 Guideline for the Prevention of Intravascular Catheter-Related Infections
2009 Guideline for Prevention of Catheter-.A!sociated Urinary 'fract Infections
2009 Guidance for Control of Infections with Carbapenem-Resistant or Carbapenemase-Producing Enterobacteriaceae in Acute Care
Facilities
2008 Guideline for Disinfection and Sterilization in Healthcare Settings
2007 Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare Settings
2006 Management of Multidrug-Resistant Organisms in Healthcare Settings
2006 Influenza Vaccination of Healthcare Per30nnel
2005 Guidance on Public Reporting of Healthcare-Associated Infections: Recommendations of the Healthcare Infection Control
Practices Advisory Committee
200!1 Guidelines for Preventing Healthcare-Associated Pneumonia
200!1 Guidelines for Environmental Infection Control in Healthcare Facilities
200!1 Recommendations for Using Smallpox Vaccine in a Pre-Event Vaccination Program
2002 Guidelines for the Prevention oflntravascular Catheter-Related Infections
2002 Guidelines for Hand Hygiene in Healthcare Settings
1999 Guideline for Prevention of Surgical Site Infection (In Revision)
1998 Guideline for Infection Control in Healthcare Per30nnel (In Revision)
1997 hnmunization ofHealthcare Workers
1995 Recommendations for Preventing the Spread ofVancomycin Resistance
• . {;C :f §:f , , . Selected Consensus Documents for Infection Prcva1tion and Control
Document/Guideline Author(•) or Publillber(11)
Multisociety guideline on reproces&ing flexible GI endoscopes: Petersen B, et al. Infect Controi.HospEpidemiol. 2011;32:527-5!17.
2011
Consensus standards and performance indicators for prevention Coobon B, et al. J Hasp Inftct. 20 11;79:260-264.
and control of healthcare-associated infection in Europe.
Strategies to prevent catheter-a.s.rociated urinary tract infections Lo E, et al. InfliCt ControlHaspEpidemiol. 2008;29 (suppl1 ):S41-S50.
in acute care hospitals
Strategies to prevent central line-associated bloodstream infec- Marschall], et al. Infoct Control Hasp Epidemiol. 2008;29 (suppl 1) :S22-S30.
tions in acute care hospitals
Strategies to prevent transmWion of methicillin-resistant Calfee DP, et al. InfliCt Control Hasp Epitlemiol. 2008;29(suppl1) :S62-s80.
Staphylococcus aum~S in acute care hospitals.
Strategies to prevent ventilator-associated pneumonia in acute Coffin SE, et al. InfliCt Controi.HaspEpidemiol. 2008;29(suppl1):S!I1-S40.
care hospitals
Strategies to prevent Clostridium difficile infections in acute care Dubberlr.e ER, et al. Infoct Ctmtroi.HospEpidemiol. 2008;29(supp11):S81-S90.
hospitals
National voluntary consensus standards for the reporting of http://www.qualityforum.org/Publications/ 2008/ 03/ NationaL
healthcare-associated infection data Voluntary_Consensus_standards..Ior_the....Reporting_o[..Healthcare-
.Associated_Infection_Data.aspx Accessed August 2012.
Compendium of strategies to prevent healthcare-associated infec- Yokoe DS, et al. Infect Control Hasp Epidemiol. 2008;29(suppl1) :S12-S21.
tions in acute care hospitals
Infectious Diseases Society of America and the Society for Health- Dellit TH, et al. Clin Infect Dis. 2007;44:159-77.
care Epidemiology of America guidelines for developing an
institutional program to enhance antimicrobial stewardship
Management of outbreaks of methicillin-resistant Stap!rJlococcus Gerber Sl, et al. Infoct Control Hasp Epidemiol. 2006;27:1!19-145.
aum~S infection in the neonatal intensive care unit: a consen-
sus statement
Multisociety guideline on reprocessing flexible gastrointestinal Nelson DB, et al. Dis Colon Rectum. 2004;47:413-420 .
endoscopes
Infection control recommendations for patients with cystic fibro- Saiman L, Siegel J. Cystic Fibrosis Foundation. Infea Control Hosp E~
sis: microbiology, important pathogens, and infection control miol. 2003;24:S6-S52.
practices to prevent patient-to-patient transmission
Anthrax as a biological weapon, 2002: updated recommendations Inglesby TV, et al. JAMA. 2002;287:2236-2252.
for management
NIH consensus statement on management of Hepatitis C: 2002 NIH Consens State Sci Statements. 2002;19:1-46.
Requirements for infrastructure and essential activities of infec- Friedman C, et al. AmJ Infect Omtrol. 1999;27:418-430.
tion control and epidemiology in out-of-hospital settings: a
consensus panel report
Global consensus conference: final recommendations Am]Infect Omtrol.1999;27:503-51!1.
Requirements for infrastructure and essential activities of infec- Scheclr.ler WE, et al. Infoct Control Hasp Epidemiol. 1998;19:114-124.
tion control and epidemiology in hospitals: a consensus panel
report. Society for Healthcare Epidemiology of America.
Methicillin-resistant Sklphylococcus aum~S outbreak: a consensus Wenzel RP, etal. Am]Inft!Ct Control. 1998;26:102-110.
panel's definition and management guidelines
Society for Healthcare Epidemiology of America and Infectious Shlaes DM, et al. Infect Control Hasp Epi&miol. 1997; 18:275-291.
Diseases Society of AmericaJoint Committee on the Preven-
tion of Antimicrobial Resistance: guidelines for the prevention
of antimicrobial resistance in hospitals
Infectious disease testing for blood transfusions. NIH Consensus JAMA.. 1995;274:1!174-1!179.
Development Panel on Infectious Disease Testing for Blood
Transf'u.sions
the certification process for professionals in infection control Since its inception, the organization has expanded its membership
and applied epidemiology through a certifying examination for to include IPs and a greater proportion of international members.
IPs and epidemiologists (119). SHEA's efforts to influence the IPC profession have led to the
creation of the Education & Research Fonndation to advance the
field, educate and recognize leaders, promote the international
THE SOCIETY FORHEALTHCARE EPIDEMIOLOGY
exchange of ideas, and foster a scientific research agenda (120).
OF AMERICA (SHEA)
In addition, SHEA created the SHEA Research Network, a con-
In 1980, a group of physicians (mainly specialists in infectious dis- sortiwn of nearly 200 hospitals that collaborate on research pr~
eases) fonnded SHEA, a professional organization dedicated to ects of importance to healthcare epidemiology ( 121). SHEA has
developing, applying, and disseminating the science of healthcare also embarked on a program to forge strong relationships with
epidemiology to prevent HAis and other adverse outcomes. One emerging leaders in epidemiology throughout the world. In its
of SHEA's goals is to translate knowledge into effective policy and first years, The International Ambassador Program has been note-
practice (109). Currently, SHEA has more than 2,000 members. worthy in educating and supporting 42 hospital epidemiologists
and IPs-representing 22 countries in Asia, Afiica, Latin Amer- vaccination rates in their IPC plans, to incrementally increase
ica, the Middle and Far East, and Europe--as they endeavor to institutional influenza vaccination goals consistent with achiev-
improve care and reduce infections, often with limited resources ing the Healthy People 2020 goals of a 90% influenza vacci-
(122). And lastly, SHEA continually reviews challenging issues in nation rate, to have a written methodology that describes how
healthcare epidemiology and publishes white papers, position they determine their influenza vaccination rates, to evaluate
papers, and compendiums/guidelines, including those address- reasons for vaccination declination, and to provide vaccination
ing such topics as antimicrobial stewardship, influenza inununiza- rates to key stakeholders. The standard stopped short, however,
tion, management of special pathogens, and policy issues. of mandating vaccination for HCP (51). APIC (126) and SHEA
SHEA and APIC actively advocate for sensible and pragmatic (127) also endorse required annual influenza vaccination as a
IPC policies and the resources necessary to sustain active IPC and means to protect patients and HCP.
hospital epidemiology programs. Both organizations publish po- Despite these recommendations from numerous organiza-
sition papers, consensus documents and guidelines, scientific tions, only 63.5% of HCP reported receiving influenza vaccina-
research studies in their peer-reviewed journals-The American tion during the 2010-2011 influenza season (128). Moreover,
Journal of Infection Control (AJIC) and Infection Control and only 13% of HCP reported that influenza vaccination was re-
Hospital Epidemiology (ICHE)-and thought-provoking articles quired in their organizations (127). Great disparities were seen in
about the state of the field and policy issues for the field. These vaccination rates among organizations that mandated influenza
associations also endorse guidelines from other organizations, vaccination compared to those that did not. Vaccination rates
such as IDSA or IHI, to strengthen their own recommendations were 98.1% among HCP subject to mandatory inununization vs.
that promote best practices. APIC and SHEA also proactively ed- 58.3% among HCP not subject to required vaccination (127).
ucate their members and engage lawmakers, regulatory agencies, NQF endorsed a measure of influenza vaccination among
the CDC, and others regarding the development of IPC regula- HCP in May of 2012 (129), which will be incorporated into the
tions and standards and responses to emerging issues. SHEA and CMS Hospital IQR program measures in 2015.
APIC are instrwnental in contributing to HICPAC guidelines. In response to public pressure, increased government at-
tention, promotion, and acknowledgment of this important
patient safety issue, greater numbers of healthcare organiza-
tions are now mandating influenza immunization for their
THE INTERPLAY AND INFLUENCE staff (130-133) with strong support from HICPAC, ACIP, IDSA,
OF INFECTION PREVENTION APIC, and the AHA. These efforts are directed to improving
PROFESSIONALS AND MULTIPLE the safety ofHCP and patients by reducing the transmission of
AGENCIES ON PRACTICE: INFLUENZA influenza in healthcare organizations.
VACCINATION FORHEALTHCARE
PERSONNEL, A CASE STUDY CONCLUSIONS
Efforts to increase influenza immunization among HCP illus-
A wide range of professional, governmental, regulatory, volun-
trate the interplay between various accreditation standards,
tary, public, and accrediting agencies and leaders and not-for-
professional societies, and regulatory bodies.
profit state, national, and international collaborating partners
ACIP has recommended influenza vaccination for all HCP
are focused on reducing HAis. The collaboration between
since 1984 (123). Despite this recommendation, HCP vaccina-
these agencies and professional societies to prevent infections
tion rates have remained consistently low. Influenza immuniza-
in patients and HCP has grown stronger over time. As never
tion of HCP is a patient safety issue because HCP can transmit
before, IPs, epidemiologists, and standards-setting and advisory
the influenza virus at least a day before they develop symptoms
groups have the ground support to be able to reduce HAis in
and because many patients have conditions that put them at
the United States and around the globe.
increased risk for morbidity and mortality from influenza.
CMS CoP §482.42(a) (1) requires that "the infection control
officer or officers must develop a system for identifying, report-
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14 Robert C. Owens, Jr. and William R. Jarvis
Antimicrobial Stewardship: Progranunatic

Efforts to Optitnize Antimicrobial Use
INTRODUCTION Stewarding these precious resources has become a priority for
many organizations, including the Infectious Diseases Society
Microbes account for 90% of the 1014 ceUs in the human of America (IDSA), the Society of Healthcare Epidemiology of
body ( 1). Thus, it should not be surprising that the well-known America (SHEA), the Society of Infectious Diseases Pharma-
benefits of antimicrobials must be balanced with an apprecia- cists, the Alliance for the Prudent Use of Antimicrobial!, the
tion of their unintended effects on beneficial microbiota and Centers for Disease Control and Prevention (CDC), and the
the evolution of resistance. In essence, use of antimicrobials is World Health Organization. In fact, joint guidelines endorsed
a double-edged sword. Their lif~aving benefits and disease- by multiple societies have recendy been published that reitel'-
modifying effects can be nothing short of miraculous; however, ate the need for proactive, programmatic efforts to optimize
the opposing edge of the sword can be just as sharp. Exam- the use of antimicrobials in healthcare settings (6).
ples include serious patient harm in the form of adverse drug Since the initial work of Finland and Mc.Gowa:u, a variety of
events (e.g., hepatotoxicity, tonades de pointes, anaphylaxis, interventional strategies has been shown to reduce unneces-
renal failure), development of potentially Iife..threatening Clos- sary antimicrobial use, to optimize the dose and duration, and
tridium ~associated disease (CDAD), and the emergence to minimize the collateral adverse effects of their use (7-9).
of antimicrobial resistance (2,3). While the first two can occur Most studies have evaluated the impact of interventions on in-
during therapy and are more tangible to the practicing clin.i.- patient antimicrobial use and, to a lesser degree, outpatient
cian, the emergence of reaiatance often OCCUI'3late and may be antimicrobial use. This chapter shall reinforce why the judi-
less obvious. cious use ofantimicrobials is essential and the implementation
It has been said that those who move forward without taking (including potential barriers) of an institutional approach is
a moment to look back are doomed to repeat history. In 1956, necessary to optimizing antimicrobial use. It shall also dis-
noted microbiologist EmestJawetz once wrote: cuss the collaborative nature of these programs with infec-
On the whole, the position of antimicrobial agents in medi- tion control and prevention programs and the microbiology
cal therapy is highly satiafactory. The majority of bacterial in- laboratory.
fections can be cured simply, effectively, and cheaply. The
mortality and morbidity from bacterial diseases has fallen so
low that they are no longer among the important unsolved
RATIONALE FOR OPTIMIZING
problems of medicine. These accomplishments are widely
ANTIMICROBIAL USE
known and appreciated (4).
ANTIMICROBIAL RESISTANCE
He goes on to state the intentions of hia paper: "the autlutr
wishes to call tlftlmtion to the abuse of anlibiotiu, its cower and Optimizing antimicrobial use through appropriate selection,
mult3 ... " (4). In the current antimicrobial era, some 50-plus dosing, and duration can be viewed as a strategy to minimize
years after these initially optimistic observations were made, an the development of resiatance among clinically important
increasing number of infections are not easily treated, morbid- pathogens (10). Factors promoting resistance are complex, nu·
ity and mortality are appreciable, and many infectious diseases merous, and extend beyond the use of antimicrobial agents in
have become unsolved proble~ns of modern medicine. The humans; as such, it is not surprising that they do not allow for
theme ofJawetz's latter plea remains a challenge facing many a prompt resolution (11). Although antimicrobial resistance
infectious disease experts today, calling attention to the abuse has been present on this earth since the days of the primor-
of antimicrobials and its causes and results. dial soup, its practical onset began in the 1920s with the ob-
In fact, published data note that many prescribers today still servation that Pfeiffer's bacillus (now Hanwphilw injlum.z,ae)
do not fully value the importance of preserving these therapeu- showed a natural resistance to penicillin before its introduc-
tic resources. '!Wenty-five million pounds of antimicrobials are tion for human use (12). With the introduction of Gerhard
produced yearly for human consumption and are administered Domagk.'s sulfa drugs in the 1930s, strains of Nf:isseri4 ~
to 30% to 50% of hospitalized patients, with nonhospitalized and Smptot:ot:cus fmetl.m.an.Uu! were noted to have developed the
Americans receiving 160 million courses (5). Yet, data show so-called "insensitivity" (12). Observations from the laboratory
that as much as 50% of all antimicrobial use is inappropriate. moved to the clinic in the 1940s shortly after the introduction
169
of penicillin for the treatment of human infections. The mira- PROGRAMS TO OPTIMIZE
cle drug, penicillin, while initially effective for the treatment of ANTIMICROBIAL USE
Staphylococcus aureus bloodstream infection (BSI), began to fail
to treat infections caused by penicillinase-elaborating strains as HOSPITAL-BASED ASPS
reported in Time magazine on May 15, 1944.
Important to this discussion is the fact that studies have es- A variety of studies has evaluated the impact of interventions on
tablished a strong relationship between antimicrobial use and antimicrobial use in healthcare systems. These studies have been
resistance. Levy et al. developed a biologic model that showed a conducted using a wide range of resources, methodologies, in-
clear relationship between antimicrobial use and the selection terventions (often multiple), and outcome measures (usually
of resistance in humans (13). Additionally, supportive data can considering cost, antimicrobial consumption, patient safety, and
be gleaned from in vitro investigations, ecologic studies corre- less frequently resistance). The culmination of these studies was
lating drug exposure with resistance, controlled trials in which considered and led to a guidance document developed jointly
patients with previous use of antimicrobials were more likely to by IDSA and SHEA to provide the framework for developing,
be colonized or infected with resistant bacteria, or prospective implementing, and monitoring the impact of ASPs (6).
studies in which antimicrobial use was associated with the de-
velopment of resistant flora (13-15). With many pharmaceuti- IDSA/SHEA GUIDELINES FORDEVEWPING
cal companies no longer supporting anti-infective development AN INSTITUTIONAL PROGRAM TO ENHANCE
and fewer new chemical entities being identified, we, now more ANTIMICROBIAL STEWARDSHIP
than ever, should be concerned about the consequences of
antimicrobial resistance ( 16). An effective ASP is financially self-supporting and is aligned
Data from surveillance studies demonstrate that for with patient safety goals (8,27-33). For these reasons, there
community-acquired respiratory pathogens, resistance among should be no excuse for an institution not to have a formal
S. pneumoniaeor H. injluenzaecan be an obstacle in selecting and program dedicated to improving the quality of antimicrobial
dosing the ideal regimen (17,18). For healthcare-associated in- use. Realizing that institutions vary in size and type of specialty
fections (HAis), resistance is an important impediment to treat- services offered, the ASP should be customized accordingly.
ing patients with the correct antimicrobial and dose in a timely
fashion. The effects of selecting the wrong antimicrobial and
INTERVENTIONAL STRATEGY
at the incorrect dose have measurable effects on patient out-
comes as highlighted by several recent studies (19,20). Thus, Two major interventional styles have evolved over recent
an important value provided by a programmatic approach dedi- years. The first is prospective audit and feedback ("back-end" pro-
cated to the oversight of antimicrobial use and employed by the gram). This entails obtaining a daily (or every other day for
healthcare system is to "quarterback" and operationalize efforts smaller hospitals) list of patients receiving antimicrobials and
to maximize the benefits of antimicrobials. Antimicrobial stew- determining interventions, such as pharmacodynamic dosage
ardship programs (ASPs) are able to drive the multidisciplinary adjustment, streamlining the de-escalation and identification
development of locally customized disease- or pathogen-based of redundant therapy based on culture and susceptibility re-
guidelines, protocols, and order sets and to provide real-time sults, parenteral-to-oral conversions, drug-interaction identifi-
human and, where available, computerized decision support in cation, guideline/protocol compliance, and recommendation
addition to their day-to-day interventions. of more cost-effective treatments (Figure 14.1). Recommen-
dations are provided to the prescriber in either written form
or by direct conversation. Written forms of communication
PATmNT SAFETY
usually take place on nonpermanent forms placed in the pa-
Whether being used appropriately or inappropriately, antimi- tient's medical record that are removed at discharge. This al-
crobials have the potential for causing serious harm to patients. lows flexibility in what can be written and allows the ASP team
For example, macrolides, ketolides, orfluoroquinolones are as- member to communicate educational messages effectively and
sociated with QT interval prolongation; macrolides or ketolides to provide citations or references on why the intervention is
are associated with metabolic liability in the form of cyto- being recommended. The benefits of this type of program are
chrome P450 3A4 inhibition; trimethoprim-sulfamethoxazole its customizability to smaller- (29) or larger-size healthcare fa-
is associated with Stevens-Johnson syndrome; and B-lactams cilities (9,27); it avoids taking away the prescriber's autonomy,
are best known for hypersensitivity reactions (3,21,22) while which also increases productive "educational" dialogue; and it
all antimicrobials are associated with CDAD (23). Disturb- circumvents the potential for delays in initiating timely antimi-
ingly, the rate and severity of CDAD is increasing and our tra- crobial therapy since the antimicrobial is already prescribed.
ditional treatment options appear to be less effective (24,25) . The downside is that recommendations are optional (although
The potential harm caused by antimicrobials should incentiv- there are ways to correct repeated unaccepted recommenda-
ize even the most temerarious clinicians not to casually pre- tions by communicating with either the department chief or
scribe antimicrobials in the setting of a nonbacterial infection an institutional committee [e.g., medical executive committee,
or to stop therapy in a timely manner and carefully monitor pharmacy and therapeutics committee, patient safety commit-
patients off antimicrobials (2). In addition, antimicrobials are tee]). A program at Maine Medical Center (MMC) has em-
unique and unlike any other drug class. One can develop an ployed this primary strategy for >5 years (8,27,33), and others
infection because of a resistant pathogen without ever having have operated for longer periods of time (28).
received the particular antimicrobial it is resistant to; hence, The second chief strategy is a preautlwrization or "front-end"
antimicrobials are considered societal drugs because their use program that restricts most antimicrobials to an approval pro-
has societal consequences (26). cess. A team member carries a pager or telephone and receives
Chaptu 14 • Antimicrobial Stewardship: Programmatic Effarts to optimize Antimicrobial Use 171
Dally Antibiotic
Reports Generated
Identify Patients
Requiring Potential .... ... Supplemental Strategies:
Intervention "'""1-----t.,.~ • Clinical Practice Guidelines
• Pharmacodynamic close
optimization
• Streamlinlng/o.escaiatlon
• IV to Oral Therapy
Focused Patient l'lll....t---1""'~ • Education
r
Record Review/
Computer
Record Review
Additional Clinical
No Intervention Routine Intervention Input/Evaluation
Necessary
Recommendation/Educational
Note Left in a Non-Permanent
Fashion in the Patient's Medical
Figure 14.1. Concurrentreview Record OR Prescriber Contacted
program workflow diagram.
approval requests for restricted antimicrobials. At the time of require approval (8) . One of the most valuable aspects of an
interaction, the antimicrobial either is justified and approved ASP is the institution-wide responsibility for overseeing the use
or an alternative recommendation is given. The University of of antimicrobials. Although in moderate-size or larger hospitals
Pennsylvania (34,35), The University of Pittsburgh (36), and an infectious diseases (ID) physician consultation service, ID
others (37) have used preauthorization as their primary strategy pharmacist, and infection control department often are pres-
for several years. The benefits of this strategy include the ability ent and coexist or collaborate on specific areas of interest,
to funnel all initial antimicrobial prescribing through experts responsibility at the institutional level for antimicrobial stew-
versed in antimicrobial therapy and the typical demonstration ardship is usually not assigned. An administratively supported
of these programs for immediate and significant cost savings. ASP aligns resources from these various specialties and assigns
The potential downsides to this strategy include the loss of pre- responsibility to them.
scriptive autonomy that may lead to "gaming the system" (38)
and the fostering of potentially adversarial relationships (if not
TEAM MEMBERS
properly implemented with buy-in from important and opin-
ionated prescribers), the potential for delaying initial therapy, The IDSA/SHEA guidelines for developing an institutional pro-
time- and resource-intensive plans (usually 7 days per week with gram to enhance antimicrobial stewardship are very clear about
contingency plans for night coverage), and the necessity to the following: the ASP is directed or codirected by the two core
make decisions when the least amount of information is known team members, an ID physician and an ID-trained pharmacist,
about the actual infection (culture and antimicrobial suscepti- both receiving remuneration for their time. The pharmacist
bility results are not available for 2 to 3 days, and the quality of should have formal training in ID or be knowledgeable in the
information relayed to the ASP team member by prescriber can appropriate use of antimicrobials, with training being made
be variable (39)). available to maintain competency. Other team members opti-
In reality, although ASPs may lean toward one of the two pri- mally include a dedicated computer information support spe-
mary strategies, overlap often exists. For example, the program cialist, microbiologist, and an infection preventionist/ hospital
at MMC, while relying primarily on prospective audit and feed- epidemiologist. Figure 14.2 illustrates an optimal schematic for
back, does incorporate a limited number of antimicrobials that collaboration and partnership that MMC uses and was adapted
ASP Directors
• ID PharrnD
• ID Physician
Figure 14.2. Multidisciplinary

involvement and core team members.
from pre\ious models ( 40). Administrative and committee The intervention group also showed a trend toward reduced
support (e.g., pharmacy and therapeutics committee) is criti- mean length of stay compared to the controls (20 vs. 24 days,
cal. The particular interventional philosophy, responsibilities, respectively). Fifty percent of patients receiving targeted regi-
remuneration, and reporting measures should be discussed mens had their treatment refined on the third day of therapy,
in advance of implementation to address expectations and re- resulting in narrower spectnnn therapy and lower antimicro-
sources. Effective communication between the ASP, adminis- bial costs; most important, reducing antimicrobial use did not
tration, and an appropriate committee should be maintained adversely impact patient outcomes. This study was later used as
to facilitate dialogue over time as the healthcare environment a platform to implement an ASP that is more robust in types
continues to change. of activities and numbers of patients served by the program.
The team currently includes a part-time ID physician (2 hours
per day, 5 days per week) and a full-time ID PharmD. A close
PROSPECTIVE AUDIT AND FEEDBACK collaboration exists with the Department of Epidemiology and
Infection Prevention, the ID division, the pharmacy, adminis-
AND PREAUTHORIZATION STUDIES tration, the patient safety officer, and the pharmacy and thera-
peutics committee.
PROSPECTIVE AUDIT AND FEEDBACK
Srinivasan et al. studied the impact of an antimicrobial
STRATEGY
management program on antimicrobial expenditures at Johns
Fraser et al. (27) designed a prospective randomized con- Hopkins Hospital. Before the introduction of a comprehensive
trolled study of interventions for targeted antimicrobials in hos- ASP, the hospital used a closed formulary system and employed
pitalized patients. The team included a part-time ID physician prior approval requirements for several antimicrobials. The
and a PharmD with antimicrobial expertise. The intervention ASP consisted of a hospital-funded ID physician, ID PharmD,
group (N = 141) received suggestions (written or verbally). and data analyst. The team concurrently re\iewed antimicro-
whereas the control group did not (N = 111). Controlling for bial therapy in all areas of the hospital except pediatrics and
severity of illness between groups, the outcomes were similar oncology. Their interventions included a survey and the use of
with respect to clinical and microbiologic response to therapy, institution-specific guidelines, concurrent antimicrobial review,
adverse events, inpatient mortality, or readmission rates. Inter- and educational sessions. A "knowledge, attitude, and beliefs"
ventions included change to oral therapy (31%), regimen or survey was used to determine the awareness of antimicrobial
dosing changes (42%), stopping therapy (10%), or ordering use and resistance and sense deficiencies in knowledge that
additional laboratory tests (18% ); 85% of the suggestions were could lead to targeted education among house staff (41). Inter-
instituted. Multiple logistic regression models identified ran- estingly, only 18% viewed the program as an obstacle to patient
domization to the intervention group as the sole predictor of care and 70% wanted additional feedback on antimicrobial
lower antimicrobial expenditures. A conservative annualized re- choices. Hospital guidelines were published and updated an-
duction in antimicrobial expenditures of $97,500 was realized. nually. Antimicrobial therapy interventions occurred before
culture, and susceptibility results were available only when ac- in each newly introduced period, one cannot ignore the cumu-
tively solicited or when called for prior authorization of an anti- lative impact of the overall impact on cost. In addition, the final
microbial agent. For all others, interventions were suggested at period offers a comprehensive mechanism for long-standing
the time the microbiologic data became available. Compliance success and serves as a template to introduce other initiatives
with suggested recommendations by the ASP was 79%. The as deemed necessary. Part of the success related to reduction
costs for antimicrobial agents for the covered areas decreased in antimicrobial resistance rates noted by this program is re-
by 6.4% the first year and 2.2% the second year. Assuming a lated to the high rate of carbapenem or ceftriaxone use and
steady inflation rate of 4.5%, savings translated to $224,753 and the "seldom"-ordered cefepime or aminopenicillin/sulbactam
$413,998 for fiscal years 2002 and 2003, respectively. in conjunction with the types of problem pathogens noted
Bantar et al. demonstrated the impact of their ASP's inter- at their hospital (e.g., AmpC phenotypes and carbapenem-
ventional component on antimicrobial use, cost savings, and resistant P aeruginosa). Penicillin-based inhibitor combinations
antimicrobial resistance (42). The ASP consisted of an ID or cefepime have been noted to more often favorably impact
physician, two pharmacists, a microbiologist and laboratory the environment, in contrast to the high usage rates of carbape-
technologist, an internal medicine physician, and a computer nem or third-generation cephalosporin (9,43,44) .
systems analyst. In 6-month periods, four consecutive interven- Another study demonstrated the impact of a multidisci-
tion strategies were unveiled. During the first 6 months, an plinary ASP using a blend of interventions including minimal
optional antimicrobial order form (ID diagnosis, pertinent formulary restrictions, comprehensive education (e.g., direct
epidemiologic data) was introduced and baseline data were col- communication, antibiograms, peer feedback every 6 months),
lected (i.e., bacterial resistance, antimicrobial use, prescribing rounding with medical teams, and introduction of guidelines
practice, HAl, and crude mortality rates). In the second period, (appropriate initial empirical therapy, transitional therapy,
an "initial intervention" period consisted of transforming the duration of therapy) (31). All adult patients admitted to the
optional order form to a compulsory form and providing feed- medicine service were consecutively evaluated before the in-
back to clinicians on the basis of a review of the data collected troduction of the program (N = 500 patients) and postimple-
in the first period. In the third period, called the "education" mentation. Using DDD data and hospital expenditure data,
period, clinicians were verbally engaged with each new antimi- this study showed a 36% reduction in overall antimicrobial use
crobial order by members of the multidisciplinary team. The (p < 0.001), intravenous antimicrobial use (46%, p < 0.01), or
fourth or "active control'' period was similar to the third period, overall expenditures (53%, p = 0.001) without compromising
but the ASP team member modified prescriptions if necessary. the quality of patient care (determined by inpatient survival,
During the four periods, no antimicrobial agent was restricted. clinical improvement/cure, duration of hospitalization, or re-
To estimate the rates of use of a particular drug in relation to admission rates <30 days). These benefits were sustained for
other drugs, an index was calculated (e.g., rate of cefepime use the 4-year period evaluated.
to that for third-generation cephalosporins-ceftriaxone and Carling et al. (28) evaluated their ASP over a 7-year period.
ceftazidime-equaled cefepime/ consumption of ceftriaxone It consisted of a physician (one-quarter-time support) and
and ceftazidime X 100). Consumption data were measured PharmD (full-time support), both with specialty training in ID.
in defined daily doses (DDD). The program periods were as- Antimicrobial consumption was measured by using DDD/1,000
sociated with declining cost savings as time advanced (peri- patient-days for targeted antimicrobial agents. This program
ods 2, 3, and 4 were associated with a reduction of $261,955, operated 8 hours per day and 5 days per week, and during
$57,245, and $12,881, respectively). Comparing antimicrobial this time, new orders are typically evaluated within 4 hours of
order forms from period 1 (voluntary form and preinterven- their entry. Orders falling outside the 8-hour day were reviewed
tion, N = 450) with period 4 (mandatory form with active as a priority the next time the PharmD was on duty. Informal
intervention, N = 349), the ASP identified an increase in mi- written notes were generated when the team identified a prob-
crobiologically based treatment intent (27% vs. 62.8%, respec- lematic regimen and then was placed in the patient's chart.
tively, p < 0.0001). The team intervened on 27% of the period "Academic detailing" also occured between the PharmD and
4 antimicrobial order forms. Of the interventions, either the the prescribing clinicians to supplement the written recommen-
dose or duration (not specified) was reduced in 11.5%, 47% dations. They evaluated their impact on vancomycin-resistant
involved streamlining therapy to a narrower choice, and 86.1% enterococcus (VRE), MRSA, and CDAD by means of internal
was associated with cost reduction. HAl impact (e.g., length of benchmarking and externally benchmarking themselves with
hospitalization and mortality; only length of stay was impacted similar hospitals within the CDC's National Nosocomial Infec-
significantly [p = 0.04]). The increased rate ofcefepime use rel- tions Surveillance (NNIS) system. Over the 7 years, a 22% re-
ative to third-generation cephalosporins was associated with de- duction in parenteral broad-spectrum antimicrobials occurred
clining third-generation cephalosporin resistance rates among (p < 0.0001), during which time there was a 15% increase in
Proteus mirabilis or Enterobacter cloacae but not to Escherichia coli the acuity of their patient population observed. Reductions in
or Klebsiella jlmutTUmiae. The increased rate of aminopenicillin/ HAis caused by C. difficile (p = 0.002) or resistant Enterobacte-
sulbactam use relative to the third-generation cephalosporins riaceae (p = 0.02) were reported. The MRSA rates remained
in conjunction with a sustained reduction in vancomycin use unaffected.
was associated with a reduction in methicillin-resistant S. au:fl!US A smaller hospital (120-bed community hospital) also suc-
(MRSA) rates. In addition, Pseudomonas aeruginosa resistance cessfully implemented an ASP using a prospective audit and
rates to carbapenems declined to 0% and were strongly associ- feedback strategy (29). The ASP involved an ID physician, a
ated with the reduction in carbapenem consumption. clinical pharmacist, and representatives from infection control
The particular study by Bantar et al. is different than oth- and the microbiology laboratory. The ID physician was involved
ers in that it used a staggered approach to implementation. approximately 8 to 12 hours per week. Antimicrobial therapy
Although the cost reduction appeared to dwindle significantly was reviewed 3 days a week in patients receiving targeted drugs
or prolonged durations of therapy. Recommendations were agent can be detrimental to critically ill patients who need ini-
conveyed using a form that was temporarily placed in the tial broad-spectrum antimicrobial therapy. White et al. showed
patient's chart and by telephone, if necessary. During the first no delay in the administration of antimicrobial agents before or
year, 488 recommendations were made with a 69% acceptance after the introduction of its program; however, approval times
rate; antimicrobial expenditures were reduced by 19%, saving and time to antimicrobial administration must be monitored
an estimated $177,000. Common interventions were the dis- as a process measure (37). The perception of threatened au-
continuation of redundant antimicrobial therapy, the discon- tonomy can be a significant impediment to the efficacy of the
tinuation of treatment due to inappropriate use or excessive program. The experience of LaRocco et al. (29) and Owens
duration, the transition from intravenous to oral therapy, or et al. (8) using the prospective audit and feedback strategy
the substitution or addition of an antibiotic to the regimen. with few restricted antimicrobials promotes education at the
point of intervention, neutralizing negative emotions. Thus, re-
gardless of approach, constant communication with frontline
PREAUTIIORIZATION STRATEGY
prescribers and education are vital. The concept of gaming the
White et al. (37) implemented an ASP restricting the use system cannot be ignored and is a function of human nature.
of antimicrobials based on cost and/or spectra of activity. One program reported an HAl outbreak following introduc-
A 24hour-per-day, 7-day-per-week on-call system was established tion of its ASP (38). A 30% relative increase in HAl documenta-
via a dedicated pager that clinicians would call to receive ap- tion in the medical record occurred (HAl incidence increased
proval for restricted agents. In their quasi-experimental study, from 11 to 14.3 per 1,000 patient<are days, p < 0.05) (38). Af-
patients in the preimplementation period were similar to the ter further investigation into this counterintuitive finding, the
post implementation period in severity of illness. Outcome HAl outbreak was termed a "pseudo-<>utbreak." Clinicians were
measures that were not statistically significant between groups required to document infection in the medical record to justify
were survival (p = 0.49), infection-related length of stay for antimicrobial use; thus, more clinicians were documenting in-
BSI (p > 0.05), or, more important, time to administration fections in an attempt to use particular restricted antimicrobials.
of the antimicrobial (p > 0.05). Benefits received in the post- The perception that ASPs are solely financially driven can
ASP implementation group were improved susceptibilities to a also be an impediment. However, the guidelines of the IDSA/
number of bug--drug combinations, primarily involving nonfer- SHEA and other authorities endorse these programs not based
menting Gram-negative rods or Enterobacteriaceae, significant on the potential for cost savings but as a means to improve
reduction in the use of a number of broad-spectrum agents, patient safety and to reduce the selective pressure exerted by
and a significant reduction in annualized antimicrobial costs unnecessary antimicrobial use that facilitates the evolution of
($803,910) and costs per patient-day ($18 to $14.4). antimicrobial resistance. Typically, as a side effect of interven-
Various well-conducted studies at the University of tions to optimize antimicrobial use to improve efficacy and re-
Pennsylvania over the last two decades have contributed to our duce resistance, a cost saving is observed that financially justifies
current knowledge of ASPs in general (40). Grosset al. (34) ini- the program. Administrators need to be cognizant of this when
tially employed a dedicated beeper schedule for weekdays dur- helping to develop ASPs. Program funding can be a barrier for
ing normal business hours that was covered by an antimicrobial some institutions, but as mentioned in SHEA/IDSA guidelines
management team (AMT) member (an ID PharmD or ID physi- and as numerous studies in the area of ASPs point out, ASPs
cian). Second-year ID fellows covered evenings and weekends. typically pay for themselves as a side effect of their existence.
At night, restricted drugs were released pending next morning
follow-up, taking advantage of their existing program. The AMT
evaluated interventions performed by the ID fellows versus those SUPPLEMENTAL PROGRAMS
made by the ID PharmD and/or ID physician. They concluded
that interventions performed by the veteran ASP team members
TO THE PRIMARY ASP STRATEGY
(ID PharmD and/or ID physician) were more cost-effective and
FORMULARY INTERVENTIONS
resulted in narrower spectrum therapy compared with interven-
tions made by ID fellows. On the basis of the results of their A survey of teaching hospitals suggests that 80% of them limit
study, the ID fellows have been more fully incorporated into prescriber access to antimicrobials using a variety of mecha-
their ASP and work with the PharmD and ID physician more nisms (45). Formulary restriction is the most direct way to
directly. The AMT also have published their intranet/lnternet influence antimicrobial use and is central to the primary pre-
resource list of restricted antimicrobials and guidelines on a authorization ASP strategy. Most hospitals, regardless of having
Web site that can be accessed, at least in part, by others (www. an ASP, employ this strategy by limiting access to the numbers
uphs.upenn.edu/bugdrug). In addition to the preauthorization of antimicrobial drugs within a class. This limitation is a passive
method for active interventions, the AMT also work closely with intervention strategy, whereas enforcement through ASPs us-
the hospital epidemiologist, are involved in establishing guid~ ing either preauthorization or prospective audit and feedback
lines for antimicrobial use and dosing, are proactively involved strategies shifts the ASP strategy to an active intervention.
in the antimicrobial formulary, work closely with the pharmacy Careful selection of agents within a class not only involves
and therapeutics committee, provide education, and continu- an in-depth analysis of the basics (efficacy, safety, and cost),
ously evaluate antimicrobial consumption trends (40). but also includes an evaluation of resistance-evoking potential
when possible and a pharmacodynamic evaluation of the agent.
A benefit of having an ASP allows this process to be centralized,
POTENTIAL BARRIERS
and working closely with the pharmacy and therapeutics com-
The literature reports some pitfalls that some programs have ex- mittee helps to establish an optimal formulary stocked with the
perienced. Delays in the approval for a necessary antimicrobial best drugs for the given institution. The cost evaluation should
extend beyond purchase prices, although leveraging contracts use of the drug and has the power (in many facilities) to be
is a useful tool (46). An important factor is that the overall cost an effective countermeasure to correcting inappropriate use by
of care should be considered when an antimicrobial is evalu- intervening.
ated, but this is not always done because of the compartmen- The ASP's involvement in the antimicrobial formulary is not
talization of costs within an institution (also referred to as the limited to drug evaluations, but should work periodically with
"silo" mentality). For example, although 8- to 10-fold more ex- the pharmacy to evaluate pricing contracts, which can be com-
pensive than intravenous vancomycin in purchase cost, the use plicated and may fluctuate. Having someone with an expertise
of orallinezolid has been shown to decrease the length of stay in antimicrobials working with the pharmacy buyer can greatly
and improve discharge dynamics for patients with MRSA infec- improve the institutional purchase costs and ensure that the
tions (47-50). This is particularly financially appealing for in- hospital/healthcare system is receiving competitive pricing.
stitutions from the perceptions of those operating at maximal Also, frequent communication with the pharmacy buyer has
census (because bed costs far outweigh drug costs) and with been a requisite over the last several years due to antimicrobial
high MRSA rates, of the infection control of reduced trans- shortages. The ASP can (a) facilitate preparation for shortages
mission dynamics when length of stay is shortened, and, most when advanced notice is given, (b) be helpful in maintaining
important, of the patient who can be at home rather than hos- par levels of necessary drugs, (c) can provide insight into al-
pitalized. At the MMC, the ASP, working with the care coordi- ternative drugs that will likely be used in their place, and (d)
nation and infection control departments, has taken advantage can communicate these shortages with alternatives to the pre-
of efficiently transitioning the patient after becoming clinically scribers. For example, a nationwide shortage of piperacillin/
stable to an oral MRSA therapy, such as linezolid and, in some tazobactam led the MMC to develop a product that can be eas-
instances, minocycline. The purposes of this transition is to re- ily substituted. The combination product (i.e ., cefepime com-
duce the barrier to discharge posed by home intravenous ther- bined with metronidazole in the same mini bag) can be given
apy arrangement or skilled nursing facility placement, if solely as a single administered product because of its stability and
for administering intravenous vancomycin (33). compatibility in combination, is administered on average two
Practical, evidence-based examples of preferentially re- fewer times per day (i.e., cefepime and metronidazole can be
placing drugs with increased resistanc~oking potential given every 12 hours for most infections), and is approximately
(e.g., ceftazidime) with a member of the same class exist, but 30% less expensive than piperacillin/tazobactam (58). Because
these examples have demonstrated a reduced ability to select MMC has an institutionally supported ASP, it was able to cre-
for resistance (e.g., cefepime) (8,9,42,51). A number of stud- atively dedicate resources to an idea that is both beneficial to
ies of hospitals still characterized by high third-generation patients and cost-effective.
cephalosporin use have demonstrated that the replacement
of third-generation cephalosporins with either cefepime or
PHARMACODYNAMITCDOSEOP~ON
piperacillin/ tazobactam is an effective strategy (particularly
in concert with infection control interventions) to minimize Dose optimization interventions are likely to be one of the
the selective pressure that facilitates the appearance of prob- most common interventions by an ASP. Although formerly
lematic 13-lactamases (e.g., AmpC enzymes, extended-spectrum viewed as a means to efficiently trim excess drug exposure
.B-lactamases) or VRE (9,52-54). The contrast between van- secondary to renal dysfunction, the modem application of
comycin and daptomycin is another example that highlights pharmacodynamic principles is important to maximize drug
the point that not all drugs are created equal in their poten- exposure for organisms with elevated minimum inhibitory
tial to select for antimicrobial resistance. Fewer high-level concentrations (MICs), patients with excess body mass indices,
vancomycin-resistant S. aureus (VRSA) strains have been re- redosing during surgery, and for closed-space or otherwise-
ported than daptomycin-nonsusceptible S. aureus strains. The difficult-to-penetrate sites of infection (e.g., meningitis, endo-
difference is that vancomycin has been used for severely ill carditis, pneumonia, and bone and joint infections) . A recent
patients with BSis, endocarditis, or meningitis for more than paper provides a more in-depth review of the subject and serves
three decades. Many (6) daptomycin-resistant strains were se- as a primer for all ASPs that are incorporating optimal dosing
lected during therapy in a single trial (55). Also, it has been strategies (59). Although MMC approached its program with
observed that linezolid resistance can occur more readily in en- the thought that many patients would receive downward dose
terococci than in staphylococci (56). However, staphylococcal adjustments for renal impairment, what was found instead was a
resistance to linezolid remains low after over a decade of use. significant proportion of patients requiring increased drug ex-
Nuances related to the propensity for the antimicrobial to be- posure (8,33). Other examples of pharmacodynamic dose op-
come resistant to the pathogens of interest within a particular timization include regimens intended to more effectively treat
institution's patient population should be considered from a higher MIC pathogens such as continuous or "prolonged" infu-
formulary perspective, and monitoring the drug's susceptibility sion of short-half-life 13-lactams (e.g., piperacillin/ tazobactam,
performance in a perpetual manner is an important compo- cefepime, meropenem), and extended-interval aminoglycoside
nent of an ASP working directly with the hospital epidemiolo- dosing. As previously mentioned, MMC has exploited the fact
gist and the microbiology laboratory (57). that metronidazole with its prolonged half-life (~10 hours)
Finally, determining when an antimicrobial may fit into and active metabolite can be given every 12 hours instead of
order sets and guidelines and how its use will be monitored every 6 to 8 hours for non-C. difficile, noncentral nervous system
completes a comprehensive evaluation of how the antimicro- infections. As mentioned before, MMC has created a clinical
bial will be most effectively used within the institution. For program that integrates cefepime and metronidazole into a
follow-up of an antimicrobial's use in the institution, the sup- single administration product that can be infused twice daily,
port of the pharmacy and therapeutics committee is vital be- mimicking the spectrum of activity provided by piperacillin/
cause it provides a mechanism to report back inappropriate tazobactam (58).
EDUCATIONAL EFFORTS Patient-specific data had to be entered into the PDA, which
provided a logic-based recommendation that was measurably
The first step in any process leading to change is the develop-
useful in the prescribing process.
ment of pertinent information and its dissemination. Early at-
tempts at influencing prescribing behaviors relied heavily on
educational efforts. It was simplistically believed that the reason ADAPTATION OF LOCALLY CUSTOMIZED
physicians frequently inappropriately prescribed antimicrobi- PUBLISHED GUIDELINES
als was that they were "therapeutically undereducated" (60).
National guidelines by the IDSA and SHEA are available and
The assumption was that the misuse of antimicrobials was more
are useful to construct clinical pathways locally for a variety
often the result of insufficient information rather than inap-
of infections. In some instances, as when sufficient time has
propriate behavior.
passed between the publication of national guidelines and the
Over the years that MMC has taught antimicrobial prin-
change of the disease process, there should be a mechanism to
ciples and specifics of therapy, what has been found is an in-
develop updated evidence-based guidelines. A good example
tense interest of both physicians in training and established
of this is the management of CDAD. Being one of the first iden-
practitioners in learning more about antimicrobials. Equally as
tified institutions in North America with a hypervirulent strain
impressive is the laisstflrjaire and even fatalistic attitude toward
(BI/NAP1) of C. dif.ficile, MMC saw the clinical and prescrib-
retaining and applying lessons learned in these educational
ing impact almost immediately. Shortly thereafter, the center
sessions. Without direct application to current patients, pre-
intervened by developing consensus among feuding special-
scribers often refer to antimicrobials as "alphabet soup" and
ties on the proper approach to managing CDAD and created
"impossible to understand." These impressions are supported
guidelines, a clinical pathway, and a follow-up order set, all of
in the literature. Although a supplemental cornerstone to any
which could be accessed on its intranet site and/or in its CPOE
ASP, educational efforts when applied alone are the least effec-
system (23). From the identification of the BI/NAP1 strain of
tive and certainly the shortest lasting way to affect prescriber
C. difftcile to its proper management, the ASP in conjunction
behaviors. Active intervention that is supplemented by educa-
with MMC's department of epidemiology and infection preven-
tion is a synergistic method for changing behavior.
tion, environmental services, and administration spearheaded
an institutional approach to managing this high morbidity-
associated infection. MMC also evaluated and reported the
COMPUTER-ASSISTED DECISION
SUPPORT PROGRAMS impact of the CDAD guidelines that supplemented active in-
terventions made by its ASP on the use of non-evidence-based
Direct computer-based physician order entry (CPOE) is rapidly treatment strategies and demonstrated a significant improve-
becoming the standard of care, and has been adopted as one ment in the treatment variability of CDAD (67).
of the Leapfrog initiatives to avoid medication errors and im- Guidelines published by the American Thoracic Society (ATS)
prove the quality of care (33). CPOE fits nicely with the current and the IDSA for the management of healthcare-associated,
emergence of electronic medical records. Computer-assisted ventilator-associated, or hospital-acquired pneumonia suggest
decision support programs have been designed to provide real- a very broad-spectrum approach for the empiric treatment of
time integrated patient and institutional data including culture these infections because of the high probability of mortality as-
and antimicrobial susceptibility results, laboratory measures of sociated with inadequate therapy. In addition, these guidelines
organ function, allergy history, drug interactions, cumulative or recommend shortened durations of therapy. From these rec-
customized location-specific antimicrobial susceptibility data, ommendations, MMC developed a consensus and published a
and cost information. These programs provide therapeutic locally customized (per our susceptibility patterns) guideline,
choices for clinicians and allow for the incorporation of clini- and continues to meet monthly to discuss the tracking of pro-
cal judgment by overriding suggestions. Autonomy is preserved cess measures. One difficulty with simply creating and making
while ensuring that important variables in the choice of antimi- guidelines available to clinicians is that compliance is voluntary,
crobial therapy are considered. and we have found that without active follow-up, clinicians fall
Almost all published data on the effect of computer-assisted back on old habits. Thus, one benefit of having an ASP is having
decision support programs on antimicrobial use are from re- the resources to provide active intervention in the intensive care
searchers at the Latter Day Saints Hospital in Salt Lake City, unit (ICU), from whether it is recommending streamlining/
Utah. The approach of these studies has been associated de-escalation when culture and susceptibility results are known
with reductions in antimicrobial doses, inappropriate orders, to stopping antimicrobial therapy at day 7 to 8 instead of the
costs, treatment duration, and associated adverse drug events traditional 14 or more days.
(61-63). This degree of computer sophistication is not univer-
sally available but has been made available through a variety
PROCESS AND OUTCOME MEASUREMENTS
of commercial systems (64,65). MMC has used its own CPOE
system to design a logic-based algorithm to optimize the The IDSA/SHEA guidelines for developing an institutional
treatment of pneumonia (e.g., community-, healthcare-, and program to enhance antimicrobial stewardship recommend
hospital-acquired). A recent randomized control trial of clini- that outcomes be measured (6). This guideline is one reason
cal decision support on the appropriateness of antimicrobial for having a data system and an information specialist assist
prescribing demonstrated an improved appropriateness and the ASP members in quantifying their impact. Without this
reduced overall use of antimicrobials for respiratory tract infec- support, the ASP team members could spend more time jus-
tions (66). In this rural outpatient setting, handheld personal tifying their positions and measuring outcomes than on the
digital assistants (PDAs) and paper forms of decision support actual day-to-day functioning of the program and evaluating
supplemented the prescribing decision and choice of therapy. antimicrobial therapy, which is the team's primary purpose.
Antimicrobial consumption can be measured for targeted (or time-strapped clinician. Additionally, national guidelines for
all) antimicrobials. Using antimicrobial expenditure data has the diagnosis and treatment of URTis provide the basic tenets
significant limitations, but is helpful in evaluating where money for the treatment of these infections, but clinicians unfor-
is being spent. A more meaningful measure of antimicrobial tunately appear to frequently ignore them. In a study of two
consumption is the use of DDD data; standardized definitions private practices, 71% of pediatricians indicated that a parent
are available at www.whocc.no/atcddd/. Converting grams of had requested an unwarranted antimicrobial at least four times
antimicrobial used to DDD per 1,000 patient-days allows for a within the previous month (69). In 35% of these instances, the
useful internal and external benchmark of antimicrobial con- pediatrician admitted prescribing an antimicrobial. In 61% of
sumption. Another measure would be antimicrobial-days of instances, the parent requested a different antimicrobial than
therapy. Regardless of the mechanism chosen, establishing a that selected by the prescriber.
baseline of antimicrobial use before implementing a program In addition, a lo.issez-Jaire attitude regarding national treat-
allows the team to track the progress of interventions on use ment guidelines for diagnosing and treating infection exists. In
over time. These measures can also be used to quantifY the a study conducted by the CDC, pediatricians and family prac-
impact of parenteral-to-oral conversions. In addition, periodi- titioners were evaluated for self-reported versus actual prac-
cally reporting to the pharmacy and therapeutics committee or tice regarding antimicrobial use for URTis (70). While 97%
other committee stlucture allows other clinicians and adminis- agreed that the overuse of antimicrobials is a chief factor driv-
trators to be aware of both the successes and the challenges the ing antimicrobial resistance and 83% believed that they should
ASP has faced. consider selective pressure for antimicrobial resistance when
deciding to prescribe antimicrobials for URTis, a large contin-
gent ignored the basic tenets of judicious antimicrobial use.
OPTIMIZING OUTPATIENT For example, 69% considered purulent rhinitis diagnostic for
ANTIMICROBIAL USE sinusitis, 86% prescribed antimicrobials for bronchitis regard-
less of the duration of cough, and 42% prescribed antimicrobi-
Although a departure from the institutional approach to pro- als for the common cold (70). In addition, family practitioners
grammatically addressing antimicrobial stewardship, discussing were more likely than pediatricians to omit the requirement
the importance of antimicrobial stewardship in the outpatient for prolonged symptoms to diagnose and treat sinusitis (4 vs.
setting is worthwhile. More casual prescribing of antimicro- 10 days, respectively) and to omit laboratory testing for pharyn-
bials, patient demand, and managed care constraints have gitis (27% vs. 14%, respectively) (70).
plagued the optimal use of antimicrobials in this venue. Many
times, the prescription of an antimicrobial is issued under less OUTPATIENT INTERVENTIONS
than scientific circumstances and with less information avail- TO IMPROVE ANTIMICROBIAL USE
able. Unfortunately, whatJawetz (4) reported in the 1950s is
still true today. Several studies have demonstrated successful outcomes in out-
He (the physician) is under great pressure to prescribe the patients including a decrease in overall antimicrobial use and
"newest," "best," "broadest," antibiotic preparation, prescribe improvement in the appropriateness of therapy. Several meth-
it for any complaint whatever, quickly, and preferably without ods have been used to effect change including education, con-
worrying too much about specific etiologic diagnosis or proper sensus guidelines, data feedback, medical information system
indication of the drug. The pressures come from several main reminders, financial disincentives, and the use of opinion lead-
sources: (a) In lay magazines and newspapers patients read ers (71-73). Most of the literature evaluating the impact of in-
exaggerated, uncritical, and often misleading claims made terventions on antimicrobial use has occurred in the acute care
for newly discovered drugs. "Scientists announce new potent inpatient setting and may not be generalizable to the outpa-
weapon against colds." "Antibiotic cures and prevents many in- tient venue. With that said, there is an increasing body of litera-
fections." "New drug saves lives." Most of these accounts are ture in evaluating the impact of multiple educational strategies
quite meaningless, yet patients proceed to demand the new, aimed at both the prescriber and the patient.
marvelous drug from their doctors. The physician may be em- Razon et al. (74) conducted a 1-day seminar on the diag-
barrassed to admit that he knows nothing of this supposed dis- nosis and prudent use of antimicrobials for the treatment of
covery (many doctors find it necessary to read medical news in URTis in children. Using a quasi-experimental study design to
TirM, Reader's Digest and similar media to cope with their pa- determine the impact of the educational intervention, the re-
tients' pseudo-knowledge), or, he may prefer to not get into searchers determined that the appropriateness of treatment im-
lengthy explanations as to why he thinks little of the new drug. proved for both otitis media (OR 1.8, p < 0.01) and pharyngitis
It may be simpler and quicker to yield to the patient's insistent (OR 1.35, p < 0.01) (74). In addition, the overall antimicrobial
demand, and prescribe. use for otitis media and URTI decreased {p < 0.05) (74). No
So have we made any progress? change in appropriateness or antimicrobial use was noted for
sinusitis, however.
A statewide educational intervention performed by the
TO TREAT OR. NOT TO TREAT
Wisconsin Antibiotic Resistance Network (WARN) used a two-
National guidelines for the management of a variety of upper pronged approach. On one hand, clinicians were the targeted
respiratory tract infections (URTis) provide objective criteria recipients of education at professional conferences, meetings,
for when to prescribe antimicrobials (68). Optimizing treat- grand rounds, and satellite conferences, and multiple mailings
ment begins with this question, "Does the patient need antibi- and CD-ROM presentations were distributed. On the other
otics?" In both pediatric and adult practices, the patient often hand, the public was educated by means of multilingual bro-
extracts the unnecessary antimicrobial prescription from the chures and posters, tear-off sheets, coloring sheets, stickers,
magnets, and handouts. These educational means were dis- campaign materials, and print and other educational materials.
tributed statewide to clinics, pharmacies, childcare facilities, In addition, some State Health Departments have either initi-
managed care organizations, and community groups. In addi- ated antimicrobial use surveillance systems (primarily at acute
tion, mass media events included radio and television advertis~ care facilities) (80) or even initiated statewide ASPs in their
ments. Minnesota was used as the control state. Postintervention acute care facilities (81) . Internationally, Brazil has evaluated
(in 2002), Wisconsin clinicians perceived a significant decline the use of telemedicine to enhance antimicrobial stewardship
in the number of requests by patients for antimicrobials (50% for rural hospitals (82) and the entire country of India has ad-
in 1999 to 30%; p < 0.001) and in requests by parents for their opted a plan to improve antimicrobial stewardship country-wide
children (25% in 1999 to 20%; p = 0.004) (75). The decisions (83). In the United Kingdom, emphasis has shifted from con-
of clinicians in Wisconsin to treat with antimicrobials were less ducting surveillance of antimicrobial resistance to enhancing
influenced by nonpredictive clinical findings (purulent nasal and evaluating ASPs at National Health Service (NHS) hospi-
discharge, p = 0.044; productive cough, p = 0.010) (75). For tals (84). Across Europe, awareness of antimicrobial usage and
both states in the postintervention period, treatment scenarios stewardship was evaluated on November 18, 2012 as a part of
involving viral respiratory illnesses in adults were less likely to the fifth annual European Antibiotic Awareness Day (EAAD);
include antimicrobials; however, the same scenario in pediatric this was an opportunity to raise public and professional aware-
patients was lower only in Wisconsin. ness about the importance of prudent antibiotic use and the
In a somewhat similar intervention, Rubin et al. (76) evalu- threat of antibiotic resistance to public health (85). In Scotland,
ated their efforts to improve antimicrobial prescribing for the Scottish Antimicrobial Prescribing Group has developed
URTis in a rural community. They used patient-education ma- prescribing indicators for hospital and primary care, which are
terials, a media campaign, a small group session conducted with measured and reported in all14 NHS board areas (86). Thus,
physicians, and a treatment algorithm for URTis. Although we are seeing an expansion of ASPs from the individual hospi-
Medicaid claims data and community pharmacy data demon- tal to hospital networks and even state- or country-wide.
strated a reduction in the rate of antimicrobial prescriptions,
a third data source (using medical record review) did not sup-
port a reduction in diagnosis-specific rate of antimicrobial use. CONCLUSIONS
All three data sources did, however, demonstrate a reduction in
macrolide use. In a similar rural community, clinical decision The problem of increasing antimicrobial resistance--due in
support (on paper and handheld computers) to aid clinicians part to suboptimal antimicrobial use coupled with the fact that
in the diagnosis and management of acute respiratory tract in- a growing number of pharmaceutical companies have aban-
fections plus a community-wide educational intervention was doned anti-infective research and development-has resulted
compared with a community-wide educational intervention in a growing public health crisis. Because of their intensity of
alone (77). The community-wide educational intervention with antimicrobial use, both institutional and community settings are
clinical decision support demonstrated a reduction in overall target-rich environments for proactive interventions to improve
antimicrobial use and increased the appropriateness of therapy. antimicrobial stewardship. Various studies have concluded that
Changing prescribing behaviors is one thing; maintaining programmatic means to steward the use of antimicrobials opti-
those changes is another. As aids to sustaining any process im- mizes patient safety, addresses antimicrobial resistance, reduces
provement effect, mechanisms available to inpatient facilities unnecessary antimicrobial use, and, as a side effect, minimizes
(e.g., point-of-use information reminders and computerized direct and indirect costs to the healthcare system. The IDSA/
decision support as well as formal ASPs) are needed to sustain SHEA guidelines for developing an institutional program to
outcome measures. As Samuel Johnson said >200 years ago, enhance antimicrobial stewardship serve as a starting place for
"Men more frequently need to be reminded than informed. • institutions considering adopting an ASP. Finally, Calvin Kunin,
The long-term effectiveness of this strategy has been demon- MD, once stated: "there are simply too many physicians pr~
strated in hospitals (8,9), but the optimal method to sustain scribing antibiotics casually. The issues need to be presented
initial efforts in the community remains unclear. Of the tested forcefully to the medical community and the public. Third-party
outpatient strategies, combining clinical decision support tools payers must get the message that these programs (antimicrobial
in addition to education appears to provide the most promising stewardship) can save lives as well as monef (87).
opportunity for sustainable antimicrobial stewardship. Perhaps
as a result of many of the state and local educational interven-
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15 Michael Y. Lin, Robert A. Weinstein, and Mary K Hayden
Multidrug-Resistant Organisnts:
Epidemiology and Control
OVERVIEW virulence, such as yeast, methicillin-resistant coagulase-negative
staphylococci, and Q,ry1Uibacterium.fei'Mium. also became significant
The diJcovery of penicillin in the 1940s heralded an age of HAl pathogens. In the 1990s, resistance to fluoroquiuolones and
antibiotic development and cures for infections encountered vancomycin emerged among staphylococci, while carbapenem
in the hospital. However, each antibiotic iwtovation has been resistance was reported in multiple species of Enterobacteriaceae
tempered by the subsequent emergence of organisms resistant and became widespread among P. aeruginosa and A~
to the drug. Antibiotic resistance is not a modern phenom- baumannii Since 2000, a group of multidrug-resistant organisms
enon: highly diverse genes encoding re~istance to ,8-Jactam, {MDROs) have emerged as dominant in hospitals: E~~
tetracycline, and glycopeptides antibiotics were present in cium, S. IJUmU, KlBbsitil1a Jmt:umtmiae, A. baumannii, P. aeruginGsa,
bacteria recovered from 30,000-year-old permafrosts (1). Yet, and E'llll.frJbader species, sometimes collectively referred to as the
the development of "multiply drug-resistant" pathogens- "ESKAPE bugs" (5).
that is, organisms that are resistant to most or all of available The specter of pan-resistant "ruperbugs" with little to no
antibiotics-is a modern phenomenon and increasingly en- reasonable antimicrobial treatment has raised concern that,
countered among patients in hospitals (2) . .Antimicrobial- at least for some infectious, we have effectively entered a post-
resistant pathogen infectious create a burden of increased antibiotic age (6). Understanding the force~ that promote an·
morbidity, mortality, and cost among hospitalized patients (3). tibiotic resistance is the basis of hospital infection control (IC)
The hospital is an epicenter for colonization and infec- efforts. In this chapter, we review the epidemiology of multi·
tion by drug-resistant pathogens, due to three forces (4). First, drug-resistant pathogens in hospitals and discuss prevention
in treating the sickest of patients, hospitals have traditionally and control strategie~.
been place& where the usage and potency of antimicrobial
agents is IUgh. Such "antibiotic presrure" provides a driving
force for selecting and maintaining organisms that are able to DEFINITIONS
evolve or acquire mechanisms of resistance. Second, patients
in hospitals are often severely ill and immune-compromised, When a pathogen is described as "resistant," it usually refers
increasing the likelihood of acquiring bacterial colonization to loss of susceptibility to key drugs that are normally used
or iufection. Third, hospitals provide a convenient meeting in treatment. The key drug may be either a first-line antimi·
ground for patient:J to acquire resistant organisms, from res- crobial that is preferred for treatment of a specific organism
ervoirs such as other patient:J, the envirownent, shared equip- because of superior efficacy or low toxicity (e.g., oxacillin for
ment, or hospital personnel. S. aun!'W') or an antimicrobial to which resistance may be a
Over the past 50 years, various reJistant bacteria have risen marker for broader nowsusceptibility (e.g., ceftazidime resis-
to prominence in the hospital setting (Figure 15.1). In the tance in K pntumooiu suggesting production of an extended·
early 1960s, penicillin-reJistant Staphyllxoccus au~ became spectrum P.Jactamase [ESBL]).
epidemic and quickly widespread. Subsequent attempts to Traditionally, antibiotic resistance has been defined pheno-
treat resistant S. atm!W' infectious with methicillin were soon typically using culture-based techniqUeJ, that is, by the ability of
thwarted by the emergence of methicillin resistance. In the the microbe to grow in a specific concentration of the antibiotic
1970s, as vancomycin became available for treatment of infec- of interest. Alternatively, genotypic testing can be used, employ-
tiows due to gram-positive cocci, gram-negative bacilli, such as ing molecular techniques such as polymerase chain reaction
~ aeruginora and Enterobacteriaceae, became domi- (PCR) to directly detect the presence of resistance genes (such
nant healthcare-associated infection (HAl) pathogens. By the as m«A that confers methicillin resistance in S. atm'W). There
1980s, the introduction of broad-spectrum antimicrobials, ruch are advantage~ and disadvantages to either approach; in prac-
as advanced-generation cephalosporins to better treat gram- tice, phenotypic and genotypic tests are used alone or together,
negative infections, was countered by the emergence of novel depending on the clinical context. Phenotypic testing is widely
P.Iactamases in Enterobacteriaceae. During the same time, the available and can sometimes detect resistance that would be
proportion of hospital S. a'ltllmS strains resistant to methicillin otherwise missed by PCR (ruch as some ESBUI that are caused
increased steadily, and vancomycin-resistant enterococci (VRE) by point mutations or small genetic changes). On the other
surfaced. Other multidrug-resistant (MDR) pathogens of low hand, genotypic testing yields results faster in screening for
181
ESBLs, CREs,
Staphylococci
(Enterobacteriaceae,
Gram-negatlw rods
Pseudomonas,
Aclnetobacter)
MRSA
~ VRE
_ / " - - - - - - VISA, VASA
1920 1930 1940 1950 1960 1970 1980 1990 2000 2010 2020
Figure 15.1. Schematic representation of emerging healthcare-associated infections over time. MRSA,
methicillin-resistant Staphylowccus aureus, VRE, vancomycin-resistant enterococci; VISA, vancomycin-
intermediate S. aureus, VRSA, vancomycin-resistantS. aureus, ESBL, Extended""pectrum P.Iactamase-producing
Enterobacteriaceae; CRE, carbapenem-resistant Enterobacteriaceae; Acinetobacter, multidrug-resistant
Acimtabacter baumannii; Pseudomonas, multidrug-resistant Pseudomonas aeruginosa.
Adapted from Herwaldt LA, Wenzel RP. Dynamics of hospital-acquired infections.
specific resistance elements directly in clinical samples (such as to a key single antibiotic (e.g., resistance to methicillin/oxacillin
screening for the K pneumuniae carbapenemase gene in a rectal defines methicillin-resistant S. auJruS, while resistance to
swab specimen) (7). vancomycin defines VRE). For gram-negative bacteria, in part
From the standpoint of the hospital clinical microbiology because of larger variability in resistance mechanisms, multidrug
laboratory, there are common pitfalls in defining resistance. resistance is not as well-standardized (20). Some definitions may
Newer generations of automated antimicrobial susceptibility refer to a certain threshold level of antimicrobial resistance
systems (e.g., VITEK®2, bioMerieux, Durham, NC) have the (such as multidrug-resistant P. aeruginosa defined as resistant to
ability to detect susceptibility to multiple common antimi- ~g antimicrobial classes) or to a specific resistance pattern as-
crobials via fluorescence-based methods. Limitations to such sociated with multidrug resistance (such as multidrug resistant
systems include failing to detect resistance in certain antimi- K pneumuniae resistant to either ceftriaxone or ceftazidime, as
crobial classes, particularly those that are expressed heteroge- a phenotypic marker of ESBL carriage). Interim standardized
neously or that require induction for optimal expression, such definitions for MDR, extensively drug-resistant (XDR), and pan-
as ,8-lactams and vancomycin (8). Both automated and manual drug-resistant (PDR) bacteria have been proposed by a group of
susceptibility testing methods, such as the Kirby-Bauer disk experts (Th.ble 15.1) (2).
method, may yield inaccurate results due to device or operator- MDROs can be associated with infection (i.e., symptom-
dependent errors, such as the use of outdated or incorrectly atic illness) or with colonization (i.e., asymptomatic carriage)
placed antimicrobial disks, variations in bacterial inoculum, (18). Patient and healthcare worker colonization with resistant
and incorrect agar depth or pH (see Chapter 11) . organisms is an important epidemiologic problem because it
With the emergence of novel resistance, there is sometimes increases the reservoir of resistant bacteria (Figure 15.2) and
a lag between recognition of resistance and the general avail- is often a precursor to clinical disease (21,22). Distinguishing
ability of an accurate method for its detection. Examples of this between colonization and infection at times can be difficult; site
problem include detection of vancomycin resistance in entero- of culture may help. Positive microbiologic cultures from nor-
cocci (9,10) and staphylococci (11,12), carbapenem resistance mally sterile sites (such as the bloodstream, cerebrospinal fluid,
inK. pneumoniae (13,14), and ESBL production in Enterobac- pleural fluid, synovial fluid, bone, and peritoneal fluid) usually
teriaceae (15). The minimum inhibitory concentration (MIC) indicate infection, while positive cultures from nonsterile sites
of an antibiotic that defines resistance for a particular bacte- (such as sputum or wounds) may indicate either colonization
rial species (i.e., the "breakpoint") may be revised to improve or infection, depending on clinical interpretation (23).
a test's sensitivity for the detection of decreased susceptibility For epidemiologic purposes, infections are further clas-
to an antibiotic, such as lowering third-generation cephalospo- sified by location at time of onset, that is, healthcare facility
rin and carbapenem breakpoints to better detect resistance to versus community (18). Such classification can be challeng-
these agents in Enterobacteriaceae (16,17). ing because patients may acquire MDROs before hospitaliza-
There is no standard definition for "multiple resistance" or tion, and infections can be incubating asymptomatically at
"multidrug-resistance" (18). Individual hospitals may define the time of hospital admission. For example, 15% to 25% of
multidrug resistance based on local context, as long as the defi- patients colonized or infected with aminoglycoside-resistant
nition is consistent over time to allow for comparability; alterna- gram-negative bacilli and as many as 50% of patients who ap-
tively, hospitals may use definitions distributed by public health pear to acquire cefazolin-resistant Enterobacteriaceae after
agencies (19). Clarifying definitions of multidrug resistance surgery were found to have brought these strains into the hos-
is important for the purposes of outbreak investigation, IC pital (24,25). Nevertheless, by reviewing a patient's prior clini-
surveillance, and inter-facility communication. In general, gram- cal history and exposures to healthcare facilities, an infection
positive MDROs are relatively well-defined, usually by resistance can be categorized as "healthcare-associated," "nosocomial," or
TABLE 15.1 Interim Standard De&Ditions for Multidrua-Baistant (MDB.), &:trcmcly Drua-Baistant
(XDll), and Pan-Drua-:Baistant (PDll) Bactma
Defiaiticm
MDll The iaolate is noosUJCeptible to at least I II(P!Dl in ~5 antimicrobial categoria.
XDR. The iaolate is noosUJCeplible to at least 1 agent in all but S:2 antimicrobial categories.
PDll Nonauaceptibility to all agents in antimicrobial categories.
MDR, multi.drug-resistant; XDR, es.tenaively drug-reailtant; PDR, pan~-resistant. 'I'he.9e criteria have been proposed for the following
bacteria: SfGIA'loetJ«w t.MetU, ~ spp., Enterobacteriaceae (other than s.z-,u, and smplo), ~ ~ and
~.,.
Adapted &om Magiorakoa AP, Sriniwaan A. Carey RB, et al. :Multi.drug-resistant. ntenaively drug-resistant and pandrug-resistant bacteria:
an international espen proposal for interim standard definitions for acquired resistance. am Mit:rdliollnfoct 2012;18:26~281.
"community-;wociated• (Table 15.2). "Healthcare associated• simply dichotomizes infections as "hospital onset" or "commu-
refen to acquisition from any facility associated with healthcare nity onset" using time (with hospital onset defined as clinical
(e.g., a hospital, outpatient clinic, residence in a long-term specimen collected > 3 calendar days after patient was admitted
care facility, rehabilitation center, hemodialf~is, surgery). The to the hospital, with first day as date of admission) ca:n be useful
subset of HAb specifically acquired in hospitals is called "noso- for routine SUIVeillance.
comial." "Community associated" refers to infections without For further details regarding metrics for MOROs, a position
association with current or prior healthcare exposure. In prac- paper published by the Society for Healthcare Epidemiology
tice, such clinical definitions are labor-intensive to apply and of America a:nd the Healthcare Infection Control Practices
ca:n lack specificity. & an altemative, a temporal definition that Advisory Committee is available (18).
,---... ----.........
Readmissions -.... """ ./ / Otherwaros
Transfers - PAnENT 1 PAnENT - Environmental contamination
Nursing home patients _.,.. -Food
'-...., Antibio1ic PI'988Ur&
( \
I RESiflrAJii "ICEBERG"
r l'"
Figure 15.2. The dynami.cl ofhealthcare-auociated infection pathogen resistance: resilltance iceberg. (Reprinted
with permission &om Weinstein RA, Kabins SA. Strategies for prevention and control of multiple drug-resistant
nosocomial infection. Am]M«/.. 1981;70:449.)
TABLE 15.2 Definitions Used for Epidemiologic Classification of Infections with Multidrng-~t
Organisms (MDROs)
Classification Def"mition
TEMPORAL
Hospital onset Specimen collected from patient >3 calendar days after patient was admitted to the hospital (first day is date
of admission). All hospital-oiL!Iet infections are considered healthcare associated.
Community oiL!Iet Specimen collected from patient :S3 calendar days after patient was admitted to the hospital. A subset of
community-onset infections may be healthcare associated.
CLINICAL
Healthcare-associated Infection occurred in a patient with an identified contact (current or recent) with healthcare delivery.
Nosocomial The infection was lilely to have been acquired during the hospital stay, without any evidence that the
infection was incubating or present on admission.
Community-associated Infection occurred in a patient with no recent contact with healthcare delivery.
Temporal definitions require only knowledge of timing of specimen collection for clinical cultures. Clinical definitions require evaluation of
the patient's clinical history, in addition to timing of specimen collection for clinical cultures. >3 calendar days is also known as "3 midnight
~e For example, if a patient is admitted to the hospital at any time on a Monday, only MOROs that are isolated after midnight Wednesday
m.ght would be considered to represent hospital-onset infection (i.e., specimen was collected on day 4 of hospitalization).
Adapted from Cohen AL, Calfee D, Fridkin SK, et al. Recommendations for metrics for multidrug-resistant organisms in healthcare settings:
SHEA/HICPAC Position paper. Inftct Control Hosp Epidemiol. 2008;29:901-913.
MECHANISMS AND GENETICS OF to overexpression of antibiotic-inactivating enzymes, such as

RESISTANCE the ,S.lactamase AmpC, leading to third-generation cephalo-
sporin resistance (32).
Bacterial resistance has arisen to each class of new antimicro- Horizontal gene transfer is ubiquitous in bacterial commu-
bials developed to date, often in <3 years from the time of nities and represents the major mechanism by which bacteria
introduction, due to the remarkable genetic diversity and ad- are able to adapt to hostile natural environments and to antimi-
aptation of bacteria (26,27). Bacteria acquire antibiotic resis- crobial innovation. Bacteria may exchange DNA information
tance through two main mechanisms: de novo chromosomal through transformation (incorporation of exogenous DNA
mutation or through horizontal gene transfer. Both are im- from the surrounding environment), transduction (transfer
portant mechanisms and not mutually exclusive. Furthermore, of genetic material via bacteriophage vectors), or conjugation
under selective pressure, bacteria frequently aggregate several (direct cell-to-cell transfer of genetic material) (26). Horizontal
mechanisms to confer broad resistance to multiple classes of transfer of resistance genes is facilitated by their location on mo-
antimicrobials. bile genetic elements, such as integrons, transposons, and plas-
Chromosomal antimicrobial resistance usually is the result mids. The permutations of mobile elements are vast integrons
of genetic mutation and natural selection of strains that survive are found alone, or inside transposons; both integrons and
under the antimicrobial selection pressure. Conditions that transposons can be carried by plasmids or bacteriophages (33) .
favor spontaneous chromosomal mutation include an over- Such variations allow for gene shufiling and provide bacteria
whelming number of organisms (increasing the likelihood of with vast capacity to adapt to changing environments or antimi-
a favorable mutation), incomplete or ineffective antimicrobial crobial pressure, particularly in situations where large numbers
therapy (allowing mutants to survive), and a relatively small of bacteria live in communities (such as the gastrointestinal
number of mutations needed for resistance. Some subpopula- tract or environmental reservoirs) (34).
tions of bacteria (e.g., P. aeruginosa) have also been identified The rapid spread of extended spectrum ,S.lactamases
as hypermutators, which can increase the likelihood of de novo among Enterobacteriaceae world-wide has been a closely stud-
resistance (28). ied model of horizontal gene transfer. For example, the CTX-
Classic examples of chromosomal-mediated antibiotic re- M extended-spectrum ,S.lactamase gene ( blacrx-M) is thought
sistance include genetic mutations of antimicrobial targets to have mobilized multiple times from chromosomal DNA of
leading to resistance for rifamycins (via mutations of the Kluyvera into plasmids, which have subsequently spread through
rpoB gene) (29) and for fluoroquinolones (via mutations in conjugation into other Enterobacteriaceae species; such events
DNA topoisomerase) (30). Alteration of promoters of gene have happened worldwide (35,36) . Unfortunately, mobile ele-
expression via chromosomal mutation, thereby changing ments frequently carry multiple resistance mutations simulta-
the production level of antibiotic-inactivating enzymes, an- neously, allowing for broad resistance to be conferred quickly
timicrobial targets, or membrane influx or effiux systems, from one bacterial species to another. Plasmids that carry the
also can lead to resistance. For example, mutations in the carbapenemase gene b~M-l have also been shown to carry
promoter controlling the expression of the DprD porin in aminoglycoside, macrolide, rifampin, and sulfamethoxazole
P. aeruginosa can block the entry of carbapenems, rendering resistance genes, creating Enterobacteriaceae that are nearly
them ineffective (31). Mutations of repressor genes can lead pan-resistant (37).
Chapter 15 • Multidrng-Resistant ~nisms: Epidemiology and Control 185
OVERVIEW OF SPECIFIC RESISTANCES early 1980s to the late 1990s. However, since 2000, the CIX-M
family of ,8-lactamases has become increasingly dominant, dis-
Several sobering trends in resistance have been observed over the placing other ,8-lactamases and invading both community and
years (Figure 15.1, Table 15.3). A surge in aminoglycoside resis- hospital reservoirs through its association with E. coli in addi-
tance became a chief concern in the 1970s and 1980s, particularly tion to Klebsiella spp. (42).
in healthcar~ciated Enterobacteriaceae and P. aeruginosa. Because carbapenems are currently the broadest-spectrum
Although aminoglycoside importance and use has since declined antimicrobials commercially available, and because they are
with the development of alternative and often safer antimicrobi- critical in treating ESBL-producing bacteria as well as other
als, such as advanced-spectrum ,8-lactam antibiotics and fluoro- highly resistant gram-negative organisms such as A. baumannii,
quinolones, a.minoglycoside resistance rates have been stubbornly the increases seen in carbapenem resistance have been alarm-
persistent (38). Rates of tobramycin resistance among Entero- ing. Carbapenem resistance is mediated by various mechanisms,
bacteriaceae sampled in the United States increased from 1.7% such as loss of the outer-membrane proteins and upregulation of
to 8.8% from 1999 to 2008 (39). Aminoglycoside resistance is effiux systems (43). In the past decade, many different plasmid-
probably propelled by co-selection with other antibiotic resistance mediated carbapenemase:t-broad-spectrum ,8-lactamases that
genes, such as fluoroquinolones (40). hydrolyze carbapenems as well as other ,8-lactam antibiotic:t-
The availability of second-generation cephalosporins (such have emerged and spread worldwide, raising the risk ofuntreat-
as cefoxitin and cefuroxime), third-generation cephalosporins able infections (37). The emergence of multidrug-resistant
(such as ceftriaxone and ceftazidime), and of,8-lactam-,8-lactamase strains of gram-negative bacteria that produce New Delhi
inhibitor combination agents (such as piperacillin-tazobactam) metallo-,8-lactamase (NDM-1) carbapenemase, as well as there-
has highlighted an additional set of resistance risks in gram- markable ability of the NDM-1 gene to disseminate across gram-
negative bacilli. For instance, Enterobacterspp. were initially con- negative species including community-acquired bacteria such as
sidered susceptible to cephalosporins but frequently developed E. coli, Shigella buydii, and Vrbrio cholerae, will present perhaps the
resistance during therapy. The culprit was a spontaneously dere- biggest challenge to IC to date (44,45).
pressed intrinsic chromosomal AmpC,S.lactamase (41). Further The prevalence of trimethoprim and sulfonamide resis-
discovery of plasmid-mediated P-lactamases (such as ESBLs) tance in gram-negative bacteria remains a concern primar-
conferring broad resistance to various penicillins and cephalo- ily in outpatient settings, where oral trimethoprim alone or
sporins has made many gram-negatives such as E. coli and ~ trimethoprim-sulfamethoxazole (TMP-SMX) combination is
siella spp. difficult to control without turning to "antibiotics of often prescribed empirically for the treatment of urinary tract
last resort" such as carbapenems. The earliest recognized ESBLs infections (UTis). Resistance to trimethoprim is mediated via
evolved by point mutations from common, older plasmid-borne alterations in the target enzyme dihidrofolate reductase (46),
enzymes and were primarily found among hospital-acquired while resistance to sulfonamides is mediated by alterations in its
gram-negative organisms, particularly Klebsiella spp., from the target enzyme dihydropteroate synthase (4 7). These resistance
• . ftC :f f~1 fj. Key Rcristance Problems of Select Hcalthcarc-Assodated Infection Pathogens
Organism Key Resistanc:es Additional resistances
Staphylococcus a111WS Methicillin (all ,8-Iactams), vancomycin Macrolides, tetracyclines, dindamycin,
trimethoprim-su1famethoxazole,
fluoroquinolones, daptomycin,
linezolid
E11terocoawfaecium, Ampicillin (P,.Iactamase producing), Daptomycin, tigecycline, linezolid
Enterococcus ftw:ali.s vancomycin, aminoglycosides
Curymbacterium jeilt.eium Penicillins, cephalosporins, Macrolides, tetracyclines
fluoroquinolones
Enterobacteriaceae Cephalosporins (all ,8-Iactams), Aminoglycosides
carbapenems, fluoroquinolones,
trimethoprilll-8ulfamethoxazole
Anti-pseudomonal penicilliru,
anti-pseudomonal cephalosporins,
aminoglycosides, fluoroquinolones,
carbapenems
Acif'letobacler baumannii Sulbactam, carbapenems, Cephalosporins, penicillins,
aminoglycosides trimethopri1IH1u1famethoxazole,
fluoroquinolones
Trimethoprim.,.ulfamethoxazole, Carbapenems, cephalosporins,
ticarcillin-davulanate penicillins, aminoglycosides,
fluoroquinolones
Trimethoprim.,.ulfamethoxazole, Cephalosporins, penicillins,
carbapenems, fluoroquinolones aminoglycosides, tetracyclines
genes are often linked to other resistance genes on transmis- interaction with DNA gyrase and fluoroquinolone-modifying
sible elements, allowing for efficient spread and indirect selec- enzymes ( aac(6')-lb-cr)) also accounts for the explosive world-
tive pressure from associated antibiotics. Over the past decades, wide increase in fluoroquinolone resistance over time (58).
there has been an increasing trend in TMP-SMX resistance
over time; surveillance data from 2000 to 2010 among US uri-
nary E. coli isolates showed an increase from 17.9% to 24.2% HOST FAGrORS PREDISPOSING TO
( 48). Reductions in trimethoprim use alone do not appear to COWNIZATION OR INFECTION WITH
be sufficient to reduce the rate of trimethoprim-resistant E. coli, ANTIBIOTIC-RESISTANT ORGANISMS
probably explained by the low fitness cost of trimethoprim re-
sistance and the co-selection of trimethoprim resistance when A number of patient risk factors have been associated with ac-
alternative antibiotics are used (49,50). quisition of resistant bacteria (Table 15.4). Our epidemiologic
Methicillin resistance has been a major concern in staphylo- understanding of these factors remains limited because most
cocci since the 1980s. In 63 U.S. hospitals from 1974 to 1981, studies have been retrospective due to practical restraints, limit-
the percentage of S. aureus infections resistant to methicillin ing the covariates to more easily obtainable data, such as recent
increased modestly from 2.4% to 5%, due primarily to epidem- antimicrobial exposures. Many of the identified factors are un-
ics in four large teaching institutions (51). In 1992, the pooled doubtedly linked and may serve as indirect markers of more
percentage of resistance had risen dramatically to 32.1 %, and difficult-to-measure covariates such as frequency of patient-to-
in 2004, to 53% (52,53). Methicillin resistance in healthcare- staff contact. It also is important to recognize that risk factors
associated S. aureus and coagulase-negative staphylococci is may differ depending on whether epidemic or endemic peri-
endemic in most U.S. hospitals. ods are being studied, and whether the resistant pathogen is
Fluoroquinolones target enzymes responsible for bacterial isolated during episodes of colonization or infection.
DNA replication, such as DNA gyrase and topoisomerase, giv- Attention has been directed at specific methodologic is-
ing them broad efficacy against many gram-negative, and some sues that may lead to biased estimates of risk for antibiotic
gram-positive, organisms (54). Since the 1980s, their potency resistance (59). First, results of case-control designs, used ex-
and oral bioavailability have made their use widespread in tensively in studying the risk of acquiring resistant bacteria,
treatment of infections (particularly pulmonary, urinary, and are influenced by how the control group is selected. In many
gastrointestinal), as well as in prophylaxis (e.g., in neutropenic studies, control groups are selected either from patients in the
patients). Widespread increases in fluoroquinolone resistance population who are uninfected, or from patients who carry the
have been reported in many bacteria, in particular Enterobac- antibiotic-susceptible form of the bacterium of interest (60).
teriaceae, P. aero.ginosa, Streptococcus pneumoniae, and Staphylo- Use of either control group may result in slightly differing esti-
coccus. aureus (55-57). Ciprofloxacin resistance among E. coli mates of risk. When resistant cases are compared to uninfected
urinary isolates from the United States increased from 3% to controls, risk factors for acquisition of both the susceptible
17% from 2000 to 2010 (48). Although mutations to fluoro- and the resistant phenotype of the organism may be identified
quinolone targets and effiux mechanisms explain some of ( 60) . If instead, controls are selected that are already colonized
the increase in resistance rates, the discovery of two dissemi- or infected with the susceptible form of the organism, the
nated classes of plasmid-mediated fluoroquinolone resistance odds of association between certain variables and acquisi-
mechanisms ( QJ'r proteins that interfere with fluoroquinolone tion may be overestimated (61). An alternative study design,
TABLE 15.4 Examples of Host Factors Associated with Healthcare-Assodated Colonization or

Infection by an Antimicrobial-Resistant Organism in Selected Case-Control Studies
Factor Reference
MORE FREQUENTI..Y IDENTIFIED

Duration of hospital or ICU stay (adjusted or matched in many studies) (63-65,4!10)
Prior antimicrobials (65, 7!1,191,4!11-445)
Intensive care unit (65,433,443,445)
Invasive devices or procedures (4!1!1,4!18)
central venous catheter (191,434)
endotracheal intubation (4!14,442)
urinary catheter (436)
nasogastric tube (4!15,446)
Underlying comorbidities (7!1,191,434,4!16)
Prior colonization or infection with resistant organism (73,447)
Prior hospitalization or residence in long-term care facility (6!1,64,444)
RISK FACTORS LESS FREQUENTLY IDENTIF1ED

Age (64,443)
Sex ( 434,435,444)
Chemotherapy (448)
Endoscopy (448)
Surgery (or number of operations) (64)
Proximity to other patients (191)
"case-case-control," uses both types of controls and two separate opportunities for horizontal acquisition of the organism (69).
case-control analyses within a single study in order to differen- The use of anti-anaerobic drugs appears to facilitate fecal excre-
tiate risk factors associated with acquisition of the susceptible tion of resistant enterococci, leading to further opportunities
and resistant phenotypes of the organism (60). for transmission (70). On a population level, the emergence
A second important methodologic principle is adjustment of VRE in the 1980s was likely due to the accelerating use of
for time at risk (59). Not surprisingly, duration of hospital stay vancomycin during that decade (71). However, many classes
(and specifically, "time at risk" before the index colonization or of antibiotics have been associated with VRE emergence; prior
infection) is often identified as a significant risk factor for ac- receipt of vancomycin by an individual patient appears to have
quisition of bacteria (62-64). In case-control studies that iden- minimal effect on the risk of VRE acquisition once VRE have
tify risk factors for antibiotic resistance, time at risk needs to be become established in a locality (72,73).
accounted for via multivariable analysis or by matching cases
and controls (59).
A third methodologic principle is adjustment for comor- SOURCES OF RESISTANT STRAINS
bid conditions (59). Such adjustment is particularly important
when the risk factor of interest is antimicrobial use. As a corol- The source of most resistant strains in hospitals appears to
lary, measurement of comorbid conditions and severity of ill- be patients who are colonized or infected (74-77). Because
ness should be performed at a time point before acquisition the normal oropharyngeal and intestinal flora of hospital pa-
of the organism of interest, in order to make causal inference tients may be displaced by multiply resistant enteric bacteria
valid (65). and P. aeruginosa (urine, perineum, and wounds may be simi-
A final methodologic concern is the analysis of aggregated larly affected), there are often many colonized patients for
antibiotic use data to estimate patient-level risk of acquiring each patient with recognized infection, the so-called "iceberg
an antibiotic-resistant organism (66). Analysis of aggregated effect" (Figure 15.2) (74). This shift in flora often occurs
data may not accurately reflect the risk of exposure to an indi- within a very few days of hospital admission and affects the
vidual patient, since population studies do not link individual older, generally sicker, or more debilitated patients. The causes
outcomes to individual exposures {66). Population studies are of shifting commensal bacteria are unclear, and may involve
useful in allowing the measurement of the total effect of an a combination of hospital-related factors (e.g., specific treat-
exposure. ment exposures vs. more hands-on care in general) and patient
There is a striking commonality of risk factors for coloniza- host factors (e.g., possible changes in membrane receptors or
tion or infection with pathogens such as antimicrobial-resistant ligands, antibiotic suppression of normal flora, potential contri-
S. aureus, Enterococcus spp., or gram-negative bacilli (67). These bution of biofilm formation on devices such as nasogastric and
risk factors include advanced age; underlying diseases and endotracheal tubes) (78-81). Some shift in endemic strains
severity of illness; inter-institutional transfer of the patient, may result from emergence of low-count communit}'-acquired
especially from a nursing home; prolonged hospitalization; flora in the face of antibiotic exposure rather than from true
gastrointestinal surgery or transplantation; exposure to invasive healthcare-associated acquisition (82,83).
devices of all types, especially central venous catheters; and ex- It is important to realize that multidrug-resistant bacte-
posure to antibiotics, especially cephalosporins ( 67) . Other risk ria can be recovered from the normal, intact skin of patients
factors are identified in Table 15.4. (76,84-86), as well as from body fluids, secretions, and wounds.
The role of antimicrobials in promoting resistant organisms While the perineal or inguinal areas of patients usually are
has attracted much attention in the literature, perhaps because most heavily contaminated, the axillae, trunk, arms, and hands
of its potential for modification. Although it is accepted that also are frequently colonized (87) . Pathogens most often found
rising antimicrobial consumption promotes resistance, the re- at these sites are A. haumannii, Staphylococcal spp., and Entero-
lation between antimicrobials and resistance at the patient level coccal spp., perhaps in part because these pathogens are more
and population level remains unclear. Thus, it often is difficult resistant to desiccation compared to other bacteria (87-89).
for hospitals to decide between diverse antimicrobial steward- In one study, VRE were cultured from the antecubital fossae
ship strategies, such as reducing all classes of antimicrobial use, of 29% of ventilated patients studied in a medical ICU (76).
targeting specific antimicrobial classes, or rotating available These findings have implications for control strategies aimed
antibiotics. at these pathogens, which are addressed later in this chapter.
For many important drug-resistant organisms, such as Personnel have been documented sources of resistant
Methicillin-resistant S. aureus (MRSA) and VRE, resistance is gram-positive strains, such as MRSA (90,91-93) and even
mediated by complex genes that would unlikely occur spon- coagulase-negative staphylococci (94). However, personnel car-
taneously in any individual patient. In such cases, develop- riage of resistant gram-negative bacilli (other than transient
ment of resistance involves horizontal acquisition of either hand carriage described in the following section) appears to be
resistant organisms themselves or genetic vectors such as plas- very unusual. Exceptions include outbreaks reportedly traced
mids carrying resistance genes. Furthermore, many impor- to carriers of Acinetobacterspp., Citrobacterspp., or Proteus species.
tant drug-resistant organisms, such as enterococci, colonize Acinetobacter sp., one of the few gram-negative bacilli that may
the gut or skin, allowing opportunities for indirect exposure be among normal skin flora, was noted in one outbreak to re-
to the selective pressures of antimicrobials intended for other cur periodically despite disinfection of the apparent environ-
pathogens. mental reservoirs. The outbreak was ultimately traced to the
Thus, the use of antimicrobials may lead to a rise in the prev- colonized hands of a respiratory therapy technician who had
alence of resistant organisms on a population level through a dermatitis and apparently contaminated respiratory therapy
variety of indirect mechanisms (68). In the case of VRE, use equipment while assembling it (95). There have also been clus-
of cephalosporins eliminates competitive gut flora, promoting ters of Citrobacter spp. infections of the central nervous system
in neonates (96,97), traced to hand carriage by nurses, and in 10.6% of opportunities (112). Similarly, healthcare workers
an outbreak of Proteus mirabilis infections in newborns traced were found to contaminate their gloves with MRSA by touch-
to a nurse who was a chronic carrier (98) . In another study, ing only environmental sites in patient rooms (113). For high-
endemic Pseu.domtmas aernginosa infection was maintained in a risk immunocompromised patients, especially those who have
neonatal ICU by persistent carriage on the hands of healthcare the opportunity for environmental exposures (e.g., the debil-
workers; artificial fingernails or nail wraps were both risk fac- itated oncology patient who sits at the sink to wash), strains
tors for hand colonization in this study (99). from sink surfaces have been linked to patient colonization
Foodbome contamination with multiply resistant gram- and infection (1 02).
negative bacilli has been cited in several investigations
(51,100,101) and has been incriminated particularly in on-
cology units (102). Despite the potential importance of these MODES OF TRANSMISSION
observations, however, the overall role of food in introducing
resistant strains into the general hospital remains unclear. Traditional teaching is that resistant bacteria are spread in
Environmental sources and reservoirs of resistant strains the hospital from an infected patient to a susceptible pa-
have been a recurrent problem, especially when patient care tient via transient carriage on hands of health care personnel
equipment becomes contaminated. Extensive outbreaks ofUTis (Table 15.5). Such spread contributes to the iceberg of colo-
(and respiratory tract, perineal, or intestinal colonization) may nized patients and greatly increases the source and reservoir
result when urine measuring devices, contaminated by enteric of resistant strains in the hospital (Figure 15.2). While much
bacilli or P. aernginosa, are shared by many patients (74,103). of the evidence incriminating hands of personnel is circumstan-
MRSA contamination of ultrasonic nebulizer filters was linked tial and based on finding resistant bacteria colonizing or con-
to an outbreak of infection and colonization in a head and taminating healthcare worker hands, both experimental and
neck surgical ward (104), and electronic thermometers con- mathematical models, as well as observational studies in patient
taminated with vancomycin-resistant Enterococcus faecium were care settings have demonstrated that healthcare workers can
implicated as vehicles of transmission in an outbreak in a medi- transfer pathogens from their hands or gloves to patients' skin
cal-surgical ICU (105). or devices (112,114-118). Moreover, the weight of experience,
Finally, there has been perennial concern about contamina- dating back to the successful introduction of hand hygiene as a
tion of many areas of the inanimate environment with which control measure by Semmelweis, strongly supports this concept.
patients do not have regular contact, such as flowerpots and The contribution of transfer of pathogens from contami-
sink traps (106-108). These sites, despite sometimes heavy con- nated environmental surfaces to patients via the hands of
tamination, have not been consistently linked with the spread healthcare workers is receiving renewed attention (112). Given
of bacteria in hospitals. the lower colony counts typically found at environmental sites
Contamination of inanimate environmental surfaces that compared to patient sites (76), for many pathogens, this route
are touched by healthcare workers may be a more important of transmission appears to be less important than transfer from
source of transmission, particularly for multidrug-resistant bac- patient to patient (Table 15.5).
teria (such as VRE and Acinetohacter spp.) that survive well on Healthcare workers who are persistently colonized with
inanimate surfaces ( 109-111). In one report, healthcare work- antibiotic-resistant bacteria can sometimes transfer these
ers were shown to transfer VRE from contaminated sites in a pathogens directly to patients (Table 15.5) (99,119). This is par-
patient's room-such as a blood pressure cuff, bed rail, or soap ticularly important for MRSA, and may be under-appreciated
dispenser-to clean sites in the room or on a patient's skin in settings where MRSA is endemic and cross-transmission is
via their hands or gloves during routine patient care activities frequent (119), thereby obscuring the contribution of carriers.
TABLE 15.5 Relative Importance of Selected Factors in the Emergence of Some Multidrug-&sistant
Organisms within Hospitals•
Patient-to-Patient
Transmission via Environment-to-Patient Colonized Endogenous
Multidrug-R.esistant Contaminated via Contaminated Healthcare Selection by
Organism, Deimed by Healthcare Worker Healthcare Worker Worker Directly Antibiotic
Key Resistance Marker Hands Hands to Patient Pressure
Methicillin-resistant +++ +/++ + +/- +
Staplry7ocouw auRIW
Vancomycin-resistant +++ ++ ++
enterococcw
Multidrug-resistant +++ + + ++
Enterobacteriaceae
Imipenem-resistant + + + + ++
Pseudomonas aeruginosa
Imipenem-resistant +++ ++ ++
Acinetobacter' baumannii
"The relative importance is an indication of the need to address each factor in control measures for specific resistant pathogeru.
Common-source spread of resistant strains has been noted antibiotic-resistant bacteria in hospitals has allowed the rec-
primarily in outbreak settings. The attention of the medical ognition of outbreaks caused by mobile genetic elements such
community (and newspaper and journal editors) is often at- as integrons, plasmids, or transposons. While horizontal gene
tracted to such epidemics because of striking features, such transfer due to these elements is clearly important in the dis-
as large numbers of patients infected with very resistant bac- semination of antibiotic resistance in gram-positive bacteria
teria, unusual breaks in techniques or protocols, or contami- (124,125), the rapid spread of resistance in this manner is
nated commercial products. Perhaps more common than such recognized more often in gram-negative species. Several plas-
"extravaganzas" are the ongoing episodes of limited cross- mid outbreaks have been described in which a resistance plas-
infection due to contamination of shared patient care equip- mid has caused either simultaneous or sequential resistance
ment, which probably account for a significant portion of to occur in epidemic fashion in different species or genera
seemingly endemic infections (120). (126-128). Mobile genetic resistance elements have been
Airborne spread of resistant bacteria has been documented found to spread throughout a city, states, and even entire
rarely. For S. aureus, aerosolization was implicated in one hos- countries (129-133).
pital outbreak involving an MRSA-colonized physician with The epidemiology of most of these outbreaks, specifically
an upper respiratory infection (93) and subsequently demon- the reservoirs for the resistance elements, time and place of
strated under experimental conditions with colonized volun- transfer of genetic material, and pressures involved, has been
teers (121). Airborne MRSA has also been detected in the air of largely speculative (134,135). Transfer can occur in the gut, on
hospital rooms with patients suffering from MRSA respiratory skin, in urine, and in the environment (e.g., in urine contain-
infections (122). The direct implications of these findings with ers) and may be facilitated by antimicrobial therapy (136,137).
respect to general control ofMRSA are currently unclear. Moreover, relatively avirulent bacterial strains may serve as
Various insect vectors, such as flies and cockroaches, are "Trojan horse" reservoirs for resistance. For example, intes-
probably unimportant in the transmission of resistant bacteria tinal anaerobes, which are present in high numbers but are
in most modern hospitals. relatively avirulent, can harbor mobile antibiotic resistance
elements that are subsequently passed to other more patho-
genic bacteria such as E. coli (138). Since clonal dissemina-
EPIDEMICS tion or clustering is identified in many integron and plasmid
outbreaks, it appears that cross-transmission plays a major role
The events leading to any healthcare facility epidemic are prob- in their dissemination (129,139-141).
ably multifactorial. In most outbreaks ofMDR bacteria, precipi- Outbreaks due to plasmids and integrons may be difficult
tating events have not been well elucidated. Factors that could to detect (139), but should be sought through surveillance for
increase person-to-person spread include poor aseptic prac- the occurrence of multiple species or genera with identical or
tices, as in crowded units or when the nurse-to-patient ratio very similar multiple drug (or even just key drug) resistance
becomes too low. Spread from the environment is facilitated by patterns. Molecular characterization of such outbreaks relies
poor housekeeping practices that lead to reservoirs of resistant on sophisticated technology that may not be available in many
organisms within the hospital, as when infected urine is allowed laboratories, such as PCR, restriction endonuclease digestion,
to remain in urine measuring or testing devices. Excessive use or DNA sequencing (128). Once recognized, epidemics due to
of antibiotics may increase the selective pressure for resistant transferrable genetic elements are at present controlled much
strains. like single-strain outbreaks (see under the heading "Control"),
Certain chance events may precipitate outbreaks, such as although more research is needed to determine the most effec-
contamination of a commercial product, admission of a patient tive control measures.
who is a heavy shedder of MDR bacteria (123), or acquisition
of resistance by a bacterial species that is adept at colonization
or unusually resistant to disinfection. Advances in medical tech- OTHER MULTIPLE STRAIN
nology, such as transplantation, dialysis, and new prosthetic de- OUTBREAKS
vices, create additional epidemic risks.
Particular areas within the hospital, especially ICUs, burn, Occasionally, common sources may become contaminated with
trauma, transplant, oncology, and neurosurgical units are prone several bacterial species, leading to outbreaks of otherwise un-
to outbreaks. These areas house acutely ill patients who are sub- related strains. For example, one multiple-strain outbreak of
jected to many invasive procedures and are often exposed to orthopedic wound infections was traced to a common bucket
multiple antibiotics under circumstances in which asepsis may used to mix cast material. The bucket was not routinely disin-
be trampled in the rush of crisis care. We have found that MDR fected and contained a variety of contaminants that probably
bacteria may breed in such units, or epicenters (Figure 15.2) were inoculated into wounds during application of casts. An
(74). As colonized patients are transferred to other areas of the unusual series of outbreaks of postoperative infection due to
hospital, they may leave a trail of resistance. multiple organisms at seven different hospitals was linked to
exposure to propofol, an anesthetic agent with a lipid-based ve-
hicle that is able to support the rapid growth of a variety of mi-
OUTBREAKS DUE TO PLASMIDS AND croorganisms at room temperature (142). Apparently, lapses in
OTHER MOBILE GENETIC ELEMENTS aseptic technique by anesthesia personnel at or near the time
of surgery resulted in extrinsic contamination of syringes or vi-
Most reported healthcare facility outbreaks have been als containing this agent. Such outbreaks may go unrecognized
due to epidemic spread of single strains. Application of unless one strain predominates or the strains or epidemiologic
newer molecular laboratory techniques to investigation of circumstances are very unusual.
CONTROL (165-167). Although we believe that additional research in

this area is needed to attempt to resolve the controversies, we
Antibiotic resistance is important to control primarily because strongly feel that we must work now, with the information avail-
its presence limits treatment options, sometimes to less effective able, toward controlling multidrug resistance in hospitals. This
or more toxic therapies. Delayed or ineffective treatment may is particularly important because of increasing pressure from
underlie the reported increases in morbidity and mortality as- the lay public and legislatures who will otherwise mandate our
sociated with infection due to several MDR bacteria (14~148). response to the problem (168,169).
Excess cost or length of stay has also been found to be asso- It is likely that various combinations of control measures
ciated with infection due to these pathogens, suggesting that are effective, and that success or failure is dependent on the
control may result in cost savings for hospitals (143,149-151). epidemiology of the problem (e.g., monoclonal outbreak vs.
The past decade has yielded a large body of knowledge polyclonal endemicity, the population affected, the intensity of
related to the epidemiology of MDR bacteria in hospitals. care required, and the degree of compliance with individual
Molecular epidemiologic studies have discriminated those measures that constitute the intervention). Based on our stud-
pathogens that disseminate primarily by clonal expansion ies and a critical review of the literature, we suggest a multifac-
(which should be more effectively eradicated by interruption eted and flexible approach to the control of antibiotic-resistant
of cross-transmission) (124), from those which arise mainly by bacteria in acute care hospitals. Some potential components to
mutation and selection of patients' endogenous flora (which include in such a program are discussed below.
might better be controlled by relieving antibiotic pressure)
(152,153). Mathematical models of transmission have allowed EDUCATION
predictions about the effectiveness of various interventions that
would be difficult or impractical to study in large clinical trials Antibiotic resistance is a problem for the entire healthcare com-
(154-158). Study design and analysis have become more rigor- munity, not just for infection preventionists. All hospital per-
ous, providing better information about the effects of IC mea- sonnel should be educated to recognize the deleterious effects
sures (59-61). of antibiotic resistance, and their role in controlling it. Several
Nevertheless, it is clear that there is still much we do not studies have demonstrated that physicians tend to perceive
know. Many of the published reports of successful control of antibiotic resistance as less important in their own institutions
healthcare-associated MDR bacteria have important limitations. than nationally, even if they have access to information show-
First, most were conducted during epidemics, while hospitals ing that local rates of resistance are high (170,171). Mandatory
confronting these pathogens often face endemic resistance; education sessions should emphasize local data and response,
the epidemiology of the problem and the effectiveness of and should be tailored to clinicians' areas of interest; frequent
control measures are likely to be different in these two settings. reminders such as posters with simple messages or educational
Second, most studies implemented multiple interventions (also alerts may be effective adjunctive educational measures (170).
known as "bundles"), either simultaneously or sequentially,
making it difficult to determine the relative contribution of WCAL HOSPITAL LEADERSHIP
each component of the bundle. This information is especially
important in controlling resistance in endemic settings: be- Hospital administration must support efforts to control antibi-
cause of the long-term investment required, and the potential otic resistance by providing adequate funding for an effective
for adverse outcomes related to some interventions (159-161), IC program and by incorporating IC into the objectives of the
it is essential that we implement only measures that are both organization's patient and occupational safety programs. In ad-
necessary and sufficient to achieve control. Third, while re- dition, senior hospital leadership, including department heads
search methodologies have improved, few intervention trials and other opinion leaders should be recruited to conspicu-
have used optimal study designs (e.g., randomized cluster or ously promote these objectives and to model good behavior,
cros11-0ver). Most of the information available to us comes from such as strict adherence to hand hygiene (87,172-175).
quasi-experimental (before-after) studies that may have failed In the United States, several forces have elevated the im-
to take into account stochastic or secular changes, that did not portance of IC in the eyes of hospital leadership, including
adequately control for bias or confounding, or that may have a greater role for public reporting of hospital infection rates
had very short periods offollow-up (162-164). Fourth, in stud- (176) and increased financial consequences of HAis (e.g.,
ies of IC interventions that required the active participation of nonpayment for several HAis by the Centers for Medicare and
healthcare workers in a clinical setting, such as studies of the Medicaid [CMS]) (177).
effect of contact isolation on the acquisition of colonization by
a MDRO, compliance monitoring was rarely performed. Stud-
REGIONAL LEADERSHIP
ies that did monitor compliance often found it to be poor, rais-
ing questions about the validity of the causal inferences made The fluidity of patient movement among different types of
by the authors. Finally, the reason for the success of isolation healthcare facilities (such as acute care hospitals and long-term
interventions is not known; that is, whether the outcome is re- care facilities) within geographic regions has raised the impor-
lated to improved hand hygiene, a positive, intended effect, or tance of coordinated, regional control efforts. In one regional
to fewer healthcare worker contacts with colonized or infected outbreak, rapid spread of KPC-producing Enterobacteriaceae
patients, an unintended effect with potentially additional involved extensive transfer of KPC-positive patients throughout
unintended negative consequences (159-161). a network of 14 acute care hospitals, 2 long-term acute care
For some pathogens, such as MRSA, the lack of definitive hospitals, and 10 nursing homes (178).
information has resulted in a divergence of opinion in the IC There is evidence on several levels that coordination of ef-
community about the interventions that should be endorsed forts regionally and even nationally (179-183) may result in
substantial and durable reductions in antimicrobial resistance. of bacteria on the hands of personnel (190), and their introduc-
Multi-facility collaborations should be sought when feasible, for tion to a healthcare facility improved hand hygiene adherence
example, in integrated healthcare systems or in regions with (191) (see Chapter 3) . A ~or challenge in improving hand hy-
strong public health coordination. giene is adequate monitoring of hand hygiene adherence; auto-
mated monitoring of adherence using various teclmologies have
been developed, but their efficacy and acceptance among health-
PREVENTION OF INFECTION
care workers is still uncertain (192-194) .
Prevention of infections, particularly device-related infections,
can lead to decrease in antimicrobial resistance. Although the GWVES
strength of evidence in support of some IC interventions is
debated, there is a consensus on the effectiveness of "bun- Gloves, a key element of both standard and contact precau-
dling" preventive measures that have been effective individu- tions, have been found to be highly effective in preventing
ally, combined with monitoring and feedback, to significantly contamination of healthcare worker hands during routine care
reduce or eliminate device-related and surgical-site infections activities that require touching a patient or the patient's imme-
(184). Reducing infection rates would not only decrease in- diate environment (117,118]). Wearing gloves for all patient
dividual patients' risk of morbidity from antibiotic-resistant encounters (universal gloving) was a m~or component of a
bacteria, but should also result in reduced antibiotic prescrib- successful program to control MRSA in a surgical ICU; in a dif-
ing, thereby lessening antibiotic pressure selective for ecologic ferent study, requiring healthcare workers to wear gloves for
resistance. contact with any patient body substance was associated with a
decreased incidence of Clostridium difficile diarrhea compared
to wards where gloves were not required ( 195) . Although gloves
PASSIVE SURVEILLANCE
are not a substitute for hand hygiene, they can help fill the gap
Surveillance of clinical laboratory results should be maintained between actual and optimal hand hygiene practice. Glove effec-
to detect clusters of resistant bacteria (e.g., 2:3 patients with tiveness may be limited by small tears or defects that may result
similarly resistant organisms on the same ward within 2 weeks) in inapparent soiling of hands, and by contamination of hands
so that cross-infection or significant environmental reservoirs at the time of glove removal. In addition, cross-transmission of
can be identified and controlled. Newer automated methods resistant bacteria is facilitated if healthcare workers fail to re-
using computer programs linked to microbiology results may move gloves between patients.
improve the ability of infection preventionists to identify HAl
outbreaks using statistical rules (185).
CONTACT PRECAUTIONS
Use of molecular epidemiologic tools, such as pulsed-field
gel electrophoresis (PFGE), ribotyping, or even whole-genome Contact precautions are used to minimize patient-to-patient
sequencing, can sometimes enhance standard laboratory sur- transfer ofMDROs in a healthcare facility. General contact pre-
veillance efforts and reveal relationships between isolates that caution principles include use of gown and gloves by healthcare
are not otherwise obvious (186,187). If supported by the hos- workers caring for patients with MDROs. Ideally, such patients
pital and laboratory information systems, electronic alerts that should be placed in private rooms or placed in a cohort with
notify admitting personnel of patients who were colonized or other patients who are colonized with same pathogens. Sev-
infected with a resistant pathogen on a previous admission can eral studies have provided evidence in support of the effi-
help expedite isolation of patients (188,189). cacy of clean cover gowns to interrupt pathogen transmission
Guidelines have been developed to better define useful (196-200). The requirement of gown was cited as a key compo-
metrics to monitor MDROs (18). Such metrics, which use data nent in a successful multimodal control of an outbreak of VRE
from the microbiology laboratory, capture the following essen- (201). Three prospective evaluations of the added benefits of
tial elements of pathogen surveillance: (a) tracking patients gowns compared to gloves alone to prevent VRE transmission
with important pathogens, (b) monitoring pathogens suscepti- yielded varying results (197,199,200). In one study, although
bility patterns, (c) estimating infection burden, (d) estimating gowns did not demonstrate additional benefit, gown use was as-
colonization pressure, and (e) quantifying healthcare acquisi- sociated with increased compliance with IC procedures (200).
tion. For details, the reader is referred to the following position Gowns likely provide the most benefit when worn to care for
paper (18). patients who are shedding large numbers of resistant bacte-
ria in urine, stool, secretions or drainage; or who are carrying
antibiotic-resistant bacteria that are known to contaminate and
HAND HYGIENE
survive in the hospital environment, such as antibiotic-resistant
Since most cross-transmission of pathogens in hospitals occurs A. baumanni~ VRE, and MRSA (110,112,202-204).
from patient to patient via contaminated healthcare workers'
hands (Figure 15.1, Table 15.5), promotion of hand hygiene
ACTIVE SURVEn.LANCE TESTING
is an essential component of any policy to prevent spread of
antibiotic-resistant bacteria. Strategies for the successful pro- Active surveillance testing, defined as screening of asymptom-
motion of hand hygiene in hospitals have included education; atic patients for specific drug-resistant organism colonization,
observation and feedback; engineering changes (extra sinks, is a mainstay of targeted IC efforts. In contrast to "horizon-
well-stocked hygiene supplies); posters, cartoons, and other vital" or "global" interventions such as chlorhexidine bathing
sual reminders; administrative sanctions or rewards; and avoid- (discussed later) that affect more than one drug-resistant
ance ofexcessive workload and understaffing (87). Alcohol-based pathogen, active surveillance is a "vertical" tool that focuses on
handrubs are the most efficacious agents for reducing the number a single pathogen (205,206).
From an epidemiologic point of view, active surveillance DISINFECTION AND CLEANING OF THE
testing is beneficial in identifying the entire population of ENVIRONMENT
pathogen-colonized patients ("resistance iceberg"), notjust the
minority of patients identified by clinical cultures. For MRSA, Careful attention to cleaning and disinfection of patient rooms
may be particularly important for control of antibiotic-resistant
active surveillance testing can identity an additional 20% to
bacteria that have been shown to persistently contaminate the
60% of MRSA carriers beyond those identified by routine clini-
inanimate environment in hospitals, such as VRE, antibiotic-
cal cultures alone (63,207). For VRE, the benefit is even larger,
resistantA. baumannii,andMRSA (204,219,220) .Recent evidence
an approximately three-fold increase in the detection of VRE
has implicated contaminated surfaces as significant reservoirs
carriers beyond those identified by routine clinical cultures
for these pathogens; these findings, in turn, have revitalized in-
(208). Furthermore, routine active surveillance testing pre-
vents misclassification of some patients with positive clinical terest in environmental "source control"(l10,112,113,221,222).
Evidence that improved environmental cleaning results in
cultures with resistant pathogens as incident cases. For exam-
ple, approximately 17% of all MRSA cases and 43% of all VRE less cross-transmission of MDR bacteria is mixed. In a quasi-
experimental study we performed, strict enforcement of
cases may be misclassified as "incident cases" if only clinical cul-
tures are available without knowledge of admission surveillance routine environmental cleaning procedures was effective in
controlling VRE over an 11-month period in a medical ICU
testing results (207,208).
where this pathogen was endemic. The intervention was as-
Active surveillance testing can be useful in controlling an
sociated with less environmental contamination with VRE, de-
outbreak, when more conservative control measures have
creased contamination ofhealthcare worker hands, and a more
not succeeded. Active surveillance testing may be particu-
than three-fold reduction in VRE acquisition by patients (221).
larly useful for outbreaks involving emerging pathogens (e.g.,
These improvements occurred despite ongoing admission of
carbapenem-resistant Enterobacteriaceae) or for pathogens
that colonize the gastrointestinal tract (enterococci, Entero- VRE-colonized patients and only moderate rates of healthcare
worker adherence to proper hand hygiene. In contrast, a ran-
bacteriaceae) for which a large undetected reservoir of patients
may be present (209,210). However, in endemic (nonout- domized crossover study in critical care units in two hospitals
found that enhanced cleaning reduced environmental con-
break) settings, the role of active surveillance testing is unclear,
particularly for MRSA (see the "MRSA" section later for MRSA- tamination and healthcare worker hand contamination with
MRSA, but had no effect on patient acquisition ofMRSA (223).
specific discussion).
Standard cleaning and disinfection methods remain the
For VRE, active surveillance testing has been a compo-
foundation of environmental decontamination, although
nent of successful multifaceted programs throughout a hos-
thoroughness of cleaning is often suboptimal. Adherence of
pital or a region during outbreak as well as endemic periods
environmental services personnel to cleaning protocols can
(179,211,212). However, the importance of active surveillance
be improved by education coupled with close monitoring and
testing for VRE control during endemic periods is question-
able, as the only randomized controlled trial published showed feedback (224). In a study of environmental hygiene in 27 ICUs,
the number of targeted sites cleaned improved from 49.5% to
no impact of active surveillance testing on VRE acquisition
among ICU patients in a nonoutbreak setting, although the 82% after implementation of a structured educational, proce-
dural, and administrative intervention that included use of a
testing methodology used was not optimal (213).
Occasionally, healthcare workers are the source of an out- fluorescent marker to monitor surface cleaning (225).
Several technologies have been developed to reduce envi-
break or cluster of infections; this has been demonstrated
ronmental contamination by resistant pathogens, although
especially for MRSA and group A Streptococcus (91-93,214).
their effectiveness in reducing infections during routine (non-
Surveillance of healthcare workers and decolonization of
epidemic) hospital cleaning remains uncertain. Hydrogen
carriers may be necessary to control transmission.
peroxide vapor or aerosol, as well as ultraviolet radiation, have
each been developed using machine hardware for terminal
ADHERENCE MONITORING room decontamination (226-229). The use of self-disinfecting
materials or transition metals for touch surfaces in the hospital,
Adherence to interventions is crucial to the success ofiC mea- such as copper and silver, have also been studied (230,231) .
sures such as hand hygiene and contact precautions. Based Further research is needed to document the efficacy of these
on observational and interventional studies and behavioral technologies in reducing HAis before these technologies be-
models, it is probably unrealistic to expect 100% compliance come widespread.
with any intervention, and the adherence threshold for suc-
cess of measures such as hand hygiene is not known. N onethe-
PATmNT DECONTAMINATION AND
less, the Joint Commission (TJC) expects that hand hygiene
DECOWNIZATION
adherence should occur with no more than a "sporadic miss."
Monitoring and feedback of results, especially if immediate, Improving the cleansing of patients' skin, to reduce the burden
has been shown to improve compliance with IC procedures in of drug-resistant organisms and thus decrease the potential of
several studies (191,215-218). Direct observation by monitors patient-to-patient transmission of bacteria as well as complica-
that are known to the observed worker may yield inaccurate tions of central line-associated bloodstream infections (CLA-
results due to a Hawthorne effect. Alternative methods of ad- BSis), has become an important tool in IC. Chlorhexidine has
herence monitoring include tracking use of supplies (such as been the best studied; it is a topical antiseptic that has a wide
alcohol hand rub or gowns) as well as employing automated spectrum of activity (Gram-positive and Gram-negative bacteria,
(e.g., electronic or video) adherence monitoring systems (for as well as fungi and some viruses, but not spores) and an excel-
hand hygiene) (192). lent safety profile (232). Compared to routine soap-and-water
bathing, daily chlorhexidine bathing has been demonstrated to In general, antibiotic control programs should promote
reduce the burden ofVRE on patients' skin, lower rates ofVRE good antibiotic stewardship, such as curbing overall antimicro-
contamination of healthcare workers' hands as well as the room bial consumption and de-escalating or narrowing antimicrobial
environment, and decrease the rate of VRE acquisition by pa- therapy when appropriate (247). Hospitals should have an an-
tients in the ICU (233). In a controlled crossover clinical trial, timicrobial stewardship program to monitor the appropriate-
daily chlorhexidine bathing has also been shown to reduce pri- ness of antimicrobial therapy; guidelines for developing such
mary BSis (234,235). Chlorhexidine bathing has been shown a program have been published (248). Reducing antimicrobial
to reduce cross-transmission of both MRSA and VRE among therapy should focus on three points: (a) identifying the nature
ICU patients (236). Whether broader use of chlorhexidine will of the infection and treating only those patients who are truly
promote development of chlorhexidine resistance is a concern. infected, (b) narrowing antimicrobial therapy when appropri-
In one study, introduction of a chlorhexidine-based antiseptic ate, and (c) treating only for as long as is required to cure the
protocol to an ICU where MRSA were endemic resulted in a infection. The Centers for Disease Control and Prevention
significant reduction in the acquisition of most MRSA strains (CDC) has promoted the ~Get Smart" campaign to improve the
but an increase in the acquisition of a MRSA strain that carried stewardship of antibiotics (249).
the qacA/ B genes, which have been associated with elevated Antimicrobial use strategies that have not been effective in
chlorhexidine MICs (237). To date, no randomized control of reducing antimicrobial resistance include using routine com-
chlorhexidine bathing has been performed and most of the bination (two or more) antimicrobial therapy to reduce on-
studies have been limited to ICUs. treatment resistance and antimicrobial cycling (changing classes
Decolonization of patients has sometimes been a com- of preferred antimicrobial on a scheduled basis) (247,250).
ponent of control programs, especially if more routine
IC measures could not be employed or were unsuccessful
(219,238). Decolonization of enteric pathogens such as VRE THRESHOLD FOR INVESTIGATION
and Enterobacteriaceae is generally more difficult. Routine AND GOALS OF CONTROL PROGRAM
decolonization of MRSA-positive patients with various combi-
nations of intranasal mupirocin, chlorhexidine bathing, and Some organisms always warrant prompt attention because of
systemic antibiotics has been shown to be effective in decolo- key resistances. Such bacteria include MRSA, S. aureus with
nizing patients, at least in the short term (239-241). The im- reduced susceptibility to glycopeptides, VRE, carbapenem-
pact of MRSA decolonization on infection outcomes is being resistant Gram-negative rods, and ESBL-producing Enterobac-
studied in a cluster-randomized trial, comparing targeted de- teriaceae. The responses of different hospitals to control of
colonization (only for MRSA-positive ICU patients) vs. global any of these pathogens may differ depending on the context
decolonization (all patients in the ICU regardless ofMRSA sta- of patient care; for example, a patient housed in an ICU or
tus) for IC (242). The results, not available at the time of this transplant ward is more likely to suffer serious morbidity from
writing, will add important information to the role of MRSA VRE colonization than is a patient in a rehabilitation facility.
decolonization in the ICU. Also, the potential risk of a pathogen to an institution will also
influence action; isolation of vancomycin-resistant S. aunus
(VRSA) would evoke a more aggressive response than isolation
ANTIMICROBIAL STEWARDSHIP ofMRSA Once an outbreak is recognized as significant, acting
Because antimicrobial consumption appears to drive both the as soon as possible is the key to containing and eliminating the
pathogen before it becomes endemic.
emergence and transmission of MDR organisms, much effort
has gone into studying antibiotic management in the hopes of Taking these variables into account, hospitals should set
long-term goals for control programs aimed at these or other
curbing selective pressure. On a population level, the amount
of antimicrobial consumption is associated with rates of an- MDROs. First, a hospital should determine which pathogens
and units to target. Next, an assessment of the extent of the
timicrobial resistance (243,244). However, at the individual
level, the direct relation between prior antimicrobial use and problem should be made, that is, rare or occasional MDRO in-
fections, one or more ongoing outbreaks, or low- or high-level
subsequent development of drug-resistant infection or coloni-
zation is more complex and nonlinear. For example, there is endemicity. Finally, the hospital should determine whether
minimal evidence that limiting vancomycin exposure decreases the goal is eradication of a specific organism, control of an
the risk ofVRE acquisition in VRE-free patients (73). Also, re- outbreak, or reduction of the number of endemic infections
striction of one antibiotic may be associated with a reduction to the lowest achievable level (165). We caution against too
narrow a focus; close attention to control of a single MDRO
in resistance to another; a 10-fold decrease in fluoroquinolone
use was associated with a statistically significant decline in the may result in disregard of another, leading to its uncontrolled
dissemination (205,251).
incidence density and prevalence of MRSA in a French hospi-
tal (245). Unfortunately, a decrease in one class of antibiotic
may be followed by an increase in resistance in another class.
In 1995, in response to the rising incidence in ESBL-producing
SPECIFIC ORGANISMS
K pneumoniae, one hospital reduced the use of cephalosporins
STAPHTLOCOCCUSAUREUS
through formulary restriction and guideline modifications.
An 80% reduction in cephalosporin use led to a 44% reduc- MRSA is one of the most common causes of antimicrobial-
tion in the incidence of ceftazidime-resistant K pneumoniae resistant HAl and has attracted particular attention from
hospital-wide, but at the apparent expense of a 69% increased healthcare providers and patients alike. MRSA was first discov-
incidence of imipenem-resistant P. aeruginosa (246). ered in 1961, merely 2 years after methicillin was introduced
as a treatment for penicillin-resistant So aureus (252)0 Methicil- overexpresses the vancomycin-binding target (D-AlG-D-Ala) ,
lin resistance is conferred by the mecA gene, which produces thus inhibiting the antibiotic from diffusing to its cellular target
penicillin-binding protein (PBP) 2ao This altered component (267). The first VISA strain was reported in 1997 from Japan
of the bacterial cell wall resists antibiotics that bind to PBPs, (268), with subsequent reports of VISA isolates worldwide, and
thus rendering ineffective nearly all ,8-lactam antibiotics and although VISA are a magnitude more common than VRSA, they
carbapenems (253) o are still relatively rare. For example, in The Surveillance Net-
To date, at least eight major clones of MRSA, defined by al- work data from the United States in 2005 showed that vanco-
lotypes of the genomic subunit called the staphylococcal cas- mycin MICs 2:4 mcg/mL among clinical S. aureus isolates were
sette chromosome mtc (SCCm«:) that carries mecA, have been uncommon (0.2%, n = 520) VSo vancomycin MIC = 2 mcg/mL
identified (254)o From the 1960s to 1990s, most MRSA clones (16.2%, n = 39,223) (269).
(predominantly, SCCmtctypes I-III) were found among patients Our understanding of VISA epidemiology has been ham-
with epidemiologic contact with hospitals (hospital-associated, pered by laboratory detection challenges. Because the genetic
or HA-MRSA) o However, since the 1990s, distinct strains of determinants of VISA are incompletely understood and likely
MRSA carrying SCCmec IV were detected among people in involve multiple genetic alterations, there is no molecular-
the community without prior healthcare contact (community- based (PCR) test for VISA isolates; rather, culture-based sus-
associated, or CA-MRSA) (254)o Over time, in geographic ar- ceptibility testing with the CLSI definitions noted above have
eas where CA-MRSA is highly prevalent, CA-MRSA strains have been used. One difficulty with using current susceptibility test-
entered the hospital environment to intermix with traditional ing is in identifying heteroresistant vancomycin-intermediate
hospital strains and cause HAls (255-257) o So aureus (hVISA), in which some cultures of So aureus that test
In the United States, data reported to CDC from 2006 to as "susceptible" to vancomycin based on routine microbiologic
2007 show that roughly half of hospital-associated So aureus iso- testing actually contain subpopulations of bacteria with vanco-
lates are methicillin resistant (258)o In Europe, the proportion mycin MICs in the intermediate range (270). Infections with
of methicillin resistance among hospital-acquired So aureus iso- h VISA strains likely lead to worse clinical outcomes because of
lates in 2009 varied substantially by country, with nine coun- incomplete response to vancomycin treatment (271). Practical
tries reporting <10% MRSA, nine countries reporting 10% to approaches to detecting h VISA and VISA have been proposed,
25%, nine countries reporting 25% to 50%, and one country but most methods are not used routinely (267). Popular auto-
>50% (259)o The incidence of invasive MRSA infection ap- mated susceptibility systems have fuir sensitivity for detecting
pears to be declining: from 2005 to 2008, the CDC observed a VISA but poor sensitivity for detecting h VISA, complicating
28% decrease in hospital-onset MRSA infection, and from 2006 both clinical decision-making and epidemiologic research.
to 2009, the European Center for Disease Control (ECDC) Resistance to other important treatment options for MRSA,
observed a decline among eight countries in Europe as well. such as linezolid and daptomycin, are uncommon but important
HA-MRSA clones (generally SCCmtC types I-III) often carry if identified. Prevalence of linezolid resistance among S. aUfliUS
genes that confer broad resistance to aminoglycosides, macro- is estimated at <0.14% (2002 to 2010 surveillance in the United
tides, lincosamides (such as clindamycin), and tetracyclines, States and worldwide) (272), although it is notable that line-
in addition to ,8-lactam resistance (260)o CA-MRSA strains zolid-resistant S. aufliUS has been involved in clonal outbreaks
are generally more susceptible to non-,8-lactam antibiotics, al- within and across healthcare facilities (272,273) . Daptomycin
though in certain regions, non-,8-lactam resistance appears to resistance has been reported sporadically, with case reports
be increasing (261)0 demonstrating the in vivo emergence of resistance during un-
Because vancomycin has been the key first-line therapy for successful treatment of MRSA (274,275). There appears to be
MRSA, trends in vancomycin resistance have been monitored some correlation between vancomycin and daptomycin non-
closely. In 2006, the Clinical and Laboratory Standards Institute susceptibility among So au1!l'US, suggesting a common resistance
(CLSI) established new MIC breakpoints for defining vancomy- mechanism through thickened cell walls (276), although other
cin susceptibility to better predict clinical response to therapy: resistance mechanisms that affect the actual daptomycin target
vancomycin susceptible, :S 2 mcg/mL; vancomycin intermediate of So aufliUS (i.e., cell membrane) are important as well (277).
(VISA), 4 to 8 mcg/mL; vancomycin resistant (VRSA) ~ 16 meg/ The main hospital reservoir of resistant So au1!l'US, like that
mL (262). Nearly all vancomycin-intermediate resistantS. aufliUS of susceptible strains, is the anterior nares of patients (278).
(VISA) and VRSA strains reported have expressed multidrug re- Extra-nasal sites can be colonized, including open skin wounds,
sistance, including resistance to methicillin (263). throat, lower gastrointestinal tract, perineal/inguinal region,
To date, VRSA has been rare (around 13 known clinical and axillae (279,280). In addition, the inanimate hospital en-
isolates worldwide (263)) and self-limited, with no known vironment (high touch areas, as well as medical equipment
patient-to-patient spread. For unclear reasons, a majority of such as blood pressure cuffs) is a major reservoir (204) . Health-
VRSA isolates from the United States have been isolated from care workers who contact either MRSA-colonized patients or
a single state, Michigan (264). In a detailed review of seven their contaminated environment may carry MRSA transiently
known patients with VRSA from 2000 to 2006 in the United on their hands or equipment, acting as a vector for patient-to-
States, all patients with VRSA had characteristics in common, patient spread (281).
including chronic underlying conditions, history of MRSA and The optimal strategy to control of resistant S. aUfliUS in
VRE infection or colonization, and prior vancomycin exposure hospitals continues to be debated (281). Control strategies
(265). Vancomycin resistance in S. aureus is believed to have have generally focused on either global interventions (such
emerged independently on multiple occasions from horizontal as hand hygiene programs, improved environmental clean-
transmission of the vanA gene from VRE (266). ing, enhanced patient bathing with chlorhexidine, bundled
Intermediate resistance to vancomycin in S. aureus occurs interventions to reduce HAls) or targeted interventions (ac-
through the synthesis of an unusually thickened cell wall that tive surveillance testing for MRSA with contact precautions,
decolonization of MRSA-colonized patient!!) (206). In partic- E.faecium (298). Sporadic reports of resistance to quinupristin-
ular, the role of active surveillance testing for the control of dalfopristin, linezolid or daptomycin, often the only drugs
MRSA is controversial. The rationale for active surveillance test- available to treat VRE, emerged soon after release of each anti-
ing is to identify all patients (symptomatic or asymptomatic) biotic (299-302). Healthcare-associated outbreaks of linezolid-
who are carriers of MRSA: identifying these patients allows resistant enterococci have been reported (303,304). The
for enhanced controls (such as contact precautions) or op- prospect of untreatable enterococcal infection in the future
portunities for decolonization (which may both decrease risk remains.
of transmission and decrease risk of subsequent MRSA infec- Antimicrobial pressure is an important risk factor for patient
tion) (282). Studies that have investigated active surveillance acquisition of VRE in the hospital. Antecedent use of cepha-
testing have had different methodologic approaches and have losporins, as well as antimicrobials with anti-anaerobic effects,
had conflicting results. Some studies have shown a reduction have been associated consistently with colonization with VRE
in MRSA infection (283-285) while others have not (213,286), (69,72). These data suggest a model in which antimicrobials
although the studies are difficult to compare because of differ- that are active against endogenous gut flora but inactive against
ences in the interventions themselves, study design, and patient enterococci promote enterococcal colonization and high level
population. It is our opinion that, except for MRSA outbreaks, of shedding in the stool (69, 70). In contrast, prior exposure to
"global" or "horizontal" strategies for IC that affect all poten- vancomycin itself does not appear to be a strong risk factor for
tial pathogens (and not just MRSA) are more beneficial, given acquisition of VRE in settings where these strains are already
constraints on IC resources, although no randomized trial has prevalent (72).
assessed this approach and there are very limited data (before/ In hospitals, VRE usually spread by horizontal transmission
after studies) documenting the efficacy of this approach (205). of resistant clones on the contaminated hands of healthcare
workers; transfer of plasmids or other genetic element!! plays a
lesser role (124,305). The number of colonized patients usually
ENTEROCOCCUS SPP.
is far greater than the number of those who are infected; this
Since the mid-1980s, enterococci have emerged as significant "iceberg effect" (Figure 15.2) also plays an important part in the
HAl pathogens, becoming the second most frequent cause dissemination of these pathogens in healthcare settings (305).
of BSI in the United States (258). Two species, E. Jaecalis and Strategies for control of epidemic and endemic MDR
E. faecium, account for the vast majority of enterococcal in- enterococci, in particular VRE, are based on several observa-
fections. Enterococci are not highly virulent organisms. They tions. First, enterococci survive easily on intact patient skin,
cause infections primarily in debilitated or immunocompro- environmental surfaces and on hands and clothing of health-
mised patients, for whom they are associated with significant care workers, providing ample opportunity for horizontal
attributable morbidity, mortality, and increased length of hos- transmission (86,112,117,306). In epidemic settings, proximity
pital stay (69,287-289). to an index patient has been shown to be an important factor
Enterococci are intrinsically resistant to all cephalosporins, in the acquisition of resistant enterococci; in endemic settings,
penicillinase-resistant penicillins, and clindamycin. The rise "colonization pressure," or the proportion of VRE-colonized
in incidence of enterococci since the 1970s is temporally cor- patients, when high, is the most important variable influenc-
related with increased use of antimicrobials with little or no ing acquisition ofVRE (188,307) . Second, in the United States,
anti-enterococcal activity, particularly cephalosporins (69). Am- patients in acute care hospitals or residing in long-term care
picillin, the preferred therapy for enterococcal infections, can facilities constitute the most important reservoir for resistant
be rendered ineffective in the face of a low-affinity penicillin- enterococci (308). In Europe, community colonization with
binding protein, PBP-5 (290). Alterations or overproduction of VRE is common, and probably related to widespread use of the
this protein are responsible for high-level ampicillin resistance glycopeptide avoparcin in animal farming during the last de-
in E. faecium (291). Rarely, ampicillin resistance is attributable cades of the 20th century (309). The epidemic strains causing
to ,8-Iactamase production (292). infection in European hospitals appear to be more pathogenic
The spread of vancomycin resistance among enterococci re- than non-epidemic community strains, however, and may be
mains a concem. Such resistance was not described until the differentiated from them by detection of the variant esp gene,
late 1980s (293), and approached rates as high as 29% of all en- a virulence factor (156). Third, antibiotic exposure may influ-
terococcal infection in the United States in 2003 (294). More ence the epidemiology ofVRE in at least two ways: by elevating
recent prevalence estimates suggest a decline in vancomycin a VRE-negative patient's risk of acquiring VRE, and by increas-
resistance in the United States (20% in 2006 to 2007) and in ing the density of VRE in the stool of VRE-positive patient!!,
Europe (7.4% in 2010) (258,259). Vancomycin resistance is as- thereby raising the odds of skin or environmental contamina-
sociated primarily with V(.mA or vanB gene clusters, which are tion and facilitating cross-transmission (73,310). Finally, estab-
complex genetic elements frequently found on transferrable lishment ofVRE endemicity, a situation faced by many hospitals
plasmids (295). Vancomycin resistance has never been demon- in the United States often follows a predictable course from
strated to develop as a de novo mutation under antimicrobial detection of rare and sporadic cases, to monoclonal outbreak,
pressure (296); therefore, the first step toward colonization or to polyclonal endemicity (305). As is the case for antimicrobial
infection with VRE must be exposure to a resistant enterococ- resistance in general, control of VRE is substantially easier if
cal strain. Most VRE are E. faecium:, in this species, vanB resis- implemented in the earlier stages than in the later ones.
tance has sometimes been found linked to high-level ampicillin Approaches to control of VRE should highlight contact iso-
resistance on a large mobile genetic element (297). lation for known cases and hospital hygiene (221,311-313).
Resistance to aminoglycosides, which are used for synergy in Active surveillance testing to detect VRE colonization may
treating serious enterococcal infections, ranges in the United enhance control efforts in both epidemic and endemic situ-
States from 30% to 60% and more often is associated with ations (179,311,314,315), and might be warranted especially
in healthcare settings comprising patients at high risk for se- Fluoroquinolone resistance among Enterobacteriaceae
rious enterococcal infection, such as transplant, oncology, or has increased significantly since its use began in the 1980s.
ICUs. & with MRSA, accurate and sensitive laboratory iden- Data from England and Wales reflecting hospital bacteremias
tification and recognition of previously colonized patients at showed that from 1990 to1999, ciprofloxacin resistance rates
readmission are important (316). In a mathematical model, for Enterobacter spp. and Klebsiella spp. rose from 2.1% and
staff cohorting was shown to be very effective in reducing VRE 3.5%, to 10.9% and 7.1 %, respectively (55). In the United
transmission, even with moderate levels of compliance, but this States, the rate of fluoroquinolone resistance among E. coli was
strategy has not been tested in a clinical setting (157). Cohort- reported as 7.3% across ICUs from 1992 to 2004 (294), while in
ing was a component of a successful multifaceted program to 2006 to 2007, the rate was estimated at 22.7% (258) . Increasing
control a large outbreak of esp-positive VRE in a hospital in trends have been seen for the most common Enterobacteria-
the Netherlands (315). In another study, bathing patients in ceae, particularly in HAis (320). Multiple chromosomal point
an ICU daily with 2% chlorhexidine-impregnated cloths low- mutations affecting topoisomerase targets as well as cell wall
ered VRE acquisition nearly three-fold (RR, 0.4), an effect permeability and effiux contribute to the resistance phenotype
similar to the reduction reported in a study of enhanced IC (321). Alarmingly, plasmid-mediated fluoroquinolone resis-
measures that used at least seven interventions in an oncology tance, which was first identified in 1998, has now been found
unit (233,317). No antibiotic regimen has yet proven useful for worldwide (40,322). Increases in fluoroquinolone resistance
intestinal decolonization. have been epidemiologically linked to other resistance genes,
particularly those encoding ESBLs (40).
The major driving force of the evolution of cephalospo-
ENTEROBACTERIACEAE
rin and carbapenem resistance among Enterobacteriaceae
The Enterobacteriaceae comprise a large group of aerobic, has been the rise and dissemination of .8-lactamases (323).
Gram-negative bacteria that frequently cause clinically signifi- .8-lactamases inactivate some or all of ft-lactam antibiotics,
cant infection in hospital patients. In this group, E. col~ Klebsiella broadly circumventing an array of first-line antibiotics for
spp., and Enterobacterspp. have particular epidemiologic impor- treating serious gram-negative infections. Over 1,000 natu-
tance by virtue of their tendency to develop broad antibiotic rally occurring .8-lactamases exist, and their spread has been
resistance. Other Enterobacteriaceae that may develop MDR facilitated by their movement on mobile genetic elements
phenotypes include Serratia marr:escens, Citrobacter spp., Proteus as well as pairings with extraordinarily successful bacterial
spp., Providencia spp., and Morganella spp. clones. Currently, the most dominant ft-lactamases worldwide
Antibiotic resistance in Enterobacteriaceae has accelerated are extended-spectrum .8-lactamases, or ESBL, enzymes (par-
over the past two decades. Although a multitude of resistance ticularly CTX-M-14 and CTX-M-15), AmpC cephalosporinases
pathways exist for gram-negative organisms (including amino- (CMY family), serine carbapenemases (KPC enzymes), and
glycoside, tetracycline, trimethoprim/sulfamethoxazole, and metallo-.8-lactamases (NDM-1, VIM, and IMP) (Table 15.6).
polymyxin) (318), this discussion on Enterobacteriaceae will We will discuss .8-lactamases as they relate to specific resis-
focus on the resistance to fluoroquinolones, cephalosporins, tance phenotypes.
and carbapenems, because these antibiotics are considered key Resistance to extended-spectrum cephalosporins among
first-line choices for serious gram-negative infections, and their Enterobacteriaceae usually is conferred by ESBLs. Although
presence usually is associated with multiple resistance to other there is no consensus on a precise definition of ESBLs, a com-
antibiotics. The mechanisms of resistance currently seen have monly used definition is a .8-lactamase that confers bacterial
converged to the development of pan-resistance, which already resistance via hydrolysis of penicillins, first-, second-, and third-
has been recognized among some Enterobacteriaceae (319). generation cephalosporins, and aztreonam (but not cephamycins
Such a development is of great concern because the genetic or carbapenems), and is inhibited by .8-lactamase inhibitors such
elements (plasmids and integrons) that confer broad resistance as clavulanic acid (42) . ESBLs have been identified primarily in
are often mobile and easily transferred from one gram-negative E. coli and Klebsiella spp., but are found in many other enterobac-
species to another, making their recognition and control teria such as Enterohacter, Serratia, Citrobacter, and Proteus. Resis-
difficult (139). tance to third-generation cephalosporins serves as a phenotypic
Clinically Important P-lactamases in Enterobacteriaceae

Enzyme Families AmblerClau Selected Enzymes Remarb
AmpC cephalosporinases c CMY Less common than ESBLs. Certain bacteria (e.g., Enttfrobactnspp.)
naturally carry inducible chromosomal AmpC. Hyperproducing
AmpC clones are well described. Abo, plasmid-mediated AmpC
have expanded rapidly since first description in 1989.
ESBL A,D crx The CTX-M-15 clone (found primarily in E . colJ) has expanded
worldwide since 2000, found in both the hospital and community
environment
Serine carbapenemases A KPC KPC emerged from northeast United States in late 1990s and now i.s
spreading worldwide as the dominant carbapenemase.
Metallo-,8-lactamases B NDM-1, VIM, IMP Outbreaks of VIM- and IMP-producing Enterobacteriaceae are
reported regionally. NDM-1 has quicldy spread worldwide from
South Asia and i.s associated with pan-resistance.
Chapter 15 • Multidrug-Resistant ~nisms: Epidemiology and Control 197
marker for ESBL presence among K coli and Klthsiella spp. In the Metallo-ft-lactamases are carbapenemases that historically
United States, from 2006 to 2007, third-generation cephalospo- have been represented by VIM (Verona integron-encoded
rin resistance was found in 5% ofhospital-acquired E. coli strains MBLs) and IMP (active on imipenem) family enzymes and
and 14.8% of K Jmeumtmiae (258). In Europe, third-generation primarily identified in HAl K . pneumoniae or P. aerugirwsa
cephalosporin resistance for E. coli ranged from 1.8% to 19.2%, (209). However, a new metallo-,8-lactamase identified in
with 9 of 28 countries reporting > 10% resistance, while resis- 2008, called NDM-1, has threaten ed to become the domi-
tance in K pneumtmiaeranged from 0% to 69.5%, with 20 coun- nant carbapenemase in the world (44). Plasmids carrying
tries reporting >10% resistance (259). ESBL resistance appears the blaNDM-l gene are diverse and carry an extraordinarily
to be rapidly increasing worldwide (323). high number of concomitant resistance genes, including r~
The epidemiology of infections due to ESBL-producing spe- sistance to other ft-lactams (other carbapenemases, cephalo-
cies continues to evolve. From the first report ofESBLs in 1983 sporinases, ESBLs), aminoglycosides, macrolides, rifampin,
(324) until roughly 2000, the m~ority of ESBLs belonged to and sulfamethoxazole (37). Most NDM-1 Enterobacteriaceae
the TEM and SHV families, which primarily were identified in are only susceptible to a few remaining antibiotics such as
patients with prior healthcare exposure. Since 2000, the TEM tigecycline and colistin. In contrast to other carbapenemase
and SHV family ESBLs have been displaced by the CTX-M enzymes that are usually associated with a single clone, the
family, invading into human, animal, and environmental res- NDM-1 carbapenemase has easily spread among non-clonally
ervoirs around the world (36). In particular, ESBL-producing related species and genera, primarily E. coli and K. pneur
Enterobacteriaceae, primarily E. coli strains cal1)'ing a CTX-M muniae. E. coli is ubiquitous in human, animal, and environ-
genotype, have been described in community settings in pa- mental reservoirs, and is a major community-acquired human
tients without prior hospital contact (325,326). CTX-M En- pathogen; its ability to disseminate NDM-1 worldwide (as it
terobacteriaceae now represent the most prevalent ESBLs in has for CTX-M) is worrisome.
global surveillance, and present challenges for both hospital Laboratory detection offt-lactamases is challenging because
and community IC. strains producing these enzymes can appear falsely susceptible
Although not as widespread as ESBLs, A.mpC ,8-lactamases in routine testing. This problem has been addressed in part
play a significant role in multidrug resistance among Entero- by lowering breakpoints for third-generation cephalosporins
bacteriaceae (32). A.mpC ,8-lactamases inactivate penicillins, and carbapenems in order to improve sensitivity of detection of
first-, second-, and third-generation cephalosporins, and (vari- ESBLs and carbapenemases (~34). The presence of an ESBL,
ably) aztreonam. Many Enterobacteriaceae, notably Entm:r AmpC, or a carbapenemase can be confirmed in some genera
bacter spp., Citrobacw spp., Serratia spp., Providencia spp., and of Enterobacteriaceae by performing one or a combination of
Morganella spp., carry intrinsic chromosomal AmpC enzymes phenotypic tests (336). Definitive identification offt-lactamases
that are derepressed in the setting of ft-lactam treatment. can be done only by molecular assays that detect multiple ge-
Of concern are Enterobacteriaceae that develop mutations netic targets or by DNA sequence analysis. While commercial
leading to stable hyperproduction of A.mpq these clones can assays are under development (335), most hospital clinical mi-
spread from person-to-person and become endemic (327). crobiology laboratories do not offer such testing. Recommen-
AmpC enzymes that have mobilized onto plasmids have been dations for laboratory detection of ESBLs and carbapenemases
well~escribed and are found worldwide. In the United States, have been published (37,42,~~) (see Chapter 11).
in 2007, stably derepressed .AmpGmediated third-generation Resistant Enterobacteriaceae commonly colonize the gastro-
cephalosporin resistance rates among Citrobacter and Enterobav intestinal, urinary, and respiratory tracts; chronically colonized
wspp. were estimated at 18.8% and 21.2%, respectively (328). patients often are a source fur large numbers of cross-infections
As carbapenem use increased in response to ESBL and AmpC (337,123). In hospitalized patients, skin colonization (particu-
resistance among Enterobacteriaceae, carbapenem resistance has larly the inguinal skin) appears to be a common location of
emerged as a threat against these antibiotics of "last resort." In colonization by Enterobacteriaceae and may facilitate patient-
the United States, meropenem resistance among K Jmeumtmiae to-patient spread via healthcare worker hands (338,339) . Some
increased from 0.6% in 2004 to 5.6% in 2008 (329). In Europe in Enterobacteriaceae, such as Serratiaspp., survive well in the wet
2010, 8% of K pneumoniaewere carbapenem resistant, although inanimate environment. There have been several outbreaks d~
striking rates of resistance were identified in Greece (49.1% of K scribed in which devices or equipment contaminated with resis-
pneumoniae isolates resistant), Cyprus (16.4%), and Italy (15.2%) tant S. man:escens, notably ventilators and graduated cylinders
(259). Carbapenem resistance is mediated primarily through two used to measure urine, led to epidemics of UTI, peritonitis, or
classes of ,8-lactamases: serine carbapenemases (such as KPC) and pneumonia (123). Such evidence suggests that contact precau-
metallo-ft-lactamases (such as NDM-1). Both the mechanism of tions and environmental decontamination are important for
action and epidemiology differ between these carbapenemase epidemic control.
types. The optimal means fur control of resistant Enterobacteria-
KPC was identified first in the United States in 2001 (330). ceae depend on which bacterial genus and mechanism of resis-
Subsequently, KPC became epidemic in the northeast United tance are involved. Clonal outbreaks, such as KPC-producing
States, Israel, and Greece, and have now spread globally (37). K pneumuniae, may be best controlled through interruption
Most KPC have been reported from HAl K pneumuniae iso- of patient-to-patient spread using contact precautions, hand
lates, primarily a single clone (multilocus sequence type [ST]- hygiene, and possibly active surveillance testing or patient
258) (331), although other Enterobacteriaceae like E. coli can skin decontamination with chlorhexidine bathing (340,341).
produce KPC. Enterobacteriaceae-producing KPC are usually Hyperproduction of chromosomal AmpC ,8-lactamase, such as
resistant to other antimicrobials such as fluoroquinolones is seen in E. cloacae, probably is best controlled by reducing
and aminoglycosides (332). Some KPC-producing strains are selective pressure by cephalosporins. In general, IC person-
resistant to all antibiotics tested (333). nel should work closely with the microbiology laboratory in
identifying MDR Enterobacteriaceae. If an outbreak is occur- thus far suggest more geographically limited rather than world-
ring, active surveillance testing may be helpful in identifying wide spread (347,348).
patients carrying resistant Enterobacteriaceae, since clinical Prevalence of multidrug resistance in P aeruginosa (defined
cultures alone identify only a minority of colonized patients as resistant to 2:3 antimicrobial classes) is estimated at 10% in
(342). For carbapenem-resistant Enterobacteriaceae, bundled the United States (349,350) and 15% in Europe (259). These
IC interventions (341) and coordinated public health surveil- population-averaged data do not capture the high burden of
lance (180) have reduced prevalence rates. resistance seen regionally (e.g., four countries in Europe had
an estimated 25% to 50% multidrug resistance rate among
P aeruginosa (259)) or locally in individual ICUs, bum, or CF
PSEUDOMONAS .AER.UGINOSA
units.
P aemginosa is a glucose non-fermenting Gram-negative rod Within the hospital environment, P aeruginosa is ubiquitous
with intrinsic antibiotic resistance that causes infection among in animate and inanimate reservoirs (351). It can be cultured
hospitalized patients. Its ability to survive in diverse environ- from almost any wet surface including water faucets (352, 353) ,
mental sources and to colonize the animate and inanimate patient-related equipment (354) , and containers of fluid such
reservoirs of hospitals makes it a difficult organism to control. as distilled water (355) and dialysate (356). Furthermore, pa-
P aeruginosa has shown the ability to acquire resistance to all tient gastrointestinal colonization serves as an important reser-
traditionally effective agents, such as anti-pseudomonal penicil- voir for endogenous infection, as well as a source of horizontal
lins, third- and fourth-generation cephalosporins, aminoglyco- transmission to other patients (357). While epidemics are well-
sides, fluoroquinolones, and carbapenems. described secondary to contaminated environmental sources,
Although all gram-negative bacteria possess an outer mem- the dynamics between the endogenous and exogenous reser-
brane that acts as a semipermeable barrier to antibiotics, the voirs that contribute to endemic colonization and infection in
outer membrane of P aeruginosa is particularly impermeable the hospital setting are less clear. Recent evidence suggests that
(only 8% as permeable as that of E. colt), creating natural an- periods of endemicity, characterized by polyclonal infection,
tibiotic resistance (343). P aeruginosa survives by managing are promoted by patients who are subclinically colonized on ad-
influx and efflux of vital molecules via water-filled channels mission. In these patients, exposure to antimicrobial pressure
called porins. Antibiotics, such as P.lactams, aminoglycosides, then becomes a risk factor for overt colonization and eventual
tetracyclines, and fluoroquinolones, cross the outer membrane clinical infection. While some studies suggest gastrointestinal
via porin channels; loss of specific porin channels (such as and respiratory colonization to be the most important source
porin Opr!J) can lead to decreased susceptibility to antibiotics for endemic HAl (358), other studies suggest important contri-
such as carbapenems. bution from environmental sources (359,360). Control ofMDR
Other chromosomally mediated resistance elements are P aeruginosa u1timately requires a multifaceted approach, with
important. The outer membrane of P aeruginosa contains mu1- hospital hygiene to prevent horizontal transmission from exog-
tiple efflux pumps, including ~DprM and MexXY-DprM, enous sources, and control of antimicrobial pressure to prevent
that remove a heterogeneous group of molecu1es including endogenous infection (351).
antimicrobials from its intracellular space. Upregulation of
efflux pumps can confer resistance to P.lactams, fluoroqui-
ACINETOBACTER SPP.
nolones, meropenem, and aminoglycosides (31). Further-
more, P aeruginosa carries an inducible chromosomal AmpC Acinetobacter spp. comprise at least 17 named species, including
cephalosporinase (similar to that found in some Enterobac- the highly resistant A. haumannii. Because individual Acinett>-
teriaceae) that does not cause clinically significant resistance bacter spp. are difficult to differentiate phenotypically, com-
at low levels of production seen in wild-type P aeruginosa, but monly clinically encountered species are sometimes grouped as
if derepressed through mutations, can lead to resistance to all A. calcoaceticus-A. baumannii complex (361) . Acinetobacter spp.
anti-pseudomonal ,S.lactams (including cefepime, but exclud- have emerged as important HAl pathogens, particularly among
ing carbapenems) (31). Pan-aminoglycoside resistance occurs patients with impaired host defenses, and can be resistant to
via aminoglycoside-modifying enzymes coupled with increased many or all available antibiotics. Multidrug resistance among
efflux and decreased membrane permeability (344). F1uoroqui- A. baumannii (defined as resistance to 2:3 drug classes) is com-
nolone resistance is mediated by mutations of fluoroquinolone mon, estimated at 60% among US HAl isolates (350).
targets, DNA topoisomerase IV (gyrA and gyrB), and DNA gy- A variety of resistance mechanisms, of which P.Iactamases
rase (parCand parE) (31). Sequential acquisition of mutations are the most prevalent, have been described among Acinetohacter
is facilitated by a subset of P aeruginosa "hypermutators" (345) , spp. (361). Chromosomally encoded AmpC ,S.lactamase, al-
well-described in cystic fibrosis (CF) patients, though perhaps though not inducible like that of some Enterobacteriaceae, can
more rare in ICU patients (346), that have the propensity to be upregulated by an upstream insertion sequence, ISAbal,
develop genetic changes such that virtual pan-resistance can oc- leading to clinically relevant resistance to cephalosporins
cur with a small group of mutations, such as increased efflux, (except cefepime) (362). ESBLs are common among Acinett>-
loss of OprD, and aminoglycoside impermeability. bacter spp., although their impact is unclear. More concern-
Transferrable resistance also provides an important path- ing is emerging carbapenem resistance, mediated by serine
way for P aeruginosa resistance with respect to P.Iactam and carbapenemases (OXA) and metallo-,S.lactamases (IMP,VIM),
aminoglycoside resistance. Though less widespread compared commonly found on transmissible genetic elements (363) .
to that of Enterobacteriaceae, a variety of plasmid-encoded Other resistance mechanisms are important. Porin changes
P.Iactamases have been well-described, particularly metallo-P. commonly affect ,S.lactams, and are associated with carbape-
lactamases (IMP,VIM) (327). P aeruginosa also appears to be nem resistance. Mu1ti-drug efflux pumps remove quino-
capable of disseminating KPC across clone types, although data lones, tetracyclines, disinfectants, and tigecycline from the
periplasmic space. HAl strains may develop fluoroquinolone appear de novo during therapy and appears unrelated to vanA-
resistance via modifications to DNA gyrase or topoisomerase IV, or vanB-mediated vancomycin resistance seen in VRE.
and aminoglycoside resistance via aminoglycoside-modifying High levels of patient colonization with methicillin-resistant
enzymes (364). coagulase-negative staphylococci in the hospital have rendered
In the hospital, Acinetobacter spp. are a common cause of control measures ineffective. Resistant coagulase-negative
ventilator-associated pneumonia (VAP; in the US, ranked third staphylococci are present in low numbers on the skin of pa-
among all pathogens, representing 8.4% of all VAPs), as well tients and emerge in the hospital as predominant flora and
as healthcare-associated BSis, UTis, and surgical site infections potential pathogens, especially under antimicrobial selection
(258). Risk factors for Acinetobacter spp. infection include ICU (376,377). Prevention of infection associated with catheter and
stay, recent surgery, invasive devices (including mechanical ven- prosthetic devices by adhering to aseptic strategies remains im-
tilation and intravascular catheters), and treatment with broad- portant. Colonized surgeons have been implicated as sources
spectrum antibiotics such as cephalosporins, fluoroquinolones, of staphylococcal postoperative infections, suggesting the need
or carbapenems (365). to consider this mode of transmission when postoperative in-
The ability of Acinetobacter spp. to survive on dry, inanimate fection rates exceed expected norms (94) .
surfaces for long periods of time (89,366) suggests that the
hospital environment serves as a reservoir for MDR strains.
COR.TNBBA.CI'ERIUM]BIKBIUM
Although several Acinetobacter spp. are common constituents
of healthy human skin flora, A. baumannii is rarely found ex- Corynebacterium jeikeium, in contrast to other Corynebacterium
cept on the skin of hospital patients during outbreaks, and spp., is notable for its intrinsic resistance to a wide variety of
transiently on the hands or other skin of healthcare workers antimicrobials, including ,8-lactams, aminoglycosides, macro-
working in these settings (366,367). It is likely that animate and lides, tetracycline, and fluoroquinolones; vancomycin most of-
inanimate vectors have led to numerous hospital outbreaks, ten is used for treatment (378). C. jeikeium is a cause of HAl,
which are usually clonal or oligoclonal in nature (368). Re- particularly among patients with malignancies, neutropenia,
gional inter-hospital spread ofMDR Acinetobacterspp. has been intravenous catheters, or who are exposed to broad-spectrum
reported (369). antimicrobials (379).
Knowledge of control interventions for MDR Acinetobacter Like most diphtheroids, C. jeikeium commonly colonizes
spp. has been derived primarily from outbreak experiences, the skin of hospitalized patients, and its prevalence is corre-
and is reviewed elsewhere (365,370). Commonly employed lated with degree of hospital exposure (380-382). Further-
strategies include identifying and eliminating common sources more, C. jeikeium colonization may be related to testosterone
of contamination (e.g., contaminated respiratory equipment), levels (which affect the amount of sebum in the skin that may
optimizing contact isolation and hand hygiene to minimize promote Corynebacterium growth), as post-pubescent males
cross-transmission, enhancing environmental cleaning to re- and post-menopausal females appear to be at higher risk of
duce contamination, and reducing broad-spectrum antibiotic C. jeikeium colonization (381). C. jeikeium is endemic in hos-
use. In general, control is most successful when a common pitals, and different strains likely are transferred horizontally
source of contamination is identified and eliminated. Aggres- between patients (383). Control of endemic infection with
sive control, if instituted early in an epidemic, can prevent C. jeikeium, like control of coagulase-negative staphylococci, de-
the establishment of MDR Acinetobacter spp. as an endemic pends in large part on good aseptic technique to prevent peri-
pathogen. operative or device-related infections.
COAGULASE-NEGATIVE STAPHYWCOCCI STENOTR.OPHOMONAS MALTOPHILIA

MDR coagulase-negative staphylococci have become endemic S. maltopkilia is a MDRO that causes a variety of infections,
in hospitals across the world. Greater than 70% of all coagulase- particularly pneumonia and bacteremia, in immunocompro-
negative staphylococci isolates are resistant to methicillin (371). mised and critically ill patients (384). It is ubiquitous in the
Furthermore, despite their relative avirulence, coagulase-negative environment, found in water, soil, and plants. In the hospital,
staphylococci are routinely one of the most common causes of S. maltophilia has been isolated from a variety of aqueous reser-
BSis in the hospital, especially in patients with central venous voirs and equipment, including tap water (385), chlorhexidine
catheters (258). Coagulase-negative staphylococci infections disinfectant diluted with contaminated deionized water (386),
often are associated with prosthetic implanted devices such as and components of mechanical ventilators (387) .
joints, heart valves, and neurosurgical shunts (372); the rising S. maltopkilia intrinsically carry multiple mechanisms for
use of such therapies portends a continued burden of coagulase- broad antimicrobial resistance, including multidrug efflux
negative staphylococcal infection. pumps, a relatively impermeable outer membrane with se-
Glycopeptide resistance has been noted sporadically in lective membrane porins, and ,8-lactamases (including an
Staphylococcus haemolyticus and Staphylococcus epidermidis. In inducible ESBL and metallo-carbapenemase), that provide
Europe, where the glycopeptide teicoplanin is used, teico- protection against extended-spectrum penicillins, cephalo-
planin resistance across intermediate and highly resistant sporins, aminoglycosides, carbapenems, and fluoroquinolones
ranges has been detected (373). Over the same period of time, (388,389). S. maltophilia is not known to carry significant muta-
however, vancomycin has remained effective, with only spo- tions in topoisomerases, and quinolone resistance is mediated
radic episodes of resistance described (374). The mechanisms through effiux (390); later-generation quinolones such as levo-
of vancomycin resistance in coagulase-negative staphylococci floxacin and moxifloxacin may be effective (391).
remain ill-defined, but are probably related to cell wall changes Trimethoprim-sulfamethoxazole remains the first choice
similar to that employed by VISA (375). This mechanism can in treatment, based on in vitro susceptibility testing and
clinical experience. Overall, resistance to trimethoprim- the community reservoirs, expanding mobility of people (and
sulfamethoxazole remains low (4.7%) (392), although higher thus their hitchhiking microbes) across the world, and sicker
rates of resistance have been described locally (e.g., 26% re- patients in hospitals as medical science pushes the boundaries
sistance in one Spanish hospital (393)) as well as in specific of human longevity and immunosuppression.
patient groups (e.g., 86% resistance among CF patients (394)). Our ability to outsmart bacterial pathogens requires better
Resistance to ticarcillin-clavulanate, which is used as second- understanding of normal and pathologic bacterial ecology in hu-
line therapy, is estimated at 44% (392). mans, in the natural environment, and on inanimate o~ects such
Most S. maltophilia recovered from hospitalized patients as medical devices. In the 17th century, Antonie van Leeuwen-
probably represent importation from outside the hospital, hoek, known as the "Father of Microbiology," pioneered use of
given the high genetic diversity of HAl strains, although small the microscope to describe microorganisms. In the 21st century,
clusters of hospital transmission clearly occur ( 395,396). Con- our understanding of bacterial ecology has taken a quantum leap
trol of S. maltophilia, like other ubiquitous environmental or- through the use ofadvanced genomic sequencing, effectively serv-
ganisms, rests primarily on identifying common sources during ing as a new "microscope" to view the entire microbiome, includ-
epidemics and maintaining optimal hospital hygiene. ing cultivatable and non-cultivatable organisms, in places such
as the human gastrointestinal tract, skin, and wounds (410,411).
The study of biofilms has also deepened our understanding of
BURKHOLDERIA CEPAClA
how bacteria form communities and communicate with each
B. cepacia is widely distributed in the environment; it is particu- other (412). Furthermore, genome sequencing is enabling epi-
larly suited to growing in liquid reservoirs and on moist sur- demiologists to more confidently track the complex movement
faces (397,398). Outbreaks have been traced to nutritionally of individual bacterial strains or mobile genetic elements in the
deficient and biologically hostile sources including tap water; hospital setting (413).
deionized water; intrinsically and extrinsically contaminated New technology undoubtedly will be important to compen-
dilute, aqueous benzalkonium chloride; povidone-iodine; sate for human imperfections with respect to IC adherence.
and nebulized solution in respiratory equipment (399). Com- Health information exchanges can facilitate regional surveil-
munity- and hospital-acquired B. cepacia infections have been lance of important microbes, as well as improve inter-institution
well-described in CF patients, in whom both colonization and communication of IC needs as patients move across the spec-
infection are associated with increased mortality (400). Health- trum of healthcare fucilities (414). IC software can provide
care-associated transmission of B. cepacia between CF patients better recognition of outbreaks, streamline routine HAl surveil-
has been documented through person-to-person contact (401) , lance, and potentially monitor and motivate healthcare worker
as well as via shared respiratory equipment (402) . Besides in- adherence with hand hygiene (192,415,185,416-417).
fecting CF patients, B. cepacia is an opportunist, causing respira- The global public health crisis posed by pathogens such as
tory infections, UTis, and BSis in critically ill patients. carbapenem-resistant Enterobacteriaceae, which has quickly
B. cepacia is intrinsically resistant to aminoglycosides, anti- spread in the community, across continents, and through
pseudomonal penicillins, and polymyxins (403). Much of the healthcare facilities of all different types (acute and long-term
intrinsic resistance may be attributed to decreased outer memcare facilities) has highlighted a new challenge for the IC
brane permeability (404), presence of efflux pumps (405), community-learning how to coordinate control efforts on a
and an inducible chromosomal ,8-Iactamase (406). nime- regional or even worldwide scale (178,418). Recent history has
thoprim-sulfamethoxazole is the most active antibiotic (91% taught us that MDROs can be spawned in any part of the world,
susceptibility worldwide), followed bymeropenem (82%), and and that our interdependent efforts to control resistance and
ceftazidime (81 %) (392). preserve antibiotics are only as successful as the weakest link.
Control of B. cepacia epidemics usually involves identifY- IC of MDROs has firmly moved from the local confines of the
ing a common source, if one is present (399). Cohorting of hospital to the stage of global public health.
colonized patients and contact precautions may prevent hori-
zontal spread ( 407), although this strategy has been studied
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16 Gopi Patel and Robert A. Bonomo
Molecular Biology of Resistance: A Brief

History of Resistance Mechanisnts and
the Discovery of Gene Transfer
The w:i.deapread availability of penicillin in the 19408 is credited was reported. Integrons are mobile genetic elements contain-
with the survival of many wounded soldiers in World War :0:. ing antibiotic-resistance genes aa well as a site-specific recom-
This feat marked the beginning of the antibiotic era. During bination sy5tem capable of inserting these genes into plasmid
the next several decades, robust antimicrobial development or chromosomal DNA (10,11). In the late 1990s emerged the
provided the opportunity to safely and effectively treat a variety description of the staphylococcal chromosomal cassette (sec),
of pathogens. Along with every new antimicrobial agent came responsible for housing and transferring the genes associated
the inevitable development of resistance. With the increasing with methicillin resistance in S. aumu (methicillin-resistant
number of novel and potent antimicrobials being developed, StDphjlococcus aunm.s; MRSA) (12). More recently, an 86 kb
sporadic antimicrobial resistance rerulting from random spon- "resistance island" capable of accommodating a large number
taneous mutations was not initially considered a serious threat. of antimicrobial and heavy metal resistance determinants bas
The description ofpenicillinases (enzymes capable of destroy- been described in an epidemic multidrug-resistant strain of
ing penicillin) in Escherichi4 coli (1) followed by St4phylococ- Acinttobacter baumannii (18).
cw aunN.f (2) suggested that antimicrobial resistance may be Understanding the growing complexity of antimicrobial re-
more complex. Active efflux of antimicrobials (3), drug target sistance may assist in the development ofnovel agents, rapid and
modification (4), and bacterial expression of drug-modifying accurate diagnostics, and infection control recommendations.
enzymes (5) have collectively contributed to the intricate web
of antimicrobial resistance. The introduction of carbapen-
ems in the 1980s promised to be a solution for patients and
MECHANISMS OF RESISTANCE
practitioners struggling with the treatment of severe health
care-associated drug-resistant gram-negative infectiows. Unfor-
INTK.INSIC RESISTANCE
tunately, reports of resistance to these last resort antibiotics are
no longer rare, and despite increasing accounts of reaistance Absence of an intended target, decreased permeability, active
and the growing clinical isolation of multidrug-resistant strains, drug efflux, or chromosomal expression of a drug-modifying
the number of new antibiotics with original mechanisms of ac- or inactivating enzymes are responsible for intrinsic resistance
tion in development is discouraging and many are predicting to some antimicrobials (14). For example, Mycoplasma spp. lack
the end of the era of antibiotics (6). a peptidoglycan cell wall and thus are inherently resistant to
In the late 1950s, the remarkable finding that susceptible penicillins, cephalosporins, and other ft-lactam antibiotics.
Shigtlla species were able to acquire a multiple drug reaistance Most enterococci demonstrate low levels of aminogJycoside re-
phenotype (7) introduced the concept of horizontal transm~ sistance because of the inability of the drug to traverse the cell
sion of resistance genes and suggested that these resistance wall's peptidoglycan layer to reach their target, the ribosome.
determinants could be shuttled between species. Re&istance in However. in the presence ofinhibitors ofcell wall synthesis, such
this case was coupled with the presence of a plasmid, which as ampicillin or vancomycin, aminogJycosides can reach their
through the process of conjugation could be transferred be- site of action and provide a synergistic bactericidal effect (15).
tween bacteria. Plasmid-mediated transfer of multiple res~ The size and structure of vancomycin prevents it from being
tance determinants appears to be responsible for much of the able to navigate the outer membrane of gram-negative bacilli,
multidrug resistance seen in gram-negative bacilli today. thus limiting its activity to gram-positive pathogens. Chromo-
Subsequently, in the 1960s, bacteriophages (or viruses ca- somally encoded enzymes with the ability to modify or destroy
pable of infecting bacteria) were noted to be capable of trans- antimicrobials also can be respowsible for innate resistance.
ferring antimicrobial reaistance genes and even small plasmids For example, AmpC ft-lactamases are intrinsic to several clini-
between bacteria through a process called transduction (8). cally relevant gram-negative pathogens including Enttrobacter
This was followed in the 1970s by the description of transpo- spp., ~ jreundii, SmGtia mtmescens, and Pseudomonas
sons, chromosomal or plasmid-borne transposable elements atl'f'Ulino:sa (16). In the absence of.P-lact.am. exposure, these en-
with the ability to move independent &om normal DNA. recom- zymes can be expressed at low levels. Spontaneous mutations
bination (9). In the 1980s, the basic structure of the integron in regulatory regions can lead to derepression and subsequent
208
Chapter 16 • Moltcular Biology ofRe.sistanct: A Brief History ffj Resistance Mechanisms and the Discooery of Gnu Transfer 209
enzyme hyperproduction, thus rendering these bacteria resis- be due to ft.Iactamase production (27), but high-level ampi-
tant to most commonly employed penicillins, cephalosporins, cillin resistance among Enterococcus frucium is the result of the
cephamycins, aztreonam, as well as commercially available expression of a low-affinity target, PBP5 (28-30). Mosaic genes
~lactam/~lactamase inhibitor combinations. resulting in altered PBPs are also responsible for penicillin and
cephalosporin resistance among Neisseria gorwrrftoea.e (31-34).
In gram-negative bacilli, ,8-lactam resistance primarily re-
ACQUIRED RESISTANCE sults from the expression of ~lactamases (Table 16.1). This
Of greater concern is the development of resistance among tra- heterogenous group of enzymes efficiently hydrolyze the am-
ditionally susceptible bacteria through mutation or through the ide bond of the ~lactam ring, thus inactivating the ~lactams.
acquisition of new genetic material. Transfer of genetic material These enzymes can be intrinsic (e.g., AmpC P.,Iactamases
often is mediated by integrons, transposons, or plasmids. These in Enterobacter cloacat and P. aeruginosa) or acquired (e.g.,
mobile DNA elements can encode multiple determinants, thus plasmid-mediated), and over 1,000 unique P.,lactamases have
conferring resistance to more than one type or class of anti- been described with different structures and spectra of ac-
biotics. The resultant multidrug resistance severely handicaps tivity (http:/ /www.lahey.org/ studies/ ). These enzymes are
practitioners treating patients infected with these pathogens. classified by two different schemes: the Ambler molecular
Examples of acquired resistance mechanisms for several classes classification, based on the amino acid structure (35), and the
of antimicrobial agents are described in the following sections the Bush-Jacoby-Medeiros functional classification scheme,
with a focus on common clinically relevant mechanisms as well based on the substrate and/ or inhibitor profile (36) . For the
as mechanisms for multidrug resistance among gram-positive sake of simplicity, we will reference the Ambler classification
and gram-negative bacteria. scheme here.
Resistance to ampicillin among E. coli and Kkhmlla pneu-
moniae is mediated by narrow""'pectrum penicillinases (e.g.,
MECHANISMS OF RESISTANCE TO TEM-1 in E. coli and SHV-1 in K pneumoniat) (37,38). The
clinical introduction of third-generation cephalosporins in the
SELECTED ANTIBIOTICS
1980s, which were stable against these penicillinases, was soon
followed by the description of,8-lactamases capable of inactivat-
RESISTANCE TO ft-LACTAM AGENTS
ing these broad""'pectrum antibiotics. Remarkably, a single point
P,lactam agents include penicillins, cephalosporins, mono- mutation in the genes encoding the narrow""'pectrum penicillin-
bactams, and carbapenems. These agents bind to penicillinases was responsible for expanding the substrate spectra (39).
binding proteins (PBPs), which are enzymes (e.g., transpepti- These group of enzymes were designated as extended-spectrum
dases) involved in the synthesis and maintenance of the pepti- ~lactamases, or ESBLs (40). The expression ofESBLs confers
doglycan cell wall of gram-positive and gram-negative bacteria. resistance to penicillins, first-, second-, and third-generation
P,lactam resistance can be conferred by decreased access to cephalosporins, and aztreonam. In the absence of other resis-
the PBPs through efflux or outer membrane porin mutations, tance mechanisms, cephamycins and carbapenems retain ac-
reduced PBP affinity for P,lactams, and by the expression of tivity. Interestingly, ESBLs are readily inhibited by ~actamase
p.tactamases. inhibitors (e.g., clavulanic acid). This property has been an im-
As previously referenced, staphylococcal ~actamases are portant characteristic used for detection of ESBL production
narrow""'pectrum penicillinases with relatively poor activity in clinical microbiology laboratories. Clinically, however, ESBI.r
against semisynthetic anMtaphylococcal penicillins like methi- producing K pneumoniae and E. coli tend to be resistant to avail-
cillin and oxacillin, cephalosporins, and carbapenems. On the able ~actam/~actamase inhibitor combinations (41,42).
other hand, the majority of P.,lactam resistance in clinically Recently, there has been a dramatic shift in the prevalence
relevant gram-positive bacteria (e.g., streptococci, enterococci, and types of ESBLs identified both in the community and in
and staphylococci) is secondary to expression of low-«ffinity many health care settings. The CTX-M family of P.,lactamases,
PBPs (altered drug target). particularly CTX-M-15, have become the dominant ESBL type
Methicillin resistance in S. au:m£S (MRSA) is due to the ex- in Europe, North and South America, and Asia (4~6). Unlike
pression of PBP2a ( 17). This low-affinity PBP is encoded by the SHV-type (e.g., SHV-2) and TEM-type ESBLS, which evolved
meGA gene. This gene has been mapped to mobile chromosomal primarily from mutations in plasmid-mediated penicillinases,
elements referred to as staphylococcal chromosomal cassettes CTX-M type ESBLs appear to have evolved from a chromo-
(SCCmec) (12,18). Eleven variants of this element have been de- somal cephalosporinase of Klu:yvera spp. (47). C1X-M-15 has
scribed (19-22). The sizes of these chromosomal cassettes vary, been associated with a specific clone of E. coli, ST131 (44,48-
and smaller cassettes (e.g., SCCmec IV and SCCmec V) appear 51), that has contributed to the successful global dissemination
to carry fewer concomitant resistance genes (23,24). These cas- of this particular resistance determinant. CTX-M type enzymes
settes contain the mec gene complex as well as unique cassette were considered rare in the United States a few years ago, but
recombinase genes (cagene complex) responsible for excision contemporary suiVeys demonstrate that its prevalence is in-
and integration (18). Contemporary SCCmectyping is based on creasing at an impressive rate (52,53). Many plasmids carrying
variations in these components (19). ESBLs also harbor genes associated with fluoroquinolone and/
Similarly, penicillin resistance among Streptococcus pneu:moniae or aminoglycoside resistance (44,54).
is due to the expression of low-affinity PBPs from mosaic gene Carbapenems are considered the drug of choice to treat pa-
products (modifications in genes for PBP2b, 2x, and 1a). These tients at risk for or with documented severe infections caused
mosaic genes are derived from DNA recombination between by ESBI.rproducing organisms, even in the setting of reported
chromosomal PBP genes and those from less virulent strepto- in vitro susceptibility, due to clinical failures obseiVed with alter-
coccal species (25,26) . Ampicillin resistance in enterococci can native therapy (55).
TABLE 16.1 Examples of Commonly Encountered ,8-lactamases among Epidemiologically Significant

Gram-Negative Badlli
Ambler Bush-Jacoby- Representative
Class Med.eiros Class Common Name fllactam Resistance Prome Examples
A 2b Penicillinase Penicillins, first generation SHV-1, TEM-1
cephalosporins (narrow spectrum)
A 2be ESBL Penicillins, cephalosporins, aztreonam, SHV-2, CTX-M
not inhibited by clinically available
P.!actamase inhibitors"
A 2f Carbapenema&e Penicillins, cephalosporins, aztreonam, KPC
P.lactam/P.!actamase inhibitor
combinations, carbapenems
B Metallo-P. All P.!actams including carbapenems IMP, VIM, NDM-1
lactamases EXCEPT aztreonam, not inhib-
ited by P.!actamase inhibitors but
inhibited by EDTAb
c 1 Cephalwporinase Penicillins, cephalosporins, not AmpC P.lactamases
inhibited by P.!actamase inhibitors
D 2df Carbapenema&e Penicillins, cephalosporins, aztreonam, OXA-23, OXA-48, OXA-58
P.lactam/P.!actamase inhibitor
combinations, carbapenems
"davulanic acid
hethylenediaminetetraacetic acid
Phenotypic carbapenem resistance in Enterobacteriaceae was Carbapenem resistance among gram-negative bacilli also
initially considered sporadic, but during the last decade has be- can be mediated by the Class B ,8-lactamases, the metallo-,8-
come alarmingly more common. Carbapenem resistance results lactamases (MBLs) (6g). These enzymes use metal, commonly
from one or more of the following mechanisms: derepression zinc, as a cofactor for ,8-lactam hydrolysis. With the exception
and hyperproduction of AmpC ,8-lactamases or ESBLs with of aztreonam, MBLs can hydrolyze all ,8-Iactam antibiotics and
concomitant alteration in outer membrane porins, augmented are not inhibited by commercially available ,8-lactama:se inhibi-
drug effiux, alterations in PBPs, and/or carbapenemase tors. Co-expression of MBLs with ESBLs, AmpC ,8-lactamases,
production (56). and/or other carbapenemases can result in concomitant resis-
Currently, most carbapenem resistance among Entero- tance to aztreonam.
bacteriaceae in the United States and Israel is attributed to Intrinsic carbapenem resistance in Stenotroplwmonas malto-
plasmid-mediated expression of a KPC-type (K. pneumoniae philia is due to chromosomal MBLs. Initially these MBLs were
carbapenemase) carbapenemase. These Class A serine car- described in Pseudomf:mas spp. but reports in Enterobacteriac~
bapenemases hydrolyze carbapenems as well as penicillins, are now quite common. Frequently detected MBLs include
cephalosporins, and aztreonam and are not overcome in vitro the IMP-type (active against imipenem) and VIM-type (Verona
by clinically available ,8-lactamase inhibitors (57). KPCs have integron-encoded MBL), with the most prevalent being VIM-
been identified in several species of Enterobacteriaceae as well 2. As of 2009, international attention has turned toward the
as Pseudomonas spp. and A. baumannii (56), with KPC-2 and increasing recovery ofNDM-1, that is, New Delhi MBL. Due to
KPC-3 being most commonly isolated subtypes in Enterobac- the conveniences of travel and medical tourism, NDM-1 is not
teriaceae. The bk;u.c gene has been mapped to a Tn3 based only endemic to the Indian subcontinent, this relatively novel
transposon, Tn4401 (58), explaining the efficient transfer of MBL has disseminated worldwide ( 64-68).
these ,8-lactamases between strains and species. Five isoforms The rapid spread of NDM-1 exemplifies the fluidity of
ofTn4401 have been described (59,60). Reports of many of the gene transfer between bacterial species. Although b~DM-l
plasmids harboring bk;u.c include genes conferring resistance was initially and repeatedly mapped to plasmids isolated from
to fluoroquinolones and aminoglycosides are unsettling and carbapenem-resistant E. coli and K. pneumoniae, reports of both
not uncommon (61,62). plasmid and chromosomal expression of blarmM-l has been
KPC-production confers variable levels of carbapenem resis- noted in other species of Enterobacteriaceae as well as Acinetobacter
tance with reported minimum inhibitory concentrations (MICs) spp. and P. aeruginosa (56,66). It is currently held that blaNDM-l is
ranging from susceptible to ~16 pg/mL. Analysis of 14 KPC a chimeric gene that may have evolved from A. baumannii (69) .
harboring K. pneumoniae isolates with MIC ~16 7Jg/mL dem- A small percentage of the Class D ft-lactamases, com-
onstrated that high level of resistance may be secondary to in- monly referred to as oxacillinases, demonstrate low-level car-
creased gene copy number (i.e., dose response) or the loss of a bapenemase activity. These carbapenemases contribute to the
functional outer membrane porin, OmpK35 and/ or OmpK36. carbapenem resistance in Acinetobacter spp. and can be chro-
The highest level of resistance was seen with isolates lacking mosomal or plasmid-mediated. Examples of acquired Class D
both porins and with augmented KPC enzyme production (59). carbapenemases include OXA-23, OXA 24/40, OXA-58, and
Chapter 16 • Molecular Biology ofResistance: A Brief History of Resistance Mechanisms and the Discooery of Gene Transfer 211
OXA-48. OXA-23 (originally ARI-1) was the first of these types AMINOGLYCOSIDE RESISTANCE
of carbapenem-hydrolyzing oxacillinases described (70). Both
Aminoglycoside resistance is common in both gram-positive
OXA-23 and OXA-58 are responsible for the carbapenem re-
sistance reported in many isolates of A. baumannii recovered and gram-negative organisms. Resistance can be due to target
modification, alterations in outer membrane proteins, result-
from skin and soft tissue infections in military and civilian per-
ing in decreased intracellular drug concentrations (86,87), ef-
sonnel returning from the military operations in the Middle
flux (88), and enzymatic drug modification (5). The latter is
East and Mghanistan (71). OXA-48 appears to have the highest
the most common and includes phosphorylation, acetylation,
affinity for carbapenems of this class of carbapenemases and
or adenylylation of the antimicrobial agent by plasmid- or trans-
has been described with increasing frequency in 1\lrkey, the
poson-encoded enzymes. This group of enzymes is exceedingly
Middle East, and Europe (72). High-level carbapenem resis-
tance is usually conferred by the concurrent presence of other diverse and a detailed comprehensive review was recently pub-
lished (5).
resistance determinants including alterations in porins (e.g.,
Cart) in A. baumannit) (73), modifications in PBPs, increased AAC(6')-Ib is a commonly produced aminoglycoside
N-acetyltransferase responsible for amikacin resistance among
transcription mediated by insertion sequences, increased gene
copy number, and amplified drug effiux (74). Acinetobaderspp., Vibriospp., Pseudomonasspp., and Enterobacfeli.
aceae. Like other aminoglycoside-modifying enzymes, the genes
Carbapenem resistance in P. aeruginosa is frequently
encoding these enzymes often are mapped to integrons, trans-
due to a variety of mechanisms including expression of
posons, or plasmids. Variants of these enzymes have reduced
carbapenem-hydrolyzing P.Iactamases. Other contributors to the
susceptibility to other aminoglycosides like gentamicin and
carbapenem-resistant phenotype in this species include effiux
some transmissible elements carry additional genes associated
and alterations in outer membrane proteins. Unlike carbapen-
with fluoroquinolone resistance (89) and ,S.Iactamase produc-
emases that, in general, do not discriminate between carbapen-
ems, upregulated expression of certain multidrug effiux pumps tion including carbapenemase production (90).
AAC(6')-Ib-cr is a notable variant of AAC(6')-Ib in that a
(e.g., MexAB--OprM) found in P. aeruginosa appear to exclude
imipenem but confer resistance to meropenem (3,75). The loss two base pair change has permitted acetylation of ciprofloxacin
and norfloxacin in addition to amikacin. This appears to be the
or alteration of the outer membrane porin OprD, however, is spe-
cific for imipenem resistance exclusive of other ,Biactams (76). first description of a single function drug-modifying enzyme
that can inactivate unrelated antibiotics (91).
Another mechanism of high-level aminoglycoside resistance
RESISTANCE TO ERYTHROMYCIN mechanism involves the expression of 16S rRNA methylases
AND OTHERMACROLIDES (e.g., rmt genes and annA). These enzymes methylate the ribo-
somal RNA (rRNA) associated with the 30S ribosomal subunit
Macrolide resistance has been reported in numerous bacteria,
preventing aminoglycoside binding (92,93). The genes encod-
but is of great clinical significance when treating community-
associated gram-positive pathogens like S. pneumoniae and ing these enzymes also have been mapped to transposons and
plasmids harboring other resistance determinants (92,94).
S. au1mS. In pneumococci, two phenotypes of macrolide
resistance appear to be common worldwide, although preva-
lence varies geographically (77). One is isolated low-level
TETRACYCLINE RESISTANCE
macrolide resistance and the other is high-level resistance to
macrolides, lincosamindes (e.g., clindamycin), and strepto- Tetracycline inhibits protein synthesis by preventing the associ-
gramin B (MLSB) (78). ation between aminoacyl-tRNA and the ribosome. Tetracycline
Low-level macrolide resistance is mediated through expres- resistance is widespread in both gram-positive and gram-neg-
sion of an effiux pump (encoded by mejA.) that efficiently re- ative bacteria and is most often mediated by drug effiux or ri-
moves macrolides from the cytoplasm preventing interaction bosomal protection (95) . Most acquired tetracycline resistance
between drug and the bacterial ribosome (79,80). High-level genes that mediate effiux reside on transposons, plasmids, or
macrolide resistance, the MLSa phenotype, is secondary to the integrons allowing for efficient horizontal gene transfer (96).
expression of erm genes (erythromycin rRNA methylase), spe- Effiux effectively decreases intracellular drug concentra-
cifically ermB, which results in dimethylation of adenine 2058 tions, thus preventing inhibition of protein synthesis. Over 30
in the 23S rRNA of the 50S ribosomal subunit, thus modifying tet effiux genes have been characterized, all of which encode
the drug target for erythromycin, clindamycin, and the strepto- energy-dependent membrane-associated proteins (95,96). TetK
gramin quinupri.stin. Expression of the erm genes can be con- and telL are found primarily in gram-positive species including
stitutive or induced. S. aureus and confer resistance to tetracycline but not minocy-
The expression of incompletely homologous erm genes cline (97) . TetB appears to have the widest host range among
(ermA and ermC) appears to be responsible for a similar phe- gram-negative bacilli and confers resistance to tetracycline and
notype in S. aureus, irrespective of methicillin susceptibility minocycline but not the glycylcycline, tigecycline (95).
(81,82). In vitro, S. aureus isolates with constitutive expression Ribosomal protection proteins confer resistance to tetracy-
of the erm gene demonstrate resistance to both erythromycin cline, doxycycline, and minocycline. 'JetM is widely dispersed
and clindamycin. Isolates with inducible resistance, however, among Staphylococcus spp. as well as Enterococcus faecalis, Neisseria.
can test susceptibility to clindamycin despite testing resis- gonorrhoeae, Mycoplasma pneumoniae, and Bacteroides fragilis (95).
tance to erythromycin. The inducible nature of these genes Due to association with transmissible genetic elements, descrip-
and the associated poor clinical outcomes led to the develop- tion of cotransfer with other resistance elements including the
ment of the phenotypic D-test (83,84). Macrolide effiux pumps aforementioned erm genes has been described (96).
(e.g., msrA) are responsible for isolated macrolide resistance in Tigecycline resistance, although rare among Enterobaderirr
Staphylococcus spp. (85). aaeand gram-positive pathogens, is being increasingly reported
and appears to be due to drug effiux mediated by multidrug ef- susceptible to teicoplanin (115,117). Both of these resistance
flux pumps (e.g., AdeABC in A. haumannit) (98-102). determinants have been localized to transmissible elements,
vanA to a transposon Tn1546, and plasmid-mediated transfer
of vanA from E. faecalis is responsible for high-level vancomycin
GLYCOPEPTIDE RESISTANCE
resistance inS. aumw (VRSA) (118).
Vancomycin was licensed in 1958 for the treatment ofMRSA and
remains the mainstay for treatment of infections with MRSA and
FLUOROQUINOWNE RESISTANCE
other gram-positive bacteria in the setting ofintolerance or resis-
tance to ft-lactam agents (e.g., ampicillin-resistant enterococci). Resistance to the fluoroquinolones in gram-negative and
Unlike penicillins and cephalosporins where the development gram-positive pathogens is frequently the consequence of an
of resistance was relatively rapid, episodes of reduced suscepti- accumulation of spontaneous point mutations in the genes en-
bility to vancomycin were reported decades later with the first coding either DNA gyrase or topoisomerase IV (e.g., gyrA, gyrB,
reports of vancomycin-resistant Enterococcus faecium (VRE) in the and parC), thus altering the drug target of fluoroquinolones.
mid-1980s (103) and the first report of S. aumw with reduced Single point mutations appear to confer modest resistance but
vancomycin susceptibility in the late 1990s ( 104,105). accrual of a number of these mutations can confer high-level
Vancomycin binds the C-terminal D-alanine-D-alanine resi- resistance. These mutations pass vertically but do not appear to
due of peptidoglycan precursors inhibiting the cross-linking pass horizontally (119). Mutations resulting in drug efflux have
and the incorporation of these precursors into the cell wall. In been described as well (3,120).
S. aureus cell wall, synthesis is a dynamic process and the pri- Plasmid-mediated fluoroquinolone resistance, qnrA, was first
mary location for nascent wall synthesis at the division septum. reported in 1998 (121). Several variants of the qnrgene have been
For vancomycin to reach its intended target, it needs to diffuse characterized. The qnrgene product is a pentapeptide repeat pro-
through the cell wall. Reduced susceptibility to vancomycin, or tein that protects DNA gyrase from the action of fluoroquinolones
vancomycin-intermediate S. aureus (VISA), appears to result (122). Other plasmid-mediated fluoroquinolone resistance deter-
from an amassing of mutations leading to thickening of that minants include the previously described AAC(6')-fu.cr as well as
cell wall. Cell wall thickening seems to be the consequence of efflux pumps, QepA (123) and OfxAB (124). Individually, these
accelerated peptidoglycan synthesis with or without decreased resistance determinants also confer low levels of fluoroquinolone
autolytic activity and the accumulation of peptidoglycan pre- resistance. However, in combination with other plasmid-mediated
cursors (106). The increased concentration of drug target es- fluoroquinolone resistance genes and/or mutations in DNA
sentially results in "trapping" the vancomycin in the thick cell topoisomerases, high-level resistance is achieved Not surprisingly,
wall preventing diffusion to the division septum (105,107). plasmid-mediated fluoroquinolone resistance has been linked to
Heteroresistance also has been described and appears to large plasmids thus associated with other resistance mechanisms
be an intermediary between vancomycin-susceptible S. aureus including ESBLs (125), KPCs (126), and NDM-1 (127).
and VISA (106). Heteroresistant VISA (hVISA) refers to popu-
lations of S. aumw that contain subpopulations with elevated
TRIMETHOPRIM AND SULFONAMIDE RESISTANCE
MICs to vancomycin (4 to 8 ~/mL) (108). The low frequency
of these smaller populations of vancomycin nonsusceptible Sulfonamides, like sulfamethoxazole, inhibit dihydroptero-
S. aum.tS contributes to the inability of clinical microbiology ate synthase (DHPS), which converts p-aminobenzoic acid to
laboratories to accurately detect this phenotype using rou- dihydrofolate. Trimethoprim inhibits dihydrofolate reductase
tine methods. Techniques to increase laboratory detection of (DHFR), thus inhibiting the conversion of dihydrofolate into
h VISA include using higher inoculums, prolonging incuba- tetrahydrofolate. Both of these steps are required for the pro-
tion periods, employing of nutrient-enriched media, and the duction of folic acid in many bacteria. Resistance to one or both
macromethod Etest (MET) or GRD Etest. Population analysis, of the components of the combination agent trimethoprim-
however, remains the most accurate laboratory method and is sulfamethoxazole is common in Enterobacteriaceae as well as
considered the gold standard (109). St:reptococr:us spp. and staphylococci.
The prevalence of h VISA and VISA is variable and the clini- Sulfunamide resistance is due to alterations in DHPS (128). In
cal significance remains undefined. However, poor clinical pneumococci, nucleotide repeats lead to amino acid changes that
outcomes have been associated with elevated vancomycin MICs result in a conformational change in the enzyme structure ( 129).
and treatment with vancomycin (106,108,110). In both Streptococcus pyogmes and Neisseria meningitidis, mosaic genes
Glycopeptide resistance in enterococci is primarily due to alter- (e.g., foiP) secondary to either transformation, transduction, or
ations in peptidoglycan precursors due to the presence ofvan gene recombination result in altered DHPS with lower sulfunamide
clusters. To date, eight different genotypes have been described affinity (128,130). Plasmid-mediated resistance to sulfunamides
(111,112). vanA and vanB are the most clinically relevant. vanC also has been reported in Enterobacteriace (7,131-133). sulgenes
is responsible fur the intrinsic low level of vancomycin resistance appear to encode for alternative DHPSs that are sulfonamide-
found in Enferococcus gallinarum and E cassOiftavus/E. ftavescens resistant. The sufl gene is often mapped to Tn21 transposons and
(113). The characteristics that distinguish these eight gene clusters associated with other resistance genes (10,134).
were recently reviewed, but it should be noted that levels of pheno- Trimethoprim resistance can be due to decreased perme-
typic vancomycin resistance are variable (112-114). ability, increased amount of target enzyme, and by alterations
Vancomycin resistance in Enterococcus faecium is most com- in the target enzyme, DHFR, decreasing its affinity for trime-
monly secondary to vanA and is associated with high levels thoprim (134). Mutations in the chromosomal gene encoding
of resistance to both vancomycin and teicoplanin (115,116). DHFR have been described in both S. aureus and S. pneumoniae
vanB has been linked with outbreaks of VRE and demon- (134). In gram-negative bacilli, plasmid-borne resistance is
strates variable levels of vancomycin resistance and usually tests common and the consequential DHFR variants tend to have a
low affinity for trimethoprim and are found frequently among the multidrug-resistant phenotype in bacteria. However, efflux
gram-negative pathogens. Dkfrl was the first of over 30 dhfr pumps and alterations in outer membrane porins also can confer
genes characterized and remains the most common (130,135). multidrug resistance. There are five classes of efflux pumps: the
resistance-nodulation division (RND) family, the m.;:yor fucilitator
(MF) superfamily, the adenosine triphosphate (ATP) binding
OXAZOLIDINONE AND LIPOPEPTIDE RESISTANCE
cassette (ABC) fiunily, the small multidrug resistance (S:MR) fam-
Since 2000, very few antimicrobial agents with unique mecha- ily, and the multidrug and toxic compound extrusion (MATE)
nisms of action have become commercially available. Linezolid family (148). The RND-type efflux pumps are most commonly
and daptomycin are among those drugs and are potential op- found in gram-negative bacteria and include the MexAB-OprM
tions for the treatment of resistant gram-positive cocci includ- of P. aeruginosa and the AdeABC efflux pump of A. baumannii (3).
ing MRSA and VRE. MexAB-OprM is intrinsic to P. aeruginosa and one of several
Resistance to linezolid, an oxazolidinone, remains rare but efflux mechanisms found in this species (149). Overexpression
has been described in both staphylococci and enterococci of this efflux system occurs with a mutation in regulatory genes
(136). Two mechanisms responsible for linezolid resistance are and results in resistance to P..lactams (except imipenem), fluo-
described (137). The first is single nucleotide polymorphisms in roquinolones, tetracyclines, chloramphenicol, and macrolides.
the 23S ribosomal rRNA that prevents linezolid from successfully Concomitant imipenem resistance has been seen with the nftC
binding and interrupting protein synthesis. Plasmid-mediated mutation at mexT, which upregulates expression of another
transfer of the cfr gene ( chloramphenicol-florfenicol resis- efflux pump, MexEF-OprN, and also decreases expression of
tance) is associated with production of an rRNA methyltransfer- OprD (150). The AdeABC efflux pump in A. baumannii can
ase. Methylation of A2503 of the 23SRNA confers resistance to efficiently remove aminoglycosides, cefotaxime, tigecycline,
chloramphenicol, clindamycin, and linezolid (138,139). erythromycin, chloramphenicol, trimethoprim, and fluoro-
Resistance to daptomycin, a lipopeptide, commonly used to quinolones from the cytoplasm preventing drug-target in-
treat infections with S. aureus, is rare (140) but has been re- teractions (88). When overexpressed in conjunction with
ported. Although not a licensed indication, many anecdotal carbapenem-hydrolyzing Class D ft-lactamases, high-level car-
reports of daptomycin being used to treat enterococcal infec- bapenem resistance is observed (151).
tions, specifically VRE, exist. With these reports come descrip-
tions of resistance. In one report using genomic sequencing
of a susceptible and a resistant E. Jaecalis strain, resistance DISSEMINATION OF RESISTANCE
appeared to be secondary to concurrent mutations in genes GENES
associated with regulation of the cell envelope, liaF, and phos-
pholipid metabolism, gdpD (141). The effective transfer and acquisition of resistance genes be-
In S. aunms, daptomycin resistance has been linked to point tween strains and species has proven to be decisive for the dis-
mutations in genes responsible for maintenance of cell sur- semination of resistance (Table 16.2). Bacteria can exchange
face charge (e.g., mpiF and dltABCD) (142,143) and the cell genetic information by means of transformation, transduction,
membrane (e.g., cls and pgsA mutations). It also has been hy- and conjugation. The transferred genetic information can origi-
pothesized that in the setting of VISA or hVISA, decreased sus- nate from a bacteria's chromosome or on plasmids, integrons, or
ceptibility to daptomycin may be due to an inability to traverse transposons. Each of these genetic elements has unique features.
a thickened cell wall and to reach the cell membrane (144).
PLASMIDS
POLYMYXIN RESISTANCE
Plasmids are stabile extrachromosomal segments of DNA
Polymyxin use including polymyxin E, or colistin, decreased that can independently replicate and are found in many spe-
substantially with concerns of nephrotoxicity and neurotoxic- cies of bacteria and can be lost or gained without affecting
ity and the introduction of aminoglycosides. Colistin's clinical the host. In general, they are circular and range in size from
resurgence is associated with the increasing isolation of car- 2 to 400 kb. The number of proteins encoded on plasmids
bapenem-resistant gram-negative bacilli and a paucity of agents can be substantial, with larger plasmids (-300 kb) encoding
available to reliably treat these organisms. Colistin is a cationic 50 to 75 proteins. In addition to resistance genes, plasmids
antimicrobial peptide that interacts with the anionic lipid A often encode for the machinery necessary for plasmid trans-
moiety of lipopolysaccharide (LPS) and disrupts the outer fer as well as maintenance. Plasmids are categorized based on
membrane. Mutations in genes responsible for lipid A synthesis their ability to transfer themselves to other organisms. Conju-
(e.g., lpxA) (145) or alterations in membrane charge have been gative plasmids are those that are capable of mediating their
associated with polymyxin resistance (146). Other described own cell-to-cell transmission. In gram-negative bacteria, con-
mechanisms of resistance include alterations in the PmrAB two- jugation often is facilitated by the formation of an external
component system that is involved in sensing the environmen- proteinaceous appendage, a pilus, forming a bridge between
tal milieu and moderating the expression of lipid A (147). two cells, thus allowing transfer of plasmid DNA Conjugative
plasmids of gram-positive bacteria do not use pili for conjuga-
tion and can be further classified as pheromone-responsive
RESISTANCE TO MULTIPLE ANTIMICROBIAL
and non-pheromone-responsive conjugative plasmids (152).
AGENTS
Pheromone-responsive plasmids have been described primar-
Accumulation of numerous mutations, concurrent carriage of ily in E. faecalis ( 153-155). The conjugative process, in this set-
multiple plasmids, and the considerable capacity of some trans- ting, is initiated in response to short peptides, pheromones,
missible elements to carry a variety of resistance genes can confer produced by pheromone-responsive plasmid-free recipient
TRANSPOSONS AND INSERTION SEQUENCES

TABLE 16.2 Abbreviated. Glossary of
Common Terms Used in Within plasmids, resistance genes often are carried on transpo-
Desaibing Transfer of sons. These are small pieces of DNA that can move from one
Raistance Genes Between location to another including between plasmids, between plas-
Bacteria mids and bacteriophages, and between plasmids and the na-
tive chromosome (160). Unlike plasmids, transposons cannot
Term Definition independently replicate. Transposons encode a transposase, an
STilUCTURE endonuclease, which facilitates excision and insertion of the
transposon from donor to recipient, in either a "copy and paste"
Plasmid Extrachromosomal DNA, usually (replicative) or "cut and paste" (conservative) fashion (9). In-
circular, that self-replicates sertion sequences (IS) are small transposons that encode for
Conjugative plasmid A plasmid capable of mediating its movement, including the transposase enzyme, and promote
own transfer gene rearrangement. They can modify or induce the expression
Non-<onjugative Unable to mediate its own transfer of resistance genes by inserting promoter elements upstream
plasmid of those genes. Composite transposons are transposons with a
Traruposon Segments of DNA that cannot pair of ISs flanking a DNA segment not only encoding for a
self-replicate but can transfer transposase but also containing at least one gene. Transposons
between replicative DNA species encoding resistance genes to a variety of antimicrobial agents
(i.e., plasmids and chromosome) have been described. Some transposons, particularly those in
Insertion sequence Small transposons encoding genes gram-positive organisms, such as enterococci and S. pneumoniae,
required for its own movement are conjugative and facilitate their own transfer from the donor
Integron Segments of DNA containing a site- chromosome to the recipient cell (152,161,162).
specific recombination system
capable of inserting into plasmids,
transposons, and/ or chromosome INTEGRONS
Bacteriophage A bacterial virus Integrons are mobile DNA elements that use site-specific re-
MECHANISMS OF GENE TRANSFER combination and facilitate the acquisition and expression of
resistance gene cassettes. They are widely distributed among
Conjugation Transfer of genetic material from cell
gram-negative species and can occur within plasmids and
to cell. In gram-negative bacteria,
transposons. Integrons harbor three key elements in addition
usually mediated by the formation
ofapilus to the gene cassette: a gene encoding an integrase (inti), a pri-
mary recombination site (e.g., attl), and a promoter to direct
Transduction Movement of genetic material from cell
transcription of the included genes (1 0,163) . All integron-
to cell is mediated by an infecting
bacteriophage
associated gene cassettes contain a 59-base-pair region at their
3' end, an attC site, which is recognized by the integrase and
Transformation The uptake of genetic material from
thus required for insertion. Five classes of mobile integrons are
the environment and recombination
known and have been linked to transmissible genetic elements
with the host chromosome
like IS, transposons, and plasmids (164). Class 1 integrons ap-
pear to be the most prominent and have been important in the
strains mediating intercellular aggregation and subsequent dissemination of some resistance genes including sull (130)
DNA transfer. The mechanism of transfer of nonpheromone and VIM-type MBLs (165,166).
nonconjugative plasmids is unclear (156).
Non-conjugative plasmids often are smaller than conjuga-
DEVELOPMENT AND DISSEMINATION OF
tive plasmids and lack the genes encoding the functions that
MULTIDRUG-RESISTANT ORGANISMS
enable cell-to-cell transfer. These plasmids can take advantage
of the plasmid-encoded machinery of a coresident conjugative Multidrug resistance can develop in the setting of successive
plasmid and can be mobilized to a recipient cell with the conju- acquisition of mutations and resistance genes (61). In the set-
gative plasmid. In addition, both non-conjugative and conjuga- ting of antimicrobial pressure, spontaneous mutations may por-
tive plasmids may be transmitted through transduction. In this tend a survival advantage and thus are transferred vertically to
process transfer of genetic material is facilitated through a viral progeny bacteria. Likewise, antibiotic pressure may select for
intermediary, a bacteriophage. Genetic material from the bac- pathogens carrying resistance determinants harbored on one
teria is packaged into the viral protein coat of an infecting bac- or more transmissible elements (e.g., integrons, transposons,
teriophage. Progeny viruses infect an appropriate recipient cell and/or plasmids) or for pathogens that have upregulated
and the "foreign" DNA is released into the cytoplasm of that expression of resistance determinants in the setting of spon-
new host. This is assumed to be a significant mechanism of gene taneous mutation or acquisition of effective transcription pro-
transfer in Staphylococcusspp. including S. au:nms (157-159). moters or ISs (16,74). Knowledge of the propensity to bundle
Neisseria spp. and streptococci among other bacterial genera resistance determinants on the same transmissible element,
can absorb and incorporate exogenous genetic material from and thus travel together, can aid in the choice of empirical an-
the environment, thus creating mosaic genes and novel low-af- timicrobials in the appropriate scenario (152) . The successful
finity drug targets (4,26,31,32). This is referred to as "natural" transfer and maintenance of these multidrug-resistant pheno-
transformation. Transformation as a mode of plasmid acquisi- types threatens our current antimicrobial armamentarium, and
tion appears to be uncommon. with limited antimicrobial options available or in development,
understanding and controlling the continuing spread of these community was associated with the historical use of the glyco-
multidrug-resistant pathogens becomes paramount. peptide avoparcin as a growth promoter in animal husbandry
Widespread dissemination of successful multidrug-resistant (179,180). KPC and VIM-type carbapenemases have been iso-
phenotypes is of grave concern. Often, successful propagation lated from patients in long-term health care facilities, but com-
of these resistant phenotypes initially is reported on a local level munity acquisition has not been reported (171,181). NDM-1,
in the setting of outbreaks or in intensive care units (ICUs). however, has been isolated in the community water supplies
However, the recent continental outbreak of foodbome ill- and sewage systems in India and among fairly virulent patho-
ness and hemolytic uremic syndrome associated with a CI'X- genic Enterobacteriaceae in that setting (182).
M-producing E. coli (167-170) and the association between a
specific strain of K pneumoniaeand regional and global dissemi-
nation of KPCs suggest that dissemination may occur not only EPIDEMIOWGIC STUDIES OF
in the hospital setting but also in the community as well as the BACTERIAL RESISTANCE
long-term health care setting ( 171) .
Characterizing the molecular epidemiology of antimicrobial-
resistant bacteria requires typing methods that are both dis-
CONDffiONS THAT FAVOR THE criminatory and reproducible. When an outbreak is suspected,
DEVEWPMENT OF RESISTANT several techniques can be used to confirm that the isolates are
ORGANISM5---SELECTIVE PRESSURE clonal (i.e., derived from a common parent). Biochemical pat-
terns and the results of routine antimicrobial susceptibility test-
Due to metabolic costs, resistant organisms, particularly those ing may provide some clues in the identification of resistance
that develop through spontaneous mutation, usually will not determinants. More definitive information, however, can be
survive unless there is an advantage to maintaining the resis- provided using some of the various techniques described here.
tance phenotype. Antibiotic use and it!! "selective pressure"
favors the maintenance of the resistant phenotype ( 172). & PULSED-FIELD GEL ELECTROPHORESIS
such, practical and judicious use of antimicrobials, antibiotic
stewardship, is imperative in stemming the tide of multidrug Pulsed-field gel electrophoresis (PFGE) was first described
resistance ( 173-175) . This includes prudent use of antimicrobi- in the mid-1980s, (183) and remains the "gold standard" for
als in the community setting. establishing relatedness between bacterial strains, especially
in the setting of institutional outbreaks. PFGE uses restriction
endonucleases to digest chromosomal DNA into a relatively
HEALTH CARE-ASSOCIATED
small number of fragments. The fragments are then subjected
SELECTIVE PRESSURE
to gel electrophoresis in which the direction of the electrical
The most frequently encountered health care-associated infec- current is alternated frequently and at specific intervals to fa-
tion pathogens, staphylococci, enterococci, and gram-negative cilitate separation of these DNA fragments. By removal of chro-
bacilli, have demonstrated the ability to successfully acquire mosomal DNA, plasmids also can be separated and sized. The
and disseminate resistance genes ( 176). Moreover, even the observation of discrete banding patterns allows for comparison
appropriate use of broad-spectrwn agent!! potentially creates and interpretation of relatedness. Computer-assisted analysis
an environment favoring increasingly resistant pathogens. An often is employed in the setting of large numbers of isolates
unintentional consequence of broad-spectrwn antimicrobi- and can differentiate subtle band differences. Interpretive
als is the alteration and elimination of commensal susceptible criteria for analyzing and comparing banding patterns have
flora, thus promoting asymptomatic carriage of more resistant been published (184). Drawbacks to this type of molecular
strains. This, in tum, likely contributes to enhanced gene trans- analysis include difficulties in distinguishing or resolving bands
fer among organisms, particularly in the gastrointestinal tract of similar size and difficulties in reproducing results between
(177) as well as enhanced horizontal transmission between pa- laboratories.
tients in the health care environment. Immunocompromised
patients, like transplant patients, and critically ill patients in REPETITIVE ELEMENT POLYMERASE
whom frequent receipt of antimicrobials is inevitable, are often CHAIN REACIION
reservoirs for the horizontal transmission of resistant pheno-
types. Outbreaks of resistant pathogens, like ESBL-producing Repetitive element polymerase chain reaction (REP-PCR)
Enterobacteriaceae and VRE, are associated with the use of shared uses primers that target repetitive sequences interspersed
equipment, and health care workers have proven to be success- throughout the genome to generate banding patterns that
ful vectors of resistant organisms. can be analyzed in a fashion similar to the banding patterns of
PFGE (185,186). The commercial adaptation of this technol-
ogy allows for rapid turnaround, improved reproducibility, and
COMMUNITY-ASSOCIATED SELECTIVE PRESSURE
electronic and shared data analysis and reporting ( 186).
Selective pressures, outllide of the inpatient environment, in-
clude the use of antibiotics in the community setting. Large
MULTIPLE-LOCUS VARIABLE NUMBER TANDEM
surveillance studies looking at outpatient prescribing practices
REPEAT ANALYSIS
continue to associate outpatient antimicrobial use in pediatrics
with penicillin resistance among pneumococci ( 178). In con- Multiple-locus variable number tandem repeat analysis (MLVA)
trast to the United States where VRE acquisition appears to be takes advantage of the organism-specific natural variation in
exclusively associated with health care exposure, in Europe in the number of tandem repeats of DNA (variable number of
the 1990s, asymptomatic gastrointestinal carriage ofVRE in the tandem repeats [VNTR]) in different loci of the genome of
216 Section I • General Considerations of Hospital Infections
specific bacteria. MLVA determines the number of repeats in elements between strains of the same species and to other spe-
multiple loci using multiplex PCR (187,188). cies through transformation, transduction, and conjugation.
MLVA has been used to type a diverse group of highly mono- Specialized structures, including integrons, transposons, and
morphic organisms, including S. aunous, potential agents of plasmids, allow bacteria to gain and lose genetic information
bioterrorism like Bacillus antkracis, Yemnia pestis, and Francisella outside of the conventional processes of spontaneous muta-
tularmsis, Mycobacterium tuberculosis, and enteric pathogens such tion and generalized recombination. The contemporary saga
as Shiga-toxin-producing E. coli and Salmonella species (187,189). of gram-negative resistance includes repeated themes of bacte-
ria harboring multiple resistance genes and multiple plasmids.
The effects of antimicrobial resistance transcend the hospital
MULTI-LOCUS SEQUENCE TYPING setting and, with very little in the drug pipeline to combat some
Multi-locus sequence typing (MLST) is a DNA sequence-based of these multidrug-resistant organisms, we are forced to shift
typing that takes advantage of variations in housekeeping genes our focus to antimicrobial stewardship and antibiotic conserva-
among different strains of the same species (190). This typing tion, diagnostics, and infection control and prevention.
method primarily is used for studying population biology and the
evolution of bacterial species, but has been used to identify strains
that can successfully disseminate resistance genes (e.g., CTX- ACKNOWLEDGMENT
M-15 in E. coli and KPC-type enzymes inK pneumoniae). The con-
cept ofMLST originates from an older technique that examined Robert A Bonomo, MD, is supported by the Veterans Affairs
variations in the electrophoresis patterns of multiple enzymes, Merit Review Board and the National Institutes of Health.
multi-locus enzyme electrophoresis (MLEE) (191). In MLEE,
various electromorphs were equated with alleles. Similarly, in
MLST, isolates are classified based on polymorphi.sms in the
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17 Eli N. Perencevich and Sara E. Cosgrove
Econontic Evaluation of Healthcare-

Associated Infections and Infection-
Control and Antitnicrobial-Stewardship
Interventions
INTRODUCTION to justifY the importance of funding IC and AS activities at a
broader level through the completion of cost-effectiveness anal-
The recent U.S. Department of Health and Human Service's yses from the .societal perspective. For example, hospital-based
National Action Plan to Prevent Health Care-Associated Infec- vaccination programs, rucb as pneumococcal vaccination at dis-
tions (HAis) estimated that HAis are associated with between charge, would not be expected to be cost-effective from a hospi-
$28 and $33 billion dollars in preventable healthcare expen- tal perspective since the vast m~ority of benefits would manifest
ditures per year (1). Current proposed and enacted health in the community setting (4). This problem also can be seen
reforms, such as accountable care organizations, value-based when assessing AS programs, since benefits such as preventing
financial incentives, and public reporting of H.Ais, provide ~m dijJicile infection.s would often appear outside the
significant financial and nonfinancial incentives for hospitals hospital setting, and would be difficult to measure (5).
to focus resources on preventing HAls and other conditions. This chapter will detail important concepts in economic anal-
Despite these incentives, hospital administrators frequently ysis, including types of economic analyses and their strengths,
require economic justification for maintaining and expand- the different perspectives of analyses, and placing monetary val-
ing infection-control (IC) and antimicrobiakteward!bip (AS) ues in constant dollar terms. Then, it will describe approaches
progratru. This is a particular challenge because healthcare to assess the financial impact of specific HAis and of control
administrators generally view infection control programs as interventions and provide a methodology for developing a cost-
cost centers, as they do not generate revenue for the institu- effectiveness analysis at a societal level. After completi.ug the nec-
tion. Thus, hospital epidemiologists, infection preventionists essary review of health economics, it will describe the basic steps
(IP.s), and AS programs need the tools to prove the worth needed to complete a business case analysis of a specific IC inter-
of the surveillance and interventions that they perform for vention for an individual institution. While we have attempted
their healthcare institution. Additionally, with the increasing to outline important considerations regarding economic mea-
focus on bundled interventions to prevent infections, such as surement ofHAis and related interventions, more detailed texts
central-line-associated blood stream infections (ClA-BSI) and about design and analysis of economic research are available
methicillin-resistant Slaphy~ au~ (M:RSA) transmis- elsewhere (6-8). While most of the provided examples focus
.sion, increasing focus will also be placed on determining which on infection prevention activities, similar analyses can be com-
bundles and bundle components are the mo.st effective and pleted wben a.ssessing AS interventions and programs (9).
cost-effective.
HAls are a significant risk to patient safety. Unfortunately,
this has not opened the door to improving the resources pro- BASIC ECONOMIC CONCEPTS
vided to prevent HAis. Although .society would benefit from
reduced HA.Is, there is currently no direct reimbursement to This section defines important concept! regarding economic
ho.spitals for the purpose of IC or AS. This has led to the cur- analy.se.s, including types of co.st analyses, tbe perspective of the
rent situation in wbicb hospitals must make economic decisions analysis, and discounting and inflating costs.
about funding IC and AS interventions on an individual-insti-
tutional ba.sis. This situation also bas impacted the literature
TnffiSOFEOONONUCANALY~S
such that most .studies describe the hospital perspective of the
impact of HAis (90% of studies), with only 3% taking a .societal There are four basic types of economic analysis used in health-
perspective (2,3). Ju we emphasize here, it is important to com- care: cost-minimization analysis, cost-effective analysis, cost-utility
plete a business cost analysis from a hospital perspective so as analysis, and cost-benefit analysis (Thble 17.1). Experts have
to inform local decisions; however, these analyses are not useful noted that the disti.uctions between these various forms ofanalysis
on a public health level. It has become increasingly important are often blwred, yet it is important to consider what is included
220
Chapter 17 • Economic E'llaluation ofH~althcrm-Associated Infections and Infection-Control and Antimicrobial-Stewardship Intl!'r'llmtions 221
most natural unit of comparison, such as lives saved or infec-

TABLE 17.1 Differential Bvaluations of tions prevented (6). Programs then are compared in terms of
Outcomes Among Bconomic dollars per life-year gained or dollars per infection prevented.
Analyses
Formulation of Cost-Utility An~~lysis
Valuation of Final Reported
Analysis Type Outcomes Outcome Cost-utility analysis is very similar to cost-effectiveness analy-
sis except that benefits of a specific intervention are adjusted
Cost- None Dollars saved by health preference scores or are utility weighted (6). Thus,
minimization programs are compared in terms of quality-adjusted life-years
(CMA)
(QALYs) gained. The rationale of this approach is that it allows
Cost- Natural units (e.g., Cost per infection the incorporation of health-related quality of life (HRQOL)
effectiveness infections prevented, prevented or factors, such as disability or side effects associated with the con-
(CEA) life-years saved) cost per life- dition being treated or the treatment side effects. For instance,
year saved a year spent in an intensive care unit (ICU) discharge would be
valued differently from a year spent completely healthy. One
Cost-utility Healthy years (QALYs) Cost per QALY
estimate is that a year after discharge from an ICU for respira-
(CUA) saved
tory failure is associated with an HRQOL of 0.68, such that for
Cost-benefit Monetary units Net benefit (or every predicted year oflife expectancy, QALYs are increased by
(CBA) loss) in dollars only 0.68 (13). A good example of a cost-utility analysis (and a
cost-effectiveness analysis) in the IC literature is one that stud-
Business case Monetary units Net benefit (or
ied the use of vancomycin as perioperative prophylaxis during
loss) in dollars
coronary-artery bypass graft surgery (14).
and not included in each specific analysis so that informed deci-

sions can be made (6). A review of the IC literature found that of Cost-benefit analysis is a different form of economic evaluation
30 publications reporting to be economic analyses, only 8 were in that all aspects of the analysis, including the consequences
cost-effectiveness or cost-consequences analyses. Of note, in the of the intervention, are valued in monetary or dollar terms. If
IC and quality-improvement literature, there is increasing use of an intervention's benefits measured in dollars exceed its costs,
the term business case analysis, which is an extension of a simple then it is considered worthwhile (7). The m,Yor impediment
cost analysis from a hospital or payer prospective that excludes to the use of cost-benefit analysis in healthcare is the require-
dollar valuation of human life and morbidity (10,11). ment to value human life or health benefits in monetary units,
A detailed discussion of performing a business case analysis such as a human life-year equaling $200,000. Of note, most eco-
appears later in this chapter. nomic analyses of IC interventions that claim to be cost-benefit
analyses are mislabeled because they do not include a dollar
value for the important outcomes of interest (e.g., they do not
Cost-Minimiz~Jtion Anlllysis
place a dollar value on a human life or quality of life, and do
In cost-minimization analysis, the effectiveness of two interven- not include dollars saved from saving a life or improving quality
tions or products are assumed to be the same (equal efficacy of life in the analysis) .
and side effects), and the analysis is aimed at determining
which can be delivered least expensively ( 12). An example of
Whith Type ofAnlllysis Is Preferretl?
a cost-minimization analysis in IC is the choice between two
brands of nonlatex gloves. In this example, most would just Cost-effectiveness analysis and the closely related cost-utility
choose the less expensive brand. Note that this type of analysis analysis have emerged as the preferred methods for economic
does not apply to the choice between a brand of latex and a evaluation in healthcare (7,11). Importantly, it is recom-
brand of nonlatex gloves, because these can be associated with mended to compare new interventions to a reference case
different levels of healthcare worker (HCW) satisfaction and whenever possible, using standard units such as cost per lives
also allergic side effects. saved or QALYs saved (7) . If an agency wanted to choose be-
tween funding a hand-hygiene promotion initiative and a
cancer-screening program, it would be difficult to compare
Cost-Effecti:veness Anlllysis
cost per infection prevented with cost per cancer detected.
In contrast to cost-minimization, cost-effectiveness analysis However, if the comparison was cost per life-years saved or
compares interventions or products that have different costs cost per QALY saved with each program, an informed decision
and different effectiveness. If a specific new intervention costs could be reached.
more and is less effective or alternatively costs less and is more
effective than an existing intervention, the choice is easy.
What Is Considered Cost-Ejfecti11e?
However, if a new intervention delivers more at increased cost,
which occurs frequently in the setting of rapid technologic in- A standard threshold for calling a program cost-effective is for
tervention, the choice often is difficult. In cost-effectiveness the intervention to cost less than $50,000/QALY saved; how-
analysis, the benefits of an intervention are measured in the ever, some suggest the threshold has increased to $100,000/
QALY saved (15). The World Health Organization recom- and most useful when comparing disparate medical interven-
mends that a threshold for calling an intervention cost-effective tions. The U.S. Panel on Cost-Effectiveness in Health and Med-
be three times the country's gross domestic product per capita, icine states that even when a particular analysis is requested
so this threshold is $119,849 in the United States (16). Fr~ from a nonsocietal perspective, a complete societal perspec-
quently, but incorrectly, researchers will state only that an IC tive analysis also should be completed (7). hnportantly, a so-
intervention is cost-effective or cost-beneficial, if it is cost sav- cietal perspective analysis will inform broader comparisons of
ing from a hospital perspective. Most healthcare interventions programs and could lead to more equitable distribution of re-
are not cost saving. A review of all cost-effectiveness analyses sources to improve public health. It is possible that an analysis
published between 1976 and 2002 found only 130/1,433 (9%) from the societal perspective would suggest a different strategy
cost-effectiveness ratios actually saved costs, meaning that they than a more limited perspective (7).
saved lives and money at the same time (17). For example, an economic analysis done from a hospital
perspective would not include patient morbidity (e.g., reduced
functional mobility) and outpatient drug costs (Table 17.2).
PERSPECTIVE
Thus, a hospital might decide not to fund an SSI prevention pro-
The economic impact of HAis and interventions can be as- gram, because it will cost more in implementation and equip-
sessed from the perspective of society, the hospital, a third-party ment costs than it could recoup through reduced SSI costs,
payer (e.g., a health maintenance organization or the Centers such as in shortening length of stay or decreasing antimicrobial
for Medicare and Medicaid Services [CMS]), a government costs. However, an insurance company that must pay for ad-
agency (e.g., the Veterans Health Administration [VHA]), or ditional outpatient physician visits, medications, and home-
the patient. Studies that examine one perspective can underes- health visits attributable to the preventable SSis might want
timate the full economic effect of an infection or intervention; to fund the same SSI prevention program. Of course, neither
thus, it is important to recognize the perspective of a study to the hospital nor the insurance company perspective includes
appropriately interpret its results and to design a study from the patient morbidity, mortality, and other important factors, such
perspective of interest (Table 17.2). For instance, outpatient as the opportunity cost of lost wages. A societal perspective
physician visits to treat a surgical site infection (SSI) would be would include all such factors. It might be that a proper cost-
important to include in an analysis for the CMS, but would not effectiveness analysis of the SSI prevention program showing
be included in a typical acute care hospital cost analysis. large cost savings and lives saved from a societal perspective
The societal perspective is one that incorporates all costs would inform CMS or VHA to fund the program to the entire
and all health outcomes, regardless of who incurs the costs and society's benefit. It is likely that the continued lack of societal
who obtains the benefit (7).'I)'pically, except in instances when perspective cost-effectiveness analyses of IC interventions has
a specific organization is funding the analysis, the investigator facilitated the current underfunding of IC programs and the
should choose the societal perspective, which is the broadest continued incidence of preventable HAis.
TABLE 17.2 Examples of Costs and Outcomes Included Under Several Potential Analysis Perspectives
for Health Care-Associated Infection Prevention Interventions
'l)'pe of Resource Societal Perspective Payer Proapective Hospital Prospective
HOSPITALIZATION COSTS
Antibiotics X X X
Excess length of stay X X X
Intensive care stay X X X
INTERVENTION COSTS
Test costs X X
Gown and glove X X
Nurse and physician time X X
halation room X X
OUTPATIENT EXPENSES
Physician visits X X
Antibiotics X X
Home-health visits X X
Rehabilitation center stay X X
PATIENT EXPENSES AND OUTCOMES
Mortality X
Morbidity X
Infections X
Lost wages X
'liavel expenses X
PLACING MONETARY VALUES IN CONSTANT available to estimate the costs attributable to HAis was recently
DOLLAR. TERMS published by Roberts et al. (21).
AtljHstmentfor Injl11:tion
DEFINING COSTS
When data on costs used in economic analyses come from dif-
ferent years, they should be brought into current year values. Of critical importance is deciding which "costs" to measure. Po-
For instance, if you wanted to include the cost of an MRSA bac- tential approaches to evaluating the economic burden of HAis
teremia in a business case analysis for your hospital and you within an institution include measurement of hospital costs,
had only an estimate of the cost from 2006, you would need to hospital charges, resources used, and actual reimbursed charges
inflate that amount to current year dollars. The typical method (22). Hospital costs include daily operating costs (sometimes
for handling these adjustments is to inflate the dollar amounts called fixed costs) that do not vary based on patient volume
using a standard price index (e.g., the Medical Component of and the cost of drugs, tests, and other patient care-related ac-
the Consumer Price Index) (7,18). tivities (sometimes called variable costs), which depend on the
number of patients admitted or their length of hospitalization
(23). A hospital must ensure that all of its costs are reimbursed;
Discounting therefore, it assigns fees to hospital resources that are seen on
It is widely accepted that in economic analyses, all future costs a patient's bill as charges. Insurance companies, Medicare, and
and future health consequences should be stated in terms of Medicaid will not pay the amount on the bill because they re-
their present value (6,7). The process of converting both future ceive discounts; therefore, the charge on the bill for all patients
dollars and health outcomes to their present value is called dis- is greater than the actual hospital costs so as to cover these
counting. The U.S. Panel on Cost-Effectiveness in Health and "losses" (24). Hospital costs can be a useful outcome measure
Medicine recommends using a discount rate of both 5% and for an individual hospital because they best reflect the actual
3% (7). For example, if you assume that you will save $10,000 economic burden of the hospital. However, while some institu-
in preventing an MRSA infection next year by decolonizing a tions, such as the VHA (25), have implemented complex cost
patient with intranasal MRSA colonization this year, using a 3% accounting systems that track resources used and assign costs,
discount rate, the discounted savings would be $10,000/ (1 + in most institutions costs are more difficult to retrieve (26).
0.03)", or $9,709, where n is the number of years in the future In contrast, hospital charges are less reflective of actual cost,
the benefit is accrued. but usually are easy to retrieve from administrative databases and
are consistent from patient to patient in most settings. Because
hospital charges typically overestimate actual cost by 25% to
67%, adjustment using cost-to-charge ratios can be performed
MEASURING THE ECONOMIC IMPACT (26,27). Both hospital and departmental cost-to-charge ratios
OF AN HAl OR INFECTION-CONTROL are determined annually based on data submitted to the CMS.
INTERVENTION Hospital cost-to-charge ratios may be a more accurate measure of
costs for a cohort of patients in multiple diagnosis-related groups
Measuring the economic impact of an HAl or an intervention (DRG) while departmental cost-to-charge ratios may be more
to reduce HAis is important for two reasons. First, these data accurate for a cohort of patients in the same DRG (26,28,29).
can be valuable at the local institutional level. Obtaining data Direct measurement of resource utilization through the
regarding the incidence and attributable cost of an HAl allows use of micro-costing assesses specifically what services or pro-
an individual institution to understand the financial burden of cedures are used by a patient. However, for comparative pur-
the HAl, and assessing the impact of an intervention is criti- poses, use of resources must be translated into monetary value
cal in determining whether it has been successful and whether by multiplying the number of tests by their cost or charge. It
extensions of the interventions should be planned. Second, re- is important to note that physician professional fees and costs
sults regarding costs associated with infection and cost savings to the patient in the form of lost work are not captured when
associated with interventions provide raw data for use in cost- assessing only hospital costs or charges. In addition, economic
effectiveness, cost-utility, and cost-benefit analyses. This section measures of health care are not necessarily set by a market-
describes the design and analysis of studies that quantify the based pricing system. The costs of care for a specific patient
impact ofHAis and measure the outcomes ofiC interventions. are artificial and arbitrary computations that may vary between
sites and at different time periods.
Depending on the perspective of the study, the investigator
MEASURING THE ATI'RIBUTABLE COST OF HAis
must determine what proportion of hospital costs are reim-
Many studies that aim to define the attributable cost of HAis bursed by payers. If a portion of the costs of an infection are
have been published. Generally, these studies involve a set of reimbursed by an insurer, then only the portion not reimbursed
patients who develop the infection of interest and a reference should be included in a cost analysis from a hospital perspec-
group who do not develop the infection. Outcomes such as tive (30). This also is the proper cost estimate of a specific HAl
attributable mortality, length of hospitalization, and costs are that should end up in the business case analysis discussed later.
compared for the two groups. These studies are by definition Hospitals may use different ways to limit costs based on their
cohort studies because the outcomes of interest (e.g., morbid- method of reimbursement. For example, if reimbursement oc-
ity, mortality, and cost) occur after the exposure of interest curs per diem, the hospital will focus on reducing costly excess
(i.e., HAl). Examples of these studies include examinations lengths of stay, such as ICU or surgery days, rather than the
of the mortality and costs associated with ClA-BSI or MRSA- total length of stay; if reimbursement occurs based on the DRG
SSis (19,20). A particularly nice example of analytic methods or capitation, total expenses are the focus of cost reduction.
The ratio of the total costs or charges of patients with HAis of hospitalization and risk of HAl, cost, length of stay after in-
compared with those without HAis within one institution over a fection, and mortality. Studies involving no adjustment for the
relatively short period provides the most generalizable estimate "time at risk" for the development of an HAI have been shown
of the magnitude of the economic impact of HAis. In contrast, to lead to "time-dependent bias" in outcome measurements and
absolute values of cost or charge cited in studies should be overestimation of the length of hospitalization and costs that
interpreted with more caution because they may not be appli- are attributable to the HAI by up to 2-fold (33). For example, a
cable beyond the institution in which they were collected. It is recent study reported that excess length of stay attributable to
important to note that some administrators may view business HAis fell from 11.2 to 1.4 days when adjusting for length of stay
case analyses with skepticism if the cost data used are not from that occurred before development of the HAI (34).
the local institution. Multicenter studies must report measures Several methods have been proposed for accurately estimat-
that are standardized across institutions. ing the extra days spent in the hospital as a result of HAis and
If costs of HAis cannot be measured within your own in- the associated increased costs. At a minimum, patients in the
stitution, it may be necessary to use literature sources for the reference group who do not develop an HAl should be hos-
estimation of the economic impact of specific infections be- pitalized at least as long as the patients who develop an HAI
fore completing a business case analysis of an intervention. were hospitalized before acquiring the HAI. This can be ac-
A synthesis of the published literature on the cost of HAis was complished by matching case- and comparator-patients based
published by Stone et al. both for the periods from 1990 to on length of stay before the HAI or by performing more com-
2000 and from 2001 to 2004 (2,31); an additional summary plicated statistical analyses (33,35).
was published in 2009 (32). These estimates were limited by
the variable methods used in the studies that estimates costs,
Adjustmentfor Untlerlying Snerity ofIllness
yet provide the most complete available data of the costs and
11ntf. Comorbitf.ities
outcomes associated with the most common HAis (Table 17.3).
Care must be taken in controlling pre-HAl illness severity and
comorbidity. In studies assessing the impact of HAl, adjustment
MBTHODOLOGIC ISSUES IN COST
for underlying illness severity and comorbidities is essential
OUTCOMES STUDIES
because patients who develop HAis often have a more severe
Several methodologic issues in the design of these cohort stud- underlying disease than those who do not, which can indepen-
ies merit discussion, including controlling length of hospital- dently result in adverse outcomes.
ization before infection, adjusting underlying severity of illness, Various methods have been proposed and employed to
and selecting the reference group. grade severity of illness, including su~ective scores, ICU-data
driven measures, or administrative severity scores. However,
there is currently no well-validated aggregate illness severity
Adjustmentfor Length of Hospi:mliu.tion
score for infectious disease outcomes. McCabe and Jackson
before Infection
used a simple three-category score to predict mortality in pa-
Adjustment for differences in length of hospital stay before the tients with gram-negative bacteremia (36). This scoring system
onset of infection in patients with HAis and total length of hos- is widely used but is subjective, based completely on the judg-
pital stay of the comparator group who did not develop an HAI ment of the individual reviewing the patient record. No objec-
is important because there is a direct correlation between length tive physiologic data are included, limiting its generalizability
from study to study. This system works better as a predictor for
mortality than as a predictor for morbidity and cost.
TABLE 17.3 Attributable Outcomes
Other scores that have been proposed also have significant
and Costs of Health~ limitations. The Acute Physiology, Age, and Chronic Health
ABsodated Infections Based Evaluation (APACHE) score relies heavily on physiologic pa-
on Site of Infection• rameters, the majority of which are collected only in ICU set-
Hospital Total Hospital tings, and the score has been validated only to predict mortality
Cost Per Cost (in MilliODll) Deaths in ICU patients (37). Scoring systems such as the Medical Ill-
HAl Infection in U.S. Per Year ness Severity Grouping System (MedisGroup) admission sever-
ity group score and the All Patient Refined Diagnosis-Related
CLA-BSI ~.411 9,062 !0,665 Groups (APR-DRG) that were developed for administrative pur-
SSI 25,546 7,421 13,088 poses for risk acljustment have questionable utility in predicting
infectious disease outcomes and need further evaluation (38).
Ventilator- 9,969 2,494 35,967 The timing of the assessment of underlying disease severity
a!SOciated is of significant importance. Severity of illness is strongly influ-
pneumonia enced by the presence of infection and, therefore, may represent
Urinary tract 1,006 565 8,205
an intermediate variable in the chain of events between the expo-
infection sure (i.e., the infection) and the outcome of interest if assessed
when the patient is actively infected. Because acljustment for an
IIJ:n U.S. Dollars. intermediate variable usually causes an underestimation of the
Adapted from AHRQ. Action plan to prevent healthcare-associated effect of the exposure of interest on the outcome, care must be
infectiom. Department of Health and Human Services; 2009.
taken to assess severity of illness before (e.g., >48 hours) the first
http;//www.hhs.govI ash/ initiatives/hail actionplan/hhs_hai_
signs of infection (39). Results of studies that assign the illness
action_plan_final_06222009.pdf. Accessed july 18, 2012.
severity score at the time of the infection should be interpreted
with caution because they may underestimate the magnitude of the economic impact of antimicrobial-resistant pathogens (22,27).
the effect that the HAl has on outcomes (40). However, a 2005 survey of all IC intervention studies published
Aggregate comorbidity measures such as the Charlson Co- fuund that 69% used the quasi-experimental design, and only 4%
morbidity Index (41) or the Chronic Disease Score (42) have incorporated a cost analysis (50). From the periodJanuary 2001 to
been used to sununarize patients' underlying comorbidities June 2004, of the 30 studies claiming to be economic anal}'llis ofiC
for the purpose of adjustment in studies examining risk fac- interventions, only 5 were proper cost-effectiveness anal}'lles (2).
tors and outcomes of patients with HAis (43-46) . In particular, So few studies assessing the cost-effectiveness of interventions have
these scores can be a useful method to summarize the degree been published that there is a glaring need fur proper economic
of comorbidity when it is not feasible to include all individual evaluation of most IC interventions. Importantly, even in the few
comorbidities in an analysis with small numbers of subjects. studies completed, many have inherent methodologic weaknesses
The Charlson Comorbidity Index was originally designed as a that bias against reporting an IC intervention as "cost-effective."
measure of the risk of 1-year mortality attributable to comorbid- Following are the strengths and weaknesses of the basic study de-
ity in a prospective study of hospitalized patients and has been signs, which should be used when assessing the effectiveness and
adapted so that it can be calculated using International Classifi- cost-effectiveness of IC interventions.
cation of Diseases, Ninth Revision (ICD-9) codes obtained from
administrative databases (4 7). Commonly, it is used, although
Rsmdomizetl Controlled Trisls sntl
not well validated, in HAl risk factor and outcome studies.
Clwter-R.Jnulomizetl Control Trillls
The Chronic Disease Score is calculated based on current
medication use. It was originally based on outpatient medica- Infection-control interventions can be broken down into two
tions and used to predict physician-rated disease status, self- basic categories. The first is when the patient who is being inter-
rated health status, hospitalization, and mortality. It has since vened is the same patientwho directly benefits from the interven-
been modified by investigators to be based on medications tion. An example of this type of intervention is optimal timing of
prescribed on the day of hospital admission to predict SSI risk antimicrobial prophylaxis to reduce SSI risk (51). In this exam-
and the economic impact of SSI (44,48). In addition, other in- ple, the person who receives the correct antimicrobial(s) at the
vestigators have developed and validated new comorbidity risk correct time would be at reduced risk of developing an SSI and
measures based on the Chronic Disease Score for use in HAl no other patients in the hospital would directly benefit from this
risk factor studies and infections due to MRSA or vancomycin- intervention. Therefore, it can be said that the "unit of analysis"
resistant enterococci (VRE), although these have not been is the individual patient, if the purpose is to try to measure the
validated to predict outcomes due to infections ( 46) . benefit of appropriately timed antimicrobial use. In this exam-
ple, the gold standard study design to evaluate the efficacy and
safety is the randomized controlled trial. Even though observa-
Selection of the &ference Group
tional trials, such as cohort studies, can yield similar results to
The majority of studies assessing HAis have compared outcomes randomized controlled trials, a properly designed randomized
in patients with the infection of interest to patients without the controlled trial is considered the gold standard for evaluating
infection. This design assesses the independent impact of HAl the efficacy of interventions (52-54).
acquisition. However, studies that aim to assess the impact of an The second category of IC interventions is one in which the
HAl caused by a specific organism with a particular antibiotic re- specific IC program is directed at either individual patients or a
sistance pattern may have two reference groups, one with infec- specific population of patients, and a group of patients benefits
tion due to the susceptible organism and one without infection. from the program. An example of this type of intervention is ac-
For example, the outcomes of patients with SSI caused by MRSA tive surveillance testing for MRSA and isolation of colonized pa-
can be compared with those with SSI caused by methicillin- tients in a medical ICU setting. To study these types of programs,
susceptible S. aumJS (MSSA) to determine the incremental cost a cluster-randomized trial may be most useful to adjust for the
associated with methicillin resistance or can be compared with clustering effect that is inherent in control programs of trans-
patients without infection to determine the cost associated with missible infectious diseases (55,56). Patients impacted by these
MRSA-SSI. The latter type of comparison results in a much types ofiC programs represent a cluster (e.g., an ICU) exposed
higher estimate of adverse events attributable to resistance (20). to a common environment, care practices, and other patients
who are colonized with MRSA Studies that fail to control for
the nonindependence of patient outcomes may overestimate
MEASURING THE ECONOMIC IMPACT
the effectiveness of the intervention. Thus, the "unit of analysis"
OF INTERVENTIONS TO REDUCE HAis
in this case is the entire ICU, if the purpose is to try to mea-
Optimal decisions concerning IC programs must incorporate sure the benefit of active surveillance testing in reducing MRSA
the comparative effectiveness (49) and the economic impact colonization and infection. Instead of randomizing individual
of the specific interventions. Most of the utility of economic patients, individual ICUs need to be randomized so that mul-
analyses in the area of IC is in convincing hospital administra- tiple hospitals will need to be involved at great economic and
tion or public health authorities to fund and support a specific time costs. These types of trials are called cluster-randomized
intervention. Unfortunately, the current literature is lacking in trials or group randomized trials and are used increasingly by
high-quality studies, such as randomized controlled trials, that public health officials to study group interventions and individ-
can be used to support the effectiveness and cost-effectiveness ual interventions that have group-level effects (57). Numerous
of specific interventions. articles have been written about the specific methodologic and
Decision making around IC interventions requires the availabil- ethical issues in duster-randomized trials (56-60).
ity of proper cost-effectiveness analyses. Several important papers Situations in which randomized trials cannot be ethically
have outlined the optimal methodologies to use when measuring completed are frequent in hospital epidemiology, such as
evaluating the costs and effectiveness of an intervention to stop all possible baseline characteristics. Creation and analysis of
an active outbreak (61,62). Quasi-experimental studies, also mathematical models can typically be done more quickly and
known as pre-post intervention studies, and decision-analytic allow investigation within populations with varying characteris-
models can be used when it is not feasible to perform random- tics. Therefore, models can be an ideal way to determine which
ized controlled trials or duster-randomized control trials. interventions are most cost-effective and when, in preventing
the spread of transmissible pathogens, including MRSA or VRE
(73-75). As an example, active surveillance testing and isolation
of patients as a tool to control the spread of resistant organisms
Like randomized controlled trials, quasi-experimental studies in hospitals has been available for years, but is not universally
aim to demonstrate causality between an intervention and an implemented in hospital ICUs due to perceived costs and lack
outcome (63). They differ from randomized trials in that pa- of definitive clinical trial or other data (76). Many factors or
tients are put in the intervention arm and control arm with- variables that are related to the population (e.g., size of an ICU,
out randomization. As a result, these studies have a potentially discharge rate), individual patients (e.g., comorbidities, age), or
lower internal validity in that multiple potential confounders infectious organisms being evaluated (e.g., duration of coloniza-
and biases may affect their quality (64). Even with these limitation, likelihood of infection) can be individually evaluated with
tions, the quasi-experimental study design has been used with modeling strategies to assess their individual and combined im-
increased frequency in IC research; a 2004 review of the pub- portance in causing the observed outcome. This evaluation is
lished studies that assessed interventions to reduce HAis found called "sensitivity analysis" and is used in most mathematical and
that 69% used a quasi-experimental design and 23% used a decision models ( 73, 77) . Thus, mathematical models can focus
randomized trial (50). future clinical trials, greatly benefit patients, and optimize the
The most basic quasi-experimental design is the one-group expenditures within the limited budgets of microbiology and IC
pretest and posttest design in which a pre-intervention period departments. Given the number and great variety of hospitals
is compared with a post-intervention period in the same popu- and other healthcare institutions that exist, it would be nearly
lation. An example of this type of study is one in which MRSA impossible to perform clinical trials to test the cost-effectiveness
infection rates and associated treatment costs in a medical ICU of all potential IC interventions for all settings.
are measured 1 month before and 1 month after an interven-
tion when patients are bathed with chlorhexidine. One would
expect MRSA rates and associated costs to fall after the inter- PERFORMING A COST-EFFEGriVENESS
vention, but because there is only one measurement before ANALYSIS
and after and no control group, many alternative explanations
for the fall in MRSA rates could exist. Plenty of existing works describe the step-br-step completion
There are a variety of suggested improvements in the basic of a cost-effectiveness analysis (6,8,77). A complete descrip-
quasi-experimental design. These include adding multiple pre- tion of a cost-effectiveness analysis is beyond the scope of this
intervention and post-intervention measurements of rates and chapter; however, it is important to review the steps typically
costs (e.g., increasing the number of months in which MRSA taken in such an analysis to better interpret the literature for
infection rates and associated treatment costs are measured use in your specific clinical or hospital situation. Undertaking
before and after the intervention), including a nonequivalent a thorough cost-effectiveness analysis is quite complicated and
control group population (e.g., comparing changes in MRSA usually is completed with the assistance of a healthcare econo-
rates and costs in the medical ICU to those in a surgical ICU mist. It is important to contrast the methods and results of a
where the intervention has not occurred during the same cost-effectiveness analysis to those of the more commonly used
time period), and removing the intervention (e.g., compar- business case cost analysis, which we will discuss in detail later.
ing MRSA rates and costs before the intervention, during the
intervention, and after the intervention is stopped). A more
COST-EFFECTIVENESS ANALYSIS EXAMPLE
detailed explanation of options for quasi-experimental study
designs can be found elsewhere (63-66). The method of completing a cost-effectiveness analysis can be
A recent systematic review of IC and AS articles published broken down into several steps, starting with the clear state-
during 2002 and 2003 found that 39/73 studies (53%) used the ment of the problem and the proposed interventions. For
most basic quasi-experimental study design with single measure- example, you may wish to compare several different interven-
ments before and after the intervention and no control group tions or strategies for reducing CIA-BSis. These strategies
(65). Importantly, studies that assess the cost-effectiveness of might include an education program that improves catheter-
specific IC interventions using the basic quasi-experimental de- insertion techniques, use of antibiotic/antiseptic-coated cath-
sign should be interpreted with caution. eters, scheduled replacement of catheters, or elimination of
femoral venous site catheters. Inherent in the initial framing
of the problem is the determination of the perspective of the
Decision-Anslytic Models 11ntl.MJJthem~~tiud Models
analysis, such as hospital or societal perspective.
Mathematical models are useful tools for evaluating interven- The second step is then to develop or use a conceptual model
tion strategies before implementing them in human popula- for the infection of interest and the potential interventions (8).
tions (67-73). Models have been suggested as a method for A conceptual model allows the investigator to describe the full
completing virtual comparative-effectiveness analyses when range of outcomes and costs that occur with the condition of
available data are limited or lack generalizability ( 49). Impor- interest and are potentially impacted by the interventions under
tantly, clinical trials are expensive, labor intensive, and do not study. In our example, patient outcomes attributable to CIA-BSI
necessarily answer the question adequately for populations with could include excess length of stay, ICU admission, increased
Bacteremia life saved). In cost-utility analysis, outcomes are presented in

Antibiotic/antiseptic- QALYs so that the results would be reported in cost per QALY
impregnated saved (e.g., $2,000 per QALY).
catheters
Decision model analysis, like all types of epidemiologic inves-
tigation, is associated with uncertainty in the results, particularly
when many data inputs are from lower-level studies. It is likely
No bacteremia that several input parameters used in the model will be uncer-
Decision
tain or have wide confidence intervals. Importantly, a sensitivity
node
Bacteremia analysis should be performed by varying the model's parameter
data and model structure within expected ranges to confirm the
model's predictions and assess under what assumptions (e.g.,
Do nothing excess length of stay or mortality associated with a ClA-BSI or
cost of antibiotic/antiseptic-coated catheters) an intervention
will be most cost-effective in reducing the infections of interest
No bacteremia Sensitivity analyses improve the generalizability of the reported
findings, so that individual institutions or systems can determine
Figure 17.1. Hypothetical decision tree comparing the use of
antibiotic/antiseptic-impregnated catheters to a "do nothing" strategy under what conditions the intervention will be cost-effective in
in controlling CLA-BSI. their own unique hospital or healthcare system.
PERFORMING A BUSINESS
antimicrobial exposure, and associated mortality. Costs could CASE ANALYSIS
include acute care hospital costs, outpatient treatment costs,
and lost wages. In many instances, the conceptual framework Given the current reimbursement structure, IC and AS pro-
in a cost-effectiveness analysis is a decision-analytic model in the grams often are cost centers, not revenue generating, so they
form of a decision tree (Fig. 17.1). Thus, the creation of a deci- are identified as potential areas for budget cuts (78). In fact,
sion tree is commonly used to frame the conceptual model and many programs have faced downsizing in recent years (79,80).
complete the analysis. A decision tree or Markov model are not Demonstrating value to administrators is increasingly impor-
the only methods available for completing a cost-effectiveness tant because health executives are faced with many initiatives
analysis; however, they are now the standard methods used be- and shrinking budgets (81). To fend off downsizing, programs
cause they allow for sensitivity analysis. often must complete a business case economic analysis to initi-
After a framework in the form of a decision tree is com- ate a new program or justify continuing a program during bud-
pleted, the next step is to gather the data necessary to complete get negotiations.
the analysis, such as the probability of each outcome and the A business case analysis is a type of hospital perspective cost
expected decrease (or increase) in each outcome under each analysis because it typically leaves out patient outcomes. Broadly
intervention. In our example, it would be important to have an defined for use in a healthcare improvement intervention, a
estimate of the daily probability of a ClA-BSI for each day that business case "exists if the entity that invests in the interven-
a catheter is in place. In addition, the probability and length tion realizes a financial return on its investment in a reasonable
of both excess hospital and ICU stays and mortality associated time frame, using a reasonable rate of discounting" (10). The
with CIA-BSI would be needed. Most importantly, one would reasonable return can be through profit, reduction in losses, or
need the proportion of ClA-BSis prevented under each of the cost avoidance. In this instance, the purpose is to look purely
potential interventions and the costs of each intervention. at the dollar costs and benefits of an IC intervention or entire
The data inputs for the decision-analytic model can be gath- program to justify its existence to hospital administrators. The
ered from existing published literature or from primary data difficulty in making a business case cannot be overlooked be-
collection using existing hospital administrative or clinical data- cause many IC programs lack the economic expertise necessary
bases. Use of existing literature is important because investiga- to complete such an analysis. Anyone considering a business
tors cannot be expected to complete every possible clinical trial case analysis should contact local institutions' finance adminis-
to obtain data for the analysis. Investigators should preferen- trators for assistance in using the available local cost data.
tially use randomized clinical trials, followed by well-designed Often a certain intervention program has been in existence
upper-level quasi-experimental trials and other observational for several years and has kept rates of infections low. If these
studies ( 63) . Occasionally, estimates are generated by the use infections are now rare and no longer perceived as a problem,
of expert opinion; however, this is typically discouraged and administrators might want to cut a program focused on con-
should be carefully examined during the sensitivity analysis. trolling the infections, not realizing that the program is highly
When all of the necessary outcome probabilities and cost effective and even cost saving. The same difficulty arises when
estimates are available, the decision tree can be solved and an trying to initiate a new intervention program because it is easy
estimate of the cost-effectiveness of each intervention is com- to quantify the costs of a new program, but often difficult to
pleted. Basically, the completed analysis yields a net benefit estimate the benefits, particularly when very few clinical trials
(benefit of Intervention A minus benefit of Intervention B) are available to convince administrators and likely even fewer
and net cost (cost of Intervention A minus cost of Interven- resources to complete studies at your own institution.
tion B) of one intervention compared with another alternative One partial solution to facilitate saving an existing program
intervention. The cost-effectiveness is the ratio of net cost to net is to examine areas in which the intervention is not in place
benefit (e.g., $5,000 per infection prevented, or $15,000 per and compare infection rates in those areas to areas in which the
intervention is used. An example would be comparing CIA-BSI hiring an IP will save $500,000 in SSI costs alone. However, a
rates in a medical ICU where a prevention program exists to certain percentage of these costs is currently reimbursed by
those in a surgical ICU that does not have a CIA-BSI preven- third-party payers. Perhaps at your institution, 75% of costs are
tion program. Alternatively, if cost reductions force elimination reimbursed, so the cost savings from preventing 20 SSis would
of a specific program, it would be helpful to stagger the elimi- fall to $125,000. One study found that profits on surgical pa-
nation of a program so that as infection rates rise in certain tients fell from $3,288 when there were no complications to
units where an intervention is eliminated, this evidence could $755 when complications occurred (30) . Thus, the hospital still
be used to reinstitute the program. made money when complications occurred, but lost a potential
When an identified problem, new mandate, or new technol- profit of approximately $2,500 per complication.
ogy leads to the desire to introduce a new IC intervention, it is Completing the business case requires taking the estimated
important to remember that this is the time to collect outcome, cost savings or additional profits and subtracting the costs of the
cost, and implementation data that will justify this intervention up-front outlay, in this example, the salary and benefits of an IP.
in the future if it faces elimination when the institutional will In this example, the total gain to the hospital is estimated to be
dissipates. To that end, it often is helpful from an analysis and $50,000. Many IC interventions have multiple benefits. For in-
more importantly from an implementation perspective to roll stance, hand-hygiene education that is increased in response to an
out a new intervention in a stepwise fashion. This allows com- Acinetobacter baumannii outbreak also would be expected to reduce
parisons to control populations (wards or ICUs where the in- MRSA and VRE infections (82). To further make the business
tervention has not yet been implemented) using a higher-level case for an additional IP, one could include reduced infections
quasi-experimental design (63). and costs associated with other types of potentially preventable
infections that an additional IP could impact, such as ventilator-
associated pneumonia. A business case can also be developed to
BUSINESS CASE ANALYSIS EXAMPLE
justifY an AS program as demonstrated in a recent article (83).
The steps of a business case analysis parallel those of the cost- Even though a business case analysis does not include the
effectiveness analysis described earlier. The initial step is fram- adverse consequences of HAis, such as patient mortality, hos-
ing the problem and developing a hypothesis regarding the pital administrators do respond to those issues. While patient
potential solutions. For example, you may wish to implement safety cannot be the whole argument, some calculation of the
an intervention to reduce SSis in your hospital. To implement patient safety improvement associated with the intervention
an intervention to reduce these infections, it might be neces- should be included. If mortality associated with an SSI is 5%,
sary to hire additional staff for your IC department. Thus, you preventing 20 SSis is estimated to prevent one death. Addition-
are faced with the task of convincing your hospital administra- ally, preventing complications, such as SSis, might be associated
tion that the cost of an additional full-time employee (FTE) with reduced medicolegal costs. These must be included in a
will be offset by the cost savings through reduced infections, proper business case and can influence hospital administration.
including SSis. Thus, a hospitals risk management group should be involved
The next step is to determine the annual cost of the pro- early in any quality-improvement program economic analysis.
gram, in this instance, the salary of an FI'E including benefits.
This is available from many sources, including your own institu-
tional budgets or available online surveys. For example, an FI'E
REFERENCES
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You must now determine what costs can be avoided through
1. U.S. Department of Health I< Human Serviceo. Nalional Amon Pt.m to l'mlmt HBtlllllc,_.
reduced infections to determine whether the up-front cost of AuO<iatod hoftcOOns: RotJdttrtJfJ to Eliminotion. W31hlngton, DC: HHS; 2012.
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...,. fto~ Srd ed. O..Cord, UK: ODord Uni:vel'lity Preu; 2005.
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Oxford U ni:vel'lity Prcso; 2005.
vented, the next step is to determine the costs associated with 12. Stone PW, Hedblom EC, Murpby DM, et al. The economic impact of infection control:
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18 Victor D. Rosenthal
Epidetniology and Control

of Healthcare-Acquired Infections
in Litnited-Resource Settings
BACKGROUND the main causes of patient morbidity and mortality world-
wide. In studies from developed countries, it has been well-
Among the principal precepts of medical ethics is the old man- documented that HAis are responsible for increasing h011pital
date "fint, do no harm." During the first half of the 18th cen- costs as well (8,9) .
nny, healers from all over the world voiced their concern over Because of the great vulnerability of critically ill patients,
patient safety and their rilka of acquiring infections in hospitals HAis pose the most serious threats in the intensive care
as part of an iatrogenic consequence. unit (ICU) setting. For that reason, device-associated HAis
The concept of h ealthcai'e"Usociated infection (HAl) hu (DA-HAis) such aa cenml line-associated bloocbtream in-
been developed since then thanks to the work of enthusiasts fection (CLA-BSI) (10-1~), ventilator-a.uociated pneumonia
such as N"~ghtingale (1), Semmelweil (2), Pasteur (3), Koch (4), (YAP) (14-16), and catheter45Sociated urinary tract infec-
and I..i.ster (5) at the beginning of the •Bacteriological Era... tion (CA-UTI) (1'1) represent the most serious challenges to
After hospital reforms and asepsiJ, the victory over HAl was patient safety and quality healthcare in ICUs. In a review
Short-lived, as infections did not only occur in obstetric and about CLA-BSI in limited-resource countries by Rotenthal, a
surgical patients, but also in medical patients. The source of number of structural and behavioral reasons were associated
infection was not only bacterial but viral as well, spreading with higher rates of CLA-BSI, and among their most common
infection via air. The diNemination of Smptococcus fJ'Jopes observation~ were overcrowded ICUs, insufficient rooms for
railed clinical awareness during the tint decades of the ilolation, lack of sinb, lack of medical supplies in general, in-
20th century, declining its importance after the introduction cluding but not limited to alcohol hand rub, antiseptic soap,
of sulfonamides and p enicillin, and improved hospital hy- and paper towels (18) . In addition, a lack of supplies for the
giene methods. With the advent of serologic typing, the high wearing of maximal barriers during catheter insertion, a lack
incidence of crost-infection in scarlet and puerperal fever was of chlorhexidine for hand hygiene (HH) and akin antisepsis
finally elucidated (6) . purposes, and a lack of needleless connectors (and the subs~
It was not until the second half of the 20th century, however, quent use of three-way stopcocks) were noted. Moreover, poor
that infection prevention programs were structured and sys- performances in infection control practices, such as using cot-
tematized in hospitals. StophyWcoccus aumu became a focus of ton balls already impregnated with antiseptic contained in a
medical attention for hospital cross-infection in the late 1950s, contaminated container, not covering the insertion site with a
but it Willi the emergence of •phage 80/81 staphylococcus" in sterile dressing, storing drugs in open single-use viab, reming
the 1960 that caused notorious epidemica worldwide (1). It single-use vials, leaving needles inserted in multipl~use vials,
soon became more evident that rilks for HAl increased despite taking fluids from a 1,001kc container for the dilution of pal'-
the growing sophistication on healthcare tools and procedures. enteralsolu.tions, and using tacky mats were paramount ( 18).
Infectious diseases have been identified as the second most The World Bank. classifies countries into four economic
common came of death in the world (7). A wide diversity of strata on the basis of 2011 gross national income per capita:
factors strongly influences the occurrence and transmission low-income, middle-income (subdmded into lower-middle
of infectious diseases. The 1ocioeconomic &cton such as pov- and uppel'-middle), or high-income. Together, low-income
erty, homelesmess, and high unemployment rates have been countries, lower-middle-income countries, and upper-middle-
acknowledged to expand infections, including HAls. Other income countries' economies are sometimes referred to as
factors such aa global travel, emergence of old debilitating developing economies, developing countries, lower-income
and mortal diseases, and wars also play a substantial role in countries, low-resource countries, or emerging countries. In thil
transmitting pathogen~. Confronted with these threats, which chapter, they will be referred to as limited-resource countries.
are out of the direct medical scope, infection control profes- Limited-resource countries represent 144/209 (68.8%) coun-
sionals may feel ove rwhelmed by the challenge of reducing tries of the world and > 75% of the world population (19). In
and controlling HAis. HAis have been shown to be among high-income countries, such as the United States, the Centers
230
Chapter 18 • EpidemWlogy and Control ofHealthcare-Acquired Inf«tions in Limittdr.Resource Settings 231
for Disease Control and Prevention (CDC) National Health- Asia, Europe, and Latin America (Argentina, Bolivia, Brazil,
care Safety Network (NHSN) (previously, the National Nosoco- Bulgaria, China, Colombia, Costa Rica, Croatia, Cuba, Czech
mial Infections Surveillance [NNIS] system) (20) has provided Republic, Dominican Republic, Ecuador, Egypt, El Salvador,
standardized definitions for HAis, thereby allowing prospective Greece, India, Italy, Iran, Jordan, Kosovo, Lebanon, Lithuania,
surveillance targeted on DA-HA!s rates per 1,000 device-days to Macedonia, Malaysia, Mexico, Morocco, Nigeria, Pakistan,
be benchmarked against rates determined in different health- Panama, Peru, Philippines, Poland, Puerto Rico, Romania,
care facilities worldwide (21-23). Furthermore, using the CDC Saudi Arabia, Serbia, Singapore, Slovakia, Sri Lanka, Sudan,
methodology, surveillance data for the calculation of DA-HAI Thailand, Thnisia, Thrkey, Uruguay, Venezuela, and Vietnam)
rates include specific risk factors, which is fundamental to detect (31-35). Data from these hospitals has greatly expanded our
and improve problems at the hospital level. knowledge of the epidemiology of and prevention of HAis in
In the context of an expanded framework for HAl control, limited-resource countries (36-53).
most of the relevant studies of ICU-acquired infections have
been carried out in high-income countries (24). In the United
States, HAis are among the top 10 causes of death, being the PRIORITIES FOR INFECTION CONTROL
main healthcare complication. A study from the United States IN LIMITED-RESOURCE SETIINGS
reported that the number of annual deaths attributable to
HAis ranged from 44,000 to 99,000 (25). In different studies, Allocation of national resources comes within the competence
most from developed countries, it has been shown that with ef- of governments, and decisions on funding are made according
fective HAl preventive interventions, many lives and extra costs to different priorities. So, public health needs must compete
can be saved. Findings in the scientific literature have shown for funding against other important national matters, many
that original CDC infection control programs that include HAl times more visible, including educational, environmental, po-
surveillance can reduce their incidence by >30% (26). Accord- litical, social, economic, and other fundamental issues. Given
ing to an estimate by the CDC in 2002, US national costs for the high visibility of improvements in a country's infrastructure,
HAl were approximately $6 billion (27); these extra costs can not-so-visible positive outcomes of HAl prevention programs
be reduced by 32% with the implementation of effective HAl may be left behind by policy makers and managers of national
prevention programs (28). programs. Thus, the resources needed for the implementation
In different countries, national conferences were organized of infection control strategies at the hospital level are often
to examine the burden of HAl from a broader perspective. insufficient. However, even if underestimated, public health is
This issue became of primary importance in several countries, primary for the successful functioning of other national priori-
where medical institutions established committees to start the ties, affecting different social aspects, such as work and social
appointment of Infection Control coordinators in healthcare well-being. Promoting global health, therefore, is beneficial to
facilities, the implementation of infection control programs, the population as a whole, and should be treated as a global
and the organization of workshops to respond to the need for priority not only in instances of epidemic diseases, but ideally,
training in infection control. to cover every aspect of health and infection prevention.
There have been good examples of global planning, such There are several factors that may render infection con-
as during the severe acute respiratory syndrome (SARS) world- trol initiatives ineffective, namely lack of attention and proper
wide outbreak in 2003, which resulted in great mobilization of promotion of health improvement by agencies at national and
resources from the World Health Organization (WHO), in coor- international levels. Poverty and insufficient engagement by
dination with experts, pharmaceutical research and laboratories hospital administrators, governments, and health ministers are
in national agencies worldwide. This global approach resulted in among the other negative factors. Moreover, professional infec-
successful tracking and containment of spread. Additionally, in tion control societies of nurses, physicians, and laboratorians
2005 the WHO has launched a global health initiative related (if any) are not fully committed to the promotion of infection
for HAl prevention called "Clean Care is Safer Care" with the prevention.
aim of promoting HH worldwide (29). Then in 2009, the WHO A m~or limitation on the progress of infection control has
publillhed its guidelines, including a combination of previ- been lack of priority in the agenda of policy makers. Fortu-
ously published data, a new formulation for alcohol hand-rub nately, the field of infection prevention and control of HAis
products, among several other recommendations (30). via surveillance programs has reached the limited-resource
In limited-resource countries, with the emergence of the In- countries during the last decade. Many problems remain un-
ternational Nosocomial Infection Control Consortium (INICC) resolved, such as how to implement surveillance programs
in 1998 in Argentina, which was expanded internationally in for the effective prevention and control of HAis. A lack of a
2002, HAl surveillance and HAl prevention interventions were global perspective has limited the scope of organized strategies
expanded worldwide (31-35). INICC started to conduct surveil- and research agenda, whose items revolve around minor ques-
lance by applying standardized definitions of the CDC-NNIS, tions and fragmented approaches, squandering considerable
and NHSN (20-23). In order to raise global awareness and resources.
help reduce HAl rates, INICC has been dedicated to provide Global initiatives focused on the prevention and control of
free tools, to measure HAis and their adverse consequences, HAis have only emerged in the last decade. At present, different
and to measure and improve compliance with infection control global health initiatives have been well-coordinated and have
practices (31-35). INICC became the first international HAl provided great benefit to the recipients and donors. A list of pri-
surveillance program to measure, prevent, and control HAis orities that addresses these issues and provides a framework for
by means of the analysis and feedback of outcome and process finding a solution for these needs in limited-resource settings
surveillance data collected by hospital collaborators worldwide; was developed by a wide range of independent international or-
this system currently exists in hospitals in 46 countries ofAfrica, ganizations, including INICC, the WHO, the Joint Commission
International (JCI), the International Federation of Infection • Vision: A society that recognizes the legitimate right of
Control (IFIC), the International Healthcare Worker Safety a hospitalized patient to be delivered safe healthcare.
Center, the Asia Pacific Society of Infection Control (APSIC), A society in which the scientific and medical community
Eastern Mediterranean Regional Network for Infection Con- works for the safeguard of good infection control and
trol (EMR-NIC), Baltic Network for Infection Control and surveillance practices. A society with the minimum inci-
Containment of Antimicrobial Resistance (BALTICCARE), dence of HAis.
Southeastern Europe Infection Control (SEEIC), Pan American
Association of Infection Control, The Infection Prevention &
WORLD HEALTH ORGANIZATION: FIRST GLOBAL
Control Africa Network (IPCAN), and others.
PATIENT SAFETY CHALLENGE: CLEAN CARE IS
These priorities focus on raising awareness, fostering re-
SAFER CARE
search, developing guidelines, promoting education, surveil-
lance, prevention, and control of HAl and can be condensed • The goal of Clean Care is Safer Care is to ensure that
into the following: infection control is acknowledged universally as a solid
and essential basis toward patient safety and supports the
1. Assessment of facilities, infrastructure, supplies, and hu-
reduction of HAis and their consequences.
man resources dedicated to surveillance, prevention, and
• As a global campaign to improve nn among healthcare
control ofHAis.
workers (HCWs), Save Lives: Clean Your Hands is a ma-
2. Surveillance of DA-HAis in ICUs (CIA-BSI, VAP, and CA-
jor component of Clean Care is Safer Care. It advocates
UTI) and their consequences, such as mortality, extra
the need to improve and sustain nn practices of HCWs
length of stay (LOS), and cost.
at the right times and in the right way to help reduce the
3. Surveillance of surgical site infections (SSis), and their
spread of potentially lif~threatening infections in health-
consequences such as mortality, extra LOS, and cost.
care facilities.
4. Assessment of prevention strategies for CIA-BSI, VAP, and
CA-UTI.
5. Assessment of prevention strategies for SSI. JOINT COMMISSION INTERNATIONAL
6. Measuring the financial impact of complications and the
• Mission: To continuously improve healthcare for the
cost-effectiveness of interventions.
public, in collaboration with other stakeholders, by
7. Studies related to improved antibiotic usage and manage-
evaluating healthcare organizations and inspiring them
ment of antibiotic resistance.
to excel in providing safe and effective care of the
8. Development, edition, promotion, and distribution of
highest quality and value.
guidelines to prevent and control HAis (DA-HAis and SSis).
• Vision: All people always experience the safest, highest
9. Improving compliance with practices known to be ben-
quality, best-value healthcare across all settings.
eficial, especially nn, appropriate staffing in healthcare
• As the international arm ofJCI has been working
institutions, and other components for HAl control and
with healthcare organizations, ministries of health,
prevention programs.
and global organizations in more than 80 countries
10. Improving compliance with specific interventions proven
since 1994.
effective for prevention and control of each specific
• Our focus is on improving the safety of patient care
DA-HAI.
through the provision of accreditation and certification
11. Preventing occupational transmission of bloodborne
services as well as through advisory and educational ser-
pathogens.
vices aimed at helping organizations implement practical
12. Establishment of worldwide, national, regional, and local
and sustainable solutions.
networks to provide support and information, improve
practices, and reduce the steep learning curve more effi-
ciently and economically. INTERNATIONAL HEALTHCARE
13. Surveillance and reduction of healthcare-associated trans- WORKER SAFETY CENTER
mission of epidemic respiratory diseases, such as influenza.
• Mission: Protecting HCWs. Millions ofHCWs around the
globe face a daily risk of contracting lif~threatening oc-
cupational infections, such as HIY, hepatitis B, and hepa-
MISSION, VISION, AND GOALS OF titis C, from occupational exposures to patients' blood
INTERNATIONAL ORGANIZATIONS and body fluids. The International Healthcare Worker
DEDICATED TO SURVEll.,LANCE, Safety Center at the University of Virginia is dedicated to
PREVENTION, AND CONTROL reducing this serious risk.
OF HEALTHCARE-ASSOCIATED
INFECfiONS AND SAFETY IN INTERNATIONAL FEDERATION
LIMITED-RESOURCE COUNTRIES OF INFECTION CONTROL
• Vision: To become the leading worldwide network
INTERNATIONAL NOSOCOMIAL INFECTION
facilitator between organizations and individuals active in
CONTROL CONSORTIUM (INICC)
the prevention and control of HAis.
• Mission: We are an international scientific community • Mission: To facilitate international networking in
that works interactively through a network aiming at order to improve the prevention and control of HAis
reducing healthcar~associated infections. worldwide.
THE INICC PROGRAM meetings and publishing in peer-reviewed journals, and (k) co-
operates with hospitals and organizations worldwide in order to
The INICC (www.INICC.org) is a nonprofit, open, multicenter, improve surveillance and control of HAis.
international, collaborative program modeled on the U.S. INICC sends a protocol to INICC members, who review it
CDC.NNIS/NHSN system. Founded in Argentina in 1998, it is with their research committees and agree to full participation
the first international research network that includes prospec- by signing a commitment letter and sending it to the INICC
tive, targeted, outcome and process surveillance designed to central office in Buenos Aires, which then processes data, and
identify and reduce HAl rates and their consequences in the provides analyses and reports on a monthly basis, answers ques-
participating facilities (~H-35). tions, and augments the tutorial with personal instructions
Its objectives are the following: To create a global network when needed.
using standardized HAl surveillance definitions and method- Forms and software designed to record data and direct infec-
ology in order to reduce HAis, their attributable mortality, tion control activities are used for both control patients without
bacterial resistance, length of hospital stay, and extra cost. To HAl and patients with HAis. These forms include age, gender,
collaborate in the development, adaptation, promotion, and underlying diseases, and severity of illness score at the time of
edition of local guidelines for the control and prevention of entrance to the ICU. On a daily basis, information regarding
HAis. To enhance safety and quality of healthcare in every temperature, blood pressure, device-days, cultures taken, pres-
healthcare facility. To optimize antimicrobial use for prophy- ence of clinical pneumonia, antibiotic use, and characteristics
laxis or treatment. To stimulate, support, guide, and advice on of any surrogate of infection is collected both for cases and
the development of research projects aimed at reducing HAis. controls. Thus, it is also possible to validate received data and
To train HCWs in order to improve their skills for scientific re- analyze cases and controls in a prospective cohort nested study
search. To foster relevant scientific evidence-based literature (36-37,40,42-53).
for the surveillance, prevention, and control ofHAis by design- At the same time, process surveillance and performance
ing, coordinating, and publishing scientific research studies on feedback are done for HH compliance, vascular and urinary
the clinical and cost-effectiveness of proved or new infection catheter care, mechanical ventilator care, and measures to
control interventions. prevent SSis. Data collected for process surveillance purposes
INICC does the following activities with hospitals of limited- include HH compliance and key interventions to prevent CLA-
resource countries: (a) provides tools for and training for out- BSI, CA-UTI, VAP, and SSI, such as practices for insertion of the
come HAl surveillance, (b) provides tools for and training for central line, skin antisepsis, placement of gauze on intravascu-
HAl process surveillance, (c) develops and provides charts and lar (IV) access insertion sites, marking the date on the IV ad-
tables for feedback of HAl rates, (e) develops and provides ministration set, condition of the gauze, position of the urinary
charts and tables for performance feedback, (f) provides an catheter regarding the leg and position of urine bag regarding
infection control bundle with targeted interventions guided the bed, among many others.
by risk-factor analysis and cost-effective interventions guided INICC has reported HAl rates by country (Tables 18.1
by cost analysis, (g) provides education and training in infec- and 18.2), and in international global reports (Table 18.2),
tion control guidelines application, (h) provides secretarial mortality rates (Tables 18.3 to 18.5), as well as extra LOS
and administrative support in entering data, (i) develops and (Tables 18.6 to 18.8), and extra cost (Tables 18.9 and 18.10)
sends charts, scientific data analysis, and data interpretation to from several participating hospitals that applied the INICC
guide actions, (j) analyzes, edits, and shares data at scientific methodology (31).
TABLE 18.1 Overall Healthcare-Associated Infection Rates in Facilities Reported by Hospitals

from Economics Defined as Low-, Lower-Middle, and Upper-Middle Income by the
World Bank Rqlortcd as Crude Rates: Proportion Infec:ted over Patients Discharged or
Admitted to the Units and Reported as Proportion Infected per 1,000 Patient-Days in
the Unit or Hospital
Country Type of Study/Unit Type of HAl HAl Rate(%) Year Ref
Argentina (INICC Study) Multicenter adult ICU Overall 27.0 2003 (37)
Brazil Multicenter newborn ICU Overall 28.1 2004 (194)
Brazil (INICC Study) Multicenter adult ICU Overall 29.6 2006 (195)
Brazil NewborniCU Overall 50.7 2002 (79)
Chile Hospitalwide Overall 14.0 2001 (81)
China Hoapitalwide Overall 3.04 2005 (80)
Colombia NewborniCU Overall 5.3 2005 (196)
Colombia (INICC Study) Multicenter adult ICU Overall 12.2 2006 (40)
Croatia (INICC Study) AdultiCU Overall 7.0 2006 (197)
Costa Rica (INICC Study) AdultiCU Overall 4.8 2009 (198)
Cuba (INICC Study) Multicenter adult ICU Overall 22.4 2011 (49)
Egypt Pediatric ICU Overall 2!1.0 2005 (199)
India (INICC Study) Multicenter adult ICU Overall 12.3 2005 (200)
Mexico Hospitalwide Overall 21.0 2002 (201)
Mexico Multicenter adult ICU Overall 23.2 2000 (82)
Mexico (INICC Study) Multicenter adult ICU Overall 24.4 2006 (42)
(continued)
TABLE 18.1 Oftrall Hcalthcarc:-Assodated Infection Rates in Fadlitics Kcportcd by Hospitals

World Bank Reported as Crude Rates: Proportion Infected over Patients Discharged or
Admitted to the Units and Reported as Proportion Infected per 1,000 Patient-Days in
the Unit or Hospital (Omri•Wil)
Country 'I)pe of Study/Unit 'l)'pe of HAl HAl Rate (%) Year Ref
Morocco (INICC Study) AdultmedicaliCU Overall 19.3 2005 (202)
Peru (INICC Study) Multicenter adult ICU Overall 11.2 2005 (203)
Philippines (INICC Study) AdultiCU Overall 19.1 2006 (204)
Saudi Arabia Multicenter hospitalwide Overall 2.8 2004 (205)
Saudi Arabia Hospitalwide, maternity Overall 4.0 2002 (206)
hospital
Saudi Arabia Hospitalwide Overall 8.5 2002 (207)
Saudi Arabia AdultiCU Overall 19.8 2002 (207)
Saudi Arabia NewborniCU Overall !15.8 2002 (207)
Thnzania Multicenter hospitalwide Overall 14.8 2003 (208)
Thnzania AdultmedicaliCU Overall 40.0 2003 (208)
Turkey AdultiCU Overall 12.5 2000 (84)
Thrkey AdultiCU Overall !13.0 200!1 (209)
Thrkey (INICC Study) Multicenter adult ICU Overall 20.5 2005 (211)
Turkey Multicenter adult ICU Overall 48.7 2004 (212)
Turkey Neurology ICU Overall 88.9 2005 (213)
INICC 8 countries: Argentina, Brazil, Colombia, Multicenter adult ICU Overall 14.7 2005 (32)
India, Mexico, Morocco, Peru, and Thrkey
(INICC Study)
Kuwait AdultMSICU Overall 10.6 2008 (214)
China NewborniCU Overall 11.6 2007 (215)
Turkey General pediatric wards Overall !W2 2012 (216)
India Pediatric ICU Overall 19.3 2011 (217)
Thrkey NewborniCU Overall Range: 14.1-29.7 2010 (220)
Macedonia (INICC Study) AdultiCU Overall 2.1 2010 (222)
Tunisia (INICC Study) Newborn and Overall 4.1 2010 (223)
pediatric ICU
Bangladesh AdultiCU Overall 30 2011 (224)
Albania AdultiCU Overall !11.6 2008 (225)
Albania Surgical ICU Overall 22.0 2008 (225)
Pakistan AdultiCU Overall !19.7 2007 (226)
Lebanon (INICC Study) AdultiCU Overall 9.8 2012 (52)
Poland (INICC Study) AdultiCU Overall 24.3 2012 (53)
Egypt (INICC Study) AdultiCU Overall !12.8 2012 (227)
Egypt (INICC Study) Pediatric ICU Overall 24.5 2012 (227)
Bulgaria NewborniCU Overall 1.9 2011 (228)
Kosovo AdultiCU Overall 64.3 2008 (229)
Kosovo Adult and newborn ICU Overall 17.4 2006 (230)
Serbia AdultiCU Overall 1.5-40.8 2006 (231)
Argentina (INICC Study) Multicenter adult ICU Overall 90.0 per 1,000 patient-days 200!1 (37)
Brazil Multicenter adult ICU Overall !10.6 per 1,000 patient-days 2006 (195)
Brazil Multicenter newborn ICU Overall 24.9 per 1,000 patient-days 2004 (194)
Brazil NewborniCU Overall 62.0 per 1,000 patient-days 2002 (79)
Colombia (INICC Study) NewborniCU Overall 6.2 per 1,000 patient-days 2005 (196)
Colombia (INICC Study) Multicenter adult ICU Overall 18.2 per 1,000 patient-days 2006 (40)
Croatia (INICC Study) AdultiCU Overall 25.6 per 1,000 patient-days 2006 (297)
Costa Rica (INICC Study) AdultiCU Overall 13.9 per 1,000 patient-days 2009 (232)
Egypt Pediatric ICU Overall 40.0 per 1,000 patient-days 2005 (199)
India (INICC Study) Multicenter adult ICU Overall 21.4 per 1,000 patient-days 2005 (200)
India Hospitalwide Overall !16.2 per 1,000 patient-days 2004 (23!1)
Mexico (INICC Study) Multicenter adult ICU Overall 39.0 per 1,000 patient-days 2006 (42)
Morocco (INICC Study) AdultmedicaliCU Overall 20.4 per 1,000 patient-days 2005 (202)
Peru (INICC Study) Multicenter adult ICU Overall 25.3 per 1,000 patient-days 2005 (203)
Philippines (INICC Study) AdultiCU Overall 27.5 per 1,000 patient-days 2006 (204)
Turkey (INICC Study) Multicenter adult ICU Overall 48.4 per 1,000 patient-days 2005 (43)
Turkey (INICC Study) Neurology ICU Overall 84.2 per 1,000 patient-days 2005 (211)
Cuba (INICC Study) Multicenter adult ICU Overall !10.6 per 1,000 patient-days 2011 (49)
INICC (INICC Study) Multicenter adult ICU Overall 22.5 per 1,000 patient-days 2005 (!12)
Thrkey BumiCU Overall 18.2 per 1,000 patient-days 2009 (234)
TABLE 18.1 Ovc:rall Hcalthcare-.Assodatcd Infection Kates in Facilities kportcd by Hospitals

World Bank Reported as Crude Kates: Proportion Infcd:cd over Patients Discharged or
Admittal to the Units and :hported as Proportion Infcd:ed per 1,000 Patient-Days in
the Unit or Hospital (Omri•wil)
Country Type of Study/Unit Type of HAl HAl Rate(%) Year Ref
Lithuania 5 pediatric ICUs Overall 24.5 per 1,000 patient-days 2009 (235)
Kuwait AdultMSICU Overall 20.6 per 1,000 patient-days 2008 (214)
China NewbomiCU Overall 14.9 per 1,000 patient-days 2007 (215)
Turkey General pediatric wards Overall 3.17 per 1,000 patient-days 2012 (216)
India Pediatric ICU Overall 21 per 1,000 patient-days 2011 (217)
Turkey ICU Overall 21.6 per 1,000 patient-days 2011 (218)
Egypt Pediatric ICU Overall 8.6 per 1,000 patient-days 2011 (236)
Egypt Multicenter ICU Overall 20.5 per 1,000 patient-days 2012 (237)
Egypt (INICC Study) AdultiCU Overall 52.9 per 1,000 patient-days 2012 (227)
Egypt (INICC Study) Pediatric ICU Overall 22.8 per 1,000 patient-days 2012 (227)
Turkey NewbomiCU Overall Range: 10.9-17.3 per 2010 (220)
1,000 patient-days
Lebanon (INICC Study) AdultiCU Overall 11.85 per 1,000 2012 (52)
patient-days
Turkey AdultiCU Overall 30.2 per 1,000 patient-days 2012 (238)
Poland (INICC Study) AdultiCU Overall 21.9 per 1,000 patient-days 2012 (53)
Serbia AdultiCU Overall 1.5-65.6 per 1,000 2006 (231)
patient-days
Macedonia (INICC Study) AdultiCU Overall 4.5 per 1,000 patient-days 2010 (222)
1\misia (INICC Study) Pediatric and Overall 6.88 per 1,000 bed-days 2010 (223)
newbomiCU
INICC, International Nosocomial Infection Control Consortium; ICU, intensive care unit; MS, medical surgical; Ref, reference.
TABLE 18.2 Derice-.Assodated lnfectiom per 1,000 Dericc-Days :&ported by Hospitals from Economics
Dc:6ncd as Low-, or Lower-Middle, or Upper-Middle Income by the World Bank
VAPper CA-UTI
Number CLA-BSiper 1,000 per 1,000
Country ICUType of patients 1,000 CL-clays device-day~~ deviceGay5 Year Ref
Argentina (INICC Study) Adult 3,319 30.3 46.3 18.5 2004 (239)
Argentina (INICC Study) Adult 2,525 2.7 2004 (52)
Argentina Adult 11.4 2002 (240)
Albania Adult, PICU, 968 40.0 41.0 (86)
NICU
Brazil (INICC Study) Adult 1,mn 9.1 20.9 9.6 2008 (36)
Brazil NICU 1,443 17.3 3.2 2010 (87)
Brazil (INICC Study) Adult,PICU 320 34.0 26.0 2003 (57)
Brazil PICU 515 10.2 18.7 1.8 2003 (88)
Brazil (INICC Study) NICU 6,243 3.1 4.3 2007 (195)
China (INICC Study) Adult 391,527 3.1 20.8 6.4 2011 (51)
China (INICC Study) Adult 2,631 7.66 10.46 1.3 2012 (146)
Colombia (INICC Study) Adult 2,172 11.3 10.1 4.3 2006 (40)
Cuba (INICC Study) Adult 1,982 2.0 52.5 8.1 2011 (49)
Egypt (INICC Study) Adult 473 22.5 73.4 34.2 2011 (227)
Egypt (INICC Study) PICU 143 18.8 31.8 2011 (227)
El Salvador (INICC Study) PICU 1,145 10.1 12.1 5.8 2011 (48)
El Salvador (INICC Study) NICU 1,270 16.1 9.9 2011 (48)
India (INICC Study) Adult 10,835 7.9 10.4 1.4 2007 (44)
India Adult, PICU, 0.48 21.9 0.6 2010 (89)
NICU
India NICU 27.0 2011 (90)
Iran Adult 106 147.3 275 137.5 2004 (91)
Mexico (INICC Study) Adult 1,055 23.1 21.8 13.4 2006 (42)
Morocco (INICC Study) Adult 1,731 15.7 43.2 11.7 2009 (47)
Peru (INICC Study) Adult 1,920 7.7 31.3 5.1 2008 (45)
Peru PICU 414 18.1 7.9 5.1 2010 (92)
Philippines (INICC Study) Adult 2,887 4.6 16.7 4.2 2011 (50)
Philippines (INICC Study) PICU 252 8.23 12.8 0.0 2011 (50)
Philippines (INICC Study) NICU 1,813 20.8 0.44 2011 (50)
(continued)
TABLE 18.2 Dcvk.c-Assodatal Infa:tiom per 1,000 ~-Days &:ported by Hospitals from Bconomks
De:6ned as I.Dw-, or Lower-.Middle, or Upper-Middle Income by the World BaDk (Ctnait~flell)
VAP per CA.-UTI
Number of CLA-BSiper 1,000 per 1,000
Country ICUType patients 1,000 CL-days d~~ de~ Year Ref
Poland (INICC Study) Adult 847 4.01 18.2 4.8 2011 (53)
Saudi Arabia NICU 8.2 2009 (93)
Tunisia Adult 340 15.3 4.4 2006 (94)
Tunisia Adult 647 14.8 2007 (95)
Thrkey (INICC Study) Adult 3,288 17.6 26.5 8.3 2007 (43)
Turkey Adult 509 11.8 27.1 9.6 2010 (96)
Thrkey Adult 6,005 2.8 21.2 11.9 2011 (97)
Lebanon (INICC Study) Adult 666 5.2 8.1 4.1 2011 (52)
Kuwait Adult 1,173 5.5 9.1 2.3 2008 (214)
China NICU 638 18 (per 1,000 63.3 2007 (215)
umbilical-days)
Turkey NICU 600 3.8 13.76 2012 (241)
Thrkey Adult 204 19.02 2012 (242)
lithuania PICU 1,239 7.7 28.8 3.4 2009 (235)
Croatia (INICC Study) Adult 369 8.3 47.8 6.0 2006 (197)
Costa Rica (INICC Study) Adult 125 4.65 29.9 2009 (198)
Macedonia (INICC Study) Adult 1,558 1.47 6.58 0.45 2010 (222)
Thnisia (INICC Study) PICU,NICU 367 8.65 5.56 0.0 2010 (223)
INICC 8 countries: Argentina, Brazil, Adult, PICU, 21,069 18.5 24.1 8.9 2006 (32)
Colombia, India, Mexico, Morocco, NICU
Peru, and Turkey (INICC Study)
INICC 18 countries: Argentina, Brazil, Adult, PICU 43,114 9.2 19.5 6.5 2008 (33)
Chile, Colombia, Costa Rica, Cuba,
India, Kosovo, Lebanon, Macedo-
nia, Mexico, Morocco, Nigeria,
Peru, Philippines, El Salvador,
Turkey, and Uruguay (INICC Study)
INICC 18 countries: Argentina, Brazil, NICU 1,323 14.8 7.5 2008 (33)
Chile, Colombia, Costa Rica, Cuba,
India, Kosovo, Lebanon, Macedonia,
Mexico, Morocco, Nigeria, Peru,
Philippines, El Salvador, Turkey, and
Uruguay (INICC Study)
China, Colombia, Costa Rica, Cuba,
Greece, India,Jordan, Kosova,
Lebanon, Lithuania, Macedonia,
Mexico, Morocco, Pakistan,
Panama, Peru, Philippines,
El Salvador, Thailand, Tunisia,
Thrk.ey, Venezuela, and Vietnam
(INICC Study)
Greece, India, jordan, Kosova,
Lebanon, lithuania, Macedonia,
Mexico, Morocco, Pakistan, Panama,
Thailand, Thnisia, Thrkey, Venezuela,
and Vietnam (INICC Study)
Bulgaria, China, Colombia, Costa
Rica, Cuba, Dominican Republic,
Ecuador, Egypt, Greece, India,
jordan, Kosova, Lebanon, Lithuania,
Macedonia, Malaysia, Mexico,
Morocco, Pakistan, Panama, Peru,
Philippines, Puerto Rico, El Salvador,
Saudi Arabia, Singapore, Sudan,
Sri Lanka, Thailand, Tunisia, Turkey,
Uruguay, Venezuela, and Vtetnam
(INICC Study)
TABLE 18.2 Dcvkc-Asaodatal Infm:ioDs per 1,000 Device-Days lkportal by Hospitals from Emnomk:s
Defined as Low-, or I..owu-Middlc, or Upper-Middle Income by the Workl Bank (Omn•Wil)
VAP per CA-UTI
Number of CLA-BSI per 1,000 per 1,000
Country ICU 'I)'pe patients 1,000 CLdays device-days device-daya Year Ref
Bulgaria, China, Colombia, Costa
Rica, Cuba, Dominican Republic,
Ecuador, Egypt, Greece, India,
Jordan, Kosova, Lebanon, Lithuania,
Philippines, Puerto Rico, El Salvador,
Saudi Arabia, Singapore, Sudan, Sri
Lanka, Thailand, Tunisia, Turkey,
Uruguay, Venezuela, and Vietnam
(INICC Study)
Colombia, Dominican Republic,
India, Jordan, Malaysia, Mexico,
Morocco, Peru, Philippines,
El Salvador, Thailand, Tunisia, and
Turkey (INICC Study)
CLA-BSI, central line-associated bloodstream infection; VAP, ventilator.rusociated pneumonia; CA-UTI, catheter.rusociated urinary tract
infection; Ref, reference; ICU, intensive care unit; PICU, pediatric intensive care unit; NICU, neonatal intensive care unit; CL, central line;
INICC, International Nosocomial Infection Control Consortium.
TABLE 18.3 Bxtra Mortality of Central Line-Associated Bloodstream Infection &ported

by Hospitals from Economies Defined aa Low-, Lower-Middle, and Upper-Middle
Income by the World Bank
Morbility Extra
without Morbility with Morbility
Country ICU 'I)'pe HAl(%) CLA-BSI (%) (%) RR 95% CI p Year Ref
Argentina (INICC Study) Adult 29.6 54.2 24.6 2003 (144)
Brazil (INICC Study) Adult 19.2 47.1 27.8 2.44 1.46--4.09 0.0001 2008 (36)
Colombia (INICC Study) Adult 18. 1 36. 6 18.5 2.02 1..42-2.87 0.0001 2006 (40)
Cuba (INICC Study) Adult 33.0 50.0 17.0 1.52 0.4--6.1 0.5552 2011 (49)
El Salvador (INICC Study) PICU 13.6 25.0 11.4 1.84 0.97-3.50 0.0586 2011 (48)
El Salvador (INICC Study) NICU 12 . !1 38.0 25.7 !1.09 2 .. 17--4.42 0.001 2011 (48)
Macedonia (INICC Study) Adult 2.4 30.0 28 6.80 5.25--8.81 0.0001 2010 (222)
'1\misia (INICC Study) PICU, NICU 8.2 14.7 6 1.79 0.69--4.62 0.2226 2010 (223)
India (INICC Study) Adult 6.6 10.6 4.0 1.60 1.08--2.37 0.0001 2007 (44)
Mexico (INICC Study) Adult 21..8 41..8 20 1..92 0 ..95---3.85 0.06 2007 (150)
Morocco (INICC Study) Adult 24.9 100 75.1 4.02 1.50--0.77 0.0027 2009 (47)
Peru (INICC Study) Adult 14.0 29.0 15.0 2.07 1..07--4.04 0.0280 2008 (45)
Philippines (INICC Study) Adult 6.8 10.0 3.2 1.48 0.21-10.56 0.695 2011 (50)
Philippines (INICC Study) PICU 3.8 50.0 46.3 13.3 2.88--61..7 0.0001 2011 (50)
Philippines (INICC Study) NICU 5.6 25.0 19.4 4.46 0.62-32.3 0.1033 2011 (50)
Lebanon (INICC Study) Adult 19.1 60.0 40.9 !1.14 1.38--7.13 0.0039 2011 (52)
INICC 8 countries: Argentina, Adult, PICU, 17. 1 35.2 18.0 2006 (24!1)
Brazil, Colombia, India, Mexico, NICU
Morocco, Peru, and Turkey
(INICC Study)
INICC 18 countries: Argentina, Adult, PICU 15.!1 29.6 14.!1 2008 (33)
Brazil, Chile, Colombia, Costa
Rica, Cuba, India, Kosovo,
Lebanon, Macedonia, Mexico,
Morocco, Nigeria, Peru,
Philippines, El Salvador, Turkey,
and Uruguay (INICC Study)
(continued)
TABLE 18.3 Extra Mortality of Central Lin~Assodatcd Bloodstream Infection Reported
by Hospitals from Economics Defined as Low-, J..owao-Middle, and Upper-Middle
Income by the World Bank (Ctlrm•wtl)
Mortality Extra
without Mortality with Mortality
Country ICUType HAl(%) CLA-BSI (%) (%) RR 95% CI p Year Ref
INICC 18 countries: Argentina, NICU 14.3 39.7 25.4 2008 (33)
INICC 25 countries; Argentina, Adult,PICU 14.4 38.1 23.6 21.6-25.7 2009 (34)
Brazil, China, Colombia, Costa
Rica, Cuba, Greece, India,
Jordan, Kowva, Lebanon,
Lithuania, Macedonia, Mexico,
Philippines, El Salvador, Thailand,
1\misia, Thrkey, Venezuela, and
Vietnam (INICC Study)
INICC 25 countries; Argentina, NICU 8.8 34.5 25.7 26.7-42.9 2010 (34)
Jordan, Kowva, Lebanon,
Tunisia, Turkey, Venezuela, and
INICC !16 countries; Argentina, Adult,PICU 10.0 24.7 14.7 12.8-16.6 2010 (35)
Brazil, Bulgaria, China, Colombia,
Costa Rica, Cuba, Dominican
Republic, Ecuador, Egypt, Greece,
India,Jordan, Kosova, Lebanon,
Lithuania, Macedonia, Malaysia,
Panama, Peru, Philippines, Puerto
Rico, El Salvador, Saudi Arabia,
Singapore, Sudan, Sri Lanka,
Thailand, Thniaia, Thrkey, Uruguay,
Venezuela, and Vietnam (INICC
Study)
INICC !16 countries; Argentina, NICU 9.1 35.!1 26.2 20.3-32.4 2010 (35)
India,Jordan, Kosova, Lebanon,
Thailand, Tuniaia, Turkey, Uruguay,
Venezuela, and Vtetnam (INICC
Study)
INICC 15 countries: Argentina, NICU 9.4 37.1 27.7 21.1-34.5 2011 (167)
Brazil, Colombia, Dominican
Republic, India,Jordan, Malaysia,
Mexico, Morocco, Peru, Philippines,
E'J Salvador, Thailand, '1\misia, and
Thrkey (INICC Study)
HAl, healthcare-associated infection; CLA-BSI, centralline--11»0ciated bloodstream infection; Ref, reference; ICU, intensive care unit; PICU,
pediatric intensive care unit; NICU, neonatal intensive care unit; RR, relative risk; CI, confidence interval; INICC, International Nosocomial
Infection Control Consortium.
238
TABLE 18.4 Extra Mortality ofVcntilator-.Assodatcd P.ncum.onia Kcportcd by Hospitals from

Economics Dc6ncd as Low-, Lower-Middle, and Upper-Middle Income by the World Bank
Mortality Mortality Extra
ICU without with Mortality
Country Type HAl(%) VAP (%) (%) RR 95%CI p Year Ref
Argentina (INICC Study) Adult 33.2 63.5 30.3 0.0001 2005 (145)
Brazil (INICC Study) Adult 19.2 34.5 15.3 2.91 2.72-3.13 0.0001 2008 (36)
Colombia (INICC Study) Adult 18.1 35.0 16.9 1.93 1.24-3.00 0.003 2006 (40)
Cuba (INICC Study) Adult 33 80 47 2.42 0.9-6.5 0.0693 2011 (49)
El Salvador (INICC Study) PICU 13.6 19.0 5.5 1.4 0.78-2.53 0.2592 2011 (48)
El Salvador (INICC Study) NICU 12.3 2lt0 10.7 1.88 1.20-2.93 0.0050 2011 (48)
India (INICC Study) Adult 6.6 25.6 19.0 3.87 2.70-5.54 0.0001 2007 (44)
Macedonia (INICC Study) Adult 2.4 45.5 43 19.05 5.25-8.81 0.0001 2010 (222)
Tunisia (INICC Study) PICU, 8.2 100 92 12.17 3.71-39.96 0.0001 2010 (223)
NICU
Costa Rica (INICC Study) Adult 5.0 20.0 15.0 3.97 0.45-32.95 0.1678 2009 (198)
Croatia (INICC Study) Adult 17.4 7.56 0.96-59.64 0.0236 2006 (244)
Morocco (INICC Study) Adult 24.9 81.6 56.7 3.28 2.51-4.29 0.0001 2009 (47)
Peru (INICC Study) Adult 14.0 38.5 24.5 2.75 2.00-3.78 0.0001 2008 (45)
Philippines (INICC Study) Adult 6.8 9.7 3.0 1.44 0.67-3.06 0.3454 2011 (50)
Philippines (INICC Study) PICU 3.8 0.0 -3.8 Undef Undef 0.7373 2011 (50)
Philippines (INICC Study) NICU 5.6 2011 (50)
Lebanon (INICC Study) Adult 19.1 15.0 0.78 0.25-2.47 0.6780 2011 (52)
INICC 10 countries: Argentina, Adult, PICU, 14.0 2-27 2011 (17!1)
Brazil, Colombia, Greece, India, NICU
Lebanon, Mexico, Morocco,
INICC 8 countries: Argentina, Adult, PICU, 17.1 44.9 27.8 2006 (243)
Brazil, Colombia, India, Mexico, NICU
Morocco, Peru, and Thrkey
(INICC Study)
INICC 18 countries: Argentina, Adult, PICU, 15.!1 42.8 27.5 2008 (33)
Brazil, Chile, Colombia, Costa NICU
INICC 18 countries: Argentina, NICU 14.3 46.5 !12.2 2008 (33)
INICC 25 countries: Argentina, Adult, PICU 14.4 43.7 29.!1 27.1-!11.4 2009 (34)
jondan,~,Lebanon,
V~etnam (INICC Study)
INICC 25 countries: Argentina, NICU 9.4 27.3 17.9 11.0-25.8 2010 (34)
Jondan, Kosova, Lebanon,
1\misia, '1\.Jrkey, Venezuela, and
V~etnam (INICC Study)
(continued)
TABLE 18.4 Extra Mortality ofVcntilator-Assodatal Pneumonia Reported by Hospitals from F..mnomics
Defined as Low-, l..owa'-Middle, and Upper-Middle Income by the World Bank (Cmm•fllll)
without withVAP Mortality
Country ICUType HAl(%) (%) (%) RR 95% CI p Year Ref
INICC 36 countries: Argentina, Adult, PICU 10.0 25.2 15.2 2010 (35)
Brazil, Bulgaria, China,
Colombia, Costa Rica, Cuba,
Dominican Republic, Ecuador,
Egypt, Greece, India,Jordan,
Kosova, Lebanon, Lithuania,
Morocco, Pakistan, Panama,
Peru, Philippines, Puerto Rico,
El Salvador, Saudi Arabia,
Thailand, Tuni..ia, Turkey,
Uruguay, Venezuela, and
INICC 36 countries: Argentina, NICU 9.1 24.0 14.9 8 .9--21.1 2010 (35)
India, jordan, Kosova, Lebanon,
Mexico, Morocco, Paki..tan,
Puerto Rico, El Salvador, Saudi
Arabia, Singapore, Sudan, Sri
Lanb., Thailand, Tuni..ia, Turkey,
(INICC Study)
INICC 15 countries: Argentina, NICU 9.4 27.3 17.9 2011 (167)
Brazil, Colombia, Dominican
Republic, India,jordan,
Malaysia, Mexico, Morocco,
Thailand, Tunuia, and Turkey
(INICC Study)
HAl, healthcare-associated infection; VAP, ventilator-usociated pneumonia; ICU, intensive care unit; PICU, pediatric intensive care unit;
NICU, neonatal intensive care unit; RR, relative risk; CI, confidence interval; INICC, International Nosocomial Infection Control Consortium;
Ref, reference.
TABLE 18.5 Extra .Mortality of Catheter-Associated Urinary Tract Infection Reported by Hospitals
from Economics Defined & Low-, Lowa--Middle, and Upper-Middle Income by the
World Bank
Mortality
Mortality with Extra
ICU without CA-liTI Mortality
Co101try Type HAl(%) (%) (%) RR 95% CI p Year Ref
Argentina (INICC Study) Adult !17.2 42.9 5.7 200!1 (100)
Brazil (INICC Study) Adult 19.2 !10.0 10.7 1.56 0.69-3.52 0.2875 2008 (36)
Colombia (INICC Study) Adult 18.1 28.6 10.5 1.58 0.78-!1.18 0.199 2006 (40)
Cuba (INICC Study) Adult 40.0 50.0 10.0 1.25 0.40-3.93 0.7018 2008 (49)
El Salvador (INICC Study) PICU 13.6 18.2 4.6 1.34 0.33--5.41 0.681 2011 (48)
India (INICC Study) Adult 6.6 18.2 11.6 2.8!1 2.57-!1.12 0.0001 2007 (44)
Morocco (INICC Study) Adult 24.9 43.6 18.7 1.75 1.08-2.85 0.0218 2009 (47)
Peru (INICC Study) Adult 14.0 18.2 4.2 1.!10 0.49--!1.49 0.6028 2008 (45)
Philippines (INICC Study) Adult 6.8 3.8 -2.9 0 .57 0.08-4.06 0.5683 2011 (50)
Lebanon (INICC Study) Adult 19.1 12.5 0.65 0.16-2.65 0.5487 2011 (52)
TABLE 18.5 Extra Mortality of Cathctu-.Assodated Urinary Tract Infection Reported by Hospitals
from Economics Defined As Low-, Lower-Middle, and Upper-Middle Income by the
World Bank (Ctmti•wtl)
ICU without with Mortality
Country 'I)'pe HAl(%) CA-UTI (%) (%) RR 95% CI p Year Ref
INICC 10 countries: Argentina, Adult, 15.0 3--28 2011 (151)
Brazil, Colombia, Greece, India, PICU,
Lebanon, Mexico, Morocco, NICU
INICC 8 countries: Argentina, Brazil, Adult, 17.1 38.4 21.3 2006 (243)
Colombia, India, Mexico, Morocco, PICU
INICC 18 countries: Argentina, Adult, 15.!1 !15.8 20.5 2008 (!13)
Brazil, Chile, Colombia, Costa PICU
Rica, Cuba, India, K.osovo,
INICC 25 countries: Argentina, Adult, 14.4 !12.9 18.5 15.1-22.1 2009 (!14)
Brazil, China, Colombia, Costa PICU
jordan, Kosova, Lebanon,
Morocco, Pakistan, PanaJDa, Peru,
INICC 36 countries: Argentina, Adult, 10.0 17.3 7.!1 5.7-9.1 2010 (35)
Brazil, Bulgaria, China, Colombia, PICU
India, jordan, K.osova, Lebanon,
Lanka, Thailand, Tunisia, Turkey,
(INICC Study)
HAl, healthcare-associated infection; CA-UTI, catheter-associated urinary tract infection; ICU, intensive care unit; PICU, pediatric intensive
care unit; NICU, neonatal intensive care unit; RR, relative risk; CI, confidence interval; INICC, International Nosocomial Infection Control
Consortium; Ref, reference.
Extra Length of Stay of Central ~.Associated Bloodstream Infection Reported by

Hospitals from Economics Defined. as Low-, Lower-Middle, and Upper-Middle Income
by the World Bank
LOS LOS with Extra
ICU without CLA-BSI LOS
Country Type HAl (days) (days) (days) RR 95% CI p Year Ref
Argentina (INICC Study) Adult 12.14 26.08 1!1.9 2003 (100)
Cuba (INICC Study) Adult 4.9 23.3 18.3 4.7 9.4-85.8 2011 (48)
El Salvador (INICC Study) PICU 6.2 19.1 12.9 2.08 14.1-26.5 2011 (48)
El Salvador (INICC Study) NICU 16.7 37.7 21.0 31.3--45.9 2011 (48)
India (INICC Study) Adult 4.4 9.4 5.0 2.15 2.06-2.24 0.0001 2007 (44)
Macedonia (INICC Study) Adult 4.3 22.2 17.9 2010 (222)
Tunisia (INICC Study) PICU, 5.5 6.8 1.3 2010 (223)
NICU
(continued)
TABLE 18.6 Extra Length of Stay of Central Linc-Assoc:iatal Bloodstream Infection llqJortal by
Hospitals &om Economies Defined as Low-, Lower-Middle, and Upper-Middle Income
by the World Bank (Conri•Wil)
LOS LOS with Extra
ICU without CLA-BSI LOS
Country 'I)'pe HAl (days) (days) (days) RR 95%CI p Year Ref
Croatia (INICC Study) Adult 2.1 11.0 8.9 5.34 2.95--9.69 0.001 2006 (244)
Mexico (INICC Study) Adult 7.34 13.4 6.05 2007 (150)
Morocco (INICC Study) Adult 5.3 10.0 4.7 0.0004 2007 ( 150)
Philippines (INICC Study) Adult 4.3 16.2 11.9 3.79 9.0-33.5 2011 (50)
Philippines (INICC Study) PICU 5.6 17.0 11.4 3.03 6.9-62.5 2011 (50)
Philippines (INICC Study) NICU 12.6 28.0 15.4 2.21 11.2-104.2 2011 (50)
Poland (INICC Study) Adult 6.9 10.0 3.1 1.4 3.24!7.7 2011 (53)
Lebanon (INICC Study) Adult 7.3 13.8 6.5 1.88 7.7-28.4 2011 (52)
Algeria NICU 15.1 24.3 9.2 2008 (245)
China, Colombia, Costa Rica, Cuba, PICU
Greece, India,Jordan, Ko&Jw,
Mexico, Morocco, PalWtan, Panama,
Thailand, TunWa, Turkey, Venezuela,
INICC 25 countries: Argentina, Brazil, NICU 11.1 22.2 17.9-27.5 2009 (34)
Greece, India, Jordan, Kosova,
Peru, Philippines, E1 Salvador,
Thailand, Tunisia, Turkey, Venezuela,
INICC 36 countries: Argentina, Adult, 6.2 17.1 10.9 2011 (35)
Brazil, Bulgaria, China, Colombia, PICU
Lithuania, Macedonia, Malaf5ia,
Lanka, Thailand, Thnisia, Thrkey,
(INICC Study)
INICC 36 countries: Argentina, NICU 9.1 35.3 26.2 20.3--32.4 2011 (35)
El Salvador, Saudi Ambia, Singapore,
Sudan, Sri Lanka, Thailand, Tunisia,
Turkey, Uruguay, Venezuela, and
V1.etnam (INICC Study)
INICC 15 countries: Argentina, Brazil, NICU 11.4 29.8 18.4 2011 (167)
Colombia, Dominican Republic,
India, Jordan, Malaf'ia, Mexico,
Morocco, Peru, Philippines,
El Salvador, Thailand, Tunisia, and
Thrkey (INICC Study)
LOS, length of stay; HAl, healthcare-associated infection; CLA-BSI, central line-associated bloodstream infection; Ref, re ference ; ICU,
intensive care unit; PICU, pediatric intensive care unit; NICU, neonatal intensive care unit; RR, relative risk; Cl, confide nce interval; INICC,
International Nosocomial Infection Control Consortium.
TABLE 18.7 Extra Length of Stay ofVcntilator-Assoclatcd Pneumonia in Hospitals kportcd by

Hospitals from Economies Defined as Low-, Lower-Middle, and Upper-Middle Income
by the World Bank
LOS LOS
ICU without withVAP Extra LOS
Country Type HAl (days) (days) (days) RR 95%CI p Year Ref
Argentina (INICC Study)) Adult 10.73 19.3 8.95 2005 (145)
Cuba (INICC Study) Adult 4.9 23.8 18.9 4.9 10.5-73.3 2011 (49)
El Salvador (INICC Study) PICU 6.2 18.6 12.4 11.8--24.0 2011 (48)
El Salvador (INICC Study) NICU 16.7 42.3 25.5 34.8-51.9 2011 (48)
India (INICC Study) Adult 4.4 15.3 11.0 3.50 3.34--3.67 0.0001 2007 (44)
Morocco (INICC Study) Adult 5.3 10.8 5.5 0.0001 2007 (150)
Macedonia (INICC Study) Adult 4.3 23.0 4.1 2010 (222)
Tunisia (INICC Study) PICU, 5.5 20.0 14.5 2010 (223)
NICU
Croatia (INICC Study) Adult 2.1 14.2 12.1 6.90 5.40-8.80 0.001 2006 (244)
Philippines (INICC Study) PICU 5.6 10.7 5.1 1.90 4.0--52.1 2011 (50)
Poland (INICC Study) NICU 6.9 15.5 8.6 2.2 6.4--56.9 2011 (53)
Thrkey (INICC Study) Adult 6.6 16.1 0.0001 2007
Lebanon (INICC Study) Adult 7.3 18.8 11.4 2.56 12.3--30.5 2011 (52)
INICC 10 counoies: Argentina, Brazil, Adult, 2.03 1.52-2.54 2011 (173)
Colombia, Greece, India, Lebanon, PICU,
Mexico, Morocco, Peru, and Thrkey NICU
(INICC Study)
INICC 25 counoies: Argentina, Brazil, Adult, 5.0 15.58 10.58 2009 (34)
China, Colombia, Costa Rica, Cuba, PICU
Greece, India,Jordan, Kosova,
INICC 25 countries: Argentina, Brazil, NICU 11.1 27.3 16.2 22.6-33.3 2009 (34)
Greece, India, Jordan, Kosova,
Bulgaria, China, Colombia, Costa Rica, PICU
Cuba, Dominican Republic, Ecuador,
Egypt, Greece, India, Jordan, Kosova,
Malaysia, Mexico, Morocco, Pakistan,
Singapore, Sudan, Sri Lanka, Thailand,
1\misia, Thrkey, Uruguay, Venezuela,
INICC 36 counoies: Argentina, Brazil, NICU 9.1 24.0 14.9 8.9-21.1 2011 (35)
Bulgaria, China, Colombia, Costa Rica,
Cuba, Dominican Republic, Ecuador,
Egypt, Greece, India,Jordan, Kosova,
Malaysia, Mexico, Morocco, Pakistan,
Singapore, Sudan, Sri Lanka, Thailand,
Tunisia, Turkey, Uruguay, Venezuela,
(continued)
TABLE 18.7 Extra Length of Stay of Ventilator-.Associated Pneumonia in Hospitals Reported by

by the World Bank (Conri•Wil)
LOS LOS
ICU without with YAP Extra LOS
Country 'IyPe HAl (days) (days) (days) RR 95%CI p Year Ref
INICC 15 countries: Argentina, Brazil, NICU 11.4 37.0 25.6 2011 (167)
Colombia, Dominican Republic, India,
Jordan, Malaysia, Mexico, Morocco,
Peru, Philippines, El Salvador, Thailand,
Tunisia, and Turkey (INICC Study)
LOS, length of stay; HAl, healthcare-as.sociated infection; VAP, ventilator-associated pneumonia; Ref, reference; ICU, interuive care unit; PICU,
pediatric intensive care unit; NICU, neonatal intensive care unit; RR, relative risk; CI, confidence interval; INICC, International Nosocomial
Infection Control Consortium.
TABLE 18.8 Extra Length of Stay of Cat:hctcr-.Assodatcd Urinary Tract Infection Reported by
by the World Bank
LOS LOS with
ICU without CA-UTI ExtraLOS
Country Type HAl (days) (days) (days) RR 95% CI p Year Ref
Argentina (INICC Study) Adult 12.14 17.5 5.36 200!1 (100)
El Salvador (INICC Study) PICU 6.2 13.5 7.4 7.8-26.8 2011 (48)
India (INICC Study) Adult 4.4 12.4 8.0 2.83 2.57-!1.12 0.001 2007 (44)
Morocco (INICC Study) Adult 5.3 13.8 8.5 0.0001 2007 (150)
Peru (INICC Study) Adult 4.0 10.8 6.8 2.71 2.38-!1.08 0.0001 2008 (45)
Croatia (INICC Study) Adult 2.1 7.0 4.9 3.40 2.00-5.77 0.001 2006 (244)
Poland (INICC Study) Adult 6.9 15.0 8.1 2.2 4.5-1!12.6 2011 (53)
Lebanon (INICC Study) Adult 7.3 15.8 8.5 2.16 9.9-27.4 2011 (52)
INICC 10 countries: Argentina, Adult, 1.59 0.58-2.59 2011 (151 )
Brazil, Colombia, Greece, India, PICU
Lebanon, Mexico, Morocco,
Peru, and Thrkey (INICC Study)
Brazil, China, Colombia, Costa PICU
Jordan, Kosova, Lebanon,
Morocco, Paki.uan, Panama, Peru,
Vtetnam (INICC Study)
Brazil, Bulgaria, China, PICU
Colombia, Costa Rica, Cuba,
Dominican Republic, Ecuador,
Egypt, Greece, India, Jordan,
Kosova, Lebanon, Lithuania,
Morocco, Pakistan, Panama,
El Salvador, Saudi Arabia,
Thailand, Thnisia, Thrkey,
Uruguay, Venezuela, and
LOS, length of stay; HAl, healthcare-associated infection; CA-UTI, catheter-associated urinary tract infe ction; ICU, intensive care unit; PICU,
pediatric intensive care unit; NICU, neonatal intensive care unit; RR, relative risk; CI, confide nce interval; INICC, International Nosocomial
Infection Control Consortium; Ref, reference.
TABLE 18.9 Extra Cost ofVcntilator-Assodatcd Pneumonia Reported by Hospitals from Economics
Defined as Low-, Lower-Middle, and Upper-Middle Income by the World Bank
Country Cost of controls (no HAl) (USD) Cost of patient with VAP (USD) Extra cost (USD) Year Ref
Argentina (INICC Study) 4,946.46 2,69!1.58 2,252.88 2005 (145)
HAl, healthcareoQSSOciated infection; VAP, ventilator-associated pneumonia; INICC, International Nosocomial Infection Control Consortium;
Ref, reference.
TABLE 18.10 Extra Cost of Central Line-Associated Bloodstream Infection lleportcd by Hospitals
from Economics Defined as Low-, Lowcr-Middle, and Upper-Middle Iru:omc by the
World Bank
Cost of patient
Country Cost of controls (no HAl) (USD) with CLA-BSI (USD) Extra cost (USD) Year Ref
Argentina (INICC Study) 7,971.74 !1,08!1.!12 4,888.42 200!1 (144)
Mexico (INICC Study) 28,966.!14 17,!175.41 11,590.9!1 2007 (150)
Algeria 1,!115 2008 (245)
HAl, healthcareoQSSOciated infection; CLA-BSI, centralline-lll!Sociated bloodstream infection; INICC, International Nosocomial Infection
Control Consortium; Ref, reference.
THE INTERNATIONAL NOSOCOMIAL For this reason, the infection control bundle serves as a means
INFECTION CONTROL CONSORTIUM to ensure that all interventions are carried out consistently for
(INICC) MULTIDIMENSIONAL all patients and at all times. The effective implementation of
any infection control bundle depends on the full development
APPROACH of team work, since it is necessary to improve the reliability lev-
els (72). The application ofDA-HAI control bundles in the ICU
The INICC multidimensional approach, designed to reduce
setting provides specific evidence to support possible changes
HAl and mortality rates, cost, LOS, as well as bacterial resistance
for additional improvements in patient safety. The effectiveness
includes the following six activities: (a) bundle of infection con-
of the implementation of an infection control bundle is mea-
trol interventions, (b) education about outcome surveillance,
sured by recording full adherence to all bundle elements; if any
process surveillance, and infection control guidelines, (c) out-
of these elements is not included in the record, this is counted
come surveillance of HAl rates and consequences, (d) process
as incomplete implementation, unless the missing element re-
surveillance of infection control interventions, (e) feedback of
fers to a specific medical contraindication. This focus on the
HAl rates and consequences, and (f) performance feedback of
application of all the elements contained in the infection con-
infection control practices (54-64).
trol bundle enables HCWs' awareness of the importance of
compliance with the collection of elements, rather than with
isolated interventions. Furthermore, this team-oriented, whole-
BUNDLE OF INFECTION CONTROL
method strategy provides a fundamental boost to improvement
INTERVENTIONS
changes in the healthcare delivery system as whole.
An infection control bundle consists of a collection of interven-
tions based on scientific evidence and key recommendations for
EDUCATION
practice. The INICC multidimensional approach includes an in-
fection control bundle for the prevention ofHAis that is based Another crucial factor for an effective implementation of any
on practical and cost-effective measures that are described in infection control program is education of HCWs. It is essential
the guidelines published by the Society for HealthCare Epide- that HH practices be deeply rooted and embedded in hospi-
miology of America (SHEA) and the Infectious Diseases Society tals' customs, traditions, and culture.
of America (IDSA) published in 2008 (65-69), by the Associa- Education must at least include basic information that raises
tion for Professionals of Infection Control and Epidemiology, awareness of the risk involved in patient safety if healthcare
Inc. in 2009 (70), by the WHO published in 2009 (30), by the delivery practices are not adequately performed. Each HCW
CDC in 2011 (68), and by the JCI in 2012 (71). needs to be grounded in updated infection control guidelines,
The hospital infection control team members are aware that implementation of bundle elements, and surveillance meth-
these interventions are the most adequate practices for effec- ods. This requires regular, proper training in the correct pro-
tive infection control; however, the actual application of each cedures for infection control practices and safe care delivery.
bundle element may not be consistent in routine patient care. Consequently, instructions must be clearly provided to HCWs
by means of a uniform approach that focuses on the user and countries (84,85). In turn, from 2003, there have been more
applies practical methods so as to avoid subjective and ambigu- scientific publications from limited-resource countries in which
ous interpretations. HAl rates are reported per 1,000 device-days (86-97).
An education program should be targeted not only at HCWs
but also at observers and trainers. Education must be provided
PROCESS SURVEILLANCE
to all HCWs, whether to start the HH training or to update or
check competence and learned skills. The education program Process surveillance consists of the regular supervision of a
should be led by a coordinator and subcoordinators (manag- series of infection control practices involved in the routine
ers or committee members) who select trainers and observers, patient care. Similar to outcome surveillance, process surveil-
based not only on their knowledge and experience in infec- lance is a standardized collection of data, but it is focused on
tion control but also on their capability of leadership. Finally, the actual performance of infection control practices in the
the education program must be supported by and subjected to healthcare facility. These practices include the monitoring of
regular evaluations to improve teaching and learning methods. compliance with HH recommendations, vascular catheter care,
urinary catheter care, measures to prevent VAP (such as posi-
tion of the head and type of secretion suctioning), and mea-
OUTCOME SURVEILLANCE
sures to prevent SSI (e.g., presurgical shower, hair removal,
Outcome surveillance is the measurement of the rates and con- antibiotic prophylaxis, and so on).
sequences of HAis, including but not limited to, the following Surveillance of infection control practices is among the
few variables: HAl rates, mortality, extra LOS, cost, microorgan- most important indicators evaluated at the hospitals' facilities.
isms, and bacterial-resistance rates. Outcome surveillance data Accompanying the other components of the multidimensional
are also analyzed through case-control studies to identify risk strategy to reduce DA-HAis, process surveillance is crucial
factors and determine extra cost and mortality. The results of to provide a basis to focus on the areas needing more atten-
HAl outcome surveillance allow infection control profession- tion: first, it measures the actual situation of compliance with
als to define the magnitude of the problem, identify devices infection control practices and provides a general overview of
with the highest risk, and provide the framework for plans HCWs' perception and knowledge of the burden of DA-HAis.
to reduce infection risk, including the evaluation of the cost- Second, this evaluation and measurement permits the identifi-
effectiveness of specific infection control interventions (26). In cation of problem areas in healthcare delivery, which is essential
summary, outcome surveillance is the infrastructure for HAl to implement localized interventions. Third, it also allows the
management. measurement of the outcome of such interventions in relation
Outcome surveillance of DA-HAI has become an integral to the other components of the multidimensional approach
feature of infection control and quality assurance programs in and their translation into improvements in infection control
high-income countries, since risk adjustment by device use and practices and reduction of DA-HAis. In other words, the onset
duration of stay provides a more precise estimate ofrisk (73,74). and the outcome of the whole multidimensional approach are
Standards for institutional surveillance have been adopted in the evaluated through process surveillance.
United States (73), United Kingdom (75),Australia (76), Canada Process surveillance is conducted by an observer (usually an
(77), and Germany (78), among other countries. These devel- infection control nurse) who directly monitors HCWs' practices
oped countries report rates as DA-HAI per 1,000 device-days, by following a standardized protocol and completing specific
which allows them to further analyze the impact of specific risk surveillance forms at regular intervals (31). These observations
factors and guide their targeted interventions. are conducted unobtrusively at specific time periods distrib-
In limited-resource countries, the general perception is that uted in three work shifts (morning, afternoon, and evening).
HAl rates are low and that compliance with infection control The HCWs are not aware of the actual schedule of the monitor-
practices, such as HH recommendations, is high. However, it ing, so they cannot avoid or minimize the observer effect.
is frequent that no formal outcome and process surveillance is Process surveillance data include key interventions to con-
conducted at hospitals, hence the impossibility to confirm the trol and reduce the incidence ofHAis, such as HH compliance,
scientific validity of such perception. Studies on HAl rates in specific measures to prevent VAP (i.e., position of the head,
limited-resource countries have been scarce, and in most in- cleanliness of tubes, aspiration technique), CLA-BSI (i.e., care
stances, authors have reported percentage (cases over discharges practices for insertion site of the central lines, skin antisep-
or admissions) of HAis (79-83), or HAl rates are reported as sis, placement of gauze on intravascular access insertion sites,
number of infections per 1,000 patient-days (79), rather than marking the date on the IV administration set, condition of the
DA-HAis per 1,000 device-days. Because the denominator of the gauze dressing, by assessing the presence or absence of mois-
number of device-days is unknown, it is not possible to compare ture, blood, gross soilage, and the appearance of the insertion
the rates between hospitals, and reported rates are less useful site), CA-UTI (i.e., position of the urinary catheter regarding
for secular trend comparisons within the same hospital as well. the leg and position of urine bag regarding the bed), VAP
This situation has changed markedly since 2002, as there has (i.e., position of the head of the bed, evaluation of time to wean
been an increase in studies that present DA-HAI rates per 1,000 patients off ventilation), and SSI (i.e., proper hair removal,
device-days from limited-resource countries (36-37,40,42-53). optimal antimicrobial prophylaxis.).
As part of the INICC, DA-HAI rates per 1,000 device-days The INICC multidimensional approach, including ~pro
have been reported in many recent studies at the country cess surveillance~ for vascular catheter, urinary catheter,
(36,37,40,42-53) and global levels (32-35). and mechanical ventilator care, has been effective in reduc-
As stated in two recent reviews by the WHO, by applying ing associated HAis in several previous studies conducted in
INICC outcome surveillance method, it is possible to benchmark limited-resource countries, such as CLA-BSI (54-57}, VAP
HAl rates in limited-resource countries against high-income (58-61,98-99), and CA-UTI (62--64) among others.
FEEDBACK OF HEALTHCARE-ASSOCIATED contain a running tally of compliance with infection control

INFECTION RATES practices by HCWs along with information on how improve-
ments are being made in the compliance with key infection
The goal of measuring HAis through outcome surveillance preventive intervention, comparing several variables, such as
is directly related to the need to communicate the results to
gender, HCW status, ICU type, contact type, and work shift.
HCWs, who are expected to bring about meaningful changes.
Those charts are reviewed at monthly staff meetings and also
This communication process entails providing HCWs with
posted in prominent locations in the ICUs in order to give per-
feedback of the incidence of HAl rates and their adverse con-
formance feedback to the participating HCWs of the ICUs.
sequences. The concept of using feedback of outcome surveil-
lance is a powerful control measure in hospitals with limited
resources, whose effectiveness has been reported from 1999 to
2002 in studies within individual Argentine hospitals before the HAND HYGIENE COMPLIANCE IN
inception ofiNICC in 2002 (54,100). LIMITED-RESOURCE SETIINGS
As part of the INICC multidimensional approach, data con-
tained in completed outcome surveillance forms are submitted EARLIEST STUDffiS SHOWING BENEFIT
to the INICC Central Office in Buenos Aires, which in tum OF HH ON HEALTHCARE-ASSOCIATED
sends monthly reports that contain the analysis of outcome INFECTION RATE REDUCTION
surveillance data, such as microorganism profile, and monthly
The impact of HH before each patient contact for infection
rates for each DA-HAI. Through this communication process,
prevention was demonstrated 160 years ago when Semmelweis
it is possible to evaluate the validity of each infection case, as studied the relationship between improved hand antisepsis and
data include the recorded signs and symptoms of infection and
reduced mortality from puerperal sepsis (101). Since then, it
results of positive cultures, which can be matched with the in- has been proven that improved HH practice reduces HAl rates
dividual patient's forms. Infection control professionals review
and antimicrobial resistance (102,105). HCWs commonly carry
the forms filled out in the ICU and are able to verifY that the HAl pathogens on their hands (106,107). Most pathogens
criteria for infection are met accurately in each case. Addition-
responsible for HAis are thought to be transmitted from one
ally, the original patient data forms are further validated at
patient to another patient via the HCW's hands (106-107). the
the INICC Central Office, before data on the reported infec-
comerstone in the prevention of cross-infection among pa-
tion are entered into the INICC's database. To that end, que-
tients. However, HCWs' compliance with good HH practice is
ries may be submitted from the INICC office in Buenos Aires
low in most settings (1 04,108--111). Most reports of successful
to the hospital's investigators, challenging those cases with
interventions have been conducted in high-income countries
suspected VAP, and data are uploaded after receiving the reply (112-114); only a few have been conducted in settings with lim-
(validation) from the hospital teams. Finally, the INICC team
ited resources, such as Argentina and Mali (100,105,115).
performs consistency analyses of database, such as age, gender,
dates, among other data, and reviews of medical records that
compared data registered in forms and data in medical records. HAND HYGffiNE COMPLIANCE-ASSOCIATED
To foster the effective implementation of the multidimen- RISK FACTORS
sional approach, and the adoption of each component, remind-
Monitoring HH is one of the key examples of process surveil-
ers of outcome surveillance in the workplace play a substantial
lance. Achieving higher adherence to HH guideline recommen-
role. These messages are aimed at pointing out the basic infor-
dations has been a difficult issue, which remains unresolved in
mation on the significance of HAl prevention. Such reminders
many healthcare facilities worldwide (116) . Table 18.11 shows
include posters with the graphs and charts showing monthly
examples of HH in limited-resource countries. Low HH rates
changes in rates of HAis and their adverse effects, such as ex- were reported in many studies in which HH compliance rates
tra mortality and extra LOS. The information contained in
ranged from 9% to 75%. Lack of a mandatory national HAl
the reminders must be updated regularly. Reminders are to be control program, lack of a national HAl surveillance system,
displayed and disseminated all around the hospital settings in
and lack of a national healthcare facility accreditation process
order to obtain a higher level of awareness. in some countries probably contribute to low HH compliance.
HH performance is influenced by different factors, and its
promotion is particularly complex in limited-resource coun-
PERFORMANCE FEEDBACK
tries, because limited resources and culture-specific issues
Providing feedback to HCWs in order to assess performance strongly influence practices (117).
levels is one of the most motivating aspects of the INICC multi- The factors predicting poor HH adherence level include
dimensional approach from the perspective ofHCWs. To know male gender (100), type of HCW (100,118), type of ICU
the outcome of their efforts reflected by the measurement of (119,120), type of procedure (118,119), and so on. Different
their practices and the incidence of HAis can be the most re- studies have shown that there is a higher HH compliance by
warding or conscious-raising factor to ensure the effectiveness females (121,122). Women usually wash their hands more
of the multidimensional improvement strategy. frequently than men, and in many countries, females are the
On a monthly basis and from the first month of imple- predominant gender in nursing. Guinan et al. found a higher
mentation of the infection control program, the INICC Head- HH compliance by female students in middle and high school
quarters team prepares and sends to each participating ICU a (123), and another study found similar findings in the rest-
final month-by-month report on compliance with healthcare room of Penn Station in the Wirthlin Worldwide observational
practices based on the data compiled by the hospital infection study in 1996 ( 124). In limited-resource countries, at least from
control professionals at the participating ICUs. These charts Latin America, the cultural construction of the traditional role
TABLE 18.11 Baseline Hand Hygiene Compliance before Contact with Patients Rqlorted by Hospitals
from Bconomies Defined as Low-, Lower-Middle, and Upper-Middle Income by the
World Bank
Number of Hmd.Hygieoe
Country Type of Study/Unit Obaenati.ODII Compliance (%) Year Ref
Algeria Multicenter hospitalwide 18.6 2006 (246)
Argentina (INICC Study) Multicenter adult ICU 15,5!11 17.0 200!1 (100)
Argentina (INICC Study) AdultiCU 1,160 2!1.1 2005 (105)
Brazil Multicenter adult ICU !1,407 71.5 2004 (247)
China NewborniCU 40.0 2004 (112)
Eritrea (Africa) Hospitalwide !10.0 2005 (248)
South Africa Hospitalwide 65.2 200!1 (249)
Colombia (INICC Study) Multicenter adult ICU 1,692 48.9 2004 (250)
Egypt Multicenter hospitalwide 52.8 2006 (246)
India (INICC Study) Multicenter adult ICU 588 74.8 2005 (251)
Mexico (INICC Study) Multicenter adult ICU 6,861 !15.8 2004 (252)
Mexico (INICC Study) Pediatric ICU !121 64.5 2004 (25!1)
Mexico (INICC Study) NewborniCU 1,070 46.!1 2005 (254)
Morocco (INICC Study) AdultiCU 1!19 64.0 2005 (255)
Morocco Multicenter hospitalwide 16.9 2006 (246)
Peru (INICC Study) Multicenter adult ICU 1,!129 6!1.1 2004 (256)
Russia NewborniCU 1,027 44.2 2003 (257)
Thailand Hospital wide 24.1 200!1 (258)
Tunisia Multicenter hospitalwide 32.!1 2006 (246)
Thrltey AdultiCU 12.9 2002 (249)
Turkey (INICC Study) Multicenter adult ICU 4,657 28.8 2004 (260)
Turkey (INICC Study) Hospitalwide 1,400 31.9 2005 (261)
Turkey Hemawlogy unit 638 9.0 2005 (262)
INICC 8 countries (INICC Study) Multicenter adult ICU 62,626 50.9 2006 (26!1)
INICC 19 countries (INICC Study) Multicenter adult ICU, PICU, NICU 11,267 48.!1 2012 (131)
Mali Hospitalwide 8.0 2010 (115)
Iran Hospitalwide 47.2 2008 (264)
Pakistan Hospitalwide 211 4.7 (physicians) 2009 (265)
Ghana NewborniCU 97 14.1 (nurses) 15.4 (physicians) 2009 (266)
Brazil 3 adultiCUs 46.7 2009 (267)
El Salvador 5 high-ri8k pediatric wards 3!1.8 2009 (268)
Indonesia 2 hospitals and 8 clinics 281 20 2010 (269)
(private and public)
Ghana Hospitalwide 4 2010 (270)
Brazil Medical surgical 2,249 62.3 2010 (271)
Saudi Arabia Hospitalwide 1,023 50.3 2011 (272)
India MedicaliCU 911 43.2 2011 (273)
Saudi Arabia 5ICUs !1,940 42 (58% noncompliance) 2012 (274)
Brazil Medical surgical ICU !1,895 36.9 2012 (275)
Iran Hospitalwide 438 47.9 2012 (276)
Eritrea Hospitalwide 30 2005 (248)
ICU, intensive care unit; PICU, pediatric intensive care unit; NICU, neonatal intensive care unit; INICC, International Nosocomial Infection
of women continues to be directed by the patriarchal model (126,127). In a study conducted by Rosenthal et al. in 2005,
of family. According to this sociocultural construction, the the performance was lower among physicians and ancillary
"natural" role of women lies in the catering for children and staff compared to nurses (105). Professional status also can
the ill. The influence exerted by gender in HH compliance influence the HH compliance level (118). Watanakunakom
should be regarded a strong factor that contributes to male et al. also found differences in HH compliance rates in differ-
HCWs' lower internal motivation for HH healthcare in general ent work categories: resident physicians (59%), staff physician
(in contrast to females), and also to the unquestioned predis- (37%), nurses (33%), and others (4%) (128). Avila et al. found
position of women to be the predominant gender in nursing subtle differences between nurses (67%) and ancillary staff
and related professions. This factor has not been fully acknowl- (62%) (127), whereas Wurtz found a HH compliance rate of
edged as a useful parameter for further research in the design 33% for nurses, 35% for physicians, 25% for physiotherapists,
ofHH programs (125). and between and 20% among technicians ( 126).
If HCWs are stratified by type of professional, HH com- Some have found HH compliance differences between
pliance was found to be higher in nurses in different studies work shifts. Possible explanations include the fact that during
day shifts ICUs may be more crowded and busy than during • Introduction of alcohol-based hand rub by Graham in
night shifts. In 1982, Haley and Bregman (129) showed that 1990 (111);
overcrowding and understaffing hindered HCWs' efforts to • Effectiveness of education by Dubbert (135),
perform HH as adequately and frequently as needed to pre- Tibballs (138), Dorsey in 1996 (134), Larson in 1997
vent cross-infection. Similarly, in 2001, O'Boyle et al. (117) (139), and by Rosenthal in 2003 (100) and 2005 (105).
claimed that lower adherence to HH was related to high level • Combining these various interventions, multidimen-
of intensity of work in health care settings-which predisposed sional approaches have been designed and imple-
HCWs to a lower awareness of their actual HH performances- mented with successful results since the late 1980s. In
rather than to a lack of internal motivation. If related to un- 1989, Conly (110) concluded that an educational and
derstaffing, the morning and afternoon (compared to night enforcement program was an efficient tool to achieve
shift) shifts are risk factors associated with poor administrative higher HH compliance. In 1990, Dubbert et al. reached
support, particularly in the context of limited-resource coun- the same conclusions combining education, monitoring,
tries, as shown by Rosenthal et al. in 2003 (100) in a study and performance feedback (135). But, it was not until
that evaluated the relationship between greater administrative 1997 that Larson et al. explicitly referred to a multidi-
support and higher HH adherence. In this respect, many dif- mensional strategy that considered several interven-
ferent studies from developed countries have demonstrated tions in a study conducted in the United States (139) .
that active administrative support is an especially important Similarly, in 1998, Won et al. launched a multimodal
issue to deal with HH compliance, not only in making hospi- campaign for HH promotion in a university hospital in
tal infrastructure readily available for timely and properly HH Th.iwan, which included lectures, written instructions,
performance, but also to focus on the adoption of systemati- reminding posters on adequate HH techniques, moni-
cal societal marketing methods that were proved effective in toring, financial incentives, and performance feedback
sustaining HH in clinical settings (130). (113). Likewise, in 2003 and 2005, Rosenthal et al. pub-
Although Watanakunakorn et al. (128) found no HH com- lished the results of studies implemented in Argentina
pliance differences between work shifts, there were remark- in 1993 combining administrative support, supplies
able variations by unit, with compliance being 56% in ICUs availability, education and training, process surveillance,
compared to 23% in non-ICUs. Thus, the type of unit also has and performance feedback, which produced a sustained
an influence on HH compliance. Watanakunakorn et al. also improvement in HH compliance (100), coinciding with
showed that prevalence of HH was higher in surgical (56.4%) a reduction in HAl rates (105).
and medical ICUs (39.2%) than in intermediate (30.0%) or • Table 18.12 shows examples ofintervention to improve
general ICUs (22.8%). Newborns are the most vulnerable pa- HH in limited-resource countries.
tients, which may explain higher HH compliance by HCWs
In 1993, the INICC started applying a HH multidimensional
in this type of ICU (131). The type of contact also may influ-
approach in Argentina and in 2002 in several limited-resource
ence HH performance: superficial contacts were significantly
countries in Asia, Europe, the Middle East, and Latin America
associated with lower compliance. This coincides with the
(i.e., Argentina, Brazil, China, Colombia, Costa Rica, Cuba,
findings of Lipsett, which showed that nursing groups were
Greece, El Salvador, India, Lebanon, Lithuania, Macedonia,
significantly less likely to perform HH in low-risk vs. high-risk
Mexico, Pakistan, Panama, Peru, Philippines, Poland, and Tur-
situations (118).
key). In 2002, the CDC published their HH guideline, includ-
ing a recommendation to apply previously published strategies
INTERVENTIONS TO IMPROVE (140,141). In 2005, the WHO launched a program, also com-
HAND HYGIENE COMPLIANCE bining previously published data, called "Clean Care is Safer
Care" with the aim of promoting HH worldwide (29,142). In
The effectiveness of different interventions had been analyzed 2009, the WHO published its guidelines also including a combi-
and published from the early 1980s by several investigators, nation of these previously published data, and introducing the
such as: five moments for HH in order to prevent cross-transmission of
microorganisms with hands (30).
• Contribution of supplies availability evaluated by Preston
in 1981 (108), Mayer in 1986 (132), and Doebbeling in
1992 (102);
• Contribution of use of reminders and posters evaluated WORLD HEALTH ORGANIZATION:
by Conly in 1989 (110), Graham and Simmons in 1990 CLEAN CARE IS SAFER CARE: GLOBAL
(104,111), Lohr in 1991 (133), Dorsey in 1996 (134), PATIENT SAFETY CHALLENGE
and by Avila-Aguero in 1998 (127);
• Contribution of use of monitoring and performance A hopeful sign related to HH is "Clean Care Is Safer Care,"
feedback by Mayer in 1986 (132), Conly in 1989 (110), the first global challenge of the WHO World Alliance for
Graham and Dubbert in 1990 (111,135), Lohr in 1991 Patient Safety (143). In October 2004, the World Alliance for
(133), Ra,ju in 1991 (136), Berg in 1995 (137), Tibballs Patient Safety was formed, focusing first on prevention of HAis
in 1996 (138), Larson in 1997 (139), Avila-Aguero through a combination of initiatives that include mobilizing
in 1998 (127), and by Rosenthal in 2003 (100) and patients and patient safety organizations, generating teaching
2005(105); tools, directing and conducting research, developing a taxon-
• Contribution of administrative support by Larson et al. omy of definitions and data management methods, and coordi-
in 1997 (139) and 2000 (139), and by Rosenthal in 2003 nating international efforts on future solutions. The intent is to
(100) and 2005 (105); engage all countries in infection prevention.
TABLE 18.12 &suits Rcportal by Programs to Improve Hand Hygiene Compliance kportal by
by the World Bank
Hand Hygiene Compliance
Country Type of Study/Unit Improvement (%) Year Ref
Argentina (INICC Study) Multicenter adult ICU 17.0-44.0 2003 (100)
Argentina (INICC Study) AdultiCU 23.1-64.5 2005 (105)
China NewborniCU 40.0-53.0 2004 (112)
Mexico (INICC Study) Multicenter adult ICU 35.8-75.8 2004 (277)
Mexico (INICC Study) NewborniCU 46 .3~7 .7 2005 (278)
Rwsia NewborniCU 44.2-48.0 2003 (257)
Mali Hospitalwide 8.0--21.8 2010 (115)
Turkey (INICC Study) Multicenter adult ICU 11 .9--43.9 2005 (279)
INICC 19 countries (INICC Study) Multicenter adultiCU, PICU, NICU 48.~.0 2012 (131)
El Salvador 5 high-risk pediatric wards 33.8-40.5 2009 (268)
Congo Hospitalwide 9.0--45.0 2008 (280)
ICU, intensive care unit; PICU, pediatric intensive care unit; NICU, neonatal intensive care unit; INICC, International Nosocomial Infec tion
Countries were invited to adopt this challenge for their own Although the components are presented individually, they
healthcare systems with the following main principles ( 143) : must be interpreted as interactive elements that are dependent
on each other on a reciprocal basis, and not as separate ele-
• Formally assessing the scale and nature ofHAis within
ments. As will be noted below, one is implied on the other, and
their healthcare system.
all of them must concur for any "multidimensional" approach
• Adopting an internationally recognized approach to
to be effectively implemented. The components of the HH
surveillance of the problems so that current baseline
multidimensional approach started to be implemented at each
incidence of HAl can be established and change can be
of the INICC participating ICUs after documenting baseline
monitored.
compliance episodes for 2 months.
• Conducting an analysis of the root causes of the problem
with particular emphasis on "systems thinking."
• Developing solutions to improve safety and reduce risk by
RESULTS OF INICC MULTIDIMENSIONAL
focusing on five action areas in particular: (a) nn, particu-
APPROACH TO IMPROVE nn COMPLIANCE
larly use of alcohol hand rubs, (b) blood safety, (c) injec-
tion practices and immunization, (d) water, basic sanitation, In 1999, INICC started a prospective surveillance study in
and waste management, and (e) clinical procedures. INICC member hospitals-which is still ongoing-to determine
• Relying on evidence-based best practice in all aspects of the baseline HH compliance rate by HCWs before patient con-
addreMing the challenge. tact, analyze risk fuctors for poor adherence, and implement
• Fully engaging patients and service users as well as HCWs and evaluate the impact of the ~INICC multidimensional ap-
in improvement and action plans. proach for HH," which included the above-mentioned six items
• Ensuring the sustainability of all action beyond the initial (131). The study was conducted from Aprill999 to December
2-year challenge period. 2011 in 99 ICUs from 51 cities in 19 countries in 4 continents
(i.e., Argentina, Brazil, China, Colombia, Costa Rica, Cuba,
Pittet and Donaldson (143) state the vision of the World
Greece, El Salvador, India, Lebanon, Lithuania, Macedonia,
Alliance for Patient Safety: "to catalyse commitment by all
Mexico, Pakistan, Panama, Peru, Philippines, Poland, and
players-policy makers, frontline staff, patients and managers-
Turkey). Each participating hospital was successively incorpo-
to make 'Clean care is safer care' an everyday reality in all
rated into the study over the years of the study period. During
countries and everywhere healthcare is provided."
the study, the authors recorded 149,727 opportunities for HH
before patient contact. The baseline HH compliance rate of
HCWs at INICC ICUs was 48.3%. A total of 41,759 procedures
INICC: SIX-COMPONENTS were recorded for males and 76,645 for females. The authors
MULTIDIMENSIONAL APPROACH found a statistically significant relation between HH compli-
TO IMPROVE HAND HYGffiNE ance and gender. There was higher compliance in females.
COMPLIANCE Observations amounted to 97,450 HH events in nurses, 28,609
in physicians, and 23,668 in ancillary staff. The authors found
INICC has been implementing its multidimensional approach higher compliance in nurses than in other HCWs. HH proce-
combining the following six components: (a) administrative dures also were elaMified into work shifts: during the morning
support, (b) supplies availability, (c) education, (d) remind- shift, they recorded 68,584 opportunities, during the evening
ers in the workplace, (e) process surveillance, and (f) perfor- shift, the number decreased to 46,741, and for the night shifts,
mance feedback. it was 34,402. The results showed that morning and afternoon
TABLE 18.13 Hand Hygiene Compliance .&:mrding to Each Variable in INICC ICUs: Univariate and
Multivariate Analysis
Univariate AnalyBis Multivariate analysis
% (I#IUl/1# 95% Adjlut«l 95%
YariGbk ~) compan- RR Cl p OR Cl p
GENDER Female 70% Fvs.M 0.90 0.89--{1.91 1.0

Male 63% 0.0001 0.91 0.89--0.93 <.001
HCW Nurses 72% NSvs. Ph 0.86 0.85--0.88 0.0001 1.0
Phf!icians 62% NSvs.AS 0.78 0.77--{1.80 0.0001 0.68 0.66-0.70 <.001
Ancillary Staff 57% Phvs.AS 0.91 0.8-0.93 0.0001 0.52 0.51--{1.54 <.001
PROCEDURE Noninvasive 68% Nlvs. I 0.98 0.97--{1.99 0.0037 0.95 0.93-0.98 <.001
Invasive 69% 1.0
UNIT AdultiCU 67% Advs.Pe 0.94 0.92--{1.97 0.0001 0.49 0.47--{1.52 <.001
Pediatric ICU 71% Advs.Nb 0.83 0.81--{1.85 0.0001 0.58 0.54-0.62 <.001
NewbomiCU 81% Nbw.Pe 0.88 0.85--0.91 0.001 1.0
WORK SHIFf Morning 67% Mvs.A 1.00 0.99-1.02 0.7926 0.83 0.81--{1.86 <0.001
Afternoon 67% Mvs.N 0.92 0.91--{1.94 0.0001 0.79 0.76-0.81 <0.001
Night 72% Avs.N 0.92 0.91--{1.94 0.0001 1.0
HCW, healthcare worker; ICU, intensive care unit; AS, ancillary staff; F, female; M, male; NI, noninvasive; I, invasive; Ad, adult; Pe, pediatric;
Nb, newborn; M, morning work shift; A, afternoon work shift; N, night work shift; NS, nursing staff; Ph, physicians.
shifts were significantly associated with lower HH compliance period of the INICC ICUs was 3 months, and their average inter-
compared with night shift (Table 18.13). The authors strati- vention period was 23.9 months. During the baseline phase, HH
fied opportunities for HH by type of ICU, and found that there before patient contact was 48.3% (95% CI: 47.6 to 48.9) and
were 131,822 in adult ICUs, 9,081 in pediatric ICUs, and 8,764 after our intervention, it was 71.4% (95% CI: 71.2 to 71.6), (RR:
in newbom ICUs. There were significant differences between 1.47, 95% CI: 1.45 to 1.51, p < .01). Furthermore, there was
HH compliance by ICU type, with the highest HH compliance a change in HH compliance in INICC participating ICUs over
in newbom ICUs (Table 18.14). time since the beginning of the HH surveillance (Table 18.15).
The authors stratified opportunities for HH by type of hos- Finally, the there was a change in the type of product used
pital, and found that there were 50,515 in academic, 40,530 in for HH over the years. During the first years of the study,
public, and 58,682 in private. Seventy percent of HH observa- chlorhexidine was the most used product, particularly from
tions (105,181 opportunities) were before noninvasive patient 1999 to 2002, ranging from 100% and 80%. From 2002, how-
contacts, and 27% (40,548 opportunities) were before invasive ever, the use of common soap started to rise, displacing the pre-
procedures. The results showed that the type of contact influ- dominant use of chlorhexidine gradually until 2008. Alcohol
enced HH performance: superficial contacts were significantly rub increased gradually from 5% in 2007 to take the lead in
associated with lower compliance. INICC participating ICUs that 2011 with 55%, which was strongly correlated with the steep de-
had been members for more than 3 months had significantly cline in the use of chlorhe:xidine from 62% to 20% from 2010
improved HH compliance among HCWs. The average baseline to 2011 (Figure 18.1).
11· (;! :f f ~1 f:ft I Ill Distribution of Hand Hygiene Compliance per ICU Type in INICC ICUs
ICUs (n) Opportunities for HH (n) HH compliance (n) HH Compliance Means % (95% CI)
Bum 1 1,324 1,176 89% (87-90.5)
Medical cardiac 7 16,067 10,729 64% (63.4-64.9)
Cardio!urgical 3 4,975 3,943 79% (78.1~0.4)
Medical 4 8,87!1 7,150 81% (79. 7~1.4)
Medical surgical 48 74,683 46,547 62% (62.0-62.7)
Newborn 9 8,764 7,101 81% (80.2~1.8)
N euro!urgical 6 9,715 7,767 80% (79.1~0.7)
Pediatric 10 9,081 6,44!1 71% (70-71.9)
Respiratory 1 413 272 66% (61.1-70.4)
Surgical 8 8,299 4,963 60% (58. 7-W.9)
'!Jauma 1 6,671 5,449 82% (80.7~2.6)
Ward 1 862 757 88% (85.4--89.9)
All 99 149,727 101,877 68% (67.8-68.3)
ICU, intensive care unit; HH, hand hygiene.

TABLE 18.15 Hand Hygiene Improvement by Year of Participation in INICC ICUs

Ye11111 Since Joining INICC HH Oblervatiom Number of ICUslncluded HH % (95% Cl) Adjusted OR
First 3 months (baseline) 11,267 99 48.3% (47.6-49.0) 1.0
Second 3 months 7,214 99 61 .2% (60.5-61.9) 1.72 (1.65-1.81)
Third 3 months 5,511 89 67.2% (66.4-67.8) 2.10 (1.99-2.2)
Fourth 3 months 4,639 81 69.4% (68.6--70.1) 2.21 (2.10-2.33)
Second year 8,190 69 71.4% (70.9-71.9) 3.07 (2.92-3.23)
Third year 5,573 45 69.1% (68.4-69.7) 3.03 (2.84-3.22)
Fourth and fifth year 4,278 32 81.2% (80.1-81.6) 3.3 (3.07-3.52)
Sixth and seventh year 1,120 15 86.0% (85.2-86.8) 2.87 (2.57-3.19)
Considering time since the intervention as a 149,727 99 68% (67.8--68.3) 1.27 (1.25-1.28)
continuous variable per year of participation
Note: Comparisons were made using only the ICUs with follow-up. That is, for the comparison of hand hygiene compliance with baseline for
the third year only, hospitals with at least ~years follow-up were included and the same with the following periods.
p = <.001
HH, hand hygiene; ICUs, intensive care units; INICC, International Nosocomial Infection Control Consortium.
In this study, which includes a large and remarkably diverse In such instances, the denominator of the number of device-
patient population in the ICUs of 51 cities of 19 countries in days was not known, and thus it was not possible to have a basis
3 continents around the world, the authors have shown that of comparison between hospitals. Furthermore, the reported
administrative support, supplies availability, education, process DA-HAI rates were less useful for secular trend comparisons
surveillance, and providing continuous performance feedback within the hospital itself (Table 18.1). Since 2002, there has
in each ICU resulted in very substantial improvements in HCW been a significant increase in studies that present DA-HAI rates
HH compliance (131). Two previous studies published by IN- per 1,000 device-days in limited-resource countries. As part of
ICC member hospitals from Argentina applying this multidi- the INICC multidimensional approach, DA-HAI rates per 1,000
mensional strategy also showed an improvement on HCW HH device-days have been reported in different recent studies at
compliance (100,105). the country and global levels. As stated in two recent WHO
reviews (83,85), the INICC outcome surveillance method has
enabled infection control professionals to benchmark DA-HAI
DA-HAI RATES IN INTENSIVE CARE rates in limited-resource countries against high-income coun-
UNITS OF LIMITED-RESOURCE tries. From 2002 onward, there have been more scientific publi-
COUNTRIES cations from limited-resource countries in which DA-HAI rates
are reported per 1,000 device-days (Table 18.2).
Studies on DA-HAI rates in limited-resource countries had From the available literature, it is highly visible that
been very limited before 2002, and in most instances, authors the adverse consequences of DA-HAI in limited-resource
had reported percentages (cases over discharges or admis- countries-that is, attributable mortality (36,40,47,50,144-146) ,
sions) ofDA-HAis, or DA-HAI rates as number of infections per prolonged LOS (31,36,37,44,47-50,52,53,144-151), extra hos-
1,000 patient-days, rather than DA-HAis per 1,000 device-days. pital costs (144,145,150) , and increased bacterial resistance
Typa of product usad In HH ovar tha years

1.0 lii:""""""-------------------;:==========::::::;1
0.9 1----~------------------1 ~ %alcohol
-+- % chlorex
0.8 .........._ % iodine
0.4 ~----------------------~~~~~--~~~------~--~
0.3 ~--------~~~~--L--------~--+~~~
0.2 1---------~~---.~~--------~~-~~---~
o.1 I-----::~"7~;;::::-J..:::ooo..-<>-=-~-----..;;:=-::::::::;;;OO""'=---------'-"'---I
o LI~~~~~~~~~~--~~~~----~
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Figure 18.1. The type of product used in HH over the years in INICC ICUs.
(44,47,50,52,53,147)-are more far-reaching in severity than in During the 6-year study period, wing CDC's NHSN defini-
high-income countries. tions for DA-HAI, the authors gathered prospective data from
The risk of DA-HAI is higher among seriously ill patients 313,008 patients hospitalized in INICC member hospitals'
who often have several indwelling devices, thw the higher infec- ICUs for an aggregate of 2,194,897 ICU bed-days. Data were
tion rates are in ICUs. In the case of DA-HAis in INICC reports, included from 94 academic, 75 public, and 46 private hospitals.
the rate of device we was found to be analogow or even lower The hospitals' length of participation in the INICC Program
than reported in U.S. ICUs by the CDC's NNNIS/NHSN system was a mean length of participation of 23.9, standard deviation
(152,153). However, pooled mean rates identified in ICUs from (SD) of 21.7 months, and range of 1 to 72 months. The char-
limited-resource countries by the INICC Study and by other inves- acteristics of the 422 reus that contributed data for this report
tigators (32,153,154) were found to at least double the rates pub- are presented in Table 18.16.
lished by the European Centre for Disease Prevention and Control DA-HAI rates and device utilization (DU) ratios were strati-
(155), and triple those reported from CDC's NHSN ICUs (156). fied by infection type (CLA-BSI, CA-UTI, and VAP) in adult,
The systematic review and meta-analysis on the burden of pediatric, and neonatal ICUs. The DU ratio constitutes an
endemic HAl in limited-resource countries by Allegranzi et al. extrinsic risk fuctor for DA-HAI (20,21). DU also comprises
concluded that HAl prevalence was significantly higher in low- a marker for severity of illness of patients, vis-a-vis, patients'
and middle-income countries compared to high-income coun- susceptibility to DA-HAI (Table 18.16). The data for neonatal
tries. The density of DA-HAI in critically ill patients was found ICUs were stratified by birth weight (Table 18.17).
to be from 2- to 19-fold higher than those reported from devel- Analyses included crude ICU mortality in patients hospital-
oped countries (85). ized in each type ofunit during the surveillance period, with and
In a review on incidence of CIA-BSis in limited-resource without DA-HAI, and crude excess mortality of adult and pedi-
countries, the CIA-BSI rate ranged from 1.6 to 44.6 infections atric patients with CLA-BSI, CA-UTI, and VAP (Table 18.18),
per 1,000 central line-days in adult and pediatric ICUs and from and infunts in NICUs with CLA-BSI orVAP (Table 18.19).
2.6 to 60.0 infections per 1,000 central line-days in neonatal The analysis also included data on crude LOS of patients
ICUs, and was associated with significant extra mortality (18). hospitalized in each type of unit during the surveillance pe-
Similarly, in a systematic review by Arabi et al. on VAP in riod, with and without DA-HAI, and crude excess LOS of
adults in limited-resource countries, from 1966 to 2007, the adult and pediatric patients with CLA-BSI, CA-UTI, and VAP
rates ofVAP were higher overall than CDC's NHSN benchmark (Table 18.18), and infunts in NICUs with ClA-BSI or VAP
rates, and ranged from 10.0 to 41.7 per 1,000 ventilator-days. (Table 18.19).
The review found that the crude mortality attributable to VAP CLA-BSI, CA-UTI, and VAP rates in 2012 were compared
ranged from 16% to 94% (157). with the respective rates of previous INICC reports published
in 2006, 2008, and 2010 (Table 18.20).
The overall rates of CLA-BSI, CA-UTI, and VAP (164)
INICC INTERNATIONAL REPORT ON DA-HAis
in INICC in 2012 and in CDC's NHSN ICUs were compared
The results of a surveillance study reported by the INICC Study (158). Despite a similar device we in INICC and CDC's par-
from january 2004 through December 2009 in 422 ICUs in 36 ticipating, the rates of DA-HAI were significantly higher in the
countries in Latin America (123 ICUs), Asia (241 ICUs), Africa ICUs of the INICC hospitals: the pooled rate of CIA-BSI in the
(6ICUs), and Europe (52 ICUs) are analyzed in this section (35). INICC ICUs, 6.8 per 1,000 central line-days, is almost 3-fold
TABLE 18.16 Number ofiCUs, Patients, Patient-Days, Pc:ded. .Means of Central Line-Associated
Bloodstream Inm:ti.on Rata (per 1,000 Central Line-Days), Qrtbctrr-.Assodmd Urinary
Thtct: Inm:ti.on Rata per 1,000 Urinary Catheta.--Days, Vc:ntilator-.Assodaud Pneumonia
Rata per 1,000 Ventilator-Days, Central Line Utilization Ratios, Urinary Catheter Utitiurioo
Ratios, Ventilator Utilization Ratios, by 1YPe ofAdult and Pediatric ICU in INICC Hospitals
Pooled Pooled Pooled Pooled Pooled
No. of No. of Patient- Pooled Mean Mean Mean Mean Mean Mean
'type ofiCU units patients days CLA-BSI rate CLDUR CA-UTirate UCDUR VAPrate MV-DUR
Medical 42 lKI,823 151,243 14.7 0.50 6.3 0.65 7.7 0.57
Medical cardiac 27 26,704 94,180 6.2 0.57 :5.7 0.55 10.8 0.23
Medical surgical 138 109,237 944,836 6.8 0.53 7.1 0.56 18.4 0.:58
Neurologic 4 3,869 22,860 12.9 0.36 14.3 0.85 28.1 0.18
Neurosurgical 25 8,109 47,019 4.6 0.43 6.2 0.75 20.9 0.31
Pediatric 45 20,905 165,046 10.7 0.38 4.7 0.24 6.5 0.53
Respiratory 18 2,710 39,942 4.9 0.62 9.8 0.53 27.7 0.46
Surgical 50 63,270 !182,523 5.0 0.52 5.0 0.45 16.3 0.!15
Surgical 28 25,130 97,426 1.5 0.69 1.6 0.58 14.9 0.33
cardiothoracic
Thauma 9 4,507 26,201 2.5 0.56 7.2 0.71 40.0 0.47
Overall 386 295,264 1,971,276 6.8 0.52 6.3 0.53 15.8 0.39
ICU, intensive care unit; CLA-BSI, central line-associated bloodstream infection; CA-UTI, catheter-associated urinary tract infection; YAP,
ventilator-a!Sociated pneumonia; CL, central line; UC, urinary catheter; MY, mechanical ventilator; DUR, device me ratio.
TABLE 18.17 Pooled Means and 95% CI of the Distribution of Central Linc-.Assoclatcd Bloodstream
lnfcc:tion Rates per 1,000 Central Line-Days, Ventilatm-Assodatcd Pneumonia Rates per
1,000 Ventilator-Days, Central Line Utilization Ratios, Ventilator Utilization Ratios, for
Level-Ill NICUs in INICC Hospitala
Birth-Weight Pooled Mean Pooled Mean Pooled Mean Pooled Mean
Category (Kg) No. of Units No. of Patientll Patient-Days CLA-BSI Rate CL-DUR VAPRate MV-DUR
<0.750 9 7!1 2,716 10.9 0.41 3.1 0.47
0. 750--1.000 27 1,163 22,796 13.5 0.40 7.2 0.31
1.001-1.500 30 1,916 40,875 13.7 0.29 8.8 0.1!1
1.501-2.500 32 5,598 65,!158 11.9 0.22 10.1 0.11
>2.500 !13 6,670 59,569 10.0 0.18 11.1 0.12
OVERALL 36 15,420 191,!114 12.2 0.25 9.0 0.14
NICU, neonatal intensive care unit; CLA-BSI, central line-associated bloodstream infection; VAP, ventilator-aMociated pneumonia; CL, central
line; MV, mechanical ventilator; DUR, device we ratio.
TABLE 18.18 Pooled Means and 95% CI of the Distribution of Crude Mortality and Length of Stay
and Crude Excess Length of Stay of ICU Patients with DA-HAl, Adult and Pediatric
ICUs Combined in INICC Hospitals
Pooled Average
No. of Patients LOS, Total Days LOS, Days No. of Deaths Pooled Crude Mortality, %
Patients without DA-HAI 119,501 746,251 6.2 11,908 10.0%

Patients with CLA-BSI 1,679 28,709 17.1 414 24.7%
Patients with CA-UTI 1,677 30,982 18.5 290 17.3%
Patients with VAP 5,020 90,146 18.0 1,265 25.2%
Cl, confidence interval; ICU, intensive care unit; DA-HAI, device..wociated healthcare-usociated infection; CA-UTI, catheter-associated
urinary tract infection; CLA-BSI, central line-associated bloodstream infection; VAP, ventilator-associated pneumonia.
~ftC :f §:f f:d fII Pooled Means and 95% CI of the Distribution of Crude Mortality and Length of Stay
of Infants in NICUs, All Birth-Weight Categories Combined in INICC Hospitals
Pooled Average
No. of PatientiJ LOS, Total Days LOS, Days No. of Deaths Pooled Crude Mortality (%)
lnfunts without DA-HAI 5,910 537 9.1 537 9.1%
Infunts with CLA-BSI 204 72 35.3 72 35.3%
Infunts with VAP 175 42 24.0 42 24.0%
CI, confidence interval; ICU, intensive care unit; DA-HAI, device..wociated healthcare-usociated infection; CA-UTI, catheter-associated
urinary tract infection; CLA-BSI, central line-associated bloodstream infection; VAP, ventilator-associated pneumonia.
higher than the 2.0 per 1,000 central line-days reported in DA-HAis IN NEONATAL INTENSIVE CARE UNITS
comparable CDC-NHSN ICUs, and the overall rate ofVAP was
In the developing world, most births occur at home ( 159), and
also far higher, 15.8 vs. 3.3 per 1,000 ventilator-days, as was the
most delivering mothers have no skilled attendant present at
CA-UTI rate, 6.3 vs. 3.3 per 1,000 catheter-days (Th.ble 18.21).
the delivery. Women with problem pregnancies need access to
Data on HAl pathogen bacterial resistance isolated from pa-
expert prenatal care. However, such care often exposes women
tients with DA-HAI in adult and pediatric ICUs and NICUs are
shown in Table 18.22. Noticeably, the frequencies of resistance to unhygienic perinatal practices, thereby increasing their
infant's and their own risk of HAis. ICUs usually receive bet-
of Pseudomrmas aeruginosa isolates to imipenem (47.2% vs. 23.0%
respectively), Klebsiella pneumoniae isolates to ceftazidime (76.3% ter funding and staffing than other hospital wards, and, thus,
care in the ICU often represents the best care available. There
vs. 27.1% respectively), Escherichia coli isolates to ceftazidime
are few, if any, data on the morbidity and mortality rates in
(66.7% vs. 8.1% respectively), and S. aumusisolates to methicillin
neonatal intensive care unit (NICU) patients due to DA-HAis
(84.4% vs. 56.8% respectively) were also higher in the INICC's
in limited-resource countries.
ICUs, and the crude unadjusted excess mortalities of DA-HAis
Neonatal infections are estimated to cause 1.6 million an-
ranged from 7.3% (CA-UTI) to 15.2% (VAP) (Th.ble 18.23).
nual deaths, or 40% of all neonatal deaths, in limited-resource
TABLE 18.20 Comparison of Device-Associated Hcalthcarc-.Assodatcd Infc:ction Rates, per 1,000

Device-Days in the Intensive Care Units of the International Nosocomial Infection
Control Consortium Published in 2006, 2008, 2010, and 2012 Reports
INICC 2002-2005 INICC 2002-2007 INICC 2003---2008 INICC 2004--2009
(Published in 2006) (Published in 2008) (Published in 2010) (Published in 2012)
(32) Pooled Mean (33) Pooled Mean (34) Pooled Mean (35) Pooled Mean
(95% CI) (95% CI) (95% CI) (95% CI)
Number of countries 8 18 25 lJ6
Number of cities 28 48 75 11:i
Number ofiCUs 55 98 173 422
Number of hospitals 46 71 114 215
Number of patients 21,069 43,114 155,358 31:i,008
Numberofpatient~~ 137,740 272,279 92:i,624 2,194,897
Number ofDA-HAh 3,095 5,446 13,291 26,593
Number of CLA-BSis 930 1,820 4,241 7,603
Number ofVAPs 1,277 2,314 5,660 12,395
Number of CA-UTis 888 1,312 3,390 6,595
PU"ddpadnr Countries Argentina, Brazil, Argentina, Brazil, Chile, Argentina, Brazil, Argentina, Brazil,
Colombia, India, Colombia, Costa China, Colombia, Bulgaria, China,
Mexico, Morocco, Rica, Cuba, India, Costa Rica, Cuba, Colombia, Costa
Peru, and Turkey Kosovo, Lebanon, Greece, India, Rica, Cuba,
Macedonia, Mexico, Jordan, Kosovo, Dominican Republic,
Morocco, Nigeria, Lebanon, Lithuania, Ecuador, Egypt,
Peru, Philippines, Macedonia, Greece, India,
El Salvador, Thrkey, Mexico, Morocco, Jordan, Kosovo,
and Uruguay Pakistan, Panama, Lebanon, Lithuania,
Peru, Philippines, Macedonia, Malaysia,
El Salvador, Mexico, Morocco,
Thailand, Tunisia, Pakistan, Panama,
Turkey, Venezuela, Peru, Philippines,
and Uruguay Puerto Rico,
Fl Salvador, Saudi
Arabia, Singapore,
Sri Lanka, Sudan,
Thailand, Thnisia,
'furkey, Venezuela,
Vietnam, and
Uruguay
CLA-BSI RATES
Pooled 12.5 (11.7-13.3) 9.2 (8.8--9. 7) 7.6 (7.4-7.9) 6.8 (6.7-7.0)
Medical cardiac ICU 9.9 (8.7-11.3) 8.5 (7.5-9.7) 6.2 (5.6--6.9)
Medical surgical ICU 8.9 (8.4-9.4) 7.4 (7.2-7.7) 6.8 (6.6--7.1)
Pediatric ICU 6.9 (5.6--8.3) 7.8 (7.1-8.5) 4.6 (3.7-5.6)
Newborn ICU (1,501-2,500 g) 15.2 (10$-21.5) 13.9 (12.4--15.6) 11.9 (10.2-13.9)
CA-unRATES
Pooled 8.9 (8.3--9.5) 6.5 (6.1~.9) 6.3 (6.~.5) 6.3 (6.2~.5)
Medical cardiac ICU 6.4 (5.3--7.7) 4.4 (3.5-5.3) 3.7 (3.2-4.3)
Medical surgical ICU 6.6 (6.2-7.0) 6.1 (5.9~.4) 7.1 (6.9-7.4)
Pediatric ICU 4.0 (2.~.2) 4.4 (:i.6--5.4) 4.7 (4.1-5.5)
VAPRATES
Pooled 24.1 (22.8--25.5) 19.5 (18.7-20.3) 13.6 (13.3-14.0) 15.8 (15.5--16.1)
Medical cardiac ICU 20.2 (17.0-23.9) 14.9 (12.4-17.9) 10.8 (9.5-12.3)
Medical surgical ICU 19.8 (14.2-27.1) 14.7 (14.2-15.2) 18.4 (17.9-18.8)
Pediatric ICU 7.9 (6.0-10.1) 5.5 (4.~.0) 6.5 (5.9-7.1)
Newborn ICU (1,501-2,500 g) 6.68 (3.0-12.7) 9.50 (7.9-11.3) 10.1 (7.9-12.8)
Cl, confidence interval; ICU, intensive care unit; DA-HAI, device-associated healthcare-w.rociated infection; INICC, International Nosocomial
Infection Control Consortium; CA-UTI, catheter-associated urinary tract infection; CLA-BSI, central line-associated bloodstream infection;
VAP, ventilator-associated pneumonia.
TABLE 18.21 Comparison ofDA-HAI rata, per 1,000 Dc:rice-Days in the ICUs of the International
Nosocomial Infection Control Consortium and the US National Healthcare Safety
Network
INICC 2004--2009 DA-HAI Rates US NHSN 2006--2008 DA-HAI Rates
Pooled Mean (95% Cl) Pooled Mean (95% Cl)
MEDICAL CARDIAC ICU

CLA-BSI 6.2 (5.6--6.9) 2.0 (1.8-2.1)
CA-UTI 3.7 (3.2-4.3) 4.8 (4.6--5.1)
YAP 10.8 (9.5-12.3) 2.1 ( 1.9-2.3)
MEDICAL SURGICAL ICU
CLA-BSI 6.8 (6.6--7.1) 1.5 ( 1.4-1.6)
CA-UTI 7.1 (6.9-7.4) 3.1 (3.0-3.3)
YAP 18.4 (17.9-18.8) 1.9 (1.8-2.1)
PEDIATRIC ICU
CLA-BSI 4.6 (3.7-5.6) 3.0 (2.7-3.1)
CA-UTI 4.7 (4.1-5.5) 4.2 (3.8-4.7)
YAP 6.5 (5.9-7.1) 1.8 (1.6--2.1)
NEWBORN ICU (1,501-%,500 1)
CLA-BSI 11.9 (10.2-13.9) 1.5 (1.2-1.9)
YAP 10.1 (7.9-12.8) 0.8 (0.04-1.5)
CI, confidence interval; ICU, intensive care unit; DA-HAI, device-a&Sociated healthcare-a&Sociated infection; INICC, International Nosocomial
Infection Control Consortium; NHSN, National Healthcare Safety Network; CA-UTI, catheter-aMociated urinary tract infection; CLA-BSI,
central line-associated bloodstream infection; YAP, ventilator-associated pneumonia.
TABLE 18.22 Antimicrobial-B.aistance Rates in the ICUs of the lntcmational Nosocomial Infection
Control Consortium
No. of Pathogenic Resistance No. of Pathogenic Resistance No. of Pathogenic Resistance
Isolated Tested, Percentage Isolated Tested, Percentage Isolated Tested, Percentage
Pooled (%) Pooled (%) Pooled (%)
Pathogen,
Antimicrobial (CJA.BSI) (CJA.BSI) (YAP) (YAP) (CMJTI) (CA-U71)
STAPHYLOCOCCUS AUREUS
OXA 646 84.4% 634 73.2% 42 71.4%
ENTEROCOCCUS FAECALIS
VAN 98 5.1% 18 11.1% 59 5.1%
PSEUDOMONAS AERUGINOSA
FQ8 285 42.1% 997 46.2% 148 50.7%
PIP orTZP 589 36.2% 1,789 40.2% 254 41.7%
AMK 278 27.7% 1,008 28.3% 127 29.9%
IPMorMEM 517 47.2% 1,777 42.7% 255 !16.5%
FEP 2 100.0% 8 !17.5% 2 50.0%
KLEBSIEllA PNEUMONIAE
CRO orCAZ 447 76.3% 662 68.9% 194 72.2%
IPM, MEM, or ETP 508 7.9% 688 7.0% 237 7.2%
ACINETOBACTER BAUMANNII
IPM orMEM 667 55.!1% 1,466 66.3% 113 52.2%
ESCHERICHIA COLI
CRO orCAZ 171 66.7% !123 67.5% 320 49.7%
IPM, MEM, or ETP 182 4.4% !160 4.2% 326 5.5%
FQ8 133 53.4% 164 54.9% 211 !12.2%
AMK, ami.lacin; FEP, cefepime; CRO, ceftriaxone; ETP, ertapenem; FQ8, lluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin,
or ofloxacin); IPM, imipenem; MEM, meropenem; OXA, oxacillin; PIP, piperacillin; TZP, piperacillin-tazobactam; CAZ, ceftazidime;
VAN, vancomycin.
TABLE 18.23 Comparison of Antimicrobial-Resistance Kates(%) in the ICUs of the International

Nosocomial Infection Control Consortium and the U.S. National Nosocomial
Surveillance System
INICC %004-%009 U.S. NHSN %006-%007
Pathogen, Antimicrobial &ristance ~, % (CLABSI) Resistance Percmtage, % (CLABSI)
STAPHYLOCOCCUS AUREUS
OXA 84.4 56.8
ENTEROCOCCUS FAECALIS
VAN 5.1 78.9
PSEUDOMONAS AERUGINOSA
FQ 42.1 30.5
PIPorTZP 36.2 20.2
AMK 27.7 4.3
IPMorMEM 47.2 2lt0
FEP 100.0 12.6
KLEBSIELLA PNEUMONIAE
CTRorCAZ 76.3 27.1
IPM, MEM, or ETP 7.9 10.8
ACINETOBACTER BAUMANNII
IMPorMEM 55.3 29.2
ESCHEIUCHIA COU
CfRorCAZ 66.7 8.1
IPM, MEM, or ETP 4.4 0.9
FQs 53.4 30.8
ICU, intensive care unit; INICC, International Nosocomial Infection Control Consortium; NHSN, National Healthcare Safety Network; CIA-BSI,
central line-associated bloodstream infection; AMK, amikacin; FEP, cefepime; CRO, ceftriaxone ; ETP, ertape nem; FQs, fluoroquinolones
(ciprofloxacin, levofloxacin, moxifloxacin, or ofloxacin); IPM, imipenem; MEM, meropenem; OXA, oxacillin; PIP, piperacillin; TZP,
piperacillin-tazobactam; CAZ, cefta.zidime; VAN, vancomycin.
countries (160). Neonatal deaths account for more than one- In this study, DA-HAI rate data were collected for all NICU
third of the global burden of child mortality (161). Neonatal patients at participating hospitals from September 2003
mortality rates (deaths in the first 28 days of life) are as high as through February 2010 using CDC-NHSN DA-HAI definitions
40 to 50 per 1,000 live births in many of the poorest countries (20,23). At each hospital, numerator data (i.e., patients with
of the world. Infections are the major cause of neonatal deaths DA-HAis) and denominator data (i.e., device-da}'5 and patient-
in limited-resource countries. Every year, >4 million neonates da}'5) were collected. Data were prospectively collected during
die in their first 28 da}'5 of life. In fact, more than one-third the study period from all patients whose stay in the NICU was
of all deaths in children <5 years old occur during this neo- ~24 hours (32-35). INICC methodology includes a process for
natal period, and most die in their first 5 days of life (159). adjudication of and validation of reported HAis as previously
It is estimated that approximately 1.6 million neonates die of described (32-35). The DU ratio was calculated by dividing the
community-acquired infection or HAl (162-164). total device-da}'5 by the total bed-days. Countries were classified
The largest health disparities in the world are found in ma- according to the World Bank's four economic strata on the ba-
ternal and neonatal mortality rates between the industrialized sis of 2011 gross national income per capita. These economic
countries and the poorest sections of the poorest countries groups are calculated using the World Bank Atlas method. The
(165). In September 2000, almost all countries worldwide ad- groups are low income, $1,025 or less; lower-middle income,
opted the Millennium Declaration, focused on global health $1,026 to $4,035; upper-middle income, $4,036 to $12,475; and
and poverty improvement (166). Endorsed by 189 countries, high-income, $12,476 or more (19,168) . In our study, DA-HAI
the Millennium Development Goals (MDGs) established eight rates were stratified by country socioeconomic level (e.g., low-
goals to be reached by 2015, including MDG 4 to reduce by 2/3 income countries, lower-middle-income countries, or upper-
mortality in children <5 years (166). middle-income countries) and by type of hospital (i.e., public,
The association between either the type of hospital academic, and private).
(e.g., public, academic, or private) or country socioeconomic During the study period, data were reported from 30 NICUs
level classified by World Bank (low-, lower-middle-, and upper- (at 30 hospitals) in 15 countries in Latin America, Asia, Africa,
middle-income economies) (19) and NICU population DA- and Europe (i.e., Argentina, Brazil, Colombia, Dominican
HAI rates has not been addressed systematically. A recent study Republic, India, Jordan, Mala}'5ia, Mexico, Morocco, Peru,
by Rosenthal et al. (167) assessed whether the economy or Philippines, Salvador, Thailand, Thnisia, and Thrkey) . Those
hospital type influenced DA-HAI rates in patients admitted to reporting had participated in the INICC surveillance S}'5tem
30 NICUs in 151imited-resource countries. for a mean of 12.9 ± SD 13.0 (range: 1 to 70) months. Of the
30 reporting NICUs, 4 (13%) are low-income countries, 14 patients without DA-HAis by hospital type ranged from 5.8%
(47%) are lower-middle-income countries, and 12 (40%) are (private hospitals) to 12.5% (academic and public hospitals)
upper-middle-income countries, and 14 (47%) are academic (p < .001). DA-HAI-related mortality was 37.1% for CLA-BSis.
teaching, 11 (37%) are private, and 5 (17%) are public hos- Excess crude mortality was 27.7% for CLA-BSI. CLA-BSI crude
pitals. Of the four reporting low-income countries hospitals, or excess mortality rates were not different in academic and
three (75%) are private hospitals. public hospitals and thus these rates were pooled. Crude excess
When lNICC vs. CDC's NHSN data were compared, VAP ac- mortality rates for CLA-BSI were not different at academic and
counted for nearly one-third of the DA-HAis in lNICC, whereas in public hospitals compared to private hospitals (25.3 vs. 10.9, p
NHSN they accounted for approximately one-fifth of the DA-HAis, = .1487). DA-HAI-related mortality was 27.3% for VAPs. Excess
and CIA-BSis accounted for nearly 70% of the DA-HAis in INICC crude mortality was 17.9% for VAPs. Crude excess mortality
and nearly 80% of the DA-HAis in NHSN. In lNICC, the largest rates for VAP were not different at academic and public hospi-
number of device-days was for central lines (61 %) followed by tals compared to private hospitals (15.2 vs. 0, p = .4564).
mechanical ventilation (39.1 %). When we compared DU ratios Interestingly, the LOS of patients without DA-HAI was not
(DUR) in INICC vs. CDC-NHSN NICUs, the centnd-line DURl! different in academic and public hospitals compared to pri-
(CL-DURl!) were similar (0.25 vs. 0.24), whereas the mechanical vate hospitals ( 11.4 vs. 11.8 days). The excess LOS of patients
ventilator DURl! (MV-DURs) were lower in lNICC than NHSN with CLA-BSI was not different in academic or public hospitals
NICUs (0.16 vs. 0.21). Despite similar or lower NICU DURs, both (29.8 vs. 32.9 days). When compared to academic and public
the CIA-BSI and VAP rates at lNICC hospitals were significantly hospitals, private hospitals had a slightly lower CLA-BSI patient
higher than at CDC's NHSN hospitals (p < .001 in both instances). excess LOS of 21.1 days. The extra LOS of patients with VAP
Next, NICU CLA-BSI rates and CL-DURs were examined was significantly higher in academic and public hospitals than
by hospital type and socioeconomic status. CLA-BSis can be re- at private hospitals (25.6 vs.10.2 days, p < .01).
ported as laboratory-confirmed BSI (LC-BSI) or clinical sepsis Regarding process surveillance, the authors reported that
(CSEP) using CDC definitions. LC-BSI was significantly more HCW HH compliance rates were higher in private than public
commonly reported at academic or private hospitals than at or academic hospitals (75.2% vs. 65.0% [p < .005]; vs. 60.8%
public hospitals (56% vs. 73% vs. 26%). Although CLA-BSI rates [p < .002]), with an overall rate of65.7%.
were lower at NICUs in private than academic hospitals (10.8 vs.
14.3 CLA-BSI per 1,000 catheter-days [p < .03]), they were not
DA-HAis IN PEDIATRIC INTENSIVE
different in public or academic hospitals (14.6 vs. 14.3 CLA-BSI
CARE UNITS (PICUS)
per 1,000 catheter-days [p < .86]). The CL-DUR was higher at
public than at either academic or private hospitals (0.50 vs. 0.28, Similar to NICU settings, there are very limited data regard-
p < .001; or 0.50 vs. 0.15, p < .001). When the NICU CLA-BSI ing the association between country socioeconomic level
rates were examined by socioeconomic level, CLA-BSI rates in and DA-HAI rates, or the association between type of hospi-
low-income countries were higher than lower-middle-income tal (i.e., public, academic, or private) and DA-HAI rates in
countries or upper-middle-income countries (37.0 vs. 11.9 PICUs. In a recent study by Rosenthal et al. (169), the authors
CLA-BSis per 1,000 catheter-days [p < .01], vs. 17.6 [p < .05]). assessed whether the socioeconomic or hospital type influ-
ClrDUR was lower at low-income countries hospitals and signifi- enced DA-HAI rates in the PICU setting of limited-resource
cantly higher at lower-middle-income countries or upper-middle- economies. This study was carried out from January 2004 to
income countries (0.11 vs. 0.26, p < .001; vs. 0.25, p < .001). December 2009 in 33 PICUs from 32 hospitals in 16 countries
When VAP rates and MV-DURs were examined by hospi- (i.e., Argentina, Brazil, Colombia, Egypt, El Salvador, India,
tal type and country socioeconomic level, it was found that Jordan, Lithuania, Malaysia, Mexico, Peru, Philippines, Sri
the MV-DUR was higher at public than at either private or Lanka, Thailand, Thnisia, and Thrkey.) The selected PICUs
academic hospitals (0.33 vs. 0.14, p < .001, or 0.33 vs. 0.16, had participated in the INICC surveillance system for a mean
p < .001). NICU VAP rates were higher in academic than at of 28.9 to 24.7 SD (range: 1 to 67) months. Sixteen (50%)
private or public hospitals (13.2 vs. 2.4 VAPs per 1,000 venti- of the 32 participating hospitals were academic teaching,
lator-days [p < .001]; vs. 4.9 [p < .001]). The NICU MV-DUR 12 (38%) were private, and 4 (13%) were public hospitals.
was higher in UMICs than in either low-income countries or Three (75%) of the four reporting low-income country hos-
lower-middle-income countries (0.21 vs. 0.14, p < .001; or 0.21 pitals are private hospitals.
vs. 0.14, p < .001). The NICU VAP rate in lower-middle-income During the study period, the largest number of device-days
countries was higher than at low-income countries ( 11.8 vs. 3.8 was for mechanical ventilation (46%) followed by central line-
per 1,000 ventilator-days [p < .001]; the rates ofVAP were not days (36.7%) and urinary catheter (UC) -days (17.2%) . Mechan-
different in low-income countries and upper-middle-income ical ventilator use was 0.58 in this study's ICUs, and 0.42 in the
countries (3.8 vs. 6.7 per 1,000 ventilator-days [p =.57]). CDC-NHSN PICUs. Central line use was 0.46 in this study and
Furthermore, the authors analyzed CLA-BSI and VAP rates 0.48 in the CDC PICUs. Urinary catheter use was 0.22 in these
and DURs stratified by birth-weight category. The CL-DUR was PICUs, which is lower than the 0.29 rate in the CDC's PICUs.
highest in the <750 g birth-weight group. The CLA-BSI rates Data from the CDC's NHSN and for INICC were similar for
were higher in the 750 to 1,000 g vs. >2,500 birth-weight group PICU patients in that CLA-BSis accounted for the greatest num-
(17.4 per 1,000 CL-days vs. 10.2 per 1,000 CL-days, p < .001). ber ofDA-HAis (INICC 46.4% vs. NHSN 57.2%). However, in
The MV-DUR was higher in the >2,500 g birth-weight groups NHSN, the second most common DA-HAI was CA-UTI (23.2%),
compared with <750 g group (11.4 per 1,000 CL-days vs. whereas in INICC, the second and third most common DA-HAI
4.9 per 1,000 CL-days, p = .0125). site was VAP (42.8%), followed by CA-UTI (10.8%) . TheCLA-
With respect to mortality, the overall crude mortality rate for BSI and VAP rates at INICC hospitals were significantly higher
patientswithoutaDA-HAiwas9.4%,andmortalityratesforNICU than at CDC's NHSN hospitals, but theCA-UTI rate was similar.
The authors found that the overall PICU CLA-BSI rate was with public and private hospitals (31.5% vs. 17.6%, p = .216).
8.1 CLA-BSis per 1,000 catheter-days. The CLA-BSI rate was Crude excess mortality of CA-UTI and VAP was higher in
similar for PICU patients at public, academic, or private hospi- public and private hospitals, but the authors reminded that it
tals (8.4 vs. 8.2, p = .83; 8.4 vs. 7.3, p = .42). The overall central should be taken into account that the number of patients with
line pooled mean DUR was 0.46, which was similar to the CDC's these infections was lower in these types of hospitals.
NHSN for PICU patients. The CL-DUR was higher at public hos- Finally, regarding process surveillance, the authors found
pitals than at either academic or private hospitals (0.60 vs. 0.56, that HCWs' HH compliance rates were higher at public hos-
p = .001; or 0.60 vs. 0.21, p = .001) and the average of central pitals than at academic or private hospitals (65.2% vs. 54.8%
line-days was higher in the public hospitals. When the CLA-BSI compliance, p < .01, or 65.2% vs. 13.3% compliance, p < .03) .
rate was examined by socioeconomic level, the authors found
that the CLA-BSI rate was significantly higher at lower-middle-
income countries than at upper-middle-income or low-income SURGICAL SITE INFECTIONS (SSIS)
countries (12.2 vs. 7.0, p = .001 or 12.2 vs. 5.5, p = .023). The IN LIMITED-RESOURCE SETIINGS
CL-DUR was lower at low-income hospitals and significantly
higher at lower-middle-income or upper-middle-income coun- A recent systematic review and meta-analysis by the WHO
tries (0.23 vs. 0.50, p = .001, or 0.23 vs. 0.47, p = .001). showed that the incidence of SSI in limited-resource coun-
Next, the authors evaluated urinary catheter use and CA-UTI tries was markedly higher than in developed countries, with
rates. They found that the CA-UTI rates were similar at public, rates ranging from 1.2 to 23.6 per 100 surgical procedures
academic, and private hospitals (5.2 vs. 4.2 CA-UTis per 1,000 (Th.ble 18.24). However, these data reported by limited-resource
catheter-days, p = .41, or 5.2 vs. 3.0 CA-UTis per 1,000 catheter- countries was not stratified by surgical procedure; and in a few
days, p = .19, respectively), although urinary catheter DUR was instances it was stratified by level of wound contamination.
higher at academic hospitals than at private or public hospitals
(0.36 vs. 0.16, p = .001 or 0.36 vs. 0.10, p < .001). The aver-
INTERNATIONAL NOSOCOMIAL INFECTION
age length of urinary catheter use was slightly higher in public
CONTROL CONSORTIUM (INICC) SURGICAL
hospitals. Urinary catheter DUR was similar at all hospitals at
SITE INFECTION DATA
all socioeconomic levels (range: 0.2 to 0.3), but the average of
days per patient was higher in the lower-middle-income coun- A recent study conducted in 30 countries of Asia, Europe, and
tries. However, the CA-UTI rates were significantly higher at Latin America and published by INICC show SSI rates strati-
lower-middle-income country hospitals than at either upper- fied by 31 CDC-NHSN surgical procedures, and providing their
middle-income or low-income countries (5.9 vs. 3.7, p = .01, or percentiles (170).
5.9 vs. 0.6, p < .004). The INICC-reported data on SSis within surgical procedures
Then the authors examined the VAP rates and mechanical were collected between January 2005 and December 2010
ventilation use, and found that mechanical ventilator DUR was (Table 18.25). Data were collected from 82 hospitals in 66 cit-
lower at private hospitals than at public and academic teaching ies from 30 countries (i.e., Argentina, Brazil, Colombia, Cuba,
hospitals (0.43 vs. 0.63, p = .001, or 0.43 vs. 0.67, p = .001), but Dominican Republic, Egypt, Greece, India, K.osovo, Lebanon,
the average length of ventilator use was higher in public hospi- Lithuania, Macedonia, Malaysia, Mexico, Morocco, Pakistan,
tals. The VAP rates were higher in academic teaching hospitals Panama, Peru, Philippines, Poland, Salvador, Saudi Arabia,
and public hospitals than at private hospitals (8.3 vs. 4.7 VAPs Serbia, Singapore, Slovakia, Sudan, Thailand, TUrkey, Uruguay,
per 1,000 ventilator-days, p = .001, or 8.3 vs. 3.5 VAPs per 1,000 and Vietnam). Of the hospitals included, 55% were academic,
ventilator-days, p = .001). When the authors examined VAP by 20% were public, and 21% were private. Data were collected on
socioeconomic level, they found that DUR and average days of 260,973 surgical procedures, and included the identification
use was the highest for lower-middle-income and upper-mid- of 7,523 surgical site infections. For data collection, standard
dle-income countries in comparison with low-income countries CDG-NHSN definitions for HAl were applied. These data were
(0.59 vs. 0.60, p = .001, or 0.59 vs. 0.31, p = .001). Likewise, then stratified by type of surgical procedure, including 31 cat-
the VAP rate was higher in lower-middle-income countries com- egories (20). Infection control professionals collected data on
pared with upper-middle-income and low-income countries SSI occurring in patients after a surgical procedure.
(9.0 vs. 5.4 VAP per 1,000 ventilator-days, p = .001, or 9.0 vs. 0.5 The classification by type of surgical procedure included
VAPs per 1,000 ventilator-days, p < .001). the following 31 CDC-NSHN categories: abdominal aortic
The authors explained that the extremely low VAP rate in aneurysm repair (AAA); limb amputation (AMP); appendix
low-income countries-and the overall low rates of CLA-BSI surgery (APPY); bile duct, liver, or pancreatic surgery (BILl);
and CA-UTI as well-was related to the fact that three of the breast surgery (BRST); coronary bypass with chest and donor
four PICUs from low-income countries were private hospitals incision (CBGB); cardiac surgery (CARD); gallbladder surgery
with a developed DA-HAI prevention program. (CHOL); colon surgery (COLO); craniotomy (CRAN); cesar-
Regarding mortality, the overall crude mortality rate for pa- ean section (CSEC); spinal fusion (FUSN); open reduction of
tients without DA-HAI was 9.3%. Mortality related to DA-HAI fracture (FX); gastric surgery (GAST); herniorrhaphy (HER);
ranged from 32.3% for VAPs to 26.1% for CLA-BSis to 25.0% hip prosthesis (HPRO); knee prosthesis (K.PRO); laminectomy
for CA-UTis. Excess crude mortality ranged from 23.0% for (LAM); neck surgery (NECK); kidney surgery (NEPH); pros-
VAPs to 16.9% for CLA-BSI to 15.7% for CA-UTis. When ex- tate surgery (PRST); peripheral vascular bypass surgery (PVBY);
amined by hospital type, the overall crude mortality for PICU rectal surgery (REC); small bowel surgery (SB); spleen surgery
patients without DA-HAis ranged from 7.9% (private or pub- (SPLE); thoracic surgery (THOR); thyroid and/or parathyroid
lic hospitals) to 10.6% (academic hospitals). CLA-BSI crude surgery (THYR); vaginal hysterectomy (VHYS); ventricular
mortality was similar in academic teaching hospitals compared shunt (VSHN); exploratory abdominal surgery (XLAP) (20).
TABLE 18.24 Surgical Site Infection Rates per Procedure~ by Hospitals from Economics
Number of Pooled SSI Clean Clean Contaminated Dirty
Country Patients Rate(%) (%) Contaminated (%) (%) (%) Year Ref
Africa 76 23.6 14.3 19.3 27.3 60 2009 (281 )
(Sub-Sahara)
Brazil 332 23.6 2004 (282)
Brazil 16ll 11 2006 (28ll)
Brazil 609 24.5 2006 (284)
Columbia llli,027 2.6 1.28 ll.9 15.4 ll8.4 200ll (285)
Georgia 872 14.6 2007 (286)
(Republic of)
Kyrgyzstan 20.2 1997 (287)
India 615 18.86 200ll (288)
Morocco ll10 5.2 2005 (289)
Russian 14,5ll 9.5 2007 (290)
Federation
Thailand 15,319 2.7 1.3 1.5 5.1 9.7 1995 (291 )
Thailand 18,456 9.1 2005 (292)
Nigeria 144 17.4 (abdominalsurg) 2011 (293)
(abdominal surg)
Tanzania 26.0 2011 (294)
Burkina Faso 681 2ll.4 2011 (295)
Tanzania 19.4 2011 (296)
Brazil 10.ll 8.ll 2010 (297)
Brazil 258 38.8 (head and neck) 2008 (298)
Turkey 50ll 6.2 2005 (299)
Thailand 17,869 1.4 2009 (300)
Thailand 2,139 1.2 (appendicectomy) 2009 (300)
(appendicectomy)
Brazil 609 (digestive tract 24.5 (digestive tract 2006 (284)
surgery) surgery)
Ethiopia 770 11.4 2012 (301)
Cote d'Ivoire 318 13.2 2009 (302)
Nepal 507 7.ll 2008 (30ll)
Tanzania 24.0 2006 (304)
Bolivia 12 200ll (305)
Pakistan 460 13 5.3 12.4 36.3 40.0 2008 (306)
Kosovo 25ll 12 2008 (307)
SSI, surgical site infection; Ref, reference.
Surgical procedures with the highest SSI rates were ventricu- ADVERSE CONSEQUENCES OF HAIS
lar shunt (12.9%), colon surgery (9.4%), and bile duct, liver, or IN LIMITED-RESOURCE SE'ITINGS
pancreatic procedures (9.2%). The lowest rates were found in
cesarean section procedures (0.7%) and thyroid and/or para- EXTRA WS AND COST OF HAIS
thyroid procedures (0.3%). IN LIMITED-RESOURCE SETTINGS
The report also included a comparison of SSI rates in INICC
and CDCNHSN's report from 2006 to 2008 (171). As the data Among the adverse effects of HAis are prolonged LOS and
had not been stratified by risk categories, the authors pooled the correlated extra hospital costs. Costs attributable to HAl
the different risk categories included in the CDCNHSN report include hospital stay (room and board), drugs and treatment,
from 2007 to 2009 to obtain the mean rate of SSis for the rate diagnostic tests, outbreak investigations, and surgical interven-
comparison. tions; usually uncounted costs include time off work for patient
The majority of the SSI rates were significantly higher in and family, outpatient care, and societal loss of productivity.
INICC than in CDCNHSN hospitals (in 18/31 surgical pro- Many of these costs cannot be adequately quantified, but some
cedures [58%]). Thirteen percent (4/31) of the surgical pro- costs can be determined from some hospitals.
cedures (CSEC, HER, PVBY, REC) were significantly lower Stone et al. reported results of a systematic audit linking
in INICC than in CDCNHSN hospitals. Twenty-nine percent costs of HAis and infection control interventions. Fifty-five in-
(9/31) of the surgical procedures were similar in INICC and in fection control studies published between 1990 and 2000 from
CDCNHSN hospitals. North America, Europe, Australia, Asia, and South America
In conclusion, the data presented in this report strengthen were reviewed. The investigators found that LOS decreased
the fact that HAis, particularly SSis in hospitals internationally, from 7.9 to 5.3 during the period, but that HAl rates increased
pose a grave and, many times, concealed risk to patient safety, from 7.2 to 9.0 per 1,000 patient-days. The average cost for
as compared with some countries of the developed world. HAis was US $13,973 (172).
TABLE 18.25 Surgical Site Infections of the Participating International Nosocomial Infection Control
Consortium Hospitals, 200S-2010. Comparison of Surgical Site Infection Rata in the
Hospitals of the International Nosocomial Infection Control Consortium and the US
National Hcalthcare Safety Network
INICC CDC-NHSN
2005-2010, 2006--2008 SSI Rate
CODE Procedure Name SSIRate,% (Pooled IWik Categories) RR 95% CI p
l.AAA Abdominal aortic aneuryun repair 7.7% 3.2% 2.41 0.33-17.40 0.3668
2.AMP Limb amputation 2.7% 2.3% 1.18 0.80--1.74 0.4099
3.APPY Appendix surgery 2.9% 1.4% 2.05 1.61-2.59 0.0001
4.BIU Bile duct, liver, or pancreatic surgery 9.2% 9.9% 0.93 0.70--1.22 0.5945
5.BRST Breast surgery 1.7% 2.3% 0.77 0.55--1.06 0.1111
6.CBGB Coronary bypass with che5t and donor incision 4.5% 2.9% 1.52 1.44-1.61 0.0001
7.CARD Cardiac surgery 5.6% 1.3% 4.32 3.81-4.88 0.0001
8.CHOL Gallbladder surgery 2.5% 0.6% 3.94 3.10--5.01 0.0001
9.COLO Colon surgery 9.4% 5.6% 1.69 1.52-1.87 0.0001
10. CRAN Craniotomy 4.4% 2.6% 1.69 1.46-1.96 0.0001
11. CSEC Cesarean section 0.7% 1.8% 0.39 0.34--0.43 0.0001
12.FUSN Spinal fusion 3.2% 1.5% 2.10 1.48-3.00 0.0001
13.FX Open reduction of fracture 4.2% 1.7% 2.44 2.02-2.93 0.0001
14.GAST Gastric surgery 5.5% 2.3% 2.41 1.82-3.19 0.0001
15.HER Herniorrhaphy 1.8% 2.3% 0.78 0.63-0.96 0.0197
16.HPRO Hip prosthesis 2.6% 1.3% 2.06 1.80--2.37 0.0001
17.HYST Abdominal hysterectomy 2.7% 1.6% 1.66 1.36-2.03 0.0001
18.KPRO Knee prosthesis 1.6% 0.9% 1.84 1.56--2.18 0.0001
19.LAM Laminectomy 1.7% 1.0% 1.67 1.33-2.09 0.0001
20.NECK Neck surgery 3.7% 3.5% 1.07 0.60--1.91 0.8116
2l.NEPH Kidney surgery 3.1% 1.5% 2.12 1.07-4.18 0.0267
22.PRST Prostate surgery 2.1% 1.2% 1.82 0.97-3.43 0.0598
23.PVBY Peripheral vascular bypa&'l surgery 2.5% 6.7% 0.37 0.28--0.49 0.0001
24.REC Rectal surgery 2.3% 7.4% 0.32 0.16-0.63 0.0005
25.SB Small bowel surgery 5.5% 6.1% 0.91 0.72-1.14 0.3937
26. SPLE Spleen surgery 5.6% 2.3% 2.39 0.93-6.10 0.0606
27. THOR Thoracic surgery 6.1% 1.1% 5.50 3.59-8.44 0.0001
28. TilYR. Thyroid and/ or parathyroid surgery 0.3% 0.3% 1.27 0.13-12.19 0.8366
29. VHYS Vaginal hysterectomy 2.0% 0.9% 2.24 1.52-3.28 0.0002
30. VSHN Ventricular shunt 12.9% 5.6% 2.30 1.96--2.69 0.0001
3l.XLAP Exploratory abdominal surgery 4.1% 2.0% 2.05 1.64-2.55 0.0001
ALL 2.9% 2.0% 1.45
AAA, abdominal aortic aneurysm repair; AMP, limb amputation; APPY, appendix surgery; BILl, bile duct, liver, or pancreatic surgery; BRST,
breast surgery; CBGB, coronary bypa&'l with chest and donor incision; CARD, cardiac surgery; CHOL, gallbladder surgery; COLO, colon
surgery; CRAN, craniotomy; CSEC, cesarean section; FUSN, spinal fusion; FX, open reduction of fracture; GAST, gastric surgery; HER,
herniorrhaphy; HPRO, hip prosthesis; KPRO, knee prosthesis; LAM, laminectomy; NECK, neck surgery; NEPH, kidney surgery; PRST, prostate
surgery; PVBY, peripheral vascular bypass surgery; REC, rectal surgery; SB, small bowel surgery; SPLE, spleen surgery; THOR, thoracic surgery;
TIIYR, thyroid and/or parathyroid surgery; VHYS, vaginal hysterectomy; VSHN, ventricular shunt; XLAP, exploratory abdominal surgery;
INICC, International Nosocomial Infection Control Consortium; SSI, surgical site infection; CI, confidence interval; CDC, Centers for Diseases
Control and Prevention; NHSN, National Healthcare Safety Network; RR, relative risk.
SSI Risk index 0
CDC.NNISS report 2004
In order to calculate the cost of CIA-BSI in ICUs, a 5-year at three hospitals in Mexico City, members of INICC, in four
prospective nested case-control study was undertaken in six ICUs. Fifty-five patients with CIA-BSI (cases) and 55 patients
adult ICUs from three hospitals of Argentina, members of without CIA-BSI (controls) were compared by analyzing hos-
INICC. One hundred and forty-two patients with CIA-BSI pital, type of ICU, year of admission, LOS, gender, age, and
(cases) and 142 patients without CIA-BSI (controls) were average severity of illness score. The results indicated that extra
matched for hospital, type of ICU, year of admission, LOS, gen- LOS of patients with CIA-BSI was 6.05 days. The mean extra
der, age, and average severity of illness score. The mean ex- co11t of antibiotics amounted to $598, the mean extra cost of
tra LOS for cases (compared to the controls) was 11.90 days, other dmgs was $25.77, and the mean extra cost of hospitaliza-
the mean extra antibiotic-defined daily doses was 22.6, the tion was $8,326. The mean extra co11t for cases (compared to
mean extra antibiotic cost was $1,913, the mean extra cost was the controls) amounted to $11,591. Finally, the extra mortality
$4,888.42, and the excess mortality was 24.6% (144). attributable to CIA-BSI was 20% (150).
To calculate the cost of CIA-BSis in ICU patients, an To estimate the excess LOS in an ICU due to CIA-BSI, a
18-month prospective nested case<ontrol study was undertaken study was performed in INICC hospitals in three Latin American
countries (Argentina, Brazil, and Mexico). A cohort of 3,560 inappropriate administration of antimicrobials. The increase in
patients hospitalized in 11 ICUs were followed for 36,806 days. antimicrobial treatments and generalized overuse of antimicro-
The average excess LOS due to a CLA-BSI increased and varied bials during the last decades has turned some once-common
between 1.23 and 4.69 days (149). infections that were easy to treat into a serious and, many times,
To calculate the cost of healthcare-associated pneumonia in life-threatening infection (174) .
ICUs, a 5-year matched cohort study was undertaken at six ICUs Patient safety is at high risk because of AMR, including
in three INICC hospitals in Argentina. Three hundred and seven multidrug resistance, because increasingly different bacteria,
patients with VAP (exposed) and 307 patients without VAP (unex- viruses, fungi, protozoa, or helminths are no longer sensitive
posed) were matched for hospital, ICU, period, LOS more than to the agents commonly administered to control the infections
7 days, gender, age, and average severity of illness score (ASIS). they cause. AMR threatens most clinical and public health
The mean extra LOS for 307 cases (compared to the controls) practices both in limited-resource countries and high-income
was 8.95 days, the mean extra antibiotic-defined daily doses was countries--from complex therapies to those routinely used for
15, the mean extra antibiotic cost was $996, the mean extra total common infectious diseases.
cost was $2,255, and the extra mortality was 30.3% (145). AMR imposes an extra financial burden upon healthcare facil-
In a study performed in INICC member hospitals in 10 ities, affecting limited-resource countries severely. Acting against
limited-resource countries to estimate extra LOS and mortality AMR not only has an effect at public health level, but it also af-
in an ICU due to a VAP, a cohort of 69,248 admissions were fol- fects different economic sectors, such as those involved in inter-
lowed for 283,069 days in ICUs. Extra LOS and increased risk of national trade and travel, because of the cross-border spread of
death were estimated independently in each country, and their resistant infections (174). AMR is related to loss of productivity
results were combined using a random-effects meta-analysis. (loss of income and reduced worker productivity) and increased
The findings of the analysis showed that a VAP prolonged LOS cost of diagnostics, testing, and treatment (costs related to infra-
by an average of 2.03 days (95% CI: 1.52, 2.54 days), and in- structure, screening, equipment, consultation, and drugs).
creased the risk of death by 14% (95% CI: 2, 27%) ( 173) . In studies from Europe, it has been shown that extra mortality
To estimate the excess LOS and mortality in the ICU attrib- caused by AMR exceeds $25,000 annually, and the extra health-
utable to CA-UTI, a statistical model that accounted for the care costs and loss in productivity have been estimated to be
timing of infection was applied in 29 INICC member hospital €1.5 billion each year (174). Because the data available on the
ICUs in 10 countries: Argentina, Brazil, Colombia, Greece, In- health and financial burden of AMR is scarce in many countries,
dia, Lebanon, Mexico, Morocco, Peru, and Thrkey. In a cohort it is difficult to make an accurate estimate on the actual magni-
of 69,248 admissions followed for 371,452 days in 29 ICUs, a tude of the problem. In addition, the stress and suffering caused
multistate model was applied to estimate the extra LOS due at patient level is even more difficult to measure. Furthermore, it
to infection. This model included specific censoring to ensure is a fuct that antimicrobials are extensively used in the animal food
that estimations considered the independent effect of urinary industry, which together with the use of inadequate measures to
tract infection, and not the combined effects of multiple in- control the spread of infection, increases the difficulties to convey
fections. The extra LOS and increased risk of death were es- the sheer complexity of the situation. AMR, thus, affects entities
timated independently for each country, and then the results from several sectors, public and private, whose commitment is
were combined using a random-effects meta-analysis. The con- necessary to confront this evolving threat at different levels.
clusions showed that a CA-UTI prolonged the length of ICU Usually, reports on AMR are generated by laboratory results.
stay by an average of 1.59 days (95% CI: 0.58, 2.59 days), and These data are used as evidence for policy makers' decisions and
increased the risk of death by 15% (95% CI: 3, 28%) (151). for decisions on individual patient's treatment. Such reports
document that AMR is increasingly affecting the prevention and
control of infections not only at healthcare facilities but also in
EXTRA MORTALITY OF HAIS
the community. Moreover, anti-infective agents are fundamen-
IN LIMITED-RESOURCE SETTINGS
tal for many of the medical advances in recent years, such as
Mortality attributable to HAl in limited-resource countries chemotherapy for cancer treatment and organ transplantation,
has been shown in different publications to range from 3% to which are dependent on their availability to control infections.
75.1% (5,9-14). Rosenthal et al. have shown that mortality due Healthcare fucilities worldwide experience a wide variety of
to CLA-BSI ranged from 4% to 75.1% (Table 18.3). Rosenthal, patterns and diverse prevalence of AMR, which contributes to
in 2009, demonstrated that the CLA-BSI rate was associated fuilures in antibiotic therapies and increased cost, morbidity, and
with significant extra mortality, with an odds ratio ranging from mortality (175). There are different options available to coun-
2.8 to 9.5 (18). Similarly, mortality attributable to VAP has been teract the evolving nature of AMR, which can be implemented
found to be as high as 56.7% (Thble 18.4). With respect to mor- to effectively maximize the limited life span of antibiotics. The
tality due to CA-UTI, reports are scarce and there has been di- available strategies and interventions, however, should be applied
versity in the interpretation of findings. In some publications, globally to optimize their beneficial effects. Over the last two de-
it was stated that CA-UTI was not associated to mortality, but cades, AMR has been recognized as part of a public health crisis,
other findings specified rates up to 21.3% (Table 18.5). and international agencies and different organizations worldwide
have been implementing strategies in different sectors (176).
The evolving public health threat of AMR is driven by both
ANTffiiOTIC RESISTANCE
appropriate and inappropriate use of anti-infective agents for
It is known that eventually bacteria react to antibiotics treat- human and animal health and food production, together with
ment and become resistant to them. This means that the inadequate measures to control the spread ofinfections (176).
effectiveness of the antibiotic life span is limited. Antimicro- The burden of AMR is difficult to assess for bacteria that
bial resistance (AMR) is influenced by the unnecessary or cause community-acquired infections. In laboratory reports, it
has been shown that resistance is increasing in bacteria caus- existence of a black market, and individual financial interests at
ing pneumonia, which is responsible for the death of approxi- local, national, regional, and international levels (183).
mately 1.8 million children annually (174). However, as described in recent studies (184), high-income
Around 90% of antibiotic treatments for humans are pre- countries are also affected by counterfeit antibiotics, where the
scribed as part of the general medical practice. This has led to a World Wide Web has played a fundamental role through In-
generalized use of antibiotics, which is based on national treat- ternet pharmacies, which even licensed, are increasingly buy-
ment guidelines, and not considered from a global perspective. ing counterfeit drugs themselves from foreign sources to meet
The use of second- and third-line agents adds higher costs to demand (185).
treatment, and development of treatment guidelines has be- Infection prevention and control activities also are essential
come extremely difficult for many common infections (174). to limit the spread of AMR, as they spread from individuals to
Resistant bacteria spread both in hospitals and community- other individuals or to the environment and then again to in-
wide. Several bacteria can inactivate carbapenems and resist dividuals. Effective control of HAis helps reduce the impact of
third-generation cephalosporins, causing significant numbers AMR (Table 18.26).
of HAis and community-acquired infections (174). Recently,
there has been a development in apparent shift in AMR, which
might be occurring between the main classes of pathogenic TABLE 18.26 Key hcommendations of
bacteria (from gram-positive to gram-negative pathogens). It the WHO Global Strategy
is likely that recent achievements to control gram-positive or- for Containment of
ganisms are outweighed by the emergence of highly resistant Antimicrobial &sistana:
gram-negative bacteria (174). It has been considered that the
1. Educate all groups of prescribers and dispenaers (including
lack of new antibiotics render some multidrug-resistant (MDR)
drug sellers) in the importance ofappropriate antimicrobial
infections untreatable. In spite of the implementation of AMR use and containment of antimicrobial resistance.
containment and antibiotic stewardship programs, AMR is very 2. Promote targeted undergraduate and postgraduate
slow to reverse or even irreversible (174). That is why the in- educational prograzru for all healthcare workers, veterinar-
troduction of interventions to avoid the initial spread of AMR ians, prescribers, and dispensers on accurate diagnosis and
should be considered a priority in public health. management of common infections.
Addressing AMR from a comprehensive perspective requires !. Encourage prescribers and dispensers to educate patients on
that environmental aspects are also considered (174). Water, antimicrobial use and the importance of adherence to pre-
air, and soil are being examined for the presence and possible scribed treatments.
4. Improve antimicrobial use by supervision and support of clin-
spread of resistant bacteria (174). Contaminated eilluent and
ical practices, especially diagnostic and treatment strategies.
manure have been shown to contain significant amounts of an-
5. Monitor prescribing and dispensing practices and utilize peer
tibiotic. It is therefore essential that sanitation and water supply group or external standard comparisons to provide feedback
services be appropriately rendered to halt or reduce the spread and endorsement of appropriate antimicrobial prescribing.
of bacteria, including AMR. 6. Encourage development and use of guidelines and treatment
The general interventions to reduce AMR include surveil- algorithiilll to foster appropriate use of antimicrobials.
lance of antimicrobial resistance and use, although resistant- 7. Empower formulary managers to limit antimicrobial use to the
bacteria proportions may vary from one area to another, and prescription of an appropriate range of selected antimicrobials.
in many hospitals and medical centers there are no local data 8. Link professional registration requirements for prescribers
on resistance patterns. It has been reported that data on an- and dispensers to requirements for training and continuing
education.
timicrobial use and AMR are useful in serving as guides for
9. Establish effective hospital therapeutics committees with
treatment options, knowing and understanding AMR trends,
responsibility for oversight of antimicrobial use in hospitals.
making information known for public health policy, and iden- 10. Develop and regularly update guidelines for antimicrobial
tifying areas in need of priority, and monitoring the impact of treatment, prophylaxis, and hospital antimicrobial formularies.
interventions to contain AMR. 11. Monitor antimicrobial usage, including quantity and patterns
Another important aspect for AMR control is using anti- of use, and feedback results to prescribers.
microbial rationally and imposing antibiotic regulation. It is 12. Ensure on~ite availability of microbiology laboratory services,
known that the development of resistance is the natural re- which are appropriately matched to the level of the hospital
sponse of any bacteria when they are under threat. Individual (e.g., secondary, tertiary).
use, overuse, and inappropriate use have a considerable effect 1!. Ensure performance and quality assurance of appropriate diagnos-
tic tests, bacterial identification, antimicrobial susceptibility tests of
in the evolution of AMR. For this reason, containment strat-
key pathogens, and timely and relevant reporting of resullll.
egies are to include regulations for the appropriate use of
14. Ensure that laboratory data are recorded (preferably on a data-
antibiotics (177). balle) and are used to produce clinically and epidemiologically
In limited-resource countries, there are socioeconomic and be- useful surveillance reportll of resistance patterns among com-
havioral factors that can lead to increased AMR ( 178). Particularly mon pathogens and infections in a timely manner and feed
in rural areas, lack of adequate laboratory support and insufficient back to prescribers and the infection control programme.
knowledge on the epidemiology of antibiotic resistance patterns 15. Make the containment of antimicrobial resistance a national
may force prescribers to empirically administer broad-spectrum priority through the creation of a national intersectoral
antibiotic combinations (179). Limited-resource countries are task force to raise awareness about antimicrobial resistance,
confronted with m~or difficulties arising from substandard or organize data collection, and allocate resources to promote
counterfeit antibiotics (180-182). Unfortunately, it has been re- the implementation of interventions to contain resistance
including appropriate utilization of antimicrobial drugs,
ported that the WHO &sential Drug Program has not obtained
control and prevention ofinfection, and research activities.
satisfactory results in most countries, because of the continued
In 1992, the Alexander Project was launched in seven coun- improving compliance with infection control interventions
tries to fight against the evolving threat of antibiotic resistance and, consequently, reducing the rates of HAl and mortality.
in Europe (175). The WHO has also called upon member In adult ICUs, INICC member hospitals have reduced the rate
states and the international community to take measures to of CLA-BSI by 54% (56), of CA-UTI by 37% (64), ofVAP by
counteract the spread of AMR by means of a global strategy for 56% (101), and of mortality by 58% (56). Similarly, in PICUs,
containment of AMR published in 2001, which set out a collec- INICC member hospitals have reduced the rate of CLA-BSI by
tion of recommendations for AMR control. 52% (57), ofCA-UTI by 57% {63), and ofVAP by 31% (60). In
Several world health assembly resolutions have called for ac- NICUs, the INICC member hospitals have reduced the rate of
tion on specific health aspects related to AMR, and the WHO CLA-BSI by 55% (186) and ofVAP by 33% (61).
published its global strategy to contain AMR in 2001. Ten years
later, in 2011, the WHO on world health day (WHD) published
CENTRAL LINE-ASSOCIATED INFECTIONS
a six-point policy package addressed to countries worldwide to
(CLA-BSI) RATE REDUCTION: INICC
(a) commit to a comprehensive, financed national plan with
STUDIES AND OTHERS
accountability and civil society engagement; (b) strengthen sur-
veillance and laboratory capacity; (c) ensure uninterrupted ac- In a prospective before-after trial performed at INICC mem-
cess to essential medicines of assured quality; (d) regulate and ber hospitals in Argentina, the rates of CLA-BSI determined
promote rational use of medicines in animal husbandry and to during a period of active surveillance without education or
ensure proper patient care; (e) enhance infection prevention performance feedback (phase 1) were compared to the rates
and control, and (f) foster innovations and research and devel- of CLA-BSI after sequential implementation of an infection
opment of new tools (174). control program that included education (phase 2) and per-
INICC promotes evidence-based infection control in hos- formance feedback (phase 3). The overall rates of CLA-BSI
pitals in low- and middle-income countries, and in hospitals were reduced by 75%, from 46.63 to 11.10 CIA-BSis per 1,000
worldwide with lack of experience in HAl surveillance, pre- IVD-days (RR: 0.25, 95% CI: 0.17 to 0.36, p < .0001) (54). A
vention and control through the analysis and feedback of prospective, controlled, time-series, cohort trial was under-
voluntarily collected surveillance data {31,35). Regularly up- taken in adult patients admitted to four level-III adult ICUs in
dated data are crucial to show trends in the bacterial-resis- Argentina to study the impact of open- and closed-infusion sys-
tance patterns related to specific HAis. Table 18.22 provides tems on rates of CLA-BSI. The rates of CLA-BSI during a period
data on bacterial resistance of pathogens isolated from pa- of active surveillance with an open-infusion system (baseline;
tients with DA-HAI in adult and pediatric ICUs and NICUs in externally vented, semirigid, noncollapsible, one-port plastic
INICC ICUs. bottles) were compared with rates after switching to a closed
Political commitment and stimulating innovation in antibi- system (intervention; nonvented, collapsible, two-port plastic
otic development are key interventions to be applied to control bags). The incidence of CLA-BSI during the use of the closed
AMR. Developments in effective drugs have declined during system was significantly lower than during use of the open
the last decades, especially for MDR infections. Phannaceutical system (2.36 vs. 6.52/1,000 central line-days, RR: 0.36, 95%
companies are not financially incentivized by this type of de- CI: 0.14 to 0.94, p = .02) (187).
velopment. Furthermore, new technologies and innovations In Mexico, a prospective before-after trial was performed at
are needed for other areas such as rapid diagnostic tests and level-ill adults ICUs in one public university, an INICC mem-
infection control, which are essential for controlling AMR ef- ber. During a period of active surveillance without process
fectively. Consequently, the role played at governmental level is control, the rates of CLA-BSI were determined (phase 1) and
crucial, as it comes to policy makers to take the necessary steps were then compared to rates of CIA-BSI after implementing
toward the implementation of effective actions. an infection control program that applied process surveillance
and performance feedback (phase 2) . Compliance with CL site
care and HH improved significantly from baseline during the
DEVICE-ASSOCIATED HAl RATE study period: placing a gauze dressing over the catheter inser-
REDUCTION IN LIMITED-RESOURCE tion site improved from 86.69% to 99.24% (RR: 1.14, 95% CI:
1.07 to 1.22, p < .001), proper use of gauze over the central
SETTINGS
line insertion site improved from 84.21% to 97.87% (RR: 1.16,
95% CI: 1.09 to 1.24, p < .001), documentation of date of place-
BACKGROUND
men t of administration set of vascular catheter improved from
From its very inception in 1998, INICC has brought the use of 40.69% to 93.85% (RR: 2.34, 95% CI: 2.14 to 2.56, p < .001),
feedback of HAl surveillance data as a means to improve quality HH before contact with the patient improved from 62% to
in healthcare to a new level, monitoring and providing contin- 84.9% (RR:1.37, 95% CI: 1.21 to 1.51, p < .001). The overall
uous feedback not only of outcome data-HAl rates-but the rates of CLA-BSI were significantly reduced by 58% after imple-
results of process surveillance--rates of compliance with nn menting a process control program, from 46.3 to 19.5 CLA-BSis
and other simple but highly effective, evidence-based infection per 1,000 CL-days (RR: 0.42, 95% CI: 0.27 to 0.66, p < .0001).
control practices-and combining education with feedback of Finally, the overall rates of crude unadjusted mortality were low-
both outcome and process surveillance can bring quantum re- ered significantly from baseline rates, from 48.5% per 100 dis-
ductions in the risk of life-threatening HAis in ICUs. Through charges to 32.8% (RR: 0.68, 95% CI: 0.50 to 0.31, p < .01) (55) .
these last 13 years, INICC has undertaken a global effort in In Brazil, an educational program was developed by a mul-
America, Asia, Mrica, and Europe to respond to the burden of tidisciplinary task force to highlight correct practices for CL
HAis and reduce their adverse effects, such as mortality. This care. Before intervention, the CLA-BSI rate was 20 per 1,000
joint effort was rewarded with extremely successful results by CL<Iays, and after the educational intervention and policy
changes-such as standardized use of povidone-iodine dur- adult patients who received MV for at least 24 hours in four,
ing dressing care-the number of CLA-BSis dropped to 11 per level-III adult ICUs in two Argentinean hospitals. The rates
1,000 CL-days (188). of VAP were determined during a period of active surveil-
In Tunisia, a randomized, controlled trial was conducted in lance without an infection control program (phase 1) and
which 246 patients with nontunneled CL were randomly as- compared with rates ofVAP after the implementation of an
signed to receive a heparin-coated line with 50 mL/d of nor- infection control program that included educational and
mal saline solution as a continuous infusion (heparin-coated surveillance feedback components (phase 2) . One thousand
group) or a noncoated catheter with a continuous infusion of six hundred and thirty-eight MY-days were accumulated in
low-dose unfractionated heparin (control group: continuous phase 1, and 1,520 MY-days were accumulated during phase
infusion of100 U/kg/d). CLA-BSI occurred in 0.9 events per 2. The results of the study showed that the rates of VAP
1,000 days in the heparin-coated group and in 3.5 events per were significantly lower in phase 2 than in phase 1 (51.28
1,000 days in the control group (3.5 events per 1,000 days; vs. 35.50 episodes of VAP per 1,000 MY-days, respectively;
p = .027). The conclusion of this study was that the use of hep- RR: 0.69, 95% CI: 0.49 to 0.98, p < .003) (58).
arin-coated lines could be a safe and effective approach to the A prospective before-after trial was performed in China
prevention ofCLA-BSI in patients with hematologic-oncologic with the aim to analyze the impact of a multidimensional infec-
disease (189). tion control approach on the reduction ofVAP in ICU patients
In Turkey, a study was conducted to analyze the effect of edu- of one hospital. The study period was from January 2005 to
cation on the rate of CLA-BSI. During the preeducation period, July 2009, which was divided into baseline (phase 1) and in-
the CLA-BSI rate was 8.3 infections per 1,000 CL-days, and dur- tervention (phase 2) periods. During phase 1, active prospec-
ing the posteducation period, the CIA-BSI rate was 4.7 infections tive outcome surveillance of VAP was performed by applying
per 1,000 CL-days (190). In another study conducted in Turkey, the definitions of CDC's NHSN, and the methodology of the
133 patients requiring CL were chosen at random to receive ei- INICC. During phase 2, the multidimensional approach was
ther an antiseptic-impregnated triple-lumen catheter (N = 64) implemented. The authors recorded data from 16,429 patients
or a standard triple-lumen catheter (N = 69). The CLA-BSI hospitalized in three ICUs, for a total of 74,116 ICU bed-days.
rates were 5.3/1,000 CL-days for the antiseptic line group and The VAP rates obtained in phases 1 and 2 were compared
1.6/1,000 CL-days for the standard line group (p = .452). The in yearly periods. The VAP baseline rate was 24.1 per 1,000
results of this study indicated that the use of antiseptic-impreg- ventilator-days. During phase 2, the VAP rate significantly de-
nated central lines had no effect on the incidence of either line creased to 5.7 per 1,000 ventilator-days in 2009 (2009 vs. 2005:
colonization or CIA-BSI in critically ill patients, although the RR: 0.31, 95% CI: 0.16 to 0.36, p = .0001), or a 79% cumulative
power of this study may have been inadequate ( 191). VAP rate reduction (59).
In a time-sequence analysis of the effectiveness of this mul- In Cuba, an observational prospective study was conducted
tifaceted approach in reducing rates of CLA-BSI in 15 limited- to evaluate the impact of the INICC multidimensional ap-
resource countries from INICC, it was concluded that after proach for the prevention ofVAP in an adult ICU. This mul-
implementing the infection control program, adherence to in- tidimensional approach included the following measures:
fection control compliance significantly improved, the CIA-BSI (a) bundle of infection control interventions, (b) education,
incidence was reduced by 54% (16.0 to 7.4 CLA-BSis per 1,000 (c) outcome surveillance, (d) process surveillance, (e) feed-
CL-days; RR: 0.46, 95% CI: 0.33 to 0.63,p < .001), and the num- back ofVAP rates, and (f) performance feedback of infection
ber of CLA-BSI-associated deaths decreased by 58% (56). control practices. The baseline rates of VAP were compared
A recent PICU study was performed in six limited-resource to the rates obtained after intervention. The impact of their
countries to analyze the impact of a multidimensional infection interventions was analyzed with Poisson regression analysis.
control approach on CLA-BSI rates. The approach included During baseline, the authors recorded 114 MY-days, and dur-
(a) a bundle ofinfection control interventions, (b) education, ing intervention they recorded 2,350 MY-days. The baseline
(c) outcome surveillance, (d) process surveillance, (e) feed- rate ofVAP was 52.63 per 1,000 MY-days, and 15.32 per 1,000
back of CLA-BSI rates, and (f) performance feedback of in- MY-days during intervention, which accounted for a 70%
fection control practices. After intervention, the CLA-BSI was reduction on the rate of VAP (RR: 0.3, 95% CI: 0.12 to 0.7,
reduced from baseline by 47% (13.0 to 6.9 CLA-BSis per 1,000 p < .003) (99).
CL-days; RR: 0.53, 95% CI: 0.29 to 0.94, p < .0271) (57). A simi- In Pakistan, an observational pre- and postintervention
lar multidimensional approach for CLA-BSI reduction was ad- study was conducted to assess whether an educational program
opted in another study conducted by INICC in NICUs of four focusing on preventive practices for VAP could reduce its inci-
limited-resource countries: El Salvador, Mexico, Philippines, dence. An evidence-based guideline for preventive practices at
and Tunisia. During baseline, the CIA-BSI rate was 21.4 per the bedside was developed and disseminated to the ICU staff.
1,000 CL-days, and after intervention, the CLA-BSI rate de- The VAP infection rates were reduced by 51%, from a mean of
creased to 9.7 per 1,000 CL-days (RR: 0.45, 95% CI: 0.33 to 13.2 VAP in the preintervention period to 6.5 VAP per 1,000
0.63), showing a 55% CLA-BSI rate reduction (186). device-days in the postintervention period (mean difference:
6.7, 95% CI: 2.9 to 10.4, p = .02) (192).
In Thailand, a study was performed to determine the long-
VENTILATOR-ASSOCIATED PNEUMONIA
term effect of an educational program to prevent VAP in an
(VAP) RATE REDUCTION: INICC STUDIES
MICU. The educational program involved respiratory therapists
AND OTHERS
and nurses, and included a self-study module with preinterven-
In an INICC member hospital in Argentina, a study was tion and postintervention assessments, lectures, fact sheets,
conducted to ascertain the effect of an infection control and posters. Before the intervention, there were 20.6 cases per
program on rates of VAP in ICUs. The study included all 1,000 ventilator-days in the MICU, and after intervention the
rate ofVAP decreased by 59% to 8.5 cases per 1,000 ventilator- measures, (b) education, (c) outcome surveillance, (d) pro-
days (p = .001) (193). cess surveillance, (d) feedback of CA-UTI rates, and (e) feed-
In another multicenter study conducted by INICC in adult back of performance. The rates of CA-UTI obtained in phase
ICUs of 16limited-resource countries, a multidimensional ap- 1 were compared with the rates obtained in phase 2, after the
proach was applied with the aim of reducing the rates of VAP. interventions were implemented. During the study period,
The VAP rate at baseline was 20.8, and after intervention, it the authors recorded 253,122 UC-days: 30,390 in phase 1
decreased to 16.5 per 1,000 MV-days (RR: 0.79, 95% CI: 0.70 to and 222,732 in phase 2. In phase 1, before the intervention,
0.90, p < .0003), or a 21% VAP rate reduction (64). With the theCA-UTI rate was 7.86 per 1,000 UC-days, and in phase 2,
same approach, in a study conducted in PICUs of five limited- after intervention, the rate of CA-UTI decreased to 4.95 per
resource countries, it was shown that the rate ofVAP at baseline 1,000 UC-days (RR: 0.63, 95% CI: 0.55 to 0.72), or a 37% rate
was 11. 7, and after the intervention, it had decreased to 8.1 per reduction (64).
1,000 MV-days (RR: 0.69, 95% CI: 0.5 to 0.96, p < .02), or a 31% A study was conducted by INICC in PICUs from six limited-
VAP rate reduction (60). resource countries; the study analyzed the impact of a multi-
A prospective cohort study was conducted by INICC from dimensional approach developed to reduce CA-UTI rates. In
October 2003 to October 2010 in NICUs of INICC member phase 1, theCA-UTI rate was 5.9 per 1,000 UC-days, and in
hospitals from 15 cities of 10 developing countries: Argentina, phase 2, after implementing the multidimensional infection
Colombia, El Salvador, India, Mexico, Morocco, Peru, Philip- control approach for CA-UTI prevention, the CA-UTI rate de-
pines, Tunisia, and Turkey. The VAP rates were determined creased to 2.6 per 1,000 UC-days (RR: 0.43, 95% CI: 0.21 to
during a first period of active surveillance without the imple- 1.0), showing a rate reduction of 57% (62).
mentation of the multidimensional approach (phase 1) and
then compared with the VAP rates after the implementation
INICC OVERALL HAl RATE REDUCTION
of the INICC multidimensional infection control program that
included the following practices: (a) bundle of infection con- With regard to HH compliance, and association with HAl rate
trol interventions, (b) education, (c) outcome surveillance, reduction, three Argentinean hospitals, members of INICC,
(d) process surveillance, (e) feedback ofVAP rates, and (f) per- were studied for adherence to an HH protocol, and 15,531
formance feedback of infection control practices (phase 2). patient contacts were observed. The baseline rate of HH be-
This study was conducted by infection control professionals ap- fore contact with patients was 17%. The implementation of a
plying CDC's NHSN HAl definitions, and INICC surveillance program consisting of a multidimensional approach including
methodology. During phase 1, the authors recorded 3,153 MY- a bundle, education, process surveillance, supplies availability,
days, and during phase 2, they recorded 15,981 MV-days. The and administrative support has as an outcome that HH before
results indicated that the VAP rate during phase 1 period was contact with patients increased to 44% (RR: 2.65, 95% CI: 2.33
17.8, and during phase 2 period was 12.0 per 1,000 MV-days to 3.02, p < .001), and when adding performance feedback,
(RR: 0.67, 95% CI: 0.50 to 0.91, p < .001), or a 33% VAP rate HH further increased to 58% (RR: 1.86, 95% CI: 1.38 to 2.51,
reduction (61). p < .001) (100). In another publication, this multidimensional
approach was associated with a reduction in HAl rates in the
ICUs. HH adherence improved progressively from 23.1%
CATHETER-ASSOCIATED URINARY TRACT
(268/1160) to 64.5% (2056/3187) (RR: 2. 79, 95% CI: 2.46 to
INFECTION (CA.-UTI) RATE REDUCTION:
3.17, p < .0001). During the same period, the overall HAl rate
INICC STUDmS AND OTHERS
in both ICUs decreased by 41% from 47.55 to 27.93 HAis per
In an open trial in an Argentinean INICC member hospital, 1,000 patient-days (RR: 0.59, 95% CI: 0.46 to 0.74, p < .0001)
the rates of CA-UTI were determined during a baseline period (105).
of active surveillance without education and performance feed-
back, and then were compared with rates of CA-UTI after im-
CONCLUSION
plementing education, process surveillance, and performance
feedback regarding catheter care measures and HH compli- As documented in this chapter, data from limited-resource
ance. The findings showed that the CA-UTI rate decreased countries illustrate that, similar to developed countries, it is
significantly by 42%, from 21.3 to 12.39 CA-UTis per 1,000 a paramount to implement a multidimensional infection con-
catheter-days (RR: 0.58, 95% CI: 0.39 to 0.86, p = .006) (63). trol program-including a bundle of targeted infection con-
A prospective before-after surveillance study conducted trol measures, education, outcome and process surveillance,
on a cohort of 56,429 patients hospitalized in 57 adult ICUs, feedback of HAl rates, and performance feedback-since
during 360,667 bed-days from April 1999 to February 2011, they were associated with significant reductions in rates of
with the aim to evaluate the impact of the INICC multidimen- DA-HAI and their adverse effects. There is representative and
sional infection control approach for the reduction of the consistent evidence of the effectiveness that multidimensional
incidence of CA-UTI in patients hospitalized in adult ICUs infection control strategies can have in reducing HAis in lim-
of hospitals, members of the INICC from 40 cities of 15 de- ited-resource countries (54-64). These findings reveal that
veloping countries: Argentina, Brazil, China, Colombia, Costa the reduction of DA-HAis is feasible and cost-effective even
Rica, Cuba, India, Lebanon, Macedonia, Mexico, Morocco, in limited-resource countries; therefore, this valid evidence
Panama, Peru, Philippines, and Turkey. The study was di- should lead to the mandatory organization of multidimen-
vided into baseline period (phase 1) and intervention period sional infection control programs in every healthcare facility in
(phase 2) . In phase 1, active surveillance was performed. In all countries-developed or resource-limited. The data from
phase 2, the authors implemented a multidimensional infec- these studies published from 2002 to 2011 are summarized in
tion control approach that included (a) bundle of preventive Tables 18.27 and 18.28.
TABLE 18.27 Intcrventional Studies Aiming at Device-Associated Infection Raluction :kportcd by Hospitals &om Economics Defined as
Low-, Lower-Middle, And Upper-Middle Income by the World Bank
Studied Outcome
Country DAI ICUstudied Study design Intervention measurement DAI rate p Year Reference
Argentina (INICC Study) CLA-BSI Medical Pre-/postintervention Hand hygiene, catheter CLA-BSI per 1,000 45.94 11.10 0.001 2003 (54)
surgical and care, education, per- Cl.rdays
coronary formance feedback
Argentina (INICC Study) CLA-BSI Medical Pre-/postintervention Closed-infusion system CLA-BSI per 1,000 6.52 2.36 0.02 2004 (187)
surgical and Cl.rdays
coronary
Brazil CLA-BSI Medical Pre-/postintervention Hand hygiene, CLA-BSI per 1,000 20 16 NA 2005 (188)
education, perfor- Cl.rdays
mance feedback
Brazil (INICC Study) CLA-BSI ICUs Pre-/postintervention Closed-infusion system CLA-BSI per 1,000 6.5 3.2 0.03 2009 (308)
Cl.rdays
Mexico (INICC Study) CLA-BSI ICUs Pre-/postintervention Hand hygiene, CLA-BSI per 1,000 46.3 19.5 0.001 2007 (55)
education, perfor- Cl.rdays
mance feedback
Mexico (INICC Study) CLA-BSI ICUs Pre-/ postintervention Closed-infusion system CLA-BSI per 1,000 16.1 3.2 <0.0001 2010 (148)
Cl.rdays
Senegal CLA-BSI NICU Pre-/postintervention Multidimensional CLA-BSI per 1,000 10.9 2.9 0.03 2011 (309)
approach bed-days
Tunisia CLA-BSI Adult and Randomized Heparin-coated catheter CLA-BSI per 1,000 3.5 0.9 NA 2007 (189)
pediatric with 50 mL/d contin- Cl.rdays
hospi.talwide uous saline infusion
vs. noncoated cath-
eter with continuous
heparin infusion
Thrkey CLA-BSI Medical Randomized Central venous catheters CLA-BSI per 1,000 5.3 1.6 0.452 2006 (191)
surgical impregnated with Cl.rdays
chlorhexidine and
silver sulfadiazine
Thrkey CLA-BSI Hospitalwide Pre-/postintervention Education, performance CLA-BSI per 1,000 13.04 7.6 0.004 2007 (190)
feedback Cl.rdays
INICC 15 countries (INICC Study) CLA-BSI Adult, PICU, Pre-/postintervention Multidimensional CLA-BSI per 1,000 16.0 7.4 <0.001 2010 (56)
NICU approach Cl.rdays
INICC 6 countries: Colombia, CLA-BSI PICU Pre-/postintervention Multidimensional CLA-BSI per 1,000 13.0 6.9 <0.001 2011 (57)
India, Malaysia, Mexico, Phil- approach Cl.rdays
ippines, and Turkey (INICC
Study)
INICC 4 countries: El Salvador, CLA-BSI NICU Pre-/postintervention Multidimensional CLA-BSI per 1,000 21.4 9.7 <0.001 2012 (186)
Mexico, Philippines, and Tunisia approach Cl.rdays
(INICC Study)
Argentina (INICC Study) VAP Adult Pre-/postintervention Education, performance VAP per 1,000 51.28 35.50 <0.003 2006 (310)
feedback MY-days
China (INICC Study) VAP Adult Pre-/postintervention Education, performance VAP per 1,000 24.1 5.7 <0.001 2012 (59)
feedback MY-days
Cuba (INICC Study) VAP Adult Pre-/postintervention Multidimensional VAP per 1,000 52.63 15.32 0.003 2012 (99)
t.)
0\ approach MY-days
"'' (continued)
too)
0\ TABLE 18.27 Intcrvcntional Studies Aiming at Device-Associated Infection :hduction :&ported by Hospitals &om Economics Defined as
00
Low-, Lower-.Middle, And Upper-Middle Income by the World Bank (Ctmrit~wtl)
Studied ICU Outcome
Country DAI studied Study design Intervention measurement DAI rate p Year Reference
Pakistan VAP Hospitalwide Pre-/postintervention Education, performance VAP per 1,000 13.2 6.5 0.02 2004 (192)
feedback MV-days
Thailand VAP MICU Pre-/postintervention Education, performance VAP per 1,000 20.6 8.5 0.001 2007 (311)
feedback MV-days
Thailand VAP ccu Pre-/postintervention Education, performance VAP per 100 40.5% 24% <0.001 2005 (312)
feedback patients
Turkey CA-UTI Adult Pre-/postintervention Nationwide hospital CA-UTI per 1,000 10.2 5.7 <0.001 2012 (238)
infection control UC-days
program
Thrkey CLA-BSI Adult Pre-/postintervention Nationwide hospital CLA-BSI per 1,000 5.3 2.1 <0.001 2012 (238)
infection control CLdays
program
Argentina (INICC Study) Overall Adult Pre-/postintervention Multidimeruional DAI rate per 1,000 47.56 27.9 <0.0001 2005 (105)
DAI approach bed-days
Brazil (INICC Study) l.VD-BSI Adult Pre-/postintervention Multidimeruional CLA-BSI per 1,000 14.0 7.1 0.002 2005 (313)
approach CLdays
Brazil (INICC Study) IVI)..BSI Adult Pre-/postintervention Multidimemional CLA-BSI per 1,000 7.1 3.2 0.02 2006 (314)
approach CLdays
Colombia (INICC Study) l.VD-BSI Newborn Pre-/postintervention Multidimeruional CLA-BSI per 1,000 54.8 6.0 O.ol 2005 (315)
approach CLdays
India (INICC Study) Overall Adult Pre-/postintervention Multidimeruional DAI rate per 1,000 12.0 5.3 0.020 2007 (316)
India (INICC Study) Overall Adult Pre-/postintervention Multidimemional DAI rate per 1,000 3.89 0.3 0.001 2006 (243)
India (INICC Study) Mortality Adult Pre-/postintervention Multidimeruional Mortality per 100 1.7 0.5 0.001 2007 (317)
approach patients
India (INICC Study) l.VD-BSI Adult Pre-/postintervention Multidimeruional CLA-BSI per 1,000 12.0 5.05 0.0013 2007 (318)
approach CLdays
India (INICC Study) VAP Adult Pre-/postintervention Multidimemional VAP per 1,000 26.3 10.9 0.005 2007 (317)
approach MV-days
India (INICC Study) CA-UTI Adult Pre-/postintervention Multidimeruional CA-UTI per 1,000 7.4 2.2 0.048 2007 (316)
approach catheter-days
Mexico (INICC Study) Overall Newborn Pre-/postintervention Multidimeruional DAI rate per 1,000 13.0 5.0 0.0 2005 (319)
Mexico (INICC Study) Mortality Adult Pre-/postintervention Multidimemional Mortality per 100 48.5 32.8 O.ol 2005 (55)
approach patients
Mexico (INICC Study) IVI)..BSI Adult Pre-/postintervention Multidimemional CLA-BSI per 1,000 17.0 3.0 0.001 2004 (320)
approach CLdays
Mexico (INICC Study) l.VD-BSI Newborn Pre-/postintervention Multidimeruional CLA-BSI per 1,000 40.7 10.!1 O.ol 2005 (!119)
approach CLdays
Mexico (INICC Study) VAP Adult Pre-/postintervention Multidimensional VAP per 1,000 17.6 8.3 0.026 2010 (321)
approach MV-daf!
Turkey (INICC Study) Overall Adult Pre-/postintervention Multidimensional DAI rate per 100 55.0 18.8 0.014 2007 (322)
DAI approach patients
Thrkey (INICC Study) IVD-BSI Adult Pre-/postintervention Multidimensional CLA-BSI per 1,000 10.0 1.8 0.001 2006 (323)
approach Clrdaf!
Turkey (INICC Study) IVD-BSI Adult Pre-/postintervention Multidimensional CLA-BSI per 1,000 29.1 13.0 0.007 2006 (324)
approach Clrdaf!
Turkey (INICC Study) IVD-BSI Adult Pre-/postintervention Multidimensional CLA-BSI per 1,000 23.1 15.5 0.001 2009 (325)
approach Clrdaf!
Cuba (INICC Study) VAP Adult Pre-/postintervention Multidimensional VAP per 1,000 43.5 9.2 0.009 2008 (326)
approach MV-daf!
Morocco (INICC Study) Mortality Adult Pre-/postintervention Multidimensional Mortality per 100 35.7 26.5 0.001 2008 (327)
ap~ach tr¥Jnts
Philippines (INICC Study) CA-UTI Adult Pre-/postintervention Mulu · ensional CA- per 1,000 7.92 2.66 0.010 2010 (328)
approach catheter-da}'!
INICC 16 countries: Argentina, VAP Adult Pre-/postintervention Multidimensional VAP per 1,000 20.8 16.5 0.0002 2011 (98)
Brazil, China, Colombia, Costa approach MV-daf!
Rica, Cuba, India, Lebanon,
Macedonia Malaf!ia, Mexico,
Morocco, Panama, Peru,
Philippines, and Thrkey (INICC
Study)
INICC 5 countries: Colombia, VAP PICU Pre-/postintervention Multidimensional VAP per 1,000 11.7 8.1 0.02 2011 (60)
E1 Salvador, India Philippines, approach MV-daf!
and Turkey (INICC Study)
INICC 11 countries: Argentina, VAP NICU Pre-/postintervention Multidimensional VAP per 1,000 17.0 12.1 0.02 2011 (61)
Colombia, India, MalOl)'!ia, approach MV-daf!
Mexico, Morocco, Peru,
Philippines, El Salvador, Thnisia,
and Thrk.ey (INICC Study)
Argentina (INICC Study) CA-UTI Medical Pre-/postintervention Education, CA-UTI per 1,000 21.3 12.39 0.006 2004 (63)
surgical and performance catheter-da}'!
coronary feedback
INICC 15 countries: Argentina, CA-UTI Adults Pre-/postintervention Multidimensional CA-UTI per 1,000 7.86 4.95 0.001 2012 (64)
Brazil, China, Colombia, Costa approach catheter-daf!
Rica, Cuba, India, Lebanon,
Macedonia, Mexico, Morocco,
Panama, Peru, Philippines, and
Turkey (INICC Study)
INICC 7 countries: Colombia, CA-UTI PICU Pre-/postintervention Multidimensional CA-UTI per 1,000 5.9 2.7 <0.01 2011 (62)
El Salvador, India, Malaysia, approach catheter-da}'!
Mexico, Philippines, and Turkey
(INICC Study)
CLA-BSI per 1,000 daf! ofCVC; CA-UTI per 1,000 UC-da}'!; VAP per 1,000 MV-da}'!; CL, central line; MV, mechanical ventilator; UC, urinary catheter; HAI, healthcare-associated infection;
CLA-BSI, central line-associated bloodstream infection; VAP, ventilator-associated pneumonia; CA-UTI, catheter-associated urinary tract infection; Ref, reference; ICU, intensive care unit;
PICU, pediatric intensive care unit; NICU, neonatal intensive care unit; RR, relative risk; CI, confidence interval; INICC, International Nosocomial Infection Control Consortium.
t..)
0\
'()
2 70 Section I • General ConsideratiOfiS of Hospital Infectiuns
TABLE 18.28 Intuvcntional Studies Aiming at SSI Raluct.ion llqJortcd by Hospitals from Economics
Country ICUstudied Study design Intervention SSI rate p Year Reference
Thailand Multicenter Pre-/postintervention Monitor SSI after the implementa- 1.8 1.2 2009 (300)
hospitalwide tion of surveillance S}'5tem
Argentina Hospitalwide Pre-/ postintervention Training and the use of a protocol 3.2 1.9 <0.01 2006 (329)
with an automatic stop of anti-
microbial prophylaxis
Saudi Hospitalwide Pre-/postintervention Better enforcement of infection 4.34 0.88 0.049 2009 (330)
Arabia control practices
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I
SECTION
Functiona-l Areas of Concern II
John M. Boyce
The Inanitnate Environn1ent

INTRODUCTION that are touched more frequently by healthcare personnel and
are presumably more likely to contribute to transmission (1).
Although healthcare-a.s.sociated infection (HAl) pathogens are The guideline also included extensive discussions of air and wa-
moat frequently transmitted to patients via the transiently con- ter quality. Recently, Huslage et at. conducted a:n observational
taminated hands of personnel, there has long been a concern study of healthcare workers (HCWs) in order to more clearly
that the inanimate hospital envirownent aho may be a source define high-touch m.rfaces (4). Five surfaces were defined as
of pathogens causing HAls. The inanimate environment in high-touch surfaces: bed rails, the bed surface, supply carts,
healthcare facilities generally refers to environmental surfaces overbed tables, and intravenous pumps. The present chapter
(including floors, walls, medical equipment and instruments, cllicusses noncritical objects that come into contact with intact
furniture, and other parts of the physical infrutructure), air, skin (but not mucous membranes), air, and water.
and water. The tenn •fomite" refers to an inanimate o!riect that
may become contaminated and may play a role in the tranarnilJ.
sion of pathogens. HISTORICAL PERSPECTIVE
The widely accepted Spaulding classification of medical
equipment and patient<are items includes three categories The degree of concern regarding the inanimate environment
based on the potential for the object to transmit infection if as a source of HAls has changed markedly over the years. For
it becomes microbiologically contaminated before (or during) example, in the 1950s and 1960s, routine culturing of respi-
use (1). These categories are •critical," "semicritical," and "non- ratory therapy equipment, purchased sterile products, infant
critical" Critical items, which come in contact with sterile tissue formula prepared in the hospital, linens, kitchen utensils,
or the vascu1ar system, and semicritical items, which come in environmental surfaces, a:nd air samples was performed in
direct contact with mucous membranes or nonintact skin, are many hospitals, and the finding of contamination of ruch items
discwaed in Chapter 20. Noncritical items are thoae that come was thought to be important in the transmission of pathogens
into contact with intact skin, but not mucous membranes. The (5-8). Such routine culturing was performed despite the lack of
noncritical items can be divided into two categories: noncritical stand.arda regarding the level of microbial contamination that
patient<are items and noncritical environmental surfaces (2). would be considered acceptable, and a lack of evidence that
Examples of noncritical patient-care items include blood pres- ru.ch contamination contributed to HAis. Fogging of patient
sure cuffs, bedpans, pulse oximeters, and crutches. Noncritical rooms after patient discharge with quaternary ammonium
environmental surfaces include items such as bed rails, bedaide compounds and other disinfectants was performed in some
tables, some food utensils, patient furniture, and floors (~). hospitals to reduce airborne and surface contamination (9).
The environmental surfaces can be further classified into Although the CDC recommended in the early 1970s that hos-
medical equipment surfaces (e.g., knobs or handles on hemo- pitals stop performing ru.ch routine environmental cultures
dialf3is machines, X-ray machines, instrument carts, and den- and fogging of patient rooms, a:nd place greater emphasis on
tal units) and housekeeping surfaces (e.g., floors, walls, and HAl surveillance and evidence-based control measures, a sub-
tabletops) (1). The 2003 Centers for Disease Control and Pre- stantial number of hospita1s were still performing unnecessary
vention (CDC) environmental guideline introduced the term environmental culturing in the mid-1970s (5,10). Several sub-
"high-touch housekeeping surfaces" (e.g., doorknobs, bed sequent studies appeared to support the concept that the inani-
rails, light switches, wall areas around the toilet in the patient's mate environment contributed little to HAls (11,12). Over the
room, and the edges of privacy curtains) to refer to the objects ensuing years, routine environmental culturing was gradually
277
2 78 Section II • l'Unctional An1as of Concern
eliminated, and relatively little importance was attributed to patient (7,17-19,25,29-31). For example, studies conducted
the role of contaminated environmental surfaces in the trans- in the 1950s and early 1960s documented that a patient with
millsion of HAl pathogens. & a consequence, in the 1980s and a staphylococcal carbuncle contaminated linens, floors, and
early 1990s, much less attention was given to cleaning and dis- nearby medical equipment in the patient's room (7). Rutala
infection of environmental surfaces in healthcare facilities, and et al. documented surface contamination with MRSA in the
relatively few paragraphs were devoted to cleaning and disin- rooms of affected bum patients (32). In a study of patients with
fection of environmental surfaces in national guidelines (6,13). MRSA nasal colonization, 15% of patients had contaminated
A renewed interest in the inanimate environment was their environment within 25 hours of admission, and 25% had
most likely due to multiple factors, including the discovery of contaminated the surfaces within 33 hours of admission (33) .
nosocomial outbreaks of legionellosis and multidrug-resistant Patients with MRSA colonization or infection contaminate from
Mycobacterium tuberculosis, the increasing population of immu- a few percent to 74% of surfaces in their environment, with
nocompromised patients susceptible to airborne pathogens higher levels and frequency of contamination in patients with
such as &pergillus, and the increasing incidence of patho- MRSA in their urine or in a wound, or with heavy gastrointesti-
gens that were demonstrated to survive well on environmental nal colonization accompanied by diarrhea (17,31,34). Patients
surfaces, including methicillin-resistant Staphylococcus aum.tS colonized with VRE contaminate from 7% to 71% of surfaces
(MRSA), vancomycin-resistant enterococci (VRE), and Clos- in their rooms, with the greatest levels of contamination oc-
tridium difftcile (14-20). & a result, the CDC published a greatly curring in those with colonization at several body sites or with
expanded guideline on environmental control in healthcare diarrhea (18,19,29,30). Among Gram-negative pathogens, Aci-
facilities in 2003 (1). Since the publication of that guideline, a netobacter spp. is particularly likely to survive on environmental
growing body of evidence has provided additional insights into surfaces, even if the surfaces are dry (35-37) . Environmental
the contribution of the inanimate environment to pathogen contamination is frequent even when the patient has a remote
transmission. history of Acinetohacter spp. colonization or infection (37). The
frequency of C. diffic'ik environmental contamination varies
from 29% among asymptomatic carriers to 49% to 100% in pa-
ROLE OF ENVIRONMENTAL SURFACES tients with symptomatic C. dif.ficiltl-associated diarrhea (CDAD)
IN THE TRANSMISSION OF PATHOGENS (20,30,38,39). Patients with CDAD continue to have skin colo-
nization and contaminate their environment even after their
For organisms in the inanimate environment to cause HAls, a diarrhea has abated (25). Patients with acute norovirus or astro-
number of factors need to be present: virus infection shed large numbers of viral particles into their
(a) An adequate number of pathogenic organisms must environment (40,41).
be present in the environment, (b) microorganisms must be Microorganisms must be vh-ulent and capable of surviving
virulent and capable of surviving in the environment, (c) a in the environment. Environmental surfaces in healthcare fa-
susceptible host must be exposed, (d) an appropriate mode of cilities often have some level of contamination by bacteria that
transmission or transfer of the organism in sufficient number have a low level of virulence or are nonpathogenic. A few ex-
from source to host, and (e) there must be an appropriate por- amples include Bacillus sp., diphtheroids, and some species of
tal of entry into the host (1,21-23). The goal of this chapter is coagulase-negative Staphylococcus. In most instances, a finding
to review the evidence supporting the role of environmental of such bacteria on environmental surfaces is of little clinical
surfaces, contaminated devices that come into contact with in- significance. However, a variety of pathogens can survive for
tact skin, water, and air as sources of transmission of pathogens days, weeks, or even months on dry surfaces ( 42-44). Gram-
to patients. The transmillsion related to contaminated dialysis positive organisms including Enterococcus, S. aureus, StreptOCIX-
equipment, medications, and devices that come into contact cus pyogenes, and C. difftcile can survive for weeks to months on
with sterile tissues or mucosal surfaces will be covered in other inanimate surfaces (42,43) . C. difftcilespores can survive up to
chapters. 5 months on dry surfaces (45). Gram-negative bacilli are gen-
Frequency of environmental surface contamination by erally felt to survive less well in dry environments than Gram-
pathogeDI!I. The frequency of contamination of the environ- positive organisms (43). However, Acinetobacter spp. appears to
ment depends on a variety of factors, including the degree survive for longer time periods than other Gram-negative ba-
of shedding of the organism from the source, the ability of cilli, perhaps due to the unique characteristics that protect it
the organism to survive in the environment, the ability to from desiccation (46,47) .
culture the organism, the sampling and processing meth- The survival of an organism in the environment does not
ods used to recover the organism, the susceptibility of the necessarily mean that it will remain virulent and cause disease
organism to standard detergents and disinfectants, the ease in humans. For example, Perry et al. found that S. pyogenes sub-
with which contaminated items can be disinfected, the ad- jected to desiccation were unlikely to cause pharyngitis ( 48).
equacy of routine housekeeping practices, and whether or Studies of S. aum.tS and C. difftcile provide the most compelling
not an outbreak is occurring at the time of sampling (23). evidence that pathogens recovered from inanimate surfaces
Many studies have documented that patients are the major can cause disease. Colbeck found that sutures inoculated with
source of environmental contamination in patient-care areas S. aum.tS and allowed to dry for 10 to 14 days were still capable
(17-20,24,25). HCWs also can contaminate the environment, of causing abscesses (49). C. dijjicile spores routinely cause fa-
but to a lesser degree than patients (26-28). The frequency tal enterocolitis in hamsters, and it is generally accepted that
and number of organisms shed by patients into the envi- CDAD in humans is related to ingestion of spores, since the veg-
ronment depends in part on the type and number of body etative form of C. difficile dies rapidly on dry surfaces (50,51) .
sites colonized or infected with the pathogen, and probably A SU!ICeptible host must be exposed. Recent efforts to re-
to the level of activity of the patient and those caring for the duce the length of hospital stays and to deliver more healthcare
Chapter 19 • The Inanimate Environment 2 79
in outpatient and home settings has resulted in a greater sever- that HCWs were nearly as likely to have contaminated their
ity of illness among hospitalized patients (52). Advances in can- hands or gloves after touching the environment in a room oc-
cer chemotherapy and organ transplantation, and the type and cupied by a VRE-colonized patient as after touching the colo-
number of invasive diagnostic and therapeutic procedures that nized patient and the patient's environment (74).
patients undergo have resulted in an increasing number of pa- There must be an appropriate portal entry into the host. In-
tients with heightened susceptibility to HAis. The widespread vasive procedures-such as placement of central or peripheral
use of broad-spectrum antimicrobial agents in healthcare facili- intravenous catheters, indwelling bladder catheters, and endo-
ties puts patients at increased risk of developing infections due tracheal tubes-surgical incisions that disrupt the integrity of
to multidrug-resistant organisms (MDROs), including those the skin, and cutaneous ulcers can all serve as portals of entry
that survive in the inanimate environment (53-56). of pathogens into a susceptible host.
An appropriate mode of transmission or transfer of the In addition to the factors cited above, there are several
organism in sufficient number from source to host. Microor- other lines of evidence that support the role of environment
ganisms may be transmitted directly from the environment to in the transmission of HAI pathogens. One indirect type of
patients, or, more commonly, are transmitted indirectly from evidence that has emerged in recent years relates to the risk of
the environment to patients. For example, Bonten et al. found acquisition of pathogens that is attributed to poor cleaning/
that a few patients acquired VRE after the same strain of VRE disinfection of patient rooms following their discharge from
was found on their bedside rails, suggesting direct transmis- the hospital (terminal cleaning).
sion from the environment to the patients (19). Hardy et al. Prior room occupancy as a risk factor for pathogen acqui-
proposed that patients acquired MRSA directly from contami- sition. One case-control study and five cohort studies have
nated environmental surfaces, but did not entirely exclude found that admission to a room previously occupied by a
transmission by HCWs (57). Weist et al. provided evidence that patient with a resistant pathogen (e.g., VRE, MRSA, C. dif-
an outbreak of methicillin-susceptible S. aureus infection was ftcile) is an independent risk factor for acquisition of these
associated with a contaminated ultrasound gel to which affected bacteria bysubsequent room occupants (77-83) (Table 19.1).
neonates were exposed (58). One outbreak provided substan- For example, a case-control study conducted in a medical in-
tial evidence that MRSA was transmitted from contaminated tensive care unit (MICU) used multivariate analysis to demon-
ultrasonic nebulizers to patients via airborne or aerosol trans- strate that patients who acquired VRE were significantly more
mission (59). Other investigations have suggested that MRSA likely to have been admitted to a room with surfaces that
was transmitted by the airborne route from contaminated ven- remained contaminated even after terminal cleaning (77).
tilation grills to patients (60,61). Contaminated thermometers Huang et al. estimated that such exposures accounted
that came into direct contact with patients have been impli- for about 7% of new VRE episodes and 5% of MRSA epi-
cated as the source of VRE and C. difftcile infection (62-64). sodes (78). Subsequently, Drees et al. found that a VRE-
Direct or indirect transmission of Acinetobacter spp. to patients colonized prior room occupant, any VRE-colonized room
has been reported to occur from a variety of environmental occupant within the previous 2 weeks, and previous posi-
sources, including mattresses, pillows, curtains, faucet aera- tive room-culture results remained as the independent pre-
tors, water baths used for heating peritoneal dialysis solutions, dictors of VRE acquisition (79). More recently, Passaretti
bedside humidifiers, pressure transducers, respiratory therapy et al. reported that the risk of acquiring an MDRO from
and hydrotherapy equipment, devices used for pulsatile wound prior room occupants was reduced by effectively decontami-
therapy, and other environmental surfaces (35,36,65-71). nating the rooms using standard cleaning supplemented by
There is increasing evidence that HCWs can contaminate hydrogen peroxide decontamination (83). Because multiple
their hands or gloves by touching contaminated environmen- studies have documented suboptimal disinfection of rooms
tal surfaces, even when they have no direct contact with the following discharge of patients, it is likely that direct trans-
affected patients (17,20,23,72-74). And the greater the fre- mission from the environmental surfaces to newly admitted
quency of environmental contamination, the more likely it is patients may occur.
that HCWs will contaminate their hands or gloves (20,75). The Alternatively, residual room contamination could result in
above studies suggest that HCWs whose hands have become the contamination of the hands or gloves of HCWs caring for
transiently contaminated by touching inanimate surfaces may newly admitted patients. In contrast to the six studies men-
represent a common mode of transmission of organisms from tioned above, one small study failed to find an association be-
the environment to susceptible patients. One study found that tween prior room occupancy by an MRSA-positive patient and
VRE were transferred from contaminated sites in the environ- acquisition by subsequent patients, perhaps due to the small
ment or on patients' intact skin to clean sites via HCWs' hands study size (84).
or gloves in 10.6% of opportunities (76). Touching a contami- Decontamination or removal of the implicated source re-
nated item (e.g., blood pressure cuff) was as likely to transmit sults in the elimination of infection transmission. A number
VRE to a sterile surface as touching a colonized patient. In a of studies have reported that decontamination or removal of
study by Hayden et al., >50% of HCWs touched both the pa- an implicated source has resulted in the elimination of trans-
tient and the patient's environment; no HCW touched only the mission of pathogens. Examples include decontamination or
patient (74). Of the 103 HCWs whose hand samples were nega- removal of a contaminated operating room roll board, pillows
tive for VRE when they entered the room, 52% contaminated or mattresses, cloths, a topical cream preparation, skin lotion,
their hands or gloves after touching the environment, and 70% ultrasound gels, and soap (65,66,69,85-93) .
contaminated their hands or gloves after touching the patient Improved cleaning and disinfection practices is associated
and the environment (P = 0.001). Thirty-seven percent of with reduced acquisition or infection. A number of studies have
HCWs who did not wear gloves contaminated their hands, and shown that disinfection of environmental surfaces potentially
5% of HCWs who wore gloves did so. The authors concluded contaminated with C. difftcik or VRE can lead to decreases in
280 Section II • l'Unctional An1as of Concern
TABLE 19.1 Studies Showing Increased Risk of Infection or Colonization

from Prior Room Occupant
Author Study Design and Population Study Duration Risk Factor Adjusted Ratio
Martinez Retrospective case-control study; lW cases 9months Room with penisting VRE contamination OR: 81.7
and 60 controls; multivariate analysis
Huang Retrospective cohon study; 10,151 pts at 20months Prior room occupant with MRSA OR: 1.4
risk for MRSA; Prior room occupant with VRE OR: 1.4
10,349 pts at risk for VRE;
multivariate anal}'lis
Drees Prospective cohort study; 14 months Prior room occupant with VRE HR:3.8
638 pts at risk for VRE; Previous positive room culture HR:4.3
Cox proportional hazard modeb
Shaughnessy Retrospective cohon study; 20months Prior room occupant with CDI HR: 2.3
1,770 pts at risk ofCDI;
Cox proportional hazard model
Nseir Prospective cohort study; 12 months Prior room occupant with Pseudomonas OR:2.3
511 pts at risk; multivariate analysis Prior room occupant with Acinetobacter OR:4.2
Passaretti Prospective cohort study; 30 months Admitted to MDRO room decontaminated IRR: 0.36
6,350 room occupations; with HPV
Poisson general linear modeb Admitted to VRE room decontaminated IRR: 0.20
with HPV
VRE, vancomycin-resistant Enterococcus; OR, odds ratio; MRSA, methicillin-resistant StaphylococctiS aum~.~; pts, patients; HR, hazard ratio;
CDI, C. dWlcileinfection; MDRO, multidrug-resistantorganism; IRR, incidence rate ratio.
acquisition orinfectioncausedbythese organisms (82,83,94-1 00). MDRO acquisition even when the prior room occupant was not
For example, improved disinfection of surfaces using diluted known to be MDRO-colonized or infected. This finding suggests
bleach solutions or bleach wipes has resulted in reduced that one or more of the prior room occupants may have been
C. difficile transmission, particularly on high-incidence wards unidentified MDRO carriers.
(94,95,97,100). In one of the best studies of its kind, Hayden Strength of evidence supporting the role of environmen-
et al. provided convincing evidence that reducing VRE environ- tal surfaces in transmission. Most of the studies supporting
mental contamination resulted in reduced acquisition of the the role of environment in the transmission of HAl patho-
organism by susceptible patients (98). In an intervention study gens have been conducted in acute care facilities, with fewer
by Perugini et al., education ofHCWs and reduction in the pro- investigations conducted in hemodialysis units or long-term
portion of environmental and equipment that were contami- care facilities. Supporting studies fall into several categories,
nated with VRE were associated with a significant decrease in with some studies providing more compelling evidence than
VRE infection (99). others.
In a before-after intervention study, Boyce et al. found that There are few randomized trials dealing with the role of
decontamination of hospital rooms using hydrogen peroxide va- environmental surfaces in the transmission of HAl pathogens.
por (HPV) was associated with a significant reduction in the rate Recently, a randomized controlled trial compared antimicro-
of C. di.fficile HAis (96). While the study showed that HPV was ef- bial privacy curtains with standard curtains, and found that the
fective in eradicating C. diJftcifefrom a limited number of patient antimicrobial curtains increased the time to first contamina-
rooms, the authors did not determine if the reduction in CDAD tion (101). Another recent randomized, prospective unblinded
was accompanied by a hospitalwide reduction in C. difjicife envi- study of the impact of daily cleaning of high-touch surfaces in
ronmental contamination. A study by Datta et al. demonstrated patient rooms demonstrated reduced contamination ofHCWs'
that increased attention to room cleaning significantly reduced hands by C. difjicifeand MRSA (102).
the risk of patients acquiring MRSA when they were admitted to Another category of study that provides reasonably com-
a room previously occupied by an MRSA-positive patient, and pelling evidence implicating the environment includes retro-
also reduced to a lesser extent the risk of patients acquiring VRE spective case-control studies showing an association between
from a previous room occupant (82). Recently, the study by Pas- exposure to the environment and acquisition (colonization
saretti et al. cited above found that patients admitted to rooms or infection). These studies fall into two groups with differ-
that were decontaminated using HPV were 64% less likely to ac- ing strengths of evidence. The best evidence is provided by
quire any MDRO (incidence rate ratio [IRR] = 0.36, p < .001) case-control studies that found an association between expo-
and 80% less likely to acquire VRE (IRR = 0.20, p < .001) after sure of affected patients and a contaminated environmental
atljusting for potential confounding variables, such as hospital source, and demonstrated that pathogens recovered from pa-
unit, age, mortality risk score, HIV status, end-stage renal dis- tients and the implicated source were the same strain (often by
ease status, compliance with MDRO surveillance procedures, molecular typing) . Studies in this category provided convincing
and calendar time (83). The risk of acquiring MRSA, multidrug- evidence that patients acquired pathogens from pulsatile
resistant Gram-negative rods (MDR-GNR), or C. difficile were lavage equipment, operating room roll boards, bath toys, ice
each reduced as well, but not significantly. Another interest- machines, hydrotherapy equipment, and patient showers
ing finding was that HPV decontamination reduced the risk of (69,85,103-109).
Chapter 19 • The Inanimate Environment 281
Slightly less compelling evidence is provided by case-<:ontrol contaminated ice machines, patient showers, sinks, and a
studies showing an association between exposure of affected physiotherapy pool responsible for outbreaks or pseudo-
patients and a contaminated environmental source, and dem- outbreaks has stopped transmission of pathogens (105,108,109,
onstrated that pathogens recovered from patients and the envi- 127,130,133,135,137).
ronmental source were the same species, but did not perform The most common organism responsible for the waterborne
strain typing of isolates from patients and the assumed source outbreaks in healthcare facilities is Pseudomonas aeruginosa, fol-
(77,79,110,111). lowed by other Gram-negative rods, such as ugionella, Acinet()-
Cohort studies also have been used to link probable or bacter, Stenotrophomonas, and Mycobacteria spp. While Pseudomonas
definite environmental contamination to increased risk of in- spp. has been recovered from sinks in many healthcare facili-
fection. For example, several cohort studies have found that ties, most investigations did not provide convincing evidence
prior room occupancy by a patient with a pathogen (e.g., that the sink was the source from which patients acquired the
VRE, MRSA, C. difftcile) increased the risk of pathogen ac- organism. However, Doring et al. found that several strains of
quisition among patients subsequently admitted to the room Pseudomonas spp. were isolated from sinks before they were
(78,80-82). Cohort studies have also implicated hand cream found in patients, suggesting that the transmission occurred via
used by HCWs (112). the hands of HCWs (129). High concentrations of Pseudomonas
Another category of evidence is composed of a group of in- spp. in sinks were shown to contaminate the hands of HCWs
vestigations demonstrating exposure of affected patients to a and air above the sink. In a later study, Hota et al. used a fluo-
contaminated environmental source, and reduction or elimina- rescent marker to demonstrate that when a sink was used for
tion of transmission by removal or corrections of the implicated handwashing, sink-drain contents splashed at least 1 m from
source, but without a case-<:ontrol study implicating the proposed the sink (133). The sink was felt to be the source of an out-
source. Early studies implicating mattresses, linens, and pillows break of Pseudomonas spp. that caused infections by the same
did not confirm the genetic relatedness of pathogens recovered strain among ICU patients. Renovation of the sinks to prevent
from these sources and from affected patients (65,66,86-88). splashing onto surrounding areas terminated the outbreak.
Subsequent investigations that did not include a case-<:ontrol Potable water and cooling towers have long been implicated
study, but did demonstrate exposure of affected patients to a con- as sources of nosocomial legionellosis (14,15,138,139). Case-
taminated environmental source, documented that isolates from control studies that included strain typing have confirmed
affected patients and the implicated source were the same strain cooling towers and potable water as sources of Legionella spp.
by using molecular typing methods. Environmental sources im- infection (140-142). Thansmission may occur from ingestion
plicated by these studies include prepackaged washcloths, urol- or aspiration of potable water or by aerosol transmission
ogy forceps, a wound cart, oxygen saturation monitors, antiseptic from cooling towers or from showerheads (15,138,140-142).
soaps, and ultrasound gels (69,89,90,92,93,113-120). Although Legionella spp. is not uncommonly recovered from
hospital water-distribution systems, high-level coloniza-
tion of the water system (30% or more of distal outlets yield
ROLE OF WATER IN TRANSMISSION OF HAIS
Legionella) has been shown to be associated with episodes of
Hospital water-distribution systems have long been recognized nosocomiallegionellosis ( 143).
as a potential source of HAis, and have been implicated in A recent study raised concerns regarding electronic faucets
a number of outbreaks (121). The best evidence of the role in healthcare facilities as a source of Legionella spp. (144). The
of water in the transmission of HAl pathogens is provided by investigators found that electronic faucets installed in several
case-<:ontrol studies that found an association between expo- areas of the hospital were more commonly contaminated with
sure of affected patients and a contaminated water source, and Legionella spp. and other bacteria. When compared to tradi-
demonstrated that pathogens recovered from patients and the tional manual faucets, the electronic faucets continued to
implicated source were the same strain (often by molecular yield higher numbers of ugionella spp. and other bacteria af-
typing). Water sources implicated in such outbreaks have inter chlorine dioxide treatment of the water system. While no
cluded bath toys, hydrotherapy equipment, showers, and ice Legionella spp. infections were associated with the electronic
machines (105-109). Although Wisplinghoff et al. used a case- faucets, this study supports previous reports that electronic
control study to implicate hydrotherapy equipment as a source faucets become more heavily contaminated and are more diffi-
of infection, environmental cultures were not included as part cult to disinfect than traditional faucets (145). Concerns have
of the investigation (122). Cohort studies also have implicated been voiced regarding the use of faucet aerators, which may
water used to rinse instruments (123). A number of other in- be contaminated with the same strain of Gram-negative bacte-
vestigators performed case-<:ontrol or cohort studies that did ria responsible for colonization or infection of patients ( 132).
not specifically implicate a water source, but used strain typing Further studies are needed to determine the importance of
to confirm the relatedness of isolates from patients and water electronic faucets and faucet aerators as sources of legionel-
sources, such as sinks, tap water, showers, or physiotherapy pool losis and other HAis.
water (124-128). Decorative wall water fountains have been recently identi-
Investigations that did not include a case-<:ontrol study, but fied as another potential source of nosocomial legionellosis.
did demonstrate exposure of affected patients to contaminated Palamore et al. described a cluster of Legionella spp. infections
water sources, documented that isolates from affected patients that were attributed to a hospital decorative wall fountain con-
and implicated sinks, tap water, showers, hydrotherapy equip- taminated with the organism (136). Legionellaspp. isolates from
ment, or a decorative water fountain were the same strain by affected patients and the fountain were identical by pulsed-
using strain typing methods (35,129-136). field gel electrophoresis. Cultures from a fountain also yielded
Removal of a contaminated hydrotherapy tub and heavy growth of other bacteria, including Mycobacteria and
other patient-bathing equipment and decontamination of Pseudomonas sp., and air samples collected near the fountain
yielded heavy growth of the number of bacteria. The fountains most likely represented pathogen transmission via large-droplet
served as a source of infection despite standard maintenance aerosols rather than by true airborne transmission.
and sanitizing measures. In a more recent outbreak attributed Beck-Sague et al. performed a case-control study of a noso-
to a decorative wall fountain in a hospital, heavy growth of comial outbreak of multidrug-resistant TB and found that one
Legionella pneumophila serogroup 1 was recovered from cultures of the risk factors for acquisition of M. tuberculosis was expo-
of a foam material found above the fountain trough, and six of sure to a pentamidine treatment room that was under positive
the eight affected patients had documented exposure to the pressure when patients with active TB were being treated (16) .
wall fountain near the main hospital entrance ( 146) . Legionella Cohort studies also have implicated contaminated air (157).
spp. was still recovered from the components of the wall foun- Several investigations that did not include case-control studies
tain after routine cleaning and maintenance. The study sug- provided evidence of transmission via aerosols from ultrasonic
gests that decorative wall fountains should not be placed within nebulizers or airborne transmission from contaminated ventila-
any enclosed spaces in healthcare environments (especially in tion grills (59,61,158).
areas frequented by high-risk patients), and that regular cultur- Both patients and HCWs can shed up to 107 skin squames per
ing of wall fountains is performed to establish the effectiveness day into their environment, and those colonized with S. aUflm5
of sanitation measures ( 1,147) . and group A Streptococcus shed these organisms into the air
Prevention of nosocomiallegionellosis requires minimizing and onto environmental surfaces in their vicinity (26-28,159) .
the number of distal outlets in a facility that yield Legionella A number of investigations did not include a case-control study,
spp. (143). Effective strategies include the use of copper-silver but did demonstrate that patients developed infections after
ionization disinfection and point-of-use filters (148). Other having no direct contact with a colonized or infected HCW car-
strategies that have been used include hyperchlorination, rying the same strain. Early studies showed that patients under-
chlorine dioxide, and monochloramine. going surgery developed wound infections caused by the same
phage type of S. auflm5 that was carried by a disseminating carrier
who remained in the periphery of the operating room (160).
AIR AS A MEANS OF TRANSMISSION OF HAIS
Sherertz et al. demonstrated that a physician who developed a
Air has long been considered a potential means of transmis- viral respiratory infection when colonized in the anterior nares
sion of communicable diseases. Some of the earliest studies with S. auflm5 shed staphylococci into the air for a distance of
to provide compelling evidence of airborne transmission of at least 6 feet (26). Volumetric air sampling revealed that par-
pathogens involved exposing guinea pigs to air from a ward ticles <5 7JIIl could be recovered from the air at least 4 feet from
housing patients with active tuberculosis (TB) (149). A more the physician. A number of patients exposed to the physician
recent study involving the use of guinea pigs housed above a developed infections, suggesting that S. aureus may have been
ventilated ward with active TB patients also provided convinc- spread by the airborne route as well as by large-droplet aerosols.
ing evidence of airborne transmission (150). Increased levels of S. aureus in the air in patient rooms during
In addition to M. tuberculosis, other organisms for which activities such as bed-making have been suggested as a possible
there are numerous examples of healthcare-associated air- source of nasal colonization ofHCWs (7).
borne transmission include varicella zoster virus (VlV), influ- There is also compelling evidence that S. pyogenes can spread
enza virus, measles, smallpox, S. auflm5, S. pyogenes, and fungi from colonized or infected HCWs to patients via the airborne
such as Aspergillus (28,151-153). A few examples will be listed route. K.olmos et al. reviewed 15 outbreaks involving 136 surgi-
below. cal patients who developed streptococcal wound infections (28).
Josephson et al. investigated an outbreak of nosocomial HCWs who were colonized in the throat, anus, vagina, or skin
VZN that involved several nurses who never had direct contact but who had no direct contact with affected patients were im-
with the index patient who had localized zoster (152). Airflow plicated as the sources of infection. Some of these HCWs were
studies revealed that air from the patient's room reached the in the operating room during the surgery. However, others
number oflocations in the corridor and nursing station outside were not even present in the operating room during a surgi-
the affected patient's room, supporting the role of airborne cal procedure, and either left the operating room before the
transmission in the outbreak. Influenza virus is most commonly patient arrived or were in an adjacent room (28,161).
transmitted by large-droplet aerosols and to a lesser extent by Nearly all outbreaks of healthcare-associated aspergillosis
hand contact (154). However, recent studies have provided evi- have been attributed to airborne transmission (153) . Anum-
dence supporting possible airborne transmission of influenza ber of studies used molecular typing to confirm the genetic
over relatively short distances (155,156). However, there is still relatedness of AspergiUus spp. isolates from patients and air
considerable controversy regarding the role of airborne trans- samples or ventilation equipment to which affected patients
mission of influenza. were exposed (153,162,163). Outbreaks are most commonly
A few case-control studies found an association between expo- caused by Aspergillus Jumigatus or AspergiUus jlavus, and are
sure of affected patients and contaminated aerosols from respi- usually related to construction, demolition, or renovation
ratory equipment, and demonstrated that pathogens recovered activities, which can either be inside the hospital or outside
from patients and the implicated source were the same strain the hospital in nearby areas. Even small numbers of spores in
(often by molecular typing) (103,104). A few other case-control the air to whom immunocompromised hosts are exposed can
studies showed an association between exposure of affected result in episodes of aspergillosis, and there is no spore con-
patients and aerosols from respiratory therapy equipment concentration in the air below which one can be confident that no
taminated with the pathogen, and demonstrated that pathogens transmission will occur (153). Air in the vicinity of patients with
recovered from patients and the environmental source were the CDAD also has been shown to be contaminated with spores,
same species, but did not perform strain typing of isolates from although the role of such airborne spores in the transmission
patients and the assumed source (47,110). The above studies of C. d@cileisnotclear (164,165) .
Decontamination or removal of implicated respiratory FLOWERS

equipment such as ventilators, Ambu bags, or a humidifier also
Fresh and dried flowers are not uncommonly contaminated
has terminated outbreaks (104,111,166).
with a variety of bacteria, and it is well-established that flower-
vase water frequently becomes contaminated with Gram-
negative bacteria including Pseudomonas spp. Flowers and
OTHERENVIRONMrnNTALSOURCES ornamental plants may harbor Aspergillus spp. spores, which
OF PATHOGENS can be released into the air (1). In one study that used mo-
lecular typing techniques, identical types of Aspergillus spp.
CARPETS AND CLOTH FURNISHINGS were recovered from potted plants, environmental, and
Carpets routinely become contaminated with bacteria and clinical specimens from infected patients with hematological
malignancies ( 172).
fungi. Vacuuming and cleaning carpets can temporarily re-
duce the level of contamination, but bacterial populations CDC guidelines recommend that fresh or dried flowers and
potted plants should not be allowed in patient-care areas for
s~o~ retu~ to precleaning levels (1). Because there is very
lrm1ted eVIdence demonstrating that carpets influence HAl immunosuppressed patients (1). Flowers and potted plants
~eed not be restricted from areas for immunocompetent pa-
rates, the CDC Guidelines for Environmental and Infection
Uents. The staff who are not directly involved with patient care
Control in Healthcare Facilities do not include recommenda-
should be responsible for the care and maintenance of flowers
tions against the use of carpeting in patient-care areas where
and potted plants. If plant or flower care by patient-care staff is
immunocompetent patients are located (1). One outbreak of
unavoidable, the staff should be instructed to wear gloves when
Aspergillus spp. in a stem cell transplant unit was attributed
handling the plants and flowers and to perform hand hygiene
to carpet contamination and a particular method of carpet
cleaning (1). The CDC guidelines do recommend avoiding after removal (1).
the use of carpeting in areas where spills are likely to occur
(e.g., laboratories, around sinks) and where patients may be
at a greater risk of infection from airborne environmental
ENVIRONMENTAL SAMPLING
pathogens (e.g., stem cell transplant units, burn units, ICUs,
Routine microbiological sampling of environmental surfaces
air, or water can be expensive and time-consuming, and is no~
and operating rooms).
Feather pillows were considered to be the source of Acineto-
recommended except in two situations: biological monitoring
bacter spp. contamination in one hospital, and replacement
of ste~ization processes by using bacterial spores, and monthly
of feather pillows with synthetic pillows and correction of the
cultunng of water used in hemodialysis (1). Current guidelines
laundry procedure resulted in a significant reduction in their
mention directed microbiological sampling of the environment
frequency of Acinetobacter spp. isolates (66). One outbreak of
Salmonella spp. gastroenteritis among laundry workers in a nurs-
in four other settings: (a) to support investigation of an outbreak
of disease when environmental reservoirs or fomites are epidemi-
ing home was attributed to handling contaminated linens ( 167).
Because patient linens routinely become heavily contaminated ologically implicated, (b) forresearch purposes, (c) to monitor a
potentially hazardous environmental condition and to establish
with potential pathogens, it is important to adhere to guidelines
successful abatement ofthe hazard, and {e) to evaluate the effects
for laundering linens and other cloth furnishings ( 1) .
of a change in infection control practices or to ensure that equip-
A number of studies have documented that privacy cur-
mentor systems are performing according to expectations (1).
tains in patient rooms often become contaminated with po-
Many examples of using environmental cultures to support out-
tential pathogens such as Acinetobacter spp., MRSA, or VRE
break investigations are cited in the section on the evidence sup-
(67,168-170). Few data are available regarding the role that
porting the role of environmental surfaces in transmission of
contaminated privacy curtains play in transmission of HAl
pathogens (see above). Environmental cultures have been used
pathogens. However, recent studies have shown that they
may represent a source of HCW hand contamination (168). for research purposes in a variety of settings, including establish-
ing the levels of environmental contamination in various clinical
Whether antimicrobial-impregnated curtains reduce the trans-
mission of pathogens has not been established (101). The siruations, studying the role of environmental contamination as
a source for HCW hand contamination, evaluation of new liq-
above findings suggest that further studies are indicated to
uid disinfectants and "no-touch" area decontamination systems,
establish the importance of curtains in pathogen transmission
evaluating the methods for assessing the adequacy of cleaning
and the frequency with which they should be cleaned.
and disinfection practices, and evaluating the impact of changes
it_I housekeeping practices, to name a few. Examples of using en-
SOAP vrronmental culrures to establish abatement of potentially haz-
ardous environmental conditions include cultures of hospital
Several HAl outbreaks have been attributed to contaminated
water-distribution systems contaminated by Legionella spp. and
liquid soap. Two reported outbreaks of Serratia spp. infection
were attributed to contaminated unmedicated soap (92,171). sources of healthcare-associated aspergillosis.
Two other outbreaks were apparently caused by chloroxylenol-
based and triclosan-containing soaps (117,119). Antiseptic METHODS FOR MICROBIOLOGICAL SAMPLING
solutions containing low concentrations of chlorhexidine that OF ENVIRONMENTAL SURFACES
were used to cleanse the skin and vascular catheter sites also
have been implicated as the cause of infections caused by Bur- Many different methods have been used for sampling inani-
kholderiaspp. (93,118). Topping-off of liquid soap dispensers is mate environmental surfaces, air, and water in healthcare
to be avoided. settings, and a complete description of potential methods is
beyond the scope of this discussion. Reviews of these meth- research regarding cleaning and disinfection practices, it is
ods have been published elsewhere (1,173-175). However, a preferable to sample the same surfaces immediately before and
brief description of the more common methods is provided after cleaning has been performed. Failure to take into consid-
below. eration the level of contamination of surfaces before cleaning
The sampling of environmental surfaces has most frequently is performed may lead to an overestimation of the efficacy of
been performed using either swab cultures, agar contact plates, cleaning and disinfection practices (188,197). When assessing
or dipslides. The swabs used for sampling the surfaces should cleaning practices, it is desirable to periodically change the sur-
be moistened in order to improve the recovery of organisms faces that are monitored so that housekeepers do not change
from dry surfaces (176,177). The types of swabs used include their behavior and clean only surfaces that are known to be
those made of cotton, rayon, flocked nylon, or foam-headed monitored.
(174,175). Recent studies have shown that flocked nylon swabs Liquids can be sampled by immersing swabs into the speci-
may increase the yield of bacteria from the surface by up to men to be cultured and then using the swab to inoculate solid
60% (178). Swab specimens can be directly inoculated onto agar. An alternative is to use a dipslide to sample the liquid.
nutrient or specialized selective agar (direct plating) alone, or When large volumes of liquid need to be sampled, it is prefera-
direct plating followed by inoculation of broth cultures that are ble to filter the liquid through a membrane filter (e.g., 0.22 7JIIl
incubated and subsequently plated onto solid agar after a pe- Millipore filter) and then place the filter directly onto an agar
riod of inoculation (broth enrichment) (17,25,179-182). The plate to be incubated.
use of broth enrichment cultures often increases the percent The important problems that affect the interpretation of en-
of surfaces that will yield growth, but provides only qualitative vironmental cultures include the fact that there are no standard-
results. In contrast, direct plating provides semiquantitative re- ized methods for obtaining and processing cultures of surfaces,
sults. Swabs have the advantage of being useful when culturing and that the ideal method to establish the number of bacteria
hard-to-reach objects or items with irregular or curved surfaces, on hospital surfaces is yet to be developed (176,178,198). This
and may detect Gram-negative organisms on surfaces more makes the comparison of the results obtained in various stud-
readily than contact plates (183). ies and in different institutions problematic. Further work is
Recently, specialized cellulose sponges have been developed needed to determine if there are one or more practical, stan-
and used to sample environmental surfaces in healthcare set- dardized methods for culturing environmental surfaces during
tings (39,96,184). After the surfaces have been sampled, the research studies and assessment of routine cleaning practices
sponges are placed in a Stomacher containing neutralizers, in healthcare facilities.
and homogenized (39). The effiuent is then concentrated by
centrifugation and used to inoculate solid agar plates that are
Meth6tls for S.mpling Air
incubated and examined for growth. The advantage of using
sponges instead of swabs to sample the surfaces is that a much Sampling indoor air in healthcare facilities is generally per-
larger area can be sampled easily, and as a result, larger num- formed for research purposes or as part of epidemiologic
bers of colony-forming units (CFUs) are recovered. The main investigations. When contemplating sampling of air for epide-
disadvantages of using sponges are the specialized equipment miologic purposes, it is important to first determine if the re-
needed and technician time required to process the sponge sources and expertise to perform air sampling are available in
cultures. Gauze pads also have been used to sample environ- the institution, or whether it is more appropriate to obtain the
mental surfaces (25). services of an environmental microbiologist with experience in
Agar contact plates (often referred to as RODAC [replicate air sampling (1). The CDC Guidelines for Environmental and
organism direct agar contact] plates) and dipslides provide Infection Control in Healthcare Facilities contains a more in-
quantitative results since the number of aero hie colonies recov- depth discussion of the issues that need to be considered and
ered from a defined surface area allow results to be expressed as methods for air sampling. Only the most common methods
a number ofCFUs/cm2 (185--191). Dipslides are small dispos- used in healthcare facilities will be mentioned briefly below.
able plastic paddles with agar covering each side of the paddle. The most common methods used for sampling air in health-
They can be used for sampling both surfaces as well as liquids. care settings include impingement of air in liquids, impaction
Contact plates have been reported to detect Gram-positive or- on solid agar surfaces, and sedimentation methods (use of settle
ganisms on surfaces more effectively than using standard swab plates). The method used will depend in part on the resources
methods (183). Standard aerobic colony counts are obtained available in the institution and the type of microorganism (bac-
by using nonselective media (preferably containing neutraliz- teria, fungal spores, or viruses) of interest. Special equipment
ers if residual disinfectant is likely to be present on surfaces). are needed for impingement in liquids, as air is drawn into a
Dey-Engley (D/E) neutralizing agar plates are an example of small jet and directed against a liquid surface. Impaction on
contact plates that can be used to inactivate disinfectants that solid surfaces involves drawing air into a sampler in which the
may be present on the surfaces being sampled (186,187,192). particles are deposited onto an agar surface. Depending on
Selective agars can be used to identify pathogens such as Gram- the equipment used, it is possible to obtain data on the size
negative bacilli, MRSA, VRE, or C. difficile (175,193-196). of the particles suspended in the air. This is important if air
Other factors that influence the results of culturing environ- sampling is being conducted as part of an epidemiologic inves-
mental surfaces include the time of day of sampling, the sites tigation of respiratory disease, since particles <5 7JIIl in diam-
included, and the frequency of sampling ( 175) . If sampling eter are the most likely to reach the lungs. A number of liquid
is performed for the purpose of monitoring the adequacy of impinger and solid impactor samplers can provide information
housekeeping procedures, it is important to know if environ- on particle size and also allow the number of organisms or par-
mental cultures have been obtained before or after daily or ter- ticles present to be expressed as the number per unit volume
minal cleaning of rooms by housekeepers. When conducting of air (CFU/m~).
The use of settle plates (placing uncovered agar plates in contact (e.g., floors and ceilings) and those with frequent
various locations) does not require special equipment, and is hand contact ("high-touch surfaces") ( 1). For a detailed
most commonly used to sample air for the presence of bac- discussion of the methods, thoroughness, and frequency
teria. They are not recommended when sampling for fungal of cleaning and the products recommended, the reader is
spores (1). The results of sampling using settle plates can be referred to the CDC Guideline for Disinfection and Ster-
expressed as the number of viable particles or viable bacteria ilization (see Chapter 21) (3). Briefly, noncritical medical
per unit area of agar exposed per time period (CFU/area/ time). devices should be disinfected with an Environmental Protec-
Unlike the use of liquid impinger or solid impactor samplers, tion Agency (EPA)-registered hospital disinfectant using the
this method does not provide data on the number of particles label safety precautions and use directions. Although many
or microorganisms per volume of air sampled. product labels recommend contact times of 10 minutes,
When contemplating the use of air sampling, it is important multiple studies have shown that hospital disinfectants are
to keep in mind the fact that there are currently no uniform usually effective with contact times of at least 1 minute (3).
air-quality standards for healthcare facilities. Also, it is neces- Housekeeping surfaces, such as floors and tabletops, should
sary to consider the fact that any sampling represents air qual- be cleaned on a regular basis or when surfaces are visibly
ity during that particular time and place that sampling was soiled. Environmental surfaces should be disinfected on a
conducted. The number of organisms present in air may vary regular basis (e.g., daily, three times per week) and when
by the number of personnel present and their level of activity, surfaces are visibly soiled. High-touch housekeeping sur-
temperature, relative humidity, time of day or year, and the per- faces in patient-care areas (e.g., doorknobs, bed rails, light
formance of air-handling systems ( 1,199-201) . switches, wall areas around the toilet in the patient's room,
and the edges of privacy curtains) should be cleaned and/
or disinfected more frequently than surfaces with minimal
Methods for Silmpling WIJtl:r
hand contact (1).
Routine sampling of water in healthcare facilities is generally Despite well-established guidelines for cleaning and dis-
limited to monitoring the quality of water used in dialysis set- infection of environmental surfaces in healthcare facilities,
tings (1). However, sampling water in the facility's distribution many hospitals have had difficulties in ensuring that daily and
system may be helpful in epidemiologic investigations when terminal cleaning of rooms is performed as recommended
the organisms involved suggest water as a potential source. The (202-205). Often times, it is not dear to HCWs who is responsi-
more common waterborne pathogens include Pseudomonas, ble for cleaning and disinfection of various items. As a result, it
Aeromonas, Legionelk, Acinetobacter, and Mycobacteria spp. Water may be helpful to develop a written guideline assigning respon-
samples should be collected in sterile specimen containers, sibility for cleaning of various types of equipment and surfaces
transported to the laboratory in cold conditions (-4°C), and to nurses and housekeepers (206).
tested as soon as possible, since the number and types of organ-
isms suspended in water can change over time (1). If water in
NEW STRATEGIES TO MINIMIZE DAILY
the distribution system is suspected as a source, samples taken
CONTAMINATION OF SURFACES
from a water tap should be obtained after flushing the system
and removing faucet aerators. If aerators are suspected to be Recently, a number of new strategies have been developed in
the source, then specimens can be obtained without removing an effort to minimize the number of bacteria that are present
the aerator or by culturing the aerator. on environmental surfaces in patient rooms. The approaches
If bacterial contamination is expected to be at a high level, include applying a microbicidal metal such as copper or sil-
it may be adequate to inoculate small quantities of water onto ver to the hospital's surfaces, incorporating an antimicrobial
agar plates. However, in many situations, suspected pathogens substance such as triclosan into products, or applying a liquid
may be present in low numbers, and membrane filtration (e.g., organosilane-containing product) that has prolonged
should be used to sample a minimum of 100 mL (1). After pass- antimicrobial activity to surfaces (207-210). Other strategies
ing the water samples through the membrane filter, the filter include the use of engineered microtopography (objects with
is placed faceup on an agar plate and incubated. Depending a topography similar to shark skin) or light-activated antimi-
on the organisms suspected, specialized or selective media crobial coatings. The potential advantages and disadvantages
may be needed, particularly for some gram-negative bacteria of these approaches have been summarized recently by Weber
and Legionella spp. To facilitate the interpretation of water and Rutala (207). Some of these techniques have shown sig-
cultures, control samples should be taken from parts of the nificant reductions in the number of bacteria that accumulate
water-distribution systems that are not suspect. A more detailed on environmental surfaces. However, a number of unresolved
discussion of sampling water in healthcare facilities is included questions that need to be answered regarding these approaches
in the CDC Guidelines for Environmental and Infection Con- include their cost, durability of effect, level to which they are
trol in Healthcare Facilities (1). affected by routine cleaning and disinfection practices, and
their impact on HAis. Further studies of these approaches are
clearly warranted.
CLEANING AND DISINFECTION
OF ENVIRONMENTAL SURFACES New trzVo-touch» Approaches to Room
or Are• DeconmminiJtion
Environmental surfaces can be divided into two categories:
noncritical patient-care devices (e.g., blood pressure cuffs) In the 1960s and 1970s, some hospitals disinfected rooms va-
and housekeeping surfaces (3). Housekeeping surfaces can cated by patients with communicable diseases by a technique
be further divided into two groups: those with minimal hand known as fogging (10). Fogging involved nebulization of a
disinfectant in a sealed patient room until all surfaces were wet, hydrogen peroxide system appeared to have yielded lower log
followed by wiping off residual fluid from surfaces by masked reductions of vegetative bacteria than the other hydrogen per-
and gowned personnel. The disinfectants used included qua- oxide systems, and little information is available regarding its
ternary ammonium compounds, phenolics, hypochlorite solu- activity against spores (Table 19.2) (213). All of the hydrogen
tions, or formaldehyde. Studies at CDC concluded that such peroxide-based systems require sealing of the room, and moni-
fogging procedures were ineffective, and recommended that toring for hydrogen peroxide leakage from the room during
hospitals abandon fogging as a means of terminal disinfec- the decontamination process.
tion of hospital rooms (10). The subsequent CDC guidelines, Three studies have evaluated an automated mobile UV light
including the Guideline for Disinfection and Sterilization in system (Tru-D) by Lumalier (187,188,211,216) . The Tru-D
Healthcare Facilities published in 2008, recommended that UV light system also has been shown to significantly reduce
disinfectant fogging should not be performed for routine pur- environmental contamination by a variety of HAl pathogens.
poses in patient-care areas (3). In one comparative study, the UV light system did not reduce
Recently, a number of newer technologies have been de- bacterial counts on surfaces to the same degree as the HPV
veloped for "no-touch" room or area decontamination. Vapor- system, and was somewhat less effective for sites that were out
based or aerosol-based technologies use hydrogen peroxide, of direct line of sight of the device ( 217) . However, the UV
gaseous chlorine dioxide, gaseous ozone, alcohol-based or light system is easier to use, requires less training of operators,
peracetic acid fogging, and saturated steam devices. Vapor- and has shorter cycle times of 15 minutes to 1.5 hours. A re-
based hydrogen peroxide, chlorine dioxide, and ozone are not duction in C. diffici~ infection rates was associated with the
fogging technologies, as the disinfectant is in the form of a gas, use of the automated UV light system in one short-duration
not larger (often visible) particles. Other technologies include study published in abstract form (211) . A multicenter trial of
mobile ultraviolet (UV) light devices, a pulsed-xenon UV light the impact of the Tru-D UV light system on HAis is currently
device, and high-intensity narrow-spectrum light. Most of these underway.
"no-touch" automated decontamination systems have been re- A pulsed-xenon UV light system achieved a significant
viewed in detail by Otter et al. (211). reduction in VRE surface contamination in one small study
Two vapor-based hydrogen peroxide technologies and an that utilized a 12-minute cycle time (218). In addition, a re-
aerosol- or "dry mist"-based hydrogen peroxide system that cent conference abstract reported that the use of the pulsed-
have been shown to be effective in reducing surface contamina- xenon device was associated with a reduction in C. difftcik
tion are commercially available in the United States, and at least disease (211). The characteristics and effectiveness of gaseous
one "dry spray" system is available in other areas (Table 19.2) ozone, gaseous chlorine dioxide, and various fogging systems
(211-213). Both the HPV system by Bioquell and the vapor- are briefly reviewed by Otter et al. (211).
ized hydrogen peroxide by Steris (VHP) have been shown to
reduce Geobacillus stearothermokilus spores by >6 logw and
METHODS FOR MONITORING CLEANING
achieve >6-log10 reductions against C. difftci~ spores, a variety
AND DISINFECTION PRACTICES
of viruses including norovirus surrogates, and vegetative patho-
gens such as MRSA, VRE, and Acinetobacter baumannii (211). Cleaning housekeeping surfaces on a regular basis or when
The Bioquell HPV has been shown to significantly reduce spills occur and when surfaces are visibly soiled is recom-
C. dif.ficik disease rates in one before-after study, has been mended (3). In recent years, it has become apparent that
used to remove environmental reservoirs during outbreaks, daily cleaning in patient rooms or terminal room cleaning (af-
and has been shown to significantly reduce the risk of acquir- ter patient discharge) often are not performed according to
ing VRE among patients admitted to rooms where the prior healthcare facility policies and procedures. As a result, there
occupant was colonized or infected with VRE (83,96,211). The is increased emphasis on developing programs to monitor the
Steris VHP system appears to have contributed to the control adequacy of cleaning and disinfection practices and on the
of an outbreak of A. baumannii in a long-term acute care hos- need for ongoing education and feedback of housekeepers
pital (114). The cycle times range from 1.5 to 2.5 hours for (219,220). Strategies for monitoring cleaning and disinfection
the HPV system and 8 hours for the VHP system. The aero- practices are listed below.
solized hydrogen peroxide system has been shown to signifi- Visual inspection. For many years, visual inspection of sur-
cantly reduce bacterial contamination of surfaces, but achieves faces by housekeeping managers represented the most fre-
lower reductions of spores than the HPV system (214,215). quently used method for assessing the adequacy of cleaning
The cycle times for the aerosolized hydrogen peroxide system environmental surfaces in healthcare facilities. However, re-
range from 2 to 4 hours (212,215). The "dry spray" or "dry fog" cent studies have shown that visual assessment is an unreliable
• . ij :J ft j@. Rdative Efficacy of No-Touch Hydrogen Pero:dde Decontamination Systems

Miaocondensation Dry Gas Vaporized Dry Mist Aerosol Dry Fog Aerosol
Reduction in Bacterial Levels HPVBioquell HP Steris HP Sterinis (ASP) HP NocoSpray
Log reduction vegetative bacteria 103-104.5
Log reduction bacterial spore strips -101-<104
Log reduction C. difficile spores 104
HPV, hydrogen peroxide vapor; HP, hydrogen peroxide.

method for assessing the cleanliness of high-touch surfaces Currently, there are no validated and widely accepted criteria
in hospitals (190,221-224). More useful methods include for how to define environmental surfaces in healthcare facilities
sampling the surfaces by using swabs, by using contact plates as dean using ACCs. Early standards from the food-processing
or dipslides and performing aerobic colony counts (ACCs), industryclassifiedsurfacesas clean iftheACCwas <5 CFU (219).
use of ATP bioluminescence assays, and fluorescent marker In contrast, several investigators have used <2.5 CFUs/cm2
methods. Each of these methods has its advantages and to classify hospital surfaces as "clean" (189,191,192,222). It
disadvantages. has also been proposed that a colony count of an indicator
Fluorescent marker systems. In 2006, Carling et al. de- organism (e.g., MRSA) should be <1 CFU/cm2 (219,233).
scribed a new method of monitoring and improving cleaning However, it is important to point out that, at the present time,
and disinfection practices following patient discharge (225). there are no convincing data that these are the levels of sur-
A novel fluorescent gel, which is invisible when dry, was used face contamination below which there is less transmission of
to mark high-touch surfaces in patient rooms after terminal HAl pathogens. Further studies are clearly needed to establish
cleaning in three hospitals. The fluorescent marker is easily re- evidence-based criteria for defining environmental surfaces in
moved by wiping the surface with a damp doth for 5 seconds. healthcare facilities as "clean."
After two other patients had occupied the room, and discharge The disadvantages of ACCs include the technician time re-
cleaning was performed, a black light was used to determine if quired to process cultures, the cost of culture media, the need
it had been cleaned, either by complete removal or substantial for microbiology laboratory support, and the fact that there-
removal of the marker. The study showed that the proportion sults are generally not available until 48 hours after sampling
of target sites that have been cleaned increased from 4 7% be- is performed.
fore the intervention to 76% to 92% during the intervention, Adenosine triphosphate (ATP) bioluminescence assays.
which included education and feedback to housekeepers. The ATP is found in all organic material, including microorgan-
same strategy has been used in a number of subsequent stud- isms, food, and human excretions and secretions. ATP biolu-
ies: one involving 23 hospitals, another took place in 36 acute minescence assays have been used for years in the food and
care hospitals, and two others involving ICUs in 16 hospitals beverage industries as a method for assessing the cleanliness
and 27 hospitals (203,204,220,226,227). Similar programs have of surfaces. Special swabs are used to sample environmental
been implemented in a number of other hospitals for which surfaces, the swabs are placed in a handheld luminometer,
publications are not yet available. Blue et al. described a short and the results are expressed as relative units (RLUs). The
trial using a different fluorescent solution that showed that the more organic material on a surface, the higher the ATP and
proportion of surfaces cleaned improved from 23% at baseline RLU levels. In 2000, Griffith et al. proposed using ATP biolu-
to >80% (228). minescence to monitor cleaning practices in hospitals (189).
The advantages of fluorescent marker systems include that In early studies, surfaces were defined as clean if they yielded
they require minimal equipment and are simple to use. Also, ATP readings of <500 Rl.Us (189,222,223). More recently,
when combined with education and feedback of housekeep- several investigators have defined hospital surfaces as clean
ers, the use of fluorescent marker systems has been shown in if an ATP bioluminescence assay yielded a reading of <250
numerous hospitals to improve the frequency with which sur- Rl.Us (192,197,230,233). However, like microbiological crite-
faces are cleaned (203,204,220,226,227). Fluorescent marker ria for cleanliness, the ATP level at which the transmission of
systems have several disadvantages, including the fact that pathogens is significantly reduced or eliminated has not been
they provide only information about the frequency with which determined. Additional studies are necessary to determine if
surfaces are wiped, and cannot provide information about <250 RLU is the optimal criteria for surface cleanliness in
the level of bacterial contamination or overall cleanliness of healthcare settings. In fact, it is possible that a single level will
surfaces. Furthermore, there is evidence that when the high- not be appropriate for all types of surfaces encountered in
touch objects with a fluorescent marker are changed with- healthcare settings. For example, bed rails have been found to
out notifying housekeepers, appropriate cleaning may drop be in some of the most difficult surfaces to clean, as reflected
substantially (212). by ATP readings (192,230,235). Furthermore, surfaces such as
Culturing surfaces to monitor cleaning practices. Quali- bed rails can be made from a variety of different materials,
tative cultures obtained by using swabs and quantitative and the more rough the surface of an item, the more difficult
cultures, expressed as ACCs, have been used widely for it is to dean and to yield low ATP levels (236) . Also, ATP bio-
monitoring cleaning and disinfection practices. Moistened luminescence assay systems and luminometers from different
swabs that have been directly plated onto agar media, or that manufacturers have different levels of sensitivity (199). The
have been placed in broth and incubated before inoculat- cutoff point for cleanliness using the 3M Clean-Trace system is
ing solid media have been used by a number of investigators <250 RLU, whereas a cutoff of <100 RLU has been proposed
(29,97,205,223,229-231). Another qualitative method that for the Hygiena system (224).
has been used occasionally involves using a sterile cloth to One thing that must be kept in mind when using ATP
sample the surfaces, followed by incubation in broth before bioluminescence assays to monitor the effectiveness of clean-
inoculation of solid media (232). ing practices is the fact that ATP readings correlate relatively
Dipslides have been used frequently to assess cleanliness in poorly with the results of micro biological sampling of surfaces
the United Kingdom, whereas agar contact plates have been (ACCs) (224,230,233,237,238). This is because biolumines-
used more frequently for this purpose in the United States cence assays detect ATP from aerobic bacteria, anaerobic bac-
(186,189-192,219,221,222,224,233;234). ACCs have the advan- teria, and presumably nonculturable microorganisms as well
tage that they provide quantitative data on surface contamina- as ATP from secretions, excretions, food, and any other or-
tion by aerobic organisms and can detect target pathogens or ganic material that may be on the surface (239). One study
unsuspected surface contaminants. suggested that only 33% of ATP found on hospital surfaces
TABLE 19.3 Charactcrist.ics of Methods for Assessing the Adequacy of Cleaning Practices
Fluorescent Swab or Contact ATP BiolumineBCeD.ce
Vl5Wil Inspection Marker System Plate Cultures Assay System
Ease of use Good Good Fair; requires Good
laboratory
support
Rapidity of results Good Good Tumaround time Good
~48hours
Accuracy in assessing cleaning practices Poor Good Good Good
Specific measure of bacterial contamination No No Yes No
Useful for education and feedback Poor Good Good Good
Provides quantitative results Poor Poor Good Good
was attributable to bacteria (190). Another factor that can 7. Walter CW, Kundlin Rll, Shilkret MA, et al. The opread of Staphylococci to the environ-
ment. Anti/Mtia A=uaL 1959;952-957.
affect ATP results is the type of disinfectant that may have 8. Walter CW, Ruben&tein AD, Kundoin Rll, et aL llacteriology of the bedlide carafe. NEngl]
been used on surfaces. Residual levels of certain disinfectants Mzd. 2012;259:119S-1202.
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mooi.wn COlllpouudo by uoe of a IIJ'I"Y'fug tcclwique. Appl MUribiol. 1968;16:2~227.
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for llioeaoe Control, U.S. Department Of Health; 19'72.
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14. Marko JS, Tlai TF, Martone WJ, et aL Nooocomiall.egionnairea dioeaoe in Columbua, Ohio.
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William A. Rutala and David J. Weber
Disinfection and Sterilization

in Healthcare Facilities
INTRODUCTION by the use of liquid chemicals or wet pasteurization in health
care settings. The efficacy of disinfection is affected by a num-
In the United States in 2009, there were approximately ber of factors, each of which may nullify or limit the efficacy of
48,000,000 surgical procedures and an even larger number of the process. Some of the factors that affect both disinfection
invasive medical procedures (1). For example, there are about and sterilization efficacy are the prior cleaning of the object;
11 million gastrointestinal endoacopies performed per year (2). the organic and inorganic load present; the type and level of
Each of these procedures involves contact by a medical device microbial contamination; the concentration of and exposure
or surgical instrument with a patient's sterile tissue or mucous time to the germicide; the nature of the object (e.g., crevices,
membranes. A major risk of all m.ch procedures is the introduc- hinges, and lumens); the presence ofbiofilms; the temperature
tion of pathogenic microbes, which can lead to infection. For and pH of the disinfection process; and, in some instances, the
example, failure to properly disinfect orsterilize equipment may relative humidity of the sterilization process (e.g., ETO).
lead to tramrni&sion via contaurinated instruments or devices By definition then, disinfection differs &om sterilization
(e.g., Mycolxu:terium tuberctdoJis contam.W.ated bronchoscopes). by its lack of sporicidal property, but this is an oversimplifi.ca·
Achieving disinfection and sterilization through the use tion. A few disinfectants will kill. spores with prolonged expo-
of disinfectants and sterilization practices is essential for ensure times (3 to 12 hours) and are called chemical sterilants.
mring that medical and surgical instruments do not transmit At similar concentrations, but with shorter exposure periods
infectious pathogens to patients. Since it is not necessary to (e.g., 20 minutes for 2% glutaraldehyde), these same disin-
sterilize all patient-care itema, healthcare policies must iden- fectants will kill all microorganisms with the exception of
tify whether cleaning, disinfection, or sterilization is indicated large numbers of bacterial spores and are called high-level
based primarily on each item's intended use. disinfectants. Low-level disinfectants may ltill most vegetative
Multiple studies in many countries have documented tack of bacteria. some fungi, and some viruses in a practical period
compliance with established guidelines for disinfection and steJ:Ioo of time (S10 minutes), whereas intermediate-level disinfec-
ilizati.on (3,4). Failure to comply with scientifically based guide- tants may be cidal for mycobacteria vegetative bacteria, most
lines has led to numerous outbreab (4-9). In this updated viruses, and most fungi, but do not necessarily kill bacterial
chapter (10-13), a pragmatic approach to the judicious selec- spores. The germicides differ markedly among themselves pri-
tion and proper use of disinfection and sterilization processes marily in their antimicrobial spectrum and rapidity of action
is presented, based on wel.klesigned studies assessing the effi. (Table 20.1).
cacy (via laboratory investigations) and effectiveness (via clinical Cleaning, on the other hand, is the removal of visible soil
studies) of disinfection and sterilization procedures. (e.g., organic and inorganic material) from objects and sur-
faces, and it normally is accomplished by manual or mechani-
cal means using water with detergents or enzymatic products.
DEFINITION OF TERMS Thorough cleaning is essential before high-level disinfection
and sterilization, since inorganic and organic materials that re-
Sterilization describes a process that destroys or eliminates all main on the rurfaces of instruments interfere with the effective-
fonns of microbial life and is carried out in healthcare facilities ness of these processes. Decontamination is a procedure that
by either physical or chemical methods. Steam under pressure, removes pathogenic microorganisms &om objects so they are
dry heat, ethylene oxide (ETO) gas, hydrogen peroxide gas safe to handle, use, or discard.
plasma, hydrogen peroxide vapor, ozone, and liquid chemicals Tenns with a suffix "ci.de" or "cidal" for killing action also
are the principal sterilizing agents used in healthcare facili- are commonly used. For example, a germicide is an agent that
ties. When chemicals are used for the purposes of destroying can kill microorganisms, particularly pathogenic organisms
all forms of microbiological life, including fungal and bacterial ("germs"). The term germicide includes both antiseptics and
spores, they may be called chemical sterilants. These same ger- disinfectants. Antiseptics are germicides applied to living tisrue
micides used for shorter exposure periods also may be part of and skin while disinfectants are antimicrobials applied only to
the disinfection process (i.e., high-level disinfection). inanimate objects. In general, antiseptics are only used on the
Disinfection describes a process that eliminates many or all skin and not for rurface disinfection, and disinfe<:tants are not
pathogenic microorganisms on inanimate objects with the ex- used for skin antisepsis because they may cause injury to skin and
ception of bacterial spores. Disinfection is usually accomplished other tissues. Other words with the suffix "cide" (e.g., virucide,
293
TABLE 20.1 Methods of Sterilization and Disinfection

Sterilization Disinfection
High-level
(semicritical itemJJ; Low-level
[except dental] will (noncritical itemJJ;
Critical items (will enter tissue or come in contact with Intermediate-level (some will come in
vascular system or blood will flow mucous, membrane or semicritical items1 mel contact with
through them) nonintact skin) noncritical items) intact skin)
Procedure (exposure Procedure

time 12-50 minutes Procedure (exposure (exposure time
Object Procedure Exposure Time at 2: 20"C)2.S time 2: I minute)9 2: I minute)'
Smooth, hard A MR D
surface1•4 B MR E L5 L
c MR F M M
D 10 hours at 20°-250C H N N
F 6hours Ifi p 0
GlO 12 minutes at 50°-56°C 1 Q p
K Q
H 3--8 hours
Rubber tub- A MR D
ing and B MR E
catheters5 •4 c MR F
D 10 hours at 20°-250C H
F 6hours Ifi
G 12 minutes at 50°-56°C 1
H 3--8 hours K
Polyethylene A MR D
tubing and B MR E
cathetersM,7 c MR F
D 10 hours at 20°-25°C H
F 6hours Ifi
G 12 minutes at 50°-56°C 1
H 3--8 hours K
Lensed A MR D
insttuments4 B MR E
c MR F
D 10 hours at 20°-250C H
F 6hours 1
G 12 minutes at 50°-56°C K
H 3--Shoun
Thermometers p8
(oral and
rectal) 8
Hinged A MR D
instruments4 B MR E
c MR F
The selection and use of dWnfectants in the healthcare field is dynamic, and products may become available that are not in existence when
this chapter was written. As newer disinfectants become available, persoru or committees responsible for selecting disinfectants and steriliza-
tion processes should be guided by products cleared by the FDA and the EPA, as well as information in the scientific literature.
A Heat sterilization, including steam or hot air (see manufacturer's recommendations, steam sterilization processing time from 3 to 30 minutes)
B Ethylene oxide gas (see manufilcturer's recommendatioru, generally 1 to 6 hours processing time plus aeration time of8 to 12 hours at 500C to 600C)
C Hydrogen peroxide gas plasma (see manufacturer's recommendatioru for internal diameter and length restrictions, processing time be-
tween 28 to 72 minutes).
D Glutaraldehyde-based formulatioru (2=2% glutaraldehyde, caution should be exercised with all glutaraldehyde formulatioru when further
in-use dilution is anticipated); glutaraldehyde (1.12%) with 1.93% phenol/phenate; and glutaraldehyde (3.4%) with isopropanol (26%). One
glutaraldehyde-based product has a high-level disinfection claim of 5 minutes at 35°C.
E Ortho-phthalaldehyde (OPA) 0.55%
F Hydrogen peroxide, standard 7.5% (will corrode copper, zinc, and brass)
• . fjC :f ri :fJ•ri • .Methods of Sterilization and Disinfection (Omri•wll)
Sterilization Disinfection
High-level
(semicritical iteDlllj Low-level
[except dental] will (noncritical iteDlll;
Critical iteDlll (will enter W.Ue or come in contact with Intermediafe.level (IIODle will come in
vucular syatem or blood will flow mucous, membrane or semicritical iteD1111 aod contact with
through them) nonintact skin) noncritical iteDlll) intact skin)
Procedure (exposure Procedure
time 1i--SO minutes at Procedure (exposure (exposure time
Object Exposure Time 2: !OOC)Z,S time 2: 1 minute)9 2: 1 minute) 9
D 10 hours at 200-25°C
F 6 hours
G 12 minutes at 50"-56°C
H 3-Shours
G Peracetic add, concentration variable, but 0.2% or greater is sporicidal. A 0.2% peracetic acid immersion reprocessor operates at 50"C to 56"C. Per
guidance from the IDA, most hospi.tab use the 0.2% peracetic acid reprocessor for reproc~ ~critical items that require high-le\'el disinfection.
Thus, as a general rule, the reproce350r will not be used to reproce35 critical iteDill, as critical ite!II5 should be sterile and with the reprocessor using
0.2% peracetic acid the final processed device cannot be assured to be .sterile. Thus, heat~nsitive critical dev.ices should be sterilized by other validated,
FDA-cleared, sterilization processes such as hydrogen peroxide gas plasma, ETO, vaporized hydrogen peroxide, and ozone. If a heat~mi.tive critical
device truly cannot be processed by any other modality than the reprocessor using 0.2% peracetic acid then we are left with the decision between not
using the device at all or reprocessing it in the 0.2% peracetic acid reprocessor (at 50"C to 56"C). The deciJi.on to use the 0.2% peracetic reprocessor at
50"C to 56"C for a heat~nsi.tive critical item that cannot be processed by an alternative sterilization process should be made on a ~ basis.
H Hydrogen peroxide (7.!15%) with 0.2!1% peracetic acid; hydrogen peroxide 1% with peracetic acid 0.08%; 8.!1% hydrogen peroxide, and
7.0% peracetic acid (will corrode metal instruments)
I Wet pasteurization at 700C for !10 minutes with detergent cleaning
J Hypochlorite, single use chlorine generated on-«ite by electrolyzing saline containing 2:400--675 active free chlorine; (will corrode metal instruments)
K Improved hydrogen peroxide, 2:2%
L Sodium hypochlorite (5.25% to 6.15% household bleach diluted 1:500 provides> 100 ppm available chlorine)
M Phenolic germicidal detergent solution (follow product label for use-dilution)
N Iodophor germicidal detergent solution (follow product label for use-dilution)
0 Quaternary ammonium germicidal detergent solution (follow product label for use-dilution)
P Ethyl and isopropyl alcohol
Qimproved hydrogen peroxide. 0.5% and 1.4%
MR, Manufacturer's recommendations; NA, Not applicable
1 See text for discussion of hydrotherapy.
2The longer the exposure to a disinfectant, the more likely it is that all microorganisms will be eliminated. Twenty-minute exposure at 20"C is the
minimum time needed to reliably kill M. ~and non tuberculous mycobacteria with a 2% glutaraldehyde. With the exception of ~2% glutaral-
dehydes, follow the FDA-deared high-level disinfection claim. Some high-level disinfectants have a reduced exposure time (e.g., ortho-phthalaldehyde
at 12 minutes at 20"C) because of their rapid activity against mycobacteria or reduced exposure time due to increased mycobactericidal activity at
elevated temperature (e.g., 2.5% glutaraldehyde at 5 minutes at !I5°C, 0.55% OPA at 5 minutes at 25"C in automated endoscope reprocessor).
li>Jubing must be completely filled for high-level disinfection and liquid chemical sterilization; care must be taken to avoid entrapment of air
bubbles during immersion.
4Material compatibility should be investigated when appropriate.
5A concentration of 1000 parts per million (ppm) available chlorine should be considered where cultures or concentrated preparations of
microorganisms have spilled (5.25% to 6.15% household bleach diluted 1:50 provides> 1000 ppm available chlorine). This solution may cor-
rode some surfaces.
6Pasteurization (washer-disinfector) of respiratory therapy or anesthesia equipment is a recognized alternative to high-level disinfection. Some
data challenge the efficacy of some pasteurization units.

7Thermostability should be investigated when appropriate.
Bno not mix rectal and oral thermometers at any stage of handling or processing.
~y law, all applicable label instructions on EPA-registered products must be followed. If the user selects exposure conditions that differ from
those on the EPA-registered products label, the user assumes liability from any injuries resulting from off-label use and is potentially subject to
enforcement action under FIFRA.
Modified from Simmons BP. CDC guidelines for the prevention and control of nosocomial infections. Guideline for hospital environmental
control. Am]Infect Conlrol. 198!1;11 :97-120, with permission.
Modified from Rutala WA, APIC Guidelines Committee. APIC guideline for selection and use of disinfectants. Association for Professionals in
Infection Control and Epidemiology, Inc. Am]Infect Cont7ol. 1996;24:!113-!142, with permission.
Modified from Rutala WA Disinfection, sterilization and waste disposal. In: Wenzel RP, ed. ~lion and Control ofN()S()Cornial/nfectioru. 3rd ed.
Baltimore, MD: Williams and Wilkins; 1997:539-593, with permission.
Modified from Rutala WA, Weber DJ, Healthcare Infection Control Practices Advisory Committee. Guideline for disinfection and sterilization
in healthcare facilities, 2008. cdc.gov/ncidod/dhqp/pdf/guidelines/Disinfection_Nov_2008.pdf, with permission.
Modified from Rutala WA Selection and use of disinfectants in healthcare. In: Mayhall CG, ed. Hospital Epidemioloi!J and Infection Control.
4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2012:1180-1212, with permission.
10Per guidance from the FDA, most hospitals use the 0.2% peracetic acid reprocessor for reprocessing semkritical items that require high-level
disinfection (see G above).
295
fungicide, bactericide, sporicide, and tuberculocide) can kill the following processing and during storage. Furthermore, devices
type of microorganism identified by the prefix. For example, a may require rinsing following exposure to the liquid chemical
bactericide is an agent that kills bacteria (14-20). sterilant with water that generally is not sterile. Therefore, due
to the inherent limitations of using liquid chemical sterilants in
a nonautomated reprocessor, their use should be restricted to
A RATIONAL APPROACH reprocessing critical devices that are heat-sensitive and incom-
TO DISINFECTION AND STERILIZATION patible with other sterilization methods.
Over 45 years ago, Earle H. Spaulding (15) devised a rational

SEMICRITICAL ITEMS
approach to disinfection and sterilization of patient-care items
or equipment. This classification scheme is so clear and logi- Semicritical items are those that come in contact with mucous
cal that it has been retained, refined, and successfully used by membranes or nonintact skin. Respiratory therapy and anes-
infection preventionists and others when planning methods thesia equipment, some endoscopes, laryngoscope blades,
for disinfection or sterilization ( 14, 16,18,20-23). Spaulding esophageal manometry probes, anorectal manometry cath-
believed that the nature of disinfection could be understood eters, and diaphragm fitting rings are included in this category.
more readily if instruments and items for patient-care were di- These medical devices should be free of all microorganisms
vided into three categories based on the degree of risk of infec- (i.e., mycobacteria fungi, viruses, bacteria), although small
tion involved in the use of the items. The three categories he numbers of bacterial spores may be present. Intact mucous
described were critical, semicritical, and noncritical. Although membranes, such as those of the lungs or the gastrointestinal
the scheme remains valid, there are some examples of disin- tract, generally are resistant to infection by common bacterial
fection studies with viruses, mycobacteria and protozoa that spores, but susceptible to other organisms such as bacteria,
challenge the current definitions and expectations of high- and mycobacteria, and viruses. Semicritical items minimally require
low-level disinfection (24,25). The Spaulding terminology is high-level disinfection using chemical disinfectants. Glutaral-
employed by the Centers for Disease Control and Prevention's dehyde (with and without other active ingredients), standard
(CDC's) "Guidelines for Environmental Infection Control in hydrogen peroxide, ortho-phthalaldehyde, peracetic acid with
Healthcare Facilities" (26) and "Guideline for Disinfection and hydrogen peroxide, improved hydrogen peroxide, and chlo-
Sterilization in Healthcare Facilities" (20). rine are cleared by the U.S. Food and Drug Administration
(FDA) (27) and are dependable high-level disinfectants, pro-
vided the factors influencing germicidal procedures are met.
CRITICAL ITEMS
The exposure time for most high-level disinfectants varies from
Critical items are so called because of the high risk of infec- 8 to 45 minutes at 20° to 25°C. Outbreaks occur when ineffec-
tion if such an item is contaminated with any microorganism, tive disinfectants, including iodophor, alcohol, and over-diluted
including bacterial spores. Thus, it is critical that objects that glutaraldehyde (5) are used for "high-level disinfection." When
enter sterile tissue or the vascular system be sterile because any a disinfectant is selected for use with certain patient-care items,
microbial contamination could result in disease transmission. the chemical compatibility after extended use with the items to
This category includes surgical instruments; cardiac, intravascu- be disinfected also must be considered. For example, compat-
lar and urinary catheters; implants; and ultrasound probes used ibility testing by Olympus America of the 7.5% hydrogen per-
in sterile body cavities. The items in this category should be pur- oxide found cosmetic and functional changes with the tested
chased as sterile or be sterilized by steam sterilization if possible. endoscopes (Olympus, October 15, 1999, written communica-
If heat-sensitive, the object may be treated with ETO, hydrogen tion). Similarly, Olympus does not endorse the use of the hy-
peroxide gas plasma, vaporized hydrogen peroxide, ozone, or drogen peroxide with peracetic acid products due to cosmetic
by liquid chemical sterilants if other methods are unsuitable. and functional damage (Olympus America, April15, 1998 and
Tables 20.1 and 20.2list several germicides categorized as chem- September 13,2000, written communication).
ical sterilants. These include: ~2.4% glutaraldehyde-based Semicritical items that will have contact with the mucous
formulations, 1.12% glutaraldehyde with 1.93% phenol/ membranes of the respiratory tract or gastrointestinal tract
phenate, 3.4% glutaraldehyde with 26% isopropanol, 0.55% should be rinsed with sterile water, filtered water, or tap wa-
ortho-phthalaldehyde, 7.5% standard hydrogen peroxide, 2% ter followed by an alcohol rinse (20,28,29). An alcohol rinse
improved hydrogen peroxide, 400 to 675 parts per million and forced-air drying markedly reduces the likelihood of con-
(ppm) hypochlorite/hypochlorous acid, 7.35% hydrogen per- tamination of the instrument (e.g., endoscope), most likely by
oxide with 0.23% peracetic acid, 0.2% peracetic acid, 8.3% hy- removing the wet environment favorable for bacterial growth
drogen peroxide with 7.0% peracetic acid, and 1.0% hydrogen (29). After rinsing, items should be dried and stored in a man-
peroxide with 0.08% peracetic acid. With the exception of0.2% ner that protects them from damage or contamination. There
peracetic acid ( 12 minutes at 50° to 56°C), the indicated expo- is no recommendation to use sterile or filtered water rather
sure times for sterilization range from 3 to 12 hours.l!7 Liquid than tap water for rinsing semicritical equipment that will have
chemical sterilants can be relied upon to produce sterility only contact with the mucous membranes of the rectum (e.g., rectal
if cleaning, which eliminate organic and inorganic material, probes, anoscopes) or vagina (e.g., vaginal probes) (20).
precedes treatment and if proper guidelines as to concentra-
tion, contact time, temperature, and pH are met. Another limi-
NONCRITICAL ITEMS
tation to sterilization of devices with liquid chemical sterilants is
that the devices cannot be wrapped during processing in a liq- Noncritical items are those that come in contact with intact
uid chemical sterilant, thus it is impossible to maintain sterility skin but not mucous membranes. Intact skin acts as an effective
Chapter 20 • Disinfection and Sterili:t.ation in Healthcare Facilities 297
TABLE 20.2 Summary of Advantaga and Disadvantages of Chemical Agents Used as Chemical
Stc:rilana- or as High-Level Disinfcc:tants (HLD)
Sterilant/HLD Ad.VliDtages Disadvantages
Peracetic Acid/ • No activation required Material compatibility concerns (lead, brass, copper,
Hydrogen Peroxide • Odor or irritation not significant zinc) both cosmetic and functional
Limited clinical experience
Potential for eye and skin damage
Glutaraldehyde • Numerous use studies published Respiratory irritation from glutaraldehyde vapor
• Relatively inexpensive Pungent and irritating odor
• Excellent material compatibility Relatively slow mycobactericidal activity (unless other
disinfectants added such as phenolic, alcohol)
Coagulates blood and fixes tissue to surfaces
Allergic contact dermatitis
Hydrogen Peroxide, • No activation required Material compatibility concerns (brass, zinc, copper,
standard • May enhance removal of organic matter and organisms and nick.eVsilver plating) both cosmetic and
• No disposal issues functional
• No odor or irritation issues Serious eye damage with contact
• Does not coagulate blood or fix tissues to surfaces
• Inactivates Cryptosporidium
• Use studies published
Ortho-phthalaldehyde • Fast acting high-level disinfectant Stairul protein gray (e.g., skin, mucous membranes,
• No activation required clothing, and environmental surfaces)
• Odor not significant More expensive than glutaraldehyde
• Excellent materials compatibility claimed Eye irritation with contact
• Efficacy data published Slow sporicidal activity
• Does not coagulate blood or fiX tissues to surfaces Reported to cause anaphylactic-like reactions in bladder
claimed cancer patients undergoing repeated cystoscopy
Peracetic Acid • Rapid cycle time (30-45 minutes) Potential material incompatibility (e.g., aluminum
• Low temperature (50"-55"C) liquid immersion anodized coating becomes dull)
• Environmental friendly by-products (acetic acid, 0 2, H 20) Used for immersible instruments only
• Fully automated Biological indicator may not be suitable for routine
• Single-use system eliminates need for concentration testing monitoring
• Standardized cycle One scope or a small number of instruments can be
• May enhance removal of organic material and endotoxin processed in a cycle
• No adverse health effects to operators under normal More expensive (endoscope repairs, operating costs,
operating conditions purchase costs) than high-level disinfection
• Compatible with many materials and instruments Serious eye and skin damage (concentrated solution)
• Does not coagulate blood or fix tissues to surfaces with contact
• Sterilant flows through scope facilitating salt, protein, Point-<~f-use system, no long-term storage
and microbe removal
• Rapidly sporicidal
• Provides procedure standardization (constant dilution,
perfusion of channel, temperatures, exposure)
Improved hydrogen • No activation required Material compatibility concerns due to limited clinical
peroxide(~ 2.0%) • Noodor experience
• Nonstaining Organic material resistance concerns due to
• No special venting requirements limited data
• Manual or automated applications Limited clinical use and comparative microbicidal
• 12 month shelf life, 14 day reuse efficacy data
• 8 minutes at 20°C high-level disinfectant claim
"All products effective in presence of organic soil, relatively easy to use, and have a broad spectrum of antimicrobial activity (bacteria, fungi,
viruses, spores, and mycobacteria). The above characteristics are documented in the literature; contact the manufacturer of the instrument
and sterilant for additional information.
Modified from Rutala WA. Weber DJ. Sterilization, high-level disinfection, and environmental cleaning. Infect Dis Clin North Am. 2011;25:45--76,
with permission.
Modified from Rutala WA. Weber DJ. Sterilization and disinfection. In; Jarvis WR, ed. Bennett and Brachman ~Hospital Infectiuru. 5th ed.
Philadelphia, PA Wolter Kluwer/Lippincott Williams 8c Wilkins; 2007:303--318, with permission.
Modified from Rutala WA. Weber DJ. Disinfection of endoscopes; review of new chemical sterilants used for high-level disinfection. Infect
CtmtrolHospEpidemiol. 1999;20:69-76, with permission.
barrier to most microorganisms; therefore, the sterility ofitems result in endotoxin contamination of surgical instruments
coming in contact with intact skin is "not critical." Examples of that could cause severe inflammatory reactions (36). Washer-
noncritical items are bedpans, blood pressure cuffs, crutches, sterilizers are modified steam sterilizers that dean by filling
bed rails, linens, bedside tables, patient furniture, and floors. the chamber with water and detergent through which steam
In contrast to critical and some semicritical items, most non- is passed to provide agitation. Instruments are subsequently
critical reusable items may be decontaminated where they are rinsed and subjected to a short steam sterilization cycle. An-
used and do not need to be transported to a central processing other washer-sterilizer employs rotating spray arms for a wash
area. There is virtually no documented risk of transmitting in- cycle followed by a steam sterilization cycle at 285°F (37,38).
fectious agents to patients via noncritical items (30) when they Washer-decontaminators/ disinfectors act like a dishwasher that
are used as noncritical items and do not contact nonintact skin uses a combination of water circulation and detergents to re-
and/or mucous membranes. However, these items (e.g., bed- move soil. These units sometimes have a cycle that subjects the
side tables, bed rails) do contribute to secondary transmission instruments to a heat process (e.g., 93°C for 10 minutes) (39).
by contaminating hands of healthcare workers or by contact Washer-disinfectors are generally computer-controlled units
with medical equipment that will subsequently come in contact for cleaning, disinfecting, and drying solid and hollow surgi-
with patients (31,32). Table 20.1lists several low-level disinfec- cal and medical equipment. In one study, cleaning (measured
tants that may be used for noncritical items. The exposure time as 5- to 6-log10 reduction) was achieved on surfaces that were
listed in Table 20.1 is at least 60 seconds. adequately in contact with the water flow in the machine ( 40).
Detailed information on cleaning and preparation of supplies
for terminal sterilization is provided by professional organiza-
CLEANING
tions (41,42) and books (43). Studies have shown that manual
Cleaning is the removal of foreign material (e.g., soil, and or- and mechanical cleaning of endoscopes achieves a 4-to 6-log10
ganic material) from objects, and it is normally accomplished reduction of contaminating organisms (44-47). Thus, clean-
using water with detergents or enzymatic products. Thorough ing alone is very effective in reducing the number of microor-
cleaning is required before high-level disinfection and steriliza- ganisms present on contaminated equipment. When manual
tion since inorganic and organic materials that remain on the methods are compared to automated methods for cleaning
surfaces of instruments interfere with the effectiveness of these reusable accessory devices used for minimally invasive surgi-
processes. Also, if the soiled materials become dried or baked cal procedures, the automated method was more efficient and
onto the instruments the removal process becomes more dif- achieved a >99% reduction in soil parameters (i.e., protein,
ficult, and the disinfection or sterilization process is less effec- carbohydrate, hemoglobin) in both ported and nonported lap-
tive or ineffective. Surgical instruments should be presoaked aroscopic devices (48).
or rinsed to prevent drying of blood and to soften or remove The choice for instrument cleaning is neutral or near-
blood from the instruments. neutral pH detergent solutions, as these solutions generally
Instrument cleaning is done manually when the use area provide the best material compatibility profile and good soil
does not have a mechanical unit (e.g., ultrasonic cleaner, or removal. Enzymes, usually proteases, are sometimes added to
washer-disinfector), or for fragile or difficult-to-clean instru- neutral pH solutions to assist in the removal of organic mate-
ments. If cleaning is done manually the two essential compo- rial. Enzymes in these formulations attack proteins that make
nents are friction and fluidics. Using friction (e.g., rubbing/ up a large portion of common soil (e.g., blood, pus). Clean-
scrubbing the soiled area with a brush) is an old and depending solution also can contain lipases (enzymes active on fats)
able method. Fluidics (i.e., fluids under pressure) is used tore- and amylases (enzymes active on starches). Enzymatic clean-
move soil and debris from internal channels after brushing and ers are not disinfectants, and proteinaceous enzymes may be
when the design does not allow the passage of a brush through inactivated by germicides. Like all chemicals, enzymes must
a channel (33). When using a washer-disinfector, care should be rinsed from the equipment, or adverse reactions (e.g.,
be taken as to the method of loading instruments. Hinged in- fever) could result (49). Enzyme solutions should be used in
struments should be opened fully to allow adequate contact accordance with manufacturer's instructions. Detergent en-
with the detergent solution. The stacking of instruments in zymes may be associated with asthma or other allergic effects
washers should be avoided. Instruments should be disassem- in users. Neutral pH detergent solutions that contain enzymes
bled as much as possible. are compatible with metals and other materials used in medi-
The most common types of mechanical or automatic clean- cal instruments and are the best choice for cleaning delicate
ers include ultrasonic cleaners, washer-decontaminators, medical instruments, especially flexible endoscopes (46) .
washer-disinfectors, and washer-sterilizers. Ultrasonic clean- Alkaline-based cleaning agents are used for processing medi-
ing removes soil by a process called cavitation and implosion cal devices as they dissolve protein and fat residues efficiently
in which waves of acoustic energy are propagated in aqueous (50); however, they may be corrosive (46). Some data dem-
solutions to disrupt the bonds that hold particulate matter to onstrate that enzymatic cleaners are more effective cleaners
surfaces. Bacterial contamination may be present in used ultra- than neutral detergents (51,52) in removing microorganisms
sonic cleaning solutions (and other used detergent solutions) from surfaces, but two studies found no difference in clean-
as these solutions generally do not make antibacterial label ing efficiency between enzymatic and alkaline-based cleaners
claims (34). While ultrasound alone does not cause significant (50,53). A new nonenzyme, hydrogen peroxide-based formu-
inactivation of bacteria, sonication can act synergistically to in- lation (not FDA cleared) was as effective as enzymatic clean-
crease the cidal efficacy of a disinfectant (35). Users of ultra- ers in removing protein, blood, carbohydrate, and endotoxin
sonic cleaners should be aware that the cleaning fluid could from surface test carriers (54) . In addition, this product was
able to effect a 5-log10 reduction in microbial loads with a including germicides. Clinically important asthma may occur
3-minute exposure at room temperature (54). Although the at levels below ceiling levels regulated by the U.S. Occupational
effectiveness of high-level disinfection and sterilization man- Safety and Health Administration (OSHA) or recommended
dates effective cleaning, there are no ~real-time" tests that can by CDC's National Institute of Occupational Safety and Health
be employed in a clinical setting to verify cleaning. If such (NIOSH). The preferred method of control is to eliminate the
tests were commercially available they could be used to ensure chemical (via engineering controls, or substitution) or relocate
that an adequate level of cleaning has been done (55--58). the worker.
The only way to ensure adequate cleaning is to conduct a
reprocessing verification test (e.g., microbiologic sampling),
STERILIZATION
but this is not routinely recommended (59). Validation of the
cleaning processes in a laboratory-testing program is possible Most medical and surgical devices used in healthcare facili-
by microorganism detection, chemical detection for organic ties are made of materials that are heat-stable and thus are
contaminants, radionuclide tagging, and chemical detection sterilized by heat, primarily steam sterilization. However, since
for specific ions (57,60). Data has been published describing 1950, there has been an increase in medical devices and in-
the use of an artificial soil, protein, endotoxin, X-ray contrast struments made of materials (e.g., plastics) that require low-
medium, or blood to verify the manual or automated clean- temperature sterilization. ETO has been used since the 1950s
ing process (40,61-65) and adenosine triphosphate (ATP) for heat- and moisture-sensitive medical devices. Within the
bioluminescence, fluoresence and microbiologic sampling past 25 years, a number of new, low-temperature sterilization
to evaluate the effectiveness of environmental surface clean- systems (e.g., hydrogen peroxide gas plasma, hydrogen per-
ing (66-68). Although ATP has been suggested for assessing oxide vapor, ozone) have been developed and are being used
the cleanliness of instruments, it has not been validated for to sterilize medical devices. Table 20.g reviews sterilization
this use. Minimally, all instruments should be individually in- technologies used in healthcare and makes recommendations
spected and be visibly clean. for their optimum performance in the processing of medical
Toxic anterior segment syndrome (TASS) is an acute in- devices (20,7g).
flammation of the anterior chamber, or segment, of the eye Sterilization destroys all microorganisms on the surface of
following cataract surgery. A variety of substances have been im- an article or in a fluid to prevent pathogen transmission associ-
plicated as causes of TASS and includes impurities of autoclave ated with the use of that item. While the use of inadequately
steam, heat-stable endotoxin, and irritants on the surfaces of sterilized critical items represents a high risk of transmitting
intraocular surgical instruments. General principles of clean- pathogens, documented transmission of pathogens associated
ing and sterilizing intraocular surgical instruments have been with an inadequately sterilized critical item is exceedingly rare
published (69). (74-76). This is likely due to the wide margin of safety associ-
ated with the sterilization processes used in healthcare facilities.
The concept of what constitutes "sterile" is measured as a prob-
DISINFECTION
ability of sterility for each item to be sterilized. This probability
A great number of disinfectants are used alone or in combi- is commonly referred to as the sterility assurance level (SAL) of
nations (e.g., hydrogen peroxide with peracetic acid) in the the product and is defined as the probability of a single viable
healthcare setting. These include alcohols, chlorine and microorganism occurring on a product after sterilization. SAL
chlorine compounds, formaldehyde, glutaraldehyde, ortho- is normally expressed as w-n. For example, if the probability
phthalaldehyde, hydrogen peroxide (standard), improved of a spore surviving were one in one million, the SAL would
hydrogen peroxide, iodophors, peracetic acid, phenolics, and be w-s (77,78). In short, a SAL is an estimate of lethality of
quaternary ammonium compounds (QUAT). Commercial for- the entire sterilization process and is a conservative calculation.
mulations based on these chemicals are considered unique Dual SALs (e.g., 10-!1 SAL for blood culture tubes, drainage
products and must be registered with the U.S. Environmental bags; 10-6 SAL for scalpels, implants) have been used in the
Protection Agency (EPA) or cleared by the FDA In most in- United States for many years, and the choice of a 10- 6 SAL was
stances, a given product is designed for a specific purpose and strictly arbitrary and not associated with any adverse outcomes
is to be used in a certain manner. Therefore, the label should (e.g., patient infections) (77).
be read carefully to ensure that the right product is selected for Medical devices that have contact with sterile body tissues
the intended use and applied in an efficient manner. or fluids are considered critical items. These items should
Disinfectants are not interchangeable, and an overview of be sterile when used because any microbial contamination
the performance characteristics is provided (Table 20.2), so the could result in disease transmission. Such items include sur-
user has sufficient information to select an appropriate disinfec- gical instruments, biopsy forceps, and implanted medical
tant for any item and use it in the most efficient way. It should devices. If these items are heat resistant, the recommended
be recognized that excessive costs may be attributed to incor- sterilization process is steam sterilization, because it has the
rect concentrations and inappropriate disinfectants. Finally, largest margin of safety due to its reliability, consistency, and
occupational diseases among cleaning personnel have been lethality. However, reprocessing heat- and moisture-sensitive
associated with the use of several disinfectants such as formal- items requires use of a low-temperature sterilization tech-
dehyde, glutaraldehyde, chlorine and others, and precautions nology (e.g., ETO, hydrogen peroxide gas plasma, peracetic
(e.g., gloves, proper ventilation) should be taken to minimize acid) (79). A summary of the advantages and disadvantages
exposure (70-72). Asthma and reactive airway disease may oc- for commonly used sterilization technologies is presented in
cur in sensitized individuals exposed to any airborne chemical Table 20.3.
TABLE 20.3 Summary of Advantages and Disadvantages of Commonly Used Sterilization Teclmologic:s
Sterilization Method Advantages Disadvantages
Steam • Nontoxic to patient, staff, environment • Deleterious for heat-eensitive instruments
• Cycle easy to control and monitor • Microsurgical instruments damaged by repeated
• Rapidly microbicidal exposure
• Least affected by organic/inorganic soils among • May leave instruments wet, causing them to rust
sterilization processes li11ted • Potential for burns
• Rapid cycle time
• Penetrates medical packing, device lumens
Hydrogen Peroxide Gas • Safe for the environment • Cellulose (paper),linens and liquids cannot be
Plasma • Leaves no toxic residuals processed
• Cycle time is ~28 minutes and no aeration necessary • Endoscope or medical device restrictions based on
• Used for heat- and moisture-..ensitive items since pro- lumen internal diameter and length (see manufac-
cess temperature <50°C turer's recommendations)
• Simple to operate, install (208 V outlet), and monitor • Requires synthetic packaging (polypropylene wraps,
• Compatible with most medical devices polyolefin pouches) and special container tray
• Only requires electrical outlet • Hydrogen peroxide may be toxic at levels greater
than 1 ppm TWA
100% Ethylene Oxide • Penetrates packaging materials, device lumens • Requires aeration time to remove ETO residue
(ETO) • Single-dose cartridge and negative-pressure chamber • ETO is toxic, a carcinogen, and flammable
minimizes the potential for gas leak and ETO exposure • ETO emission regulated by states but catalytic cell re-
• Simple to operate and monitor moves 99.9% ofETO and converts it to C02 and H 20
• Compatible with most medical materials • ETO cartridges should be stored in flammable liquid
storage cabinet
• Lengthy cycle/ aeration time
ETO Mixtures • Penetrates medical packaging and many plastics • Some states (e.g., CA. NY, Ml) require ETO emission
8.6% ET0/91.4% HCFC • Compatible with most medical materials reduction of 90%-99.9%
10% ET0/90% HCFC • Cycle easy to control and monitor • CFC (inert gas that eliminates explosion hazard)
8.5% ET0/91.5% C02 banned in 1995
• Potential hazards to staff and patients
• Lengthy cycle/ aeration time
• ETO is toxic, a carcinogen, and flammable
Vaporized hydrogen • Safe for the environment and healthcare worker • Medical devices restrictions based on lumen internal
peroxide • It leaves no toxic residue; no aeration necessary diameter and length-,ee manufacturer's recommen-
• Fast cycle time, 55 minutes dations, e.g., stainless steel lumen 1mm diameter,
• Used for heat and moisture sensitive items (metal 125 mm length
and nonmetal devices) • Not used for liquid, linens, powders, or any cellulose
materials
• Requires synthetic packaging (polypropylene)
• Limited materials compatibility data
• Limited clinical use and comparative microbicidal
efficacy data
Ozone • Used for moisture and heat-sensitive items • Limited clinical use (material compatibility/
• Ozone generated from oxygen and water (nontoxic) penetrability/ organic material resistance?) and
• No aeration needed due to no toxic by-products limited microbicidal efficacy data
• FDA cleared for metal and plastic instruments in-
cluding some instruments with lumens
ETO, ethylene oxide; CFC, chlorofluorocarbon, HCFC, hydrochlorofluorocarbon, TWA, time weighted average.
Modified from Rutala WA, Weber DJ. Sterilization, high-level disinfection, and environmental cleaning. lnftldDis Clin N Am. 2011;25:45-76,
with permission.
Modified from Rutala WA, Weber DJ. Clinical effectiveness oflow-temperature sterilization technologies. lnfer;t Control Hosp Epidemiol.
1998;19:798-804, with permission.
Chapter 20 • Disinfection and Sttriliwtion in Htalthcrm Facilities 30 l
NEW TECHNOLOGIES FOR instrument. "Immedia~use" is defined as the shortest pos-

STERILIZATION AND HIGH-LEVEL sible time between a sterilized item's removal from the steril-
DISINFECTION izer and its aseptic transfer to the sterile field. This implies that
the sterilized item is used during the procedure for which it
HYDROGEN PEROXIDE VAPOR was sterilized and in a manner that minimizes its exposure to
LOW-TEMPBRATURB STERILIZATION air and other environmental contaminants. The same critical
reprocessing steps (such as cleaning, decontamination, rinsing,
A new low-temperature sterilization system (V-Pro) uses va- and aseptic transfer from the sterilizer to the point of use) must
porized hydrogen peroxide to sterilize reusable metal and be followed. Immediate-use steam sterilization should not be
nonmetal devices used in healthcare facilities. The system is used for convenience, as an alternative to purchasing sufficient
compatible with a wide range of medical instruments and ma- instrument sets, or as a time saver (82,83).
terials (e.g., polypropylene, brass, polyethylene). There are
no toxic by-products, as only water vapor and oxygen are prC>-
AUTOMATED ENDOSCOPE REPROCESSORS
duced. The system is not intended to process liquids, linens,
powders, or any cellulose materials. The system can sterilize The potential for transmission of pathogens during endoscopy
instruments with diffusion-restricted spaces (e.g., scissors) remains a concern for healthcare workers and patients (84).
and medical devices with single stainless steel lumen based on Automated endoscope reprocessors (AERs) offer many poten-
lumen internal diameter and length (e.g., an inside diameter tial advantages (e.g., automate and standardize reprocessing
of 1 mm or larger and a length of 125 mm or shorter; see man- steps; reduce personnel exposure to chemicals; provide sig-
ufacturer's recommendations). Thus, gastrointestinal (GI) nificant microbial reduction (85), remove established biofilms
endoscopes and bronchoscopes cannot be sterilized in this and retards biofilm generation (86), and filter tap water) but
system at the current time. Although this system has not been some disadvantages (e.g., may not eliminate cleaning; failure
comparatively evaluated with other sterilization processes, va- has been linked to poorly designed AERs) (8,87). It is critical
porized hydrogen peroxide has been shown to be effective that correct connectors between the AER and the device are
in killing spores, viruses, mycobacteria fungi, and bacteria established to ensure complete flow of disinfectants and rinse
(Technical Data Monograph, Steris, 2008). Table 20.3 lists the water (88,89).
advantages and disadvantages of this and other processes. A variety of capabilities has been incorporated into the avail-
able AERs, and these capabilities have been summarized (90).
OZONE STERILIZATION All models have disinfection and rinsing cycles, and some have
detergent cleaning, alcohol flush, and/ or extended forced-air-
Ozone has been used for years as a drinking water disinfectant. drying cycles. Additional features may include: variable cycle
Ozone is produced when 0 2 is energized and split into 2 mona- times; printed documentation of the process; low-intensity ul-
tomic (0 1) molecules. The monatomic oxygen molecules then trasound waves; high-level disinfectant vapor recovery systems;
collide with 0 2 molecules to form ozone, which is 0 5. Thus, heating to optimize the high-level disinfectants efficacy; a vari-
ozone consists of 0 2 with a loosely bonded third oxygen atom able number of endoscopes processed per cycle; automated
that is readily available to attach to, and oxidize, other mol- leak testing; automated detection of channel obstructions; and
ecules. This additional oxygen atom makes ozone a powerful table top, floor standing, and cart-mounted models.91 Not all
oxidant that destroys microorganisms but is highly unstable reprocessors are compatible with all high-level disinfectants
(i.e., half-life of22 minutes at room temperature). or with endoscopes from all manufacturers. One newer AER
A new sterilization process, which uses ozone as the steril- integrates cleaning and has achieved an FDA-cleared clean-
ant, was cleared by the FDA in August 2003 for processing r~ ing claim (Evo-Tech) (92). The users must continue to do
usable medical devices. The sterilizer creates its own sterilant the "bedside" cleaning (wipe external surfaces and flush each
internally from U.S. Pharmacopea (USP) grade oxygen, steam- lumen with a detergent solution) and then place the scope
quality water, and electricity; the sterilant is converted back directly (within one hour) into the EVC>-Tech machine. This
to oxygen and water vapor at the end of the cycle by passing eliminates the labor-intensive manual cleaning. It also autC>-
through a catalyst before being exhausted into the room. The matically detects leaks, alcohol is flushed through the channels
duration of the sterilization cycle is about 4 hours and 15 min- before cycle completion to promote drying, and the AER inte-
utes, and it occurs at 30° to 35°C. Microbial efficacy has been grates minimum effective concentration (MEC) monitoring. In
demonstrated by achieving a SAL of 1o- 6 with a variety of mi- addition, the printer provides complete monitoring of critical
croorganisms including the most resistant microorganism, Ceo- cycle parameters, including MEC of the high-level disinfectant
bacillus stearothermophilus (80). Table 20.3 lists the advantages (orthC>-phthalaldehyde) , disinfection time, channel blockage
and disadvantages of this and other processes. detection, temperature, pressure, and time to ensure compli-
ance throughout the process. Manufacturer's residual data for
cleaning of the internal channels as well as external insertion
IMMEDIATE-USB STEAM STERILIZATION
tube surfaces were below the limit of <8.5 pg/ cm2.
"Flash" steam sterilization was originally defined by Underwood
and Perkins as sterilization of an unwrapped object at 132°C for
REPROCESSING OF ENDOSCOPES
3 minutes at 27 to 28 lbs. of pressure in a gravity displacement
sterilizer (81). It was intended for instruments when there is Physicians use endoscopes to diagnose and treat numerous
insufficient time to sterilize an item by the preferred package medical disorders. While endoscopes represent a valuable di-
method (e.g., dropped instruments). The term "flash" arose agnostic and therapeutic tool in modern medicine, and the
out of the abbreviated time of exposure of the unwrapped incidence of infection associated with use has been reported
as very low (about 1 in 1.8 million procedures) (93), more at 20°C (4- to 6-log10) (20,28,47). Because of these data, pro-
healthcare-associated outbreaks have been linked to contami- fessional organizations (at least 14 professional organizations
nated endoscopes than to any other medical device (4,5,8,89). worldwide) that have endorsed an endoscope reprocessing
In order to prevent the spread of healthcare-associated infec- guideline recommend contact conditions of 20 minutes at
tions, all heat-«ensitive endoscopes (e.g., gastrointestinal endo- 20°C (or :S20 minutes outside the United States) with 2% glu-
scopes, bronchoscopes, nasopharyngoscopes) must be properly taraldehyde to achieve high-level disinfection that differs from
cleaned and at a minimum subjected to high-level disinfection that of the manufacturer's label (28,103-105). It is important
following each use. High-level disinfection can be expected to to emphasize that the FDA tests do not include cleaning, a criti-
destroy all microorganisms; although when high numbers of cal component of the disinfection process. Therefore, when
bacterial spores are present, a few spores may survive. cleaning has been included in the test methodology, 2% glutar-
Recommendations for the cleaning and disinfection of en- aldehyde for 20 minutes has been demonstrated to be effective
doscopic equipment have been published and should be strictly in eliminating all vegetative bacteria.
followed (20,28,94,95). Unfortunately, audits have shown that
personnel do not adhere to guidelines on reprocessing (96-98),
INACTIVATION OF CREUTZFELDT-JAKOB
and outbreaks of infection continue to occur (99,100). In or-
DISEASE AGENT
der to ensure that reprocessing personnel are properly trained,
there should be initial and annual competency testing for each Creutzfeldt:Jakob disease (CJD) is a degenerative neurologic
individual who is involved in reprocessing endoscopic instru- disorder of humans with an incidence in the United States
ments (20,29,94,101). of approximately 1 case/million population/year (106,107).
In general, endoscope disinfection or sterilization with a CJD is thought to be caused by a proteinaceous infectious
liquid chemical sterilant or high-level disinfectant involves agent or prion. CJD is related to other human transmissible
five steps after leak testing: (a) clean-mechanically clean spongiform encephalopathies (TSEs) that include kuru
intemal and extemal surfaces, including brushing intemal (0 incidence, now eradicated), Gertsmann-Straussler-Sheinker
channels and flushing each intemal channel with water and (GSS) syndrome (1/40 million), and fatal insomnia syndrome
an enzymatic cleaner; (b) disinfect-immerse endoscope in (FFI) (:Sl/40 million). The agents of CJD and other TSEs
high-level disinfectant (or chemical sterilant) and perfuse exhibit an unusual resistance to conventional chemical and
(eliminates air pockets and ensures contact of the germicide physical decontamination methods. Since the CJD agent is
with the intemal channels) disinfectant into all accessible not readily inactivated by conventional disinfection and ster-
channels such as the suction/biopsy channel and air/water ilization procedures and because of the invariably fatal out-
channel, and expose for a time recommended for specific come of CJD, the procedures for disinfection and sterilization
products; (c) rinse-rinse the endoscope and all channels of the CJD prion have been both conservative and controver-
with sterile water, filtered water (commonly used with AERs), sial for many years.
or tap water; (d) dry-rinse the insertion tube and inner The current recommendations consider inactivation data,
channels with alcohol, and dry with forced air after disinfec- but also use epidemiological studies ofprion transmission, in-
tion and before storage; and (e) store-store the endoscope fectivity of human tissues, and efficacy of removing proteins
in a way that prevents recontamination and promotes drying by cleaning (106,108,109). On the basis of scientific data,
(e.g., hung vertically). only critical (e.g., surgical instruments) and semicritical de-
Unfortunately, there is poor compliance with the recom- vices contaminated with high-risk tissue (i.e., brain, spinal
mendations for reprocessing endoscopes which may result in cord, and eye tissue) from high-risk patients (e.g., known
patient exposure to blood-bome pathogens ( 102). In addition, or suspected infection with CJD or other prion disease) re-
there are rare instances where the scientific literature and rec- quire special prion reprocessing. A moist environment post-
ommendations from professional organizations regarding the contamination reduces the attachment of both protein and
use of disinfectants and sterilants may differ from the manu- prion amyloid to the stainless steel surface, so maintain moist
facturer's label claim. One example is the contact time used to conditions (110). For high-risk tissues, high-risk patients, and
achieve high-level disinfection with 2% glutaraldehyde. Based critical or semicritical medical devices, one of the follow-
on FDA requirements (FDA regulates liquid sterilants and ing methods should be used: clean the device and sterilize
high-level disinfectants used on critical and semicritical medi- using a combination of sodium hydroxide and autoclaving
cal devices), manufacturers test the efficacy of their germicide (111) (e.g., immerse in IN NaOH for 1 hour; remove and
formulations under worst-case conditions (i.e., minimum rec- rinse in water, then transfer to an open pan and autoclave
ommended concentration of the active ingredient) and in the [l21°C gravity displacement or 134°C porous or pre-vacuum
presence of organic soil (typically 5% serum). The soil is used sterilizer] for 1 hour); autoclaving at 134°C for 18 minutes
to represent the organic loading to which the device is exposed in a pre-vacuum sterilizer; or 132°C for l hour in a gravity
during actual use and that would remain on the device in the displacement sterilizer (20,106,112). The temperature should
absence of cleaning. These stringent test conditions are de- not exceed 134°C since the effectiveness of autoclaving may
signed to provide a margin of safety by assuring that the con- decline as the temperature is increased (e.g., 136°C, 138°C)
tact conditions for the germicide provide complete elimination (113). Prion-contaminated medical devices that are impos-
of the test bacteria (e.g., 105 to 106 M. tuberculosis in organic sible or difficult to clean should be discarded. Flash steriliza-
soil and dried on a scope) if inoculated into the most difficult tion (i.e., steam sterilization of an unwrapped item at l32°C
areas for the disinfectant to penetrate and in the absence of for 3 minutes) should not be used for reprocessing. To mini-
cleaning. However, the scientific data demonstrate that M. mize environmental contamination, noncritical environmen-
tuberculosis levels can be reduced by at least 8-log10 with clean- tal surfaces should be covered with plastic-backed paper, and
ing ( 4-log10) followed by chemical disinfection for 20 minutes when contaminated with high-risk tissues, the paper should
be properly discarded. Noncritical environmental surfaces commonly used surface disinfectants (123), investigators have
(e.g., laboratory surfaces) contaminated with high-risk tissues recommended the use of dilute solutions of hypochlorite (5,000
should be cleaned and then spot decontaminated with a 1:10 ppm available chlorine) for routine envirorunental disinfection
dilution of hypochlorite solutions (106). of rooms of patients with C. di.fficile-associated diarrhea or colitis
(124), to reduce the incidence of C. di.fficilediarrhea (125), or in
units with high C. difficik rates (126). Stool samples of patients
EMERGING PATHOGENS, ANTIBIOTIC-RESISTANT
with symptomatic C. difficik colitis must contain spores of the
BACTERIA, AND BIOTERRORISM AGENTS
organism since ethanol treatment of the stool is used for isola-
Emerging pathogens are of growing concern to the general tion of C. difficik in the laboratory to reduce the overgrowth by
public and infection control professionals. Relevant pathogens fecal flora (127,128). Mayfield and coworkers showed a marked
include Cryptosporidium parvum, Helicobacter pylori, Escherichia reduction in C. dif.ficile-associated diarrhea rates in the bone
coli 0157:H7, human immunodeficiency virus (HIV), Hepatitis marrow transplant unit (from 8.6 to 3.3 cases per 1,000 patient-
C virus (HCV), rotavirus, multidrug-resistant M. tuhercuWsis, hu- days) during the period of bleach disinfection (1:10 dilution)
man papilloma virus, norovirus, and nontuberculosis mycobac- of envirorunentalsurfuces compared to cleaning with a quater-
teria (e.g., M. chelonae). Similarly, publications have highlighted nary ammonium compound. Recently, Orenstein and cowork-
the concern about the potential for biological terrorism (114). ers showed that daily cleaning with bleach wipes on wards with
The CDC has categorized several agents as ~high priority" be- a high incidence of hospital-acquired C. di.fficile reduced the C.
cause they can be easily disseminated or transmitted person- difficireinfection (CDI) rate by 85% (24.2 to 3.6 per 10,000 pa-
to-person, cause high mortality, and are likely to cause public tient-days) and prolonged the median time between CDI cases
panic and social disruption (115). These agents include Bacillus from 8 to 80 days (129). We now use a chlorine solution (<::5,000
anthracis (anthrax), Yminia pestis (plague), variola maJor (small- ppm chlorine) in all CDI rooms for routine daily and terminal
pox), Jitancisella tularensis (tularemia), filoviruses (Ebola hem- cleaning (formerly used QUAT in patient rooms with sporadic
orrhagic fever, Marburg hemorrhagic fever); and arenaviruses CDI). The chlorine solution is applied one time, covering all
(Lassa [Lassa fever], Junin [Argentine hemorrhagic fever]), surfaces to allow a sufficient wetness for <::1 minute contact
and related viruses (115). time. Chlorine solution normally takes 1 to 3 minutes to dry.
With rare exceptions, the susceptibility of each of these The EPA has registered several disinfectants for use to treat
pathogens to chemical disinfectants/sterilants has been stud- hard nonporous surfaces in healthcare settings contaminated
ied, and all of these pathogens (or surrogate microbes such as with C. difficik spores. Acidified bleach and regular bleach
feline-calicivirus for norovirus, vaccinia for variola (116), and (5,000 ppm chlorine) can inactivate 106 C. difficile spores in
B. atrophaeus [formerly B. subtilis] for B. anthmcis) are suscep- s10 minutes (130). Ortho-phthalaldehyde and <::0.2% per-
tible to currently available chemical disinfectants/sterilants acetic acid (WA Rutala, April 2006, written communication)
( 117). Standard sterilization and disinfection procedures for can also inactivate <::104 C. difficile spores in 10 to 12 minutes
patient-care equipment (as recommended in this paper) are at 20°C (131). Studies have shown that asymptomatic patients
adequate to sterilize or disinfect instruments or devices con- constitute an important reservoir within the healthcare facility
taminated with blood or other body fluids from persons in- and that person-to-person transmission is the principal means
fected with blood-borne pathogens, emerging pathogens, and of transmission between patients. Thus, handwashing/hand
bioterrorism agents, with the exception ofprions (see above). hygiene, barrier precautions, and meticulous environmental
No changes in procedures for cleaning, disinfecting, or steril- cleaning with an EPA-registered disinfectant with a sporicidal
izing need to be made (20). claim against C. difficik should be effective in preventing the
In addition, there are no data to show that antibiotic- spread of the organism (132).
resistant bacteria (methicillin-resistant StaphylDcoccus aureus Contaminated medical devices such as colonoscopes and
[MRSA], vancomycin-resistant Enterococcus [VRE], multidrug- thermometers (133) could serve as vehicles for the transmis-
resistant M. tuhercuWsis) are less sensitive to the liquid chemical sion of C. difficik spores. For this reason, investigators have
germicides than antibiotic-sensitive bacteria at currently used studied commonly used disinfectants and exposure times, to
germicide contact conditions and concentrations (118,119). assess whether current practices may be placing patients at
risk. Data demonstrate that 2% glutaraldehyde (134-137) and
peracetic acid (131 ,137) reliably kills C. difficile spores using
CURRENT ISSUES IN WW-LEVEL exposure times of 5 to 20 minutes. Sodium dichloroisocy-
DISINFECTION AND ENVIRONMENTAL anurate at a concentration of 1,000 ppm available chlorine,
achieved lower log10 reduction factors against C. difficik
CLEANING
spores at 10 minutes, ranging from 0. 7 to 1.5, than 0.26% per-
acetic acid with log 10 reduction factors ranging from 2.7 to
INACTIVATION OF CWSTR.IDIUM DIFFICILE
6.0 (131).
The source of healthcare associated acquisition of C. difficik in
nonepidemic settings has not been determined. The environ-
IMPROVED HYDROGEN PEROXIDE
ment and carriage on the hands of healthcare personnel have
been considered as possible sources of infection (120,121). An improved hydrogen peroxide-based technology has been
Carpeted rooms occupied by a patient with C. di.f.ficik are more introduced into healthcare for disinfection of noncritical
heavily contaminated with C. difficile than noncarpeted rooms environmental surfaces and patient equipment (138) and
(122). Since C. di.f.ficik may display increased levels of spore high-level disinfection of semicritical equipment such as en-
production when exposed to non-chlorine-based cleaning doscopes ( 139-141) . Improved hydrogen peroxide (HP) con-
agents and the spores are more resistant than vegetative cells to tains very low levels of anionic and/or nonionic surfactants
in an acidic product which act with HP to produce micro- surfaces impregnated with a metal (e.g., copper), surfaces im-
bicidal activity. This combination of ingredients speeds the pregnated with a germicide (e.g., triclosan), and miscellaneous
antimicrobial activity of hydrogen peroxide and cleaning ef- methods such as altered topography and light-activated antimi-
ficiency (140,141). Improved HP is considered safe for hu- crobial coatings (146).
mans and equipment, and benign for the environment. In
fact, improved HP has the lowest EPA toxicity category (i.e.,
SURFACE DISINFECTION OF NONCRITICAL
category IV) based on its oral, inhalation, and dermal toxic-
ITEMS, CONTACT TIME, WIPES, AND WIPE
ity which means it is practically nontoxic and not an irritant
METHOD
(138,140,142). It is prepared and marketed by several compa-
nies in various concentrations (e.g., 0.5% to 7%) and differ- Surface disinfection of noncritical surfaces and equipment is
ent products may use different terminology for these products normally performed by manually applying a liquid disinfectant
such as "accelerated" or "activated." Lower concentrations to the surface with a cloth, wipe, or mop. Noncritical patient-
(i.e., 0.5%, 1.4%) are designed for the low-level disinfection care equipment is disinfected using an EPA-registered hos-
of noncritical environmental surfaces and patient-care objects pital disinfectant using the label's safety precautions and use
while the higher concentrations (i.e., 2:2% such as Resert) directions (Table 20.1) (18,31,147-156). Most EPA-registered
can be used as high-level disinfectants for semicritical medical hospital disinfectants have a label contact time of 10 minutes.
devices (e.g., endoscopes). However, multiple scientific studies have demonstrated the ef-
A recent study compared the bactericidal activity of a ficacy of hospital disinfectants against pathogens with a con-
QUAT to two new improved HP products. The improved HP tact time of at least 1 minute (18,31,147,150,152-154,157-167).
appeared to be superior or similar to the QUAT tested. When Healthcare facilities should ensure that the frequency for dis-
the two improved HP products were compared with standard infecting noncritical patient-care surfaces be done minimally,
0.5%, 1.4%, and 3% HP formulations, the improved HP-based when visibly soiled, and on a regular basis (such as after use on
environmental surface disinfectants proved to be more effec- each patient, or once daily, or once weekly) (147,168,169). For
tive (>6-log10 reduction) and fast acting (30 to 60 seconds) example, a hospital's policy for reusable blood pressure cuffs
microbicides in the presence of a soil load (to simulate the kept in the patient room could be that they are cleaned when
presence of body fluids) than commercially-available HP. visibly soiled and at discharge, before use for another patient.
Only 30- to 60~econd contact time was studied because longer Similarly, for rolling blood pressure cuffs the policy could be
contact times (e.g., 10 minutes) are not achievable in clinical they are cleaned daily and when visibly soiled, when used on a
practice. It appears, therefore, that the surfactants were able contact precaution patient, and when used on nonintact skin.
to significantly increase the bactericidal activity of HP. Addi- If dedicated, disposable equipment is not available, disinfect
tionally, the improved HP products have an EPA-registered noncritical patient-care equipment after using it on a patient
contact time that is substantially less than most EPA-registered who is on contact precautions before using this equipment on
low-level disinfectants (143). We also have recently shown that another patient (31,156,170,171).
the 1.4% activated hydrogen peroxide is very effective in re- The wipes used for surface disinfection are generally
ducing microbial contamination of hospital privacy curtains cotton, disposable, or microfiber. The wipe should have
(Rutala et al., 2012, unpublished data). In our study, the ac- sufficient wetness to achieve the disinfectant contact time.
tivated hydrogen peroxide completely eliminated contamina- Discontinue the use of the wipe if it no longer leaves the
tion with MRSA and VRE and resulted in a 98.5% reduction surface visibly wet for 2: 1 minute. Other practices to con-
in microbes (only Bacillus spp. recoverable). Thus, at the Uni- sider include: when the wipe is visibly soiled, flip to a clean/
versity of North Carolina (UNC) Health Care, privacy curtains unused side and continue until all sides of the wipe have
are being disinfected at the grab area by spraying the grab been used (or get another wipe); dispose of the wipe/cloth
area of the curtain with activated hydrogen peroxide at dis- wipe appropriately; do not place cleaning cloth back into the
charge cleaning. disinfectant solution after using it to wipe a surface; and do
not dip a used wipe into the clean container of presaturated
wipes. If a disposable wipe is used, ideally it should stay wet,
NEW TECHNOLOGIES FOR SURFACE long enough to meet EPA-registered contact times (e.g., bac-
DISINFECTION teria-l minute). For disposable wipes, the premoistened
wipe should keep the surface area wet for 1 to 2 minutes,
New technologies for reducing bacterial contamination of en- and the surface coverage will depend on the size of the wipe
vironmental surfaces have been offered in the scientific litera- (e.g., 12X 12 in. wipes keep 55.5 sq feet wet for 2 minutes;
ture, but not yet commonly used in healthcare. For example, 6 X 5 in. equipment wipe keeps 6.7 sq feet wet for 2 min-
a portable steam vapor system reduced bacterial levels by 90% utes). The disposable wipe size should be based on use from
and reduced pathogen levels on most surfaces to below the de- small surfaces like a blood pressure cuff to large surfaces like
tection limit (144). A hand-held decontamination technology mattress covers. Additionally, the substrate for the disposable
that utilizes far-ultraviolet radiation (180 to 230 nm) rapidly wipe should be durable so that it does not easily tear or fall
kills C. difficile spores and other healthcare-associated patho- apart, and the top should be kept closed or else the wipes dry
gens on surfaces (4.4 to 6.9log10 reduction in 5 seconds). How- out. Change the reusable cleaning cloths after every room
ever, the presence of organic material reduces the efficacy of and use at least 3 cloths per room; typically 5-7 cloths. Boyce
far UV radiation (145). Additionally, in the past several years, et al. also found that smooth surfaces (e.g., overbed tables)
several methods of reducing contamination of room surfaces were cleaned more thoroughly (as measured by ATP) than
has emerged to produce self-disinfecting surfaces to include rough or irregular surfaces ( 172). If the reusable wipe is not
changed, accumulation of bacteria can occur and increase ROLE OF SURFACES IN PATHOGEN
the chance of cross-contamination. TRANSMISSION
The efficacy of the wipe method has been recently evaluated
There is excellent evidence in the scientific literature that envi-
using C. difftcilespores. The wipe methods (i.e., saturated cloth;
ronmental contamination plays an important role in the trans-
spray [let disinfectant sit for 10 seconds] and wipe; spray, wipe,
mission of several key HAl pathogens including MRSA, VRE,
spray [let disinfectant sit for 1 minute] and wipe; disposable
wipe; spray, wipe, spray, and let air dry), all demonstrated simi-
Acinetobacter, norovirus, and CIJJstridium difficile (13,32,178,179).
All these pathogens have been demonstrated to persist in the en-
lar reductions in C. difftcile spores ( 173).
vironment for hours to days (in some cases months), frequently
An issue that has been receiving repeated attention in the
contaminate the environmental surfaces in rooms of colonized
electronic media is the contact times for disposable wipes
when there are varying times listed for bacteria, fungi, and or infected patients, transiently colonize the hands of healthcare
personnel, be transmitted by healthcare personnel, and cause
Mycobacteria. Some persons have suggested that hospitals
should use the longest kill-time on the product as the required outbreaks in which environmental transmission was deemed to
play a role. Importantly, a recent study by Steifel et al. demon-
wet/contact kill-time (e.g., 5 minutes forM. bovis). The CDC
Guideline for Disinfection and Sterilization in Healthcare strated that contact with the environment was just as likely to con-
taminate the hands of healthcare workers, as was direct contact
Facilities used the time necessary to kill bacteria on surfaces
with the patient (180). Further, admission to a room in which
(i.e., 1 minute), not the kill-time for more difficult to inac-
the previous patient had been colonized or infected with MRSA,
tivate pathogens such as M. tuberculosis (or M. bovis), which
VRE, or C. difficile, has been shown to be a risk factor for the newly
does not have an environmental surface mode of transmis-
admitted patient to develop colonization or infection (181,182).
sion. Since bacteria (with the exception of C. difftcile spores),
to include multidrug-resistant bacteria (e.g., MRSA, VRE),
cause nearly all healthcare-associated infections (HAis), and ADEQUACY OF ROOM CLEANING AND
removal and/ or inactivation of bacteria on surfaces is impor- DISINFECTION USING CHEMICAL GERMICIDES
tant in preventing environmentally-mediated HAis, bacterial
It has long been recommended in the United States that en-
kill-times should dictate the wet/contact kill-times in health-
care facilities. Thus, for the improved hydrogen peroxide vironmental surfaces in patient rooms be cleaned and disin-
fected on a regular basis (e.g., daily, 3 times per week), when
products, the recommended wet/ contact kill-times would be
surfaces are visibly soiled, and following patient discharge (ter-
30 seconds to 1 minute.
minal cleaning) (20). Disinfection is generally performed using
an EPA-registered hospital disinfectant, such as a quaternary
DECONTAMINATION OF BLOOD SPILLS ammonium compound. Recent studies have demonstrated
that adequate environment cleaning is frequently lacking. For
Promptly clean and decontaminate spills of blood and other
potentially infectious materials. Discard blood-contaminated example, Carling and coworkers assessed the thoroughness of
terminal cleaning in the patient's immediate environment in
items in compliance with federal regulations (174). Disinfect
areas contaminated with blood spills using an EPA-registered 23 acute care hospitals (1,119 patient rooms) by using a trans-
parent, easily cleaned, stable solution that fluoresces when ex-
tuberculocidal agent, or a solution of 5.25% to 6.15% sodium
posed to hand-held ultraviolet (UV) light (183) . The overall
hypochlorite (household bleach) diluted between 1:10 and
thoroughness of cleaning, expressed as a percent of surfaces
1:100 with water, or a registered germicide on the EPA Lists
evaluated, was 49% (range for all hospitals, 35% to 81%) . Us-
D and E (i.e., products with specific label claims for HIV or
ing a similar design, Carling and associates assessed the envi-
hepatitis B virus [HBV]) (174-177). For site decontamina-
ronmental cleaning in intensive-care unit rooms in 16 hospitals
tion of spills of blood or other potentially infectious materials
(OPIM), implement the following procedures. Use protective (2,320 objects) and demonstrated that only 57.1% of sites were
cleaned following discharge of the room's occupant (184). A
gloves and other personal protective equipment (PPE) (e.g.,
when sharps are involved use forceps to pick up sharps, and recent study using ATP-bioluminescence assays and aerobic cul-
tures demonstrated that medical equipment frequently had not
discard these items in a puncture-resistant container) to pre-
vent employee exposure. If sodium hypochlorite solutions are been disinfected as per protocol (185).
selected, use a 1:100 dilution (e.g., 1:100 dilution of a 5.25% to
6.15% sodium hypochlorite provides 525 to 615 ppm of avail-
able chlorine) to decontaminate nonporous surfaces after a
IMPROVING ROOM CLEANING AND
small spill (e.g., <10 mL) of either blood or OPIM. If a spill DISINFECTION, AND DEMONSTRATING
involves large amounts (e.g., >10 mL) of blood or OPIM, or THE EFFECTIVENESS OF SURFACE
involves a culture spill in the laboratory, use a 1:10 dilution for DECONTAMINATION IN REDUCING
the first application of hypochlorite solution before cleaning, HEALTHCARE-ASSOCIATED
in order to reduce the risk during the cleaning process in the INFECTIONS
event of a sharp injury. Follow this decontamination process
with a terminal disinfection, using a 1:100 dilution of sodium Investigators have reported that intervention programs aimed
hypochlorite (165,175,177). ffthe spill contains large amounts at environmental services workers resulted in significant im-
of blood or body fluids, clean the visible matter with disposable provement in cleaning practices (68,186). Such interventions
absorbent material, and discard the contaminated materials have generally included multiple activities: improved educa-
in appropriate, labeled containment (26,174). Use protective tion, monitoring the thoroughness of cleaning (e.g., by use of
gloves and other PPE appropriate for this task (26,174). ATP assays or fluorescent dyes) with feedback of performance
to the environmental service workers, and/or use of cleaning than before decontamination. Nerandzic and colleagues
checklists. We have found that assignment of cleaning respon- showed that Tru-D at a reflected dose of 22,000 mWs/cm2
sibility (e.g., medical equipment to be cleaned by nursing; en- for approximately 45 minutes consistently reduced recovery
vironmental surfaces to be cleaned by environmental service) of C. difficik spores and MRSA by >2 to 3 log10 colony form-
is also important to ensure all objects and surfaces are decon- ing units (cfu}/cm2 and ofVRE by >3 to 4log10 CFU/cm2.193
taminated, especially the surfaces of medical equipment (e.g., Thus, there are now three studies that have demonstrated that
cardiac monitors). hnproved environmental cleaning has been this UV-C system is capable of reducing vegetative bacteria in-
demonstrated to reduce the environmental contamination with oculated on a carrier by >3 to 41og10 in 15 to 20 minutes and
VRE (187,188), MRSA (188), and C. difficik (189). Importantly, C. difficik by > 1.7 to 4-log10 in 35 to 100 minutes. The studies
no study has reported in the postintervention period, proper also demonstrate reduced effectiveness when surfaces were not
cleaning of more than 85% of objects. Further, all studies have in direct line-of-sight (191-193).
only focused improvement on a limited number of "high-risk"
objects. Thus, a concern of published studies is that they have
HYDROGEN PEROXIDE (HP) SYSTEMS
only demonstrated improved cleaning of a limited number of
FOR ROOM DECONTAMINATION
"high-risk" objects (or "targeted" objects) not an improvement
in the overall thoroughness of room decontamination. Several systems which produce hydrogen peroxide (e.g., HP va-
por, aerosolized dry mist HP, vaporized HP) have been studied
for their ability to decontaminate environmental surfaces and
"NO-TOUCH" METHODS FOR ROOM
o~ects in hospital rooms. Hydrogen peroxide vapor (HPV)
DECONTAMINATION
has been used increasingly for the decontamination of rooms
As noted above, multiple studies have demonstrated that en- in healthcare (194-203). These investigators found that HP
vironmental surfaces and objects in rooms are frequently not systems are a highly effective method for eradicating various
properly cleaned, and these surfaces may be important in trans- pathogens (e.g., MRSA, M. tuberculosis, Serratia spp. C. difficile
mission of HAI pathogens. Further, while interventions aimed spores, C. botulinum spores) from rooms, furniture, and equip-
at improving cleaning, thoroughness have demonstrated ef- ment. Importantly, using a before-after design, Boyce and co-
fectiveness, many surfaces remain inadequately cleaned and workers have shown that use of the HP systems was associated
therefore potentially contaminated. For this reason, several with a significant reduction in the incidence of C. difficik infec-
manufacturers have developed room disinfection units that can tion on five high-incidence wards ( 194).
decontaminate environmental surfaces and objects. These sys-
tems use one of two methods; either ultraviolen t light or hydro-
COMPARISON OF UV IRRADIATION
gen peroxide (13). These technologies supplement, but do not
VERSUS HYDROGEN PEROXIDE FOR
replace, standard cleaning and disinfection because surfaces
ROOM DECONTAMINATION
must be physically cleaned of dirt and debris.
The UV-C system studied and the systems which use hydro-
gen peroxide have their own advantages and disadvantages
ULTRAVIOLET LIGHT FOR ROOM
(Table 20.4), and there is now ample evidence that these "no-
DECONTAMINATION
touch" systems can reduce environmental contamination with
UV irradiation has been used for the control of pathogenic HAI pathogens. However, each specific system should be stud-
microorganisms in a variety of applications, such as control of ied and its efficacy demonstrated before being introduced into
legionellosis, as well as disinfection of air, surfaces, and instru- healthcare facilities. The main advantage of both units is their
ments (10,190). At certain wavelengths, UV light will break the ability to achieve substantial reductions in vegetative bacteria.
molecular bonds in DNA, thereby destroying the organism. As noted above, manual cleaning has been demonstrated to be
UV-C has a characteristic wavelength of 200 to 270 nm (e.g., suboptimal, as many environmental surfaces are not cleaned.
254 nm), which lies in the germicidal active portion of the elec- Another advantage is their ability to substantially reduce C. dif-
tromagnetic spectrum of 200 to 320 run. The efficacy of UV ficile, as low-level disinfectants (such as QUAT) have only lim-
irradiation is a function of many different parameters such as ited or no measurable activity against spor~forming bacteria
intensity, exposure time, lamp placement, and air movement (10). Both systems are residual free and they decontaminate all
patterns. exposed surfaces and equipment in the room.
An automated mobile UV-C unit (Tru-D, Lumalier Corpora- The major disadvantages of both decontamination systems
tion) has been shown to eliminate >3-log10 vegetative bacteria are the substantial capital equipment costs, the need to remove
(MRSA, VRE, Acinetobacterbaumanniz) and >2.4-log10 C. difftcik personnel and patients from the room thus limiting their use to
seeded onto formica surfaces in patients' rooms experimentally terminal room disinfection (must prevent/minimize exposure
contaminated (191). Boyce and colleagues report the results to UV and HP) , the staff time needed to transport the system to
of assessing the effectiveness of the same UV-C unit (Tru-D) to rooms to be decontaminated and monitor its use, the need to
reduce environmental contamination with vegetative bacteria physically clean the room of dust and debris, and the sensi-
(measured using aerobic colony counts) and C. difficik inocu- tivity to use parameters. There are several important differ-
lated onto stainless steel carrier disks (192). Room decontami- ences between the two systems. The UV-C system offers faster
nation with the UV system resulted in significant reductions in decontamination which reduces the "down" time of the room
aerobic bacteria on 5 high-touch surfaces. Mean C. difficilelog10 before another patient can be admitted. The HP systems have
reductions ranged from 1.8 to 2.9 using cycle times of 34.2 to been demonstrated to be more effective in eliminating spore-
100.1 minutes. Surfaces in direct line-of-sight were significantly forming organisms. Whether this improved sporicidal activity
more likely to yield negative cultures after UV decontamination is clinically important is unclear as studies have demonstrated
TABLE 20.4 Advantages and Disadvantages of Room Decontamination by Ultraviolet (UV)

Irradiation and Hydrogen Pcro:dde (HP)
Ultraviolet Irradiation
ADVANTAGES
• Reliable biocidal activity against a wide range of healthcare-associated infection pathogens
• Room surfaces and equipment decontaminated
• Room decontamination is rapid (-15 minutes) for vegetative bacteria
• Effective against Clostridium difficik, although requires longer exposure (-50 minutes)
• HVAC system does not need to be disabled and the room does not need to be sealed
• UV is residual free and does not give rise to health or safety concerns
• No consumable products so costs include only capital equipment and staff time
• Good distribution in the room of UV energy via an automated monitoring system
DISADVANTAGES
• All patients and staff must be removed from the room before decontamination
• Decontamination can only be accomplished at terminal disinfection (i.e., cannot be used for daily disinfection) as room must be emptied of
people
• Capital equipment costs are substantial
• Does not remove dust and stains which are important to patients and visitors, and hence cleaning must precede UV decontamination
• Sensitive to use parameters (e.g., wavelength, UV dose delivered)
• Requires that equipment and furniture be moved away from the walls
• Studies have not been conducted to demonstrate whether use of UV room decontamination decreases the incidence of healthcare-associ-
ated infections
Decontamination by Hydrogen Peroxide Systems

ADVANTAGES
• Reliable biocidal activity against a wide range of healthcare-associated pathogens
• Room surfaces and equipment decontaminated
• Effective against Clostridium difficik
• Useful for disinfecting complex equipment and furniture
• Does not require that furniture and equipment be moved away from the walls
• HP is residual free and does not give rise to health or safety concerns (aeration unit converts HP into oxygen and water)
• Uniform distribution in the room via an automated dispersal system
• Demonstrated to reduce healthcare-associated infections (i.e., Closlridium difficile)
DISADVANTAGES
• All patients and staff must be removed from the room prior to decontamination
• HVAC (heating, ventilation and air conditioning) system must be disabled to prevent unwanted dilution of HP during use and the doors
must be closed with gaps sealed by tape
• Decontamination can only be accomplished as terminal disinfection (i.e., cannot be used for daily disinfection) as room must be emptied of
people
• Capital equipment costs are substantial
• Decontamination requires -2.0-5 hours
• Does not remove dust and stains which are important to patients and visitors, and hence cleaning must precede UV decontamination
• Sensitive to use parameters (e.g., HP concentration)
that although enviromnental contamination is common in the intended we of the medical device: critical items (contact ster-
rooms of patients with C. difftcile infection, the level of contami- ile tissue) must be sterilized before use; semicritical items (con-
nation is relatively low (also true for MRSA and VRE). Finally, tact mucous membranes or nonintact skin) must be high-level
the HP system was demonstrated to reduce C. difftcik incidence disinfected; and noncritical items (contact intact skin) should
in a clinical study, while similar studies with the UY.C system receive low-level disinfection. Cleaning should always precede
have not been published. If additional studies continue to dem- high-level disinfection and sterilization. Current disinfection
onstrate a benefit, then widespread adoption of these technol- and sterilization guidelines must be strictly followed.
ogies should be considered for terminal room disinfection in Since semicritical equipment has been associated with re-
healthcare facilities. processing errors that result in patient look-back and patient
notifications, it is essential that control measures be instituted
to prevent patient exposures (102). Before new equipment (es-
CONCLUSIONS pecially semicritical equipment as the margin of safety is less
than that for sterilization) (77) is wed for patient-care on more
When properly wed, disinfection and sterilization can en- than one patient, reprocessing procedures for that equipment
sure the safe use of invasive and noninvasive medical devices. should be developed. Staff should receive training on the safe
The method of disinfection and sterilization depends on the we and reprocessing of the equipment and be competency
308 Section II • .Functional Anas of Concern
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annually in all clinical areas that reprocess semicritical devices 1962;85:61Hl8.
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1997:491-514-
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164. Reoni.ck. L, Veren K, Salahuddin SZ, et al. Stability and inactivation of IITLV'ill/IAV 196. Bartell MD, Kriotofferoon K, Slotsl!jerg T, et aL Environmental methicillin...etiotaDt Sta{IA-
under clinical and laboratoryenvironmento.JMIA. 1986;255:1887-1891. y~DaJt:t:tu""""" (MRSA) dioiDfection usiDtl dry-mist-generated hydrogen pero:ride. J Hasp
165. Weber DJ, Barl>ee SL, Sohley MD, et al. The effect of blood on the antivinl activity of Infra. 2008;70:35-41 .
aodiwn byp<n:hlorite, a pheuolic, 311d a quaternary anunouiwtl «:otD.poWld. Infca Ctmtrol 197. HallL, OttcrJA, ChcwinoJ, Wengenack NL. Ute of~ pem:ride.aporfordeactiva-
HaspEpidmoiol.1999;20:821-4!27. tion of M~ ~is in a bio1ogicaloafetycabinetandamom.JCiinMicm6iol.
166. Rice EW, Clarlr. RM,Johnoon CH. Chlorine inacti.ation of &domt:hiG wli0157:H7. E~ 2007;45:81~15.
Infld/Jil.1999;5:461-46ll. 198. Hardy Ig, Goooain S, Henderoon N, et al. Rapid recontamination with MRSA of the envi-
167. Anderson RL, Carr JH, Boud WW, et al. SIIICeptibiliq- of vancomycin-resistant CDtero- ronment of ;w. intensive care unit after decontmniuati.ou with hydrogen peroxide vapour.
cocci to environmental diJinfectants. Inftd ConlrolHaspFJJM-id.. 1997;18:195-199. I Hasp Infra. 2007;66:!160-l168.
168. Aylilfe GA., Collin• BJ, Lowbury EJ, et al. Ward floors md other ourface1 "" re&enoinl of 199. Johnoton MD, Lawoon S, OtterJA. Evaluation of hydrogen pero:ride vapour ao a method
hotpital inf..:tion.J HJg. 1967;65:51.!>-5!6. for the decontamination of ourfaceo contaminated with Cl<mridi""' botuliro""' IJ>Ore>.
169. Palmer PH, Yeoman DM. A rtudy to .....,.. the value of dioinfectanu when 'W31bing ward J Mil:robtol Mllltods. 2005;60:40!1-411.
floon. Mod] AwL 1972;2:12ll7-12ll9. 200. Heckert RA, &ot M, Jordan LT, et al. Ef1icacy of vaporized hydrogen pero:ride against
170. Centers for Discue Control and p...,...,..tion. Preventing the &pread of vancomycin rem. emtic animal viruoes. ApplE-..o Mil:robtol. 1997;63(10) :3911>-3918.
tanc...-eport from the Hoopitallnfection Control Practice• Advisory Committee. Fed Rig. 201. !Oapeo NA, Veolcy D. Vapor-phaoc hydrogen pero:ride u a 1urlioA:e dccontaminant and
1994:2575&-25763. 1terilant. ApplE-..oMil:robtol. 1990;56:50!1-506.
171. Boyce JM, Pottcr-Bynoe G, Cheueout C, et al. Euvi.ronmental contamiDatiou due to 202. Bateo CJ, Pcanc R. Uoe of hydrogen pem:ridevapourfor enviromtlental control during a
metlticillin-retiotant Stt>pllj/tu;occvs - . po11ible infection control implicationo. Infra Sonulta outbreak in a neonatal intenlive care unit. j Hasp Infra. 2005;61 :364-366.
Conlrol HaspEpidmoiol. 1997;18:622~7. 203. Shapcy S, Machin K, Levi K, et al. Activiq- of a dry mist hydrogen peroxide 'l"tem againat
I 7!. !Ioyce JM, Havill NL, Lipka A, et al Variation• in hospital daily cleaning practice~. Irofra euvi.ronmental C/DJtrid;..,. diffi<ill contamination in elderly care warda. j Hasp In.focl.
Conlrol HaspEpidmoiol. 2010;31 (1):99-101. 2008;70:136-141.
Syed A. Sattar and Susan Springthorpe
Foodborne Disease Prevention

in Healthcare Facilities
BACKGROUND number of episodes of foodborne illness is nearly 11 million
(11); while comprehensive figures on the economic burden to
Healthcare facilities include a wide range of locations of vary- the nation are not available, episodes of acute gastroenteritis
ing size~ and complexities where one goes to receive health- alone are estimated to cost Can $3.4 million per year (12).
care. The time spent in such facilities may vary from a 'day-ttay' •New" pathogens are being continually incriminated in
to long-term re.Jidency. Similarly, the food providers there may foodbome illnesses (13,14), while increasing drug resistance is
range from large institutional caterel'll to small independents, seriously undermining our ability to deal with many common
with the food and beverages consumed also varying widely in and previously treatable foodbome pathogens (15). These fac.
type and nutritional quality. Further, regional trends influenc· ton together are catalyzing m~or national (16,17,18) and in·
ing food quality and safety are the food source (locally-grown ternational (19) efforts to effectively deal with the mounting
vs. remotely-sourced) and the time and conditions af storage/ issneJ of food safety.
handling in t:ramit. Increasing amounts and varieties af food in North America
Foodborne infections and intoxications are acute or long· are being imported with the attendant difficultie~ af quality
term illnesses arising from the ingestion of come~tibles con- control at origin and during packaging, storage, and transport.
taminated with pathogenic microbes or their toxins. Shellfi.sh, For example, nearly 15% of the total food supply in the U.S.
for example, accumulate enteric pathogens while feeding, and comes from nonindigenous sources, with 75% of the seafood
&uit and vegetables can acquire ruch pathogens at source from coming from abroad (20). The recently promulgated Food
fecally-polluted soil or water. In addition, contaminated bands Safety Modernization Act (FSMA) gives the U.S. Food and
of foodbandlel'll, equipment and environmental surfaces in Drug Administration (FDA) extra powers, including on-site in-
food preparation areas, as well as insects and vermin, can be spections, to verify that foreign suppliers abide by safety systems
sources of microbial contamination of food. Eating contami- to qualify as e:xportel'll of food items to the United States. Simi-
nated food raw or after improper cookmg and/or storage can larly, the Safe Food for Canadians Act [2012] now authorizes
cause infections, or the harmful microbe, on them also can the Canadian government to ensure greater food safety and
readily cross-contaminate other articles af food during han- imposition of severe fines in case of violations.
dling and processing. While everyone is at risk, the very young, Even though food can spread harmful chemicals, natura.l..t}"-
the elderly, the immunocompromised, and pregnant women occurring toxins as well as worms (17,18,21), tl'WJ chapter fo.
are more vulnerable to foodborne illnesses; tl'WJ is especially ewes entirely on foodborne infectious agents and their toxins
relevant to the safety of food in healthcare settings (1,2). with particular reference to North America (Table 21.1).
In today's world, food safety as a whole presentJJ unprec-
edented problems due to globalization af trade in food (3),
population increase~ and over-crowding, changing demo- FOOD IN HHALTHCARE SETTINGS
graphics and life-expectancy, enhanced urbanization, change~
in lifestyles and eating habits, evennore frequent and faster There are many parallels between food services in healthcare
international travel (4,5), climate change (6,7) and a higher facilities and those of restaurants and catering firms, but with
potential for deliberate or accidental contamination (8). The added complexities. Food services in large healthcare establish-
trend towards co.st-cutting and providing food to multiple in- ments typically operate 12 to 18 hours daily, 7 days a week. Like
stitutions on a regional basis abo can lead to extended periods large restaurants, ruch institutions purchase and rapidly pro-
af storage and transportation, further exacerbating risks from cess quantities offood that require enormous working sutfaces,
any problem items. numerous different utensils and pieces of equipment, and
Globally, food- and waterborne (the World Health Organi- many working hands. They also must adhere to tight schedules,
zation (WHO) cla.s.sifie~ ~ter" as "food") diarrheal diseases rapidly preparing and storing a wide variety of foods. Unlike
alone are estimated to kill 2.2 million persons annually (9). restaurants, food services in bealthcare facilities also must deal
Even in industrialized nations such as the United States no less with a much wider assortment of special diets, including en-
than 48 million indigenously acquired episode~ of foodbome teral feedings. Such special meals and supplemental feedings
infection are recorded annually, re~ulting in an economic bur- may come from a central facility or, in some cases, from ward-
den of$50 to $'18 billion (10). In Canada, the estimated annual based kitchens. Delays in the transport of meals and/ or their
3ll
~ ., ~~·:I! IJ ~- Listing of Common Foodbomc Pathogens in the United States and Canada and Their Basic Characteristics I
Class of Incubation Food Items Com-
Pathogen Species or 'I)'pe Basic Biology Period Clinical Picture monly Involved Comment.
BACTERIA,. Bacillus cemLS Aerobe; gram- 30 minutes-15 Diarrhea, abdominal cramps, Meau, milk, vegetables, This organism can cause emetic toxemia with diar-
positive, spore- hours vomiting due to toxemia fl.sh, rice, potatoes, and mea when food with preformed toxin is ingested. It
forming bacillw from heat~table toxin pro- cheese can also cause an infection upon ingestion of a large
duced in improperly stored number of the bacteria which can multiply in the gut
food containing the spores and then produce the toxin. Psychrotrophic strains,
which can multiply under refrigeration, may end up
in powered mill and then grow to hannfull.evcls in
infant formulae stored improperly
Campywbacter Microaerophile; 2-5 days Nausea, abdominal cramps, Poultry and poultry Relatively sensitive to heat and drying.
(C. jejuni causes gram-negative, diarrhea, and vomiting producu, unpasteurized Tirird leading cause of domestically-acquired
nearly 80% of motile, spirals milk and cheeses made bacterial foodborne illness in the U.S. with about
campylobacteriosis from it. Eggs, poultry, 900,000 cases/year. A one-third drop in the num-
cases in humans) raw beef, cake icing her of cases in the past decade due to better food
quality and consumer awareness. Guillain-Barre
syndrome and miscarriage are rare complications.
Those with HIVI AIDS have a 40-fold higher risk
of infection
HeliaJbacter pylmi Microaerophile; 3-7 days Epigastric pain, nausea, and Common as a part of the normal gut flora. Known
gram-negative vomiting to cause peptic ulcers and also gastric carcinoma.
bacillus However, potential for foodborne spread remains
ill-defined
Clostridium Anaerobe; gram- 12-36hours Nausea, vomiting, diarrhea, Low-acid canned foods, Much less common due to better methods of
botulinum positive, spore- fatigue, dry mouth, double- meau, sausage, fish canning food
forming bacillw vision, paralysis, respiratory
failure from toxemia due to a
heat-labile neurotoxin toxin
Clostridium Anaerobe; gram- 8-22 hours Abdominal cramps, diar- Undercooked meau Can also cause wound infections and gas
perftingms positive, spore- rhea, and dehydration due and gravies gangrene
forming bacillus to toxemia from a heat-labile
enterotoxin
Pathogenic Facultative anaer- 8 hours-4 days The pathogenic types cause Ground beef, raw milk There is an ever-widening spectrum of pathogenic
Escherichia coli obe; gram-nega- damage via heat-labile and E. coli often involved in serious cases of food- and
(enterotoxigenic, tive bacillus heat-resistant toxins, Anemia, waterborne infections. A recent example is that
enteroinvasive, hemorrhagic colitis, hemo- of serotype 01 04:H4 which cawed a significant
enteropathogenic, lytic uremic syndrome with foodbome outbreak. in Germany. Some of the
enterohemor- kidney failure due to strains strains are associated with traveler's diarrhea.
rhagic, enteroag- such as 0157:H7 These agents are also classical examples of how
gregative,and these foodbome infections could lead to long-
diffusely adherent) term damage such as kidney failure
Li.Jterill Facultative 2-3weeks Meningitis, septicemia, Raw vegetables, milk, Can grow in refrigerated food. Pregnant women,
IIIMIOt)l~ anaerobe; gram- miscarriage cheese, meat, seafood the aged, and immuno-compromised are at much
positive bacillus higher risk of infection with severe outcomes
Salmonella (several Facultative 12-72 hours Nausea, diarrhea, abdominal Meat, poultry, egg or Over a million cases of domesticall)""'lcquired non-
typhoidal and non- anaerobe; gram- pain, fever, headache, chills, milk products typhoidal salmonellosis annually in the U.S.
typhoidal species) negative bacilli prostration Mortality rate as high as 4% in outbreaks in vul-
nerable populations
Staphylococcus Facultative 1-6 hours Severe vomiting, diarrhea, Custard- or cream-filled A common type of foodborne intoxication. In the
au1l!US anaerobe; gram- abdominal cramps due to baled goods, ham, poul- U.S., about 250,000 cases and 6 deaths occur each
positive coccus heat-stable enterotoxin from try, dressings, gravy, eggs, year
certain strains potato salad, creamy
sauces, sandwich spreads
Shigella (S. sonnei, Facultative anaer- 12hours-3days Abdominal pain and severe Fresh raw vegetables, Highly infectious toxin-producers. Humans be-
S. boydii, S. .J1mmeti, obe; non-motile, cramps, fever, vomiting, dairy products, and lieved to be only hosts.
and S. dystmtlit"i&) gram-negative diarrhea with blood/mucus poultry Rare sequelae include mucosal ulceration, rectal
bacillus in stool bleeding, reactive arthritis, and hemolytic uremic
syndrome. In the U.S., of the annual 375,000,
31% may be foodborne
VWrio cJwlerae 6 hours-3 days Enterotoxin causes severe Shellfish, crab, lobster, Case-fatality rate of up to 50% if left untreated.
diarrhea (rice-water stools) shrimp, squid, and Once a major enteric pathogen, it is now rare in
and occasional vomiting with ftnfl.sh the U.S. and Canada with less than 100 foodborne
potentially fatal dehydration cases annually in the U.S. However, millions of
cases of cholera occur each year in developing
countries even today and point to the high risk of
importations via infected humans and imported
food
VWrio ( V. paraho#- Facultative 4 hours-4 days Abdominal cramps, chills, Fish and shellfish V. paruhoemolyticw and V. w.ln.ijicware halophiles
molyticus and anaerobe; gram- nausea, vomiting, fever, and (salt-loving), and can infect open wounds exposed to
v. vulnijicv.s) negative, curved bloody diarrhea sea water or after injuries from processing sea food.
rods Excrete toxins in infected In the U.S. about45,000 cases of V. paroh.aemoljti-
fish and shellfish cw inrection are reported each year, 86% of them
foodbome.
V. wJnifit;us infections may be more severe but are
rare in the U.S. and Canada
Yer:tinia Facultative anaer- 1 day-2weeks High fever, stomach pain, Meats (pork, beef, Can grow in refrigerated food.
tmterocolitica and obe; gram-nega- diarrhea (stools may have lamb, etc.), oysters, fish, Rare sequelae include reactive arthritis. May be
Y. psew.Urtuberrulosis tive bacillus blood), and vomiting crabs, and raw milk misdiagnosed as appendicitis
Brucella oborlw Microaerophile; 3weeks or Intermittent fever, chills, Raw milk and soft Highly contagious intracellular parasites of white
gram-negative longer sweating, weakness, malaise, cheeses made from blood cells. Apart from catde, free-roaming elk
bacillus headache, joint/muscle pain unpasteurized milk and bison can also be hosts. Complications include
endocarditis and myocarditis. Apart from inges-
tion, exposure can occur via aerosols and broken
skin. Roughly 800 cases offoodborne infection in
the U.S. per year. Vaccination of animals has drasti-
cally reduced risk of infection to humans
(continued)
....
Clo)
~
~ ., ~~·:I! IJ ~- Listing of Common Foodbomc Pathogens in the United States and Canada and Their Basic Characteristics (CtJ•ri•uutl) I
Class of Incubation Food Items Com-
Pathogen Species or Type Basic Biology Period Clinical Picture monly IDvolved Comments
CTOI'Illbac1er (for- Facultative 1 day to Poor feeding re!ponse, ir- Mainly powdered baby It can survive well in dried foods, such as pow-
merly Enterobac- anaerobe; gram- 3weeb ritability, jaundice, grunting formulae. dered infant formulae, and can quickly multiply
ter) saluu.aJcii negative, motile respirations, fluctuating body upon rehydration. Up to 80% of affected new-
bacillus temperature, seizures, brain horns may die from generalized infection; survi-
abscess, hydrocephalus, and vors may be brain-damaged. This otherwise severe
developmental delay infection remains rare in the U.S. and Canada
Framisella tularm.m Facultative 3-6 days Sudden onset of chills, fever, Raw milk, undercook.ed A highly prolific pathogen capable of spreading
("rabbit fever") anaerobe; and headaches with an ulcer meats (e.g., rabbit/ via food, water, air, wounds as well as insect bites.
gram-negative appearing at the site of entry. hares), foods con- Since 1950, the annual number of cases in the
coccobacillus Mild diarrhea to severe bowel taminated with rodent U.S. has dropped from about 900 to <100.
damage. droppings.
VIRUSEs• Hepatitis A Small (-30 nm), 15-45 days Fever, malaise, nausea, ab- Fresh fruit, vegetables, Only one serotype is known. Adults are often sub-
round nonenvel- dominal discomfort leading iced drinks, raw clinically infected. Vaccines now available should
oped capsid with to jaundice shel.lfuh be considered for immunizing food handlers.
a single...tranded,
positive-sense
RNA genome
Norovirus Small (-30 nm), 12-48 hours Nausea, projectile vomiting, Raw oysters/shellfish, Now recognized as the most frequent cause of
round, nonenvel- watery diarrhea, abdominal and ice, salads, frosting food- and waterborne viral acute gastroenteritis.
oped capsid with cramps, and dehydration Tiris virus has the shortest incubation period for
a single-5tranded any known infectious agent. Vaccination against it
RNA genome may soon be possible.
Rotavirus U1rge (-70nm), About 48 hours Nausea, low~ade fever, wa- Fresh vegetables Only about 15,000 of the >3 million annual cases
round, nonenvd- tery diarrhea, vomiting, and in the U.S. are considered foodbome. In young
oped capsid with dehydration children, death may ensue without timely oral or
doublewanded intravenous rehydration. Vaccination of children
RNA, segmented has drastically reduced the health impact from
genome this virus.
Hepatitis E virus Small (-30 nm), 3-Sweeb Nausea, fever, general fa- Raw or undercook.ed Pregnant women are at much higher risk. ofliver
round, nonenvel- tigue, loss of appetite; pain in meat, shellfish, raw failure and a case-fatality rate of as high as 25%.
oped capsid with stomach and joints; enlarged vegetables Pigs may be source of virus for humans. Chronic
a single-~~tranded, liver and jaundice hepatitis may occur in the immunosuppressed.
positive-sense Indigenously-acquired cases of hepatitis E are on
RNA genome the rise in many industrialized countries.
PROTOZOA Cryptosporidium 2-10 days Watery diarrhea, abdomi- Raw or undercooked The oocysts are susceptible to drying and heat-
paroum nal cramps, nausea, loss of vegetables, fruit juices ing, but highly resistant to many disinfectants and
appetite antiseptics.
Giardia lamblia l-2weeks Watery diarrhea, abdomi- Fresh vegetables and The cysts are susceptible to drying and heating,
nal cramps, and lactose fruit but highly resistant to many disinfectants and
intolerance. antiseptics.
T~ofJI,asm4 gondii 5-23 days Symptomless to mild infection Any item of food con- Oocysts in feline feces become infective for hu-
in normal, healthy adults. In- taminated with soil con- mans only after several days of maturation in the
fection in the first trimester of taining viable oocysts. environment.
pregnancy may infect the fetus
and lead to either sti.ll birth or
wrious malformations.
OydospoTa Coccidian proto- 7-10 days Nausea, fatigue, abdominal Fresh vegetables (let- Fecally-sh.ed oocysts require 1-2 weeks of residence
cayetenensis zoan which forms bloating/cramps, protracted, tuce, basil) and fruit in the environment to mature and become infective.
environmentally- relapsing gastroenteritis with (berries). Humans may be only hosts for this species, which
resistant oocysts weight loss was introduced to North America some two decades
ago via berries imported from Central America.
Sporadic ca~es and outbreaks occur in the U.S. and
Canada quite infrequendy.
Entameba hisW- 2--4 weeks In severe ca.se, it causes liver Fresh vegetables and The cysts are susceptible to drying and heat.
Iytica ("amoebic abscess. fruit. While a common infection in the developing
dysentery•) world, it remains quite rare in the U.S. and
Canada.
The table ill based on information from a wriety of sources, including the U.S. Centers for Disease Control and Prevention [2011], U.S. Food and Drug Administration [2012], Health Canada
[2012], World Health Organization [2007], and Lund and Hunter [2008].
"Bacteria such as Aeromonas hydrophila, Plesitmwnas shigriloides and others may also cause foodbome infections but much less frequendy.
IQther enteric viruses such as aden<>-, astro- Aichi-, parvo-, and Sapoviruses and may also cause foodborne infections, but our knowledge on the true extent of their human health impact and
potential for foodbome spread remain limited.
....en
Clo)
316 Section II • FunctionalAreas ofConcem
TABLE 21.2 Factors That May Contribute to Foodbornc Spread of Infections and Intoxications in
Healthc:arc Fadlitics
Facton Related to:
Food items • The proper selection and monitoring of raw food • An enormous and still expanding variety offood
ingredienu is paramount in view of the wide variety items which may originate locally or imported.
of food items as well as the types of meals to be
served several times a day.
• Pathogen contamination at source can readily im- • Complex supply chain makes tracing of
pact many types of meals and may also lead to cross- incriminated/ suspected items difficult.
contamination during in-house meal preparation.
Foodhandlers and servers • Lack of care in the preparation and serving of • Better awareness of the importance of proper
fresh salads and handling of other ready-to-eat handling of meals.
items of food may lead to contamination or • Vaccination against foodbome infections such as
cross-contamination with pathogens. hepatitis A and typhoid.
• Undue delays in serving of meals may permit the
growth of pathogens such as Staphylococcus aureus
and intoxication of the food.
• Asymptomatic viral infections among foodhandlers
and poor hygienic practices.
Facilities • Design and maintenance of food storage, meal

preparation/ serving facilities must exclude patho-
gen contamination and proliferation.
Pathogen • Foodbome pathogens vary widely in their sources,

survivability in foods, minimal infective dose and
the ability to cause secondary cases.
Patients • Many underlying factors can increase the vulner- Malignancy; achlorhydria; advanced age; diabetes;
ability of patienu to foodbome pathogens. AIDS; inflammatory bowel disease; liver cirrhosis
• Iatrogenic factors Chemotherapy; immunosuppression; gastric surgery
• Congenital factors Myeloperoxidase deficiency; Wiskott-Aidrich
syndrome; chronic granulomatous disease;
hyper-IgM; syndromes; leukocyte adhesion
deficiency, Chediak-Higashi syndrome; Severe
• Dietary restrictions combined immunodeficiency
Allergies, food intolerances, personal preferences,
diabetes, therapy, surgery, religion
Visitors • To be discouraged from bringing home-cooked

meals and those purchased ouUide the facility.
• Advised to exercise care in handling of facility-
prepared meals for patients.
inappropriate storage/handling before consumption increase or even force closure of hospitals or parts thereof (26) . It is
the risk of proliferation of foodborne pathogens. also not uncommon for asymptomatic foodhandlers to be the
While the numbers of recorded food borne outbreaks associ- source of foodborne pathogens (27). These factors together
ated with healthcare facilities may represent only about 5% of not only make prevention offoodborne disease a challenge but
the total in the United States (22), food services in healthcare a high priority in healthcare facilities.
settings face many unique challenges (Table 21.2). Therefore,
healthcare facilities require much greater care in forestalling
such illnesses as they must regularly cater to the needs of a FOODBORNE PATHOGENS
more vulnerable clientele. AND VULNERABLE PERSONS
Foods either prepared on-site (23) or brought in from the
outside (24) and served in healthcare facilities may affect pa- Patients in general and, in particular the elderly, the immuno-
tients, personnel, and visitors. suppressed, and those with chronic underlying diseases, are
A patient or staff member suffering from a foodborne infec- more vulnerable to attack by certain classical and opportunis-
tion can pass on the pathogen to others in the vicinity (sec- tic foodborne pathogens and also more likely to develop seri-
ondary spread). Settings with incontinent patients substantially ous sequelae (2,28,29,30). Moreover, a significant number of
increase the risk of secondary cases (25). Outbreaks of acute these patients might be unable to feed themselves, requiring
gastroenteritis, with food as a suspected vehicle, can sometimes additional contact with care-givers and their hands during feed-
be large enough to interfere with the delivery of proper care ing events. The minimal infective dose (MID) of foodborne
Chapter 21 • Foodbom~ Disease Prevention in Healthcare Facilities 317
pathogens also may be lower for such vulnerable individuals. separately and at the right temperature to prevent microbial
Tills enhanced susceptibility is due to a combination of age- contamination and growth.
related physiologic changes (e.g., decreased stomach acidity,
impaired intestinal motility), diminished mucosal, humoral, 1. The food handler. Remember that the food handler any-
and cellular immwtity, and chemo/radiation therapy. where is extremely crucial for food safety. Nowhere is this
Gravely ill patients with a functional digestive tract often are more important than in healthcare facilities. Therefore,
given nutritional enteral solutions. Microbial contamination of provide such staff with the necessary training and retaining
such solutions can cause serious infections, and this requires in safe handling of food (32).
extra care in preparing the solutions as well as in their storage, 2. Since regular monitoring of the health of foodhandlers
handling, and administration. For example, both extrinsically- has yielded equivocal results, encourage such workers to
and intrinsically-contaminated powdered infant formulae have self-report health problems and institute a liberal medical
been incriminated in outbreaks of Dronobacter (formerly, En- leave policy. Ensure that all personnel, regardless of work
terobacter) sakazakii infections in neonates ( 31) . Microbial con- shift, receive prompt training in good food-handling prac-
tamination of enteral feeding solutions may come from their tices; this should be reinforced through periodic in-service
ingredients, many steps needed in the feeding process, and sessions and strategically placed posters and notices in a
the mode and duration of administration; a mix of nutritive simple and direct language relevant to the target staff.
chemicals, and the absence of preservatives also may permit Large staff turnovers should be counteracted by ensuring
ready proliferation of microbes in them on improper handling training before workers commence food preparations and
and storage. by close supervision during early shifts. Attention also must
It also is obvious that contamination of prepared foods can be paid to making the workplace safe for cooks and other
occur due to contaminated vessels and utensils with which the foodhandlers (33).
food is served. Prolonged storage in a prepackaged state also 3. Standard Operating Procedures (SOPs): Develop, and up-
can lead to pathogen proliferation. date as needed, SOPs on all aspects of food handling. Use
the SOPs to train all new staff and also have copies avail-
able on-site for ready reference.
PREVENTION OF FOODBORNE 4. Facility management and infection control committee: Ac-
TRANSMISSION IN HEALTHCARE tive managerial control through development and imple-
FACILITIES mentation of food safety systems is vital to maintaining
on-going quality of all aspects of food service. Therefore,
The WHO, The Joint Commission on Accreditation of Health- encourage the healthcare facility's management and the
care Organizations (1JC), as well as the Association for Profes- infection control committee to communicate directly with
sionals in Infection Control and Epidemiology, Inc. (APIC) foodhandlers at their respective sites to convey the impor-
provide recommendations on safety of food services at hospitals tance of food safety, and recognize the key role they play in
and other healthcare facilities. But, this does not necessarily keeping patients, staff, and visitors safe.
entail regular food service inspections or food-handler train- 5. A management system based on HACCP principles is a
ing. In the United States and in Canada, it is the responsibility comprehensive framework to effectively reduce risk from
of individual states and provinces, respectively, to inspect and foodbome illness (21). This system requires that staff an-
certify healthcare-based food services wtder their jurisdictions. alyze and understand how and when in the food prepa-
A given healthcare facility's infection control committee is ulti- ration chain contamination is most likely to occur and
mately responsible for working together with their food service that special attention is paid to these critical operations.
to minimize the risk from foodbome infections by developing Proper implementation of HACCP would require super-
written policies and procedures and for reviewing these policies visory staff to have full comprehension of the potential
at least annually. risk for the various food preparation steps. Elements of
The adoption of Hazard Analysis and Critical Control Point HACCP have been shown to be effective in food safety for
(HACCP) within the food industry is now widespread though the elderly (34).
its use in catering for healthcare establishments is spotty and 6. Regulations: Consult local as well as state/provincial health
likely to only be present at some larger catering facilities. departments on regulations and standards concerning
food service personnel, food sanitation, and waste disposal
and comply with them.
GENERAL PREVENTIVE MEASURES 7. Food quality and types: Purchase all food supplies from
credible sources with an established record of safety and
The fundamental tenets of food safety are to: (a) ensure that reliability. Do not serve fresh salads to neutropenic patients
all foodhandlers are aware of and properly trained in matters due to higher risk of contamination with opportunistic
of personal hygiene, (b) obtain all food supplies only from pathogens such as Pseudmnrmas aerugino.sa. Do not serve
safe and credible sources, (c) store all such supplies safely and meals that could be potentially contaminated with Listeria
process them using clean utensils, surfaces, and equipment, monocytogrmes to the elderly, pregnant women, and the im-
(d) wash items to be consumed raw as thoroughly as possible in munosuppressed (e.g., HIV patients, transplant patients,
rwtning water to remove any visible dirt/soil, and prevent any or those wtder cancer therapy); such vulnerable individu-
cross-contamination to and from them; dry appropriately where als are 7- to 700-fold more susceptible to this opportunistic
possible, (e) use the appropriate temperature and holding pathogen (29). Do not serve wtpasteurized milk, raw eggs,
time for all items to be cooked, (f) hold raw and cooked items or wtcooked products containing them.
8. Equipment and devices: As far as possible, purchase and as our changing food preferences are continually widening the
use only those pieces of food-contact equipment that can spectrum of foodbome pathogens. In addition to all this, more
be readily disassembled for cleaning and decontamination. and more healthcare facilities now have fust-food concessions
Difficult-to·dean meat slicers, for example, can be sources (39), and also. buy prepared meals from the outside.
of food borne pathogens (35). Therefore, any effective countering of existing and emerg-
9. Exercise particular care in avoiding cross<ontamination of ing threats from foodborne infections in healthcare settings
food during storage, handling, and serving. will require an even greater emphasis on food quality control,
10. Hand hygiene: The oft-repeated message on the impor- better infrastructure for food storage, preparation and distribu-
tance of hand hygiene runs the risk of being ignored when tion, monitoring of food quality, as well as more sophisticated
regarded as a 'nag factor.' Nevertheless, such constant re- and rigorous training of staff together with enhanced checks
minders are nowhere more relevant than in healthcare on their health. These measures must be initiated or reinforced
settings. Train all foodhandlers as well as other healthcare in concert with better food safety training and education of
personnel in proper ways of hand hygiene using handwash other healthcare personnel as well as patients and visitors. Any-
with soap and water and alcohol-based hand-rub agents. one under healthcare is already burdened with numerous is-
Regularly remind all personnel of the importance of hand sues and least expects to be a victim of a foodbome infection.
hygiene to protect themselves and others from foodborne As summarized here, many aspects of foodborne infections
pathogens. Provide suitable, conveniently located, and in general and those in healthcare settings in particular remain
well-stocked handwashing stations throughout the facil- major challenges for public health. However, there are many
ity, and encourage all staff to comply with hand hygiene. changes afoot which bode well for food safety and protection
Provide hand-rub dispensers at strategic locations for hand against foodbome pathogens. Substantial reductions in the
hygiene between hand washings. Ban the use of common number of cases of significant foodbome infections such as
hand-drying cloth towels. Develop and institute a policy salmonellosis (40), and campylobacteriosis (41) have already
on the correct use of gloves in food preparation areas. been achieved through a combination of preventive measures.
Be aware that use of gloves is by no means a substitute for Vaccines are now available against hepatitis A virus ( 42) and
good hand hygiene. one against noroviruses has recently become available ( 43) .
11. Facility design: Design the layout of the entire food- Prophylactic immunization of foodhandlers could substantially
handling facility to optimize one-way flow and to minimize reduce the risk of spread of such common foodborne viruses.
food cross-contamination during food storage and process- Many hospitals have already launched initiatives to improve the
ing by avoiding exposure to aerosols, splashes, drips, in- image and quality of "hospital food", and others are phasing
sects, vermin, and wastewater backflows. out the availability of "fust" and possibly unhealthy meals in
Whenever possible, install water faucets, soap and their premises (44) .
paper towel dispensers, and warm-air hand dryers not re- As noted recently, decision makers often put a greater empha-
quiring contact with washed hands. As much as possible, sis on high-profile medical devices as compared with catering
provide exit doors to washrooms with electronic sensors services in healthcare facilities, in spite of the fact that appe-
or which allow egress without touching knobs or handles. tizing, safe and nutritious meals are as essential for a patient's
This same provision should apply to ingress to and egress recovery and general well-being as proper therapeutic and sur-
from food preparation areas. gical interventions (45). This perspective needs changing.
12. Serving prepared meals: Keep hot food hot and cold food
cold when transporting prepared meals from the site
of preparation to the point of consumption. Minimize ACKNOWLEDGMENT
handling of meals at the site of consumption, and dis-
courage delays between the delivery of the meal and its We thank our colleague Jason Tetro for help in updating the
consumption. literature for this chapter.
13. Pest and vermin control: Have in place a monitoring and
prevention program to eliminate the risk of infestation
from vermin (e.g., rats and mice) and insects (e.g., cock- REFERENCES
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Michael L. W.t.lson and L. Barth Reller
Clinical Laboratory-
Acquired Infections
Clinical laboratories are an area of special concern in hospi· noted the relative risk of infection compared with the general
tal infection control. Laboratory workers may be exposed to population, highlighting that working in a clinical microbiol-
infectious agents during all steps of collection, tr'aiiJJport, pro- ogy laboratory poses a markedly increased relative risk of ac·
cessing, and analysis of patients' specimews. The clinical micro- quiring specific infectiom (9,10).
biology staff, in particular, is at risk of occupational infection, Determining the infectious agents that are the most common
since the clinical specimens submitted for cultures are likely to cause oflaboratoxy-acquired infections is confounded by several
contain infectious agents and the process of isolation and cul- factors. First, although infections with most of these agents are
ture generates large numbers of pathogenic microorganisms. reportable to public health authorities, by their nature it may
The goals of this chapter are to provide an overview of the not be apparent where the infection was acquired. Second,
epidemiology of laboratory-acquired infections, to highlight some of the agents, such as Salt11MU1lla and EscMrichia coli 015'7
those infections of special concern to laboratories, and to make are fairly common in.f'ections; because of this, infection in a
specific recommendations for the prevention and control of laboratory worker could be assumed to be acquired in the com·
laboratory-acquired infectiom. Not discussed in this chap- munity or during an outbreak. Last, infection with agents such
ter are the individual problems of clinical virology, research, as M)cobaalrium tubert:u/o.sis may not rerult in clinical infection at
anatomic pathology, commercial reference laboratories, and the time and the exposure and thus may go undetected.
laboratories involved in the production or processing of large Hilltorically, the most common laboratory-acquired infec-
volumes of pathogenic microorganisms. The reader is referred tiows were brucellosis, Q fever. typhoid fever, hepatitis B, and
to Collins' monograph for an extensive review of the subject tuberculosis (3,4). More recent data show that the infectiows
of laboratory-acquired in.f'ections ( 1). The roles of the clinical now most commonly acquired in clinical laboratories are
microbiology laboratory in infection surveillance, investigation caused by Shigtlla, Brucella, Solmonello, Staph:Jloe6ectls atmW,
of endemic and epidemic hospital infections, and the conttol Neisseria meningitidis, and E coli0157 (9-26).
of healthcare-as.sodated infections (HAls) are discussed in The costs to healthcare l}'ltems that result from laboratory-
Chapters 5, 6, and 9, respectively. acquired infections are uuknawn. In one report (7), each
laboratory-acquired infection resulted in an avezage of 1.2 lost
work days fur hospital-based laboratories and U lost work days
TINCUOENCE,CAUSATIVE for public health laboratories. In addition to lost productivity,
AGENTS, AND COST b.owever, there are the costs of diagnosis, treatment, and screen-
iDg of coworken. Institutions also bear the costJI of investigations
The true incidence of laboratory-acquired infections remains and reporting to regulatory and public health agencies. Accu·
unknown. Early data were derived from surveys, personal com- rate estimates of the cost to healthcare systems are not possible
munications, and literature reports, information that cannot without additional data or further rtudies. The cost to infected
be used to calculate incidence rates (2-5). More recent data individuals can be high; many laboratory-acquired infections are
are derived from surveys, which again cannot be used to cd- caused by pathogens capable of causing serious and/or chronic
culate true incidence rates. One survey (6) did report an an- diseases. Fatal laboratory-acquired infections do continue to be re-
nual incidence of three laboratory-acquired infections per ported (27). Although the incidence of serious or fatal infectiows
1,000 employees, and another (7) reported annual incidences is low compared with other societal risks, these infections can be
of 1.4 and 3.5 per 1,000 employees among workers in hospital- readily prevented or. when they occur, most of them can be treated
based and public health laboratories, respectively. A survey from effectively. The goal should be to decrease the incidence and at-
United Kingdom laboratories during 1994 to 1995 reported an tributable morbidity and mortality of these infectiOWI to zero.
incidence rate of 16.2 infections per 100,000 personi'ears, com-
pared with a rate of 82.7 infections per 100,000 person-years
during 1988 to 1989 (8). Despite the limitations of the pub- SOURCES OF INFECTIONS
lished data, it seems reasonable that the annual incidence of
laboratory-acquired infections is between 1 and 5 per 1,000 em- Pike (2,3) and others (6,7,28,29) have attempted to determine
ployees. Another survey, from the United States, notes that up which laboratory procedures, accidents, or other exposures
to 1/~ of clinical laboratories reported at least one laboratory- to infectious agent! are the source of laboratory-acquired in-
acquired infection during a 3-year period (9). This survey also fections (Table 22.1). These data indicate that the source of
320
Chapter 22 • Clinical Laboratury-Acquired Infections 321
period of time and, under the appropriate environmental

TABLE 22.1 Sources of Laboratory-
conditions, can remain suspended indefinitely. Aerosols with
Acquired Infections in the droplets measuring <5 mm in diameter can be inhaled directly
United States and Abroad into alveoli; those measuring -1 mm are the most likely to be
Proved. or Number of Pen:entage retained within alveoli (35) . Many common laboratory proce-
Probable soun:e Infectioos of Total dures have been shown to produce aerosols in this size range
(36-39). Both M. tuberculosis and nontuberculous Mycobacte-
Working with agent 827 21.1 ria associated with pulmonary infections may be transmitted by
Unknown and other 783 20.0
Known accident 703 17.9 aerosols (40) .
Animal or arthropod 659 16.8 Laboratory personnel have among the highest rates of
Aerosol 522 13.!1 needle-stick injuries in healthcare workers (31,41). Most
Patient's specimen 287 7.!1 needle-stick injuries occur during disposal of used needles,
Human autopsy 75 1.9 assembly or disassembly of intravenous infusion sets, adminis-
Discarded glauware 46 1.2 tration of parenteral injections or infusion therapy, drawing of
Intentional infection 19 0.5
Total !1,921 100.00
blood, recapping of needles, or handling of waste that contains
needles (31,41-43) . Recapping needles is particularly hazard-
Adapted from Pile RM. Laboratory-associated infections; summary ous, causing 12% to 30% of needle-stick injuries (31,41). It
and analysis of3,921 cases. H«dth. Lab &i. 1976;1!1:105--114. should be noted, however, that not recapping needles may also
be hazardous ( 44). The epidemiology of needle-stick injuries
among laboratory personnel has not been studied, but since
activities such as intravenous infusion and handling infusion
infection is unknown in ::520% of cases and that the infected sets are not carried out in laboratories, recapping needles and
individual is known only to have worked with the agents in the handling waste are likely to be the most common causes of nee-
past in another 21% of cases (3). Thus, the exact source, proce- dle-stick injuries among laboratory personnel.
dure, or breach in technique can be identified in just over half
of cases. Among the recognized sources are accidents, which
account for 18% of cases. The kinds of accidents that lead to INFECTIOUS AGENTS OF SPECIAL
laboratory-acquired infections are listed in Table 22.2. CONCERN IN CLINICAL LABORATORIES
Laboratory accidents associated with exposure to infectious
materials include creation of aerosols from spatters or spills; The risk of acquiring infections in a clinical laboratory is de-
exposure of skin defects (i.e., cuts, abrasions, ulcers, derma- pendent upon several factors, the most important of which is
titis, and so on), conjunctivas, or mucosal surfaces; acciden- the likelihood of exposure to an infectious agent (45). The
tal aspiration or ingestions; and traumatic implantation (3). probability that such an exposure will result in infection is de-
Needle-stick injuries and cuts with broken glass and other pendent upon inoculum size, viability of the infectious agent,
sharp objects account for up to half of accidents associated the immune status of the exposed individual, and the availabil-
with laboratory-acquired infections (30,31) . The micro biologic ity of effective postexposure prophylactic therapy.
hazards associated with injuries from needle sticks and sharp
objects have recently been reviewed (30,31). All laboratories
PATHOGENIC BACTERIA
should prohibit the use of needles and sharp instruments to
the extent possible, as well as provide the necessary procedures Bacterial infections of special concern to laboratory per-
and training for handling or use of "sharps" (32-34). sonnel are primarily those caused by highly virulent patho-
Aerosol droplets vary in size, with larger droplets rapidly gens, such as Brucella, N. meningitidis, and Francisella tularensis
settling onto exposed surfaces. These droplets may carry in- (3,5,12-16,24-26) and the enteric pathogens Shigella, Salmonella,
fectious agents and can thus contaminate environmental sur- and E. coli 0157:H7 (5,17-23,27). In addition to these bacteria
fuces. Smaller droplets remain suspended in the air for a longer being the most common causes of laboratory-acquired infec-
tions, many of them can cause serious infections. Under certain
circumstances, even avirulent or attenuated strains of some bac-
terial pathogens pose a risk of serious infection (27). Because
TABLE 22.2 Kinds of Laboratory Accident
most laboratories do not isolate some of these bacteria on a rou-
Raulting in Infection tine basis, lack of familiarity with the bacteria may result in a
Number of Percentage period where workers are at increased risk of exposure because
Known Accident Infections of Total they may not suspect they are working with one of these species.
Spill or spatter 188 26.7
Needle stick 177 25.2 HUMAN IMMUNODEFICIENCY VIRUS (HIV)
Broken glass injury 112 15.9
Bite or scratch 95 13.5 The likelihood of exposure to specimens from patients who are
Mouth pipetting 92 1!1.1 infected with HN depends upon the patient population served
Other 39 5.5 by that laboratory. In most healthcare settings, a significant
Total 703 99.9 minority of clinical specimens will be from patients who are
infected with HIY, particularly in hospitals and clinics serving
Adapted from Pike RM. Laboratory-associated infections; summary
and analysis of 3,921 cases. H«dth. Lab &i. 1976;13; 105--114. proportionally larger groups of at-risk populations. Many hos-
pitals also may serve large populations of immigrant patients
322 Section II • F'unctWnalARas ofConcem
from areas with higher HIV prevalence, as well as travelers in microbiology laboratories, particularly those that perform
from those regions. As a result, all clinical laboratory person- mycobacteriology cultures on site rather than referring speci-
nel can expect to eventually work with clinical specimens from mens to a reference laboratory. Other laboratory personnel are
patients who are infected with HIV. Occupational exposure at risk, however, including those who process respiratory speci-
to HIV occurs as a result of contact between infected mate- mens for cytopathologic examination, perform gross examina-
rial and nonintact skin or mucosal surfaces, or as a result of tion of tissue specimens, those performing frozen sections, and
traumatic implantation of infectious material. Fortunately, the persons involved in autopsies.
estimated risk of acquiring HIV infection from a needle~tick The risk of acquiring M. tuberculosis infection in a laboratory
injury is -0.3% to 0.5% (45-47); there are fewer data about setting is mitigated through use of standard precautions, wear-
the risk associated with mucocutaneous exposures. The fre- ing of appropriate (N95) respiratory protection, processing
quency of exposures among laboratory personnel has not been specimens within a Biologic Safety Cabinet (BSC) when neces-
reported, but based on the epidemiology of hepatitis B virus sary, and adequate disinfection of equipment, such as cryostats.
(HBV) infection among laboratory personnel ( 46), it is likely Spills involving cultures of M. tuberculosis require special han-
that these personnel are among those healthcare workers most dling (see below). All healthcare facilities should have a com-
commonly exposed to HIV-infected specimens. prehensive plan for the prevention, control, and treatment of
Although effective postexposure treatment protocols ex- M. tuberr;ulosis infection (55) .
ist, prevention of HIV infection among healthcare workers
depends primarily upon prevention of exposure to the virus.
PATHOGENIC FUNGI
Guidelines for preventing HIV exposure in the workplace have
been published; they are based on the principle of standard Fungal pathogens of significance to laboratory employees in-
precautions (see Chapter 13). These guidelines also are use- dude Coccidioides immitis, Blastomyces dermatitidis, and Histo-
ful in preventing occupational exposure to other blood-borne plasma capsulatum (9,10). As with the aforementioned bacterial
pathogens. The guidelines are based on a common~ense ap- species, the risk of a laboratory-acquired infection with one of
proach to infection control, and there is evidence that occupa- these fungal pathogens may be less than it once was, but it is
tional exposures have been reduced when standard precautions not zero. Recommendations for the safe processing of clinical
are used (45-47). specimens and cultures suspected of containing any of these
agents are given later herein (56,57).
HEPATmS BAND C VIRUSES

PREVENTION OF LABORATORY-
Because the incidence of HBV infection in a given patient pop-
ulation may be high, and compliance with barrier precautions
ACQUIRED INFECTIONS
often is inconsistent, the easiest way to prevent occupational
Each clinical laboratory must develop policies and procedures
HBV infection is by vaccination (see Chapter 3). Although the
to prevent, document, and treat laboratory-acquired infections.
incidence of laboratory-acquired HBV infection has decreased
The laboratory director, in conjunction with a designated labo-
since the vaccine was introduced in 1982, not all healthcare
ratory safety officer, should take the lead role in developing and
workers have received complete vaccinations (6,48,49). Em-
implementing these policies and should integrate them into the
ployers should focus on vaccination strategies on those employ-
laboratory procedure manual (1,32-34). All employees should
ees most likely to be exposed, since vaccinating employees with
receive the appropriate education and training necessary to
little or no risk of occupational exposure is of little value ( 49).
perform their job safely. They should be aware of hazards as-
Similarly, there is no compelling evidence to routinely perform
sociated with various infectious agents, and exactly what should
postvaccination testing or provide booster doses; employers
be done should an exposure take place. Immunization against
should not divert resources for either purpose ( 49). Requiring
HBV should be required for all laboratory workers. Initial and
HBV vaccinations as a condition of employment may be the
follow-up tuberculin tests should be given according to current
simplest way to ensure compliance.
guidelines. Finally, a method for maintaining compliance with
Hepatitis C virus (HCV) (see Chapter 42) is transmitted
these policies and procedures must be implemented, along with
via the same routes as HBV. Unlike HBV, HCV is not read-
the appropriate documentation, counseling, and, if necessary,
ily transmitted via needl~tick injury; estimates of the risk of
disciplinary action to ensure that employees work safely (58,59).
transmission following needl~tick injury are in the range of
0% to 3% (46,50-52). Nonetheless, exposure is to be avoided,
since 2:50% ofHCV-infected persons progress to chronic liver BIOSAFETY LEVELS
disease, and cirrhosis or hepatocellular carcinoma or both will
The Centers for Disease Control and Prevention (CDC) and
develop in many of them. As with HBV and HIV, HCV infection
National Institute of Health (NIH) have published a document
is highly prevalent in some populations of patients, such as in-
defining four biosafety levels based on "the potential hazard of
jection drug-users (53).
the agent and the laboratory function or activity" (32). Labora-
tory design, equipment, and procedures necessary to achieve
each biosafety level are detailed in that document. Most common
MYCOBACTERIUM TUBER.CUWSIS
pathogens may be handled under biosafety level2 conditions. Cul-
Employees involved in the processing of clinical specimens or tures suspected of containing Brucella, E tularensis, M. tuberr:ulosis,
cultures from patients with tuberculosis (see Chapter 33) are at C. immitis, B. dmnatitidis, or H. capsulatum should be processed
greater risk of acquiring M. tuberculosis infection than is the gen- only under biosafety level 3 conditions. Biosafety level 4 condi-
eral population (11,54). The risk is highest for persons working tions are not needed in general clinical microbiology laboratories.
TABLE 22.3 Standard Precautions for Prevention of Transmission of HIV, HBV, and Other
Blood-Bome Pathogens in Healthcare Settings
1. All healthcare workers should routinely use appropriate barrier precautions to prevent skin and mucous membrane exposure when contact
with blood or other body fluids of any patient is anticipated. Gloves should be worn for touching blood and body fluids, mucous mem-
branes, or nonintact skin of all patients; for handling items or surfaces soiled with blood or body fluids; and for performing venipuncture
and other vascular access procedures. Gloves should be changed after contact with each patient. Masks and protective eyewear or face
shields should be worn during procedures that are likely to generate droplets of blood or other body fluids to prevent exposure of mucous
membranes of the mouth, nose, and eyes. Gowns or aprons should be worn during procedures that are likely to generate splashes of blood
or other body fluids.
2. Hands and other skin surfaces should be washed immediately and thoroughly if contaminated with blood or other body fluids. Hands
should be washed immediately after gloves are removed.
3. All healthcare workers should take precautions to prevent injuries caused by needles, scalpels, and other sharp instruments or devices dur-
ing procedures; when cleaning used instruments; during disposal of used needles; and when handling sharp instruments after procedures.
To prevent needle-stick injuries, needles should not be recapped, purposely bent or broken by hand, removed from disposable syringes, or
otherwise manipulated by hand. After they are used, disposable syringes and needles, scalpel blades, and other sharp items should be placed
in puncture-resistant containers for disposal; the puncture-resistant containers should be located as close as practical to the use area. Large-
bore reusable needles should be placed in a puncture-resistant container for transport of the reprocessing area.
4. Although saliva has not been implicated in HIV transmission, to minimize the need for emergency mouth-to-mouth resuscitation, mouth-
pieces, resuscitation bags, or other ventilation devices should be available for use in areas in which the need for resuscitation is predictable.
5. Healthcare workers who have exudative lesions or weeping dermatitis should refrain from all direct care of patients and from handling
equipment used in the care of patients until the condition resolves.
6. Pregnant healthcare workers are not known to be at greater risk of contracting HIV infection than healthcare workers who are not preg-
nant; however, if a healthcare worker develops HIV infection during pregnancy, the infimt is at risk of infection resulting from perinatal
transmission. Because of this risk, pregnant healthcare workers should be especially familiar with and stricdy adhere to precautions to mini-
mize the risk of HIV transmission.
STANDARD PRECAUTIONS among one group of healthcare workers (10,48). The CDC
recommendations for standard precautions for all healthcare
Special policies and procedures are necessary for the safe workers and clinical laboratories are given in Tables 22.3 and
handling and disposal of certain highly virulent pathogens.
22.4, respectively.
Rigorous adherence to standard precautions is sufficient to
lessen or eliminate the risk of acquiring an infection from most
patients' specimens processed in clinical laboratories. Imple-
STANDARD MICROBIOLOGICAL PRACTICES
mentation of standard precautions will be successful only if
laboratory administrators and workers integrate CDC recom- When used in conjunction with standard precautions, the
mendations into routine laboratory operations, and make ev- following practices should be effective in preventing most
ery reasonable attempt to maintain and enforce such policies. laboratory-acquired infections. These or equivalents proce-
Standard precautions have been shown to decrease the num- dures should be routine practice in all clinical laboratories
ber of occupational exposures to blood and other body fluids ( 33,34,60-65) .
TABLE 22.4 Standard Precautions for Workers in Diagnostic Pathology Laboratories

1. All specimens of blood and body fluids should be put in a well-constructed container with a secure lid to prevent leaking during transport.
Care should be taken when collecting each specimen to avoid contaminating the outside of the container and of the laboratory form
accompanying the specimen.
2. All persons processing blood and body-fluid specimens (e.g., removing tops from vacuum tubes) should wear gloves. Masks and protective
eyewear should be worn if mucous membrane contact with blood or body fluid is anticipated. Gloves should be changed and hand washed
after completion of specimen processing.
3. For routine procedures, such as histologic and pathologic studies or microbiologic culturing, a biological safety cabinet is not necessary.
However, BSCs (class I or ll) should be used whenever procedures are conducted that have a high potential for generating droplets,
including activities such as blending, sonicating, and vigorous mixing.
4. Mechanical pi petting devices should be used for manipulating all liquids in the laboratory. Mouth pipetting must not be done.
5. Use of needles and syringes should be limited to situations in which there is no alternative, and the recommendations for preventing
injuries with needles oudined under standard precautions in healthcare settings (Thble 22.3) should be followed.
6. Laboratory work surfaces should be decontaminated with an appropriate chemical germicide after a spill of blood or other body fluids and
when work activities are completed.
7. Contaminated materials used in laboratory tests should be decontaminated before reprocessing or be placed in bags and disposed of in
accordance with institutional policies for disposal of infective waste.
8. Scientific equipment that has been contaminated with blood or other body fluids should be decontaminated and cleaned before being
repaired in the laboratory or transported to the manufacturer.
9. All persons should wash their hands after completing laboratory activities and should remove protective clothing before leaving the
laboratory.
LR.bor11tory Access received in damaged, leaking or contaminated containers

should not be processed; the person who collected the speci-
Only trained personnel should be allowed in a laboratory rmder men should be notified and the specimens recollected.
ordinary circumstances. Maintenance personnel, delivery per-
sons, and other visitors with legitimate reason for being in the Microbiologiclll TechniiJ.ues
laboratory should either be escorted or be closely supervised to
prevent unnecessary exposure to infectious agents. Laboratory Mouth pipetting should be strictly prohibited; mechanical
trainees, house staff, and other students also should be super- pipetting devices should be used for all pipetting. All proce-
vised closely. Children should not be allowed in laboratories. dures should be performed in such a way as to minimize or
prevent aerosols. Procedures that do generate aerosols should
Personnel Policies be performed in a biological safety cabinet. Cylindrical electric
burners are preferable to flame burners for sterilizing inoculat-
All personnel should have training commensurate with the level ing loops or needles and the tips of other small instruments. ff
of expertise needed to safely perform all necessary procedures. flame burners are used, care should be taken to avoid spatter-
Suggested topics for such training are given in Table 22.5 (34). All ing. This can be achieved by slowly drawing loops or needles
personnel should receive the necessary continuing education and through the flame with the loop entering the flame last. Cool
training to ensure job safety. Employee job appraisals should doc- inoculating loops and needles should be used when touching
ument lapses in safety, techniques, or other behaviors that could plates, colonies, or broth cultures. Work surfaces should be de-
result in occupational exposure to infectious agents. Persons ex- contaminated at least once a day with an acceptable germicide.
hibiting such behavior should be counseled and/or retrained. Work surfaces also should be decontaminated after spills (dis-
cussed later). Infectious wastes and patients' specimens should
LR.bor11tory F11ciliPy be disinfected before disposal (see later herein). Needles,
blades, and other sharp items should be disposed of in rigid,
Laboratories should be designed to minimize traffic and un-
tamper-resistant, prmcture-proof, marked containers. Materials
necessary access to work areas. Laboratory furniture should be
removed from the laboratory should be free of infectious haz-
sturdy and easy to clean, and laboratories themselves should be
ard. Clinical specimens, cultures, or other potentially infectious
rmduttered and easy to dean. Foot-, knee-, or elbow-<>perated
materials should be packaged, labeled, and shipped according
hand-washing sinks should be available and located near lab-
to federal regulations (34).
oratory exits. The laboratory facility should be designed and
constructed to meet criteria recommended for the appropriate
S.foty Procedure Msln'UIJI
biosafety level (32).
Every laboratory should have an up-to-date safety manual that
Hygiene for Workers includes the following information:
Eating, drinking, smoking, and applying cosmetics should be 1. A designated laboratory safety officer and explicit in-
strictly prohibited within the laboratory (32). All personnel structions as to how to get in contact with that individ-
should wear and button full-length white laboratory coats while ual in the event of an accident or exposure. This officer
in the laboratory. Personnel and visitors should wash their should lead the educational program for biohazard safety
hands before leaving the laboratory. Food and other personal (Table 22.5).
items should not be stored in refrigerators or freezers used to 2. Synopsis of safety components of good laboratory practice
store clinical specimens or cultures. Refrigerators, freezers, and and hospital policies for infection control, including stan-
microwave ovens used to store or prepare food must be located dard precautions.
outside the laboratory. 3. A program for the prevention of transmission of M. tuber-
culosis to laboratory workers, developed in accordance with
current recommendations.
CliniuU Specimens 4. Location of necessary emergency equipment and spill
Specimens must be labeled with the patient's full name, hos- cleanup kits.
pital identification number, and the date drawn. Specimens 5. Detailed procedures for cleanup of spills.
6. Instructions for the effective use of BSCs.
7. Procedures for safe use of centrifuges and autoclaves.
TABLE 22.5 A 10-Step Program for 8. Vaccination policies.
Training Laboratory Workers 9. Procedures for postexposure treatment, prophylaxis, and
counseling.
in Biohazard Safety
1. Standard precautions for handling blood and body fluids
2. Aseptic technique and procedures SAFETY IN HANDLING ACCIDENTS,
3. Penonal hygiene and protective equipment USING EQUIPMENT, AND DISPOSING
4. Criteria for biosafety levels 1-4 OF WASTES
5. Effective use ofBSC'.! claDes 1-ill
6. Safe use of centrifuges and autoclaves
7. Decontamination, disinfection, and sterilization PROCEDURES FOR SPILLS AND ACCIDENTS
8. Handling, packaging, and disposal of biohazardous waste Because of the high concentration of microorganisms in pa-
9. Packaging, transporting, and shipping biohazardous waste
10. Reporting incidents and accidents tient specimens and cultures in clinical laboratories, special
procedures must be used to disinfect spills and other laboratory
accidents (34). For spills that may contain Mycobacteria, ger- 9. If the spill occurs in a room not under negative pressure,
micides should be used that are tuberculocidal when used at the clean up should begin immediately.
recommended concentrations (32). Tiris recommendation ap- 10. Protective clothing, including a cap, an N-95 respirator,
plies to all types of spills or other laboratory accidents. long sleeved gown, shoe covers, and gloves, should be worn.
Written procedures should be in the laboratory safety 11. An appropriate disinfectant should be allowed to run into
manual. Employees should be trained to safely decontaminate the spill from the sides. Disinfectant poured directly on the
and clean up spills involving those microorganisms cultured spills may generate aerosols.
or studied in their laboratory. All necessary disinfectants and 12. The area should be covered with paper towels and allowed
cleaning supplies must be readily available in the laboratory. to stand for 20 minutes.
Because spills may occur at any stage of transport, plating, pro- 13. An autoclave dustpan and squeegee or forceps should be
cessing, or storage of microbiologic cultures, specific protocols used to clean up pieces of broken glass and other sharp
should be available for spills occurring at each stage and for objects.
spills involving common-place moderate-risk microorganisms 14. Remaining liquids should be wiped up with paper towels.
and those of higher risk, such as M. tu!Jerw,losis. 15. All materials, including protective clothing, should be dis-
The hazard associated with a spill is dependent upon the carded as biohazardous waste.
nature of the spilled agent, the volume or material spilled,
the concentration of the agent within the material, and Procedures for Spills in Biological SR.frPy Cabinets
where the spill takes place. Spills involving microorganisms
such as M. t'Uherculosis, E tularensis, Brucella spp., C. immitis, or 1. BSCs should be allowed to operate to minimize further risk
H. capsulatum may pose a major hazard to laboratory workers. to laboratory workers.
Spills of large volumes of moderate-risk microorganisms or 2. Clean up should begin immediately.
those occurring in such a manner that aerosols might be gen- 3. Gloves, N-95 respirator, and a gown should be worn during
erated also should be treated as a major hazard to laboratory the dean up.
workers. 4. Work surfaces and any catch plans or basins should be
flooded with an adequate volume of disinfectant.
Procedures Used for Routine Spills of Smsll Volumes 5. The flooded area should be allowed to stand for
ofMotlerste-R.isk Microorgsnisms 20 minutes.
6. During this time, the BSC walls, work surfaces, and any
1. The affected area should immediately be flooded with a equipment within the BSC should be cleaned with a germi-
suitable disinfectant and covered with paper towels. cidal disinfectant (e.g., phenolic or iodophor compounds).
2. Other workers should be warned to avoid the contami- Flammable organic solvents, such as alcohols, should not
nated area. be used, as these compounds may reach dangerous con-
3. Personnel should wear gloves and use an autoclavable dust- centrations within certain BSCs.
pan and squeegee or forceps to pick up solid materials. 7. All contaminated materials and fluids should be disposed
4. Any remaining fluids or other materials should be wiped of as biohazardous waste.
up with paper towels. 8. Catch pans and basins should be cleaned per the manufac-
5. Contaminated materials should be disposed of as infec- turer's recommendations.
tious waste. 9. High-efficiency particulate air (HEPA) filters and other
6. Unless the laboratory worker is injured or otherwise ex- components of the BSC should not be cleaned or disin-
posed during the spill or clean up, no other specific action fected by laboratory personnel. This is not necessary with
need be taken. most spills and should be done only by factory-trained and
certified personnel. Major spills or those involving high-
Procedures for Spills of urge Volumes of Motlerate-R.isk risk agents may necessitate formaldehyde decontamination
.A,gents or Highly Pathogenic .A,gents Outside 11 Biological of the BSC. Such decontamination should be performed
SR.frPy CR.binet only by qualified personnel.
1. Employees should hold their breath, immediately evacuate
the room, and close the door.
2. Employees should assist others as needed to protect them LABORATORY EQUIPMENT
from potential exposure. Laboratory safety and diagnostic equipment must be of the
3. Other personnel should be warned to avoid contaminated proper type and should be tested and maintained according
area. Personnel in adjacent areas should be warned of any to the manufacturer's recommendations. Equally important is
potential hazard to their safety. its proper use by laboratory personnel. All personnel should
4. Contaminated clothing and protective equipment should be instructed as to the proper use, care, and maintenance of
be removed and discarded as biohazardous waste. laboratory equipment.
5. Employees should thoroughly wash exposed skin surfaces.
6. The laboratory safety officer and director should be imme-
Biological SafrPy C.hinets
diately notified.
7. BSCs should be left running to help decrease the concen- BSCs are essential for the safe handling of infectious agents.
tration of aerosols in the contaminated room. Different BSCs are available; which one to use depends primar-
8. If the spill occurs in a room under negative pressure, ily upon the infectious agents to be handled (66) . Class I BSCs
2:30 minutes should pass before personnel reenter the (Figure 22.1) have an open front into which room air flows.
affected room. All of the exhaust air is discharged through HEPA filters to the
326 Srion II • FU'ndion41A1114S ofOmam
pattems, and changes in airflow pattems caused by alterations

in air supply or exhaust, temporary shutdowns for repairs, and
construction.
Centrifuges
Centrifuges used to proceas clinical specimens or cultures
should be equipped with sealable, autoclavable, breakage-
resistant cups to prevent contamination of the centrifuge and
the release of aerosols should centrifuge tubes break during
processing. These cups must be removable from the centrifuge
rotor so that they can be cleaned and autoclaved.
Fipre 22.1. Design of class I biological safety cabinet.
An autoclave should be readily accessible to clinical laborato-

outaide environment. Although Class I BSCs protect the user ries. Routine maintenance, testing, and cleaning are essential.
from exposure to agents within the cabinet, they do not protect Autoclaves should be tested for their ability to kill standard bac-
materials within the cabinet against contamination; Class I BSOl terial spores (M). It should be emphasized that autoclave tape
are unsuitable for use in clinical microbiology laboratories (34). indicates that an object has been autoclaved, but not necessar-
Cl:w II BSQ (Figure 22.2) also have an open front into ily sterilized.
which room air flows. These BSCs differ from Class I BSCs in
that a portion of the exhausted air puaing through HEPA fil- IA/Hw11tory 11tul P,.oteet;i-pe BljfliptHent
ters is recirculated into the cabinet. The filtered air is then used
to protect clinical specimens or cultures from contamination. Other laboratory equipment should be of a type and design
Two basic types of Class n BSC, are available. Class II type A that alloWJ for easy cleaning and disinfection. Safety equipment
BSCs are the most commonly used in clinical laboratories and for the clean up and disinfection of laboratory spills should be
are sufficient for meeting biosafety level 2 or 3 criteria. Class II readily available. Proper gloves, gowns, N-95 respirators, and
type B BSCs also may be used for this pwpose, but usually are shoe coven should be handy.
more expensive to purchase and to operate (34,66). Class ill Both latex and vinyl disposable gloves have been shown to
(Figure 22.3) BSC, provide the greatest protection to labora- vary widely in their permeability (58,63). It has been found
tory penorutel, but their use is usually restricted to working that washing and reusing gloves is inadvisable and that the
with highly virulent pathogeus in biosafety level 4laboratories. proportion of hands contaminated with test microorgan-
Laboratory work.en must remember that BSCs are not isms after gloves are removed varies from 5% to 50% (62).
chemical fume hoods. Thxic, noxious, or flammable chemi- Therefore, healthcare workers should wash their hands af-
cals must not be used in these hoods, since the recirculation ter remO'Ying gloves. The iuue of wearing two pairs of gloves
of exhaust air may allow these chemicals to reach dangerously ("double-gloving") is more contentious. Although it is logical
high levels in the cabinet. BSQ should be installed, tested, and to assume that two barriers offer more protection than one,
maintained only by qualified penonnel. Regular testing and concems about loss of tactile sensation and dexterity have led
certification of BSO! is essential to assure the safety of users. to recommendations against double-gloving during routine
Laboratory personnel should be instructed in the proper use laboratory procedures (63). Wearing two pain of gloves for au-
of BSCs and should be aware of their limitations in control- topsies and in other situations where large amounts of blood
ling aerosols. Personnel working in BSQ can adversely affect are present has been recommended (33).
the ability of cabhl.ets to contain infectious aerosols (65). Us-
ers should consult with the manufacturer as to the potential
DISPOSAL OF INFECTIOUS MATBRIALS
effect of this and other factors (such as use of equipment
within BSCs) before using a BSC. Finally, personnel should Materials contaminated with infectious agents must be di&-
be aware that the BSC function depends upon proper airflow posed of properly to protect healthcare penonnel as wen as
F.igure 2:2-.Z. Design of cbw n biological safety cabinet

type! A and B.
POSTBXPOSURE TREATMENT AND PROPHYLAXIS
l Specific treatment, prophylaxis, and counseling should be
available for all healthcare workers after exposure to infectious
agenu. Of special importance to clinical laboratory workers
are recommendations for prophylaxis or treatment of expo-
sures to specimens taken from patients who are infected with
II ~ ~ 1
HBV, HCV, or lflY. Personnel working in the mycobacteriol·
ogy laboratories, and those involved in the processing or dis-
posal of materials likely to be contaminated with mycobacteria,
0000 should receive preemployment screening for M. tuberculosis in-
fection as well as the appropriate testing following a suspected
exporure (see Chapter 3).
POST.BXPOSURE INVESTIGATION
Laboratory exposure of an employee to a pathogen should
prompt an immediate investigation into the reason(s) for the
exporure. The investigation should include a review of relevant
Fipre 22.3. Design of clasiJ m biological safety cabinet. microbiologic practices, laboratory policies and procedures,
and equipment and facilities. For example, when an employee
who works with mycobacteria converts their tuberculin skin
the general public (34). Safe disposal of infectious materials test or develops active pulmonary tuberculosis, the BSC and air
begins at the source where t.he,e materials are generated. The handling sy5tems should be checked, serviced, and balanced
following procedures are recommended for the safe disposal of by qualified personnel. If the investigation does not provide a
infectious materials and waste (M). satisfactory explanation for the source of the exposure, then
it may be necessary to broaden the investigation. Using the
I. Adequate waste bim and containers for disposal of sharp same example, an employee who works in a mycobacteriology
objects must be readily available. laboratory, but has other responsibilities outside the laboratory
2. Waste bins should be lined with two autoclavable bags. (e.g., phlebotomy), could have been conceivably exposed to
3. All containers should be clearly marked. a patient with active tuberculosis. If no source of exposure is
4. Laboratory and maintenance personnel should avoid phys- found, the investigation should be expanded as appropriate,
ical contact with these materials; leaking containers should to include potential sources of exposure outside the healthcare
be treated as spills. facility (e.g., family members).
5. Infectious materials should be transported in or on carts
that can be easily cleaned and disinfected.
6. Infectious materials should be autoclaved before disposal; CONCLUSIONS
double-bagging and overlilling should be avoided, since
these practice& limit the effectiveness of autoclavmg as a Although the incidence of laboratory-acquired infections ap-
means of sterilization. pears to be declining, infections still occur at a low rate and
7. Regular monitoring of the adequacy of autoclave steriliza· are associated with significant morbidity and mortality. Labo-
tion should be part of routine laboratory quality control ratory personnel should follow recommended guidelines, poli·
procedures. cies, and procedures designed to minimize risks associated with
handling infectious materials. Laboratories must be designed,
constructed, and maintained in such a way so as to minimize ac-
cidents and facilitate cleanups. Laboratories must contain the
PREVENTION, POSTBXPOSURE necessary safety and diagnostic equipment. Most importantly,
TREATMENT, AND FOLLOW-UP however, laboratory directors and supervisors must provide the
proper training and supervision of laboratory personnel so as
VAOOINATION
to provide a safe working environment.
Laboratory workers may or may not have contact with patients,
but they should still follow recommendations regardingvaccina·
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tory. 1 am Mi<robiol. 1981 ;13:855-a58. 50. Riyooawa K. Sodeyama T, Tanaka E, et aL Hepatitio C in hoopital employeeo with needle-
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te•~in« specimem. N Eng!J M.d. 1980;303:519-521. 51. Pwo V, Petrosill.o N, Ippolito G, et al. Occupational hepatitio C virw infection in Italian
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Ar;quirld Infl<litms; ApprrJr;m Guid8iru (M2!MJ). 3rd ed. Villanova, PA: CLSI; 2005. 62. Doebbeling BN, pfa]}er MA. Houlton AK, et aL Removal of nooooomial pathogen• from
M. U.S. National Reoearch Conn<il, Committee on Ha7ard.ous Biological Subotanceo in the the contaminated glove: implicatinno for glon: reuoe and handwashing. Ann 1tllmo Mod.
Laboratory. BWofiiJ in 1M LolxnrJlury: Inllllm .l'rG<Ii<u far 1M Htmdlmg and DisposGI afInfe- 1988;1 09:S94-398.
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35. Brown JH, Cook. KM, New FG, et al. lnfluen<e of particle 1ize upon the retention of par- procedureo and implicationo for healtheare work.en. An:h 1tllmo M.d. 1989;149:27~2753.
ticulate matter in the human lung. AmJ 1'ublit; HroJJh. 1950;40:450-458. 64. Kubica GP. Your tuberculooiJ laboratory: Are you really oafe fiwn infection? Ctm Microl>id
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tory procedures. A•JCiin Patllol. 1974;62:591-000. 1991;4:207-241.
CHAPTER
23 Matthew 1. Arduino and Priti R. Patel
Dialysis-Associated Complications
and Their Control
INTRODUCTION The use of peritoneal dialysis, accompwhed by automated
machines (cycling), or manually, also increased. The three
The number of patients who h~ end stage renal disease (ESRD) modes include continuous ambulatory peritoneal dialysis
has increased dramatically in the past 40 years. Three major (CAPD), automated peritoneal dialysis (APD), and intermit-
forma of renal replacement therapy (i.e., hemodialy3is, perito- tent peritoneal dialysis (IPD) modality. Peritoneal dialyais is
neal dialyaia, and kidney transplantation) treat ESRD patients. more popular among pediatric nephrology programs (approxi-
Data from the U.S. Renal Data System (USRDS) suggests that mately 40% of all pediatric dialysis patients) (1) than adult
by the end of 2010 there 'M!re approximately 59S,086 patients programs. One must also recognize that patients may change
with ESRD. Maintenance hemodialysis patients comprise ap- modality due to vascular access failure, or failure of the perito-
proximately 65% (S83,992) of the patients in tlW population. neum to adequately perform dialysis (e.g., reCUITent peritonitis
Appromnately 5% (29,7!J!J) ofESRD patients are treated by one or peritoneal transport issues).
of the modes of peritoneal dialysis (1). All patients with chronic kidney dUease, including dialysis
In 1967, approximately 1,000 patients were undergoing patients, have a compromised immune system and other co-
maintenance or chronic hemodialysis. In 19'1S, when full Medi- morbidities that place them at increased risk for infectious
care coverage was extended to ESRD patients, approximately diseuea. Patienta on m.a intenance hemodialysis are at particular
11,000 patienu were undergoing ctialysis. By the end of 2010, risk. In-center hemodialyaia patients are at higher risk for infec-
the program had grown markedly, and ahnost 400,000 patienta tions and are at risk for other adverse events associated with the
were treated in 5,'760 dialysis centers (free-standing for profit dialysis process. In this environment, multiple patients typically
and nonprofit clinics, in addition to hospital-based units) and receive dialysis concurrently, and there are repeated opportu·
in homes. Most patients (6S.4%) were treated in centers affili. nities for person-to-person transmission of infectious agenu,
ated with one of the three large dialysis organizations (i.e., Fre- directly or indirectly via contaminated devices, equipment and
senius Medical Care, DaVita, or DCI), 11.6% of patients were supplies (including medications), environmental surfaces, or
treated by small dialylu organization&, 10% by hospital-owned the bantb of healthcare personnel when recommended infec-
units, and 15% by independent providers. There were aho tion control practices are not followed. In addition, the dialysis
81,076 full and part-time staff members (i.e., Nurses, Techni· process ia not without risks either due to errors by personnel,
ci.ana, Dieticians, Social Workers, and so on) employed by these failure of equipment, or vaacular access complications.
facilities. Home hemodialysis represents a very small fraction The Centers for Disease Control and Prevention (CDC)
of U.S. hemodialyais patients (1). The ESRD program u ad- compiled data of adverse outcomes among dialysis patienta
minutered by the Centers for Medicare and Medicaid Services from two sources. The first includes outbreak investigations
(CMS) of the Department of Health and Human Services and in dialysia settings reported to CDC and National Surveillance
is the only Medicare entitlement that is based on the diagno- data. National swveillance data was collected by CDC begin-
sis of a medical condition. & such, participating healthcare ning in the 1970s to study the incidence and prevalence of
facilitie1 must meet CMS regulation& aa pubwhed in the CMS hepatitis 8 (HBV) in thU population. These national swveya
Condition• for Coverage for End-Stage Renal Diseaae Facilities, subsequently evolved into the National Surveillance of Dialysi•
2008 (2). Associated Diseases in the United States performed by CDC in
The technology for performing dialysis as well as the poten- coll.aboration with CMS in 1976, 1980, 1982 to 1997, and 1999
tial for complications has changed markedly over the years. In to 2002 (~16). Future swveillance data will be oollected from
the early 1960s, hemodialysia was used ahnost CJ~:clusively for fAcilities and providers through the use of the National Health-
the treatment of acute renal failure . Subsequently, the devel- care Safety Network (NHSN) surveillance system ( 1'7).
opment of the arteriovenous shunt and certain other ancillary Over the past 40 years, the CDC also haJI investigated out·
teclmologic advances in dialysis equipment expanded the use brew in the dialysis setting; 24 outbreaks were infections (bac-
of hemodialysis to maintenance therapy for ESRD. In the 1970s, terial or fungal) or pyrogenic reactions, 28 outbreaks were due
the primary mode for dialylis treatment was hemodialysis per- to viral infectiom, 11 were due to exposure to chemical con-
formed with various types of dialysis machines and artificial taminants, and two allergic-type complication& during dialysis
kidneys. (Thble 2S.l). In addition, the CDC aho investigated a cluster
329
~
~
Q
TABLE 23.1 Outbreaks and Adverse Bvcnts in the Dialysis Setting Investigated by the Centers for Disease Control and Prevention (CDC)
and StatejLocal Health Departments
Description (Reference) Cause of the Events Corrective Measures/Recommendations
CHEMICAL CONTAMINATION OF DIALYSATE
Aluminum intoxication and seizures in seven Exhausted deionization tanks unable to remove aluminum Monitor deionization tanks daily; install reverse osmosis unit
patients (281) in incoming tap water
Aluminum intoxication, neurologic symptoms, dementia Aluminum pump was used to transfer acid concentrate to Utilize component! in the fluid distribution systems that are
and elevated serum aluminum levels in 64 patients; the treatment area compatible and do not leach into the dialysate
three deaths (174)
Elevated serum aluminum levels detected in 10 patient! Replacement transfer pump used to pump acid Contact manufacturer of acid concentrate for a compatible
during routine screening (176) concentrate from 55 gallon drum into jugs used at pump; utilize components in the fluid distribution
the machine contained aluminum components systems that are compatible and do not leach into the
dialysate
16 patients developed nausea, vomiting, chilb, some Water used to prepare dialysate contained volatile organic Suspend injection of citric acid (use another pH additive);
develop fever; two deaths (282) compounds (CS 2, CH3S, etc.); multiple causes: citric redesign and replace water treatment system
acid used to adjust incoming water pH to aid in removal
of chlorine by carbon tanks; water treatment system not
functioning properly; microbial quality of water above
AAMilimits
Hemolytic anemia in 41 patient! (177) Facility increased capacity of water treatment system Use larger carbon beds to give adequate empty bed contact
without adjusting size of pretreatment carbon beds; time to remove chloramines; monitor for total chlorine
potable water supplier uses monochloramine as residual breakthrough after fli'llt carbon tank
disinfectant, which was not removed completely by the
carbon tank
Fluoride intoxication in eight patients; one death (46) Accidental spill of hydrofluosilic acid at drinking water Install reverse osmosis unit
plant lead to excessive fluoride levels in water entering
a dialysis unit; water treatment at the dialysis facility
only included softening
Fluoride intoxication in nine patients; three Exhausted deionization tanks discharged a bolus of Deionization tanks should be monitored with temperature
deaths (45,283) fluoride compensated resistivity alarms that include both visual
and audible alarms
Formaldehyde intoxication in five patienu; one Disinfectant not properly rinsed from the distribution Eliminate stagnant flow areas; test for residual disinfectant
death (178) system
Decreased hemoglobin in three pediatric dialysis Hydrogen peroxide used to disinfect the system not Thoroughly rinse disinfectant from the system; use an
patients (284) adequately rinsed from the system; facility used flat appropriate residual te!t kit; installation of a storage tank
bottom storage tank that could not be drained with conical bottom and outflow at lowe!t point would
allow for storage tank to empty completely
116 of 130 patients (89%) at a dialysis center in Brazil, Water contaminated with cyanobacterial toxins not Have finished drinking water supplied to the facility;
had visual disturbances, nausea, and vomiting removed by water treatment system; patients exposed important to appropriately design (based on system
associated with hemodialysis and 50 died; following to dialysate containing microcystin-LR feed water), install, monitor, and maintain water
the initial investigation it was reported an additional treatment systems
26 patient! had died of liver failure (285,286)
Severe hypotension in nine patients (287) Dialysate contaminated with sodium azide used as a Rinse system after modification or installation of new
preservative from new ultrafilters (filters were labeled components
~not for medical use•)
BACTEREMIA, FUNGEMIA, OR PYROGENIC REACTIONS NOT RELATED TO DIALYZER REUSE
Pyrogenic reactions in 49 patients (lU) Untreated tap water contained high levels of endotoxin Install a reverse osmosis water treatment system
Pyrogenic reactions in 45 patients (30) Inadequate disinfection of the fluid distribution system Increase disinfection frequency and disinfectant contact time
Pyrogenic reactions and bacteremia in five patients; Two weeks before the outbreak a pump that pumped Routine disinfection of the fluid distribution system and
two patients had bacteremia (one with Klebsiella sodium hypochlorite through the distribution dialysis machines following repair of the pump ended
pnmmonia, the other had both K pnmmonia and and machines failed; the distribution system and the outbreak.
Pseudomonas tui"Ug'inosa) (288) machines were inadequately disinfected; P. aeruginosa,
K pneumonia, and Panto«J (Entembacter) agglomeraru
were recovered from water, dialysate, and other
environmental sources
Pyrogenic reactions in 14 patients; two with bacteremia; Reverse osmosis water storage tank contaminated with Remove or properly maintain and disinfect storage tank.
one death (29) bacteria
Bacteremia in 35 (51.5%) patients with central venous eves used as primary access; median duration of catheter Use eves only when necessary (i.e., bridge to maturing
catheters (eves) (142) use among affected patients was !lll days; improper fLStula or graft or as an access oflast resort); use
aseptic techniques appropriate aseptic techniques when inserting eve
and performing catheter care
Three pyrogenic reactions and seven EnterobacttiT cloacae Incompetent check. valves in the waste handling option Routine maintenance, disinfection, and valve competency
bloodstream infections ... ( 111) (WHO-port) of one type of dialysis machine allowed testing of the WHO should be carried out
back.flow of spent dialysate into patient blood lines
during circuit priming and dialysis initiation; Machines
and ports were contaminated with E. cloacae
Gram-negative bacteremia in 1 patient (6 E. cloactM, Incompetent check valves in the waste handling option Routine maintenance, disinfection, and valve competency
4 P. aeruginosa, 2 Escherichia coli; 2 had polymicrobial (WHO-port) of one type of dialysi5 machine allowed testing of the WHO should be carried out
bacteremia) (112) back.flow of spent dialysate into patient blood lines
during circuit priming and dialysis initiation; machines
and ports were contaminated with E. cloacae and
P. aeruginosa
Outbreak of pyrogenic reactions and gram-negative Water distribution system was not routinely disinfected and Disinfect machines according to manufacturer's instructions;
bacteremia in 11 patients (4 had bacteremia) (28) machines were not disinfected in accordance with man- include water distribution system in the weekly
ufacturer's instructions; water and dialysate cultures disinfection of the RO system. Do not use calibrated
were performed using a to-~ calibrated loop on blood loops. These are not sensitive to detect when AAMI
agar plates--results were often reported as no growth limits have been reached; use spread plate or membrane
filtration techniques and Trypticase Soy Agar (TSA) for
testing (94)
Phialtmonittm ruf'!Jattlm acces.s infections in four Phialemimittm species were only recovered from the Review infection control practices, clean and disinfect
hemodialysis patients, two patients died of systemic condensation drip pans under the blowers of the the HVAC system where water accumulates; perform
disease (289,290). HVAC system that supplied air to the dialysis center. surveillance on facility patients. Observe proper aseptic
Observations at the facility noted some irregularities technique during access cannulation.
with site prep for needle insertion; all infected patients
had synthetic grafts.
Fungemia with Phialsmonittm ruroatttm in two Both patients were dialyzed on the same machine. Facility WHO ports have been previously been associated with cases
maintenance hemodialysis patients (291). used machines with a waste handling port; Phialsmonittm of bacteremia; remediation of water distribution system
was isolated from reverse osmosis unit (WHO-port and and maintenance and discontinuing use of WHO ports
valves were not available for culture) ended the outbreak.
ADVERSE EVENTS ASSOCIATED WITH HEMODIAL'YZER REUSE

Mycobacterial infections in 27 patients (292) Inadequate concentration of dialyzer disinfectant Increase concentration of formaldehyde used to disinfect
dialyzers to 4%
My;obacterittm abscessw infection in five patients treated Inadequate dialyzer disinfection due to over diluted Use higher concentration of dialyzer disinfectant; follow
Clo) with high-flux hemodialyzers (38) disinfectant; inadequate disinfection of water manufacturer's label; more frequent disinfection of the
....
Clo)
distribution system water treatment system
(contin!W)
~
~ TABLE 23.1 Outbreaks and Adverse Bvcnts in the Dialysis Setting Investigated by the Centers for Disease Control and Prevention (CDC)
~
and StatejLocal Health Departments (Co•ri•llell)
Bacteremia and pyrogenic reactions in six patienta (293) Dialyzer disinfectant diluted to improper concentration Use disinfectant at recommended dilution and verifY
concentration
Bacteremia in six patienta (CDC, unpublished data) Inadequate concentration of dialyzer disinfectant; water for Use AAMI quality water for reprocessing hemodialyzers;
reuse did not meet AAMI standards ensure proper disinfectant concentration in reprocessed
dialyzers
Nine pyrogenic reactions and five gram-negative Inadequate mixing of dialyzer disinfectant Thoroughly mix dialyzer disinfectant and verifY proper
bacteremias in 11 patienta undergoing dialysis (67) concentration
Bacteremia in 33 dialysis patients at two dialysis New dialyzer disinfectant created holes in dialyzer Change disinfectant (manufacturer withdrew product from
clinics ( 104,294) membranes the market place)
Six chronic hemodialysis patienta acquired bloodstream Dialyzers contaminated during removal and cleaning of Do not use gauze or similar material to remove clots from
infections (BSis) with KlebsiiJUa pneumoniaeofthe same headers with a common gauze pad; staff not routinely header; rinse headers with treated water and disinfect
serotype and similar plasmid profile (72) changing gloves; dialyzers not reprocessed for several header components before reassembly; change gloves
hours after disassembly and cleaning frequently; reprocess dialyzers immediately after rinsing
and cleaning
Pyrogenic reactions in three high-flux dialysis Dialyzers reprocessed with two different disinfectanta; Do not disinfect dialyzers with multiple disinfectanta;
patienta (295) water used for reprocessing hemodialyzers did not meet disinfect water treatment system more frequently
AAMI standards
Pyrogenic reactions in 14 high-flux dialysis patients; one Dialyzers rinsed with tap water; water for reuse did not Do not rinse or clean dialyzers with city tap water; use treated
death (296) meet AAMI standards water that has been maintained to meet AAMI standards
Pyrogenic reactions in 18 patients (69) Dialyzers reprocessed with city tap water containing high Do not rinse or clean dialyzers with city tap water; use treated
levels of endotoxin; water did not meet AAMI standards water that has been maintained to meet AAMI standards
Pyrogenic reactions in 22 patients (71) Water for reuse did not meet AAMI standards; improper Use correct microbial assay procedure; disinfect water
microbial assay method was employed to monitor treatment system to maintain microbial quality of treated
dialysis fluids water and meet AAMI standards
Bacteremia with gram-negative water bacteria in Water distribution system had tlow and pressure problems; Evidence that !}'3tem had biofilm present; suggestions were
13 patients (297) B. apacia and Ral!tonia spp. were isolated from water made to consider replacing the distribution loop which
and dialysate. Water was sporadically above AAMI limita; would also help with the tlow and pressure problems.
no bacteremia in patients when reuse was suspended Scrapings of section of pipe that was removed had
evidence ofbiofilm.
Aaae h~!allergil; J"eCCdimu
Acute allergic reactions in hundreds of patients using Related to the use of angiotensin-converting-enzyme (ACE) No specific recommendations were made.
reprocessed hemodialyzers in at least 31 dialysis inhibitors, and possibly to chemicals used in cleaning
centers (70,170). dialyzer or inadequate disinfectant rinse out.
Nationwide outbreak of severe allergic-type reactions that Use of heparin manufactured by Baxter Healthcare was the Manufacturer recalled alllota implicated.
were first detected in a single hemodialysis facility. factor most strongly associated with reactions; heparin
152 cases identified (21). was found to be contaminated with oveHulfated
chondroitin sulfate (OSCS)
Hemolyftl and otMr fllilt:elltmeotu ~
Severe hemolytic events among dialysis patients in dialysis Three lots of bloodlines had a manufacturing defect that Manufacture recalled several lots of blood tubing sets
facilities in five states; at least three deaths (24) caused approximately 10% of the bloodlines to have
occlusions; these inclusions blocked between 20% and
80% of the internal diameter of the lines
State medical examiner's office notified CDC of a cluster Reviewed CMS and medical examiner records; Identified Nephrologists should review primary and secondary
of deaths due to vascular access hemorrhage (18) 88 confirmed cases; risk factors included: presence of prevention measures with their patients; particularly
an arteriovenous graft, access-related complications those who have had vascular access complications
within 6 months of death, hypertension
CDC notified of 28 patients with nephrogenic systemic 14 of 19 confirmed cases had receipt of gadolinium- Receipt of gadolinium-containing contrast solution should
fibrosis (NSF) at one medical center (19). containing contrast solution the year before onset; be avoided when possible in patients with end stage renal
gadolinium contrast exposure was associated with disease, particularly those receiving peritoneal dialysis.
NSF in a dose dependent manner
TRANSMISSION OF VIRAL AGENfS

26 patients seroconvert to HBsAg-positive (185) Blood leaks in coil dialyzers and use of recirculating bath Separation of HBsAg-positive patients and equipment from
dialysis machine susceptible patients; pressure-leak testing of reused
dialyzers was inadequate
19 patients and one staff member seroconvert to HBsAg- No specific cause identified; f.llse-positive HBsAg test Laboratory conf"umation ofHBsAg-positive results; strict
positive in a 14-month time frame (182) results caused some susceptible patients to be dialyzed adherence to glove use and use of separate (dedicated)
with infected patients equipment
40 patients (24 in-center, 12 home dialysis, and 4 home Home patients were excluded from the investigation Separation of HBsAg-positive patients and their dedicated
training) and 10 staff members convert to HBsAg- due to paucity of data; staffwere not wearing gloves; equipment from susceptible patients; proper precautions
positive during a 10 month period (186) environmental surfaces not routinely cleaned/ by staff (e.g., gloving, handling of needles and sharps,
disinfected; improper handling of sharps and disinfection of environmental surfaces)
13 patients and one staff member convert to HBsAg- Extrinsic contamination of intravenous hypertonic glucose Separate medication preparation area and blood processing
positive in a single month (180) being prepared adjacent to an area where blood work. for diagnostic tests
was handled
10 patients seroconvert to HBsAg-positive in a 1-month Extrinsic contamination ofbupivacaine that was shared No sharing of equipment, supplies, and medications between
period (179) between HBsAg-positive and susceptible patients patients
Eight patients seroconvert to HBsAg-positive over a five Sporadic screening for HBsAg; HBsAg-positive patient not Perform monthly screening of patients for HBsAg; isolate
month period (CDC, unpublished data) isolated; major bleeding incident with environmental HBsAg-positive patients with dedicated equipment and
contamination staff; vaccinate all susceptible patients
Seven patients seroconvert to HBsAg-positive during Same staff caring for HBsAg-positive and HBsAg-negative Separate HBsAg-positive patients from HBsAg- negative
a ~month period (184) patients patients; same staff should not care for both HBsAg-
positive and negative patients on the same shift
Eight patients convert to HBsAg-positive during Not consistently using pressure transducer protectors; User pressure transducer protectors and replace after each
1 month (187) same staff members cared for both HBsAg- positive patient; same staff members should not care for both
and negative patients on the same shift HBsAg-positive and -negative patients on the same shift
14 patients seroconverted to HBsAg-positive during Failure to review laboratory results of admission and Proper infection control precautions for dialysis units;
a 6-week period (188) monthly HBsAg testing; inconsistent hand hygiene and routine review of laboratory testing; hepatitis B
use of gloves; adjacent clean and contaminated areas; vaccination of all dialysis patients
<20% of patients vaccinated
Seven patients seroconverted to HBsAg-positive during Staff members cared for both HBsAg-positive and negative Dedicated staff for HBsAg-positive patients; no sharing of
a 2-month period (188) patients on the same shift; common medication medications or supplies between patients; centralized
and supply cans were moved between stations, and medication and supply areas; vaccinate all patients
multidose vials were shared; no patients were vaccinated against hepatitis B.
Four patients seroconverted to HBsAg-positive during 'fransmission appeared to occur during hospitalization at Vaccinate all patients to protect against hepatitis B
a ~month period (188) an acute care facility
11 patients seroconvened to HBsAg-positive during Staff, equipment, and supplies were shared between Dedicate staff for HBsAg-positive patients; no sharing of
a ~month period (188) HBsAg-positive and -negative patients supplies or medications between patients; vaccinate all
patients to protect against hepatitis B
Two patients seroconvert to HBsAg-positive during Same staff members cared for HBsAg-positive and -negative Dedication of staff for HBsAg-positive patients; hepatitis B
a 4-month period (181) patients; no patients were vaccinated vaccination for all patients
Clo)
Clo) (continued)
Clo)
~
~ TABLE 23.1 Outbreaks and Adverse Bvcnts in the Dialysis Setting Investigated by the Centers for Disease Control and Prevention (CDC)
Ill-
and StatejLocal Health Departments (Co•ri•llell)
36 patients with elevated liver enzymes consistent with Environmental contamination with blood Monthly liver enzyme screening; use proper infection control
non-A non-B hepatitis (298) precautions (e.g., gloving, environmental cleaning)
35 patients with elevated liver enzymes over a 22-month Inconsistent use of infection control precautions, especially Strict compliance with aseptic techniques and infection
period; 82% of cases were anti-HCV positive (189) hand hygiene and glove use control precautions for all dialysis patients
Seven of 51 patients seroconvert to anti-HCV Dialysis on same machine immediately after patient with Strict compliance with aseptic techniques and infection
positive (239,242) chronic HCV infection; preparation ofmultidose control precautions for all dialysis patients; routine
intravenous medication at the dialysis station; failure anti-HCV testing
to routinely dean dialysis machine or dialysis station
surfaces between patients
HCV infection developed in 5/95 patients (239,242) Dialysis on same machine immediately after patient with Strict compliance with aseptic techniques and infection
chronic HCV infection; preparation ofmultidose control precautions for all dialysis patients including
intravenous medication at the dialysis station; failure environmental cleaning and disinfection of the dialysis
to routinely dean dialysis machine or dialysis station machine and station, medication preparation in a
surfaces between patients; use of a mobile medication separate dean area; and discontinue use of mobile carts
or supply cart that was moved between dialysis stations to deliver supplies and medications between dialysis
stations
Incident HCV infection in 3/24 patients (239,242) Patients dialyzed at the station adjacent to that of patients Do not use mobile medication or supply carts that
with chronic HCV infection; use of a mobile medication move from station to station; deliver dean supplies
or supply cart that was moved between dialysis stations and medications to each station individually; follow
recommended infection control precautions for all
dialysis patients
Incident HCV infection in 7/64 patients (239,242) Patients dialyzed at the station adjacent to that of patients Do not use mobile medication or supply carts that move
with chronic HCV infection; receipt of intravenous from station to station; single-dose vials should not be
medication from vial (including single-dose vials) used shared; clean and disinfect dialysis machine surfaces
for <I patient; dialysis during the shift following that (including prime buckets) between patients, dean and
of patient with chronic HCV infection but not with the disinfect station area before setting up and priming
same machine; routine cleaning and disinfection of en- next patient's dialyzer and extracorporeal circuit; follow
vironmental surfaces not performed; mobile carts used infection control precautions for all dialysis patients
for delivery of medications and supplies
11/75 patients develop HCV infection (239) Preparation of injections in contaminated environment; Follow recommendations for infection control precautions
failure to separate dean and contaminated areas; for all dialysis patients, hand hygiene, and environmental
failure to change gloves and perform hand hygiene infection control
after handling contaminated dialysis equipment
7/183 patients develop HCV infection (239) Use of mobile cart to deliver injectable medications to Do not use mobile carts to deliver injectable medications
multiple patients; reuse of single-dose vials of epoetin or supplies; clean and disinfect external surfaces of
alfa on multiple patients; failure to clean dialysis the dialysis machine and patient station between each
equipment between patients patient; follow recommendations for infection control
precautions for all dialysis patients
HCV infections develop in nine patients ( 191) Multiple breaches in infection control practices including Patients transferred to other fucilities and dialysis center
inadequate cleaning and disinfection of the machine closed by the State regulatory agency, after several
and station (visible blood was present on dialysis attempts made to correct infection control deficiencies
chairs, machines, and floor) ; inappropriate glove use,
inconsistent hand hygiene; and deficiencies in training
HCV infectioru in eight patients (240) New infections were seen in patients dialyzed after or Follow recommended infection control precautioru for
on the same machine a patient with chronic HCV dialysis setting; proper use of gloves; perform hand
infection. Infection control lapses in medication hygiene and use new pair of gloves before performing
handling; lack of cleaning of access ports on CVCs; vascular access care; use antiseptic to disinfect CVC
heparin and saline were prepared at dialysis stations; hubs and injection ports prior to accessing; prepare
medications prepared and delivered using mobile carts. medications in an "clean" area dedicated for that
Patients were "bled on• to WHO-port and WHO-port purpose; parenteral medications should never be
was not disinfected between patients. Environmental prepared at the dialysis station; if facility chooses to
cleaning and disinfection were suboptimal; routine use medication and supply carts, these should remain
disinfection of machines conducted with patient still in stationary in a designated clean area; use an EPA-
dialysis chair. registered disinfectant for cleaning blood spills;
21 patients in a hospital-based outpatient dialysis unit Breaches in infection control practices identified by Strict compliance with aseptic techniques and infection
develop HCV infection (192) the local health department included: medication control precautions for all dialym patients including
preparation and delivery; suboptimal environmental environmental cleaning and disinfection of the dialysis
cleaning and disinfection machine and station, medication preparation in a
separate clean area; and discontinue use of mobile carts
to deliver supplies and medications between dialysis
stations
Two HCV infectioru in an outpatient hemodialysis No breaches in infection control identified but Follow recommendations for preventing infections
facility (193) epidemiologic and laboratory evidence suggested
in-center transmission.
HCV infection in six dialysis patients (194) Limited separation between "clean• and "contaminated• Facility should identify a staff member responsible for
areas; lab specimens processed in the same location infection control; conduct regular meetings to discuss
as medication preparation; overcrowding; significant infection control issues; iruure that monthly serology
lapses in cleaning and disinfection were observed; results are reviewed promptly; segregate clean and
blood glucose meters and clamps were not routinely contaminated areas; consider facility design and work
disinfected between patients; clean supplies obtained flow; consider redesign of treatment area to provide
by staff wearing contaminated gloves; blood glucose sufficient space between stations, and clean and
meters returned after use to "clean" supply table; ports contaminated areas; insure proper use of gloves and
on blood tubing and catheters not routinely disinfected hand hygiene; items used on more than one patient
before accessing should be cleaned and disinfected between each patient;
patient's station (chair and machine) should be cleaned
and disinfected with a EPA-registered disinfectant
13 patients at one dialym center in Colombia tested Facility reprocessed vascular access needles by soaking Access needles are single-use only; if they are to be reused
positive for HIV in 12 months; 9/13 seroconverted in a common container containing a low-level then they should be cleaned and sterilized between uses.
from negative to positive during this period and 2/9 benzalkonium chloride disinfectant; needles could have
had other risk factors (195) been shared among patients
HIV infection in 39 patients at two hemodialysis centers Practices that resulted in sharing of syringes among Do not share syringes. Follow infection control
in Egypt (196) patients were observed at both centers recommendations for preventing infections among
dialysis patients
Clo)
Clo)
en
of vascular access failures (18), cases of nephrogenic systemic chemical germicides and, as will be discussed later, have been
fibrosis due to exposure to gadolinium (19), neurologic symp- responsible for patient infections due to inadequately disin-
toms following use of aged dialyzers (20), adverse reactions and fected dialyzers that are reprocessed and inadequately disin-
death associated with heparin contaminated with over-sulfated fected peritoneal dialysis machines (35-38).
chondroitin sulfate (21), deaths following the use of dialyz- The strategy for controlling massive accumulations of gram-
ers contaminated with a perfluorocarbon performance fluid negative water bacteria or nontuberculous mycobacteria in di-
(22,23), and hemolysis due to defective bloodlines (24). This alysis systems primarily involves preventing their growth. This
chapter describes the major infectious diseases and other ad- can be accomplished by proper disinfection of water treat-
verse patient reactions that can be acquired in the dialysis cen- ment systems and hemodialysis machines. Gram-negative water
ter setting, the important epidemiologic and environmental bacteria and their associated lipopolysaccharides (bacterial en-
microbiologic considerations, and infection control strategies dotoxins) and nontuberculous mycobacteria ultimately come
for their prevention. from the potable water supply, and levels of these bacteria can
be amplified depending on the water treatment systems, dialy-
sate distribution systems, type of dialysis machine, and method
of disinfection (Table 23.2) (25,27,29,30,32). Each of these
BACTERIAL AND CHEMICAL
components is discussed separately in some detail.
CONTAMINANTS IN HEMODIALYSIS
SYSTEMS
A typical hemodialysis system consists of a water supply, a system Most dialysis centers use water from a public supply that may
for mixing water and dialysis fluid concentrates, and a machine be derived from surface, ground, or blends of surface and
to pump the dialysis fluid through the artificial kidney (com- ground waters. The source of the water may be important in
monly referred to as the hemodialy%f!T' or dialyzer). The dialyzer terms of chemical, bacterial, and endotoxin content. Surface
is connected to the patient's circulatory system as part of an waters frequently contain endotoxin from gram-negative wa-
extracorporeal circuit. Blood is pumped through the dialyzer ter bacteria and from certain types of blue-green algae (Cya-
where dialysis is accomplished by means of a membrane to re- nobacteria). Endotoxin levels are not substantially reduced by
move waste products from the patient's blood by both diffusion conventional municipal water treatment processes and can be
and convection. high enough to cause pyrogenic reactions in patients undergo-
ing dialysis (31).
Essentially all public water supplies are contaminated with
MICROBIAL CONTAMINATION OF WATER
water bacteria; consequently, a dialysis center's water treatment
Technical developments and clinical use of hemodialysis de- and distribution systems and dialysis machines are challenged
livery systems improved dramatically in the late 1960s and repeatedly with continuous inoculation of these ubiquitous
early 1970s. However, a number of microbiologic parameters bacteria. Even adequately chlorinated water supplies com-
were not accounted for in the design of many hemodialysis monly contain low levels of these microorganisms. Whereas
machines and their respective water supply systems. In many chlorine and other drinking water additives added to the city
situations, certain types of microorganisms such as gram-neg- water may prevent high levels of contamination, the presence
ative water bacteria, mycobacteria, and fungi can persist and of these chemicals in dialysis fluids is undesirable because of
actively multiply in aqueous environments associated with adverse effects on patients undergoing dialysis (39-46). Fur-
hemodialysis equipment under certain conditions. These or- thermore, the dialysis water treatment systems described in the
ganisms can adhere to surfaces and form biofilms, which are following section effectively remove chemical contaminants
extremely difficult to eradicate (25-28). This can result in including drinking water disinfectants, allowing for the unre-
the production of massive levels of microbial contamination, stricted growth of waterborne microorganisms.
which can directly or indirectly cause septicemia or endotox-
emia in patients (29-31).
W11~r 'PI'eBtrnent Systems
A number of factors can influence microbial contamina-
tion of fluids associated with hemodialysis systems (Table 23.2) Water used to produce dialysis fluid must be treated to remove
(29,32,33). The waterborne microbes can be important con- chemical contaminants. Since 1981 the Association for the Ad-
taminants in hemodialysis systems (Table 23.3), and virtually vancement of Medical Instrumentation (AAMI) has published
all disinfection strategies for fluid water distribution lines and guidelines for the chemical and bacteriologic quality of water
dialysis machines are targeted to this group of bacteria. Gram- used to prepare dialysis fluid. These guidelines and recom-
negative water bacteria are capable of multiplying rapidly in all mended practices have recently been harmonized with the
types of waters, even those containing relatively small amounts international community (47-49). However, CMS has adopted
of organic matter, such as water treated by distillation, soften- older AAMI standards covering water treatment, dialysate qual-
ing, deionization, or reverse osmosis (34). These organisms ity, and reuse of dialyzers as regulation to participate in the
can attain levels ranging from 105 to 107 colony forming units Medicare program (2,50-52).
( CFU) mL -l of water without turbidity and, under certain cir- Water systems are divided into three types of components
cumstances, can be a health hazard for patients. based on function: pretreatment, treatment, and polishing.
N ontuberculous or environmental mycobacteria also can Some pretreatment components may vary based on the area
multiply in water (Table 23.3). Although they do not con- of the United States and local water quality. Pretreatment
tain bacterial endotoxin, they are comparatively resistant to serves several purposes, the most important is protecting the
Chapter 23 • Dialysis-Associated Complications and Their Control 337
-~ {;C :f § :fJJ. Factors Influencing Microbial Contamination in Hemodialysis Systems

Facton Comments
WATER SUPPLY
Source of community water
Ground Contains endotoxin and bacteria
Surface Water Contains endotoxin and bacteria, may also contain cyanobacteria
WATER TREATMENT AT TilE DIALYSIS CENTER

None Not recommended
Pretreatment Serves to remove residual drinking water disinfectants, some organics and protect downstream
water treatment equipment from foulants, scale formation and oxidants
Multimedia Depth Filters Removes particles down to 15 microns, may act as significant reservoir of bacteria; these can be
baclwashed
Water Softener Ion exchange to remove ions associated with hard water; protects the reverse osmosis (RO) unit
from buildup of scale on the membrane; significant cause of bacteria and endotoxin
Granular Activated Carbon (GAG) Two beds/tanb in series with total empty bed contact time of 12 minutes; essential to remove
chlorine and chloramine; also removes some organics; mandatory if only using deionization for
water purification; significant source of bacteria and endotoxin
Cartridge Filter Placed prewater treatment devices such as RO unit to protect the unit from carbon fines and other
particulates in the pretreated water; may remove bacteria (depending on filter pore size);
selection of filter based on RO manufacturer's recommendations
Treatment
Reverse Osmosis Reduces inorganic chemical contaminants, bacteria, and endotoxin to safe levels; membranes
must be maintained (cleaned and disinfected)
Deionization (DI) Removes cations and anions from water to create highest ionic quality water; does not remove
bacteria or endotoxin; allows for significant bacterial growth and endotoxin production; if used
as the only water treatment device (usually as an emergency backup) GAG should always be
used as prefilter; DI tanks are often used to polish RO product water: highly dangerous when
exhausted
Ultraviolet (UV) irradiator Kills bacteria and may create UV resistant forms when energy output from the lamp decreases
Ultrafilter Removes bacteria and endotoxin; last water treatment device; usually placed after storage tank;
should be used in systems that have UV irradiators or DI tanks.
WATER AND DIALYSATE DISTRIBUTION

Distribution Pipes
Size Oversized diameter and length decrease fluid flow rate and increase bacterial reservoir for both
treated water and centrally prepared dialysate.
Construction Pipe materials, presence of rough joints, dead ends, and unused branches influence microbial
colonization and biofilm formation
Elevation Outlet taps should be located at highest elevation to prevent loss of disinfectant
Storage Thnb Can act as a reservoir for bacteria; if present, must be properly designed (including a tight fitting
lid) and vented, and routinely cleaned and disinfected
DIALYSIS MACIDNES
Single-pass Disinfectant should have contact with all parts of the machine that are exposed to water or dialysis
fluid; should be routinely disinfected
Recirculating machines/batch Recirculating pumps and machine design may allow for massive contamination levels if not
machines properly maintained and disinfected; must be rinsed and disinfected if a blood leak occurs;
see manufacturer's instructions
downstream treatment components. A variety of different water dialysis centers (13). RO possesses the singular advantage of
treatment system components are used, but most of them are being able to remove both bacterial endotoxins and bacteria
associated with amplification of water bacteria (Table 23.2). from supply water. However, low numbers of gram-negative or
The most common treatment components are ion ex- nontuberculous mycobacteria water bacteria can either pen-
change devices including water softeners (pretreatment) and etrate this barrier or colonize the downstream portion of the
deionizers (DI; treatment or posttreatment polisher). However, RO unit by other means. Consequently, reverse osmosis systems
these ion exchange components do not remove endotoxins or must be monitored and disinfected routinely.
bacteria, and both softeners and DI tanks contain large surface Various filters are marketed to control bacterial contamina-
areas and provide sites of significant bacterial multiplication tion in water and dialysis fluids. Most of these are inadequate,
(53,54). An effective means of treating water for dialysis is re- especially if they are not routinely disinfected or changed fre-
verse osmosis. By 1997, reverse osmosis (RO) or deionization quently. Particulate filters, commonly called prefilters, oper-
(DI) water treatment systems were being used by 99% of U.S. ate by depth filtration and do not remove bacteria or bacterial
• . §C :) 6JJJ. Types of Microorganisms Associated with Hemodialysis Systems

Gram-Negative Bacteria Gram-Positive Bacteria Fungi
NonfermenteD/Oxidative Gram-positive bacilli Aspergillus spp.
Bmn.t.ndimonas diminuta Bmribacterium spp. Pmicillium spp.
Burl!Jwlderia apacia complex Pasnibacillus spp. Phialemonium curoatu.m
Flavobacteria Leifscmia aquatica 'Inchoth«ium
Herbaspirillium spp. Nontuberculous mycobacteria Candida albicans
Methylobacterium spp. Mycobacterium abscssrus Candidaparopsilosi.s
Pseudomona.s aeruginosa Mycobacterium cl&elonae Candida spp.
Pseudomona.s fl~ Mycobacterium .fm1uitu.m Rlwdoturola spp.
Pseudomona.s putida Mycobacterium grwrJonae Tridw$flonm spp.
Pseudomona.s spp. Mycobacterium mucogll'licum
Ralstcmia piclcettii Mycobacterium scroftdaceum
Ralstcmia mannitolilytica
sphingrmwnas paucimobilis
Stenotroplumumas mallophila
Enterobacteriaceae
Enterobacter cloacae
Klebsiella [meumcmiae
Serratia liquefa.ciens
Serratia marusam.s
endotoxins. These filters can become colonized with gram- to ensure adequate disinfection. The multiplication of those
negative water bacteria, resulting in amplification of the levels microorganisms surviving initial exposure enhances resistance
of both bacteria and endotoxin in the filter effluent. Absolute to UVGI. In addition, UVGI does not affect bacterial endotox-
filters, including the membrane types, temporarily remove bac- ins. The use of high intensity UVGI in the pretreatment chain
teria from passing water. However, some of these filters tend to also may be used to destroy free and combined chlorine (59) .
clog, and gram-negative water bacteria can "grow through" the As mentioned, an effective means of treating water for di-
filter manix and colonize the downstream surface of the filters alysis is the correct use of a reverse osmosis unit. We recom-
within a couple of days. Furthermore, absolute filters do not mend using a water treatment system that produces chemically
reduce levels of endotoxin in the effluent water. These types adequate water with appropriately low levels of microbial con-
of filters should be changed regularly in accordance with the tamination. Such systems also are well suited for hard water
manufacturer's directions and disinfected in the same manner with appropriate pretreatment (e.g., using a softener to pre-
and at the same time as the dialysis system. vent scale formation on the RO membrane). Reverse osmosis
Granulated activated carbon (GAC) tanks remove certain is a membrane separation process for removing solvents from
organic chemicals and available chlorine (free and combined a solution using a semipermeable membrane. In this instance,
chlorine) from water by adsorption, but the filters also signifi- water is forced against the membrane (overcoming osmotic
cantly increase the level of water bacteria and do not remove pressure), which is highly permeable to water and rather im-
bacterial endotoxins. GAC readily removes free chlorine but is permeable to the dissolved contaminants. Thus, pure water is
not as efficient in removing combined chlorine (chloramines) pushed through to form product water. Water and contami-
and is greatly affected by pH of the feed water. As pH increases, nants (concentrate) that do not pass through the membrane
GAC becomes less efficient at removing chloramines. For or "rejected water" can be recirculated and diluted with feed
removal of free chlorine an empty bed contact time (EBCT) water or sent to drain. The RO is capable of removing a variety
(volume of carbon ft~ = (gallons per minute X EBCT)/7.48) of contaminants (down to atomic nuclei in size) and will rttiect
of at least 6 minutes is required and at least 10 minutes for 95% to 98% of cations and 85% to 90% of anions, depending
chloramines (55). on the RO membrane used (55,60). It is possible for bacteria
Ultraviolet germicidal irradiation (UVGI) lamps are some- to eventually get from the feed water to contaminate the prod-
times used to reduce bacterial contamination in water. These uct water, which is why RO membranes should be cleaned and
lamps should operate at a wavelength of 254 nm and provide disinfected per manufacturers' instructions.
a radiant energy dose of 30 milliwatt (mW)-sec cm-2. Several Posttreatment, RO water may be polished to chemically
studies have demonstrated that a dose of 30 mW-sec cm-2 will purify water further by using an additional treatment step, DI.
kill >99.99% of a variety of bacteria, including Pseudomonas The DI unit also may serve as an emergency backup to the RO
species, in a flow-through device (56,57). However, certain unit in case the RO fails. However, since DI units can become
gram-negative water bacteria appear to be more resistant to colonized and allow for microbial amplification, an ultrafilter
UVGI than others, and using sublethal doses of UVGI or expos- should always be placed at the final treatment step to remove
ing water for an insufficient contact time may lead to prolifera- bacteria and endotoxins (49,50,53,54,61) . The ultrafilter con-
tion of these resistant bacteria in the water system (33,58). This sists of similar types of membranes as in a RO unit, but it can be
problem may be accentuated in recirculating dialysis systems in operated at ordinary water line pressure. Depending on system
which repeated exposures to sublethal doses of UVGI are used design, ultrafilters should always be used if any one or more of
the following devices is used after the water treatment step stor- level of gram-negative bacterial contamination in dialysis fluid
age tank to remove bacterial and endotoxin: DI, UVGI. (25-27,29). Single-pass dialysis machines tend to respond to ad-
equate cleaning and disinfection procedures and, in general,
have lower levels of bacterial contamination in their dialysis
Distrilnt.tion Systems
fluid than do recirculating machines. Levels of contamination
Dialysis centers use one of two general systems configurations in single-pass machines depend primarily on the bacteriologic
for delivering water or dialysis fluids to individual dialysis ma- quality of the incoming water and on the method of machine
chines. The first type treats the incoming supply water and disinfection (29,32,33).
distributes it to individual free-standing dialysis stations either A frequent error in disinfecting single-pass systems occurs
in a direct feed system or an indirect feed system (recirculat- when the disinfectant is introduced in the same manner and
ing system). At each station, the water is mixed with dialysis through the same port as the dialysate concentrates. By so
concentrates to generate dialysate in the dialysis machine. doing, the pipes and tubing of the incoming water are not ex-
Another type of system, usually found in some large dialysis posed to a disinfectant; thus, the environment is such that bac-
centers, involves the automatic mixing of treated water and teria can readily colonize and proliferate, acting as a constant
dialysis concentrate at a central location followed by distribu- reservoir of contamination. To adequately disinfect a single-
tion of the warmed dialysis fluid through pipes to individual pass system, the disinfectant must reach all parts of the system's
dialysis stations. In some facilities the dialysis concentrates are fluid pathways (61,63).
prepared from powdered components and centrally delivered
to each station by piping systems. In these system designs, the
distribution system consists primarily of plastic piping (e.g.,
polyvinyl chloride [PVC], cross-linked polyethylene [PEX], The dialyzer (artificial kidney) usually does not contribute sig-
polyvinylidene fluoride [PVDF], polypropylene [PP]) and nificantly to bacterial contamination of the dialysate. Hemodi-
valves, though some facilities use 316L stainless steel or glass alysis patients are treated using hollow-fiber dialyzers. These
for their distribution systems ( 49,50). devices are classified as either low-flux or high-flux based on
These distribution systems can contribute to microbial con- membrane characteristics (64,65). The percentage of centers
tamination in two ways; first, they sometimes use pipes that are that reported reuse of dialyzers on the same patient increased
larger in diameter and longer than necessary to handle the from 18% to 82% during the period from 1976 to 1997, but de-
required fluid flow. This slows the fluid velocity and increases clined over the next 5 years to 63% in 2002 as one of the large
both the total fluid volume and the wetted surface area of the dialysis providers moved from reuse to nonreuse (3,13,16,66).
system. Gram-negative bacteria in fluids remaining in pipes Improper reprocessing techniques have been associated with
may multiply rapidly and colonize these wetted surfaces of the outbreaks of bacteremia and pyrogenic reactions in dialysis
pipes, producing bacterial populations and endotoxin quanti- patients (38,67-73).
ties in proportion to the volume and surface area (62). Such
colonization results in bacterial formation of protective bio-
Disinfection ofHemotli11lysis Systems
film, which is difficult to remove and protects the bacteria from
disinfection (62). The objective of a dialysis system disinfection procedure is to
Because pipes can constitute a source of water bacteria primarily inactivate bacteria and fungi in the fluid pathways as-
within a distribution system, routine disinfection should be sociated with the dialysis system and to prevent these organisms
performed at least weekly. To ensure that the disinfectant can- from growing to significant levels once the system is in opera-
not drain from pipes by gravity before contact time is adequate, tion. Routine disinfection of isolated components of a dialysis
distribution systems should be designed with all outlet taps at system frequently produces inadequate results in which the
equal elevation and at the highest point of the system. Further- hazard to the patient persists. Consequently, the total dialysis
more, the system should be free of rough joints, dead-end pipes, system (water treatment system, distribution system, and dialy-
and unused branches and taps. Fluid trapped in such stagnant sis machine) needs to be considered when selecting and apply-
areas can serve as reservoirs of bacteria capable of continuously ing disinfection procedures.
inoculating the entire volume of the system (30,32,33,61). Chlorine-based disinfectants (e.g., sodium hypochlorite so-
Incorporation of a storage tank in a distribution S}'lltem lutions) are convenient and effective in most parts of the di-
greatly increases the volume of fluid and surface area avail- alysis system when used at the manufacturer's recommended
able to act as reservoirs for the multiplication of water bacteria. concentration. Also, the test for residual available chlorine to
Storage tanks should not be used in dialysis systems unless they confirm adequate rinsing is simple and sensitive. However, be-
are properly designed, frequently drained, and adequately dis- cause of the corrosive nature of chlorine, the disinfectant nor-
infected. This may include scrubbing the insides of the tank mally is rinsed from the system after a short (20 to 30 minutes)
to physically remove bacterial biofilm. It is also recommended exposure time. This practice commonly negates the disinfec-
that an ultrafilter be used distal to the storage tank (61,63). tion procedure because the rinse water is not sterile and in-
variably contains waterbome microorganisms that immediately
resume multiplication. If permitted to stand overnight, the
Hemotlilllysis MJJ&hines
water may contain significant microbial contamination levels.
Currently in the United States, virtually all centers use single- Therefore, chlorine disinfectants are most effective when ap-
pass hemodialysis machines. In the 1970s, most machines plied just before the start-up of the dialysis system rather than
were of the recirculating or recirculating single-pass type. at the end of the daily operation (74,75). In some large cen-
The nature of their design contributed to a relatively high ters with multiple shifts, it may be reasonable to use sodium
hypochlorite disinfection between shifts (this may not be nec- dialysate have the same maximum contaminant levels (MCLs)
essary with some single-pass machines, if the levels of bacterial for microorganisms, however, maximum endotoxin levels are
contamination are below .MMI action limits) (2,47,48,50,51) 0.5 endotoxin units (EU) mL- 1 for dialysate and 0.25 EU mL - 1
and disinfection with peracetic acid, hydrogen peroxide, for water (47,49). Action levels also have been included and have
ozone, or hot water at the end of the day (75-77). been set to 50% of the MCL. They also have included standards
Hydrogen peroxide, ozone, hypochlorite solutions, heat for ultrapure dialysate and dialysate for infusion (Thble 23.4)
and citric acid, and peracetic acid can produce good disinfec- ( 47). However, in the United States, CMS (2) has adopted AAMI
tion results (27,74,77-84). They are not as corrosive as hypo- limits for water and dialysate based on the older standards with
chlorite solutions and can be allowed to remain in the dialysis MCLs of 200 CFU mL - 1 and 2 EU mL -l (50-52) .
system for long periods when it is not operational, thereby pre- The microbiologic assay is quantitative rather than qualita-
venting the growth of bacteria in the system. Aqueous form- tive, and a standard technique for enumeration should be used;
aldehyde used to be commonly used as a disinfectant in the the standard recommended method is membrane filtration
dialysis setting because it has good penetrating characteristics. (47-49,51,91). Water samples should be collected at a point
However, it is considered an environmental hazard and poten- that is as close as possible to where water enters the dialysate
tial carcinogen and is associated with irritating qualities that concentrate-proportioning unit. Samples should be collected
are objectionable to staff members. Formaldehyde is very rarely at least monthly for established units and weekly for new units
used today because of Environmental Protection Agency (EPA) until an established pattern is determined. Repeat samples
regulations regarding wastewater discharges and its potential as should be collected when microbial counts exceed the action
an occupational hazard. level (Thble 23.4) and after disinfection changes have been in-
Some dialysis systems use hot-water disinfection (pasteuri- stituted. Dialysis fluid samples should be collected at the start
zation) to control microbial contamination. In this type of or termination of dialysis close to the point where the dialysis
system, water heated to >8o•c (176.F) is passed through all fluid either enters or leaves the dialyzer. These types of samples
proportioning, distribution, and patient-monitoring devices also should be taken at least once monthly and after suspected
before use. Tills system is excellent for controlling bacterial pyrogenic reactions or changes in the water treatment system
contamination (27,84). Use of ozone also has been increasing or disinfection protocols.
as a means of sanitizing water treatment distribution loops and Samples should be assayed within 30 minutes or refriger-
central bicarbonate delivery systems (77). ated ( 4 •q and assayed within 24 hours of collection. Total vi-
able counts (standard plate counts) are the objective of the
assays, and conventional laboratory procedures, such as mem-
Monitoring W4tuo 4nd DiRlysis Fluid
brane filtration technique or spread plate, can be used; cali-
Bacteriologic assays of water and dialysis fluids should be per- brated loops should not be used because they sample a small
formed at least once a month. Chemical analysis of water used volume and are inaccurate. Current monitoring methods in-
for dialysis should be done before the system is designed and clude the use of nutrient poor media (tryptone glucose extract
then at least seasonally (since feed water quality is not static and agar (TGEA), Reasoner's 2A (R2A), standard methods agar, or
may change) to ensure that the water is of sufficient quality for other media that yield similar results), lower incubation tem-
hemodialysis applications (48). The current recommended max- peratures (17• to 23.C) , and 7 days of incubation (47,49,91) .
imum level of microbial contamination of water and standard These differ from those recommended in .MMI RD52-2004;
dialysate used for hemodialysis is 100 CFU mL- 1 (47,49). These based on the old standard that used trypticase soy agar, incu-
particular numbers are based, in part, on an increasing body bated at 35• to 37•c for 48 hours (51). Historically, there has
of evidence indicating that dialysate may be partly responsible been much discussion in the dialysis community that these
for the chronic inflammatory state in dialysis patients (85-90). older methods in fact underestimate the actual contamination
In these new AAMI recommendations, water and conventional of dialysis fluids (92-96) .
. , tiC :J 5fJI. Microbial Quality of' Standards for Dialysis Fluids

1 Endotoldn (EU mL- 1)
Microbial Bioburdeo (CFU mL- )
Fluid 'I)pe Maximum Limit Amon limit Maimum lirltit Amon Level
AMERICAN NATIONAL STANDARDS INSTITUTE (ANSI)/AAMI (48,50,51)
Water for all purposes 200 50 2 1
Conventional dial}'!llte 200 50 2 1
Ultrapure dial}'!llte 0.1 _6 O.Oll O.Oll
Dialysate for infusion 10-6a _6 O.Oll O.Oll
ANSI/AAMI/ISO (47,49)
Water for hemodialysis 100 50 0.25 0.125
Conventional dial}'!llte 100 _6
50 0.5
Ultrapure dialysate 0.1 _b O.Oll _6
"Compliance is not demorutrated by culture but by engineering process developed by the equipment manufacturer, (e.g., serial ultrafiltration).
~one specified.
In the event of an outbreak, the assay may need to be occurred at centers using dialysis machines having a port to
both qualitative and quantitative, and samples may have to dispose of dialyzer priming fluid (waste handling option)
be cultured using additional microbiologic culture media (110-114). The one-way check valves in the waste handling
and methods as is the case with nontuberculous mycobacteria option had not been maintained, checked for competency, or
and fungi. In such instances, plates should be incubated up to disinfected as recommended, allowing backflow from the drain
14 days or longer based on the organism of interest. (post-dialyzer effiuent side of machine), contamination of the
If centers reprocess dialyzers for reuse on the same patient, port, and backflow of fluid into the patients' blood lines.
water used to rinse dialyzers and prepare dialyzer disinfectants
also should be assayed at least monthly in the manner described SURVEILLANCE OF PYROGENIC REACTIONS
previously. It is recommended that microbial or endotoxin con- AND INFECTIONS
centrations not exceed those published in "Water for hemodi-
alysis and related therapies" (Table 23.4) (49). Pyrogenic reactions in patients undergoing dialysis are associ-
ated with shaking chills, fever, and hypotension. Depending on
the type of dialysis system and the level of initial contamina-
tion, the onset of an elevated temperature and chills can oc-
PYROGENIC REACTIONS cur 1 to 5 hours after the initiation of dialysis and usually are
AND INFECTION associated with a decrease in systolic blood pressure of at least
30 millimeters of mercury (mm Hg). Other less frequent but
PYROGENIC REACTIONS characteristic symptoms may include headache, myalgia, nau-
AND SEPTICEMIA/FUNGEMIA sea, and vomiting. We define a case of pyrogenic reaction as the
Pyrogenic reactions and gram-negative sepsis are the most com- onset of objective chills (visible rigors), fever (oral temperature
mon complications associated with high levels of gram-negative 2:37.8•C), or both in a patient who was afebrile (oral tempera-
bacterial contamination of dialysis fluid. Pyrogenic reactions ture :::s37.o•q and who had no signs or symptoms of infection
can result from either the passage of bacterial endotoxin before the dialysis treatment (31,69,105,115).
(lipopolysaccharide) in the dialysis fluid across the dialyzer Differentiating gram-negative bacterial sepsis from a
membrane, the transmembrane stimulation of cytokine produc- pyrogenic reaction can be difficult because the initial signs
tion in the patient's blood by endotoxins in the dialysis fluid, or and symptoms of the two conditions are identical. The most
direct contamination of the dialyzer blood compartment during reliable means of detecting sepsis is by culturing blood taken at
reuse (67,71,97-104). In other instances, endotoxins or bacte- the time of the reaction. However, because the results of these
ria can enter the bloodstream directly with fluids that are con- cultures take at least 18 to 24 hours to obtain and because ther-
taminated with gram-negative bacteria ( 105) . Bacteremia also apy for sepsis should not be withheld for this length of time,
can result from poor aseptic technique during vascular access other less reliable criteria must be used. Many pyrogenic re-
care, use of contaminated antiseptic agents, or contamination actions are not associated with bacteremia, and the preceding
of bloodlines from healthcare worker hands, priming buckets, signs and symptoms generally abate within a few hours after
or waste handling option ports. Studies indicate that chronic dialysis has been stopped. With gram-negative bacterial sepsis,
hemodialysis patients have enhanced cytokine response com- fever and chills may persist, and hypotension is more refractory
pared to nonhemodialysis patients, which may account for the to therapy (31,105).
high rate of fatal sepsis in uremic patients (106-108). The early detection of pyrogenic reactions or gram-negative
The more contaminated the dialysis fluid, the higher the sepsis depends on a thorough understanding of the signs and
probability that bacteria or endotoxin will pass through the di- symptoms of these entities by the dialysis staff and on the careful
alysis membrane. In early outbreaks of febrile reactions among charting of the patient's symptoms and changes in blood pres-
patients undergoing dialysis, the attack rates were directly pro- sure and temperature. The following diagnostic procedures are
portional to the level of bacterial contamination in the dialysis recommended for patients who meet the criteria of a pyrogenic
fluid (33). Prospective studies also demonstrated a lower pyro- reaction: a careful physical examination to rule out other causes
genic reaction rate among patients when they underwent di- of chills and fever (e.g., pneumonia, vascular access infection,
alysis with dialysis fluid that had been filtered and from which urinary tract infection); blood cultures, other diagnostic tests
most bacteria had been removed compared to patients who un- (e.g., chest radiograph), and cultures as clinically indicated;
derwent dialysis with dialysis fluid that was highly contaminated collection of dialysis fluid from the dialyzer (downstream side)
(mean 19,000 CFU mL- 1) (109). for quantitative and qualitative bacteriologic assays; and record-
In 1997, 21% of U.S. hemodialysis centers reported at least ing the incident in a log or other permanent record. Determin-
one pyrogenic reaction in the absence of septicemia in patients ing the cause of these episodes is important because they may
undergoing dialysis (13). This reported rate was fairly stable be the first indication of a remediable problem.
from 1989 to 1997 (19% to 22%) (6-13). An active surveillance
system is essential for early detection and control of these com- HEMODIALyzER REUSE
plications. Clinical reactions should be defined as they occur
because doing so may be the first clue that a problem exists. In
AND ADVERSE EVENTS
addition, the dialysis system should be microbiologically moni-
HEMODIALyzER REUSE
tored periodically by methods described previously.
Of 10 outbreaks of bacteremia and pyrogenic reactions not In the early 1960s, the most common dialyzer used in dialysis
related to dialyzer reuse investigated by the CDC, inadequate centers was the Kiil plate dialyzer, which was cleaned and dis-
disinfection of the water distribution system or machines was infected after each patient use and supplied with a new set of
implicated in 9 of them (Table 23.1). Four of these outbreaks cuprophane membranes. The dialyzer housing, however, was
reused each time. With the development of disposable coil and not performed with this type of system (123). It is emphasized
hollow-fiber dialyzers, the use of the Kill dialyzer was iliscontin- that adverse reactions associated with reuse of dialyzers are
ued. Disposable dialyzers are medical devices that are supplied accentuated in dialysis centers that are having problems with
in a sterile state and were initially intended by the manufac- their water system and that, for the most part, only a small num-
turer for one-time use and since 1995 have required specific ber of centers are experiencing an increased risk with dialyzers
labeling that identified single use or multiple use (116). that are reused more than 20 times or that include a manual
In recent years, as a cost-saving effort, more centers are reprocessing system. In 1993, only a modest and insignificant
reusing dialyzers on the same patient after employing an ap- association between dialyzer reuse and reporting of pyrogenic
propriate ilisinfection procedure. Although it has caused some reactions at U.S. hemodialysis centers occurred (10).
controversy, this is now standard practice in the dialysis com- The procedures used in dialysis centers for reprocessing
munity. In 1997, the average number of times a dialysis center hemodialyzers are not classified as sterilization procedures but
reused dialyzers was 17 (1 to 65). The mean maximum number constitute high-level disinfection ( 123,124) . In 1983, most cen-
of times a dialyzer was reused was 38 (1 to 179) (13). Dialysis ters in the United States (94%) used 2% aqueous formaldehyde
centers most likely to report reuse of dialyzers were those with with a contact time of approximately 36 hours for high-level dis-
larger patient populations (>40), those located in free-standing infection of disposable dialyzers (73). Although this procedure
facilities, and those operated for profit compared with centers may be satisfactory against the presumed microbiologic chal-
with smaller patient populations, those located in hospitals, lenge of gram-negative water bacteria, it is inadequate for the
and those not operated for profit ( 4-16) . However, one of the highly germicide-resistant nontuberculous mycobacteria.
large U.S. dialysis provider organizations made a decision to CDC investigated an outbreak of infections caused by non-
iliscontinue reuse, which accounted for the drop in reuse in tuberculous mycobacteria during which 27 infections occurred
2002 to 63% of facilities and may eventually fall to the share among 140 patients (35). The source of the nontuberculous
of the dialysis market not represented by this provider ( 16,66). mycobacteria appeared to be the water used in processing the
CDC's surveillance has not shown a correlation between dialyzers. It was evident that 2% formaldehyde did not effec-
the incidence of hepatitis B or hepatitis C and dialyzer reuse. tively inactivate populations of these mycobacteria within a
A controversial study has shown a statistical association be- 36-hour time period. It was subsequently shown that 4% form-
tween the reuse of dialyzers disinfected with glutaraldehyde or aldehyde with a minimum contact time of 24 hours could in-
peracetic acid/hydrogen peroxide and increased death rates activate high numbers of nontuberculous mycobacteria; as a
at dialysis centers (117,118). However, other factors may have consequence, 4% formaldehyde is recommended as a mini-
contributed to what appears to be a causal relationship between mum formaldehyde concentration for disinfection of dialyzers
reuse and a higher death rate, or the association may be due to (35,123,124).
unmeasured confounding factors (118-121). A similar outbreak of systemic mycobacterial infections in
In 1986, the U.S. Public Health Service (PHS) subsumed five dialysis patients, resulting in two deaths, occurred when
the AAMI's guidelines for reusing hemodialyzers and recom- high-flux dialyzers were contaminated with mycobacteria dur-
mended them as PHS guidance to CMS, which made them ing manual reprocessing and then were disinfected with a com-
conditions for participation in Medicare. In effect, the AAMI mercial dialyzer disinfectant prepared at a concentration that
guidelines, which became PHS guidance, resulted in CMS reg- did not ensure complete inactivation of mycobacteria (38) .
ulations (2). In general, if the procedures involved in repro- These two outbreaks emphasize the need to use dialyzer dis-
cessing hemodialyzers are performed according to established infectants at concentrations that are effective against the more
and strict protocols, patients do not appear to have harmful chemically resistant microorganisms, such as mycobacteria.
effects. However, the practice of reusing disposable hemodia- Pyrogenic reactions in dialysis patients caused by reprocess-
lyzers should not be considered risk free. Outbreaks of patient ing dialyzers with water that did not meet AAMI standards have
infections and pyrogenic reactions associated with user error been frequently associated with epidemics investigated by the
have occurred (Table 23.1). Many of these episodes were the CDC (Table 23.4). In most of these outbreaks, the water used
result of inadequate reprocessing procedures, such as the use to rinse dialyzers or to prepare dialyzer ilisinfectants exceeded
of incorrect concentrations of chemical germicides or failure allowable AAMI microbial or endotoxin standards because the
to maintain standards for water quality (122). In addition, in water ilistribution system was not ilisinfected frequently, the
1986, six dialysis centers reported outbreaks of pyrogenic reac- ilisinfectant was improperly prepared, or routine microbiologic
tions and septicemia that were associated with the use of a new assays were improperly performed.
germicide, the active ingredient of which was chlorine dioxide. Between 2001 and 2002, one of the large dialysis organi-
That germicide, although efficacious for disinfecting dialyz- zations reported sporadic clusters of fungemia with Candida
ers, appeared to degrade the integrity of cellulosic dialyzer pampsilosis and bloodstream infections (BSis) with Burklwld-
membranes to such an extent that leaks in the membranes eria cepacia, Ralstonia pickettii, and Stenotrophomlmas maltophilia
developed (104). Centers that reported using this germicide associated with reuse [CDC unpublished data, 2002]. Several
typically employed manual reprocessing, and most of these of these facilities were in California and were investigated by
centers reused their dialyzers more than 20 times. the California Department of Health Services. In response to
Reprocessing dialyzers in a manual reprocessing system these outbreaks, they conducted a survey of reuse practices in
has been shown to be significantly associated with a higher all California dialysis facilities. They found that the BSI dus-
reported frequency of pyrogenic reactions and was not neces- ters caused by S. maltophilia, B. cepacia complex, R. pickettii, or
sarily related to the absolute number of reuses (69,73). Some C. pampsilosis were more likely to occur in dialysis facilities that
dialyzer membrane defects may go undetected when manual refrigerated dialyzers before reprocessing them (125). Instead
reprocessing systems are used, because testing for dialyzer of reprocessing dialyzers immediately after use, these facilities
membrane integrity, as with an air-pressure-leak test is generally refrigerated and stored dialyzers to be reprocessed later.
OTHER INFECTIONS endocarditis, or meningitis. Reported rates of BSis and access

site infections among hemodialysis patients vary. Although the
VM&ulllr .Auess Site Infections
most frequent pathogens are Staphylococcus aureus or S. epider-
Hemodialysis procedures depend on direct and repeated ac- midis, gram-negative bacteria also can be responsible for BSis,
cess to large blood vessels that can provide rapid extracor- especially if the vascular access is in the patient's lower extremi-
poreal blood flow. Scribner developed a method for vascular ties. Transmission of these types of bacterial infections among
access by surgically inserting plastic tubes, one into an artery patients or from staff members to patients in the hemodialysis
and one into a vein. After treatment, the circulatory access center setting is primarily due to cross-contamination, which
would be kept open by connecting the two tubes outside the results in colonization and subsequent infection in a subset
body using a small u._,haped device, which would shunt the of these patients. Transmission can be controlled by good
blood from the tube in the artery back to the tube in the vein hand-hygiene and gloving techniques as well as good aseptic
(126,127). Although the external arteriovenous (AV) shunts techniques during access care ( 134,136-141) .
were the foundation on which modem dialysis grew, their use For many years, central (subclavian or jugular) catheters
in recent years has been limited to patients who require tem- have been used for temporary venous access for hemodialy-
porary access to treatment. The material used for these shunts sis. Technical improvements have made it feasible to use these
can be biologic or synthetic. External shunts are primarily used catheters for permanent access, usually in patients for whom
for those in emergent need for continuous renal replacement no other access is available ( 17,140,141). However, eves have
therapy (CRRT) when catheters (central or femoral lines) can- high rates of failure due to thrombosis and infection (17).
not be placed (128). Three primary types of vascular access are A catheter-graft hybrid device that is completely subcutaneous is
used for hemodialysis therapy: native AV fistulas, AV grafts, and now available for some patients who had no vascular access op-
central hemodialysis catheters (129). tions other than a eve [www.herograft.com]. Limited data on
The AV fistula is believed to provide the best long-term infection rates associated with this device have been reported.
access to circulation with the least number of complications. In 1991, CDC investigated 35 BSis among 68 patients receiving
However, in 2002 only 33% of all U.S. hemodialysis patients hemodialysis through eves; 1 patient died and 1 developed
had AV fistulas; 42% had AV grafts and 26% had a central line endocarditis that required aortic valve replacement (142).
for dialysis. The use of central venous catheters (evCs) for Improved eve care practices were recommended to control
vascular access had doubled between 1995 and 2002 while the the outbreak. Prevention involves (a) aseptic manipulation of
use of AV grafts has declined from 65% to 42% of patients. AV the eve hub and bloodlines, (b) a procedure for aseptic con-
fistula use has increased from 22% of patients in 1995 to 33% nection and disconnection of the bloodlines relative to the pa-
of patients in 2002 ( 16). In 2003, CMS began their Fistula First tient's catheter, and (c) appropriate access site care. CDC has
Breakthrough Initiative and reported that the National fistula developed a set of Core Interventions to Prevent BSis in hemo-
rate climbed to almost 60% in 2011 (130) and by April2012 had dialysis patients [http://www.cdc.govI dialysis/collaborative/in
risen to 60.6% (http://www.fistulafirst.org/). However, most terventions/index.html]. They include evidence-based practices
patients (63.2%) initiating dialysis do not have a permanent such as conducting infection surveillance (and using the data to
access and begin dialysis with a eve as their sole vascular access influence practice), performing audits of staff compliance with
and another 20.3% begin dialysis with a eve with a maturing recommended practice with feedback, educating staff members
access (graft or fistula) in place (131). and patients, improving hand hygiene, using chlorhexidine with
Access site infections are particularly important because they alcohol for eve exit site care, scrubbing the catheter hub before
can cause disseminated bacteremia/fungemia or loss of the ac- accessing, and applying an antimicrobial ointment or chlorllexi-
cess. Local signs of vascular access infection include erythema, dine-impregnated dressing to the eve exit site. Early data suggest
warmth, induration, swelling, tenderness, skin breakdown, implementing these interventions in dialysis centers can success-
loculated fluid, or purulent exudate (132-136). Vascular access fully reduce BSis [http://www.cdc.gov/dialysis/collaborative/
site infections may account for 15% to 20% of all access-related news-reports/index.html], and tools are available to assist with
complications. In general, the length of time that a catheter is implementation [http://www.cdc.govI dialysis/prevention-tools/
left in place and the duration of cannulation can be important index.html].
factors predisposing to infection. Also important are catheter
care and accessing techniques and cannulation practices. In
Infections Associllted with Peritoneal Dialysis
addition, the type of fistula (radiocephalic, brachiocephalic,
transposed brachiocephalic, loop LSV femoral, loop forearm As mentioned earlier, approximately 5% of U.S. ESRD patients
brachiocephalic, loop, loop forearm LSV fistula), nature of the were treated by peritoneal dialysis at the end of 2010 (1). In
catheter exit site dressing, number of cannulations, rotation of peritoneal dialysis, the patient's peritoneal membrane is used
the cannulation site, and personal hygiene of the patient may to dialyze waste products from the patient's blood. In the
play a role in the acquisition of infection. mid-1970s, the development of automated peritoneal dialy-
In 2008, an estimated 37,000 BSis occurred among hemo- sis systems made IPD a viable alternative to hemodialysis for
dialysis outpatients with eves (137). More than 80% ofESRD long-term management of ESRD patients. Currently, this ap-
patients initiating hemodialysis do so with a eve, and eve use proach has been replaced by CAPD and continuous<ycling
remains the greatest risk factor for BSis in this patient popula- peritoneal dialysis (CCPD also known as automated peritoneal
tion. BSis can occur, either by migration of bacteria down the dialysis or APD) in which commercially available presterilized
outer surface of a hemodialysis catheter (tunnel) or by con- dialysis fluid is either introduced by gravity or is pumped and
tamination of the lumen (via the hub) of the catheter during cycled into a patient's peritoneal cavity. In CAPD, the dialyzing
attachment or detachment during dialysis. BSis related to the fluid is self-administered by the patient who has a surgically im-
vascular access site can lead to sepsis, septic pulmonary emboli, planted catheter. The exchanges are done every 4 hours, and
the patient can be mobile between exchanges (143). The most containing the sterile dialysis fluid and the patient's catheter,
persistent problem in the management of patients treated by and (c) appropriate access site care (146,154,155).
peritoneal dialysis is peritonitis (143-146).
In the past, automated peritoneal dialysis machines were NONINFECTIOUS COMPLICATIONS
used to create dialysate from tap water. To prevent the growth
of pathogenic microorganisms that cause infection, APD ma- First-Use tnul Allergic RBt~.&tions
chines had to be cleaned and maintained properly. In theory, A variety of symptoms attributed to hypersensitivity reactions
the incidence of peritonitis should be low because the ma- may occur during dialysis. Symptoms variously reported in-
chine functions as a closed system. However, these older APD clude increased or decreased blood pressure, dyspnea, cough,
machines may themselves provide a reservoir for pathogens conjunctival injection, flushing, urticaria, headache, and pains
that cause peritonitis. Several outbreaks of bacterial peritoni- in the chest, back, and limbs. Such symptoms are more com-
tis among patients receiving IPD have been reported, and the mon during the first use of a dialyzer and have been termed
etiologic agents have included Mycobacterium chelonei-like organ- the "first-use syndrome" (157-159). These reactions are more
isms or B. cepacia (37,147). Both organisms can grow in water; common with cuprophan dialyzers; some may be attributable
investigation of these outbreaks revealed that machines were to residual ethylene oxide in dialyzers (160-163). Reports of
inadequately cleaned and disinfected and that the product first-use syndrome have decreased from 43% of centers in 1984
water and dialysis fluid contained the microorganisms respon- to 23% of centers in 1997 (13).
sible for peritonitis ( 148). In addition, one group of organ- In 1990, several outbreaks of anaphylactoid reactions associ-
isms, the nontuberculous mycobacteria such as M. chelonae, ated with angiotensin-converting enzyme (ACE) inhibitors were
is significantly and extraordinarily resistant to the commonly reported. Reactions occurred within 10 minutes of initiating di-
used disinfectants (149). Berkelman et al. recommended a set alysis and included nausea, abdominal cramps, burning, flush-
of guidelines that can ensure the production of sterile dialysis ing, swelling of the face or tongue, angioedema, shortness of
fluid and reduce the likelihood of outbreaks of peritonitis for breath, and hypotension. One outbreak was linked to the reuse
dialysis centers using APD machines (150). It should be noted of dialyzers (70), but other reports have implicated polyacrylo-
that, for all practical purposes, the use of these former APD nitrile (PAN) dialyzers in these types of reactions (164-169). In
machines has been discontinued in the United States, and the 1992, the Food and Drug Administration (FDA) issued a safety
preceding information is cited for completeness and for his- alert regarding anaphylactoid reactions in patients on ACE
torical considerations. Currently employed peritoneal dialysis inhibitors, especially those using PAN dialyzers (170).
machines or cyclers use disposables (i.e., prepackaged sterile
dialysate, tubing) so that there is no contact between machine
and fluids.
With CAPD, or CCPD catheter-related infections and peri- Dialysis encephalopathy, or dialysis dementia, is a disorder that
tonitis remain the most common cause of morbidity among affects dialysis patients who, for a variety of reasons, are subjected
peritoneal dialysis patients, contribute significantly to the cost to water that has a relatively high content of aluminum, such as
of this treatment, and are the primary reason for the aban- community water supplies treated with alum (171,172). Dialy-
donment of peritoneal dialysis. In general, peritonitis has dra- sis encephalopathy was first described by Alfrey et al. in 1972
matically decreased from the inception of peritoneal dialysis. (173). Schreeder et al. first demonstrated the role of aluminum
These infections have been reported to occur at rates of 0.56 to as a significant contributing factor in this disorder in an epide-
1.58 episodes per patient per year and have been reported as miologic study ( 42). Case definitions of dialysis encephalopathy
low as 0.23 to 0.29 episodes per patient per year (145,151-156). include three different groups of objective findings: speech im-
Clinical symptoms of peritoneal infection usually appear 12 pairment, seizure disorders, and motor disturbances. Patients
to 36 hours after bacterial contamination of the peritoneal cavity. exposed to high aluminum concentrations (>100 ng L -l) in
Symptoms include nausea, vomiting, and abdominal pain. Later, dialysate were at increased risk of developing dementia. The
vague abdominal tenderness may progress to severe, diffuse, number of episodes of dialysis dementia reported to CDC has
or localized pain associated with fever, abdominal distention, decreased from 0.4% in the years 1980 and 1983-1985 to 0.1%
and gastrointestinal dysfunction. The clinical diagnosis should in 1990 (N = 129; case-fatality rate = 21%) (7). Although it
be confirmed by bacteriologic analysis of the peritoneal fluid. is not dear what was responsible for this decrease, we believe
Cloudy peritoneal fluid often is the first sign of infection. it may be related to increased awareness in the dialysis com-
The typical causative agents of peritonitis are S. epidermidis munity of the requirement for good water treatment systems.
(30% to 40%), S. aureus (10% to 20%), streptococci (5% to In 1980, only 26% of U.S. hemodialysis centers reported that
10%), mycobacteria (less than 1%), Esherichia coli 5% to 10%, they employed a reverse osmosis system, either alone or with
Pseudomonas aeruginosa (5%), other gram-negative bacteria deionization in their water treatment systems. By 1988, 91% of
(5%), fungi (5% to 10%), and others (less than 5%). Approxi- the centers were using reverse osmosis alone or in combination
mately 5% to 20% of episodes will be culture negative (156). with deionization as an integral part of their water treatment
The primary strategy for controlling peritonitis is to prevent system (5). Control of dialysis dementia revolves around ade-
contamination of the dialysis fluid that enters the peritoneal quate water treatment systems and invariably requires the use of
cavity and to prevent tunnel and exit site infections. Similar to reverse osmosis, either alone or with deionization.
the approach for access-related infections in hemodialysis pa- It also is important to ensure that all components of the water
tients, prevention for this population involves (a) aseptic ma- treatment and dialysis fluid preparation and delivery systems be
nipulation of the sterile disposable plastic lines leading into the compatible with all fluid with which they are in contact in order
abdominal catheter that deliver the dialysis fluid into the peri- to eliminate the possibility ofleaching of harmful substances. In
toneal cavity, (b) a system for aseptic connection of the tubing one outbreak, 58/85 (68%) dialysis patients at a dialysis center
were diagnosed with acute or chronic aluminum intoxication A summary of toxic reactions in hemodial}'llis patients that
that resulted in three deaths (174). Investigation revealed that have been investigated by the CDC is given in Table 23.1.
the acidified portion (pH = 2.7) of the bicarbonate-based di-
al}'llate solution was passed through a pump with an aluminum
housing, and aluminum was leached out of the pump and into BLOODBORNE VIRUSES: VIRAL
the dial}'llate solution in concentrations exceeding 200 mg L- 1 HEPATITIS AND ACQUIRED
and was present in the dial}'llis fluid (174). IMMUNODEFICIENCY SYNDROME
More recently, an outbreak of aluminum intoxication in
the Netherland Antilles where 10 patients died was attributed Shortly after the art and science of hemodialysis was institu-
to leaching of aluminum from the incoming drinking water tionalized, it was recognized that both patients and staff mem-
pipes. The water distribution pipe was lined with a cement mor- bers were at risk of acquiring viral hepatitis. The development
tar that was probably inappropriate for transporting drinking and use of specific serologic testing identified hepatitis B vi-
water (175). In the United States, 10 patients treated at a he- rus (HBV), and later hepatitis C virus {HCV), as those most
modialysis unit in Wyoming were found to have elevated serum likely to be transmitted within the hemodialysis environment.
aluminum levels during routine screening. On investigation it Other bloodborne pathogens that need to be considered
was determined, that the source of exposure was the acid con- as potentially transmissible in hemodialysis centers include
centrate that became contaminated with aluminum as it passed hepatitis delta virus (HDV) and human immunodeficiency
through two electric drum pumps that were not intended for virus (HIV). The CDC has conducted 26 investigations involv-
use in dial}'llis (176). ing the transmission of bloodbome pathogens (Table 23.1)
(179-196).
Since HBV is the most efficiently transmitted bloodbome
virus in the dialysis setting, long-standing precautions devel-
Chemicals in water or as residuals in dial}'llis fluid can affect oped for HBV serve, in part, as a model for the prevention of
dial}'llis patients. Certain chemicals in water may not be toxic transmission of other bloodbome viruses. The primary ratio-
when ingested by humans, but the hemodialysis patient may be nale is that infection control practices that effectively control
exposed directly to 150 L of water per treatment. Two examples HBV transmission also are effective for other bloodbome vi-
will illustrate this problem. ruses, such as HCV and HIV, because their efficiency of trans-
Occasionally, suppliers of community water change their mission is much less than that of HBV.
water disinfection patterns by increasing chlorine dosages or by
switching back and forth between free chlorine and monochlo- VIRAL HEPATITIS
ramine. These changes usually occur without the knowledge
of the dial}'llis staff. Monochloramine (combined chlorine) in Hep~r:titis B Vir1U
water used to prepare dial}'llis fluid must be removed or the
patient will experience hemolysis. Patients will be exposed to
Epidemiology. HBV is transmitted by percutaneous or per-
mucosal exposure to infectious blood or body fluids. Hepatitis
this chemical if the correct water treatment system component
B surface antigen (HBsAg)-positive persons who also are posi-
(activated carbon) is not present or operating in the dialysis
tive fore antigen (HBeAg) have an extraordinary level of HBV
center. In one instance, a dialysis center changed from acetate
circulating in their blood, approximately 108 virions mL - 1.
to bicarbonate dialysate, adding an additional reverse osmosis
With these high viral titers, body fluids containing serum or
unit and tanks for preparation and dilution of the dialysate. No
blood also may contain appreciable levels of HBV. HBV can be
changes were made to increase the capacity of the carbon filter,
present on environmental surfaces in the absence of any visible
and within a few weeks, approximately 100 of the center's dialy-
blood and still contain 1<Y! to 103 infectious virions mL- 1 (197).
sis patients were exposed to chloramine-contaminated dialysate
Furthermore, HBV is relatively stable in the environment, and
when the undersized carbon filters failed. A total of 41 patients
has been shown to remain viable for at least seven days on en-
required transfusion to treat hemolytic anemia caused by the
vironmental surfaces at room temperature {198). Thus, wher-
chloramine exposure (177).
ever there is a good deal of blood exposure, the risk of HBV
Another example of chemical intoxication occurred when
transmission can be high if proper control measures are not
a city water treatment plant accidentally fed excessive levels
practiced. This is especially true in the hemodial}'llis setting.
of fluoride into the community water supply, resulting in the
In the past, dial}'llis patients also could acquire HBV infec-
death of one dial}'llis patient and acute illness in several other
tion through transfusion of contaminated blood or blood prod-
patients in a hemodialysis center receiving this community
ucts. This is currently very unlikely since all blood is screened
water supply. The center's water treatment system was not ad-
for HBsAg, HBV DNA, and antibody to hepatitis B core antigen
equate to remove excessive fluoride from water (46) .
(anti-HBc). The use of erythropoietin in dialysis patients also
In both of the preceding examples, a properly designed water
has reduced the need for blood transfusions. Dialysis patients,
treatment system consisting of adequate carbon filtration for the
once infected, frequently become chronically infected but re-
fluid flow and volume plus the use of reverse osmosis, deioniza-
main asymptomatic and are sources of HBV contamination of
tion, and ultrafiltration would have prevented toxic reactions.
many environmental surfaces.
There also have been instances in which a disinfectant, such
Given the extraordinarily high level of HBV in blood, the
as formaldehyde, was not sufficiently removed from dialysis sys-
various modes of HBV transmission can be categorized based
tems, and patients were exposed to the chemical (178). Moni-
on efficiency as follows:
toring the system for complete rinsing using the appropriate
assay S}'lltem sensitive to the disinfectant being used can prevent 1. Direct percutaneous inoculation of HBV by needle from
potential patient exposure to disinfectants. contaminated blood, serum, or plasma.
2. Percutaneous transfer of blood, serum, or plasma, such (e.g., multiple-dose medication vials, equipment, and supplies)
as may occur through cuts, scratches, abrasions, or other that can become contaminated with blood and serve as sources
breaks in the skin. of HBV transmission. This potential for the environmentally
3. Transfer of infectious blood, serum, or plasma onto muco- mediated mode of virus transmission rather than any phenom-
sal surfaces such as may occur through inadvertent intro- enon dealing with internal contamination of dialysis machines
duction of these fluids into the mouth or eyes. is the basis for the infection control strategies recommended
4. Introduction of other known infectious secretions, such as for preventing HBV transmission in dialysis centers.
saliva and peritoneal fluid, onto mucosal surfaces. Surveillance data from the CDC show that, between 1972
5. Indirect transfer of HBV from blood, serum, or plasma by and 1974, the incidence of HBsAg positivity among patients
means of environmental surface contamination. or staff increased by >100% to 6.2% and 5.2%, respectively
(202,203). In a separate survey of 15 hemodialysis centers
There is no epidemiologic or laboratory evidence of air- during the same 2-year period, Szmuness et al. showed that
borne HBV transmission, and no disease transmission occurs the point prevalence of a positive test for HBsAg was 16.8%
by the intestinal route (197,199,200). Splashes of infectious among patients and 2.4% among staff (204) . During this time
blood that enter the oral cavity may result in HBV infection period, HBV infection in dialysis units had become highly en-
because the virus enters the vascular system through the buccal demic, and outbreaks were common because of the presence
cavity but not the intestinal tract. of chronically infected patients who were asymptomatic, and
HBV transmission can occur by a number of routes in the he- serologic surveillance systems to detect these chronic infec-
modialysis center setting. Staff members may become infected tions, and the lack of infection control measures to prevent
with HBV through accidental sharps injury or blood contact transmission (185,186) .
with breaks in their skin or mucous membranes. These staff Subsequently, infection control strategies were developed to
members have frequent and continuous contact with blood incorporate precautions for preventing exposures to blood and
and blood-contaminated surfaces. Dialysis patients may acquire body fluids among both patients and staff with several extra
HBV infection in several ways, including (a) internally contami- precautions ( 205). As will be discussed, these extra precautions
nated dialysis equipment (e.g., venous pressure gauges or ve- included dialyzing HBsAg-positive patients in separate areas or
nous transducer protectors used to prevent reflux of blood into rooms in the dialysis center and using dedicated dialysis ma-
gauges) not routinely changed after each use, (b) injections chines and staff rather than including HBsAg-positive patients
(by contamination of the site of injection or the material being in dialyzer reuse programs.
injected}, or (c) breaks in the skin or mucous membranes that Continued nationwide surveillance by the CDC found that,
have contact with blood-contaminated objects. Patients who by 1983, the incidence of HBV infection had declined to 0.5%
are dialyzed in centers that routinely reuse dialyzers are not at among both patients and staff members (206) . Over the same
increased risk ofHBV infection because of this practice (201). period, the proportion of centers using separation practices in-
There is no documentation that HBV has been transmitted creased from 75% to 86%, and the proportion of centers that
from infected hemodialysis staff members to dialysis patients. screened patients monthly for HBsAg increased from 57% to
Hypothetically, this route of transmission is possible, but not 84%. In addition, the risk of acquiring HBV infection for pa-
likely because infectious blood and body fluids of dialysis per- tients was shown to be highest in those centers that provided
sonnel are not readily accessible to patients. However, dialysis dialysis to HBsAg-positive patients, but did not separate these
staff members may physically carry HBV from infected patients patients by room and machine. Other investigators also have
to susceptible patients by means of contaminated hands, gloves, shown that segregation of HBsAg-positive patients and their
or other objects. equipment reduces the incidence of HBV infection in hemo-
Environmental surfaces in the hemodialysis center can play dialysis units ( 207,208). The success of separation practices in
a role in HBV transmission. It has been shown that HBsAg, preventing HBV transmission can be linked to other control
which is considered a "footprint" of HBV, can be detected on recommendations, including frequent serologic surveillance.
environmental surfaces (especially those often touched) in Routine serologic surveillance facilitates the rapid identifica-
dialysis center settings (197). For example, HBsAg has been tion of patients who become HBsAg-positive, which allows for
detected on clamps, scissors, dialysis machine control knobs, the rapid implementation of isolation procedures before cross-
doorknobs, and other surfaces. If these surfaces or objects are infection can occur.
not cleaned or disinfected frequently and are shared among In 2002, the prevalence of HBsAg positivity among patients
patients using the same or neighboring machines, an almost was 1.0%, a figure that has not changed substantially from 1992
unnoticeable infection transmission route is created. to 2002. Similarly, the incidence ofHBV infection in hemodialy-
Although dialysis staff members may routinely change sis patients did not change substantially during that same time
gloves after caring for each patient, a new pair of gloves can period and was 0.12% (16). In 1994, five dialysis centers in three
become contaminated when the staff member touches surfaces states reported episodes of HBV transmission among their pa-
previously contaminated with blood from an HBsAg-positive tients to CDC over a 5-month period (188). In each ofthese inves-
patient. HBV can be transmitted from patient to patient when tigations it was found that the outbreaks were the result of failure
a staff member wearing contaminated gloves searches for the to follow more than one of the recommended infection control
patient's best site by applying finger pressure or by otherwise practices for the prevention of HBV transmission including: the
contaminating that site before cannulation. When donning a failure to routinely screen patients for HBsAg or routinely review
pair of new gloves, staff members should refrain from touch- results of testing to detect infected patients; assignment of staff to
ing any environmental surfaces before accessing the vascular the simultaneous care of infected and susceptible patients; and
access (fistula, graft, or catheter) on the patient. Other envi- sharing supplies, particularly multidose medication vials, among
ronmental sources of contamination include shared items patients. These same factors have typically been responsible for
most other hemodialysis-associated HBV outbreaks reported in anti-HBs levels have waned or among persons who failed to de-
the past (179,184-186,209). In addition, few patients in these velop anti-HBs. Persons in the latter category include those who
centers had received HBV vaccine. Although HBV vaccine has circulate HBliAg at levels not detectable by current commercial
been recommended for all hemodialysis patients since it became assays. However, HBV DNA has been detected in less than 10%
available in 1982, its uptake by the ESRD community was slow, of persons with isolated anti-HBc, and these persons are unlikely
even though it's use has been shown to reduce the costs of ser<)- to be infectious to others except under unusual circumstances
logic screening (210). From 1983 to 2002, the percentage that involving direct percutaneous exposure to large quantities of
had ever received at least three doses of HBV vaccine increased blood (e.g., transfusion) (220). In most persons with isolated
from 5.4% to 56% among patients and from 26.1% to 90% anti-HBc in the general population, the result appears to be a
among staff (16). As these outbreaks illustrate, the generally low false positive. Data from several studies have demonstrated that
incidence of HBV infection among hemodialysis patients does a primary anti-HBs response develops in most of these persons
not preclude the need to maintain infection control measures, after a three-dose series ofHBV vaccine (220,221) . No published
including adhering to vaccine recommendations, that were spe- data exist on response to HBV vaccination among hemodialysis
cifically formulated to prevent the transmission of bloodbome patients with this serologic pattern.
pathogens in these settings. There have been no documented A third antigen, HBeAg, can be detected in serum of per-
reports of HBV transmission in U.S. hemodialysis centers in re- sons with acute or chronic HBV infection. The presence of
cent years, likely due to better adherence to infection control HBeAg correlates with viral replication and high levels of virus
practices and improved vaccine uptake. Starting in 2008, CMS (i.e., high infectivity). Anti-HBe correlates with the loss ofrepli-
required all new outpatient hemodialysis facilities to have an cating virus and with lower levels of virus. However, all HBsAg-
isolation room for treatment of HBsAg-positive patients and positive persons should be considered potentially infectious,
mandated other CDC-recommended practices to prevent HBV regardless of their HBeAg or anti-HBe status.
transmission.
Heptztitis C
Screening and Diagnostic Tests. Several well-defined
antigen-antibody systems are associated with HBV infection, in- Epidemiology. Data are limited on the current incidence
cluding HBsAg and anti-HBs; hepatitis B core antigen (HBcAg) or prevalence of HCV infection among maintenance hemodi-
and anti-HBc; and HBeAg and antibody to HBeAg (anti-HBe). alysis patients. In 2002, 63% of dialysis centers tested patients
Serologic assays are commercially available for all of these ex- for anti-HCV, and 11.5% reported having 2:1 patient who be-
cept HBcAg because no free HBcAg circulates in blood. One came anti-HCV positive in 2002. The incidence rate in 2002 was
or more of these serologic markers are present during different 0.34%; among centers that tested for anti-HCV, the prevalence
phases ofHBV infection (211). ofanti-HCV among patients was 7.8%, a decrease of25.7% since
The presence of HBsAg indicates ongoing HBV infec- 1995 (16). Higher incidence rates have been reported from co-
tion and potential infectiousness. In newly infected persons, hort studies of U.S. dialysis patients (less than 1% to 3%),Japan
HBliAg is present in serum 30 to 60 days after exposure to HBV (less than 2%) , or Europe (3% to 10%) (190,222-228) . Higher
and persists for variable periods. Transient HBsAg positivity prevalence rates (10% to 76%) also have been reported in in-
(typically lasting less than 18 days) can be detected in some pa- dividual facilities (190,220,229-233) . A recent study of almost
tients during vaccination (212-215). Anti-HBc develops in all 3,000 U.S. hemodialysis patients identified an HCV infection
HBV infections, appearing at onset of symptoms or liver func- prevalence of 10% (234). HCV is most efficiently transmitted
tion test abnormalities in acute HBV infection, rising rapidly to by direct percutaneous exposure to blood, and like HBV, the
high levels, and persisting for life. Acute or recently acquired chronically infected person is central to the epidemiology of
infection can be distinguished by the presence of the immuno- HCV transmission. Hemodialysis staff members have rates of
globulin M (IgM) class of anti-HBc, which persists for approxi- anti-HCV comparable to those (1% to 2%) reported in other
mately 6 months (216). healthcare workers and the general population (235) . Risk
In persons who recover from HBV infection, HBsAg is elimi- factors associated with HCV infection among hemodialysis pa-
nated from the blood, usually in 2 to 3 months, and anti-HBs tients include blood transfusions from unscreened donors and
develop during convalescence. The presence of anti-HBs indi- years on dialysis (190,230,236,237). The number of years on
cates immunity from HBV infection. Mter recovery from natural dialysis is the major risk factor that is independently associated
infection, most persons will be positive for both anti-HBs and with higher HCV infection rates. As the time patients spent on
anti-HBc, whereas only anti-HBs develop in persons who are suc- dialysis increased, their prevalence of HCV infection increased
cessfully HBV vaccinated. Persons who do not recover from HBV from an average of 12% for patients receiving dialysis less than
infection and become chronically infected remain positive for 5 years to an average of 37% for patients receiving dialysis more
HBsAg (and anti-HBc), although a small proportion (0.3% per than 5 years (190,230,238,239).
year) eventually clear HBsAg and might develop anti-HBs (217). These studies and investigations of dialysis-associated HCV
In some persons, the only HBV serologic marker detected outbreaks indicate that HCV transmission most likely occurs be-
is anti-HBc (i.e., isolated anti-HBc). Among most asymptomatic cause of inadequate infection control practices. During the pe-
persons in the United States tested for HBV infection, an average riod between 1998 and 2012, the CDC investigated 11 outbreaks
of2% (less than 0.1% to 6%) test positive for isolated anti-HBc; of HCV infection among patients in chronic hemodialysis cen-
among injecting-drug users, however, the rate is 24% (218,219). ters (191-194,240,241) . All of these outbreaks involved lapses in
In general, the frequency of isolated anti-HBc is directly related well-established infection control practices, and in each instance
to the frequency of previous HBV infection in the population there were multiple opportunities for cross-contamination
and can have several explanations. This pattern can occur after among patients. The most common lapses included improper
HBV infection among persons who have recovered but whose medication handling and preparation, inadequate cleaning
and disinfection between patient treatment!!. Some of the prac- no true confirmatory test has been developed, supplemental
tice breaches that were observed included: test!! for specificity are available. The FDA-licensed or approved
supplemental tests include a serologic anti-HCV assay, recom-
1. equipment and supplies that were not disinfected between
binant immunoblot assay (RIBA), and nucleic acid test!! (NAT}
patient use;
for HCV RNA (including reverse transcriptase polymerase
2. use of common medication carts to prepare and distribute
chain reaction [RT-PCR] and transcription mediated amplifica-
medications at patient stations;
tion [TMA]) (244) .
3. sharing of multidose vials, which were placed at patient!!'
Anti-HCV testing includes initial screening with an EIA im-
stations on the top of the hemodialysis machine;
munoassay. However, interpretation of the result!! of ErAs that
4. contaminated priming bucket!! that were not routinely
screen for anti-HCV is limited by several factors: (a) these as-
changed or cleaned and disinfected between patient!!;
says will not detect anti-HCV in approximately 10% of persons
5. machine surfaces that were not routinely cleaned and dis-
infected with HCV, (b) these assays do not distinguish between
infected between patient!!; and
acute, chronic, or past infection, and (c) in populations with
6. blood spills that were not cleaned up promptly
a low prevalence of infection, the rate of false positivity for
(191,194,241,242).
anti-HCVis high. Ifthe screening testis positive, supplemental
Other risk factors for acquiring HCV include injection drug testing with a test with high specificity should be performed to
use, exposure to an HCV-infected sexual partner or house- verify the results. Among hemodialysis patients, the proportion
hold contact, multiple sexual partners, and perinatal exposure of false-positive screening test results averages approximately
(235,243). The efficiency of transmission in settings involving 15% (246). For this reason, one should not rely exclusively on a
sexual or household exposure to infected contact!! is low, and positive anti-HCV screening test to determine whether a person
the magnitude of risk and the circumstances under which these has been infected with HCV.
exposures result in transmission are not well defined. Routine testing of hemodialysis patient!! for anti-HCV on ad-
mission and every 6 months thereafter has been recommended
Screening and Diagrwstic Tests. FDA-licensed or approved since 2001 (247). For routine HCV testing of hemodialysis pa-
anti-HCV screening test!! used in the United States comprise tient!!, the anti-HCV screening immunoassay is recommended,
three types of FDA immunoassays; enzyme immunoassays and if positive, supplemental anti-HCV testing using RIBA
(EIA), enhanced chemiluminescence immunoassay (CIA). (Table 23.5). RIBA is recommended rather than NAT because
and microparticle immunoassay (MEIA) [see also http://www. serologic assay can be performed on the same serum or plasma
cdc.gov/hepatitis/HCV/LabTesting.htm] (244,245). Although sample collected for the screening anti-HCV screening assay.
TABLE 23.5 Recommendations for Reporting Results of Testing for Antibody to Hepatitis C Virus
(Anti-HCV) by Type ofRdlcx Supplemental Testing Performed
Anti-HCV Screening Supplemental
Test Result Test Result Interpretation Comments
Negative Not needed Anti-HCV negative Not infected with HCV unless recent infection is
suspected or other evidence exists to indicate
HCV infection
Positive Not done Not known Supplemental testing needed to confirm either
anti-HCV (RIBA) or HCV RNA
Positive RIBA: Not done Not known Supplemental anti-HCV (RIBA)
HCV RNA: Negative
Positive (high signal/ Not done Pwitive May be past or current infection; evaluate for
cut-off ratio) chronic infection and liver disease
Positive RIBA: Negative Negative Not infected with HCV
HCV RNA: Not needed
Positive RIBA: Positive Pwitive May be past or current infection; evaluate for
HCV RNA: Not done chronic infection and liver disease
Positive RIBA: Positive Positive May be past or current infection; repeat HCV
HCV RNA: Negative RNA; evaluate for chronic infection and liver
disease
Positive RIBA: Positive or Positive Current HCV infection; evaluate for chronic
Not Done infectionand liver disease
HCV RNA: Pwitive
Positive RIBA: Indeterminate Indeterminate HCV infection status is not
HCV RNA: Not done known; test for HCV RNA or
repeat anti-HCV testing
Positive RIBA: Indeterminate Indeterminate; Not HCV infection status is not
HCV RNA: Negative known known; test for HCV RNA or
repeat anti-HCV testing
Positive RIBA: Indeterminate Positive Current HCV infection;
evaluate for chronic infection and liver
HCV RNA: Positive disease
In addition, in certain situations, the HCV RNA result can be HIV among patients in other countries. All of these outbreaks
negative in persons with active infection. As the titer of anti- have been attributed to several breaks in infection control:
HCV increases during acute infection, the titer of HCV RNA (a) reusing access needles and inadequately disinfected equip-
declines (248). Thus, HCV RNA is not detectable in certain ment, (b) sharing of syringes among patients, and (c) sharing
persons during the acute phase of their infection, but this find- dialyzers among different patients (195,196,257). HIV infec-
ing can be transient and chronic infection can develop (249). tion usually is diagnosed with assays that measure antibody to
In addition, intermittent HCV positivity has been observed HIY, and a repeatedly positive EIA test should be confirmed by
among patients with chronic HCV infection (250-252). There- Western blot or other confirmatory test.
fore, the significance of a single negative HCV RNA result is
unknown, and the need for further investigation or follow-up
is determined by verifying anti-HCV status. Detection of HCV PREVENTING INFECTIONS AMONG
RNA also requires that serum or plasma sample be collected CHRONIC HEMODIALYSIS PATIENTS
and handled in a manner suitable for NAT and that testing
be performed in a laboratory with appropriate facilities es- Preventing transmission among chronic hemodialysis patients
tablished for NAT testing (244). Although in rare instances, of bloodbome viruses and pathogenic bacteria from both rec-
detection of HCV RNA might be the only evidence of HCV ognized and unrecognized sources of infection requires imple-
infection, a recent study conducted among almost 3,000 U.S. mentation of a comprehensive infection control program. The
hemodialysis patients found that only 0.07% were HCV RNA components of such a program include infection control prac-
positive but antibody negative (241). tices specifically designed for the hemodialysis setting, includ-
ing routine serologic testing and immunization, surveillance,
Deltll Heptztitis and training and education. CDC has published recommenda-
tions describing these components in detail (247,258).
Delta hepatitis is caused by the HDV, a relatively small defec- The infection control practices recommended for hemodi-
tive virus that causes infection only in persons with active HBV alysis units (Table 23.6) will reduce opportunities for patient-to-
infection. The prevalence of HDV infection is low in the United patient transmission of infectious agents, directly or indirectly
States with rates less than 1% among HBsAg-positive persons via contaminated devices, equipment and supplies, environ-
in the general population and more than 10% among HBsAg- mental surfaces, and hands of personnel. These practices
positive persons with repeated percutaneous exposures (e.g., should be carried out routinely for all patients in the chronic
injecting-drug users, persons with hemophilia) (253). Areas of hemodialysis setting because of the increased potential for
the world with high endemic rates of HDV infection include blood contamination during hemodialysis and because many
southern Italy, parts of Africa, and the Amazon basin. patients are colonized or infected with pathogenic bacteria.
Few data exist on the prevalence of HDV infection among Such practices include additional measures to prevent HBV
chronic hemodialysis patients; a few studies have reported transmission because of the high titer of HBV and its abil-
nonexistent to low prevalence among hemodialysis patients ity to persist in an infective state on environmental surfaces
(253-255) . In endemic areas, prevalence rates may be rela- (Table 23.6). The potential for environmentally mediated
tively high among hemodialysis patients who are HBsAg- transmission of HBV rather than internal contamination of di-
positive (256). Only one transmission ofHDV has been reported alysis machines is the focus of infection control strategies for
in the United States (183). In this episode, transmission oc- preventing HBV transmission in dialysis centers. For patients at
curred from a patient who was chronically infected with HBV increased risk for transmission of pathogenic bacteria, includ-
and HDV to an HBsAg-positive patient after a massive bleeding ing antimicrobial-resistant pathogens, additional precautions
incident; both patients received dialysis at the same station. also might be necessary in some circumstances. Furthermore,
HDV infection may occur as either coinfection with HBV surveillance for infections and other adverse events are needed
or as a superinfection in a person with chronic HBV infec- to monitor the effectiveness of infection control practices, and
tion. HDV coinfection usually resolves, but superinfection training and education of both staff members and patients are
frequently results in chronic HDV infection and severe disease. critical to ensure that appropriate infection control behaviors
High mortality rates are associated with both types of infection. and techniques are fully implemented.
A serologic test that measures total antibody to HDV is com- In each chronic hemodialysis unit, policies and practices
mercially available. should be reviewed and updated to ensure that infection con-
trol practices recommended for hemodialysis units are imple-
HUMAN IMMUNODEFICmNCY VIRUS INFECTION mented and rigorously followed. Intensive efforts must be made
to educate new staff members and reeducate existing staff
During the period between 1985 and 2002, the U.S. hemodi- members regarding these practices. Readers should consult the
alysis centers that reported providing chronic hemodialysis for CDC recommendations for details on these practices (247,258).
patients with HIV infection increased from 11% to 39%, and
the patients with known HIV infection increased from 0.3%
ROUTINE TESTING
to 1.5% (16). During this period, the proportion of patients
with HIV infection has remained fairly stable even though the All chronic hemodialysis patients should be routinely tested for
number of infected patients has increased, as has the number HBV and HCV infection and the results promptly reviewed to
of centers treating patients with HIV infection. HIV is trans- ensure that patients are managed appropriately based on their
mitted by blood and other body fluids. No patient-to-patient testing results (Tables 23.5 and 23.7) . Test results (positive and
transmission of HIV has been reported in U.S. hemodialysis negative) should be communicated to other units or hospitals
centers. However, there have been reports of transmission of when patients are transferred for care. Routine testing for HDV
• . t§ :f 6JJf.• ~mmcndations for Preventing Infections in Hemodialysis Patients

INFECTION CONTROL PRECAUTIONS FOR ALL PATIENTS
• Wear disposable gloves when caring for the patient or touching the patient's equipment at the dialysis station; remove gloves and perform
hand hygiene between each patient or station.
• Items taken into the dialysis station should be disposed of.
• When multiple-dose medication vials are used (including vials containing diluents), prepare individual patient doses in a clean (central-
ized) area away from dialysis stations and deliver separately to each patient. Do not carry medication vials from station to station.
• Do not use common medication carts to deliver medications to patients. Do not carry medication vials, syringes, alcohol swabs, or supplies
in pockets. If trays are used to deliver medications to individual patients, they must be cleaned between patients.
• Glean areas should be clearly designated for the preparation, handling, and storage of medications and unused supplies and equipment.
Clean areas should be clearly separated from contaminated areas where used supplies and equipment are handled. Do not handle and
store medications or clean supplies in the same or an adjacent area where used equipment or blood samples are handled.
• Use external venous and arterial pressure transducer protectors for each patient treatment to prevent blood contamination of the dialysis
machines' pressure monitors. Change the external transducer protectors between each patient treatment, and do not reuse them. Internal
transducer protectors do not need to be changed routinely between patients.
• Glean and disinfect the dialysis station, with special attention to all frequently touched surfaces, Discard all dialysis fluids and clean and
disinfect all surfaces and containers associated with the prime waste (including chairs, beds, tables, machines, buckets attached to the ma-
chines) between patients. Do not initiate routine disinfection of machine surfaces or other environmental surfaces until the patient has left
the station.
• For dialyzers and blood tubing that will be reprocessed, cap dialyzer ports and clamp tubing. Place all used dialyzers and tubing in leak
proof containers for transport from station to reprocessing or disposal area.
• Vaccinate all susceptible patients against hepatitis B; test for anti-HBs 1-2 months after last dose. H < 10 miU mL- 1 consider patient
susceptible, revaccinate with an additional three doses, and retest for anti-HBs. H ~ 10 miU mL- 1 consider patient immune, and retest
annually. Give booster dose ofvaccine ifanti-HBs declines to <10 miU mL -1 and continue to retest annually.
ADDmONAL PRECAUTIONS OF HBSAG-POSITIVE PATIENTS

• Dialyze H&Ag-positive patients in a separate room using separate machines, equipment, instruments, and supplies.
• Staff members caring for HBsAg-positive patients should not care for HBV-susceptible patients at the same time (e.g., during the same shift
or during patient changeover).
and HIV are not recommended for general infection control Routine HCV testing should include the use of both a
purposes. screening immunoassay to test for anti-HCV and supplemen-
Before admission to the hemodialysis unit, the HBV sero- tal or confirmatory testing with an additional, more specific
logic status (i.e., HBsAg, total anti-HBc, and anti-HBs) of all assay. Use of NAT for HCV RNA as the primary test for routine
patients should be known. Test results for patients transferred screening is not recommended because few HCV infections will
from another nnit should be obtained beforehand. ff a patient's be identified in anti-HCV negative patients. However, if alanine
HBV serologic status is not known at the time of admission, test- aminotransferase (ALT) levels are persistently abnormal in
ing should be completed within 7 days. The hemodialysis unit anti-HCV negative patients in the absence of another etiology,
should ensure that the laboratory performing the testing for testing for HCV RNA should be considered. Blood samples col-
anti-HBs is able to quantitatively detennine protective levels of lected for NAT should not contain heparin, which interferes
antibody since some labs use different cutoffs. with the accurate performance of this assay.
TABLE 23.7 Recommended Schedule for Routine Testing for Hepatitis B and Hepatitis C V11'US
Infections
Patient Status OnAdmiuion Monthly Semiannual Annual
All patients HBsAg," Anti-HBc"
(total), Anti-HBs,"
Anti-HCV, ALTb
HBV susceptible, including HBsAg
nonresponders to vaccine
Anti-HBs positive (~10 miU Anti-HBs
mL- 1 ), anti-HBc negative
Anti-HBs and anti-HBc positive No additional HBV
testing needed
Anti-HCV negative ALT Anti-HCV
"Results ofHBV testing should be known before the patient begins dialysis.
hHBsAg, hepatitis B surface antigen; anti-HBc (total), total antibody to hepatitis B core antigen; anti-HBs, antibody to hepatitis B surface
antigen; anti-HCV, antibody to hepatitis C virus; ALT, alanine aminotransferase.
Chapter 23 • Dial~Associated Complitaticns and Their Control 351
HBV vaccination is an essential component of prevention HDV

in the hemodialysis setting. All susceptible patients and staff
should receive HBV vaccine. Susceptible patients who have not Because HDV depends on an HBV-infected host for replication,
yet received HBV vaccine are in the process of being vaccinated prevention of HBV infection will prevent HDV infection in a
and those who have not adequately responded to vaccination person susceptible to it. Patients who are infected with HDV
should continue to be tested regularly for HBsAg. Detailed rec- should be isolated from all other dialysis patients, especially
ommendations for vaccination and follow-up of hemodialysis those who are HBsAg positive.
patients have been published elsewhere (247).
HIV
MANAGEMENT OF INFECTED PATIENTS Infection control precautions recommended for all hemodialy-
sis patients are sufficient to prevent HIV transmission between
HBV patients. HIV-infected patients do not have to be isolated from
HBsAg-positive patients should undergo dialysis in a separate other patients or dialyzed separately on dedicated machines. In
room designated only for them. They should use dedicated addition, they can participate in dialyzer reuse programs. Be-
machines, equipment, and supplies, and most important, staff cause HIV is not transmitted efficiently through occupational
members should not care for both HBsAg-positive and suscep- exposures, reprocessing dialyzers from HIV-positive patients
tible (HBsAg-negative) patients at the same time or while the should not place staff members at increased risk for infection.
HBsAg-positive patient is in the treatment area (188,205,247).
Dialyzers should not be reused on HBsAg-positive patients
(52,259-261) . Because HBV is efficiently transmitted through
occupational exposure to blood, reprocessing dialyzers from Contact transmission can be prevented by hand hygiene, glove
HBsAg-positive patients might place HBV-susceptible staff use, and the cleaning and disinfection of frequently touched
members at increased risk for infection. environmental surfaces (264,265). Infection control precau-
HBV chronically infected patients (i.e., those who are tions recommended for all hemodialysis patients are adequate
HBsAg positive, total anti-HBc positive, and IgM anti-HBc to prevent transmission for most patients infected or colonized
negative) are infectious to others and are at risk for chronic with pathogenic bacteria, including antimicrobial-resistant
liver disease. These patients should be counseled regarding pathogens. However, additional precautions should be consid-
preventing transmission to others, and their household and ered for treatment of patients who might be at increased risk
sexual partners should receive HBV vaccine. These patients for transmitting pathogenic bacteria. Such patients include
also should be evaluated (by consultation or referral, if appro- those with either an infected skin wound with drainage that is
priate) for the presence or development of chronic liver dis-- not contained by dressings (the drainage does not have to be
ease according to current medical practice guidelines. Persons culture positive for methicillin-resistant S. aumt.S [MRSA], van-
with chronic liver disease should be vaccinated against HAV if comycin-resistant enterococci [VRE], or any specific pathogen)
susceptible (247). or fecal incontinence or diarrhea uncontrolled with personal
HBV chronically infected patients do not require any hygiene measures. For these patients, consider using the fol-
routine follow-up testing for purposes of infection control. lowing additional precautions: (a) staff members treating the
However, annual testing for HBsAg is reasonable to detect the patient should wear a separate gown over their usual clothing
small percentage of HBV-infected patients who might lose their and remove the gown when finished caring for the patient and
HBsAg. (b) dialyze the patient at a station with as few adjacent stations
as possible (e.g., at the end or comer of the unit) (247).
Vancomycin is used commonly in dialysis patients in part be-
HCV cause vancomycin can be conveniently administered to patients
HCV-positive patients do not have to be isolated from other when they come in for hemodialysis treatments. Prudent antimi-
patients or dialyzed separately on dedicated machines. The crobial use is an important component of preventing the spread
purpose of routine testing is to facilitate early detection and in- of vancomycin resistance (266,267). Published CDC recom-
tervention to stop transmission within centers and ensure that mendations state that vancomycin is not indicated for therapy
appropriate practices are being properly and consistently used. (chosen for dosing convenience) of infections due to P..lactam
Screening also identified patients in need of management of sensitive gram-positive microorganisms in patients with renal
their HCV infection. Furthermore, HCV-positive patients can failure (266). Depending on the situation, alternative antimi-
participate in dialyzer reuse programs. Unlike HBV, HCV is not crobials (e.g., cephalosporins) with dosing intervals >48 hours,
transmitted efficiently through occupational exposures. Thus, which would allow postdialytic dosing, could be used. Recent
reprocessing dialyzers from HCV-positive patients should not studies suggest that cefazolin given three times a week in the
place staff members at increased risk for infection. dialysis unit provides adequate blood levels and could be used to
HCV-positive persons should be evaluated (by consulta- treat many infections in hemodialysis patients (268,269).
tion or referral, if appropriate) for possible treatment and the
presence or development of chronic liver disease according to
DISINFECTION, STERruZATION,
current medical practice guidelines. They also should receive
AND ENVIRONMENTAL HYGIENE
information concerning how they can prevent further harm to
their liver and prevent transmitting HCV to others (262,263). Good cleaning, disinfection, and sterilization procedures are
Persons with chronic liver disease should be vaccinated against important components of infection control in the hemodialysis
HAV if susceptible. center. The procedures do not differ from those recommended
for other healthcare settings, but the high potential for intermediate-level disinfection per the directions of the germi-
blood contamination makes the hemodialysis setting unique cide manufacturer.
(247,270--273). Additionally, the need for routine aseptic ac- Blood and other specimens, such as peritoneal fluid, from
cess of the patient's vascular system makes the hemodialysis all patients should be handled with care. Peritoneal fluid can
wtit more similar to a surgical suite than to a standard hospital contain high levels of HBV and should be handled in the
room. Medical items are categorized as critical (e.g., needles same manner as the patient's blood. Spent peritoneal dialy-
and catheters), which are introduced directly into the blood- sis fluid also should be disposed of into a dedicated sanitary
stream or normally sterile areas of the body; semi-critical (e.g., drain and splashes disinfected with an appropriate chemical
fiber optic endoscopes), which come in contact with intact mu- disinfectant (275,276).
cous membranes; and noncritical (e.g., blood pressure cuffs), HBV has not been grown in tissue cultures, and without
which touch only intact skin (271). a viral assay system, studies on the precise resistance of this
Cleaning and housekeeping in the dialysis center have two virus to various chemical germicides and heat have not been
goals: to remove soil and waste on a regular basis, thereby pre- performed. However, the resistance of HBV to both heat and
venting the accumulation of potentially infectious material, and chemical germicides may approach that of some other viruses
to maintain an envirorunent that is conducive to good patient and bacteria, but certainly not that of the bacterial endospore
care. Crowding patients and overtaxing staff members may in- or the tubercle bacillus. Furthermore, studies have shown that
crease the likelihood of microbial transmission. There should HBV is not resistant to commonly used high level and interme-
be enough space to move completely around each patient's di- diate level disinfectants (276,277) .
alysis station without interfering with the neighboring stations Blood contamination of venous pressure monitors has been
and for routine disinfection, enough time to allow disinfection implicated in HBV transmission (187,278-280) . Therefore,
of surfaces at the dialysis station without the patient present. venous pressure transducer filters should not be reused.
When space is limited, the following can improve accessibility In single-pass artificial kidney machines, the internal fluid
for cleaning: eliminating unneeded items at the dialysis station pathways are not subject to contamination with blood. Al-
and having the previous patient who has completed their treat- though the fluid pathways that exhaust dialysis fluid from the
ment leave the station. dialyzer may become contaminated with blood in the event of
After each patient treatment, frequently touched environ- a dialyzer leak, it is unlikely that this blood contamination will
mental surfaces, including external surfaces of the dialysis reach a subsequent patient. Therefore, disinfection and rinsing
machine, should be cleaned (with a good detergent) or disin- procedures should be designed to control contamination with
fected (with a detergent germicide). In the absence of visible bacterial rather than bloodbome pathogens.
soil a one-step disinfection process may be used. If visible or- For dialysis machines that use a dialysate recirculating sys-
ganic soil is present, then a separate cleaning step is necessary tem (e.g., some ultrafiltration control machines and those that
and important for interrupting the cross-contamination trans- regenerate the dialysate), a blood leak in a dialyzer, especially
mission routes. An EPA-registered hospital grade disinfectant a massive leak, can result in contamination of a number of sur-
should be used for these purposes ( 197,266-272) . Antiseptics, faces that will contact the dialysis fluid of subsequent patients.
such as formulations with povidone iodine, hexachlorophene, However, the procedures that are normally practiced after each
or chlorhexidine, should not be used because they are formu- use of a recirculating machine-draining of the dialysis fluid,
lated for use on skin (i.e., antisepsis) and are not designed for subsequent rinsing, and disinfection-will reduce the level of
use on hard surfaces (i.e., disinfection). contamination below infectious levels. In addition, an intact
There is no evidence that medical waste is any more in- dialyzer membrane will not allow passage of bacteria or viruses.
fectious than residential waste or has caused disease in the Consequently, if a blood leak does occur with either type of
community (266,274). Wastes from a hemodialysis center that dialysis machine, the standard disinfection procedure used for
are actually or potentially contaminated with blood should machines in the dialysis center to control bacterial contamina-
be considered infectious and handled accordingly. Eventu- tion also will prevent transmission of blood-borne pathogens.
ally, these items of solid waste should be disposed of properly
in an incinerator or sanitary landfill, depending on state or
local laws.
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Didier Pittet, Caroline Landelle, and Stephan A. Harbarth
The Intensive Care Unit, Part A: HAl

Epidetniology, Risk Factors, Surveillance,
Engineering and Ad.nlinistrative Infection
Control Practices, and ltnpact
The care of critically ill patients in special high-technology sites. Natural chemical barriers in the stomach are neutralized
units is a primary component of modem medicine, although by adminilltering H2-blockers or antacids that reduce acid·
the efficacy and long-term benefit of critical care has not been ity and allow growth of enteric nora. Physiologic mechanisms
established for all medical conditions (1). Invasive diagnostic for evacuating and cleansing hollow organs are disrupted and
and therapeutic procedures are essential for the diagnosis and circumvented by insertion of endotracheal tubes, nasogastric
treatment of critically ill patients. However, life support systems tubes, and urinary catheters.
disrupt normal host defense mechanisma, affecting patients Specific host defense mechanisms also might be impaired
with already impaired immune re,powse. Given the severity of by the underlying diseases. Patients with malignant disorders
the illnesses affecting patients in intensive care units (ICUs), might have abnOimal immune responses as a rerult of their
it is not surprising that mortality rates can exceed 25% (2,3). disease or stemming from therapies that diminish the num-
In addition, more than one third of the patients admitted to ber of effective phagocyte cells and blunt the normal immune
ICUs experience unexpected complications of medical care response. Patients admitted to ICUs who are at the extremes
(4). Healthcare-associated infection (HAl) is one of the most of age exhibit selected impairments in natural and specific
common medical complications affecting patients in ICUs. defense mechanisms that increase the HAI risk (6,7). A his-
Although ICUs make up only 5% to 10% of hospital beds, in- torical cohort study from Belgium revealed, however, that the
fections acquired in these units account for >20% of all HA.Is incidence of healthcare-associated bloodstream infection (BSI)
(5). Fortunately, systematic studies of the determinants of was lower among very old ICU patients when compared to
HAis, surveillance for infections, and adherence to protocols middle-aged and old patients. Yet, the adverse impact of this
for preventing infections have been effective in reducing the HAI was higher in very old patients (8).
risk for patients admitted to ICUs. Because of the precarious condition of patients in the ICU,
nonnal food intake often is suspended, leading to under- or
malnutrition (9). Injured tissue, perfusion deficits, and infec-
ICU-ACQUIRED INFECTIONS tion cause fever and tachycardia through mechanisms me-
diated by hormones and cytokines, ruch as endotoxin. The
PATHOGENESIS physiologic re,powse to these mediators is an increase in oxy-
gen consumption stemming from an increase in metabolic de-
The dynamics of ICU·acquired HA.Is are complex and depend mand. This response results in breakdown of muscle to meet
on the contribution of the host's underlying conditions, the in- the body's demand for energy. The lean body mass declines,
fectious agents, and the unique environment of the ICU. The rerulting in deficits in substrates necessary for recovery (1 0).
following discussion will consider the role of each component Under-nutrition has been associated with increased compli-
in the development of HAI. cation rates and delayed wound healing (11,12). Several stud-
ie& suggest that poor nutritional status is a predisposing factor
for HAis (13-15). Recent studies have confinued that the use
Host Dejnues of enteral nutrition vs. total parenteral nutrition (TPN), early
The ability of patients in ICUs to ward off infections is seri- initiation of enteral nutrition, and use of enteral and parenteral
ously compromised. Natural host defense mechanisms might glutamine are all associated with reduced infectious morbidity
be impaired by underlying diseases or as a result of medical in critically ill patienu (16-18). For instance, early or glutamine-
and surgical interventions. All patients admitted to an ICU enriched enteral nutrition in critically ill patients has been
will have at least one, and often several, indwelling devices reported to decrease HAis and other complications (19,20).
that break the normal skin barriers and e,tablish direct access Conversely, a meta-analysis including 26 studies which examined
between the external environment and normally sterile body the relationship between TPN and mortality rates in critically ill
357
358 Section II • Funtional.Anoas of Concern
patienlll showed that TPN had no effect on mortality and only with other factors. Factors were collected from > 10,000 ICU
lowered complication rates in malnourished patients (21). In patients, of whom 2,064 had ICU-acquired infections. Among
a meta-analysis of trials comparing enteral nutrition to TPN in the seven independent risk factors identified, four were asso-
ICU patients, Simpson et al. reported that TPN was even associated with medical devices commonly used in intensive care:
ciated with an increase in infectious complications (odds ratio central venous catheter (CVC) (OR= 1.35, 95% CI = 1.60 to
[OR]= 1.47;95% confidence interval [CI] = 0.90to2.38) (22). 1.57), pulmonary artery catheter (OR= 1.20, 95% CI = 1.01
TWo other recent meta-analyses reported negative findings. In to 1.43), urinary catheter (OR= 1.41, 95% CI = 1.19 to 1.69),
their systematic review, Peter et al. reported no mortality effect and mechanical ventilation (OR = 1.75, 95% CI = 1.51 to
with the type of nutritional supplementation, although early 2.03). Other independent risk factors for ICU-acquired infec-
enteral nutrition significantly reduced complication rates (23). tions were stress ulcer prophylaxis (OR= 1.38, 95% CI = 1.20
Ho et al. performed a meta-analysis, comparing early gastric and to 1.60), the presence of trauma on admission (OR = 2.07,
postpyloric feeding in critically ill patients and concluded that 95% CI = 1.75 to 2.44), and the length ofiCU stay. The latter
early use of postpyloric feeding instead of gastric feeding in ICU constituted the strongest predictor of infection and showed a
patienlll with no evidence of impaired gastric emptying was not linear increase in the odds for infection with time spent in the
associated with significant clinical benefits (24). ICU (29). This finding also was confirmed by the second inter-
Important alterations in T- and B-eell function affecting host national study of the prevalence and outcomes of infection in
defense and resistance to infection are found in critically ill and ICUs, published in 2009 (2).
traumatized patients (25). Alterations in T-cell activation and In another interesting cohort study (30), McLaws and Berry
cytokine production are frequently associated with trauma and analyzed the rate for CVC-associated BSI in 1,375 patienlll who
hemorrhage. Injury and blood loss result in activation of CDS were monitored for 7,467 days of eve use. They found signifi-
T-cell populations capable of altering bacterial antigen-specific cant differences in the BSI rate depending on the length of cath-
B-cell repertoires and suppressing the function of other T cells. eterization (Figure 24.1). The probability of BSI with a CVC in
Systemic hypoxia and hypovolemia also are significant con- place was 6% by day 15, 14% by day 25, 21% by day 30, and 53%
tributors to the development of infection. However, significant by day 320. Thus, the risk of infection is not homogenous, but in-
changes in perioperative care have been introduced in re- creases substantially after prolonged CVC-insertion (>2 weeks).
cent years (26,27). The maintenance or restoration of normal
physiologic characteristics after surgery becomes the key to pre-
Umlerlying Disemes
venting complications (28).
ICUs, by design, serve patients with severe illnesses that
compromise host defense. Each patient must be assessed indi-
Metlic11l De71ices
vidually to determine how the underlying illness might inter-
The results of the first European Prevalence of Infection in In- fere with host defense mechanisms. A simple assessment of the
tensive Care (EPIC) study (29) highlighted the relative impor- severity of underlying illness was developed five decades ago
tance of medical devices as risk factors for infections compared by McCabe andJackson (31), who stratified patients according
1.00-
0.95-
CVLin
situ
0.90- between
6-15
days:
0.85- 94%
j patients
t'fJtnain
t:I 0.80-
BSJ
•E frrle;
theltl
:I wasa6 CVLinsltJJ
0 /n100 bslwfl6n16-30
0.75-
days:79%
Figure 24.1. Kaplan-Meier survival
chance curve of a nonuniform hazard for the
ofBSI patients remain
or4.8 BSI frrle; the~t~ development of bloodstream infection
0.70- BSJ was a 21 in 100 (BSI) beginning with all patients (cumula-
/1000 chance of BSI or tive survival, 1.00) free ofBSI. By day 5,
fine- 10.5 BS/11000
fine-days. 99% of the patients remained free of BSI.
0.65- days.
By day 16, 94% remained free ofBSI. CVL,
central venous catheter. (Adapted from
McLaws ML, Berry G. Nonuniform risk
0.60-
of bloodstream infection with increasing
central venous catheter-days. Infect Control
0 5 10 15 20 25 30 35 40 45 50 55 60 Hospital Epidemiol. 2005;26: 715-719, with
Line-days pei1Ili&sion.)
Chapter 24 • The Intensive Can! Unit, Part A 359
to whether the underlying disease was fatal, ultimately fatal, or facing similar prevalences of highly resistant organisms,
nonfatal. Subsequent studies by Britt and colleagues (32) have confirming that efforts to control resistance should focus on
demonstrated the utility of this simple assessment for estimat- both antimicrobial use and infection control practices (50-52).
ing the risk of nosocomial BSI. Numerous other studies have In ICUs, where antibiotics are used more frequently and in
found increasing rates of infections among patients with more larger amounts than in almost any other unit in the hospital,
severe illness (33,34). antimicrobial resistance ensures the survival of some nosoco-
Although McCabe's classification has been useful, it was not mial pathogens (53). The dose proximity of patients facilitates
designed to assess patients admitted to ICUs. Therefore, several transfer of resistant organisms from patient to patient (54).
severity-of-illness scoring systems have been proposed to esti- However, the high prevalence of carriage of multidrug-resistant
mate a patient's risk of death in ICUs objectively. Great prog- microorganisms does not automatically translate into higher
ress has been observed in the last 10 years in the accuracy of overall HAl rates in the concerned services (55,56).
statistical models to assess critically ill patients and predict sur- It is noteworthy that trends in the pathogens responsible
vival (35,36). Customized or modified versions of the most fre- for HAis in the ICU have shown an increase in infections due
quently used scoring systems (e.g., simplified acute physiology to multiply-resistant gram-negative bacteria (e.g., Enterohacter
score [SAPS] III; Acute Physiology, Age, and Chronic Health spp., Acinetobacter haumanniz) and fungi such as Candida spp.
Evaluation [APACHE] ill) have been proposed to obtain sat- (2). The emergence of these pathogens is due, at least in part,
isfactory estimates of the probability of death in ICU patients, to patterns of antibiotic use and selection pressure and to the
which depends on the severity of illness, the number of acute development of antibiotic resistance among these isolates
organ failures, and the characteristics of underlying disease (57). In a multicenter study by Meyer et al.(48) performed
(37--4{)). Nevertheless, limitations persist about the capacity of between 2001 and 2008 in 53 German ICUs, the carbapenem
these scoring systems to integrate differences in overall quality use almost doubled despite no significant change in the total
of care (41). Moreover, older versions of these scores, which antibiotic use expressed as defined daily doses (DDD)/1,000
were developed in the early 1990s, have shown a decline in pre- patient-days. The exponential increase of third-generation
dictive accuracy as the models age. Therefore, mortality tends cephalosporin resistance in Escherichia coli and other Entero-
to get overpredicted when older models are applied to more bacteriaceae reported in this study led to switching empirical
contemporary data, which in turn leads to biased benchmark- therapy to carbapenems to treat infections, with subsequent
ing data of different ICUs (42). Thus, care should be applied emergence of carbapenem-resistant Klebsiella pneumoniae,
when using outdated severity scoring models to contemporary carbapenemase-producing gram-negative pathogens, and
populations. imipenem-resistant A. haumannii as a direct consequence.
A group of critical care physicians developed, by consen- This scenario will affect many ICUs around the world in the
sus, the so-<:alled "Sepsis-Related Organ Failure Assessment" near future, although resistance trends and antibiotic con-
(SOFA) score in 1994, a severity scoring system that targets sep- sumption rates will still depend on different determinants,
tic patients ( 43). Since the score is not specific for sepsis, it was that is, ICU characteristics (medical, surgical, general), local
later called "Sequential Organ Failure Assessment" The SOFA antibiotic policies, and physicians' level of education among
score is composed of scores from six organ systems, graded others. The heterogeneity of antibiotic prescriptions within
from 0 to 4 according to the degree of dysfunction. While pri- ICUs recorded by Meyer and colleagues seems to indicate
marily designed to describe morbidity, several analyses showed that antimicrobial use can be improved also in ICU settings
a relationship between the SOFA score and mortality and indi- by shortening the duration of treatment or antibiotic prophy-
cated also a good distribution of patients among the different laxis without affecting patient outcome (58).
score values (44). In contrast to multidrug-resistant gram-negative bacte-
ria, infection rates seem to have stabilized or declined for
multidrug-resistant gram-positive bacteria (e.g., methicillin-
Antimicrohitll Us11ge 11nd Sele&tion Pressure
resistant Staphylococcus aureus [MRSA], vancomycin-resistant
Different types of epidemiological studies have been used to enterococcus [VRE]) in ICUs in many high-income countries
quantify the association between antibiotic exposure and resis- (59--62). For instance, Jain et al. (60) evaluated the effective-
tance in critically ill patients (45-49). These studies included ness of a quality improvement initiative in preventing the
outbreak reports, laboratory-based surveys, randomized tri- acquisition and spread of MRSA among nearly 2 million pa-
als, and prospective or retrospective cohort studies based on tient admissions, including data from 196 ICUs in the United
analyses of individual-patient-level data or aggregated data. States. During the intervention period-with increased atten-
The different methodological approaches are not mutually tion to MRSA admission screening, contact precautions, hand
transposable, and the lack of uniformity makes the comparison hygiene, and emphasis on responsibility of all healthcare
of different studies difficult. For instance, the analysis of ag- workers in prevention procedures-an important decrease in
gregated data may be limited by "ecologic bias," which is the infections not only caused by MRSA, but also by other patho-
failure of group-level-effect estimates to reflect the biological gens was observed (60). However, others have questioned the
effect of antibiotic use at the individual-patient level ( 45). This effectiveness of the intervention and suggest that other non-
bias is a result of the fact that, unlike individual-level studies, documented factors may have contributed to the observed
ecologic studies do not link individual outcome events to indi- reduction in MRSA infection rates in the participating ICUs
vidual antibiotic exposure histories. Notwithstanding these dif- (63). Despite this ongoing controversy, the positive develop-
ficulties, the majority of studies confirm that large differences ment of reduced MRSA rates could potentially reduce the ne-
exist in the pattern of antimicrobial usage and antimicrobial cessity of empiric gram-positive coverage in many ICUs, but
resistance, between different hospitals and ICUs. Usage of anti- clinicians seem to be reluctant to adapt their treatment pat-
microbials may show important variations between institutions terns to lower MRSA rates (64).
SOURCES OF COLONIZATION study. The emergence of resistance also has been observed with
other topical decontamination regimens; thus, it is important
Host colonization is often a prerequisite for the development
to actively look for emerging chlorhexidine resistance in set-
of infection. This process involves adherence of organisms to tings with widespread chlorhexidine usage (77,78).
epithelial or mucosal cells, proliferation, and persistence at
The central role of gastric colonization in the pathogen-
the site of attachment. Although the factors promoting the
esis of HAl and pnewnonia has been called into question.
progression from colonization to infection are not well under-
Based on studying sequences of colonization in ICU patients,
stood, almost 50% of the ICU-a.cquired infections are preceded
Bonten et al. (79) concluded that the stomach is unlikely to
by host colonization with the same microorganism. Factors as-
be an important source of pathogens leading to healthcare-
sociated with microbial colonization are similar to those associ-
associated pneumonia, as diagnosed by bronchoalveolar lavage
ated with development of infection. These risk factors include (BAL) or protected specimen brush (PSB). Furthermore, the
the duration of hospitalization and length of stay in the ICU,
initial site and route of colonization might not be the same
invasive devices, prolonged antibiotic therapy, and elimination for all microorganisms (79). These results were confirmed in
of normal pharyngeal or bowel flora through the use of broad-
a large, observational cohort study conducted in two medical
spectrum antimicrobial agents (65). Other factors promoting ICUs, where specimens for culture were taken daily from nares,
colonization of patients in ICUs include disruption of normal
oropharynx, trachea, and stomach, from the time of admission
mechanical defense mechanisms (i.e., the bronchial mucocili-
to the first signs of healthcar~sociated pneumonia (80). The
ary "escalator") by drugs and tracheal intubation, changes in
stomach was an uncommon source of microorganisms that
protective antibacterial secretions (i.e., lysozyme, lactoferrin,
cause pnewnonia in ventilated patients. Preventive regimens
saliva, and gastric acid) in response to stress and therapeutic
should thus be mainly directed against colonization of the oro-
agents, and disruption of "colonization resistance."
pharynx and trachea (81,82).
A vast literature exists regarding the development of colo-
nization and subsequent infection (66). A few important stud-
ies are swnmarized. The classic article (67) ofjohanson et al., EPIDEMIOLOGY
written in 1969, showed that severe illness predisposes to oro-
Infection RR-tes 11ntl Types of ICU
pharyngeal colonization with gram-negative bacilli. In 1974,
Schimpff et al. (68) suggested that in critically ill patients, the New insights were recently reported regarding the epidemiol-
origin of infection usually is the endogenous flora. Several stud- ogy of infection in ICUs. A global, observational study (EPIC II)
ies have subsequently confirmed that patients are rapidly colo- on the prevalence and outcomes of infection in 1,265 ICUs was
nized by gram-negative bacteria after admission to ICUs, and conducted in 75 countries in May 2007. Among the 13,796 pa-
later develop HAis with the same organisms (69--73). tients, 9,084 (66%) received an antimicrobial agent and 7,087
In a landmark study, Grundmann et al. (54) prospectively (51%) were considered infected at the time of data collection
studied cross-infection in critically ill patients admitted to five (2). Unfortunately, due to methodological limitations, no
ICUs in Germany. During 28,498 patient-days, 431 ICU-ac- dear-cut distinction could be made between community- and
quired infections and 141 episodes of nosocomial transmissions HAis. However, among those patients who had stayed >7 days
were identified. A total of 278 infections were caused by the in the ICU before the study day, >70% were infected, mostly
10 species that were genotyped, and only 41 of these (14.5%) with multidrug-resistant organisms. A clear association was
could be associated with transmissions between patients. Thus, noted between prevalence of infection and hospital mortal-
modem typing methods confirmed that the patients' endog- ity, with Greece and Thrkey having the highest mortality and
enous flora is the most important source of HAl. Switzerland the lowest (Figure 24.2) . These differences are
A recently published cohort study confirmed the value of
modem molecular genotyping and genome sequencing meth-
ods to elucidate exogenous transmission pathways of MRSA
50
during an outbreak in a neonatal ICU in England, similar to o GR
an investigation of endemic MRSA transmission routes in a 45
om
tertiary care center in Thailand (74,75). Consequently, anti- ~40
septic body washes are increasingly used to reduce exogenous ~35 0 AR
transmission and acquisition of multiresistant gram-positive
bacteria. Several well-designed intervention studies have shown
!30 COc
o PT
~ 25 Dl
o ES Dc
BE D CZ
their short-term benefit in reducing MRSA and VRE carriage
j 20 DAT SCAN
and infection rates. Chlorhexidine body washes, in particular, "us D
}15 AU
have now become standard-of-care in many ICUs to reduce the 0
bacterial load on patients' skin. A British team of investigators J: 10 • CH
examined the impact of several control interventions aimed 5
at reducing cross-transmission of MRSA (76). An educational 0
campaign and cohorting had little impact on MRSA transmis- 30 35 40 45 50 55 60 65 70
sion. The introduction of chlorhexidine as a skin antiseptic re- Infection (%)
duced MRSA transmission of all but one of the strains prevalent Figure 24.2. Hospital mortality in relation to infection prevalence
in this ICU: the "TW" strain that carries the qacA/B genes which in critically ill patients, stratified by country. (From Vmcent JL, Rello J,
code for chlorhexidine resistance (76). Due to its chlorhexi- MarshallJ, et al. International study of the prevalence and outcomes
dine resistance, the acquisition of this MRSA strain increased ofinfection in intensive care units.JAMA. 2009;302:2323--2329, with
dramatically during the period of this interrupted time-series permission.)
likely to reflect differences in critical care practices between When rates of HAis have been compared over shorter in-
countries, and underline the importance of controlling for crements of time (i.e., by month) wide variations have been
case-mix when interpreting and comparing rates of HAis be- noted. Observations in different ICUs suggested that the level
tween hospitals or countries (5). of skilled nursing care relative to patient census may be an im-
Not only at a national or international level the frequency portant determinant of this variation (91,92). Indeed, there
differs with which infections occur, but also at different sites in are many studies showing that overcrowding, understaffing, or
the ICU and within a hospital. The annual U.S. Centers for Dis- a misbalance between workload and resources are important
ease Control and Prevention's (CDC's) National Nosocomial determinants of HAis and cross-transmission of microorgan-
Infections Surveillance (NNIS)-now known as the National isms in ICUs (93-95). Importantly, not only the number of staff
Healthcare Safety Network or NHSN-system report and data but also the level of their training affects outcomes. The causal
from the German ICU surveillance system KISS illustrate these pathway between understaffing and infection is complex, and
differences in the incidence ofHAis in different types of wards factors might include lack of time to comply with infection con-
and ICUs (83,84). First, predominant HAis vary by location. trol recommendations, job dissatisfaction, job-related burnout,
Urinary tract infections predominate in general wards, whereas absenteeism, and a high staff turnover (92).
the most common HAis in ICUs are lower respiratory tract in- In summary, rates of HAis vary considerably within hospitals
fections. Second, HAl rates vary by type of ICU. Rates of infec- by the type of ICU. Rates are generally lower in cardiac care
tion tend to be higher in the surgical ICU than in the medical units and higher in neonatal, surgical, trauma, and bum units,
ICU, and rates in the adult ICUs are generally higher than in reflecting the greater risk of infection of patients admitted to
pediatric ICUs (except neonatal ICUs) (85). Third, in all types these latter types of units (83).
of ICUs, the lower respiratory tract is the most common site
of infection (Table 24.1). High rates of pulmonary infections
ImpB&t of Infections Acquired in the ICU
relative to other infection sites are unique to adult critical care
units, where patients are frequently admitted because of respi- ICU-acquired HAis are harmful for the patients and expensive
ratory distress and require mechanical ventilation. Although for society. Several studies suggest that healthcare-associated
primary bacteremia and infections stemming from the pres- pneumonia and BSI are associated with a two- to three-fold
ence of vascular cannulas are less common than lower respi- increased risk of death in critically ill patients (96,97). Crude
ratory tract infections, the morbidity and mortality associated mortality rates in patients who acquire HAis in the ICU are esti-
with these infections are particularly high (86,87). mated to vary between 10% and 80%. The term attributable (or
In 2000, the CDC reported for the first time a decrease in excess} mortality defines the mortality directly associated with
HAl rates in the ICUs of participating NNIS hospitals from the infection, apart from the mortality attributable to under-
1990 to 1999 (88). Risk-adjusted infection rates decreased for lying conditions. In ICU patients, underlying conditions apart
three body sites (the respiratory tract, the urinary tract, and from HAl that may affect the outcome mainly include preex-
the bloodstream). The greatest decrease was observed for BSI isting comorbidities, severity of acute physiologic disturbance
rates, which decreased in medical ICUs by 44%, in coronary or severity of illness, and complications arising from these
ICUs by 43%, in pediatric ICUs by 32%, and in surgical ICUs by conditions (98).
31%. However, because of a progressively shorter ICU length of Assessment of mortality attributable to HAis in the ICU
stay over the last 20 years, the overall, hospital-wide rate ofHAis setting is difficult and not straight-forward because HAis and
per 1,000 patient-days has actually increased by 36%, from 7.2 mortality attributable to other causes share common risk fuc-
in 1975 to 9.8 in 1995 (89). The variable use of different de- tors that may confound the cause-and-effect relationship. Thus,
nominators also may have an important effect on trend analy- it is sometimes difficult to estimate whether the critically ill
ses and may bias benchmarking (90). patient would have survived in the absence of HAl. The most
TABLE 24.1 HAl Rates in German Intensive Care Units (ICUs): Data of the German KISS
Surveillance Systan, 2005 to 2009, According to Type ofiCU and Infection (Updated
Version Downloadable Under: http://www.nrz-hygiene.de)
Urinary Tract Central Line-Aslociated Ventilator-Aslociated
Infection BloodatreiiiD Infection Pneumonia
&IR Pw 1,000 Dap of
Type ofiCU llGtu Pw 1,000 ~· Med~Grtia~l Vt!lltilcRimi
Inter-disciplinary <400 beds 1.05 0.89 5.7!1

Inter-disciplinary ~400 beds 1.87 1.!16 6.79
Internist 1.9!1 1.!1!1 4.70
Surgical 2.52 1.!12 7.44
Neurosurgical 5.09 1.90 9.59
Pediatric 1.57 1.75 2.08
Neurological !1.54 1.26 6.58
Cardiac surgical l.M 1.40 9.29
often used approach to estimate the attributable mortality of In summary, HAis in critically ill patients unquestionably
HAis in ICU patients is to conduct a matched cohort study. In have substantial effects on morbidity and mortality. However,
this type of study design, cases are defined as patients in whom the matched cohort study design may produce bias in the esti-
HAis develop during their ICU stay. These cas~patients are mation of the effects of HAI on length of stay and costs. Cost
subsequently compared with noninfected controls. Case- and effects or excess length of stay are likely to be overestimated if
control-patients are usually matched for age, the time of the the interval to onset of HAl is not properly accounted for in the
year, the underlying diseases, and additional variables that may study design or analysis (100). Since simple prevalence stud-
contribute to excessive mortality rates of ICU stay independent ies or matched cohort studies do not allow drawing any strong
of the infection itself. In brief, the attributable mortality due to causal inferences between infection rates and excess morbid-
HAI defines the excess mortality due to the infection. For in- ity due to ICU-acquired HAis, longitudinal cohort studies with
stance, a recent French ICU-based cas~ontrol study matched more sophisticated analyses have to be conducted.
1,725 deceased patients with 1,725 surviving control-patients
to determine the excess mortality related to ICU-acquired in-
fection (3). The adjusted population-attributable fraction of
deaths due to ICU-acquired infection for patients who died Bacteria, fungi, and viruses have been reported as causative
before their ICU discharge was 14.6% (95% CI, 14.4 to 14.8). agents of HAis in critically ill patients, and many of the bac-
The attributable mortality of ventilator-associated pneumonia terial infections are polymicrobial. The Sepsis Occurrence in
(VAP) was 6.1% (95% CI, 5.7 to 6.5), an estimate close to the Acutely Ill Patients (SOAP) study performed in 2002 (103) in-
8.1% (95% CI, 3.1% to 13.1 %) provided by a multistate model vestigated a large cohort of septic patients in 198 ICUs in 24 Eu-
of another cohort study that appropriately handled VAP as a ropean countries. Among the 279 patients with ICU-acquired
tim~ependent event (36). A larg~cale cohort study includ- sepsis, staphylococci, including MRSA were most frequent
ing 10 European countries and 537 ICUs determined clinical (40%), followed by Pseudomonas spp. (21%), streptococci
outcomes of patients with HAI admitted to ICUs (99). They (19%), E. coli (17%), and C. albicans (16%). Patients with ICU-
found high excess mortality associated with BSI and pneumo- acquired sepsis had a higher incidence of mixed infections
nia, and substantially increased excess length of stay for pneu- (23% vs. 16%) compared with those with non-ICU-acquired
monia, but not for BSI. Surprisingly, antimicrobial resistance sepsis (103).
provided only a small contribution to the overall burden of Although the Sepsis Occurrence in Acutely Ill Patients
HAI, with HAI due to Pseudomonas aeruginosa generating the study reported an equal frequency of gram-positive and gram-
greatest burden (and not MRSA). negative organism, the most recent EPIC II study on the preva-
For the assessment of the morbidity and economic burden lence and outcomes of infection (community- and HAI) in
associated with HAI in the ICU, matched cohort studies should 1,265 ICUs in 75 countries reported that gram-negative organ-
not be recommended. This study design has several limitations isms were more commonly isolated than gram-positive organ-
because of the time-varying nature of the exposure. One source isms (62% vs. 47%) (2). In patients with positive microbiologic
of bias occurs when infected and uninfected patients are com- results, the most common gram-positive organism was S. aureus
pared with regard to total hospital costs or total hospital length (20.5%) including 10.2% of MRSA; the most common gram-
of stay. For infected patients, only those costs incurred after the negative organisms were Pseudunwnas spp. (19.9%), E. coli
occurrence of the HAl are possibly secondary to infection. Before (16.0%), and Klebsiellaspp. (12.7%); 17.0% were Candidaspp.
occurrence of infection, patients are unexposed. The association Authors reported a significant relationship between the time
between preinfection outcome and infection is entirely noncausal spent in the ICU before the study day and the development of
from the perspective of measuring the excess burden ofinfection. infection, particularly for infections due to MRSA, Acinetobacter,
Therefore, combining preinfection outcomes with postinfection Pseudomonas, and Candida spp. There also were significant re-
outcomes dramatically amplifies confounding (100). gional differences in the organisms isolated from microbiologic
Several recent studies have demonstrated the effect of this cultures, with a particularly striking variation in the prevalence
bias. Outcome analyses that did not account for the time b~ of Acinetobacter spp. (ranging from 3.7% in North America to
fore the occurrence of the infection yielded different results 19.2% in Asia) (2).
than studies that did account for the time before the infection. To illustrate the trends in microbial etiology of device-
Schulgen et al. (101) tested different methods and showed associated HAis, we show in Table 24.2 data from the U.S.
that the use of unmatched or matched comparisons between NHSN and the German ICU surveillance system KISS
noninfected and infected patients led to an overestimation of (84,104). These data are similar and representative of ICUs
the excess length of stay due to healthcare-associated pneumo- in the industrialized world. The leading pathogens causing
nia, compared to analyses based on a structural formulation central line-associated bloodstream infections (CLA-BSis)
of transitions between different states. In a recently published and surgical site infections (SSis) were Staphylococcus and
study, Beyersmann et al. have confirmed the validity of this sta- Enterococcus species. S. aureus and P. aeruginosa were the most
tistical approach (102). They showed that HAI significantly re- commonly listed pathogens causing VAP and E. coli was the
duced the discharge hazard (Hazard ratio [HR] = 0.72; 95% most prevalent isolate of catheter-associated urinary tract
CI = 0.63 to 0.82), that is, prolonged ICU stay. Prolongation of infections in the ICU setting.
ICU length of stay due to HAI was estimated at 5.3 days (±1.6). Marriott and colleagues have undertaken a nationwide pro-
Another approach to estimating cost and length of stay effects spective clinical and microbiologic cohort study of all episodes
of adverse events is to apply survival models, in which the ad- of ICU-acquired candidemia occurring in nonneutropenic
verse event is incorporated as a time-dependent variable. This adults in Australian ICUs between 2001 and 2004 (105,106).
strategy can be applied to costs as well as length of stay (100). Overall, 183 patients had ICU-acquired candidemia with a
TABLB24.2 Leading Nosocomial Pathogc:os by Dcricc- and Proccdurc-.Assodatcd Infcc:tions and

Frequency
HAl• Pathogens NHSN4 2006-2007 (%) Kiss& 2005-2009 (%)
CLA-BSI CNS 34.1 32.1
Enterococcus species 16.0 18.5
Candida species 11.8 NR
S. aumu 9.9 8.7
Kpneumonia 4.9 5.2
Enterobacter species 3.9 4.2
P. aervginosa 3.1 4.2
E. coli 2.7 4.7
A. bavmannii 2.2 NR
CA-UTI E. coli 21.4 27.8
Enterococrus species 14.9 26.5
K pneumonioe 7.7 8 .1
Enterobacter species 4.1 5.0
CNS 2.5 NR
S. avmu 2.2 1.4
VAP S. avmu 24.4 20.6
Enterobacter species 8.4 5 .8
A.cinetobacter species 8.4 NR
K pneumonioe 7.5 12.3
E. coli 4.6 12.2
SSI S. aumu 30.0
CNS 13.7
Enterococrus species 11.2
E. coli 9.6
P. aervginosa 5.6
Enterobacter species 4.2
K pneumonioe 3.0
Candida species 2.0
CLA-BSI, central line-associated bloodstream infection; CA-UTI, catheter-associated urinary tract infection; VAP, ventilator-associated
pneumonia; SSI, surgical site infection; CNS, coagulase-negative staphylococci.
NR, not reported.
"88% of deviciSI&!Iociated HAis were reported from ICUs, 12% were reported from specialty care areas and other inpatient noniCU areas
(Reference: [104]).
6 (Reference: (84) and http://www.nrz-hygiene.de).
3Q..day case-fatality rate of 56%. Host factors (i.e., older age, studies performed in the United States (60,107). By contrast,
mechanical ventilation, and ICU admission diagnosis) and gram-negative infections and fungal infections are becoming
failure to receive systemic antifungal therapy were significantly more common, with gram-negative bacteria, such as Klebsiella
associated with mortality on multivariate analysis. Process spp., becoming increasingly resistant to available antibiotics.
of care measures advocated in recent guidelines was imple- Taken as a whole, the shifts are away from more easily treated
mented inconsistently: follow-up blood cultures were obtained pathogens toward more resistant pathogens with fewer options
in 68% of patients, eves removed within 5 days in 80%, and for therapy ( 108) .
ophthalmological examination performed in 36%. This study
showed that crude mortality remains high in ICU patients with
Clusters ofInfections in the ICU
candidemia and is overwhelmingly related to host factors, but
not treatment-related variables (i.e., the time to initiation of Although <10% of hospitalized patients are treated in ICUs,
antifungals or fluconazole pharmacokinetic and pharmacody- many outbreaks of HAis occur in these units, frequently re-
namic factors). lated to breaks in technique or disregard for infection control
Overall, in contrast to the period before 2000, m~or shifts guidelines. Other epidemics are associated with specific strains
in the etiology of HAis have occurred in the last decade. of bacteria, usually related to a contaminated inanimate or ani-
Gram-positive infections, including MRSA, have been success- mate reservoir from which the organism may be transmitted to
fully controlled, as shown by several large-scale epidemiologic the patients.
Sdcct:al Outbreaks in Different ICUs
Sites of Infection No. of

Unit Organism or Colonization 'Inumnission Patienbl Duration Reference
Neonatal ICU MRSA Stool, nares and throat Cro55-transmi.ssion 27 11 months (207)
swabs
Neonatal ICU Pseudomonas Bloodstream infection Contaminated mineral wa- 42 3 months (208)
aeruginosa and colonization ter wed to prepare baby
bottles
MixediCU MDR Acinetobat:tsr Multiple sites Entire horizontal drainage 11 10 months (209)
baumanntt system
Neonatal ICU Parainfluenza type Respiratory infections Direct person-to-person 7 1 month (210)
3 virus contact
Neonatal ICU Candida pampstwru Fungemia Cro55-transmission 3 18days (211 )
MixediCU Linezolid-resistant Multiple sites Horizontal transmission 15 3 months (212)
Stap!rylococcus
aufftlS
Neonatal ICU ESBL producing Meningitis and Cross-transmission 26 1 month (213)
Escheridlia wli colonization
Neonatal ICU SemJtia man:esceru Respiratory infections Contaminated 5 3 months (214)
urunedicated liquid
soap
MixediCU Vancomycin-resistant Multiple sites Cross-transmission 14 I year (215 )
Enterococcus
frw:ium
Neonatal ICU SalfiWfleUa serotype Salmonellosis Cross-transmission 10 1 month (216)
Tennessee
Pediatric ICU Bacillus cerrus Pneumonia and Reusable air-flow 25 6 months (21 7)
sputum samples equipment for
mechanical ventilation
MixediCU Burlcholderia cepacia Multiple sites Moisturizing body mill 5 18days (218)
Neonatal ICU Stap!rylococcus cap;ru Multiple sites Almond oil 33 3 years (219)
Neonatal ICU BordeteUa pertv.W Pertussis Cross-transmission 4 6weeks (220)
Pediatric ICU Pmv.~ns~ci Pneumonia Direct patient-to-patient 4 9 months (221)
MixediCU SARS Pneumonia Inhalation 51 3 months (222)
MixediCU Serratia liqu.efaciens Bloodstream infection Pressure monitoring 16 3 months (223)
equipment
Neonatal ICU Pseudomunas Multiple sites Artificial fingernails 46 15 months (224)
aeruginosa
Neonatal ICU Enterobacter cloat:ae Multiple sites Cross-contamination and 8 2 months (93)
multi-dose vials
Neonatal ICU Malassezia Multiple sites Health care workers' 15 15 months (225 )
pachydem&atis pet dogs
GeneraliCU Enterococcus frw:ium Bloodstream infection Electronic thermometer 9 3 months (226)
ICU, intensive care unit; MRSA, Methicillin-resistant Staphylococcus aureus; MDR, Multidrug-resistant; ESBL, Extended.,.pectrum Beta-lactamase;
SARS, Severe Acute Respiratory Syndrome.
A literature search in the web-based repository, http://www. patient to patient (109) . Pathogens that exemplify these char-
outbreak-database.com, for outbreaks occurring in ICUs identi- acteristics include S. aunMlS and Serratia, Klebsiella, and Entero-
fied > 1,200 hits. Table 24.g summarizes important features of bacte:r species. Epidemics caused by unusual organisms, such
selected outbreaks. Leading pathogens of outbreaks in the ICU as .Acinetobacter spp., often were associated with contaminated
setting were MRSA and gram-negative bacteria. equipment or with changes in the environment (110) . HAl
Although there were unique factors in each epidemic, outbreaks were more frequently reported from neonatal ICUs
several generalizations can be made. Epidemics associated than from other types of ICUs (72,111,112) . It is important
with specific pathogens often were associated with bacteria to remember that new equipment or a new procedure may
that were relatively resistant to antibiotics, relatively virulent introduce a new reservoir or mode of transmission into the
when compared with normal endogenous and environmen- ICU (113). Finally, transplanted organs from infected donors
tal flora, capable of withstanding variations in environmental also can serve as source of unusual HAis in the critical care
conditions, and transmitted by healthcare worker hands from setting (114).
CONTROL AND PREVENTION OF HAIS efficacy of their product ( 118). Cleaning protocols for invasive
devices should be provided by the industry and be reviewed by
Sur'Peilltlnce
infection control preventionists or hospital epidemiologists
1\vo types of measures are needed to control HAis. Engineer- to ensure the adequacy of the recommendations. Sufficient
ing controls are those controls that are incorporated into the numbers of frequently used instruments should be available
structural design of the unit or equipment and over which to allow time for cleaning, disinfection, or sterilization. An
there is limited human control (see Chapter 19). Administra- increase in the initial outlay for equipment may reduce costs
tive controls are guidelines that must be learned and executed and morbidity in the long term. The routine application of
by healthcare workers (see Chapter 13). The latter are effective guidelines for the appropriate use of medical devices contrib-
only if appropriate changes in behavior are incorporated into utes significantly to the control of HAls. Guidelines for the
the routine activities ofhealthcare workers. For instance, we ex- use and control of urinary tract catheters (see Chapter 31),
perienced a cluster of invasive pulmonary aspergillosis in non- intravascular devices (see Chapter 25), respiratory devices
immunocompromised patients associated with room air filter (see Chapter 32), and other products have been published
replacement (115). Such fatal infection could have been pre- by the CDC.
vented by the establishment and application of guidelines for
this procedure. The Role of the En11ironment
For more than two decades, infection control has focused on
Engineering Control patients rather than the patients' environment as the most
The contribution of the design of critical care units to the con- important source of nosocomial pathogens and HAis. This
trol of HAis is difficult to evaluate. However, it seems prudent attitude was based on studies that failed to find improvement
to consider several issues when remodeling or designing new in the rates of HAis after the units were moved into new,
units (116). "clean" structures (119,120). However, there is a growing
body of literature emphasizing that some HAl pathogens are
1. Adequate space around beds is important for placement of ubiquitous in the environment of patient-care areas, waiting
support and monitoring equipment, allowing staff access to be transmitted on healthcare workers' hands (121,122).
to both the patient and the equipment Therefore, the widespread transmission of antibiotic-resistant
2. Individualized cubicles for each patient also may be impor- pathogens that survive for considerable periods in the envi-
tant in reducing transmission of pathogens in the unit; the ronment (VRE, MRSA, A. baumannii, Clostridium difftcile) and
nurse-to-patient ratio should, however, not be affected by recent advances in our knowledge of the transmission of
geographical distribution. nosocomial pathogens requires a change in hospital hygiene
3. Hand-rub dispensers should be located in convenient places practices (123,124). Appropriate cleaning and disinfection
to facilitate hand hygiene by healthcare workers near the programs are essential to decrease bacterial burden in the
point of patient contact and to interrupt the most important close patient environment and should minimize the likeli-
mode of microbial transmission in the ICU-the hands of hood of cross-infection of multidrug-resistant bacteria in this
healthcare workers. high-risk area ( 125).
4. Separate, designated sinks should be provided for cleaning The best-studied pathogen remains MRSA, which can sur-
equipment vive in the environment for extended periods of time. Obser-
5. All ICUs should be equipped with one or more class A iso- vational studies have shown that environmental contamination
lation rooms. Class A isolation rooms include an anteroom plays a role in the transmission of MRSA (126) . Increased
for gowning and hand hygiene, and should provide both MRSA acquisition in patients staying in a room previously oc-
positive or negative air pressure. Additional rooms for iso- cupied by a colonized patient has been observed (127). Envi-
lation precautions are necessary in units where patients are ronmental and patient isolates also have been linked through
located in large open rooms ( 117) . molecular typing. However, there is no strong evidence in the
6. Consideration also should be given to functional activities literature that directly correlates MRSA in the environment and
in the unit. Attention to traffic pattems and the location MRSA-HAI rates. For instance, a recently published prospective
of clean and dirty utilities and janitors' closets may reduce randomized crossover study compared enhanced cleaning for
opportunities for cross-contamination. Clean function and 1,252 patients and standard cleaning for 1,331 patients staying
storage should be physically separate from dirty function in 2 ICUs. Enhanced cleaning reduced MRSA environmental
and waste disposal. Housekeeping facilities and equip- contamination and MRSA hand carriage, but no significant
ment should be designated for the specific unit and stored effect was observed on patient acquisition or MRSA-HAI rates
separately from clean and dirty utilities. (128). Despite lack of strong evidence, cleaning ofpatient-<:are
surfaces continues to be advocated to reduce environmental
contamination with MRSA
Administr11tive Controls for Medic11l E1Juipment
Oelberg et al. published a spectacular experimental study
Medical technology is changing rapidly, and new diagnostic using noninfectious DNA markers designed from a cauliflower
and therapeutic devices are constantly being introduced into mosaic virus as surrogate markers to illustrate microbial trans-
ICUs. In many instances, the efficacy of the device has not mission pathways (129) . These investigators demonstrated the
been adequately evaluated, and the effect of the device on the rapid spread in a neonatal ICU, of the DNA markers via the
incidence of HAis is unknown. For example, vendors seek- hands of healthcare workers. The most consistently positive
ing to introduce new urinary catheters alleged to have antimi- sites within all pods were the blood-gas analyzers, computer
crobial activity should be challenged to provide data on the mice, telephone handles, medical charts, ventilator knobs, door
handles, radiant wanner control buttons, patient monitors, and, The extent and severity of illnesses afilicting patients in reus
of course, personnel hands (129). These experimental findings demand a high level of nursing care, and the high rate of HAis
were extended by Foca et al. (130), who conducted an epide- mandates strict application of rigid barrier nursing techniques
miologic and molecular investigation of endemic P. aeruginosa to control transmission (see Chapter 13). Breakdown in these
transmission among infuntll in a neonatal ICU that was associ- techniques during periods of understaffing or overcrowding has
ated with widespread envirorunental contamination and car- been associated with outbreaks of HAl (92). A nurse-to-patient
riage of the organisms on the hands of healthcare workers. A staffing ratio of 1:1 has been recommended to reduce lapses in
history of use of artificial fingernails or nail wraps was an addi- techniques that lead to person-to-person transmission of patho-
tional risk factor for colonization of the hands. Transmission of gens within rCUs. A study from Geneva University Hospitals un-
P. aeruginosawas stopped after reemphasis of good hand-hygiene derlines the importance of an adequate nurse-to-patient ratio
practices, the importance of reliable cleaning techniques of in- (93). In this study, a low nurse-to-patient ratio was found to be
animate surfaces and equipment, and the complete removal of an independent risk factor for transmission and acquisition of
jewelry, cosmetic nail treatments, water baths, and unnecessary R cloacae in neonates (Figure 24.3). Thus, reductions in nursing
supplies kept by the patient:!' bedsides (130). A recent investiga- staff below a critical level may cause an increase in HAis in reus
tion by Carling et al. in 27 ICUs corroborated the hypothesis by making adequate patient care difficult.
that cleaning of the patients' dose environment is suboptimal It is important that workers in reus understand their re-
in most critical care unit:!, which may play an important role as sponsibility in preventing transmission of infectious pathogens.
reservoir for transmitting nosocomial pathogens ( 131). This responsibility includes prevention of spread of pathogens
from patient to patient and from the healthcare worker to the
patient. Therefore, it is important that the hospital provides ad-
AJlministrt~-tiPe Controls ftw Het~-lthcti,re Personnel
equate staffing to cover medical absences and personal benefits
Staf.fing and training. For the patient to benefit from tech- that will not punish employees who are responsible enough to
nologic advances in medical care, healthcare workers must be avoid working when ill.
well trained in state-of-the-art intensive care. Studies have docu-
mented that cooperation among critical care personnel can di- Monitoring quality of care. The effectiveness of administra-
rectly influence outcomes from intensive care, suggesting that tive controls will depend on compliance with established guide-
the use of invasive technologies is important but not sufficient lines. Therefore, the performance and behavior of healthcare
for good care of patients (132). Therefore, healthcare workers providers should be monitored (135,136). Failure to comply
in reus should be involved in continuous postgraduate medi- with guidelines, whether on the part of physicians, nurses, or
cal education to learn new technologies and the proper use of other support personnel, should be addressed promptly to pre-
new medical devices and procedures (133,134). They also need vent the establishment of bad habits that impose unnecessary
periodic updates on new disease entities peculiar to patients risks on patients (137,138). Monitoring the quality of medical
in ICUs, including psychologic problems and end-of-life issues care in ICUs is important, albeit controversial, given the com-
associated with hospitalization in an ICU. Finally, the level of plexity of the conditions and treatment:! of the patients and the
stress in ICUs exceeds that of most other areas of the hospi- procedures performed in these units (139,140).
tal. As a result, rates of employee turnover are high in special
care units. Loss of highly skilled medical care workers requires
Atlministrt~-ti11e Controls ftw Pt~-tients
extensive training of replacement workers, including in-depth
training on infection control procedures. Changes in staff and Because of the risk of infection and other complications in
unrecognized modifications in infection control procedures reus, only patients who will benefit from high-intensity, high-
might contribute to epidemics of HAis. risk care should be admitted to reus, and patient:! should be
60 30
~ Requited staff ! Ill
-U+
~ Patients
50 25
--+- Staff on duty
40 20 Figure 24.3. Outbreak of Enterobacter

cloacae in the neonatal ICU of Geneva Univenity
c :!
.... ll
Hospitals, December 1996 to January 1997: Daily
staffing of the neonatal ICU (staff on duty [green
30 15 c
~ ~
•
D.
line and diamonds] vs. required staff [red line
and squares]) and daily number of infants (blue
20 10 line and circles). Arrows indicate Enterobacter
cloacae isolates. The horizontal line indicates the
supposed maximum capacity (15 infants) of the
10 5 unit. (From Harbarth S, Sudre P, Dharan S, et al.
Outbreak of Enterobacter cloacae related to
undentaffing, overcrowding, and poor
0 0 hygiene practices. Infect Control Hasp Epidemiol.
NOV DEC JAN 1999;20:598--603, with permission.)
discharged from the ICU as soon as possible to lower the risk testing in adult ICUs and control of MRSA. No randomized,
of HAI. Unfortunately, there is little published information to controlled trials were identified. Sixteen observational studies
assist the physician in those important decisions. Surveillance and four economic analyses were reviewed. Only two of the ob-
for HAis, monitoring rates of HAI, and reporting results to servational studies had a control group and none of the studies
personnel are important to ensure the quality of medical care were of good quality. The five fair-quality observational studies
in ICUs (141). Properly conducted surveillance can identify showed fair- to poor-quality evidence that active surveillance
behavioral, environmental, or treatment factors that, when cultures were associated with a decreased incidence of hospital-
corrected, will diminish endemic rates of infection in the unit acquired MRSA infections. The available studies exhibited het-
(142). Additional benefits of concurrent surveillance include erogeneity in terms of study design and outcome measures.
early identification of epidemics (72,112). The authors concluded that existing evidence may favor the
use of active surveillance testing, but the evidence is of poor
quality, and definitive recommendations cannot be made at the
PRACTICAL ASPECTS OF INFECTION current time. This systematic review has prompted some criti-
CONTROL IN THE ICU cism in terms of omission of certain important relevant studies,
incorrect referencing of some studies, and also on its emphasis
Methods for preventing HAis are numerous. The principles are
on the randomized controlled study design. Poorly conducted
the same throughout the hospital, and many are discussed else-
randomized trials with insufficient power may not contribute
where in the text. Only selected measures of prime importance
accurate data while other study designs, such as interrupted
in the ICU will be discussed in this section.
time series and controlled before-and-after studies, are fairly
robust if well conducted. Importantly, critics of this systematic
review emphasize the consistency of positive findings in adult
Pt~tient Screening
ICU studies, particularly when active surveillance testing are
Frequent transfers of patients through various units and levels combined with patient and environmental decontamination
of care increase the risk of transmission of resistant organisms and/or hand hygiene.
throughout the hospital (143). Colonized patients are impor- Despite the fact that culture-based MRSA screening tech-
tant animate reservoirs of resistant microorganisms during niques have proven inexpensive and sensitive if collected from
inter-institutional or international transfers and probably ac- several body sites, the time to report the results remains a ma-
count for the spread of multidrug-resistant bacteria ( 144). To jor issue. Definitive identification and testing results are usually
control the spread of resistant organisms, it is important to doc- available only 48 to 96 hours after sample collection, a time de-
ument information regarding carriage of antibiotic-resistant lay that could allow MRSA cross-transmission if patients are not
microflora in the patient's medical record and to report it to presumptively placed under contact precautions. This may be
receiving units and facilities. On-admission screening should one of the reasons (besides low hand-hygiene compliance) why
be considered for any patient transferred from institutions the recently published studies by Cepeda et al. and Huskins
with high prevalence of unusual multidrug-resistant pathogens et al. did not show a significant effect of contact isolation for
(e.g., KPC orNDM-1). MRSA carriers identified by conventional methods in their
Screening on ICU admission also should be considered for ICUs (150,151).
control of endemic and highly transmissible nosocomial patho- Systematic use of molecular screening tests may help to rap-
gens, since patients colonized with multidrug-resistant bacteria, idly detect MRSA carriers (152). We have investigated the clini-
such as MRSA or VRE, serve as a reservoir for spread within cal usefulness of a rapid on-admission screening test for MRSA
the healthcare environment, mainly through the hands of (153). A substantial decrease in MRSA infections was seen in
healthcare workers (145). Unfortunately, guidelines provided a medical ICU after increasing compliance with on-admission
by several governmental, public health, and professional soci- screening and implementing a strategy that linked the rapid test
eties, particularly the Society of Healthcare Epidemiology of to preemptive isolation of MRSA patients. However, no effect
America (SHEA) and CDC, differ in their recommendations. on MRSA rates was observed in the surgical intensive care unit,
These guidelines are similar in most respects but differ mainly although a large number of unnecessary preemptive isolation-
with regard to routine use of active surveillance testing (i.e., days could be saved by using the rapid MRSA test (153).
cultures or polymerase chain reaction) for detection of MRSA Wassenberg et al. examined the costs and benefits of
colonization. The first SHEA guidelines recommended active rapid screening of MRSA carriage in ICUs (154,155). In this
surveillance for MRSA for all high-risk patients (146). The multicenter Dutch study, BD GeneOhm™ MRSA-PCR and
CDC guideline has a staged approach and recommends active GeneXpert-MRSA were compared with culture results as
surveillance only if baseline interventions fail to adequately reference. MRSA prevalence was reported at 3.1% among
control transmission (147). The most recent SHEA recom- 163 patients at risk of carriage. The authors reported a nega-
mendations underline that specific recommendations regard- tive predictive value of 100% for both PCR methods and the
ing universal screening for MRSA cannot be made because of duration of patient isolation at 27.6 hours for GeneOhm and
conflicting results from recent studies and differences among 21.4 hours for GeneXpert, while using cultures as reference
hospitals and patient populations (148). In summary, this issue would have resulted in 96 hours isolation. There was a 44.3%
has caused division among infection control professionals with reduction in isolation-days with the PCR screening at the ad-
much debate by proponents of each strategy. ditional costs per patient screened of €327.84 (GeneOhm)
Although many studies have evaluated active MRSA and €252.14 (GeneXpert). This resulted in a net saving of
surveillance testing in ICUs, the evidence is not always of high €136.04 (GeneOhm) and €121.76 (GeneXpert) per isolation-
quality (148). McGinigle et al. (149) conducted a systematic re- day avoided. The reduction in isolation was less than previously
view of the literature regarding the use of active surveillance reported values for general wards (54% to 60%) and perhaps
reflects the complexities of ICU patients with multiple sites to CDC and the World Health Organization (WHO), have rewrit-
be screened (i.e., IV lines, multiple wounds, catheters). Addi- ten recommendations for hand hygiene in healthcare (159,161):
tionally, most of the current molecular platforms are unable to This breakthrough is due to the following important insights.
examine multiple tests in a short period of time. Thus, in order
1. The time required for fully effective handwashing with
to reduce the duration of costly and often difficult preemptive
soap and water is too long and, therefore, full compliance
isolation of high-risk ICU patients, technical improvement of
with handwashing recommendations is illusory, especially
molecular diagnostics and strategies such as pooling of swabs
iniCUs.
are required to cope with large volume testing.
2. If actively promoted, alcohol-based hand antisepsis can
improve compliance with hand-hygiene recommendations
Pt~tient Isollltion and can reduce HAl and transmission rates (162). In high-
demand settings such as ICUs, an alcohol-based hand-rub
More than 50% of patients admitted to ICUs are colonized at the
solution appears to be the only method that might allow
time of admission with the organism responsible for subsequent
reasonable compliance ( 163) .
infections. Patients who are readmitted to the hospital may carry
3. Various studies clearly demonstrate the improved antimi-
and transmit resistant organisms acquired during previous hos-
crobial efficacy of alcohol products relative to antiseptic
pitalizations (156). Not infrequently, unrecognized infection
soaps containing chlorhexidine or other antiseptics (164).
contributes to the decision for entry into the unit. The early
A few studies even raise doubts as to the efficacy of hand-
diagnosis of potentially transmissible disease requires vigilance
washing with soap and water in preventing the spread of
on the part ofiCU physicians. Patients with suspected infections
multidrug-resistant, gram-positive pathogens (165).
should be appropriately screened and segregated at the time of
4. Alcohol-based hand antisepsis with gels or rinses contain-
admission ( 15 7) . The level of isolation should account for each
ing emollients is less harmful to the skin than regular
of the following factors: the site of infection, the mode of trans-
handwashing with soap and water (166).
mission, the amount of secretions or excretions, and the viru-
5. Previous studies promoting handwashing with antimicro-
lence and antimicrobial susceptibilities of the causative agent.
bial soap and water did not properly assess the indepen-
Discussion of specific isolation techniques are beyond the
dent value of alcohol-based hand disinfection ( 167).
scope of this chapter. It should be recognized that as the duration
of stay increases, the frequency of colonization with resistant mi-
croflora also grows. Patients become animate reservoirs that facili-
tate transmission to susceptible incoming patients (54). It may be
wise, therefore, to separate long-stay patients from the short-stay There is currently little evidence that the addition of gloves in
patients who make up the major portion of the population in the the routine ICU setting has any benefit over regular hand hy-
unit. This segregation may be accomplished by moving chroni- giene in controlling pathogen transmission. Major arguments
cally ill patients to single rooms or relocating groups of patients against the routine use of gloves in ICUs rely on the fact that
to a physically separate part of the unit. A dedicated nursing staff healthcare workers frequently do not remove gloves when mov-
for the long-term patients would provide an added barrier to ing from patient to patient and forget to perform hand hy-
transmission, but this is frequently impossible to implement. giene after glove removal. This was probably one of the main
causes explaining the failure of a recently published duster-
randomized clinical study (151). Huskins and colleagues evalu-
Ht~nd Hygiene
ated >9,000 patients in 18 ICUs with an intervention aimed
Routine hand hygiene before and between contact with patients at implementing barrier precautions (such as universal gloving
is the most important feature of infection control. Virtually all until a patient's VRE or MRSA colonization status was known
medical care workers are aware of and agree with this con- to be negative), active surveillance cultures, notification of per-
cept (158). It is dismaying, therefore, to see repeated reports sonnel of adherence; however, the net result of the interven-
of low levels of compliance with this simple and inexpensive tion has been that, despite the improvement in the compliance
technique. In ICUs, compliance usually does not exceed 40% to precautions and procedures, no effect on VRE and MRSA
(159). Several reasons have been suggested to account for this acquisition rates was observed.
low level of compliance, including lack of priority over other Whereas a number of studies investigated the role of so-
required procedures, insufficient time to accomplish hand hy- phisticated forms of protective isolation in reducing high
giene, inconvenient placement of hand-hygiene tools, allergy rates of HAis in patients with profound granulocytopenia or
or intolerance to the hand-hygiene or washing solutions, lack full-thickness burns, only a few have evaluated whether simple
of leadership on the part of the senior medical staff, and lack of protective isolation would be beneficial for ICU patients. Klein
personal commitment to the routine of hand hygiene. et al. (168) conducted a prospective, randomized trial in ape-
Grossly misleading impressions about the value of alcohol- diatric ICU. In this well-designed study, the authors tested the
based hand disinfection persisted widely during the 20th cen- benefit of simple barrier precautions (i.e., disposable gown and
tury (160). Alcohol-based hand rinses for medical personnel gloves) on both colonization and subsequent infection. Coloni-
were rarely promoted systematically, and, consequently, sink- zation with ICU-acquired bacterial strains occurred an average
based handwashing with soap and water remained the pre- of 5 days later in isolated patients. The daily rate of infection
dominant tool for reducing transient hand carriage of HAl for isolated patients was 2.2 times lower than among patients
pathogens in most ICUs. provided standard care.
Only in the last ten years has the strength of evidence in favor Although previous studies have reported conflicting results
of alcohol-based hand rubbing become simply overwhelming so concerning the value of protective isolation in ICU patients,
that infection control experts around the world including the gowns and gloves may be effective in dealing with selected
high-risk patients (169). The Severe Acute Respiratory Syndrome In summary, despite the data from many clinical trials and
(SARS) epidemic has shown that hospitals with good compliance systematic reviews, it seems difficult to recommend confidently
with barrier precautions had a lower impact and less viral trans- that SDD be either abandoned or used routinely in ICUs
mission compared with institutions that lacked this response around the world. It may be premature to ignore the potential
(170). Further studies are necessary to determine the cost- benefits of SDD, because the results of most clinical trials have
effectiveness of this approach in the general ICU population. been encouraging in terms of reducing HAl rates. Therefore,
To draw definitive conclusions regarding the effectiveness of this use of SDD is more a question of philosophy and art rather
approach, compliance with isolation precautions also should be than an exact science. We believe thatSDD should be restricted
evaluated. Only a few studies have analyzed compliance with iso- to subgroups of patients at high risk of nosocomial pneumo-
lation precautions, and most reported low compliance and insuf- nia or to situations in which efficacy and cost-effectiveness have
ficient knowledge of precautions for pathogens (171,172). been established. In any of these cases, surveillance for antimi-
crobial resistance must be done (73).
CONTROVERSIAL PREVENTIVE APPROACHES

ProUJlcitonin for Imprwing Antibiotic
RELEVANT TO THE ICU SETTING
Us~r-ge ~r-nd DecreiJSing Resistance
Selecti:pe Digesti'Pe Decontll-mim:r:tion
At the current moment, procalcitonin (PCT) represents the best
Since many HAis are believed to arise from endogenous flora studied biomarker for guiding antibiotic treatment duration in
in the oropharyngeal tract, innovations in prevention have fo- hospitalized patients (182,183). Several high-quality clinical trials
cused on the control (decontamination) of potential patho- investigating the diagnostic performance and clinical effective-
gens with oral antimicrobial therapy. The aim of selective ness of PCT have been published (58,184-186). Two large-scale
digestive decontamination (SDD) is to prevent overgrowth of studies confirmed the potential usefulness of PCT to guide anti-
pathogenic gram-negative aerobic bacilli and yeasts. It involves biotic use in critically ill patients (58,185). Nevertheless, in the
the use of topical oral and intestinal antibiotics, often with a study by Bouadma and colleagues (58), more than half (53%)
systemic antibiotic added for the first few days of the regimen, of patients enrolled in the PCT-guided arm did not follow the
with the goal being the elimination of potential pathogens protocol for initial antibiotic treatment decisions, and thus an-
from the gastrointestinal tract. With eradication of endogenous timicrobial use was not completely determined by PCT levels, as
bacterial sources, infection may be avoided (173,174). recommended. In a recent multicenter RCT, Jensen et al. ran-
The role of SDD in preventing ICU-acquired infections and domized 1,200 critically ill patients to either a standard clinical
mortality remains one of the most controversial issues in critical judgment arm (blinded to PCT levels) or a PCT-guided treat-
care medicine (175,176). Hitherto, >30 randomized controlled ment arm with a mandatory drug-escalation algorithm and an-
trials have been published that evaluated the efficacy of SDD in timicrobial guidance based on daily PCT measurements (187).
preventing VAP and reducing mortality. Several meta-analyses of They failed to show any benefit on all-cause 28-day mortality in
these studies showed a positive treatment effect, although the effect the PCT arm (31.5%, 190/604) compared with the control arm
appeared to be smaller when considering only high-quality studies (32.0%, 191/596). More disappointedly, the length of ICU stay
(177,178). The crucial concern associated with use ofSDD is the increased by one day in the PCT arm (p = 0.004), while there
development and spread of antibiotic resistance; whether SDD was indication of organ-related harm (kidney injury) . The rate
contributes to or reduces antibiotic selection pressures by reduc- of mechanical ventilation also increased by 4.9% (95% CI, 3.0%
ing the incidence of HAl remains an open question. Nevertheless, to 6.7%) . There was a substantially higher use of broad-spectrum
some evidence supports the use ofSDD as an effective strategy that antimicrobials in the PCT arm without an earlier appropriate
may reduce morbidity and mortality in selected groups of critically choice of antimicrobial treatment, except among those with
ill patients hospitalized in those units where cross-transmission of proven BSis. There was a higher frequency of microbiologic
multidrug-resistant microorganisms (e.g., MRSA or Acinetobacter sampling in the PCT arm mainly due to more airway and urine
spp.) is nota predominant problem (179,180). samples and blood cultures. These findings somewhat contradict
More recently, de Smet et al. have shown the value of SDD or the recent systematic reviews, which despite no indication of im-
selective oropharyngeal decontamination (SOD) for reducing proved mortality, showed benefits among patients with respira-
mortality ofiCU patients in a large duster-randomized clinical tory tract infection and sepsis by significantly reducing antibiotic
trial (82). However, both SDD and SOD markedly affected the exposure and showed a trend towards reduced costs and length
bacterial ecology, with rising ceftazidime resistance prevalence ofiCU stay (188-190).
in the respiratory tract during intervention and a considerable In summary, for critically ill patients, PCT probably remains
rebound effect of ceftazidime resistance in the intestinal tract a suboptimal marker to strongly influence initial treatment
after discontinuation ofSDD (73). decisions or even withhold empiric therapy for potentially life-
Another potential role for SDD may be in the control of threatening infections. However, PCT measurements may in-
HAl outbreaks. Brun-Buisson and colleagues (181) reported crease the confidence of clinicians to withdraw antimicrobial
that intestinal decontamination by oral nonabsorbable antibi- therapy at an earlier time-point in the m.Yority of patients.
otics was important in resolving an outbreak of infection with
multidrug-resistant Enterobacteriaceae in a medical ICU. In units
MultimoiUJl Intenentions ~r-ntl Prnmtion
where routine infection control measures fail to control out-
Btmtlles Under Ro.aine Working Conditions
breaks, careful application of SDD, including the selection of
appropriate oral antimicrobial agents and diligent monitoring It is unclear what proportion of HAis is potentially preventable
for the emergence of new resistant strains, might be an impor- under routine working conditions. We performed a systematic
tant adjunct to conventional infection control procedures. review to describe multimodal intervention studies in order to
370 Stctionll • FuntionalAreas oJConcem
give a crude estimate of the proportion of potentially prevent- TABLE 24.4 Institute for Healthcare
able HAis (191). The evaluation of !W reports suggests that
lmprovanmt (llll)
great potential exists to decrease HAl rates, from a minimum
reduction effect of 10% to a maximum effect of70%, depend-
lnfcction Prevention Bundles
ing on the setting, study design, baseline infection rates, and for the Intcmive ~Unit
type of infection. The most important reduction effect was (ICU) Settings
identified for catheter-related bacteremia, whereas a smaller, DD VENTILATOR. BUNDLE
but still substantial potential for prevention seems to exist for
1. Elevation of the head of the bed to between SO and 45 degrees
other types of HAis.
Although the optimal approach to reducing HAis in criti- 2. Daily •sedation vacations• and assessment of readiness to extubate
cally ill patients is unclear, recent studies and large quality 3. Peptic ulcer disease prophylaxia
improvement initiatives have shown that education-based pro- 4. Deep venous thrombosis prophylaxis
grams with multiple interventions can decrease HAl rates in
(A fifth bundle element, "Daily oral care with chlorhexidine; was
different ICUs and settings (192). added in 2010.)
The bundle concept was first implemented for the prevention
DD CENTR.AL I.JNE BUNDLE
ofHAis via improved compliance with hand hygiene (162,19~).
In 2001, the U.S. Institute for Healthcare Improvement (IHI) 1. Hand hygiene
developed the bundle concept and defined it as: "a small set of 2. Maximal barrier precautions
~ interoentiuns for a rkftmd patient segment/population 3. Chlorhex:idine skin antisepsis
and ca~ setting that, when implemented togtther, willmult in signifi-
4. Optimal catheter site selection, with avoidance of using the
cantly better outcomes than when implemented individualij' (194).
femoral vein for central venous access in adult patients
Bundle design guidelines for IHI, are the following:
5. Daily review of line necessity, with prompt removal of
• The bundle has three to five interventions (elements), unnecessary lines
with strong clinician agreement.
• Each bundle element is relatively independent.
• The bundle is used with a defined patient population in
improvements in clinical outcomes such as mortality. Accord-
one location.
ing to O'Grady and colleagues, before clinicians broadly adopt
• The multidisciplinary care team develops the bundle.
the Ventilator Bundle for all patients, the evidence should show
• Bundle elements should be descriptive rather than
that clinically relevant outcomes are improved (201).
prescriptive, to allow for local customization and
Similar decreasing trends have been published regarding
appropriate clinical judgment.
the Central Line Bundle, with one study from U.S. ICUs not-
• Compliance with bundles is measured using aU-or-none
ing an association with lower CIA-BSI rates only when bundle
measurement, with a goal of 95% or greater.
compliance is high (202). The Keystone ICU project has dem-
The IHI Ventilator Bundle and the IHI Central Line Bundle onstrated that a multi-factorial approach, including adherence
were the first bundles developed. The elements of the two ini- to the five evidence-based procedures in the Central Line Bun-
tial bundles are shown in Table 24.4. The Ventilator Bundle dle, when combined with a daily goals sheet, team training and
was used subsequently in IHI's critical care initiative in the communication, a unit-based program to improve the safety
IMPACT network starting in july 2002. Data from ~5 ICUs in culture, and other factors, can lead to a sustained reduction,
the IMPACT network showed that, with high Ventilator Bundle up to 66%, in CIA-BSI rates (134).
compliance (>95%), VAP rates were reduced by 44.5% (195). The bundle concept also has been applied in other clinical
In analyzing these improved outcomes, authors determined areas, including sepsis, which also has led to improvements in
that it was more than just measuring these care elements as outcomes. Two publications have noted decreases in hospital
a bundle that led to success. The changes made to how work mortality and length of stay associated with implementation of
was done and how the team interacted contributed to the high one or both Severe Sepsis Bundles (one on resuscitation and
levels of performance (>95% compliance with the bundle). another on management) based on the 2004 Surviving Sepsis
Examples of such changes included use of checklists, revising Campaign (20~,204). By contrast, the bundle approach seems
the structure and process of daily multidisciplinary rounds, and to be less effective for the prevention ofSSis (205), a topic be-
use of daily goal sheets. yond the scope of this chapter and discussed in depth in an-
Many hospitals have continued to use these two bundles other section of this textbook (see Chapter 36).
in ICU patients and reported on their improved outcomes, Various strategies exist to implement bundles, including ed-
which have repeatedly been linked to sustained compliance ucational meetings, feedback, retninders, financial incentives,
with the bundle (196). Others have made local modifications and revision of professional roles. Unfortunately, there is no
to this bundle and reported on their success as well ( 197,198). superior strategy or so-called magic bullet that works for all in-
For example, a French multifaceted prevention program with novations in all circumstances. The challenge lies in building a
eight targeted VAP preventive measures implemented during strategy on the careful assessment of barriers and facilitators,
a ~0-month intervention period resulted in a 43% decrease and on a coherent theoretical base. To evaluate and quantifY
in VAP rates among ICU patients who received mechani- the effect of well-developed strategies to implement bundled
cal ventilation (199,200). But no large randomized study has preventive practices, a prospective clinical effectiveness trial
demonstrated that reducing VAP using any VAP prevention entitled IMPLEMENT was designed to spread and test knowl-
strategy, including those in the IHI bundle, is associated with edge on how to implement strategic bundles for infection
Chapter 24 • The Intensive Can! Unit, Part A 3 71
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aaoociated pneumortia: impact on compliance with preventive meaoureo. Crit Ctm MM. neonatal intensive care unit: contaminated unmedicated liquid ooap and ri1t factoro.
2010;58:789-796. J HOIJJ 1'rrfod. 2009;72:17-22.
200. Bouadma L, Deoiandeo E, Lolom I, et al. Loll&"term impact ofa multifaceted prevention 215. Zhu X. Zheng B, Wang S, et al. Molecular characterioation of outbrealt..-clated •train• of
program on ""R:ntilator-auociated pncwtlouia in a medical Wtc::nli.ve care ullit. Clift lKJra vam::omyciD-railtant ~ fll«iva from au intculivc care uuit in Beijing, Cb..Wa.
Dis. 2010;51:111!>-1122. J HOIJJ Infect. 2009;72:147-154.
201. O'Grady NP, MUITay PR, Ameo N. Preventing ventilator..,..ociated pneumonia: does the 216. Boehmer TR, Bamberg WM, Ghooh TS, et al. Health care.....ociatcd outbreak of
evidence mppon the practice? jl1MA. 2012;507:25!4-2559. Salmonella tenncoocc in a neonatal intensive care uniL Aa J Info:~ C0111rol. 2009;!7:
202. Fu=ya E'i; Did A, Percuccvich EN, et al. Gcutrallinc bundle implementation in U.S. 49-55.
intenaive care unita and impact on bloodotream infectiono. PLoS 0.... 2011;6:e15452. 217. Kalpoe JS, Hogenlrlrk K, nn Maaro....,en NM, ct al. Di.tocmination of Bacilluo ccrcua in
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for the early manag=ent of oevcrc oepoi.t and ocptic ohock it aooociated with decrcaoed ak.tlow oenooro.j HOIJJ Inftct. 2008;68:541-347.
mortality. Grit c- M6tL 2007;35:110!>-1112. 218. Alwr=Lcrma F, Maull E, Tc=adao R, ct a!. Moi.ttur:izing body milk ao a rcoervoir of JJUT-
204. Zambon M, Ccola M, Almci<Ja.<le.{]aotro R, et al. Implementation of the ouniving ocpoia IIIwld4ria r:tl[lal:itt;. outbreak of nooocomial infection in a multidi.tciplinary intensive care
Campaign guideline• fur severe •epoio and ocptic ohock.: we could go falter. J Crit Can. uniL Crit Can. 2008;12:Rl0.
2008;25:45!>-460. 219. Grat-Lc Guen C, Founrler S, And~Richet B, et al. Almond oil implicated in a St4p/IJI=I>-
205. Anthony T, MUITaY BW, Sum-Ping JT, et a!. Evaluating an cvidenco-bued bundle for """mfritisoutbreak in a neonatal intenmve care unit. J l'lrWJtoL 2007;27:71~717.
preventing ourgical ate infection: a randomized trial. Anh S...,. 2011;146:26$-269. 220. Vranken P, Pogue M, Komakwlki C, et aL Outbreak of pcrtwoi.t in a neonatal intcnaivc
206. Kaier R, Wiloon C, Hulocher M, et al. Implementing otrategi<: bundle• for infection pro- care unit-Louisiana, 2004. AmJ Infut CmalruL 2006;34:55!h554.
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in a neonatal intenoivc care unit. &KJ Clm MimJ/JitJIInfo:t Dis. 2011;30:909-913. 222. Ho AS, SunglJ, Chan-Ycung M. An outbreak of ocverc acute reopiratory oyndrome among
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eral water bottlco in a neonatal intenaive care unit faot typing byuoc ofhlgb-reoolution melt- 564-567.
ing anat,.is of a nriable-numbcr Wldem-repcat locua.J C1in Mierobid. 2010;48:5H6-S152. 22!. Harnett SJ, Alli:n KD, Macmillan RR. Critical care unit outbreak of s.m.tia '/iiluftuiml
209. LaForgiaC,FrankeJ,HacekDM,etal.Managcmentofamultidrug-remtantA~ from contaminated preuure monitoring equipment. J HOIJJ hlfoet. 2001;47:!01-307.
b~ftii outbreak in an intellliR: care unit uaing novel emiromnental diJinfection: a 224. Moolcnaar RL, CrutcherJM, SanJoaquin VH, etal. A prolonged outbreak of Psoutlomtmtu
511-month report. Aa J Info:~ CmalruL 2010;38:259-.26!. ~in a neonatal intenaive care unit did otaff fingernailo play a role in dioeaoc
210. Teo WY, ~adurai VS, Sriram B. Morbidity of parainfluenza ~ outbreak in prctcrm in- tranomiloion? Info:~ Control HOI/J ~ 2000;21:110-&.
fanta in a neonatal uniL A1mAcatiMtd SingrJfKm1. 2010;39:837-M::!. 225. Chang HJ, Miller HL, Watkim N, ct aLAn epidemic of Malamzia J-:itJ~ in 811 in-
211. Hemandcz.<:aotro R, Arroyo-Eocalantc S, C:arrillo-Cuaa EM, ct al Outbreak of Cazulidl> tenaive care nunery 011ociated with colonization of health care wo!hr~' pet dogl. N Eflll
~in a neonatal intcmive care uoit: a health care worken source. EvrJ Pcdian: JMM. 1998;!38:706-711.
2010;169:78!--787. 226. Livorncoe LL Jr, Diu S, Samel C, ct aL Hoopital-ecquircd infection with vancom}'dn-
212. Morala G, Picazo], Baoo E, etal.llaistance to lincwlid i> mediated by tbc di'gcne in the lint rcoiatant E~ fac<ium tranlllllitted by electrouic thcnnomctero. An" Im.m MM.
reportofanoutbrcakoflint:mlid<coiatant~-ClininjiaDU.2010;50'.821-825. 1992;117:112-116.
Nasia Safdar and Dennis G. Maki
The Intensive Care Unit, Part B:

Antibiotic Resistance and Prevention of
CVC-BSis, Catheter-Associated Urinary
Tract Infections, and C. difficile
INTRODUCTION the Efficacy of Nosocomial Infection Control (SENIC) Project
showed that surveillance can help prevent HAis (6).
Intensive care units (ICUs) have revolutionized the care ofaitically The National Nosocomial Infections Surveillance (NNIS)
ill patients with trauma, shock states, and other life.threatening syatem waa establiahed in the early 1970s to measure the impact
conditions, leading to greatly improved outcomes (1,2). However, of HAis, better understand their associated risk facton, and
healthcare-esaociated infection (HAl) (ICU-acquired) remains a develop effective strategies for their control (7). NNIS is now
m;yor challenge in the ICU patient; the xates of infection in the called the National Healthcare Safety Network (NHSN) and
ICU are three to five times higher than the rates in other hospital includes approximately 5,000 hospitals. Surveillance of HAis
wards (~,4). Although patients in the ICU represent only 10% of bas been standardized by the NNIS/NHSN syatem by pro-
all hospital ailmiS'fions, they account for nearly 50% of all HAis in viding definitions, especially for device-associated infections
U.S. hospitah. M;yor advances in our understanding of the epi- (DAis) (8). These definitions have recently been updated to
demiology and pathogenesis ofiCU-acqujred infections have oc- increase specificity and accuracy of surveillance for DAis, espe-
cw:red. over the past two decades, leading to the development of cially ventilator-associated pneumonia (VAP). Targeted surveil·
measures to greatly reduce or prevent these HAis. lance and calculation of DAI rates per 1,000 device-days allows
benclunarking with similar hospitals and detection of unique
institutional problems that need redreu and a mechanism for
EPIDEMIOLOGY assessing institutional trends and even HAl outbreaks.
Since the length of stay heavily impacts the HAl risk, infec-
Currently, HAis affe<:t >2 million patients in U.S. hospitals tion rates should be expressed per 1,000 patient-days. Device
annually, and are associated with approximately 90,000 deathll utilization affects DAI rates, and the CDC recommends surveil·
each year (5). lance ofDAis and calculation ofrat.es ofDAI per 1,000 device-
Surveillance of HAis, especially in high-risk hospital set- days. The rates of HAI vary among the different types of ICUs,
tings, such as the ICU, has become an integral feature of in- and are highest in neonatal, surgical, and bum units followed
fection control and quality assurance in all U.S. hospitals. The by medical ICUs. Patients in coronary care units have a very low
Centers for Disease Control and Prevention (CDC) Study of risk of infection (Table 25.1) (9-11).
TABLE 25.1 Rates ofDerice-ABiociated Infcc:tioos per 1,000 Deric:e-Da')'l by Type ofiCU in CDC
NHSN Hospitals, January to December 2010
'lyPeofiCU
1f(w:IWtt
Medical._,M_
(.25"· 15")
~
.v- (.25"·'5")
...... s...p:.l....,,M_
(.25"· "")
Catheter-uaociated urinuy bact infection 2.4 (0.9, 5.7) u (0.6,5.4) 5.0 (1.0, 4.4) 1.9 (0.5, 5.1)
Centtalllne-uaociated bloodstream 1.8 (0.8, 2.5) 1.4 (0.0,2.1) u (0.4,1.9) u (0.0, 1.8)
infection
Ventilator-ueociated pneumonia 1.4 (0.1, 2.2) 1.8 (0.0, 2.5) 5.5 (0.4, 4.8) 1.5(0.0,2.1)
Adapted. from Dudeck MA. Horan TC, Peterson KD, et al. National Healthcare Safety Network (NHSN) Repon, data summuy for 2010,
devic:e..uiOciated module. Aajhlfor:l CoMul. 2011;59:798-816.
375
Pseudomonas aerug1nosa 23% Pseudomonas aeruginosa • • • • • • • • • • • • • 30%
StaphylococCU$ tiUfi!IUS 22%
Staphylococcus aurous • • • • • • • • • • •25%
~oagutaS&-negatJve staphyk>ooe<:j 21%
Enteroooccus 10% Enterobacter spp . • • • • • 11%

Candida spp. 8%
Klebsiella pneumoniae
Enterobacler spp . 5%
£$Cherichi8 colj 5% Escherichia coli 5%
KlebsielltJ pneumonia& 5%
Serratia maroescens
Seffat1a marcescen& . 2%
Acinetobacter spp .
Flpre 25.1. Microbiology ofinfectioru in the ICU. (Adapted

from Richardl M, Thunky K, Buiaing K. Epidemiology, prenlence,
'Jther gram·negatlve organisms ~~~~!~~1.::5%~,...---..---.---.
and sites of infections in intensive care units. &min .RI!IIfM Orit Om
Med. 200S;24:3-22.) Flpre 25.3. Miaobiology of healthcare-associated pneumonia
in the ICU. (Adapted from Richards M, Thursky K, Buiaing K.
Epidemiology, prevalence, and sites of infections in intensive c.are
The epidemiology of ICU-acquired infection in develop- units. hill Respir Orit Qm: MlliL 2003;24:3-22.)
ing countries has recently been characterized by a new, large
multinational surveillance system in developing countries in
South and Central America, Aaia, Africa, and the Middle East mandate that every hospital have an active program for sur-
using NNlS/NHSN definitions of HAl. In a recent report, veillance, prevention, and control of HAis (13). Surveil-
the overall rates of DAI in 55 ICUs of the consortium were lance is the cornerstone of an effective control program. In
22.5 infections per 1,000 ICU-d.ays; 41% of infections were most institutions, surveillance focuses on infections caused
VAP, followed by central line-associated bloodstream infection by antibiotic-resistant bacteria and infections that greatly in-
(CLA.-BSI; 12.5 epiaodes per 1,000 catheter-days) and catheter- crease morbidity and mortality (e.g., surgical site infections
associated urinary tract infectiows (CA-Ulls; 8.9 episodes per [SSis], BSis, and VAP).
1,000 catheter-days) (12). These rates are 2- to 3-fold higher Although it is unclear whether environmental contamina-
than reported in North American ICUs, and highlight the tion with resistant bacteria translates into greater infections in
extraordinary vulnerability to HAis in ICUs around the world. patients, the inanimate environment is a reservoir of resistant
Aerobic gram-negative bacilli, especially~~ HAl pathogens. Several studies have shown that methicillin-
nosa, account for 50% of ICU infections; gram-positive cocci resistant SfD/1hylot:occus iJUR'US (MRSA), vancomycin-resistant
(20%) and Ctnulida spp. (10%) make up the remainder (3,4). enterococcus (VR.E), Clostridium diJJicile, and gram-negative
Figures 25.1 to 25.4 show the microbiology of ICU infection bacteria can be recovered from a variety of hospital surfaces.
overall and with VAP, CLA-BSis, and CA·UTis (4). Although the ICU environment cannot be made microbe-free,
certain architectural and environmental issues wammt atten-
tion. ICUs should be located in areas that limit traffic flow to
GENERAL ASPECTS OF INFECTION essential ICU personnel. An adequate number of sinks and
CONTROL dispensers of waterless alcohol-based hand rub or antimicro-
bial soap must be available for all entering personnel who will
The U.S. joint Commission (1JC), formerly the Joint Com- have contact with the patient and the immediate environment.
mi:uion Accreditation of Healthcare Organizations (JCAHO), Separate areas and sinks should be used for cleaning, for stor-
and similar regulatory agencies in many other countries age, and for reprocessing contaminated equipment. All ICUs
Coagutase· negative staphylococci

..1111111111111111111 43% Escherichia coli . . . . . . . . . .20%
Candida SIJP• . . . . . . . . . .20%
Staphylococcus aureus • 111111120%
Pseudomonas aeruginosa • • • • • • • 15%
Enterococcus • • • • 15% Enterococc.us
Candida SPP.
Enterobacter spp.
Pseudomonas aeruginosa 3% Serratia maroescens
Coagulase-negative Staphylococcus
Enterobacter spp. 3%
Staphyfococcus auretrs
Other gram·negative organisms 10%
Flpre 25.2. Microbiology of bloodstream infectioru in the ICU. Flpre 25.4. Miaobiology of catheteNSIIOci.ated urinary tract
(Adapted from Richards M, Thursky K. Buiaing K. Epidemiology, infections in the ICU. (Adapted from Richards M, 'I'hunky K. Buiaing K.
prevalence, and sites of infections in intensive care units. &min Respir Epidemiology, prevalence, and sites of infections in intensive care units.
em <:are Med. 2003;24:3-22.) Semm 1Wpir OriJ Care Med. 2003;24:3-22.)
CMfMr 25 • 1714lntmsive Om Un#: Pan B 377
should have airborne infection isolation rooms for patients

with tuberculosis or other airborne infectiona. For ICUs in-
TABLE 25.2 Strategies to Improve Hand
volved in the care of bone marrow tr.msplant patients or he- Hygiene Compliance
matologic malignancy, positive pressure isolation rooms using • Healthcare worker education
high-efficiency particulate air (HEPA) filtration should be • Routine oblenation and feedback
available. All surfaces contiguous to the ICU patient should be • Engineering controls
• Eaay, convenient lmlilability of alcohol-baaed band rub
wiped down with the general hospital disinfectant at least daily,
• Patient education
and urine-meaauring devices, a frequent reservoir of gram- • Remindenl in workplace
negative bacilli, should be rinsed with a disinfectant after each • .Adminisualive sancti0111 or rewards
use. Each ICU patient should have a dedicated stethoscope and • lmprcned skin care for healthcare workers
sphygmomanometer. • .Active participation at individual and institutional levels
Adapted from Pittet D.lmproving adherence to hand hygiene prac;

HAND HYGIENE tice: a multidisciplinary approach. E-r lnf«<Di& 2001;7:254-240.
Infected or colonized patients represent the main reservoir

of HAis in the ICU, and the major mechanism of spread of
HAI pathogens in the ICU is by carriage on the hands, ap-
parel, or equipment of healthcare workers (HCWs). This has Hygienic hand care with antiseptics is clearly more effec·
been most clearly shown in outbreak settings and for gram- tive than conventional handwashing with soap and water; the
positive pathogens in studies predating the advent of novel advantage is moat pronounced when contamination is heavy
agents, such as waterless alcohol-based hand rubs, for hand (24,25). Conventional handwaahing with plain soap and water
hygiene; the role played by HCWs in horizontal transmission results in minimal reduction or even, paradoxically, an increase
of gram-negative bacilli in the ICU in the presence of water- in bacterial counts compared to the baseline count before
le,s alcohol-containing hand rubs remains to be elucidated. the handwashing (Figure 25.5) (18,26). The increase is prob-
In a recent well-conducted cohort study, Waten et al. sought ably caused by promotion of bacterial release and dispersal
to determine whether or not hand carriage of gram-negative through shedding of colonized skin squames (27,28). In addi-
bacilli by neonatal nurses was associated with endemic HAis tion to ruperior antimicrobial activity, some antiseptics, such as
caused by gram-negative bacilli in neonates cared for by those chlorhexidine, bind to the stratum corneum, producing long·
nurses (14). The investigators found that 192/2,935 neonates term anti-infective activity on the skin mrface (29).
enrolled acquired an infection caused by gram-negative bacilli; Antiseptics commercially available in the United States in a va-
'10% of the isolates were available for molecular typing, and 9% riety offormulations include chlorhexidine, iodophors, triclosan,
(11/119) of strains causing infection were recovered from the
hands of neonatal ICU nurses. An additional 33% (39/119)
of strains were shared among infants, providing indirect evi- ALL ORGANISMS
dence of hand caniage by HCWs. In this study, sampling of 6
nurses' hands was performed quarterly immediately after hand L .T
hygiene using waterless alcohol-containing hand rubs, and be- 2 5 ~
..;
cause carriage is typically transient, it is possible that more fre- P<O. ~
quent culturing would have yielded a larger number of shared "'

.J
+
4
~
strains. It is important to note that the role of the environment IU
Ill: 3
aa a reservoir of HAl gram-negative pathogens was not assessed
in this study. ......J:::> 2 1-
Given the importance of hands as a m;yor vehicle of hori- :::>
u
zontal transmission, hand hygiene remains the fundamental 0
measure advocated to prevent HAis (15-20). Despite the uni- z
c
versal acknowledgment of handwashing/hygiene as a comer- %
.... 0
stone of HAl control programs, compliance rate& of >50% :::>
1&.
have been difficult to achieve, and handwashing/hygiene rates u GRAM-NEGATIVE BACILLI
3
have ranged from 9% to 50% in HCW studies (21,22). c-
0
Recent investigations have strived to better undentand the 0

.J 2
reasons for poor compliance in the face of the compelling
evidence of the importance of handwashing/hygiene for HAl z
prevention (21), identifying cutaneous irritation, inconvenient
c
w "/.::: .:.:.~·.
sink location, time constraints, high workload, or understaffing.
:I :·::: :::
o~~~B~A~-----~~~~-----~~~-------
Of concern, risk factors for noncompliance with hand hygiene
include being a physician (rather than a nurse), working in an SOAP IOOOPHOR CHL.OR.. £XIOINE ...,.
ICU, and, paradoxically, engaging in patient-care activities with
a high risk of cros8-transmission (21). Interventions to redre,s
Figuft 25.5. Immediate bacterial removal with 8 handwaahing
agents. Each agent was studied in 10 individuals with 1 week between
these deficiencies have included targeted education; feedback; the teats. Cultures were obtained immediately before (B) and after
convenient location of sinks and hand hygiene agents; use of (A) handwashing with the agent. The bacterial count increaaed after
alternative, less initating hand hygiene agents; and patient ed- hand washing with aoap alone. (Adapted from Mald DC. The uae
ucation (17). Table 25.2 summarizes the strategies to enhance of antiseptics for handwuhing by medical peraonnel. j C1letNJdler.
compliance with hand hygiene (23). l989;l(.suppll):3-ll.)
parachlorometaxylenol, and alcohol-based product!! (17). A The recent CDC guidelines have been endorsed by the
number of before-after studies using time-series analysis and American Medical Association (39) and the American Society
HAis as the primary outcome in ICUs (15,16,30-34) have shown for Microbiology (4Q), both of which have played an active role
that alcohol-containing waterless hand rubs were associated with in emphasizing hand hygiene in all areas of healthcare. Insti-
significant HAl reductions. Three large, well-conducted, ran- tutional commitment is essential to improve compliance with
domized trials assessing the efficacy of chlomexidine-containing recommended hand hygiene practices. The CDC guideline rec-
hand hygiene product!! showed a 27% to 4 7% relative reduction ommends that institutions (a) monitor and record adherence
in HAis (30,33,34). The CDC recommendations for hand hy- to hand hygiene by ward or service, (b) provide feedback to
giene have been published (35), emphasizing hand antisepsis HCWs about their performance, and (c) monitor the volume
with an antiseptic-containing soap or detergent, or an alcohol- of alcohol hand rub used per 1,000 patient-days.
based hand rub: (a) before and after direct contact with patient!! Monitoring compliance with hand hygiene is most often
or the environment and equipment in the immediate vicinity undertaken using direct observations by trained observers. Al-
of the patient and (b) before perfonning invasive procedures, though this remains the gold standard, there are limitations
such as insertion of an intravascular device or urinary catheter. to this method including interobserver variability as well as
Alcohol-based waterless hand rubs are now widely used in hospi- being time- and labor-intensive. More recently, a number of
tals for hand hygiene because of their convenience and broad- electronic monitoring systems for capturing hand hygiene
spectrwn activity ( 17). However, all have limited efficacy with compliance have become available; however, these systems
gross soilage so that visibly soiled hands should always be washed need to be validated and tested for efficacy before coming into
with antiseptic soap and water (36). widespread use. Th.ble 25.3 summarizes the recommendations
The mcgor factor limiting the acceptance of alcohol product!! for hand hygiene in the 2002 CDC Guideline (35).
for hand antisepsis in the past was desiccation and irritation of
skin. This is now obviated by incorporating emollient!! into al-
cohol-based hand rubs, which has enhanced HCW acceptance, ANTIMICROBIAL RESISTANCE
and may augment antibacterial activity by slowing the evapora- INTHEICU
tion of alcohol (37). A recent randomized clinical trial in 50 ICU
HCWs compared a conventional 2% chlorhexidine gluconate The global crisis in antimicrobial resistance has had a huge im-
wash with water to a waterless alcohol-based hand rub (61% eth- pact in the ICU where antibiotic pressure, critically ill patient!!,
anol with emollient!!) and showed that the use of the waterless invasive devices, and procedures all contribute to increased
alcohol-based product produced significantly less skin scaling spread of multidrug-resistant pathogens (Figures 25.6 and
and irritation (38); unfortunately, degerming was not assessed. 25.7) (41-43). Stemming the tide of antimicrobial resistance
TABLE 25.3 Handwashing and Hand Antisepsis Recommendations from the CDC/HICPAC
Guideline on Hand Hygiene
Strength of
Recommendation°
When hands are visibly dirty or contaminated with proteinaceow material or are visibly soiled with blood or other lA
body fluids, wash hands with either a nonantimicrobial soap and water or an antimicrobial soap and water.
If hands are not visibly soiled, we an alcohol-based hand rub or wash hands with an antimicrobial soap and water m
for the following situations:
Before direct contact with patients
Before putting on sterile gloves when inserting a central vascular catheter
Before inserting a urinary catheter, peripheral vascular catheter, or other invasive procedure not requiring
surgery
After contact with patient's intact skin
After contact with body fluids, mucous membranes, and wound dressings if hands are not visibly soiled
Moving from a contaminated body site to a clean body site during patient care
After contact with inanimate o~ects in the immediate vicinity of the patient
After removing gloves
Before eating and after wing a restroom, wash hands with a nonantimicrobialsoap and water or with an antimi- m
crobial soap and water.
Antimicrobial-impregnated wipes are not a substitute for using an alcohol-based hand rub or antimicrobial soap. m
If exposure to BaciUus anthracis, wash hands with nonantimicrobial soap and water or antimicrobial soap and II
water.
lA; strongly supported for implementation and strongly supported by well-designed experimental, clinical or, epidemiologic studies.
18: strongly recommended for implementation and supported by certain clinical or epidemiologic studies and by strong theoretical rationale.
II: suggested for implementation and supported by suggestive clinical or epidemiologic studies or by strong theoretical rationale.
"Categorization of recommendations.
Adapted from Boyce JM, Pittet D. Guideline for hand hygiene in health<are settings. Recommendations of the Healthcare Infection Control
Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA Hand Hygiene 'Th.U. Force. MMWR Recomm &p. 2002;51: 1-45.
CMfMr 25 • T1w lntmsive Om Un#: Pan B 379
MEOIC.AL PERSONNEL CONTAMINATED

Colonozed HOSPITAL ENVIRONMENT
lnteeled Fh"d • Contoonong Appor otus
Tro nsotnt Hond lns t•ume~''
Corrotr$
Med oeohons, Porenteroh
Food
Atr
CONTROL CD:!m:>lllt:m:~m~
Res~~OI't
EXOGE NOUS TRANSMISSION PATIENTS' OWN
Con toer COMMUNITY-ACOUIREO fLO'U
Aor
"8"'
Cutontous
TN/~~:~~~~
Ruporo t ory
KS \1 s s s s s 11 s Gostroon1utonol
Gtlllloii'IOIY
j NONCOLON IZED PATIENTS!
0 ENDOGENOUS
TRANSMISSION
Figure 25.6. The epidemiology of nosocomial infection. Transmission occurs m2inly by contact
spread to a much lesser extent by the airborne route . .Aspiration, surgi.caJ. wounds, exposure to inw-
sive devices, and antimicrobial use amplify tranmrission, colonization, and .!Wiceptibility to infection.
(Adapted &om Mali DG. Control of colonization and lranllminion of pathogenic bacteria in the
hospital. Ann Intem Mild. 1978;89:777-780, with permission.)
mandates a multifaceted approach, encompuaing antimicro- PRBVENTION OF HEALTHCARE-ASSOCIATBD

bial stewardship, hand hygiene, and barrier precautions for SPREAD OF RESISTANT ORGANISMS
HCWs in contact with high-risk patients. The CDC's Campaign
Isolation of infected or colonized patients is widely regarded as
to Prevent Antimicrobial Resistance aims to prevent antimi·
the most important measure to prevent the spread of resistant
crobial resistance in healthcare settings (44). The campaign
pathogens through the healthcare institution (50). The most
centen on four main strategies: prevent infection, diagnose
recent CDC guideline categorizes isolation precautions into
and treat infection, use antimicrobials wisely, and prevent
(a) standard precautions and (b) transmission-based precau-
transmission.
tions (51). Standard precautions specify the use of gloves for
any anticipated contact with blood, any body fluid, secretions
CONTROL OF .ANTIMICll01UAL RESISTANCE:
or excretions (except sweat), nonintact skin, and mucous mem-
OPTIMIZING ANTIMICROBIAL USAGE
branes. Gowns are recommended if patient-care activities are
Antimicrobial use drives antimicrobial resistance (45,46). Stud· likely to generate splashes of blood, body fluids, and secretions.
ies have shown that inappropriate antimicrobial use is common Hand hygiene is expected after removing gloves and between
in healthcare institutions (47,48). Antimicrobial stewal:dsbip is patients. Standard precautions apply to all patients without re-
essential to limit unnecessary antimicrobial use, optimize pa· gard to clinical diagnosis.
tient outcomes, and reduce the problem of antimicrobial resis- Tranamission-based precautions include contact, droplet,
tance (49). Various strategies have been proposed to improve and airborne precautions, each based on the mode of trallJJ-
antimicrobial use and limit the emergence of resistance (42). mission of the infectious agent within the healthcare setting.
These include the use of protocols or guidelines, formulary re- Acknowledging that multidrug-resi.stant HAl pathogens, pal'-
striction of key druga, infectious diaease consultation, comput- ticularly MRSA or VRE, are spread primarily by direct (and in-
erized physician order entry, and increased use of diagnostics direct) contact with HCWs, the guideline specifies that patients
to confinn the presence of an infection (Table 25.4). known to be colonized or infected by resistant bacteria are to
60
8
c
50
; 40
D S. Aureus (Methicillin)
1c
-
CD
~
CD
30
20
D Enterococcus (Vancomycin)
• K. Pneumoniae (Ceph 3rd)

a. 10
0 • P. Aeruginosa (Fiuoroquinolones)
1989 1993 1997 2002 2004
Year
Figure 25.7. M~or antimicrobial-resutant pathogens associated with nosocomial infections

in ICUs in 1989, 1993, 1997, 2002 and 2004. (Adapted from National Nosocomial Infectiom
Surveillance. (NNIS) System Report, data summary from january 1992 through june. 2004, issued
October 2004 and adapted from Richards M, Thursky K, Buuing K.. Epidemiology, prevalence, and
sites of infections in intensive care units. Semin R.espir Grit Care Med. 2003;24:~22.)
or the environment is anticipated. Gloves and gowns should

TABLE 25.4 Antimicrobial Usage be removed and hands treated with a medicated hand hygiene
Strategies for Reducing the product while still in the isolation room. Noncritical patient-
Emergence of Antimicrobial care items should be dedicated; if reused, they must be disin-
Resistance in the Intensive fected between patients.
Care Unit Unfortunately, the existent paradigm for preventing the
spread of resistant organisms in the hospital-waiting until
colonization or infection by MRSA, VRE, or some other resis-
Strength of
Recommendation Recommendation° tant organism is serendipitously identified by the clinical labo-
ratory, following which the patient is placed in isolation, usually
Limit unnecessary antibiotic in a single room, requiring the use of gloves, with or without a
administration II gown, for all contacts with the patient-is failing dismally, view-
Develop hospital-based guidelines for ing the inexorable growth in antimicrobial resistance (52).
antibiotic use A recent guideline from the Society for Healthcare Epidemi-
Create an antibiotic use- II
ology of America (53) recommends that surveillance cultures/
quality-improvement team
Provide professional education and II
testing to detect silent VRE or MRSA carriage be performed in
detailing on antibiotic use for II roommates ofVRE- or MRSA-colonized or infected patients and
physicians other high-risk patients at the discretion of infection control
Restrict hospital formulary I staff; patients found to be colonized must also be placed in con-
Use quantitative cultures for nosocomial tact isolation (53). ff these measures fuil to contain the spread,
pneumonia efforts should be intensified in the highest risk areas, such as
Optimize antimicrobial effectiveness the ICU. Cohorting ofstaff and screening of staff for carriage,
Avoid inadequate treatment by using II if epidemiologic data point to a link, is recommended. Veri-
automated guidelines
fication that environmental cleaning/ disinfection procedures
Use combination antimicrobial II
are effective by environmental surveillance cultures before and
treatment II
Consult with infectious dUeases staff II after cleaning areas containing VRE- or MRSA-colonized or in-
Cycling antibiotics fected patients also is recommended.
Automatic stop orders for surgical I We believe that a simpler strategy for preventing the spread
prophylaxis of all types of multidrug-resistant bacteria is the preemptive
Avoid routine selective digestive I use of barrier isolation precautions (gowns and gloves) and
decontamination II dedicated patient-care items (e.g., stethoscopes and sphyg-
Computer-assisted provider order entry momanometers) for all high-risk patients from the time of
admission to prevent HCWs from acquiring hand contamina-
"Level I, supported by randomized controlled trials; Level II,
tion by multidrug-resistant organisms (MDROs) when they
supported by nonrandomized trials and observational studies.
Adapted from Kolle£ MH, Fraser~. Antibiotic resistance in the have contact with patients with unrecognized colonization or
intensive care unit. Ann Intern Med. 2001;134:298-314. infection and block transmission to other as yet uncolonized
patients. Numerous studies have shown that the preemptive
use of barrier precautions, can effectively prevent the spread
ofMDROs, such as MRSA or VRE, in an epidemic setting (54),
be placed in contact isolation, which requires a private room and other studies have shown the effectiveness of preemptive
for the patient (or cohorting the patient in a semiprivate room isolation in high-risk populations, such as patients in an
with another patient who is also colonized or infected by the ICU, for prevention of endemic HAis, including by MDROs
same organism). HCWs are expected to wear gloves on entry (55-58). Three prospective randomized trials have been con-
to the room and gowns if substantial contact with the patient ducted to assess the efficacy of preemptive barrier precautions
Chapter 25 • The lntensiv~ Care Unit: Part B 381
(55,56,59); two showed benefit with a reduction in all HAis in obtaining blood cultures from two separate sites, at least one
ICU patients (relative risk reduction, 52% to 81 %) (55,56). of which is drawn from a peripheral vein by percutaneous veni-
puncture. In adults, if at least 30 mL of blood is cultured, 99%
of detectable bacteremias should be identified (67-69). Similar
SPECIFIC INFECTIONS operating characteristics are achieved in the pediatric popula-
tion using a weight-based graduated volume approach to blood
Intm'PIISCuUJr DePice-Relatetl Blootlstream Infections
cultures (70) . Standard blood cultures drawn through eves
The use of intravascular devices (IVDs) has become an essen- provide excellent sensitivity for diagnosis of BSI, but are less
tial component of delivering care to many patients, particularly specific than cultures obtained from a peripheral vein (71,72).
those with cancer. Unfortunately, vascular access is associated If the patient has a long-term multilumen catheter, a specimen
with substantial and generally underappreciated potential for should be obtained from each lumen of the catheter because
producing iatrogenic disease, particularly BSis originating studies have found a high rate of discordance (approximately
from infection of the percutaneous device used for vascular ac- 30%) between cultures obtained from different lumens of the
cess. Nearly 4Q% of all healthcare-associated BSis derive from same catheter (73).
vascular access in some form (60), and can be associated with Short-term IVDs should be removed from the outset in
excess mortality approaching 35% (61), increased length of unstable patients with suspected IVDR-BSI (as follows); how-
hospitalization, and excess healthcare costs (62,63). ever, it often is undesirable or difficult to do this in patients
Individual types of IVDs pose different risks of infection. In with surgically implanted IVDs, such as Hickman and Broviac
a recent systematic review of 200 prospective studies, we showed catheters. Only 15% to 45% of long-term IVDs that are re-
that point incidence rates of IVD-related BSI (IVDR-BSI) moved for suspected infection are truly colonized or infected
were lowest with peripheral intravenous (0.1 %, 0.5 per 1,000 at the time of removal (74-76). To avoid unnecessary removal
IVD-days) or midline catheters (0.4%, 0.2 per 1,000 catheter- of IVDs, methods have been developed to identify infection
days). Far higher rates were seen with short-term noncuffed and while allowing the device to stay in place: (a) paired quanti-
nonmedicated central venous catheters (CVCs) (4.4%, 2.7 per tative blood cultures drawn from the IVD and percutaneously
1,000 catheter-days). Arterial catheters used for hemodynamic from a peripheral vein (77), (b) differential time to positivity
monitoring (0.8%, 1.7 per 1,000 catheter-days) and peripherally (DTP) of paired standard blood cultures, one drawn from the
inserted central catheters (PICCs) used in hospitalized patients IVD and the second from a peripheral vein ( 78), and (c) Gram
(2.4%, 2.1 per 1,000 catheter-days) posed risks approaching stain (79) or acridine orange staining of blood samples drawn
those seen with short-term conventional eves used in the ICU. through the IVD (80,81).
Surgically implanted long-term eves-cuffed and tunneled Quantitative blood cultures are labor-intensive and cost al-
catheters (22.5%, 1.6 per 1,000 IVD-days) and central venous most twice as much as standard blood cultures. The DTP of
ports (3.6%, 0.1 per 1,000 IVD-days)-appear to have high paired blood cultures, one drawn through the IVD and the
rates of infection when risk is expressed as BSis per 100 IVDs, second concomitantly from a peripheral vein, has been shown
but actually pose much lower risk when rates are expressed per to reliably identify IVDR-BSI of both short-term and long-term
1,000 IVD-days (64). IVDs if the blood culture drawn from the IVD turns positive
Figure 25.3 sununarizes the microbial profile ofiVD-related >2 hours before the culture drawn peripherally (78).
BSis (IVDR-BSis) (4). As might be expected from knowledge If a short-term vascular catheter is suspected of being in-
of the pathogenesis of these infections, skin microorganisms fected because the patient has no obvious other source of infec-
account for the largest proportion of IVDR-BSis. tion to explain the fever, there is inflammation at the insertion
Recent evidence-based guidelines provide the best current site, or cryptogenic staphylococcal BSI or candidemia has been
information on the evaluation of the ICU patient with fever or documented, blood cultures should be obtained and the cath-
other signs of sepsis (65). Before any decision regarding initia- eter should be removed and cultured. Failure to remove an
tion of antimicrobial therapy or removal of an IVD is taken, the infected catheter puts the patient at risk of developing septic
patient must be thoroughly examined to identify all plausible thrombophlebitis with peripheral IV catheters, septic throm-
sites of infection, including VAP, CA-UTI, SSI, antibiotic- bosis of a great central vein with eves (82), or even endocar-
associated colitis, or line sepsis. ditis. Continued access, if necessary, can be established with
Despite the challenge of identifying the source of a patient's a new catheter inserted in a new site. Although small studies
signs of sepsis (65), several clinical, epidemiologic, and micro- have found some utility of guidewire exchange in the manage-
biologic findings point strongly toward an IVD as the source of ment ofevCs suspected of being infected (83--86), we believe
a septic episode. Patients with abrupt onset of signs and symp- that, in the absence of randomized studies demonstrating its
toms of sepsis without any other identifiable source should safety, guidewire exchange generally should not be performed
prompt suspicion of infection of an IVD. The presence of in- if there is suspicion of IVDR-BSI, especially if there are signs of
flammation or purulence at the catheter insertion site is now local infection such as purulence or erythema at the insertion
uncommon in patients with IVDR-BSI (66). However, if puru- site or signs of systemic sepsis without a source. In these in-
lence is seen in combination with signs and symptoms of sep- stances, the old catheter should be removed and cultured and
sis, it is highly likely that the patient has IVDR-BSI and should a new catheter should be inserted in a new site.
prompt removal of the IVD. Finally, the recovery of certain mi-
croorganisms in multiple blood cultures (e.g., staphylococci,
Prnention ofIVDR.-BSI
Corynebacterium or Bacillus spp., or Candida or Malassezia spp.)
strongly suggests infection of the IVD. An updated guideline for the prevention ofiVDR-BSis was pub-
It is indefensible to start anti-infective drugs for suspected lished in 2011 by the CDC's Healthcare Infection Control Prac-
or presumed infection in the critically ill patient without first tices Advisory Conunittee (HICPAC) (Table 25.5) (87).
TABLE 25.5 Summary of CDC/HICPAC Guideline for Prevention of Intravascular Device-Related

Bloodstream Infection
Strength of
Recommendation•
GENERAL MEASURES
Educate all healthcare workers involved in intravascular device (IVD) care and maintenance. IA
Ensure adequate nursing stafflevels in intensive care uniu (ICUs). IB
SURVEILLANCE
Monitor institutionallVD infection rates of IVD-related bloodstream infection (BSI). IA
Express rates ofevC-related BSis per 1,000 evC-days. IB
AT CATHETER INSERTION
Aseptic technique:
Hand hygiene before insertion or manipulation of any lVD IA
Clean or sterile gloves during insertion and manipulation of noncentrallVDs IC
Maximal barrier precautions during insertion of central venous catheters (evCs): mask, cap, sterile gown, IA
gloves, and drapes
Dedicated lVD team strongly recommended IA
Chlorhexidine first choice for cutaneous antisepsis IA
Subclavian vein rather than internal jugular vein catheter insertion IA
Use of sutureless securement device NR
Sterile gauze or a semipermeable polyurethane dressing to cover site IA
No systemic or topical antibiotics at insertion IA
MAINTENANCE
Remove lVD as soon as no longer required. IA
Monitor lVD !ite daily. IB
Change dressing of eve insertion site at least weekly. II
Do not use topical antibiotic ointments. IA
Change needleless IV systems at least as frequently as the administration set; replace caps no more frequently II
than every 3 days or per manufacturers' recommendations.
Complete lipid infusions within 12 hours. IB
Replace admin~tration seu no more frequently than every 72 hours. When lipid~ontaining admixtures or blood IA
producu are given, seu should be replaced every 24 hours; with propofol every 6--12 hours.
Replace peripheral IVs every 72-96 hours IB
Do not routinely replace eves or PICCs solely because of fever unless lVD infection ~ suspected, but replace IB
catheter if there ~ purulence at the exit site, especially if the patient ~ hemodynamically unstable and
IVD-related BSI ~ suspected.
TECHNOLOGY
Use antimicrobial~ated or antiseptic-impregnated eve in adult patienu if institutional rate of BSI ~ high IB
despite cons~tent application of preventive measures and catheter likely to remain in place for >5 days.
Use chlorhexidine-impregnated sponge dressing for patienu with uncuffed eves or other catheters likely to IB
remain in place for >5 days.
Use prophylactic antibiotic lock solution only in patients with long-term IVDs who have continued to experience II
IVD-related BSis despite con!istent application of infection control practices.
"''CDC/HICPAC system of weighting recommendations based on scientific evidence.

lA: strongly supported for implementation and strongly supported by well-de!igned experimental, clinical, or epidemiologic studies.
IB: strongly recommended for implementation and supported by certain clinical or epidemiologic studies and by strong theoretical rationale.
IC: required for implementation as mandated by federal or state regulation or standard.
ll: suggested for implementation and supported by suggestive clinical or epidemiologic studies or by strong theoretical rationale.
NR: no recommendation for or against at this time; unresolved issue involves practices for which insufficient evidence or no consensus emts
about efficacy.
BSI, bloodstream infection; eve, central venous catheter; IVD, intravascular device; PICC, peripherally inserted central catheters.
Adapted from O'Grady NP, Alexander M, Bums IA, et al. Guidelines for the prevention of intravascular catheter-related infections. Clin Infect
Dis. 2011;52:el62-i:l9!l.
Ventil11tor-Associstetl Pneumoni11 with prolonged h011pitalization (91-93), increased healthcare

costs (94), and a 15% to 45% attributable mortality (95-97).
Mechanical ventilation is an essential feature of modem ICU Understanding the pathogenesis of VAP is essential to de-
care. Unfortunately, mechanical ventilation is associated with a vising strategies for prevention of these infections (98). Ad-
substantial risk ofVAP, the most common HAl in the ICU with vances in our understanding of pathogenesis have led to the
an incidence ranging from 9% to 40% (88-90); it is associated
CMfMr 25 • T1w lntmsive Om Un#: Pan B 383
development of specific measures that can greatly reduce the tract (ll2-ll4), (b) direct extension of a contiguous infec-
risk. ofVAP (99-102). tion, such as a pleural space infection, (c) inhalation of con-
In the mechanically ventilated patient, a number of factors taminated air or medical aerosols, and (d) hematogenous
corupire to compromise host defenses: critical illness, comor- carriage of microorganisms to the lung from remote sites of
bidities (103), and malnutrition impair the immune system local infection, such as CVCBSI.
(104), and, most important, endotracheal intubation thwarts Outbreaks of VAP due to contamination of respiratory
the cough renex. (105), compromises mucocili.ary clearance therapy equipment (ll5-123) and diagnostic equipment, such
(106), injure& the tracheal epithelial surface (107), and pro- as bronchoscopes and endoscopes, have been well described
vides a direct conduit for rapid access of bacteria from above (124-130). For example, Thkigawa et al. reported 16 episodes
into the lower respiratory tract (108,109). It probably would of hospital-acquired pneumonia due to Ilt¥dtholderia cepaciiJ
be more accurate pathogenetically to rename VAP as "endotra· caused by contamination of inhaled medication nebulizer res-
cheat intubation-related pneumonia." Invasive devices and pro- ervoirs (123). Likewise, Srinivasan et al. reported 28 episodes
cedures and antimicrobial therapy create a favorable milieu for of pneumonia cawed by P. aeruginosa linked epidemiologically
antimicrobial-resistant HAl pathogens to colonize the aerodi- to contaminated bronchoscopes with defective biopsy port caps
gestive tract ( 110). This combination ofimpaired host defenses (130). This outbreak occurred despite the adherence to disin-
and continuous exposure of the lower respiratory tract to large fection and sterilization guidelines (131).
numbers of potential pathogens through the endotracheal Since the first reports of large outbreaks of severe acute re-
tube (Figure 25.8) (ll1) puts the mechanically ventilated pa- spiratory syndrome (SARS) in 2003 in which >8,000 persons in
tient at greatjeopardy of developing VAP. China, Hong Kong, Singapore, Vietnam, Taiwan, and Canada
For microorganisms to cause VAP, they must first gain ac- ultimately became infected and 9.6% died (132), major ad-
cess to the normally sterile lower respiratory tract where they vances have been made in our understanding of the epidemiol-
can adhere to the mucosa and produce sustained infection. ogy and mode of transmission of this new human Coronavirus
Microorganisms gain access by one of four mechanisms: (133). SARS spreads almost exclusively through respiratory
(a) aspiration of microbe-laden secretions, either from the droplets from person to person, rarely by the airbome or con-
oropharynx directly or, secondarily, by reflux from the stom- tact route. The risk. of SARS acquisition is far higher in the
ach into the oropharynx and then into the lower respiratory hospital than in the community, and nearly one-half of the
Fipre 25.8. Route& of coloDizatiOD/iDfection in mechanically ventilated patients. Colonization of the

aerodigestive tract may occur endogenously (A,B) or e.:ogenou.sly (C-F). E.:ogenou.s colonization may result
in primary colonization of the oropharynx or may be the result of direct inoculation into the lower respira-
tory tract during manipulations of respiratory equipment (D), during using of respiratory devices (E), or
from contaminated aerosols (E). (Adapted from Cmich CJ, Safdar N, Maki DG. The role of the intensive
care unit environment in the pathogenesis and prevention of ventilator.associated pneumonia.Ile5frir Con\
2005;50:815-8!16,discussion ~!J8.)
early episodes involved HCWs or hospitalized patients infected found that upon admission to the ICU, patients were colonized
secondarily upon admission (134). Although SARS has been mainly with S. aum.LS, Haemophilus injluenzae, or Streptococcus
contained for now, if it returns, it will comprise an ongoing pneumonia& However, follow-up cultures showed replacement
threat to patients and HCWs as a cause ofhealthcare-associated of the normal oropharyngeal flora by enteric gram-negative ba-
pneumonia. Outbreaks of other respiratory pathogens, such as cilli and P. aeruginosa. Oropharyngeal colonization was a pow-
Legionella spp., influenza A, or respiratory syncytial virus, are erful independent predictor of subsequent tracheobronchial
well described in healthcare settings (64-70). colonization ([odds ratio] OR: 23.9, 95% [confidence interval]
In the mid-1980s, tuberculosis (TB) rates in the United CI: 3.8--153.3) (113).
States rose after half a century of decline, and large healthcare- Aspiration of oropharyngeal contents containing a large
associated outbreaks with multidrug-resistant strains occurred. bacterial inoculum overwhelms host defenses already compro-
In one such outbreak investigated by the CDC, six episodes of mised by critical illness and the presence of an endotracheal
TB occurred following exposure to a source-patient who had tube, thus leading to the development ofVAP.
spent several weeks in the hospital before being placed in respi- Understanding this sequence of pathophysiologic events, it
ratory isolation (135). Transmission of Mycobacterium tuberculosis would seem logical that reducing concentrations of oral micro-
through contaminated bronchoscopes and respiratory equip- organisms should have a beneficial effect on VAP prevention.
ment also has been reported (136,137). Five studies have evaluated the use of scheduled oral care with
Although reported pseudo-outbreaks with nontuberculous a chlorhexidine antiseptic solution for the prevention of VAP
mycobacteria far outnurn ber the epidemics of true disease, HAl (148--152); chlorhexidine oral care reduced the incidence of
outbreaks caused by these ubiquitous environmental organisms oral microbial colonization and VAP. The use of chlorhexidine
are well described, most often in association with contaminated for oral antisepsis warrants further study and consideration for
hospital water (138--140). application in clinical practice.
For most endemic VAPs, the most important mechanism The stomach has been posited to be an important reservoir
of infection is aspiration of oropharyngeal organisms into the of organisms that cause VAP (153). In healthy persons, few bac-
distal bronchi followed by bacterial proliferation and parenchy- teria entering the stomach survive in the presence of gastric
mal invasion. Inflammation of the bronchiole wall involves the acid. Conditions that reduce the gastric pH (e.g., achlorhydria,
alveolar septi and airspaces leading to bronchopneumonia. H2 antagonists, and enteral nutrition) predispose to bacterial
Pathogens causing VAP may be part of the host's endog- proliferation in the stomach (154-157). Several studies have
enous flora at the time of hospitalization or may be acquired shown a powerful relationship between a high gastric pH and
exogenously after admission to the healthcare facility from the massive overgrowth of gastric bacteria (154-157) . Gastric mi-
hands, apparel, and equipment ofHCWs, the hospital environ- croorganisms reflux up the esophagus abetted by recumbent
ment, and the use of invasive devices. position and the ever-present naso- or orogastric tube and are
Although most VAP epidemics have stemmed from direct aspirated into the trachea. Direct and indirect evidence exist
infection of the lower airway by exogenous organisms, such as to implicate the stomach as a potential reservoir of bacteria
Gram-negative bacilli, Legionella spp., or Aspergillus spp., epi- causing VAP (158-160). Numerous studies have shown that
demics can be more insidious with colonization of the upper gastric contents can be aspirated into the lower airways despite
airway and episodes ofVAP occurring days or weeks later. the presence of an endotracheal cuff (161,162). However, re-
The normal flora of the oropharynx in the nonintubated cent literature suggests that the stomach, although a reservoir
patient without critical illness is composed predominantly of for enteric gram-negative bacteria, is not the primary site for
viridans streptococci, Haemophilus spp., and anaerobes. Salivary colonization of pathogens and that the gastropulmonary route
flow and content (immunoglobulin, fibronectin) are the m,Yor is not a major pathogenic route for the development of VAP
factors maintaining the normal flora of the mouth (and den- (144,163). In a prospective, randomized, double-blind study in
tal plaque). Aerobic gram-negative bacilli are rarely recovered ICU patients, Bonten et al. compared antacids and sucralfate
from the oral secretions of healthy patients (141,142). During and measured intragastric acidity. Colonization by Enterobac-
critical illness, especially in ICU patients, the oral flora shifts teriaceae occurred in the stomach, trachea, and oropharynx;
dramatically to colonization by aerobic Gram-negative bacilli however, intragastric acidity did not influence the incidence of
and S. aum.LS (143). Bacterial adherence to the orotracheal VAP (164). In another analysis of the same study, the same in-
mucosa of the mechanically ventilated patient is facilitated by vestigators showed that oropharyngeal colonization by Entero-
reduced mucosal IgA and increased protease production, ex- bacteriaceae was an important independent risk factor for VAP;
posed and denuded mucous membranes, elevated airway pH, in contrast, gastric colonization by Enterobacteriaceae was not
increased numbers of airway receptors for bacteria due to acute found to increase the risk ofVAP (165).
illness, and antimicrobial use. The diagnostic criteria and tests for VAP include clinical cri-
A large number of studies show that colonization of the oro- teria, qualitative or quantitative endobronchial cultures, bron-
pharynx by aerobic gram-negative and gram-positive pathogens, choalveolar lavage (BAL) or culture of protected specimen
such as S. aum.LS, is a near-universal occurrence in critically ill brush samples obtained by bronchoscopic techniques, and
patients receiving mechanical ventilation (112-114,144-147). specimens, including bronchial washings, mini-BAL, or pro-
In a study of 80 ventilated patients, de Latorre et al. found that tected specimen brush samples, obtained by blind nonbron-
in 19 patients with secondary tracheal colonization, 46% of choscopic procedures. A negative Gram stain of a respiratory
the microorganisms isolated in the trachea already had been specimen in a patient with low likelihood ofVAP has excellent
isolated in the pharynx (112). George et al. reported similar negative predictive value for VAP; a positive Gram stain how-
findings with 42% of the pathogens isolated in 26 patients with ever lacks specificity (166) . Clinical criteria (e.g., fever, leu-
VAP previously recovered from the oropharynx (114). In a kocytosis, purulent secretions, new or changing radiographic
more recent study performed in 48 trauma patients, Ewig et al. infiltrate} have high sensitivity but relatively low specificity.
Clinical criteria are useful for the initial screening for VAP a lower respiratory sample. The silver-coated tube was associ-
and for selecting patients for invasive procedures that have ated with a 35.9% relative reduction in the incidence of VAP
semitivities and specificities in the range of 80% (167). The (4.8% vs. 7.5%, p = .03) (185) . Subsequent studies by the
optimal methods for defining VAP in clinical practice and the same investigators have found the silver-coated tube to be cost-
impact of different diagnostic techniques on patient outcome saving (186) and associated with a reduction in mortality (187).
are the subject of much debate (168). The NHSN surveillance However, few healthcare institutions have widely adopted the
definition ofVAP has been recently modified and is now called silver-coated endotracheal tube, primarily because of cost issues
ventilator-associated events (VAE), a subset of which may be coupled with a modest reduction in VAP.
VAP. This is an effort to reduce interobserver variability, im- Measures aimed at improving host and lung defenses against
prove objectivity, and increase accuracy when comparing VAP aspirated pathogens are not yet ready for implementation.
across institutiom (169-171).
NHSN data show that, based on clinical diagnosis, the most
CWSTRIDIUM DIFFICILE INFECTION
common pathogens isolated from pneumonia in patients in
ICUs areS. auJmS, P. aerugi1WSa, Enterobacterspp., and Klebsiella C. difficileis the m~or infectious cause ofhealthcare-associated
pn.eumoniae, with varying prevalences depending on the type diarrhea, and is associated with prolonged hospitalization and
of ICU (11) (Figure 25.6). Early-onset VAP, which manifests increased hospital costs (188). The incidence of infection with
within the first 4 days of hospitalization, is more often caused this organism is increasing in hospitals worldwide because
by community-acquired pathogens, such as S. pn.eumoniae and of the widespread use of broad-spectrum antibiotics, with re-
Haemophilus spp. When invasive techniques are used to diag- ported rates ranging from 1 to 10 episodes per 1,000 discharges
nose VAP, the frequency of recovery of enteric gram-negative and 17 to 60 episodes per 100,000 bed-days (189) .
bacilli decreases from 50% to 70% of isolates to 35% to 45%. C. difficile infection (CDI) encompasses a spectrum of con-
VAP is polymicrobial in as many as 20% to 40% of patients. A ditions ranging from asymptomatic colonization to fulminant
number of recent studies have shown that anaerobes do not disease with toxic megacolon (190). The usual presentation
play a m~or role in VAP (172). is acute watery diarrhea with lower abdominal pain and fe-
ver occurring during or shortly after beginning antimicro-
bial therapy. The antibiotics that most predispose to CDI are
CONTROL MEASURES
third- or fourth-generation cephalosporins, fluoroquinolones,
A number of nonpharmacologic and pharmacologic preven- clindamycin, or penicillins (191); however, virtually any antimi-
tive measures have been recommended for clinical use in ICUs crobial may trigger CDI.
(Table 25.6) (173). The use ofnonabsorbable oral antibiotics to The diagnosis of CDI can be reliably made by polymerase
eradicate or reduce gastrointestinal carriage of pathogenic bacte- chain reaction (PCR) with detection of the toxigenic genes in
ria, a process widely termed selective digestive decontamination a stool sample. Tiris test provides rapid results and is >95% sen-
(SDD), has been extensively studied (174,175). A short course of sitive and specific for diagnosis of em (192). Alternative tests
parenteral antimicrobials and a longer duration of topical antimi- include detection of C. difftcile toxins A and/or B by enzyme-
crobials have been used in most studies evaluating the efficacy of linked immunoassay (EUSA) in a stool sample (192). If this
SDD for the prevention ofVAP. More than 40 randomized con- test is negative and CDI is strongly suspected, cytotoxin testing,
trolled trials (176,177) and 8 meta-analyses (178-182) have been or PCR, widely regarded as the reference standards, should be
undertaken to determine the efficacy of SDD for reducing the performed. The cytotoxin test, while 94% to 100% sensitive and
incidence ofVAP; most, but not all, have found a beneficial effect 99% specific, takes at least 48 to 72 hours before results are avail-
on VAP, but an inconsistent effect on ICU mortality. Regardless able. In severely ill patients, flexible sigmoidoscopy provides
of efficacy, a very real concern relates to the potential for anti- a rapid means of diagnosis because 90% of episodes of pseu-
microbial resistance with long-term use of SDD (183,184). Re- domembranous colitis involve the left side of the colon; the
cent studies have justified this concern and further dampened visualization of colonic pseudomembranes is essentially pathog-
the enthusiasm for this approach. Moreover, most of the studies nomonic for CDI. Computerized tomography (Cf) of the abdo-
were not designed to assess the relative effect of the components men, while useful for identifying bowel wall thickness, does not
of SDD (topical and systemic) on the prevention ofVAP. Future differentiate between C. di.fficile and other causes of bowel wall
studies need to more dearly evaluate antimicrobial resistance as a thickening, such as ischemic colitis (194) .
~or end point, including the use of selective media for surveil- C. difftcile has become a m~or HAl pathogen widely preva-
lance cultures to enhance the recovery of healthcare-associated, lent in healthcare facilities, and control ofhealthcare-associated
antibiotic-resistant pathogens. transmission is essential. A growing body of literature suggests
The use of sucralfate rather than H2 blockers for stress ulcer that the inanimate environment may contribute to the trans-
prophylaxis, with a goal of maintaining gastric pH and thereby mission of C. di.fficile. Commonly used hospital disinfectants are
suppressing gastric colonization by potential VAP pathogens, not germicidal against C. difftcile spores, which may persist for
initially appeared to be a promising preventive strategy but was prolonged periods on surfaces. A recent before-after study us-
not effective in a large, multicenter, randomized trial (141). ing sodium hypochlorite solution to disinfect a bone marrow
Preventive measures aimed at reducing the risk of aspiration, transplant ward found that the rates of CDI decreased from
particularly by semirecumbent positioning of patients, have 8.3 per 1,000 patient-days to 3.4 per 1,000 patient-days; when
been among the more successful and less costly strategies. In hypochlorite disinfection was discontinued, the rates returned
a recent multisite, randomized controlled trial, 9,417 patients to baseline levels ( 195) . While the application of chlorine-based
were randomized to either a standard endotracheal tube or disinfectants is the cheapest and considered the simplest of
silver-impregnated endotracheal tube. The primary outcome methods with which to reduce environmental contamination,
was the incidence of VAP based on quantitative culturing of the routine use of high-level disinfectants poses challenges
. ,ftC:!! fJJ·. Measures for Prevention ofVentilator-Associated Pneumonia

Strength of
Recommendation Recommendation"
GENERAL PROPHYLAXIS
Effective infection control measures: staff education, compliance with alcohol-based hand disinfection, and I
isolation to reduce cross-infection with MDR pathogens should be used routinely.
Surveillance of ICU infections to identify and quantify endemic and new MDR pathogens and prepare II
timely data for infection control and to guide appropriate antimicrobial therapy in patients with SWI-
pected HAP or other nosocomial infection are recommended.
INTUBATION AND MECHANICAL VENTILATION

Intubation and ventilation should be avoided, if pmsible, because it increases the risk ofVAP. I
Noninvasive ventilation should be used whenever possible in selected patients with respiratory :tailure. I
Orotracheal intubation and orogastric tubes preferred over nasotracheal intubation and nasogastric tubes to II
prevent nosocomial sinusitis and to reduce the risk ofVAP.
Continuous aspiration of subglottic secretions can reduce the risk of early-<mset VAP and should be used, if I
available.
Endotracheal tube cuff pressure should be maintained at >20 em H 20 to prevent leakage of bacterial II
pathogens around the cuff into the lower respiratory tract.
Contaminated condensate should be carefully emptied from ventilator circuits, and condensate should be II
prevented from entering either the endotracheal tube or inline medication nebulizers.
Passive humidifiers or heat-moisture exchangers decrease ventilator circuit colonization but have not consis- I
tently reduced the incidence ofVAP; thus, they cannot be regarded as a pneumonia-prevention tool.
Reduced duration of intubation and mechanical ventilation may prevent VAP, and can be achieved by proto- II
cols to improve the use of sedation and to accelerate weaning.
Maintaining adequate staffing levels in the ICU can reduce length of stay, improve infection control prac- II
tices, and reduce duration of mechanical ventilation.
ASPIRATION, BODY POSmON, AND ENTERAL FEEDING
Patients should be kept in the semirecumbent position. I
Enteral feeding is preferred over parenteral nutrition. I
MODULATION OF COLONIZATION: ORAL ANTISEPTICS AND ANTIBIOTICS
Selective decontamination of the digestive tract is not recommended for routine use. II
Prior administration of systemic antibiotics has reduced the risk of nmocomial pneumonia in some patient II
groups, but if a history of prior administration is present at the time of onset of infection, there should
be increased suspicion of infection with MDR pathogens.
Prophylactic administration of systemic antibiotics for 24 hours at the time of emergent intubation has been I
demonstrated to prevent ICU-acquired HAP in patients with clmed head injury, but routine use is not
recommended until more data become available.
Routine use of oral chlorhexidine is not recommended until more data become available. I
Use daily interruption or lightening of sedation to avoid constant heavy sedation and try to avoid paralytic II
agents.
STRESS BLEEDING PROPHYLAXIS, TB.ANSEUSION, AND HYPERGLYCEMIA
H needed, stress bleeding prophylaxis with either H2 antagonists or sucralfilte is acceptable.
Transfusion of red blood cells and other allogeneic blood products should follow a restricted transfusion
trigger policy; leukocyte-depleted red blood cell transfusions can help to reduce HAP in selected patient
populations.
Intensive insulin therapy is recommended to maintain glucose levels between 80 and 110 mg/ dL in ICU I
patients.
~~Level I, supported by randomized controlled trials; Level II, supported by nonrandomized trials and observational studies.
MDR, multidrug resistant; VAP, ventilator-associated pneumonia; HAP, hospital-acquired pneumonia.
Adapted from Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.
Am]&spiT Cril Ca.TII Med. 2005;171:388-416, with permission.
such as being corrosive, being inhibited by organic matter, and or chlorine dioxide, is generated to decontaminate a sealed
occasionally presenting an occupational and environmental specific area or room. A major advantage of gaseous decon-
risk. Manual chemical disinfection is also both time- and labor- tamination technologies is that medical equipment that would
consuming. In recent years, a number of novel technologies otherwise be difficult to disinfect can be fully decontaminated
have become available for environmental disinfection for CD I. and the inherent variability associated with manual disinfection
Gaseous decontamination is the process whereby a gas or va- reduced. However, a manual clean may still be necessary espe-
por form of a chemical disinfectant, such as hydrogen peroxide cially when heavy contamination is present (196).
Hydrogen peroxide is an oxidizing agent that produces highly patient. Hand hygiene with an antiseptic agent or soap and wa-
reactive hydroxyl radicals that attack DNA, membrane lipids, and ter is essential. It is important to note that alcohol-based hand
other elll!ential cell components. It is genernlly regarded as less rubs do not have activity against the spore form of C. difficile.
toxic than many other gaseous decontaminants, since it breaks Equipment such as stethoscopes and sphygmomanometers
down to water and oxygen. Boyce et al. undertook a prospective should be dedicated to the patient, and consideration should
before-after study with a hydrogen peroxide vapor (HPV) decon- be given to disinfecting the environment with sodium hypo-
tamination system (Bioquell Ltd, Basingstoke, UK) and found a chlorite or an equivalent agent with activity against the spore
significant reduction in CDI across the wards where it was used; form of C. difficile.
however, no concurrent control group was present, which is a
major limitation of the study (197). Other gaseous agents for
CATHETER-ASSOCIATED URINARY
decontamination include chlorine dioxide and ozone; however,
TRACT INFECTION
clinical data for reduction of CDI with these is very limited.
Ultraviolet light (UV) systems have traditionally been ap- Each year, urinary catheters are inserted in > 5 million pa-
plied to reduce the transmission of aerosol-transmitted organ- tients in acute-care hospitals and extended-care facilities (201).
isms such as M. tuberculosis, or to decontaminate surfaces in CA-UTI is the most common HAl in hospitals and nursing
the food industry, and, consequently, modem UV technologies homes, comprising >40% of all institutionally acquired infec-
have been tested on nonsporulating microorganisms that are tions (11). Healthcare-associated bacteriuria or candiduria
less resistant to UV such as Escherichia coli and Listeria monocy- develops in up to 25% of patients requiring a urinary catheter
togmes. The use of UV for the disinfection of C. difficile from for ?:!7 days with a daily risk of 5% (201). CA-UTI is the second
surfaces has not been well examined for clinical efficacy against most common cause of healthcare~sociated BSI (202); some
CDI (198,199). The Society for Healthcare Epidemiology of studies have also found increased mortality associated with it
America has published a guideline for the prevention and (203). Although most CA-UTis are asymptomatic (204), rarely
treatment of CDis (Table 25.7) (200). extend hospitalization, and add only $500 to $1,000 to the
Patients with CDI should be placed in private rooms and direct costs of acute-care hospitalization (205), asymptomatic
staff should wear gowns and gloves for all contacts with the infections commonly precipitate unnecessary antimicrobial
Prevention and Control of Clostridium tlifficile Infection (CDI)

Strength of
Recommendation Recommeodation°
SURVEILlANCE AND DIAGNOSIS

Surveillance for CDI should be performed in every institution. B-ill
Appropriate and prompt diagnostic testing should be performed in patients with antibiotic-associated diarrhea. A-II
Diagnostic tests for C. diffo;ile should be performed only on diarrheal (soft or unformed) stool specimens unless B-ill
ileus is suspected.
Testing of stool specimens from asymptomatic patients for C. diffo;ile (including •test of cure• after treatment). B-II
PREVENTION AND CONTROL

hnplement policies to ensure prudent antimicrobial use. A-II
Surveillance of antimicrobial utilization in the facility should be conducted. B-ill
Healthcare providers in the facility should be educated about the epidemiology of C. d~ociated disease B-ill
(CDI).
Patients with CDI and fecal incontinence should be in a private room. If possible, all patients with CDI should be B-ill
in private room.!!.
Meticulous hand hygiene with soap or an antiseptic agent is recommended after contact with patients, their body B-ill
substances, or their potentially contaminated environment.
Healthcare providers should wear gloves for contact with patients with CDI. A-I
Use of disposable, single-use thermometers (rather than shared electronic thermometers) is recommended. A-II
Patient<are item.!!, such as stethoscopes and sphygmomanometers, should be dedicated. If they must be shared, B-ill
they should be disinfected between patients.
Disinfection of the environment of a patient with CDI should be done using sporocidal agents, such as a diluted B-II
sodium hypochlorite solution.
Patients with CDI may be removed from contact isolation when their diarrhea has resolved. B-ill
Category:
A. good evidence to support a recommendation for use.
B, moderate evidence to support a recommendation for use.
Quality of evidence:
I, evidence from ~ 1 properly randomized controlled trial.
II, evidence from ~1 well-designed observational study, multiple time-series, or dramatic results of uncontrolled experiments.
ill, expert opinion, descriptive studies.
Adapted in pan from the 2010 Society for Health care Epidemiology ofAmerica guidelines for the prevention of Clostridium difJicile associated
diarrhea, with permission.
therapy (206). CA-UTis comprise perhaps the largest institu- infectiom caused by gram-positive organisms or yeast!!, which
tional reservoir of healthcare-associated antibiotic-resistant are most likely to be acquired extraluminally from the periure-
pathogem, the most important of which are multidrug-resistant thral flora. These data suggest that microbial adherence to the
Enterobacteriaceae other than E. coli, such as Klebsiella, catheter surface is important in the pathogenesis of many, but
Enterobacter, Proteus, or Citrobacter, P. aeruginosa; enterococci and not all, CA-UTis. Infections in which the biofihn does not play
staphylococci; and Candida spp. (207). a pathogenetic role probably are caused by mass transport of
Excluding rare hematogenously derived pyelonephritis, intraluminal contaminant!! into the bladder by retrograde re-
caused almost exclusively by S. aureus, most microorganisms flux of microbe-laden urine when a catheter or collection sys-
causing endemic CA-UTI derive from the patient's own colonic tem is moved or manipulated.
or perineal flora or from the hands of HCWs during catheter Several catheter-care practices are universally recommended
insertion or manipulation of the collection system (208). Or- to prevent or at least delay the onset of CA-UTI (Table 25.8)
ganisms gain access in one of two ways. Extraluminal contami- (208,212): avoid unnecessary catheterizations, consider a con-
nation may occur early by direct inoculation when the catheter dom or suprapubic catheter, have a trained HCW insert the
is inserted or later by organisms ascending from the perineum catheter aseptically, remove the catheter as soon as no longer
by capillary action in the thin mucous film contiguous to the needed, maintain closed drainage, ensure dependent drain-
external catheter surface. Intraluminal contamination occurs age, minimize manipulations of the system, and separate cath-
by reflux of microorganisms gaining access to the catheter lu- eterized patients.
men from failure to maintain closed drainage or contamina- Technologic innovations to prevent HAis are likely to be
tion of urine in the collection bag. Recent studies suggest that most effective if they are based on a clear understanding of the
CA-UTis most frequently stem from microorganisms gaining pathogenesis and epidemiology of the infection. Novel technol-
access to the bladder extraluminally (209), but both routes are ogies must be designed to block CA-UTI by either the extralu-
important. minal or intraluminal route, or both. Impregnated catheters,
Most infected urinary catheters are covered by a thick bio- which reduce the adherence of microorganisms to the catheter
film containing the infecting microorganisms embedded in a surface, may confer the greatest benefit for preventing CA-UTI.
matrix of host proteins and microbial exoglycocalyx (210). A Two catheters impregnated with anti-infective solutions have
biofilm forms intraluminally, extraluminally, or both ways, usu- been studied in randomized trials, one impregnated with the
ally advancing in a retrograde fashion. The role of biofilms in urinary antiseptic nitrofurazone (213) and the other with a
the pathogenesis ofCA-UTI has not been established. However, new broad-spectrum antimicrobial combination of minocycline
anti-infective-impregnated or silver hydrogel catheters, which and rifampin (214). Both catheters showed a significant reduc-
inhibit the adherence of microorganisms to the catheter sur- tion in bacterial CA-UTis; however, the studies were small, and
face, significantly reduce the risk of CA-UTI (211), particularly the selection of antimicrobial-resistant uropathogens was not
TABLE 25.8 Centers for Disease Control and Prevention Guideline for Prevention of Catheter-
Associated Urinary Tract Infection
Strength of
Recommendation Recommendationa
Educate personnel in correct techniques of catheter insertion and care. I
Periodically reeducate personnel in catheter care. II
Catheterize only when necessary. I
Consider alternative techniques of urinary drainage before using an indwelling urethral catheter. ill
Emphasize hand hygiene. I
Insert catheter using aseptic technique and sterile equipment. I
Use smallest bore catheter suitable. II
Secure catheter properly. I
Maintain closed sterile drainage. I
Replace the collecting system when sterile cla&ed drainage has been violated. ill
Avoid inigation unless needed to prevent or relieve obstruction. II
Refrain from daily meatal care with povidone-iodine or soap and water. II
Obtain urine samples aseptically. I
Maintain unobstructed urine flow. I
Do not change catheters at arbitrary fixed intervals. II
Spatially separate infected and uninfected patients with indwelling catheters. ill
Avoid routine bacteriologic monitoring. ill
HCA-UTI rates remain high, consider antimicrobial/antiseptic catheters. m
OLevel I, supported by randomized controlled trials.
Level II, supported by nonrandomized trials and observational studies.
Level III, expert opinion, descriptive studies.
NR, no recommendation.
Adapted from Gould CV, Umscheid CA, Agarwal RK, et al. Guideline for prevention of catheter-associated urinary tract infections 2009. Infect
Control Hosp Epidemid. 2010;31:319-326, with permission.
Chapter 25 • The Intensive Om Unit: Part B 389
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heartourgery. .AmJOr# ea... 2002;11:567...,570. 183. Bonten ),ijM, Grundmaoo. H. Selective digestive decontamination and antibiotic n:si.
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reduces the incidence of venti.lator..,.oociated pneumouia. AIR J R.Gp;r Grit C.... M.a. cheal tube to reduce the incidence ofventilator......,ciated pneumonia. Infld Control Hasp
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(SHEA:) and the infectinua dioeueo &ociety ofAmeril:a (IDSA). hlfot:l CtmlroiH..p EpidMol. 212. Gould CV, Umocheid CA, Agarwal RK, ct al. Guideline for preo=tion of cathcter-
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201. WarnnJW. The catheter and urimorytractinfection. MMC/inNOithA111. 1991;75:481-493. 21S. Mali DG, Knasinoli V, Halvonon K.T. A proopero..,, rand.onrlzed, inveotigator-blinded
202. Bryan CS, Rqnoldo KL. Hoopitakcquin:d bacteR:JnU: urinory tract infection: cpidellliology trial of a novel uitrofurazoll<>4mpn:gnated urimory catheter. In: Proceedinp and Ab-
and outoome.Jlhol. 1984;132:494-498. ltracll of the Society for Healthcare Epidemiology in America Annual Meeting; April
203. Platt R, Polk BF, Murdock B, et al. R<:duction of mortality aJOOciatcd with nooocomw r.-1, 1998; Orlando, Florida.
urinory tract infection. l.4n<-. 1983;1:89!1-.'197. 214. DarouichellO, SmithJA, HannaH, et al. Efficacy of antimicrobial-impregnated bladder
204. Thmbyah PA, Maki DG. Catheter.....ociatcd urinory tract infection is rarcly oymptomatic: ca.tbctcn in n::ducing cathetcr-ul!lociated bacteriuria: a pro1pcctivc, nwdornized, multi-
a proopecti.., otudy of1,497 cathmriud patienta. Amlnllm Md. 2000;160:67~2. center clinical trial. Urol~Jci. 1999;54:976-981.
205. Tambyah PA, Knasinoli V. Maki DG. The direct roB II of nooocomial catheter...,Bociatcd uri- 215. SaintS, Elmore JG, Sullivan SD, et al. The effu:acy of si]..,. alloy<oated urimory catheten
nary tract infection in the era of managed. care. Infoct Omtro/H..p~ 2002;U27-ll1. in preventing urinary tract infection: a meta.;onalyoio• .A,.JMMt. 1998;105 (5):236-241 .
Thomas J. Sandora and Nalini Singh
The Newborn Nursery and the

Neonatal Intensive Care Unit
The newborn nursery includes healthy, full-tenn infants who microflora are derived from environmental sources. Healthy,
weigh 2:2,000 g at birth in the normal newborn areas as well term infants usually have a short hospital stay (often
as high-risk infant! who weigh <2,000 g at birth and are term <48 hours). Therefore, infections are acquired infrequendyin
infants but have complex medical problems in the neonatal the nonnal newborn nursery (<1% of all admissions) and of-
intensive care unit (NICU). These infants have an increased ten are not manifest until after discharge, making surveillance
risk ofacquiring infection because all components of their host particularly challenging. In contrast, VLBW infants often re-
defense system are deficient compared with those of older chil· main in the NICU for several weeks to months with continued
dren or adults, and the severity of these deficiencies is increased exposure to many devices and invasive procedures, antibiotic·
as ge..tati.oual age decreases (1). The survival of prematurely resistant hospital flora, and antimicrobial agents that further
born infants has improved as a result of more advanced high- influence the composition of their microflora. Thus, meaning-
risk obstetrical care and neonatal supportive care, including ful analysis of HAl rates in the newborn nursery/NICU must
the use of rurlactant replacement for the treatment of hyaline use consistent definitions and risk. stratification to account for
membrane disease, mechanical ventilation including conven· the heterogeneity of its population. The NICU is the focus of
tional and high-frequency ventilation, extracorporeal mem· HAI surveillance and prevention because of the associated in·
brane oxygenation (ECMO) and continuous hemofiltration to crease in morbidity and mortality relative to newborn nurseries.
support cardiopulmonary and renal function, noninvasive ven-
tilation (e.g., continuous positive airway pressure [ CPAP]) and
cardiac intervention techniques, improved IUJ'gical techniques,
and screening and chemoprophylaxis for early-onset group B
DEFINITIONS
streptococcal (GBS) disease. Therefore, increasing numbers of
TIMB OF ONSET
infimts of very low birth weight (VLBW, 1,000 to 1,499 g) and
e:x:ttemely low birth weight (ELBW, <1,000 g) are surviving but Various investigators define early-onset disease as positive cul-
require prolonged length ofNICU stay and are at increased risk tures ofa nonnally sterile body fluid obtained within the first 3,
for healthcare-associated infection (HAI). The 2010 data sum- '1, or 10 days of life. For the study of HAl!, the most appropriate
mary from the National Healthcare Safety Network (NHSN) time interval is 3 days. Infections that appear at <48 hours of
of the Centers for Disease Control and Prevention (CDC) (2) age are considered to be maternally acquired. Approximately
reported that ELBW and VLBW infants have the highest rates 15% of bloodatream infections (BSU) and pneumonias in
of central line-associated bloodstream infections (CLA-BSis) high-ruk nurseries are matemally acquired (9). Outbreaks of
per 1,000 central line-days compared with all other birth- early-onset infections are rarely reported, and have remained
weight categories among infants in level m NICUs; CLA-BSI either unexplained (10) or have been associated with fetal
rates in thiJJ group alJJo are higher than in all other NHSN pe- scalp electrode placement during labor (11), contaminated
diatric critical care unit categories (Thble 26.1). The rates of resuscitation equipment in the delivery room (12,13) or con·
infection caused by bacteria and Candida sp. vary considerably taminated material! used within the fint few hours of life {e.g.,
among NICUs in the United States (3,4) and Canada (5) even hydrocolloid dressings manufactured in large sheets precut by
after adjustment for known risk. factors that could be practice- healthcare workers [HCWs] and used to secure umbilical cath-
related. Identification of practices in the best-performing units eters or endotracheal tubes contaminated with AcinetobGcter
followed by widespread implementation has been a successful baumann") (14).
strategy of the Vermont Oxford Network and other collabora- For the purposes of HAl tracking, positive cultures obtained
tives to reduce infection rates and other complications associ- > 3 days after birth are considered as late-onset disease. Be-
ated with NICU care (6-8). Device-associated infection rates in cause the clinical manifestations of illfection often are delayed
the NICU have decreased over time as they have in other ICU and determining whether an infection was acquired &om the
types, most likely a reflection of the beneficial effect of consis- mother or from transmission within the nursery is difficult,
tent implementation of reconunended practices, measurement NHSN report! all infections except those that are transmitted
of rates, and feedback to the primary caregivers. transplacentally as HAis (9). Differentiation of early- and late-
In the absence of in utero infection, the neonate is fint onset disease is most useful when designing prophylaxis regi-
exposed to microorganisms during passage through the birth mens. It is recommended that bacterial infections, other than
canal. Subsequently, the normal skin and mucous membrane urinary tract infection (UTI), occw:ring within the first month
393
SEVERITY OF ILLNESS SCORING SYSTEMS

TABLE 26.1 Central Line-Associated
Bloodstream Infection Measures of illness severity other than birth weight have been
(CLA-BSI) Rates• in applied to the study of neonatal HAl risk since 1993 when sev-
Pediatric Intensive Care eral scoring systems were first described (22-26). The Score for
Units (ICUs) (2) Neonatal Acute Physiology (SNAP) uses the worst recorded val-
ues of >24 routinely measured physiologic variables during the
Number Pooled Device first 24 hours of stay. The SNAP-Perinatal Extension (SNAP-PE)
ofiCUs Pooled Mean Utilization adds scoring for birth weight, small for gestational age status,
ICUType Reporting CLA-BSI Rate (DU) Ratiob
and low Apgar score (<7 at 5 minutes). Using multiple re-
LEVEL m mcuc gression analysis, a study of coagulase-negative staphylococcal
S750g 320 2.6 0.42 (CONS)-BSis demonstrated a 53.9% increase in a patient's risk
751-1,000 g 244 2.2 0.38 of experiencing at least one nosocomial BSI episode associated
1,001-1,500 g 141 1.3 0.29 with each 5-point increment in the admission day SNAP (23).
1,501-2,500 g 97 1.0 0.19
>2,500g 89 0.8 0.26
These types of scoring systems were developed to predict mor-
Pediatric 30 2.1 0.69 tality and are not typically used to risk-adjust HAl rates in the
cardiothoracic NICU (instead, rates are generally stratified by birth-weight cat-
Pediatric medical 24 1.9 0.45 egory); further validation would be needed before they could
Pediatric 204 1.8 0.48 be applied routinely.
medical/
surgical
DISTINGUISHING TRUE PATHOGENS FROM
"(Number ofCIA-BSI/number of central line-days) X 1,000. BLOOD CULTURE CONTAMINANTS
&oevice utilization (DU) ratio = number of central line-days/
number of patient-days.
Sepsis caused by pathogens that are common skin contami-
'For NICU, central line-days include umbilical line-days. nants (e.g., CONS) can be associated with low colony counts
(27-29) and relatively few symptoms. The analysis of sites
from which the isolates are recovered (e.g., peripheral blood,
specific ports of CVCs) and time to positivity assist the clini-
cian in distinguishing blood culture contaminants from true
after discharge from the nursery be reported to the infant's pathogens or infection. Time to positivity is an indicator of the
nursery to facilitate prompt identification of an outbreak (e.g., quantity of bacteria, and is an easily implemented replacement
skin infections associated with Staphylococcus aumJS or Strept()C()C- for quantitative blood cultures. When there is a >2-hour differ-
cus group A or B, omphalitis, or bacterial diarrhea, especially ence in time to positivity for various sites, the site that turned
Sal1110'1UJlla sp.) (12,15-17). positive first is more likely to be the source of the bacteremia
or fungemia (30-32). The following suggestions can optimize
the clinician's accuracy in distinguishing true sepsis from
DEVICE-RELATED INFECTIONS
contamination:
Standardized smveillance definitions developed and updated
by the CDC are used to track the rates of NICU infections asso- 1. Obtain at least 0.5 to 2 mL of blood for culture from two
separate sites (preferably one peripheral site in patients
ciated with central venous catheters (CVCs), including umbili-
with an intravascular catheter) (27-33).
cal catheters, and ventilator-associated pneumonia (VAP) (18).
2. Isolates detected within 24 to 36 hours of submission are
Studies (19-21) have demonstrated the advantages of calcu-
more likely to be true pathogens. If blood cultures from
lating device-associated HAl rates to control for the duration
an asymptomatic neonate who is being evaluated at
of exposure to the primary risk factors. Device utilization (DU)
birth owing to the presence of maternal risk factors re-
ratios are useful for interhospital comparisons as long as each
main negative at 36 hours, bacterial sepsis can be ruled
hospital has collected the data and the calculated ratios use the
out (32).
same definitions and methods. The DU ratio is the measure of
3. Sepsis is more likely when a clinical course or serial lab-
an ICU's invasive practices that constitutes an extrinsic risk factor
oratory studies compatible with sepsis are documented
for HAl. The DU ratio can also serve as a marker for severity of
(e.g., elevated absolute total neutrophil [ATN] or absolute
illness or the patient's intrinsic susceptibility to infection. Device--
total immature cell [ATI] counts, ratio of absolute total im-
associated infection rates and DU ratios are calculated as follows:
Central line-associated bloodstream infection (CLA-BSI) mature neutrophils to total neutrophils (I:T) >0.2 (34),
and elevated C-reactive protein (35)). The likelihood of
rate:
sepsis is < 1% in the presence of three serial CBC and dif-
Number of CIA-BSis ferential counts that remain normal over 36 hours.
1 000
Number of central line-days X •
4. True sepsis is more likely if the patient responds to an-
Ventilator-associated pneumonia (VAP) rate: timicrobials that are active against the isolate, usually
Number ofVAPs X vancomycin for CONS and MRSA. Clinical improvement
1 000 and/ or failure to recover the same pathogen from repeat
Number ofventilator-days '
blood cultures when an infant is being treated with an
Device utilization (DU) ratio: antimicrobial agent that is not active against the patho-
Number of device-days gen casts doubt on the validity of that isolate as a true
Number of patient-days pathogen.
Chapter 26 • Till Newburn Nursery and the Neonatal lntensiv~ Care Unit 395
RISK FACTORS FOR HAl neutrophils from the marrow neutrophil storage pool into the
peripheral circulation and enhanced chemotaxis of neutro-
The intrinsic and extrinsic factors for HAl have been reviewed phils to the site of bacterial infection (39). Antibody replace-
(36), and are sununarized in Table 26.2. ment could be more effective by using products containing
high titers of antibody against the specific infecting agent, but
such products are not yet available for routine use ( 43). How-
INTRINSIC RISK FACTORS ever, a significant protective effect has not been demonstrated
Birth weight and gestational age are the most important risk in trials of two different preparations of intravenous S. atm~US
factors for HAl development. The decreased function of the im- immune globulin (44,45).
mune S}'5tem in the most premature infants accounts for most Neonates are particularly vulnerable to colonization with
of the increased intrinsic risk of infection (1). There is minimal virulent and/or antimicrobial-resistant bacteria because their
active transport of maternal IgG antibodies across the placenta mucosal surfaces do not have the usual protective microflora
before 32 weeks of gestation, neutrophils have defective che- of older infants and adults ( 46). Immature, fragile skin of the
motaxis or phagocytosis, and the classic and alternative com- VLBW neonate possibly does not serve as an adequate protec-
plement pathwa}'5 have decreased activity. Attempts to improve tive barrier against pathogens that colonize the skin and have
the neonate's immune function have included exchange trans- the capacity to cause invasive disease (33,47).
fusion (37), white blood cell transfusion (38), administration
of intravenous immune globulin (IVIG) therapeutically (39) EXTRINSIC RISK FACTORS
or prophylactically ( 40,41), and administration of recombinant
human granulocyte colony-stimulating factor (G-CSF) (42). Many of the extrinsic HAl risk factors in the NICU are device-
Although these studies have been instructive, they have not or environmentally related, as is observed in adult ICUs. Ex-
demonstrated efficacy in adequately controlled trials, and no trinsic risk factors can be categorized as (a) medical devices
recommendations for routine use of these products have been and equipment, (b) breast milk and formula, (c) medical treat-
made. In addition to providing enhanced opsonophagocytic ments, (d) behavioral interventions, and (e) administrative
activity, IVIG infusions are associated with a prompt release of and structural.
MediuU De11U:es t~-nd EtJ.uipment

TABLE 26.2 Risk Factors for Healthcare- CVCs, including peripherally inserted central catheters (PICC),
Assodated Infections are associated with increased risk of BSI caused by bacteria or
fungi (9,48-52). In fact, an increased risk of candidemia has
in Neonates
been associated with each day of catheter use (52). Various
Intrinsic (host) medical devices used for respiratory support (e.g., ventilators
Decreased function of the immune system and noninvasive ventilatory devices including CPAP, ECMO,
Decreased protection from natural barriers (e.g., !kin) and Vapotherm 2000i™ [Vapotherm Inc., Stevensville, MD] ox-
Developing endogenous microflora
ygen delivery device) are associated with increased risk of infec-
Gestational age
tion (53,54). The need by neonates with respiratory distress for
Severity of illness
Underlying disease proce.s.ses (e.g., congenital organ system increased humidification provides direct exposure of the respi-
abnormalities, chronic lung disease, gastrointestinal tract ratory mucosa to water that could be contaminated; therefore,
pathology) the use of sterile water in such situations is recommended (55).
Extrinsic For example, intrinsic contamination of the Vapotherm™ de-
Use of devices vice with Rolstonia sp. during the manufacturing process that
Fetal scalp electrodes could not be eradicated with various disinfection procedures
Umbilical, arterial, central venous catheters led to clinical infections and the withdrawal of this product
Mechanical ventilators from the market (56).
Extracorporeal membrane oxygenation
Ventriculoperitoneal shunts
Fluids
Total parenteral nutrition, intralipids
Despite the many benefits of breast-feeding, breast milk is a bio-
Transfused blood products
Respiratory care logic product that has the potential to transmit infection. For
Breast milk example, breast milk from a mother who was infected with GBS
Treatments or S. aureus has been implicated as the vehicle of transmission of
Intravenous steroid therapy these pathogens to infants with resulting severe sepsis (57-59).
Use ofH2 blockers/proton pump inhibitors Neonatal sepsis caused by Klebsiella pneumoniae has been associ-
Environment ated with contaminated breast milk resulting from the contami-
Acquisition of hospital flora nation ofa component ofa breast pump (60), and contamination
Overcrowding, understaffing of a milk bank pasteurizer was associated with an NICU out-
Contaminated equipment, fluids break of Pseudomonas ~nosa infections (61). Furthermore,
Traffic from other sections of hospital viral agents that could be transmitted to infants in breast milk
Radiology
or in the blood contact associated with breast-feeding from
Laboratory
dry, cracked nipples include hepatitis B virus (HBV), HIV, and
Subspecialty consultants
human T-lymphotrophic virus type 1 (HTLV-1). Therefore, in
countries where safe formula for bottle-feeding is readily avail- MediMI Tre11tment:s
able, breast-feeding is contraindicated for mothers known to be
infected with HN and H1LV-1. HBV vaccine given to neonates The use of steroids for the treatment of chronic broncho-
is protective against transmission by breast-feeding. Although pulmonary dysplasia has been associated with an increased
cytomegalovirus (CMV) is transmitted in breast milk, maternal risk of infection (67-69). The finding of an increase in the
antibody is protective against clinically significant disease. The incidence of disseminated Candida spp. infections associated
CDC's guidelines developed for banking human milk obtained with the unique practice of single-dose steroid administra-
from unrelated donors include screening all donors for HN, tion in infants with prolonged hypotension shortly after birth
H1LV-l, and HBV surface antigen and pasteurization (62.5°C further supports the role of steroids as an independent risk
for 30 minutes) of all milk specimens. Bacterial counts of 104 factor (68). The risk-benefit ratio must be carefully consid-
colony-forming units (cfu)/mL or more of nonpathogenic ered before initiating a course of steroids in neonates. The
organisms or the presence of gram-negative bacteria (GNB), use of H2 blocker/proton pump inhibitor therapy has been
S. aureus, or a- or ~-hemolytic streptococci preclude the use of associated with an increased incidence of necrotizing entero-
that milk (62). Established guidelines for human breast milk colitis (NEC) (70), with sepsis associated with GNB in VLBW
banks (www.hmbana.org), personal hygiene, and handling and infants (50), and with candidemia (71) . An increased risk of
decontaminating the components of breast milk pumps (62) invasive disease caused by extended-spectrum beta-lactamase
should be followed. (ESBL)-producing Klebsiella spp. (51) or Candida spp. (72)
Every healthcare facility that handles expressed breast has been associated with the use of third-generation cepha-
milk should have a written policy to guide storage and han- losporins. Finally, topical petrolatum applied to the skin for
dling. Expressed breast milk should be labeled as soon as it improved moisturizing effect was associated with an increased
is pumped with at least two identifiers in addition to the date risk of fungal infections (46) .
and time, and a dedicated refrigerator/freezer should be
used for storage. The American Academy of Pediatrics (AAP)
recommends refrigerating milk that will not be used immedi-
ately and freezing milk at O"F or below if it will not be used There are theoretical concerns that infection risk can increase
within 24 hours; previously frozen milk that has been thawed in association with the innovative practices of cobedding (73)
in the refrigerator must be used within 24 hours or discarded and kangaroo care (74) used in the NICU to improve develop-
(http ://www.healthychildren.org/English/ages-stages/babyI mental outcomes as a result of increased opportunity for skin-
breastfeeding/Pages/Storing-and-Preparing-Expressed-Breast- to-skin exposure of multiple-gestation infants to each other and
Milk.aspx). Powdered infant formulas are not sterile and pose to their mothers, respectively. Kangaroo care was an indepen-
a risk of infection with organisms such as Cronobacter sakaznkii dent risk factor for MRSA infection in one study (75). Although
or Salmonella sp. if not handled correctly. The World Health toys in NICU beds have been found to be contaminated with
Organization has established guidelines for safe preparation, pathogenic bacteria (76), their role in transmission ofinfection
storage, and handling of powdered infant formulas (http:// has not been established.
www.who.int/foodsafetyI publications/micro I pif_guidelines.
pdf). The key points include hand hygiene and cleaning and
sterilizing the feeding-preparation equipment before use, dis-
carding unused refrigerated formula after 24 hours, and us- Studies of outbreaks in the newborn nursery and NICUs were
ing room temperature hang times of preferably no >2 hours some of the first to demonstrate the relationship between rates
for continuous or bolus feeds. The CDC recommends a hang of late-onset infection and overcrowding and understaffing
time of not >4 hours for continuous feeds in the NICU (63). (25,77-81). One study that evaluated staffing levels of regis-
The most controversial recommendation made by WHO is tered nurses specifically found a significant reduction in the
to use water >7o•c to reconstitute powdered infant formula. BSI risk when registered nurse staffing hours were increased in
This recommendation is supported by laboratory studies dem- one NICU (81). In a large cohort study of 558 NICUs, VLBW
onstrating that higher water temperatures result in greater infants born in hospitals that received recognition for nurs-
inactivation of C. saka.zakii (64). No clinical data have been ing excellence (RNE) had a significantly lower rate of posi-
published to evaluate the comparative efficacy of different tive blood or cerebrospinal fluid (CSF) cultures >3 days after
preparation methods. Other stakeholders, including the Emu- birth compared with infants born in non-RNE hospitals (82).
pean Society for Pediatric Gastroenterology, Hepatology, and NICUs with all single-patient rooms have several advantages,
Nutrition, have argued that such high temperatures adversely including improving the neurodevelopmental effects of light-
affect the vitamins in the formula and therefore cannot be ing and sound, facilitating family-centered care, breast-feeding,
recommended (65). Some have expressed concern about the kangaroo care, and isolation precautions when needed, and
potential for bums if boiling water is used (66). The AAP rec- potentially reducing HAl rates (83,84). Although data are not
ommendations for formula preparation at home call for room yet sufficient to support an evidence-based recommendation
temperature water to be added to formula immediately before for single-patient rooms in NICUs, the most recent publication
feeding, as long as a safe water source is available (http:// of recommended standards for NICU design and of experience
www.healthychildren.org/English/ ages-stages/babyI feeding- suggests that this design will become more prevalent in the fu-
nutrition/Pages/Sterilizing-and-Warming-Bottles.aspx). This ture. Finally, exposure to construction dust or to spores during
difference from the WHO recommendations likely reflects transport could result in cutaneous or invasive aspergillosis in
both the higher risk for invasive infections from C. sakaznkii the neonate (85); thus, dust containment and air filtration dur-
among preterm infants and the practicality of formula prepa- ing construction, renovation, and any disruption of the integ-
ration for healthy infants in the home. rity of the environment (86) are especially important for the
NICU because the VLBW infant is at increased risk of develop- immaturity of gastrointestinal tract function including circu-
ing disease after exposure. latory regulation, hypoxic/ischemic injury, abnormal bacte-
rial colonization, and early feeding of formula. The role of
specific inflammatory cytokines in the pathogenesis of NEC is
SITES OF INFECTION under investigation. Sporadic episodes and clusters can occur.
Several different bacteria (e.g., Escherichia coli, K. pneumoniae,
The sites of HAis in neonates differ from those in adults (48). Enterobacter cloacae, Clostridium sp.) and viruses (e.g., rotavirus,
Primary BSis account for 30% to 50% of episodes in neonates, coronavirus, enterovirus) have been associated with NEC in
depending on birth weight, and surgical site infections (SSis) some reports of clusters (93). Outbreaks can be controlled by
and UTis are rare. In contrast, the rates of catheter-associated implementing infection control measures, including hand hy-
UTis and SSis are higher in adult patients (87). Cutane- giene, contact precautions, cohorting of infants and staff, and
ous sites are more likely to be involved in neonates. Clinical restriction of HCWs with signs of gastrointestinal tract illness
manifestations of methicillin-susceptible S. aumu (MSSA) and from duty until resolved (93).
methicillin-resistant S. aumu (MRSA) in otherwise healthy, A new NHSN surveillance definition for NEC was intro-
term neonates (88) or in those in the NICU (89) in the cur- duced in 2012 (18). The manifestations include clinical signs
rent era have been reviewed. Pustules, bullous impetigo, sub- such as bilious aspirates, vomiting, abdominal distension, or
cutaneous abscesses, scalded skin syndrome, and toxic shock occult or gross blood in stool; radiographic evidence includes
syndrome associated with either MSSA or MRSA can be seen in findings such as pneumatosis intestinalis, portal venous gas, or
outbreaks in term nurseries (often presenting after discharge) pneumoperitoneum. NEC-associated mortality rates vary from
or NICUs. Omphalitis is rare (0.7%) in developed countries 15% to 30%. When intestinal necrosis occurs, resection is nec-
where deliveries are performed aseptically and cord care to essary, often leaving the infant with short bowel syndrome and
prevent infection is performed routinely. However, the occur- dependence on parenteral nutrition.
rence of omphalitis can involve serious complications includ-
ing sepsis, superficial or deep abscesses, necrotizing fasciitis,
peritonitis, and hepatic vein thrombosis (90). Congenital mu- ETIOWGY, CLINICAL
cocutaneous candidiasis in term infants is generally not associ- MANIFESTATIONS,
ated with invasive disease, whereas fungal dermatitis caused by
Candida albicans is considered a manifestation of systemic dis-
AND EPIDEMIOWGY
ease when it occurs during the second week of life in ELBW in-
TRENDS IN NURSERY AND NICU INFECTIONS
fants after vaginal delivery, postnatal administration of steroids,
or hyperglycemia (91). Gastroenteritis and colitis also can oc- Infections acquired in normal newborn nurseries are most fre-
cur following exposure to viruses and/or bacteria circulating in quently not invasive, usually involve the skin or mucous mem-
the community. Osteomyelitis/septic arthritis and conjunctivi- branes, and result from HCW hand carriage, contaminated
tis are other less common manifestations. Meningitis and brain equipment, and medications. Impetigo, conjunctivitis (94),
abscess also can occur in neonates. omphalitis, and soft tissue abscess are the most frequently
Pulmonary infections result from exposure to respiratory observed clinical manifestations. S. aumu remains the most
viruses circulating in the community, and/or complications of frequently isolated pathogen from such infants, with MRSA
respiratory support in the NICU. VAP, which has always been an causing infection more often than MSSA in communities with
important HAl among adults and older children, is notoriously high prevalence of community-associated MRSA (CA-MRSA)
difficult to diagnose in neonates (particularly preterm infants) infections (88). Outbreaks of group A streptococcal infection
because several components of the traditional surveillance defi- (16,95) and of diarrhea caused by bacterial pathogens (e.g.,
nition, including abnormal gas exchange and radiographic in- Salmonella spp. or Shigella spp.) could occur in both term and
filtrates, can occur in infants with hyaline membrane disease or preterm nurseries (15,96,97) but have been reported less fre-
underlying cardiac or pulmonary disorders that are common in quently in recent years. CONS rarely cause early-onset disease
neonates (33). For this reason, interfacility comparison ofVAP in otherwise healthy, term neonates without any devices in
rates is plagued by ascertainment bias for infants in the NICU. place.
At the time of this writing, the CDC is developing a new sur- HCWs are rarely the source of outbreaks caused by bacteria
veillance definition for ventilator-associated events, which will and fungi, especially MRSA, but when they are, factors are usu-
encompass both pneumonia and noninfectious complications ally present to increase the transmission of infectious agents
and will be based on more objective criteria (http://www.cdc. to others (e.g., sinusitis, draining otitis extema, chronic otitis,
govI nhsn/PDFs/vae/CDC_VAE_CommunicationsSummary- respiratory tract infections, dermatitis, onychomycosis, or ar-
for-compliance_20120313.pdf). Currently, these definitions tificial nails) (98-104). An HCW colonized with an epidemic
apply to patients > 18 years of age. Further research will be nec- strain of S. aumu rarely has been identified; when it has, the
essary to evaluate the performance of any new definition(s) in outbreak has been controlled by removing that individual from
pediatric patients. direct patient care ( 105) . Individuals wearing artificial nails who
NEC is one of the most common gastrointestinal emer- have direct patient contact have been implicated in outbreaks
gencies among neonates. In fact, >90% of episodes occur in of P. aeruginosa (102,103) and ESBL-producing K. pneumoniae
infants who are born preterm, and the NEC risk is inversely (104) in NICUs, where molecular typing demonstrated that
related to birth weight and gestational age. Overall, there is both HCW and patient isolates were indistinguishable. These
about a 7% occurrence among VLBW infants with substantial studies contributed substantially to the recommendation not
variation over time and from center to center (92). Factors that to wear artificial nails or extenders when having direct contact
contribute to the development ofNEC include developmental with high-risk patients.
Unexplained shifts in the predominant etiology of bacterial to include revised algorithms for screening and prophylaxis
infections in high-risk infants have been observed over time of pregnant women as well as management of newboms with
(106,107). Invasive strains of S. aunmwere predominant in the risk factors for early-onset GBS disease (114). Following the
1950s. For unexplained reasons, GNB, especially P. aeruginosa, publication of the GBS chemoprophylaxis guidelines, the rates
Klebsiella spp., and E. coli strains prevailed in the 1960s but of ampicillin-resistant E. roli as a cause of early-onset sepsis in
were replaced by GBS in the 1970s. GBS remained as the ma- VLBW infants have increased, but no association between intra-
jor pathogen of early-onset disease throughout the 1980s and partum antibiotic exposure and overall or ampicillin-resistant
1990s but also manifested as late-onset disease, most frequently E. roli sepsis has been found (113,115). Importantly, intrapar-
meningitis, less commonly as osteomyelitis/septic arthritis, tum chemoprophylaxis has not been shown to reduce the rates
and rarely (108) as horizontal transmission within the NICU. of late-onset GBS disease (116), which likely represents the
However, in the 1980s, MRSA and CONS emerged as prevail- acquisition of the organism postnatally, including potentially
ing HAl pathogens in the NICU. Although CONS continued to from sources within the nursery or NICU (117).
account for 40% to 50% of late-onset infections in most NICUs
in the 1990s, one NICU reported a shift to predominant GNB, Cot~.gultue-Negt~.tipe Smphylococci
especially ceftazidim~resistant Enterobacter spp., as the patho-
gen from 1996 to 2001 (109), and anotherreported an increase CONS account for nearly 50% of late-onset HAis in many re-
in the number of commensals ( 107), similar to the experience ports (3,9,40,41,48,118). Several reasons for the increased rec-
of the National Institute of Child Health and Human Devel- ognition of this organism as a neonatal pathogen follow:
opment Neonatal Research Network (3). In 1999, the Pediat-
1. Increased number and survival ofVLBW infants.
ric Prevention Network conducted a croswectional study to
2. Increased we of intravascular devices in the high-risk
assess the prevalence of HAl in US NICUs; CONS accounted
neonate.
for 31.6% of infections, followed by enterococci (10.3%) and
3. Increased likelihood of identifying a blood culture positive
E. roli (8.5%) ( 48). The following three pathogens associated
for CONS as a true bacteremia with the we of more consis-
with <15% to 20% of NICU infections are particularly prob-
tent definitions and methods of obtaining blood cultures
lematic because of the difficulty in treatment: (a) enterococci,
(e.g., two blood cultures, preferably one from a eve and
especially vancomycin-resistant enterococcw (VRE), (b) mul-
one from a peripheral site).
tidrug-resistant GNB, especially Enterobacter spp. and ESBL-
producing Klebsiella spp., and (c) fungi, predominantly Candida The epidemiology of neonatal CONS-BSI has been studied
spp., especially non-albicans species. extensively using pulsed-field gel electrophoresis (PFGE), ribo-
typing, DNA-DNA hybridization, and restriction endonuclease
analysis in addition to the traditional methods of speciation,
GROUP B STREPTOCOCCUS
phage typing, and plasmid analysis. PFGE is the most reliable
From the late 1970s through the mid-1990s, GBS was the most method for confuming the identity of strains. Distinct clones
frequently isolated pathogen from term infants with early-onset of both Staphylococcus haemolyticus (119,120) and Staphylococcus
disease, accounting for approximately 70% of episodes (3). epidermidis (121-123) can become endemic in NICUs, and
This pathogen was acquired from the mother in the peripar- cause clusters of infections over periods of 6 months to as long
tum period; in approximately 70% of infants <2,000 g at birth, as 10 years. At the same time, many completely unrelated strains
GBS infections were acquired in utero with positive blood cul- can be isolated from infants within the same unit. Some NICUs
tures obtained at birth. However, following the development possibly have no related strains identified during a specific pe-
and implementation of the evidenc~based recommendations riod of time (124,125) . Eastick et al. (126) have reported rela-
published collaboratively by the CDC, the American College tively stable reservoirs of CONS in the feces, around the ear,
of Obstetrics and Gynecology (ACOG), and the AAP for the and in the axillae and nares but small, unstable numbers on the
administration of chemoprophylaxis at the onset of labor to skin of the forearm and leg. Thw, cross-contamination among
colonized women, those delivering prematurely, and those sites on the same infant as well as horizontal spread among in-
who have other risk factors that were published in 1996, there fants is an important mode of transmission. Infusion of paren-
was a 65% reduction in the incidence of early-onset GBS dis- teral fluids contaminated with CONS is a rare source of BSI in
ease from 1993 to 1998 and a plateau in 1999-2001 (110). The the NICU (127).
guidelines were updated in 2002 to include a recommendation The clinical manifestations of CONS-BSI are most often
to screen all pregnant women at 35 to 3 7 weeks gestation based nonspecific, and this pathogen is rarely considered a cawe of
on a population-based study that demonstrated a greater re- death (128). The signs of sepsis observed most frequently are
duction in disease associated with a culture-based strategy com- fever, apnea and bradycardia, feeding intolerance, and lethargy.
pared with a risk-based strategy ( 111). This change resulted in a Temperature instability, thrombocytopenia, abdominal disten-
further reduction in 2003 to 2004 to a rate of0.34 per 1,000 live tion, and persistent BSI in the absence of a eve have been as-
births reported by the CDC's active bacterial core surveillance sociated with disease cawed by CONS (129,130). Specific delta
(ABCs) network and a narrowing of the racial disparity in the toxin-producing strains have been found in pure culture in the
rates of disease (112). These data represented an 80% reduc- stool or in the blood or peritoneal fluid of patients with a mild
tion from a rate in 1,000 live births of 1. 7 in 1993 to 0.34 in 2004. form of NEC (131,132). Focal infections associated with these
A persistent reduction in early-onset GBS disease has also been pathogens include neck abscess, omphalitis, wound abscess,
reported in the VLBW infants in the National Institute of Child and mastitis (133). Right-sided endocarditis caused by CONS
Health and Human Development Neonatal Research Network must be considered in the presence of a eve, persistent BSI
(113) and by other groups who have been tracking the rates (>48 hours), and thrombocytopenia during appropriate anti-
of disease. In 2010, the guidelines were once again updated microbial therapy for BSI (134). Physical examination might
reveal no other abnormalities but an echocardiogram could contributes to the overall burden of pathogens in high-risk
demonstrate vegetations in the right atrium or on the tricuspid units. Unidentified virulence factors and environmental condi-
valve. Removal of the CVC is required for clearance of CONS if tions determine the persistence of the organism in the NICU.
BSI persists for >4 days ( 135) . In Parkland Health and Hospital System's crowded NICU in
Dallas, Texas, MRSA persisted for a 3-year period from 1988 to
1991 (25). Neither susceptible S. aureusnor MRSA nursery out-
Smphylococcus 11ureus
breaks were controlled until conditions of overcrowding and
Mter CONS, S. aureus was the second most frequently isolated understaffing were corrected (25,78). Minimizing the number
pathogen from NICU infants in a 1986 to 1993 report (9) and of nurses caring for both MRSA-colonized and -uncolonized in-
in studies from the Neonatal Research Network (3). In con- fants may be beneficial in reducing MRSA transmission (153).
trast, the point-prevalence study of 29 NICUs performed in The prevalence of CA-MRSA strains that have antibiotic suscep-
1999 reported that S. aumt.S accounted for only 3.4% of BSis tibility and molecular profiles (staphylococcal chromosomal
(48). Since the late 1980s, S. aureus outbreaks in the NICU cassette [SCC] mec types IV or V) distinct from those of the
have been associated with both MSSA (78,105,136-139) and traditional healthcare-associated MRSA strains (149) has in-
MRSA (25,140-144), and reports of outbreaks of MRSA have creased, and transmission of those CA-MRSA strains have been
surpassed those of MSSA in recent years. The incidence of late- reported within healthcare facilities (154-156). A shift from
onset MRSA infections increased >300% between 1995 and healthcare-associated MRSA to CA-MRSA in the NICU now
2004 (145). Nurseries situated in large general hospitals that appears to be occurring (157). Because CA-MRSA infections
share services (laboratory, radiology) and HCWs (nurses, respi- have been described in obstetrical patients (158) and 13 out
ratory therapists, consulting physicians) are especially vulner- of 14 MRSA strains isolated from vaginal-rectal prenatal GBS
able to the acquisition of virulent strains from geographically screening cultures were CA-MRSA by SCCmec typing (159), a
distant foci of healthcar~associated MSSA or MRSA infection. likely source for neonatal infections is the CA-MRSA-colonized
A single or multiple virulent strains can be introduced into the or -infected mother. In one recent prospective cohort study
nursery by a colonized infant, a visiting family member, and, of 471 mother-infant dyads, infants hom to mothers with
rarely, an HCW (146-148). However, the principal mode of staphylococcal colonization were more likely to be colonized,
transmission is horizontal via the hands ofHCWs who fail to fol- and this acquisition occurred primarily in the early postnatal
low recommendations for hand hygiene between patient con- period (160). S. aumt.S isolates from mother-infunt pairs have
tacts. PFGE is the most useful method to determine whether a been shown to be identical by PFGE (161). In one report, two
single or multiple strains caused an outbreak (149); a recent cases of mother-to-infant transmission of MRSA were noted
study demonstrated the improved efficacy of detecting clonal (162). The first case involved an ELBW infant delivered vagi-
strains through the use of whole-genome sequencing, although nally at 27 weeks gestation by a mother with chorioamnionitis.
this technique currently remains primarily a research tool The baby was admitted at 4 weeks of age with MRSA sepsis,
(150). High rates of colonization (30% to 70%) can become pneumonia, and a skin and soft tissue abscellll. MRSA isolates
established before clinical disease is recognized. The clinical from the mother's placenta and various infant body sites were
and economic impacts of MRSA colonization and infection identical (Fig. 26.1). In the second case, an infant with a his-
in NICUs have been quantified in several studies (151,152). tory of MRSA skin and soft ti.Sllue infection as a neonate was
Environmental sources or chronic carriers have rarely been admitted at 4 months of age with pneumonia and empyema.
implicated in nosocomial transmillllion in the NICU, but en- The mother of this infant had recurrent skin and soft tillllue in-
vironmental contamination with S. aumt.S does occur and fections in the labial region. MRSA isolates from the mother's
II Key:
1: Mother A (Placenta)
2
II 2: Patient B (Peripheral blood)
3: USA 300 Strain
3
II 4: USA 300 Strain
5: Patient A (Abdomen)
4
II 6: Patient A (Neck)
7: Patient A (Endotracheal aspirate)
8: Patient A (Peripheral blood)
5
II 9: Mother B (Peripheral blood)
6
II
7
II
8
II
9
II
Figure 26.1. Mother-to-infant 98 98.5 99 99.5 100
trammission dendrogram. % Similarity
labial abscess and the infant's pleural fluid were identical by endocarditis in neonates using either linezolid or daptomycin-
repetitive sequence polymerase chain reaction (PCR). containing regimens has been reported (174,175). These anti-
S. aufmS can colonize multiple body sites in infimts. The biotics should be used only when no other drugs are available
nares and umbilicus are the most common sites of coloniza- to reduce the risk of emergence of resistance.
tion in NICU infants, but the organism can also be isolated
from other sites including axillae, postauricular areas, and the
GRAM-NEGATIVE BACILLI
perineum (163). Comparison of colonization rates between
NICUs is difficult because the anatomic sites included in sur- Infections caused by GNB are associated with high case-
veillance culture strategies vary between hospitals (164). In a fatality rates of approximately 40% (range, 24% to 62%) .
2009 survey of members of the Society for Healthcare Epide- GNB infections in neonates have increased in many NICUs
miology of America, 86% of respondents reported that their (3,107,109,11!~,176). E. coli and Klebsiella or Enterobacter spp.
NICU screened patients for MRSA colonization, and among are the most frequently isolated GNB in the absence of an
those who screened, 85% did so on admission to the NICU outbreak (3,9,48,106,107,109,113). ESBL-producing isolates
(either as a single time point or in combination with periodic of these species have been reported by NICUs in recent years,
point-prevalence screening) and performed chlorhexidine and are especially problematic because of their resistance to
bathing on admission (164). the antimicrobial agents used routinely for empiric GNB cover-
Skin pustules, bullous impetigo, scalded skin syndrome age (51,101,104,177). In a single-center study, one in five NICU
(136--138), soft tissue abscesses, mastitis, conjunctivitis, pneu- infimts developed colonization or infection with multidrug-
monia with or without empyema, osteomyelitis, septic arthritis, resistant Enterobacteriaceae, and colonization (86%) was more
and SSis are the most frequent manifestations of both MSSA frequent than infection (14%) (178). Of note, multispecies
and MRSA infections in neonates, and the case-fatality rate outbreaks of ESBLs can represent transfer of the same plas-
associated with invasive disease can be 15% to 30% (88,89). mid among species with person-to-person transmission (176).
BSis with multiple foci of disease are characteristic of invasive Other GNB responsible for temporally related clusters in
S. aufmS disease. the NICU include P aeruginosa (61,99,102,103,179), Serratia
spp. (180-183), Citrobacter diversus (184-186), Salmonella spp.
(15,96), Acinetobacterspp. (14,187), Ch.ryseobacterium (Flavobact6-
Enterococcus
rium) meningosepticum (188), Ralstoniaspp. (56,189), and Burlc-
Enterococci have been recognized as important pathogens in hollkria cepacia (190).
the NICU since 1979 (165,166). The incidence (9,48,107,167) Molecular typing techniques (e.g., PFGE, ribotyping, PCR-
and number of reports of nursery outbreaks associated with based methods) are valuable tools for defining the epidemi-
susceptible Streptococcus Jaecium (168), Streptococcus Jaecali.s ology of GNB infections in the NICU during both epidemic
(169), and, more recently, VRE (167,170-172) have increased and nonepidemic periods (191,192), and should be used dur-
substantially since the 1980s, but enterococci still account only ing outbreaks to determine whether horizontal transmission
for a relatively small proportion of neonatal infections. In re- or selective antibiotic pressure is the predominant mecha-
gions of the United States where VRE have become problem- nism of spread and to guide the development of effective in-
atic HAl pathogens, spread to the NICU has occurred (167). terventions. Although nursery outbreaks of GNB infections
Repetitive sequence polymerase chain reaction (rep-PCR) have been associated with environmental contamination (e.g.,
DNA fingerprinting is useful to distinguish outbreak strains antiseptic solutions (182), intravenous medications and solu-
from endemic strains and "background" nursery flora and to tions (182,183,189,193), human breast milk (58-60), sinks
identify distinct clusters (171). Invasion occurs most often from (183,188), respiratory therapy and resuscitation equipment
the infant's endogenous flora. In enterococcal outbreaks, how- (15,56), and bandages (14)), such contamination is implicated
ever, environmental contamination, exposure to broad-spec- less frequently in well-developed countries with clean water
trum antimicrobials, horizontal transmission by HCW's hands supplies and well-defined protocols for sterilization of equip-
or a contaminated thermometer ( 171), and, for VRE, repeated ment and single use of disposable items. Some outbreaks of
introduction by infants transferred to a regional NICU from a Serratia marcescens have been controlled by enforcing recom-
birth hospital with endemic VRE are important factors in the mended general infection control measures, even when a
perpetuation of outbreaks. Targeted VRE surveillance after source for the Serratia spp. cannot be determined or when iso-
a positive clinical culture may be justified, as it can identify a lates are unrelated by molecular typing (181). In the absence
larger hidden pool of colonized infimts (173). of an environmental source, it is likely that a virulent epidemic
Enterococci are associated only rarely with early-onset sep- strain is acquired from the infected mother or, rarely, from a
sis. Most often, enterococci are isolated from the blood of low colonized or infected HCW or emerges from the infimt's en-
and VLBW infants with serious underlying conditions who have dogenous flora and then is transmitted horizontally to HCW's
been in the NICU for >30 to 60 days. Prolonged use of CVCs, hands. Identical strains of C. diversus have been identified in
NEC, and bowel resection in addition to exposure to antibiot- matemal infant pairs (185) and in HCWs and infected neo-
ics are associated findings. Polymicrobial BSI is especially likely nates (186). Prolonged rectal colonization in addition to hand
to occur in association with intra-abdominal disease, support- colonization has been implicated in outbreaks of C. diversus
ing the intestine as a point of invasion of enterococci. Clinical meningitis that were not controlled until colonized HCWs
manifestations of enterococcal infections are nonspecific. The were removed from the nursery (185,186) . In the absence of
unusual episodes of meningitis (168) and endocarditis require outbreaks, clones of resistant GNB have been shown to be ac-
prolonged (2::3 weeks and 2::6 weeks, respectively) treatment quired but cleared rapidly from the infant's flora after initial
with combination therapy using a cell wall-active agent com- colonization. However, horizontal transmission of these organ-
bined with an aminoglycoside for cure. Successful treatment of isms occurs and occasionally results in clinical disease ( 191) .
Chapter 26 • Till Newburn Nursery and the Neonatal lntensiv~ Care Unit 40 l
Clones of multidzug-resistant Enterobacter spp. transmitted in pathogenesis ofNEC, but an association with severe enterocolitis
the NICU were also found in geographically distinct areas of a in infants with Hirschsprung's disease has been reported (204).
children's hospital (192).
Clinical manifestations characteristic of GNB infections
FUNGAL INFECTION
include necrotizing ophthalmitis, pneumonia, ecthyma gan-
grenosum, cardiovascular collapse, and meningitis. Although Fungal infections in preterm infants are an important cause of
ecthymatous lesions are associated most frequently with morbidity and mortality in the NICU. Candida spp. are the most
P. aeruginosa invasive disease, they can be associated with other common invasive fungi in this context and account for up to
GNB pathogens or fungi. Biopsy and culture of such lesions are 12% of late-onset sepsis in VLBW infants, with a case-fatality
helpful in isolating the specific pathogen. Salmonella spp. have rate of 44% (205). In surveillance data from 1986 to 1994, Can-
a proclivity for causing osteomyelitis, septic arthritis, or men- dida spp. accounted for 7% of all BSis in the NICU, the fourth
ingitis that is especially difficult to cure even with prolonged most common etiology after CONS, GBS, and S. aumu (9).
courses of antibiotics that are highly active in vitro against the More recently, data from 128 US NICUs showed a 24% reduc-
infecting strain. C. diversw meningitis is notable for occurring tion in the number of infections per 1,000 patient-days among
in clusters in NICUs, and has an association with brain abscess neonates <1,000 g from 3.5 during 1995 to 1999 to 2.68 (p <
in 77% of patients compared to 7% of patients with meningitis 0.01) during 2000 to 2004, with a stable rate in the larger neo-
caused by other GNB (185). The combination of an aminogly- nates ( 4). The decreases occurred among both C. albicans and
coside and third-generation cephalosporin is recommended to Candida pampsilosis BSI. There was no increase in species (e.g.,
treat GNB meningitis even with organisms that are fully suscep- Candida glabrata or Candida krnset) that would be expected to
tible to aminoglycosides (194). Flavobacterium mmingosepticum, demonstrate resistance to fluconazole. NICU-specific rates of
an unusual GNB resistant to most antimicrobial agents used for hospital-acquired candidemia for infants <1,000 g varied sub-
empiric treatment of Gram-negative meningitis in the newborn, stantially: the median attack rate was 7.5%, but 25% ofNICUs
is a less frequent cause of epidemic GNB meningitis (188) and reported rates > 13.5%; this variation is similar to the 2.4% to
is treated successfully by the combination of vancomycin and 20.4% range reported from the smaller National Institute of
rifiunpin (195). Child Health and Human Development Neonatal Network.
The most consistent risk factors for candidemia in NICU
infants reported in case-control studies using multivariate
BordetelliJ pertussis
analyses are CVC use; previous bacterial BSis; gastrointestinal
Transmission of B. pertussis has been reported in normal new- pathology; abdominal surgery; gestational age <26 weeks; col-
born and intermediate care nurseries (196). The source is usu- onization, especially in multiple sites; and prolonged courses
ally an undiagnosed HCW (197) or visitor (198); therefore, of broad-spectrum antibiotics (e.g., primarily third-generation
screening and administering the Tdap vaccine according to cephalosporins) (52,71,72,206-209). The importance of other
published recommendations (196) are especially important for risk factors, including infusion of hyperalimentation fluids,
family members likely to visit infants in the nurseries and for especially those containing lipid emulsions, delayed feedings,
HCWs caring for such infants. Administration of Tdap vaccine endotracheal intubation, administration of histamine-2 (H2)
to family members of infants in the NICU has been suggested blocking agents, or corticosteroids as independent risk factors
as a method to improve vaccine uptake as demonstrated for identified in some studies is not well-established. In most in-
influenza vaccine (199). One simulation model found that if stances, candidemia develops as a consequence of endogenous
95% of HCWs in the NICU have received a pertussis booster colonization rather than as a result of cross-contamination.
vaccine, the probability of secondary transmission is reduced Baley et al. (210) reported a 26.7% fungal colonization rate in
to 2% (200). Healthcare facilities should provide the Tdap vac- infants weighing <1,500 gat birth who were followed prospec-
cine for HCWs. tively. Two-thirds of these infants were colonized within the first
week of life, probably reflecting maternal transmission during
labor and delivery. Systemic disease developed in 7.7% of colo-
Clostridium tlifficile
nized infants. Although the National Epidemiology of Mycosis
Outbreaks of Clostridium difficile infection (CDI) do not occur Survey (NEMIS) study group did not identify colonization as an
in the newborn nursery. In contrast to healthy adults who have independent risk factor in the six participating NICUs in 1993
an asymptomatic colonization rate of <5%, toxin-producing to 1995, gastrointestinal (GI) tract colonization preceded can-
strains of C. difjicik can be recovered from the stools of as many didemia in 43% of case-patients (71) . Once colonized, invasion
as 55% of asymptomatic neonates (201). Clinical disease in in- arises most often from the GI tract. Early colonization is more
fants who are colonized with toxin-producing strains remains likely to be associated with C. albicans, whereas other species,
rare; although this phenomenon is not well-understood, it has such as C. parapsilosis and Candida tropicalis, are more likely to
been proposed that the immature intestinal mucosa of the neo- be associated with late colonization that can result from hori-
nate might lack receptors for C. difficile toxin (202), although zontal transmission among infants or from HCWs.
other factors such as an inunature immune response may also C. parapsilosis is the most frequently reported cause of epi-
play a role {203). For these reasons, many experts recommend demic Candidaspp. infections (211-213) . With the use of DNA
not routinely testing infants for C. difficilewhen they develop di- fingerprinting, it has been possible to determine that several
arrhea, as interpreting a positive result is difficult. In selected nursery outbreaks of invasive Candida spp. infections, includ-
circumstances, such as documentation of pseudomembranous ing C. albicans (214-216), C. tropicalis (217), and C. lusitanitu
colitis by endoscopy in a neonate with diarrhea who has received (218), have been associated with cross-transmission from
antibiotics, testing or treating for possible CDI may be a reason- HCW's hands (211,215-217), retrograde intravenous medica-
able consideration. This organism does not play a role in the tion administration (214), and contamination of a multidose
bottle of liquid glycerin used as a suppository (212). The of disease or as one site of involvement in disseminated disease.
presence of onychomycosis in HCWs has been suggested as a Because of the risk of dissemination from primary cutaneous le-
possible source of nosocomial candidiasis spread by hand car- sions and the difficulty in distinguishing primary from secondary
riage (217). Thus, it is likely that wide variation in the rates of lesions, aggressive systemic antifungal therapy is always indi-
Candida BSis is a marker for management choices and infec- cated. Successful systemic voriconazole therapy of severe primary
tion control practices (218). cutaneous aspergillosis that was refractory to amphotericin B in
Clinical manifestations of disseminated candidiasis are usu- VLBW premature infants has been reported (224).
ally nonspecific. Neonates with a maternal history of vaginal Both Malassez.ia furfur (225) and Malasse:r.ia pachydcrma-
moniliasis rarely contract congenital mucocutaneous candi- tis (226) have been associated with BSI clusters in high-risk
diasis (91). At birth, such infants have an intensely erythema- premature infants who have received intralipids through eves.
tous maculopapular eruption of the trunk and extremities that Malassez.ia spp. isolates are most frequently isolated from blood
rapidly becomes vesicular and pustular and then resolves with obtained through a eve and are rarely recovered from periph-
extensive desquamation. Palms and soles are almost always af- eral blood. M.furfurskin colonization rates of25% to 84% have
fected. These infants who are otherwise asymptomatic do not been reported for infants during prolonged NICU admissions,
have systemic involvement and respond well to topical antifun- whereas :55% of infants hospitalized in a non-NICU setting or
gal therapy. In contrast, the development of a diffuse, erythem- attending a well-baby clinic were colonized with this organism
atous, scaling, bum-like dermatitis in an infant <1,500 g birth (225). Maksse:r.ia spp. infections can manifest as a self-limiting
weight is more likely to be a manifestation of invasive disease condition, neonatal cephalic pustulosis on the face, scalp, or
and requires systemic therapy (219). neck, and as a more severe clinical sepsis in neonates with
Candida spp. are less frequently recovered from blood cul- eves. When temporally related episodes occur, these organ-
tures of infants with invasive candidiasis than from infants with isms most likely are carried from patient to patient on HCW's
invasive bacterial disease. Candidemia is present most often in hands. However, in one outbreak of Mnlassezia pachydermatis,
association with a eve. In such patients, the eve should be transmission from pet dogs to HCWs and then to infants in the
removed as soon as possible to facilitate clearance of the blood- NICU was likely (226).
stream. Persistently positive cultures of blood for Candida sp.
is a risk factor for focal complications, and the risk increases
VIRAL INFECTIONS
with the increasing duration of positivity (220). A minimum of
2 weeks of antifungal therapy is recommended when the eve Outbreaks of viral infections in the NICU have been recog-
has been removed in the absence of other sites of focal infec- nized with increased frequency with the advent of improved
tion to prevent the development of other foci. 1hle candiduria techniques for viral isolation and identification of viral antigens
can reflect disseminated disease or localized cystitis; thus, isola- using direct fluorescent antibody, enzyme-linked immuno as-
tion of Candida sp. from the urine indicates the need to evalu- say (ELISA), and PCR technology. In nursery outbreaks of vi-
ate other potential sites of infection. An echocardiogram can ral infections, the virus can be introduced by a staff member
best detect Candida endocarditis associated with a eve in an (229), and the rates ofinfection of staff members could be high
infant with a structurally normal heart. Large vegetations can (230-234). Because staff members have mild illness, they some-
be present in the absence of a murmur and signs of congestive times continue to work and to spread the pathogen by direct in-
heart failure (221). At autopsy, fungal vegetations have been oculation of their infected secretions. Respiratory syncytial virus
found in infants with endocarditis unsuspected before death. (RSV) and rotavirus have frequently been associated with noso-
Osteomyelitis, septic arthritis, meningitis, and brain abscess are comial transmission (231,233). Other respiratory viruses, nota-
other foci of infection that can be present with relatively few bly influenza (234), parainfluenza (80), and adenoviruses (229)
specific physical signs. The most severe episodes of meningi- can be associated with clusters of respiratory infections having
tis and endocarditis require prolonged treatment courses of clinical manifestations similar to those of RSV. Manifestations
liposomal amphotericin B. Experience with the newer azoles of RSV infections in infants <3 weeks of age are atypical and
(e.g., voriconazole) and echinocandins (e.g., caspofungin, more likely to include apnea, lethargy, and poor feeding in the
micafungin) in neonates is still not sufficient to determine absence of respiratory symptoms. Beyond 3 weeks of age, bron-
whether these agents offer any advantage for treating invasive chiolitis and pneumonia are characteristic of RSV infections;
candidiasis. Medical therapy ofVLBW infants with Candida spp. apnea can precede the onset of respiratory symptoms. Infants
endocarditis with a combination of two antifungal agents has with bronchopulmonary dysplasia requiring oxygen, congeni-
been successful and is often preferred owing to the high risk tal heart disease with pulmonary hypertension, and congenital
of surgical excision of vegetations in such infants. A review of immune deficiency syndromes are at the greatest risk for de-
the literature found little difference in survival between those veloping severe disease after infection with RSV. Substantial
neonates treated with antifungal therapy only ( 65%) compared medical and economic impact of an RSV outbreak in an NICU
with those who were treated with antifungal therapy and sur- has been quantified (235). Several different types of adenovi-
gery (60%,p = 1.0) (222). rus have been associated with nursery outbreaks (229,236). The
Other fungi associated with HAl in the NICU include most common clinical manifestations are conjunctivitis and
Aspergillus spp. (223,224), Malassez.ia spp. (225,226), RhU.opus pneumonia. Direct inoculation by ophthalmologic instruments
spp. (227), and Triclwsporonspp. (228) Aspergillus, Rhizopus, and and transmission by the droplet route have been documented
Trichospuron spp. are acquired from the environment via exposure (236); specific guidelines for retinopathy of prematurity (ROP)
to either construction dust or contaminated medical supplies. ophthalmologic examinations to prevent contact transmission,
Infants with aspergillosis are notably not neutropenic but are including using gloves with change between patients, soaking
premature and do not have normal chemotaxis and phagocyto- instruments in 70% alcohol solution for 5 to 10 minutes, and
sis. Cutaneous aspergillosis can occur as the initial manifestation changing alcohol solution twice daily, have been issued (229).
Neonates can manifest multiorgan involvement with cardiovas- number of susceptible or infected neonates, mothers, visitors,
cular collapse and a bacterial sepsis-like clinical syndrome with and HCWs has decreased substantially.
a case-fatality rate of 84%. The role of additional respiratory
viruses detected in infants and young children (e.g., human
TUBERCULOSIS
metapneumovirus, bocavirus) for neonates and potential for
nursery outbreaks remains to be identified. Congenital tuberculosis (TB) is extremely rare, but can occur
Nursery outbreaks of viruses with a gastrointestinal reservoir even when the mother is asymptomatic. Infants in the NICU
have been described, and those of coxsackievirus and echovirus who have TB are unlikely to transmit Mycobacterium tuberculosis
infections have been reviewed (237). In most outbreaks, the to other infants and visitors but can transmit it to HCWs with
source patients acquired infection from their mothers and had unprotected close exposure (249). However, M. tuberculosis has
severe disease. Case-fatality rates associated with hepatitis can been transmitted to exposed neonates in the maternity unit,
be as high as 83%. Infants who acquire infection by nosocomial newborn nursery, and NICU and from visitors and HCWs with
transmission have milder disease, with case-fatality rates of12% active pulmonary TB in countries where TB is considered en-
or less. HCWs also can be vectors for spreading this group of demic (250) and in the United States (251-254) . The neonate
viruses. The most common clinical manifestations of neonatal is at great risk for developing severe disseminated disease, in-
coxsackievirus and echovirus infections are hepatitis, meningo- cluding meningitis, once exposed to an individual with active
encephalitis, myocarditis, and pneumonia, and are similar to TB. Thus, recognition of an exposure must be followed by a
the disease associated with neonatal herpes simplex encepha- comprehensive evaluation and initiation of chemoprophylaxis
litis and disseminated infections. Specific diagnostic testing us- when the exposure is significant. A decision analysis has been
ing sensitive and specific PCR assays is essential to distinguish developed to assist neonatologists and infection control per-
these agents because no antiviral agents are available to treat sonnel in managing M. tuberculosis exposures (254). When a TB
coxsackievirus and echovirus infections. diagnosis is considered in a young infant, a liver biopsy that
Rotavirus and hepatitis A virus are transmitted by the shows granulomas and acid-fast bacilli is diagnostic.
fecal-oral route. Rotavirus transmission in the nursery is well-
documented; infection can be asymptomatic or associated with
mild to moderate or severe diarrhea. Preterm infants with ro- HAl TREATMENT
tavirus infection are more likely to have systemic signs such as
feeding difficulty and neutropenia (238). Rotavirus-associated Physicians treating specific HAl can consult sources such as
outbreaks of NEC have been reported (231). HAl outbreaks their local nursery guidelines or the AAP Red Book for specific
of hepatitis A virus are extremely rare because of the relatively recommendations concerning choice of agent, dosing regi-
brief duration and low titer of viral shedding within the stool men, and duration of therapy. Empiric therapy for early-onset
(239-241). However, immunologically immature preterm in- sepsis consists of ampicillin combined with an aminoglycoside.
fants can excrete hepatitis A viral antigen and RNA for as long Ampicillin provides activity against GBS, enterococci, and Lis-
as 4 to 5 months after the acute infection (240). The source in- teria monocytogmes. If S. aunus is suspected, oxacillin, or-in
fants in reported outbreaks acquired hepatitis A virus either by areas with high prevalence of MRSA-vancomycin is recom-
vertical transmission from the mother before or during delivery mended for Gram-positive coverage. In one study, empiric use
(239) or by blood transfusion (240,241). of ampicillin and cefotaxime during the first 3 days of life was
The following viruses are not transmitted horizontally in the associated with an increased risk of death compared with am-
nursery: mv; HBV, hepatitis C, and CMV. Inadvertent exposure picillin and gentamicin, but the mechanism is unknown (255).
to expressed breast milk from a different mother who is infected In 2012, the AAP published a guideline for the evaluation of
with HIV has the theoretical risk of transmitting HIY, although asymptomatic infants with risk factors for sepsis (256).
there are no published reports of infection after exposure to a When treating suspected late-onset sepsis, the choice of
single feeding of misappropriated breast milk in the hospital. antimicrobial agents varies substantially among neonatolo-
Nevertheless, the source mother and the exposed infant should gists (257). Oxacillin can be used for Gram-positive coverage
be tested for HIV under these circumstances (62). There is no safely in NICUs that do not have MRSA as a prevalent pathogen
significant increase in the excretion of CMV in infants in the and in infants with eves who are minimally symptomatic. Blood
nursery compared with patients in other areas of a pediatric cultures from two separate sites are helpful in distinguishing
hospital (242), nor is there a significant increase in the risk CONS that are skin contaminants from true pathogens. The
of acquisition of CMV infection among HCWs on pediatric or advantage of not using vancomycin routinely is the reduced
neonatal units compared with similar adults without hospital risk of emergence of VRE, vancomycin-resistant staphylococci,
exposure;(243,244) thus, pregnant HCWs are not restricted and GNB infections (257,258). Third-generation cephalospo-
from caring for infants known to excrete CMV (244). Standard rins are not recommended for routine empiric use because of
precautions should be used as they would for exposure to any the rapidity of emergence of resistance in an individual patient
patient's potentially infectious secretions or body fluids. Trans- during therapy and in microflora of the unit (51,259-261) as
mission of either herpes simplex (245,246) or varicella-zoster well as the association with an increased risk of candidiasis in
virus (247) in the nursery is extremely rare. Although trans- VLBW infants (72). However, a combination of cefotaxime
mission from oral lesions of nursery HCWs has been reported and an aminoglycoside should be started if there is a strong
(246), the risk is so low that such individuals are no longer ex- suspicion of GNB meningitis. Once the identification and sus-
cluded from patient care as long as the lesion can be covered ceptibility of the GNB-causing meningitis is known, coverage
until dried (248). In contrast, HCWs with herpetic whitlow are may be narrowed for the completion of the appropriate course
excluded from direct patient contact in the nursery. With wide- of therapy. Ceftriaxone is not used in the neonate because of
spread use of the varicella virus vaccine licensed in 1995, the its displacement of bilirubin from albumin-binding sites (262)
and its strong suppressive effect on the neonate's developing efficacy and because of safety concems. Some experts recom-
gastrointestinal flora (263). Monitoring susceptibility pattems mend the addition of the monoclonal antibody palivizumab
for GNB is necessary to ensure that the currently recom- to treat severe RSV infection in high-risk patients on the basis
mended agents will be effective against the current pathogens. of anecdotal experience in adult bone marrow transplant pa-
With the exception of CONS-BSI, meningitis can be present in tients (274). No efficacy data in human infants have been pub-
10% to 20% ofBSis and in the absence ofBSI or abnormalities lished and the cost of palivizumab is high; therefore, further
of the CSF cell counts, glucose, and protein in 30% to 40% studies are needed.
of infants with late-onset sepsis. Therefore, a lumbar puncture
for CSF culture and analysis is essential to diagnose meningitis
(264,265). Meningitic dosages of antimicrobial agents are rec-
ommended until meningitis has been ruled out.
HAl PREVENTION
Specific anaerobic coverage is rarely required in neonates.
NURSERY DESIGN AND STAFFING
The most frequent indications are intra-abdominal sepsis,
NEC, and intestinal perforation. Clindamycin, metronidazole, The AAP and the ACOG collaborate to develop guidelines
piperacillin-tazobactam, and meropenem provide activity for all aspects of perinatal care, including infection control
against most anaerobes. in the nursery (275); they revise these guidelines at regular
Removing the catheter as soon as possible in the setting of intervals. Table 26.3 summarizes the recommended nurse-
CLA-BSI caused by Candida spp. is essential to clear the funge- infant ratios based on the acuity of the medical condition and
mia and prevent seeding of other foci. Traditionally, ampho- the amount and type of nursing care and support equipment
tericin B and fluconazole have been the only treatment options needed. Nurse-infant ratios below those recommended have
for invasive fungal disease in the neonate. While C. albicans had been associated with increased rates of bacterial invasive dis-
been nearly universally susceptible to fluconazole, the increas- ease caused by MSSA (78), MRSA (25), E. cloacae (79), and
ing frequency of infections caused by more-resistant Candida other bacteria (77,81) and viral respiratory infections (80) in
spp. and the toxicity associated with amphotericin B have made the nursery and NICU. Spatial requirements are defined in the
antifungal treatment more difficult. Fortunately, the develop- 2010 Guidelines for Design and Construction of Health Care
ment of antifungal agents with less toxicity and greater activ- Facilities published by the Facility Guidelines Institute (276)
ity against a broader range of fungi has increased (266). The and by the Consensus Committee on Recommended Standards
newer azole drug, voriconazole, is now preferred for the treat- for Newbom Intensive Care Unit Design (83) (Table 26.3).
ment of invasive aspergillosis. This drug has not been studied Single-patient rooms in the NICU can offer an infection con-
in neonates and there is theoretical concem about the effect trol advantage, but more data are needed to support a univer-
on the developing retina because of the visual adverse events sal recommendation.
reported in adults and older children. The echinocandins rep- Many experts recommend central high-efficiency particu-
resent a class of agents that interfere with fungal cell wall bio- late air (HEPA) filtration when constructing a new NICU be-
synthesis by the inhibition of an enzyme present in fungi but cause of the vulnerability ofVLBW infants to infection caused
absent in mammalian cells. These drugs are not substrates for by airbome spores and because surgical procedures (e.g.,
the hepatic cytochrome P450 enzyme system or the intestinal ECMO cannulation/decannulation, exploratory laparotomy
glycopeptides, thereby reducing drug interactions. The echi- in infants with NEC) often are performed in the NICU when
nocandins have excellent fungicidal activity against most Can- high-risk infants are too unstable to withstand transport to the
dida spp. and are fungistatic against AspergiUus spp. Although operating suite.
there is still a lack of pharmacokinetic data (267), case series
(268,269) and individual case reports indicate that caspofungin
HAl SURVEILLANCE
successfully treats refractory candidiasis in VLBW neonates and
is well-tolerated. In one randomized trial of 32 neonates with An active surveillance program is an essential component of
invasive candidiasis, caspofungin produced better response HAl prevention. In most hospitals, surveillance of positive clini-
and fewer adverse events than amphotericin (270). Micafungin cal culture results is performed by infection preventionists who
is another agent in this class that has undergone pharmaco- are responsible for several different units in the hospital. The
kinetic studies in neonates (271) and has been used in larger CDC recommends the following: (a) prospective surveillance
neonatal studies. on a regular basis by trained infection preventionists using
Acyclovir is the preferred treatment for herpes simplex and standardized definitions, (b) analysis of infection rates using
varicella-zoster viral infections. In a large, multicenter, ran- established epidemiologic and statistical methods (e.g., calcu-
domized, controlled trial of ganciclovir therapy of infants with lating rates using appropriate denominators that reflect du-
congenital CMV infection and central nervous system involve- ration of exposure and using statistical process control charts
ment, the treatment prevented deterioration of hearing (272). for trending rates), (c) regularly using data in decision mak-
A subsequent pharmacokinetic and pharmacodynamic study ing, and (d) employing an effective and trained healthcare
demonstrated that oral valganciclovir can provide plasma con- epidemiologist who develops infection prevention and control
centrations comparable to those achieved with intravenous strategies and policies and serves as a liaison with the medical
ganciclovir (273). At the time of publication, many experts are community and the administration (18,20,21,277,278). For the
using oral valganciclovir to treat symptomatic congenital CMV NICU, birth-weight categories are used for risk stratification.
infection involving the central nervous system, but further A working definition of epidemiologically important organ-
trials are needed to define optimal management. The treat- isms has been developed to assist the infection control team
ment of RSV infections is primarily supportive. Ribavirin is no in recognizing pathogens that require further investigation
longer routinely used because of conflicting data conceming and preventive measures (279). When infection preventionists
TABLE 26.3 Rrcommendcd Staffing Ratios and Space According to the Levd of Care :Ra)uired
in the Newborn Nursery and NICU (83,275,276)
Space
Registered NU1'8e- Floor Space (feet!) ~en Beds Adjacent Aisle
Care Provided to-infant Ratio Per Infant (feet) Width (feet)
Newborn admission and observation 1:4 40
Newborns requiring only routine care 1:&--8 !iO
NR
!i ..
NR
Normal mother-newborn couplet care 1:3-4 NR NR NR

Newborns requiring continuing care 1:!i-4 50 4 NR
Newborns requiring intermediate care 1:2-3 100-120 4 5
Newborns requiring intensive care 1:1-2 Multiple-bed rooms: 120-150 6 8
Single-bed rooms: 150 8
Newborns requiring multisystem 1:1 6 6 b
support6
Unstable newborns requiring complex 2:1:1 b b
critical careb
NR, No recommendation.
"No specific recommendation published; maximum of 16 infant stations per nursery room.
bJ.ncreased space requirements preferred, but no specific recommendations published.
identify temporally related clusters of clinical infections and/ ISOLATION PRECAUTIONS

or epidemiologically important pathogens, especially those
that are multidrug-resistant, they collaborate with the nursery The CDC guidelines on isolation precautions for prevent-
staff to develop a prevention program. As soon as a cluster or ing transmission of infections in healthcare settings are avail-
outbreak is suspected, infection preventionists should notify able (285) and should be consulted for managing specific
the microbiology laboratory of the need for active surveillance infections. Standard precautions (Table 26.4) remain the foun-
cultures and to save isolates should molecular fingerprinting dation in infection control to which other categories of precau-
studies be indicated. Designating a nursery staff member who tions are added. In NICUs with single-patient rooms, personal
understands the psychology and operational logistics of the protective equipment (PPE) needed for contact and droplet
unit as the infection control liaison facilitates education and precautions (e.g., gloves, gowns, or surgical masks) should be
adherence to policies for hand hygiene, isolation precautions, donned upon entry into the room. In NICUs with multibed
cohorting of patients and staff, proper cleaning, disinfection pods or bays, the space around the isolette of the infant who
and sterilization of medical equipment, and other aseptic prac- requires contact and/or droplet precautions may be desig-
tices (25,280,281). Participation ofnurserystaffmembers in the nated with tape on the floor and/ or signs on the isolette or
design of prevention programs increases adherence. Feedback in the bedspace. A separate room is not required for infants
of positive results is most important to the staff when they have on contact or droplet precautions, but spatial separation from
succeeded in controlling an outbreak; reviewing guidelines to uninfected infants is preferred. Although enclosed isolettes
prevent a similar outbreak is essential. provide a limited amount of barrier protection relative to open
Routinely culturing neonate body surfaces (i.e., skin, umbi- warmers or bassinets (139), they cannot be relied on to pre-
licus, mucous membranes, tracheal aspirates, and rectal swabs) vent pathogen spread to other infants by HCW hand carriage.
is not recommended in nonoutbreak settings because they do Neonates usually are unable to generate large-particle droplets
not predict which infants are at risk for sepsis, and are very spontaneously, but endotracheal suctioning or administration
costly (282,283). In contrast, body surface cultures are help- of aerosol treatments can generate infectious droplets. Accord-
ful during an outbreak to identify infants who are colonized ing to standard precautions, masks are indicated if splatter of
with the target pathogen in addition to infants who have posi- respiratory secretions is anticipated (e.g., endotracheal suc-
tive clinical cultures for target pathogens (e.g., MRSA, VRE, tioning or intubation). At least one airborne infection isolation
and multidrug-resistant GNB). Newly admitted infants must be room (AIIR) with negative-pressure ventilation that meets stan-
kept in cohorts separate from colonized and infected infants dard requirements is recommended for every nursery/NICU
to limit horizontal transmission of the outbreak organism. In to isolate neonates with perinatal exposure to maternal vari-
addition, it can be useful to perform active MRSA and VRE sur- cella and suspected or confirmed TB. Most other infections do
veillance cultures at regular intervals (e.g., 3, 6, or 12 months) not require special isolation rooms.
in NICUs that have no clinical episodes of MRSA or VRE to During outbreaks, the most effective method for preventing
detect the presence of target multidrug-resistant organisms horizontal transmission is cohorting infants who are colonized or
(MDROs) establishing high colonization rates and clinical disinfected with epidemiologically important pathogens away from
ease (140,279). However, it remains unclear whether routine newly admitted patients and ideally with dedicated personnel
MDRO surveillance (with subsequent contact precautions for who do not care for newly admitted infants or infants who are
colonized or infected infants) substantially changes MDRO not colonized or infected (25,140,141,286). If transmission con-
prevalence in the NICU over extended periods of time (284). tinues in the presence of strict cohorting, continual introduction
Regional collaboration for NICU surveillance and control of of the epidemic organisms from a carrier or multiple different
MRSA has proven particularly useful (140). sources or from ineffective hand antisepsis is likely (184).
TABLE 26.4 Ra:om.m.cndations for the Application of Standard Precautions for the Care of All
Patients in All Healthca.re Settings
Component Recommendations
Hand hygiene After touching blood, body fluids, secretions, excretions, contaminated items; inunediately after
removing gloves; and between patient contacts. Alcohol-<ontaining antiseptic hand rubs preferred
except when hands are visibly soiled with blood and/ or other proteinaceous materials or if exposure
to spores (e.g., C. difjicile. B. anthmcis) is likely to have occurred.
Gloves For touching blood, body fluids, secretions, excretions, contaminated items, mucous membranes, and
nonintact skin.
Gown During anticipated procedures and patient-<are activities with contact of clothing/exposed skin with
blood/body fluids, secretions, and excretions.
Mask, eye protection (goggles or During procedures and patient-<are activities likely to generate splashes or sprays of blood, body fluids,
face shield) or secretions, especially suctioning, endotracheal intubation.
Soiled patient-are equipment Handle in a manner that prevents transfer of microorganisms to others and to the environment; wear
gloves if visibly contaminated; perform hand hygiene.
Environmental control Develop procedures for routine care, cleaning, and disinfection of environmental surfaces, especially
frequently touched surfaces in patient-<are areas.
Injection practices (use of needles Do not recap, bend, break, or hand-manipulate used needles; if recapping required, use a one-handed
and other sharps) scoop technique only; use needle-free safety devices when available; place used sharps in puncture-
resistant container. Use sterile, single-use, disposable needle and syringe for each injection given.
Single-dose medication vials preferred when medications are administered to > 1 patient.
Respiratory hygiene/cough Instruct symptomatic persons to cover mouth/nose when sneezing/coughing; use tissues, dispose of
etiquette them in no-touch receptacle; observe hand hygiene after soiling hands with respiratory secretions;
wear surgical mask if tolerated or maintain spatial separation, >3 feet if possible. Restrict individuals
with active respiratory infections from the NICU whenever possible.
HAND HYGIENE AND GLOVES water between patient contact!!. As part of good hand hygiene
practices, HCWs who have direct contact with high-risk patients
Performing hand hygiene between patient contacts is the
should have well-groomed and short natural nails (287) . The
single most important measure for preventing HAis in
evidence base to support the recommendations for HCWs
the NICU (287). The CDC/HICPAC Guideline for Hand Hy-
with direct contact with patients in ICUs includes four studies
giene in Health Care Settings summarizes nine studies, three of
performed in NICUs (101-104). Novel strategies to improve
which were conducted in the NICU, newborn nursery, or gen-
adherence to recommendations for hand hygiene and moni-
eral pediatrics units, that demonstrate a temporal relationship
toring adherence are needed in the nursery/NICU as in all
between the introduction of new hand hygiene products and
other areas of healthcare facilities.
improved hand hygiene practices and decreased MRSA infec-
Gloves must be worn when contact with potentially infectious
tion rates when added to the other control measures that had
body fluids, secretions, or excretions is anticipated or when car-
been in place, including obtaining weekly active surveillance
ing for patients on contact precautions. Gloves must be changed
cultures and contact precautions. Alcohol-containing antisep-
between patient contacts and hand hygiene must be performed
tic hand gels/rubs/foams and antimicrobial soap and water
immediately before donning and upon glove removal.
are preferred in nurseries and NICUs. A hands-free handwash-
ing station should be provided in each single-patient room.
Every infant bed in multibed rooms should be within 20 feet
GOWNS, CAPS, AND MASKS
of a handwashing station but should be no closer than 3 feet to
other beds (83). Having an alcohol-based hand rub dispenser The use of gowns on entrance into the nursery is a long-standing
mounted at each bedside provides the best opportunity for us- ritual that many nurseries are hesitant to relinquish. Studies of
ing hand hygiene consistently. varying design conducted in the nursery and NICU confirm
A 2-minute scrub from hands to forearms with an antiseptic- gowns' lack of efficacy for preventing HAis {288,289) . In al-
containing soap is no longer recommended for NICU staff at ternate 2-month gowning and no-gowning cycles, Pelke et al.
the beginning of a work shift (287). However, published recom- demonstrated no significant differences in the rates of bacterial
mendations in the AAPI ACOG Guidelines for Perinatal Care colonization, HAis including RSV and NEC, and mortality (289).
for the number of nursery scrub areas are to have (a) one scrub In addition, compliance with handwashing/hand hygiene was
area at the entrance to each nursery with faucet!! operated by not increased during the gowning cycles, nor was traffic into
foot or knee controls and (b) one scrub sink for at least every the unit changed. Thus, in a nonoutbreak setting, gowns are
6 to 8 patient stations in the normal newborn nursery and for not required for staff or visitors upon entrance to the NICU
every 3 to 4 patient stations in the admission/observation, con- (290) but are indicated when soiling with blood or body fluids
tinuing care, intermediate care, and intensive care areas (275). is anticipated, when caring for patients on contact precautions,
While some scrub sinks are required because surgical proce- or when clustered infections with epidemiologically important
dures are performed in the NICU, their number can likely be organisms that are considered to have been transmitted by the
reduced. Hand hygiene should be performed using either an contact route are present. Concern about excessively soiled
antiseptic alcohol-based hand rub or antimicrobial soap and clothing may also be an indication for parents or guardians to
use a gown. In addition, long-sleeved gowns may be worn when alternate antiseptic that in 2012 received FDA labeling to "use
handling neonates outside of a bassinet or incubator. with care in premature infants or infants under 2 months of age"
Caps and masks are indicated when performing sterile pro- because it may cause skin irritation or chemical bums. Despite
cedures, including eve placement. Masks also are used by this labeling, a national survey revealed that most US NICUs do
HCWs as part of standard precautions and droplet precautions. use CHG (often with restrictions based on birth weight or gesta-
Respirators (such as N95s) are indicated for HCWs having con- tional or chronologie age) for specific indications such as eve
tact with a patient with suspected or confirmed TB. insertion or maintenance or MRSA decolonization (293). CHG
is poorly absorbed through intact skin, but trace absorption
has been documented in premature infants; it remains unclear
PREVENTION OF TRANSMISSION OF whether such absorption has any clinical consequence. Ample
MULTIDRUG-RESISTANT ORGANISMS experience has demonstrated that it can be used safely in many
Control of MDROs requires three groups of inten'entions: neonates. Alcohol-based CHG preparations have caused bums
(a) prudent antimicrobial use to prevent emergence of resis- in infants of 24 to 26 weeks gestational age (294). When intra-
tance, (b) implementation of bundled practices to prevent muscular injections are given in the delivery room as part of
device- and procedure-related infections, and (c) infection prophylaxis regimens (e.g., penicillin G to prevent early-onset
control measures to prevent transmission within the NICU GBS disease or gonococcal ophthalmia, ceftriaxone to prevent
(279). On the basis of the voluminous number of published gonococcal ophthalmia, or vitamin K to prevent hemorrhagic
studies of control ofMDROs in NICUs and in other healthcare disease of the newborn), the injection site must first be cleansed
settings, it is dear that transmission of MDROs in healthcare well with alcohol. A recent outbreak documented BaciUus cereus
settings can be controlled, but the single most effective strategy infections associated with nonsterile alcohol swabs (295). Thus,
for all settings has not been established. Seven categories of sterile alcohol swabs should be used for skin antisepsis. Use of
measures are critical for preventing MDRO transmission (279): such alcohol swabs prevents the introduction of microorganisms
such as HIV, HBV, and herpes simplex virus in maternal blood
1. Administrative measures to ensure successful implementa- and body fluids that could be contaminating the infant's skin.
tion of recommended practices including designating con- A single application within 1 hour of delivery of topical tet-
trol of MDROs as an organizational patient safety priority, racycline ( 1%) or erythromycin (0.5%) ophthalmic ointment
providing effective and timely communication of MDRO is preferred to prevent gonococcal ophthalmia. The use of 1%
status of patients upon reentry or transfer to a facility, mon- silver nitrate drops is discouraged because of the associated
itoring the implementation and adherence to precautions, chemical irritation. The eyes should not be irrigated after instil-
providing feedback to HCWs, and supporting participation lation of any of these agents. Single-use tubes or vials must be
in regional coalitions. used to prevent cross-infection. A single dose of intramuscular
2. Education of all HCWs, patients, families, and visitors. or intravenous ceftriaxone, 25 to 50 mg/kg to a maximum of
3. Judicious use of antimicrobials including developing an 125 mg, is recommended for infants born to mothers with ac-
active multidisciplinary antimicrobial stewardship team. tive gonorrhea at delivery (296).
The influence of antimicrobial exposure on emergence of The umbilical cord has been reported to become colonized
multidrug-resistant GNB has been demonstrated specifi- with S. aureus in up to 70% of infants within 48 hours after birth
cally in the NICU (51,259,260,291,292). and can potentially serve as a point of entrance for pathogens to
4. Sun'eillance, including tracking and trending MDRO rates cause invasive disease. High colonization rates in the nursery are
and actively monitoring culture results in high-risk popu- associated with an increased rate of postdischarge infection for
lations. Because HCWs rarely are the source of bacterial term infants and longer hospital stay for low-birth-weight infants.
pathogens causing outbreaks, active sun'eillance cultures Therefore, most nursery protocols include antiseptic treatment.
of HCWs are recommended only when epidemiologic evi- The role of antimicrobial applications to the umbilical cord to
dence implicates them as a source of ongoing transmission. prevent bacterial colonization and infection has been reviewed
5. Infection control precautions, including the use ofhand hy- (262,263,297,298). These reviews conclude that there is evidence
giene, standard precautions and contact precautions with that applying an antiseptic to the cord reduces bacterial coloni-
dedicated patient-care equipment and cohorting patients zation, but there is insufficient evidence to determine whether
infected with the same antibiotic-resistant pathogen(s) any agent is preferred. The delay in time to cord separation in
when single-patient rooms are not available. infants treated with topical antiseptics is not significant clinically
6. Environmental measures (e.g., adherence to recommen- and should not deter the use of antibacterial products. Iodine-
dations for cleaning and disinfecting potentially contami- containing agents are not recommended because of the possi-
nated environmental surfaces and medical equipment). bility of transcutaneous absorption and suppression of neonatal
7. MRSA decolonization on a selective basis. thyroid function. Short-term use of mupirocin ointment to con-
trol an outbreak associated with S. at.t1'lmS may be considered, but
mupirocin is not recommended routinely because of the emer-
SKIN, EYE, AND CORD CARE
gence of resistant strains after its frequent or prolonged use (299).
Initial cleansing of skin after birth is delayed until the neonate's
temperature has stabilized. Warm water alone or warm water
PREVENTION OF DEVICE-ASSOCIATED
and a mild, nonmedicated soap are recommended when the
INFECTIONS
skin is cleaned (275). Specifically, hexachlorophene is no longer
recommended for routine daily bathing of neonates because of Few controlled investigations of care practices of intravascu-
the neurotoxicity demonstrated previously when it is absorbed lar catheter or respiratory therapy equipment specifically in
in large concentrations. Chlorhexidine gluconate (CHG) is an the newborn nursery have been conducted. Consequently,
nurseries usually follow guidelines for the care of catheters and with a PICC (307). Several multicenter collaboratives between
respiratory equipment based on studies in older children and NICU s have led to reductions in BSI rates using insertion and
adults (55,300). For patients in intensive care settings, preven- maintenance bundles (308-310).
tion of several common device-associated infections is a high Diagnosing VAP in the NICU remains a challenge because
priority. Efforts have focused on ClA-BSl, VAP, and CA-UTI. the CDC NHSN surveillance definition includes subjective
The most important of these three infections for neonates and components such as findings on chest radiography ( 18). At the
premature infants is ClA-BSI. Both PICC and surgically placed time of writing, the CDC is working on revising the definition
tunneled CVCs are used in the NICU and have been shown to to focus on ventilator-associated events (both infectious and
have similar complication rates for neonates (301). One study noninfectious in nature) that can be detected using objective
of NICU patients with PICCs found that the daily risk of ClA- criteria. Studies will be needed to specifically address the per-
BSI increased substantially after a catheter duration of 35 days formance of any new definition in neonates. The optimal bun-
(302). Most ClA-BSis in neonates with PICC occur after 5 to dled practices for preventing VAP in the NICU have not been
7 days of hospitalization and are caused by CONS and occur determined, but options for modifYing the adult bundles and
as a result of intraluminal contamination (303). The bundled experiences in several institutions have been reviewed (311) .
practices for preventing ClA-BSI in children have been ap- Table 26.6 outlines the potential interventions for VAP preven-
plied to neonates and have reduced the rates of ClA-BSI signif- tion in neonates. Mouth-suctioning devices, such as the De Lee
icantly. These practices are outlined in Table 26.5. Minimizing suction trap, are no longer used because of the risk of exposure
catheter manipulation and paying specific attention to aseptic to potentially infectious aspirated material that could enter the
technique when catheters are manipulated (e.g., hub, exit site, HCW's mouth. When a mechanical suction apparatus is used,
blood sampling) are important for preventing ClA-BSI (304) . the negative pressure should not be > 100 mm of mercury when
Practices for which some, but not enough, data suggest effi- the suction tubing is occluded (275). Although closed suction-
cacy in support of recommendations for routine use include ing systems provide an opportunity for pooled secretions to be
chlorhexidine sponge dressings (BiopatchTM) (305) and vanco- introduced into the lower respiratory tract, no endorsement
mycin-heparin lock solution (306). The chlorhexidine sponge can be made for closed versus open suctioning as a VAP pre-
dressing should not be used in neonates <1,000 g or <7 days vention strategy in neonates (290). Only sterile water should
old or of gestational age <26 weeks because of reports of be used for any device that provides humidification to the neo-
exudative-type local reactions and pressure necrosis occurring nate, and all equipment must be cleaned and disinfected ac-
under the patch in these very premature infants (305) . Unique cording to manufacturers' recommendations (56). Isolation of
to the nursery is the use of umbilical arterial and venous cathe- pathogens such as B. cepacia and Ralstonia sp. from respiratory
ters for which many care issues remain unresolved. The rates of secretions should alert NICU personnel to the possibility of
colonization and associated BSis are similar for umbilical arte- contaminated equipment or oral care agents (56,190).
rial and venous catheters. The umbilical insertion site must be
cleansed with an appropriate antiseptic before catheter inser-
tion. Tincture of iodine is not used because of the potential ef- TABLE 26.6 Ventilator-Associated
fect on the neonatal thyroid (275). Umbilical arterial catheters Pneumonia (VAP)
should not be left in place for >5 days. Removing umbilical Prevention Measures for
venous catheters after 14 days is recommended, but a ran-
Neonates (311,357)
domized trial reported no increased adverse events associated
with umbilical venous catheters in neonates with birth weights Interventions applicable to Interventions for which risk-
<1,251 g for up to 28 days compared with removal of the um- neonates benefit ratio in neonates
bilical venous catheter after 7 to 10 days and its replacement is unknown but which are
generally recommended a
Hand hygiene when manipu- Elevation of the head of the bed
lating endotracheal tubes. (15•-go• for neonates).
TABLE 26.5 Central Line-Associated Wear gloves for contact with Oral care with antiseptic solution
Bloodstream Infection respiratory secretions. or sterile water.
Remove condensate
(CLA-BSI) Prevention
from ventilator circuit
Measures for Neonates (356) frequently.
Hand hygiene before inserting and manipulating lines. Change ventilator circuit
Maximal sterile barriers used during central line insertion. only when visibly soiled or
>0.5% chlorhexidine with alcohol for skin antisepsis before malfunctioning.
insertion (term infants or postgestational age >2 weeb; Disinfect respiratory equip-
otherwise use alcohol). ment before storage.
Keep dressings clean and dry and change (using aseptic technique) Daily review of need for me-
every 7 days (transparent dressings), or every !i days (gauze chanical ventilation and
dressings), or when damp, loose, or visibly soiled. extubate as soon as no
Scrub the needleless connector (cap) with a disinfectant before longer needed.
accessing central lines. Educate caregivers about VAP
Minimize line accesses. prevention and provide
Daily review of need for central line and removal as soon as no VAP rates to clinical staff.
longer needed.
Educate caregivers on CLA-BSI prevention and provide CLA-BSI "Recommended in the IHI Pediatric Supplement on VAP
rates to clinical staff. prevention.
for this indication. However, there are several reports of the

TABLE 26.7 Catheter-Associated Urinary successful use of palivizumab administration to all infants in an
Trac:t Infec:tion (CA-UTI) NICU (in addition to other infection control measures) during
Prevention Measures for an RSV outbreak (317,318). It is important to note that RSV
Neonates (358) transmission can be well-controlled by following contact precau-
Iruert urinary catheter using a..eptic technique. tions, screening visitors, and cohorting infants (233).
Hand hygiene before manipulation of urinary catheter. Varicella-zoster immune globulin (VZIG) has not been pro-
Maintain a closed drainage sy5tem. duced by a US manufacturer since 2004. However, VariZIGTM
Daily review of need for urinary catheter and removal as soon (Cangene Corp., Winnepeg, Canada), which was approved by
as no longer needed. the FDA in December 2012, is indicated for susceptible high-
Educate caregivers about CA-UI'I prevention and provide CA-UTI risk individuals exposed to varicella (319). Mter an exposure
rates to clinical staff.
in the NICU, VariZIG may be administered within 96 hours of
exposure to premature infants of >28 weeks gestation whose
mothers have no prior history of varicella or varicella immu-
nization and to all premature infants of <28 weeks gestation
CA-UTI rates tend to be lower in pretenn infants than in or :s1,000 g birth weight regardless of maternal history due
other critically ill patient populations. No pediatric-specific to lack of placental transfer of antibody in earlier stages of
CA-UTI prevention bundle has been developed, and no re- pregnancy (319,320). Most premature infants of 2:28 weeks
search studies have been published to elucidate best practices gestation whose mothers are immune have acquired sufficient
for CA-UTI prevention in neonates. However, the basic prin- maternal antibody to protect them from severe disease and
ciples of CA-UTI prevention in adults have been adopted for complications. However, chronologie age of >2 months and
use in the NICU (Table 26. 7). The duration of catheterization seven or more transfusions of packed red cells can be associ-
is the most important risk factor for CA-UTI, and prevention ef- ated with increased rates of seronegativity in infants whose
forts should focus on minimizing catheterization and removing mothers are immune (321). VariZIG is not recommended for
indwelling urinary catheters as soon as possible. healthy, term infants postnatally exposed even if their moth-
ers have a negative history of varicella. Before administrating
VariZIG in a nursery exposure, obtaining serum from the in-
IMMUNOPROPHYLAXIS AND VACCINATION
fants to confirm susceptibility is helpful. If antibody determina-
The administration ofboth standard MG preparations (39-41) tions are available within 72 hours of the exposure, VariZIG
and high-titer staphylococcal immunoglobulin products ( 43-45) administration can be delayed until results are available. If an-
either to treat or prevent neonatal sepsis has not been effica- tibody is present, the infant does not require isolation during
cious, even when serum IgG levels are maintained at >400 mg the 10 to 28 days after exposure. VariZIG is not indicated if an
per deciliter. The largest multicenter, controlled nial, which infant has received an infusion of MG for other indications
enrolled 2,416 infants, reported lot-to-lot variation in antibody within the previous 3 weeks. If VariZIG is not available, MG
profile despite the use of thousands of donors for processing can be used instead (320).
each batch of MG (41). In contrast, palivizumab, a humanized It is prudent to provide influenza vaccine to visiting family
mouse monoclonal antibody that neutralizes RSV and prevents members to protect them and the infants in the NICU (234).
viral binding to cells, is recommended for monthly intramuscu- Making influenza vaccine available for parents of NICU pa-
lar injection during the RSV season for high-risk preterm infants tients also improves HCW vaccination rates (322). The NICU
to prevent severe disease and RSV-related hospitalizations (312). also provides an excellent opportunity to counsel adolescent
Targeted groups of neonates include (a) infants with hemody- and adult family members about the importance of receiving
namically significant congenital heart disease, chronic lung dis- Tdap to protect their own infants and others in the NICU and
ease of prematurity, or birth before 32 weeks gestation and (b) to provide it to them (199).
infants born at 32 to 35 weeks gestation with at least one risk Live-attenuated rotavirus vaccines are now part of the rou-
factor for RSV-associated hospitalization (either child care atten- tine immunization series for infants. Vaccine strains of rotavirus
dance or other children under 5 years living in the household). are shed in the stools of premature infants after the first vac-
Although efficacy and safety have been demonstrated, cost- cine dose (323), creating the theoretical possibility of horizon-
effectiveness has not; therefore, targeting only those for whom tal transmission if the vaccine were administered in the NICU.
efficacy has been shown is important (313). The development of The AAP recommends that age-eligible infants should receive
motavizumab, an RSV-specific monoclonal antibody with higher the vaccine at discharge from the NICU or nursery, and that
binding affinity for fusion protein than palivizumab, was discon- if an immunized infant requires readmission to the NICU or
tinued as a potential prophylactic agent because the product had nursery within 2 weeks after vaccination, contact precautions
similar efficacy to palivizumab but was associated with increased should be used for 2 to 3 weeks postvaccination (324).
rates of cutaneous adverse events (314,315).
A single dose of palivizumab is recommended for hospital-
CHEMOPROPHYLAXIS
ized high-risk neonates at the time of discharge during the RSV
season. However, because very premature infants do not sustain Maternal screening and chemoprophylaxis have dramatically
protective serum concentrations until after the second dose, it reduced the risk of early-onset GBS disease (112). However, the
has been suggested that such infants should receive a dose at use of antibiotics for HAl prevention in the NICU is strongly
1 month before discharge from the NICU in addition to the discouraged because of the risk of the emergence of resistant
dose at discharge (316). The use of palivizumab to control an microorganisms that will require more broad-spectrum and
RSV outbreak has not been studied and it is not recommended potentially more toxic antimicrobial agents for treatment. TWo
groups of investigators have reported the efficacy of low-dose of neonatologists, only 34% of 219 respondents reported that
vancomycin, 25 ,.,g/mL of total parenteral nutrition fluid, to they use antifungal prophylaxis, and concern about resistance
decrease catheter colonization and BSI caused by CONS. In two was one of the most important fuctors cited as influencing their
different, prospective, randomized, controlled trials of 70 and decision (342). Evidence-based practices relating to manage-
150 VLBW infants, CONS-BSI was decreased in infunts weigh- ment of eves and prudent use of antimicrobials may be more
ing <1,500 g from 34% to 1.4%, respectively, and in infants likely to be long-term safe and effective measures than the use
weighing <1,000 g from 26% to 2.8%, respectively (325,326). of an antifungal agent for prophylaxis.
Despite the beneficial effect, neither set of investigators nor an
accompanying editorial recommends the routine use of this
ANTIMICROBIAL STEWARDSHIP
regimen because of the risk of the emergence of vancomycin-
resistant organisms (327). Continued exposure of the normal Antimicrobial stewardship is a key component of the effort to re-
flora to low concentrations of vancomycin creates especially fa- duce the emergence of antibiotic resistance in hospital settings.
vorable conditions for resistance to occur. In addition, morbid- Hospitals may use strategies such as prospective audit of antibi-
ity and mortality associated with CONS infection is not severe otic use with intervention and feedback to providers, formulary
enough to justify the risks. In another randomized study of 148 restriction and preauthorization, and education to improve
infants weighing <1,500 g with percutaneous eves, the use antimicrobial utilization (343). General principles to improve
of amoxicillin 100 mg/kg/ day intravenously in three divided antibiotic use are applicable to the NICU (344). A multicenter
doses had a negligible effect on the incidence of septicemia observational study of antibiotic use in four NICUs found that
because the rate in the control group was so low (2.7%) (328). 24% of antibiotic-da}'5 were nonadherent to the CDC 12-step
In conclusion, strict adherence to the recommended bundled campaign to prevent antimicrobial resistance; carbapenems
practices for eve insertion and maintenance remains the pre- and vancomycin were the agents with the highest proportion
ferred method of prevention of CLA-BSI. of inappropriate days (345). Electronic data from 56 NICUs re-
More controversial is the role of fluconazole for prophylaxis vealed a large inter-NICU variation in the proportion ofinfunts
of invasive candidiasis in the high-risk VLBW infant. Many stud- receiving vancomycin (346). The importance of antibiotic use
ies of fluconazole prophylaxis have been published (329-336), in selecting multidrug-resistant strains of GNB in the NICU has
and the results and cautions to neonatologists are best summa- been well-documented for aminoglycosides (291,292) and for
rized in editorials by Long and Stevens (218) and by Fanaroff third-generation cephalosporins (51,259,260). Monitoring for
(329). Published studies of fluconazole prophylaxis have dem- the development of resistance to the first-line aminoglycoside,
onstrated wide center-to<enter variation in the rates of inva- usually gentamicin or tobramycin, is helpful to guide changes
sive candidiasis before initiating prophylaxis, have targeted in antibiotic-prescribing patterns. In the absence of multidrug-
VLBW infants <1,500 g and ELBW infants <1,000 g and/or resistant strains, amikacin, third-generation cephalosporins,
gestational age <30 or 32 weeks, and have administered flu- and meropenem are best reserved for rare individuals whose
conazole (a) daily for the first 30 days of life, (b) daily dur- infection is resistant to routine treatment regimens. A survey
ing periods of administration of antibiotics for >3 days (334), of NICU clinicians using clinical vignettes revealed substantial
(c) every third day for 2 weeks followed by every other day for variation in antibiotic-prescribing practices and less familiarity
2 weeks and then daily for 2 weeks (330,331), (d) twice weekly with the appropriate use of agents to treat GNB and anaerobic
for 6 weeks (330), (e) every third day for 1 week followed by infections, suggesting a need for more education of NICU pro-
daily for 3 weeks (332,333,335), or (f) every third day for 4 viders about antibiotic use (347).
to 6 weeks (336). All studies have been single-center studies,
and most have been pre-post intervention studies. 1Wo small,
VISITATION AND FAMILY-CENTERED CARE
prospective, randomized placebo-controlled studies were pub-
lished in 2001 (337,338); the more recent prospective, random- Most pediatric hospitals now embrace the concept of family-
ized, double-blind clinical trial compared two different dosing centered care. However, because the acquisition of a seemingly
schedules but did not have a control group (330). In 2007, a innocuous viral infection in high-risk neonates can result in se-
Cochrane S}'5tematic review and meta-analysis on this topic was rious life-threatening disease and unnecessary evaluation and
published (339) and concluded that fluconazole prophylaxis empirical therapy for septicemia, special visitation policies are
does prevent invasive fungal infection (composed primarily required in nurseries and NICUs. All visitors with signs or symp-
of Candida spp. BSis) in ELBW infunts, but does not reduce toms of respiratory or gastrointestinal tract infection should
in-hospital mortality. There are limited data on long-term de- be restricted from visiting any patient in healthcare facilities.
velopmental outcomes of infants exposed to this therapy, but During the influenza season, it is preferred that all visitors have
one small study compared 21 children who had received flu- received influenza vaccine. Increased restrictions could be
conazole prophylaxis in the NICU with 17 placebo recipients needed in the midst of a community outbreak (e.g., RSV, noro-
and found no differences in neurodevelopment or quality virus, influenza). For infants requiring contact precautions,
of life at 8 to 10 years of age (340). One persistent concern the use of PPE by visitors is determined by the nature of the
about prophylaxis has been the potential for the emergence interaction with the patient and the likelihood that the visitor
of Candida strains that are resistant to fluconazole. Although will frequent common areas in the nursery or NICU or inter-
several studies of fluconazole prophylaxis of high-risk neonates act with other infunts' family members. Although the neona-
have not found emergence of resistance during multiple years tology staff generally encourage visits by siblings in the NICU,
of use (205,333), one report described the emergence of flu- the medical risk must not outweigh the psychosocial benefit.
conazole-resistant subclones of a single strain of C. parapsilosis Studies demonstrate that parents favorably regard sibling visita-
that was a major cause of candidemia during a 12-year period tion (348) and that bacterial colonization (349,350) or subse-
when fluconazole prophylaxis was used (341). In a 2006 survey quent infection (351) does not increase in the neonate who has
been visited by siblings, but these studies are limited by small gastrointestinal, or mucocutaneous infections must be made
numbers. Snict guidelines for sibling visitation should be estab- on an individual basis. Removal of all individuals with mild ill-
lished and enforced to maximize visitation opportunities and nesses could be impractical in an overcrowded, understaffed
minimize risks of transmission of infectious agents. The follow- nursery. Therefore, specific instructions concerning precau-
ing visitation recommendations can guide policy development: tions to prevent transmission of infection to patients must be
given. Individuals with pertussis, active TB, varicella, exudative
1. Sibling visitation should be encouraged in the well-child skin lesions, or weeping dermatitis must be removed from di-
nursery and NICU. rect patient contact until they are no longer infectious. HCWs
2. Before visitation, a trained staff member or nurse should with herpes labialis ("cold sores") are no longer excluded from
interview parents concerning the current health status of the nursery because the transmission risk is so low. Such indi-
siblings. Siblings who are visiting should have received all viduals are instructed to cover the lesions, not to touch the area
vaccines recommended for their age. Children with fever surrounding the lesions, carefully observe hand hygiene pro-
or symptoms of an acute illness, such as upper respiratory cedures, and not to kiss or cuddle neonates under their care.
tract infection, gastroenteritis, and dermatitis, should not The role of oral acyclovir is not established but its use decreases
be allowed to visit. Siblings who have been exposed to a the quantity and duration of viral shedding in treated indi-
known communicable disease and are still within the in- viduals. HCWs with herpetic whitlow must be restricted from
cubation period should not be allowed to visit. Mter the contact with neonates until the lesions are completely crusted.
interview, the staff member or nurse should place a written HCWs who are known to be infected with HIV, HBV, or HCV
consent for sibling visitation in the permanent patient re- are managed and counseled individually according to available
cord and provide a name tag for the sibling indicating that guidelines (355) . Percutaneous and mucocutaneous exposures
he or she has been approved for visitation for that day. to blood-borne pathogens are managed according to standard
3. Asymptomatic siblings who recently have been exposed to protocols.
varicella but have been immunized can be assumed to be In the nursery, there has been much concern about the
immune. exposure of pregnant HCWs to neonates with congenital in-
4. The visiting sibling should visit only his or her sibling fections, especially CMV (244). Frequently, the most anxiety
and should not be allowed in playrooms with groups of is generated over infections that pose the least risk. Several
patients. epidemiologic studies in hospitals and day care centers have
5. Visitation should be limited to periods of time that ensure established that nursery providers do not have an increased
adequate screening, observation, and monitoring of visi- risk of acquiring CMV from their patients and that exposure to
tors by medical and nursing staffs. toddlers in child care centers is associated with a significantly
6. Children should observe hand hygiene before and after higher risk of seroconversion (242-244) . Therefore, pregnant
contact with the patient. women are not restricted from caring for infants who are iden-
7. During the entire visit, sibling activity should be supervised tified as infected with CMV. All female HCWs in the childbear-
by parents or a responsible adult. ing age group must be taught to adhere strictly to standard
precautions, especially hand hygiene and the use of gloves
when contact with urine, saliva, or blood is likely.
OCCUPATIONAL AND EMPLOYEE HEALTH
All HCWs in the nursery and NICU must be immune to vaccine-
preventable diseases. All nursery staff should be screened by his- REFERENCES
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Joan Blanchard and Sharon Giarrizzo-Wtlson
The Perioperative Suite

INTRODUCTION evaluation of the severity of systemic diseases, physiologic dys-
function, and anatomic abnormalities (11).
The perioperative setting remains a high risk area for the
patient and the sw:gical team. In 2008, there were 300,000
Surgical Site Infections (SSI) reported; this was 17% of all
WOUND CLASSIFICATION
healthcare-associated infections (liAis), second only to urinary
Wo~d claasification sh~uld be documented by the circulating
tract infections (UTh) (1). Two percent to 5% of all patients
regtstered nurse at the Ume of the surgical procedure to assist
~aving surgery develo~ed SSlJ. There is a 2 to 11 times higher
in determining the state of the wound (12), in coordination
ruk of death for a patient developing an SSI compared to pa-
with the surgeon performing the procedure. Table 27.2 is an
tient:J who do not develop an SSI (2,3). Seventy five percent
adaption of BP Simmons' original wound classifications.
of deaths in patient:J with SSis wiU be attributed to the SSI
Keep in mind, a break in aseptic technique in a Class1/Clean
(4}. Long tenn disabilities account for morbidity (5). An SSI
procedure does not become Class ll/Clean contaminated,
result:J in 7 to 10 additional postoperative hospital days. The
Class ill/contaminated, or a Class IV Dirty-infected procedure.
cost ranges &:om $3,000 to $29,000 depending on the surgical
To become a SSI, there would have to have been an inocula-
procedure and the pathogen identified (6,7). This is an over.ill
tion with a pathogen (Table 27.3) that may cause an infection
approximate cost of$10 billion annually (8,3,9).
within 30 days following the surgical procedure or within a year
Stronger coUaborati.ve bonds need to be forged between
if an implant has been inserted. The break in aseptic technique
regulatory and recommending agencies that have influence
should be reported in an occurrence/incident form which
on patient care or give direct patient contact. The agencies
should alert the Infection Preventionist and Risk Manager that
that ~ most closely related to the patients care in the peri-
the patient should be monitored for a possible SSI following
operauve area are the Association of periOperative Regilltered
Nurses (AORN), American Society of PeriA:nesthesia Nurses the break in aseptic technique.
(ASPAN), American CoUege of Surgeons (ACS), American
Society of Anesthesiologists (ASA), Association of Surgical SURGICAL SITE INFECTION TOOLKIT
Technologist:J (AST), .Association for the Healthcare Environ-
ment (AHE), Association for Prof'e.uionals in Infection Con- The SSI Toolkit is available through the CDC and may be ofassis-
trol and Epidemiology, Inc. (APIC), the Society for Healthcare tance in wortcing with SSI information. The Tholkit is available
Epidemiology of America (SHEA), the Centen for Disease at http://www.cdc.gov/HAl/pdfs/toolkits/SSI_tootkit021 '710
Control and Prevention (CDC), the American Society for SIBT_revised.pdf. Note: The findings and conclusions pre-
Healthcare Engineers (ASHE), the Centers for Medicare/ sented in the SSI Toolkit are those of the authors and do not
Medicaid Services (CMS), The Joint Collllilis&ion (1JC), and necessarily represent the views of the CDC.
the American Hospital .Association (.AHA).
TABLE 27.1 'Ib.c .Am.crican Society of

SURGICAL SITE INFECTION .Anestheaiologist Physial
RISK STRATIFICATION Status Classification System
Statu8 Defillitioa of Patient Condition
Stratification is the grouping together of patients at similar
risk of acquiring a SSI, which allows hospitals to compare their A normal healthy patient
data with other hospitals or compare one surgeon and another D A patient with mUd l)'ltemic dbease
surgeon (10). m A patient with aevere syatemic diaeue
IV A patient with aevere syatemic diaeue that is a
comtant threat to life
v A moribund patient who is not expected to aunive
ANESTHESIA without the aUIJical procedure
VI A declared lmlin~ead patient whoae orpm are
being removed for donor purpoaes
The American Society of Anesthesiologist Phyaical Status Clas-
sification System (Table 27.1) is used to detennine the patient's Used with permillion from the American Society of AneathesiologUill.
phy.Jiologic condition at the time of surgery. It provides an
417
are additional modifiable risk factors, such as excessive OR

TABLE 27.2 Wound Classification traffic, inadequate wound dressing protocol, improper glucose
(13,14,4) control, colonization with preexisting microorganisms, and in-
Cbus 1/Clean; Clean wound. are uninfected surgical wound. adequate intraoperative oxygen levels (17).
with no inflammation noted; the respiratory, alimentary, Prevention strategies for SS!s include core intraoperative
genital, or uninfected urinary tract is not entered. Surgical measures, such as keeping OR doors closed during surgery
wounds that follow nonpenetrating (blunt) trauma should be except as needed for passage of equipment, personnel, and the
included if they meet the criteria. patient (4). Supplemental preoperative prevention strategies
Class IT/Clean contaminated; A surgical wound in which the are nasal screening and decolonization of Staphylococcus au1'1!'US
respiratory, alimentary, genital, or urinary tract are entered carriers undergoing elective cardiac and other implant surgi-
under controlled conditions and without unusual contamina-
cal procedures (i.e., orthopedic, neurosurgery procedures with
tion. Operations involving the biliary tract, appendix, vagina,
and oropharynx are included if there is no evidence of infec-
implants) with preoperative intranasal mupirocin, possibly plus
tion or major break in technique. chlorhexidine bathing therapy (18,19). Screening preoperative
Class ill/Contaminated; Contaminated wounds include open, blood glucose levels and maintaining tight glucose control in
fresh, accidental wounds, or wounds resulting in m~or breaks in patients undergoing select elective procedures (e.g., cardiac,
sterile technique or gross spillage from the gastrointestinal tract, arthroplasties, and spinal fusions) should also be done (20) .
and incisions with acute, nonpurulent inflammation is found. Postoperatively, feedback of surgeon-specific SSI rates should
Class IV/Dirty-infected: Old traumatic wounds with retained be shared. The supplemental strategies are not part of 1999
devitalized tissue, tissue with an existing clinical infection or Healthcare Infection Control Practices Advisory Committee
perforated viscera. MicroorganislllS' may have been present (HICPAC) Guideline for Prevention of SSis (17).
in the operative site prior to the surgical procedure.
PREVALENCE OF RESISTANT PATHOGENS

In 2010, a national prevalence survey of methicillin-resis-
TABLE 27.3 Organisms Causing Smgical tant S. au1'1!'US (MRSA) was repeated in the inpatient setting.
Site Infection, January 2006 This survey was conducted with 590 health care facilities
to October 2007, CDC responding; both colonization and infection information was
National Healthcare Safety requested. The previous MRSA survey was done in 2006. The
Network 2010 survey showed a reverse from the 2006 survey findings.
In 2006, MRSA-infected patients were 34 per 1,000 patients,
S14phy/Qroccus au1!1US 30% and MRSA-<:olonized patients were 12 per 1,000 patients; in
Coagulase-negative staphylococci 15%
EnltmJcoccus spp. 12% 2010, MRSA-infected patients were 25.3 per 1,000 patients and
Eschnichia coli 10% MRSA-colonized patients were 41.1 per 1,000. This may be
Pseudomonas aeruginosa 8% partially due to more respondents performing active surveil-
EntmJbacter spp. 5% lance testing, and the method of testing was a quicker detec-
KleiJsieUa pneumonia 6% tion of MRSA-colonized patients. MRSA-colonization increases
Candida spp. 11% the risk of MRSA infection and the risk of cross-transmission to
K/8bsiella wytoca 2%
Ad'lldobacter baumannii 3% other patients and the environment (21). Rapid testing results
N= 7,025 (15,16) may decrease the need for early preemptive isolation, shorten
the isolation protocol when needed, and prevent the MRSA-
positive patient's environment contamination with resultant
risk of cross-contamination (22,23) .
PATHOGEN SOURCES OF SURGICAL
SITE INFECTIONS PATIENT POPULATIONS Kf GREATEST RISK
OF DEVELOPING A SURGICAL SITE INFECTION
Sources of SSis are from endogenous sources; patient flora,
skin, mucous membranes, and the gastrointestinal tract; Individuals at risk for developing an SSI include persons who
exogenous sources ofSSis are from the surgical personnel (i.e., have diabetes (24,25), are aged (26-33), are obese (24,34,35),
surgeon and team), soiled attire, breaks in aseptic technique, are malnourished (34,36), or are smokers (24,25).
inadequate hand hygiene, the operating room (OR) physical Persons also at risk for a SSI may be patients who have had
environment and ventilation, instrumentation, equipment, ma- hair removal at the surgical site with a razor (37), have micro-
terials brought to the operative field, and seeding from a dis- bial colonization (38,39), do not have appropriate skin antisep-
tant focus of infection (17). sis before the surgical procedure ( 4Q-43), have a drain placed
during surgery (44,45), have prolonged duration of surgery
(25,35), or have a remote infection before surgery (46-52).
EPIDEMIOLOGY
Emerging challenges in detecting SSis are a lack of standard-
MODES OF TRANSMISSION
ized methods for postdischarge/outpatient surveillance,
increasing numbers of outpatient surgeries, and shorter post- Contact, droplet, and airborne are the three modes of trans-
operative inpatient stays. With antimicrobial prophylaxis, there mission. Some organisms may be transmitted by more than one
is an increasing trend toward resistant organisms which may un- route, both airborne and contact routes depending on the dif-
dermine the effectiveness of existing recommendations. There ferent stages of the disease (53) .
Ckapter27 • ThePtrioperativeSuite 419
NATIONAL HEALTHCARE SAFETY must then be able to survive long enough to be transferred to
NETWORK SURGICAL SITE the HCP's hands when the inanimate objects are touched. The
INFECTIONS EVENT HCP hand hygiene must then be skipped or done poorly, and
then, the HCP's contaminated hands must come in direct con-
A surveillance program includes: the use of epidemiologically- tact with another patient or an inanimate object that will come
sound infection definitions, effective surveillance methods, in contact with the patient (57,58,53).
stratification of SSI rates based on risk factors associated with In reviewing other areas where hand hygiene concerns were
the SSI development, and data feedback ( 54,55). found, there is a very good possibility that during the practice of
A CDC National Healthcare Safety Network (NHSN) anesthesia the rapid pace of providing patient care and frequent
operative procedure is an inpatient or outpatient in which contact with sources that are contaminated, bacterial transmis-
the procedure is done during an operation, in an OR by a sion may occur. Studies conducted by Loftus and Koff have
surgeon, making at least one incision through skin, mucous shown that the anesthesia work space can become contaminated
membrane, including a laparoscopic approach, and closing within 4 minutes of patient care with pathogens that can poten-
the incision before the patient exits the operating room. Note: tially cause HAis; most likely as a result of anesthesia care provid-
If the skin incision edges do not meet (e.g., drains, wires, or
er's contaminated hands or gloves. Sterile intravenous stopcocks
other extrusions from the wound) at the end of an operative were cultured aseptically at baseline and at procedure comple-
procedure, the wound is not considered a primary closure, and tion at two sites in the anesthesia work area. The conclusion was
is therefore not considered an NHSN operative procedure, and transmission of pathogenic bacteria to the anesthesia work area
any procedure-associated infection is not considered an SSI. and exterior and interior of the stopcocks (59-61).
In a study of nearly 8,000 observations of hand hygiene in
anesthesia care providers, the opportunities averaged 34 to
OPERATING ROOM (OR) 41 per hour. These observations were done over a 4-week pe-
A patient room that meets the Facilities Guidelines Institute's riod using a World Health Organization Tool. The aggregate
(FGI) or the American institute of Architects' (AlA) criteria failure rate was 82% with a range of 64% to 93% by the pro-
for an OR when the room was constructed or renovated (56). vider group. The major categories of failure were preoperative
Included are an OR, GSection room, interventional radiology assessment care from patient-to-patient, before, during, and
room, and a cardiac catheterization lab. after pain management; use of computer keyboard with soiled
hands; placement of intravenous devices and blood draws;
preparation of medications and equipment with soiled hands;
IMPLANT leaving soiled gloves on after airway placement/manipulation
A nonhuman-derived object, material, or tissue which is in- and central and arterial line; and retrieving dropped items on
serted in a patient during an operative procedure. This may the floor and then using the item (62).
include, but is not limited to: porcine or synthetic heart valves,
mechanical heart, metal rods, mesh, sternal wires, screws, PREOPERATIVE SKIN ANTISEPSIS
cement, internal staples, or hemoclips.
Skin antisepsis is done before a surgical procedure to re-
duce the risk of a SSI. The skin has transient and resident
EXCLUDED ARE NONABSORBABLE SUTURES microorganisms; removal of transient microorganisms is more
It is considered as an implant at the site/structures adjacent to easily accomplished than the removal of resident microor-
the implant until it is manipulated for diagnostic or therapeutic ganisms which are more deeply seated and may not be totally
reasons. If an infection results after the manipulation, this removed. Resident microorganisms may be reduced to a sub-
would not be attributed to the operative procedure when the pathogenic level with appropriate skin antisepsis (63).
implant was inserted; the infection would be attributed to the Patients having surgical procedures below the chin should
manipulation. If the infection is considered an NHSN opera- have two showers with chlorhexidine gluconate (CHG) before
tive procedure, then that subsequent procedure can be consid- surgery. Clinical trials found the use of preoperative show-
ered an SSI (54,55). ers reduced microorganisms on the skin, including S. aurnLS
The National Healthcare Safety Network, Patient Safety Com- (64-68).
ponent: Procedure-associated Module is available at http:/I The U.S. Food and Drug Administration (FDA) skin antisep-
www.cdc.govI nhsn/psc_pa.html. tics should be approved or cleared for use in preoperative skin
preparation. The antiseptic chosen should reduce microorgan-
isms in intact skin, have an antimicrobial ingredient that is non-
PREVENTION OF HOSPITAL-ACQUIRED irritating, be broad spectrum, fast acting, and have a residual
effect (69).
INFECTIONS
Precautions should be taken when using surgical antiseptics
which have flammable properties to prevent a surgical fire with
HAND HYGIENE
a resultant patient burn (70). The skin antiseptic should not
Health care personnel (HCP) should recognize that hand touch fabric or be allowed to pool. The skin antiseptic should
hygiene is one of the most important wa}'ll to reduce or stop the be allowed to dry and vapors to dissipate before draping, or
spread of microorganisms which are often associated with the use of electrosurgery, laser, or other heat source (70,71). Skin
transmission of disease. The sequence of transmission involves antiseptics should be thoroughly removed from the skin at the
shedding onto inanimate objects which occurs from a patient's end of the case unless directed by the manufacturer to remain
skin which contains microorganisms. These microorganisms in place (72,73) .
Hair removal is dependent on the site of the surgical inci- Hetul Coperings
sion. If it is not necessary to remove the hair, the hair should be
left in place. If it is necessary to remove the hair at the surgical Head coverings should be disposable or a fabric cap that is
site, it is preferable to use hair clippers and not a razor. Using laundered daily. The head covering should completely cover
a razor or depilatory cream to remove hair may result in abra- the hair (90,91). Human hair can become the source of patho-
sions which increases microbial growth and increases the risk genic bacteria which includes MRSA. Hair left uncovered be-
of a SSI (74-76,37). Use of depilatory cream for hair removal comes a filter and collects bacteria in proportion to its length,
may cause skin reactions which may result in cancellation of the waviness, and oiliness. In one study, it was shown that S. au1ll'US
surgical procedure ( 76). Leaving hair in place for neurosurgical and S. epidermidis have a tendency to colonize hair, skin, and the
procedures has not increased the SSI risk (77,78). Hair removal, nasopharynx (92). An outbreak of group A }-hemolytic strepto-
if necessary, should be done the day of surgery outside of an OR coccus on the scalp of scrub person was identified as the same
or procedure room to prevent contamination of the sterile field. pathogen that occurred in 20 patients who developed SSis.
Using clippers the morning of surgery results in fewer SSis (79). Group A Streptococcus is isolated in only 1% of SSis; an SSI that is
caused by group A Streptococcus can be very severe and difficult
to treat (93). Another study found that washing the hair with
SURGICAL ATTIRE FORNONSCRUBBED a neutral shampoo without an antimicrobial component has
HEALTH CARE PERSONNEL no bactericidal effect on the hair (92) . Head covering design
The U.S. Occupational Safety and Health Administration should contain hair and scalp skin, which would decrease mi-
(OSHA) surgical attire requirements for HCP include the use crobial dispersal. HCP with bald or shaved heads must also
of personal protective equipment (PPE) which must be worn wear a head covering to prevent shedding of skin squames (94).
when there is the possibility of an occupational exposure. Skullcaps do not contain hair at the nape of the neck or in
The PPE is considered appropriate if it prevents blood-borne front of the ears and should not be worn in the perioperative
or other infectious pathogens going through to the skin of suite (95).
the HCP. The PPE includes: protective eyewear, gloves, fluid-
resistant gowns, face shields, and shoe covers (80).
Nonscrubbed HCP surgical attire includes scrub tops and
scrub pants, warm-up jacket, head covering, surgical mask, A surgical mask should be worn whenever sterile supplies are
protective eyewear, gloves as needed, and protective foot- opened (4). HCP are protected from droplets >5 1liil in size
wear. Surgical attire should provide coverage to prevent skin when wearing a surgical mask (54). A single surgical mask
squames from being released into circulating air in an OR. protects the HCP's mouth and nose from blood or body fluid
Researchers found in a prospective study that 100% spun- splashes or splatters and the patient from infectious agents
bound polypropylene was effective in decreasing the bacte- the HCP may have (80,96). A study done to determine the
rial load in the air by 50% compared to surgical cotton attire range of blood splatters during a surgical procedure included
(81). Other researchers found the attire design was not as im- 8,500 members of scrubbed and nonscrubbed surgical teams.
portant as the material (82). Surgical fabrics should be made The researchers found 26% of exposures of blood splatters
of tightly woven, stain-resistant, and durable fabric; the fab- were to the heads and necks of scrubbed personnel, and 17%
ric also should be comfortable to wear as it refers to the fit, of blood exposures were to HCP circulating outside of the ster-
breathability, and the weight of the fabric (83). Cotton fabrics ile field (97).
having a porosity of 80 1liil or greater in size may allow mi- Reports of several episodes of postmyelography meningitis
croorganisms to pass through the interstices of the materials were reported by the CDC and the Infectious Disease Society
weave presenting a concern for contamination (84,85). Surgi- of America (IDSA) . Streptococcal species were identified as
cal attire made of 50% cotton and 50% polyester with 560 X the causative pathogen. Streptococcal species is consistent
395 threads/10 em is an example of a fabric that would reduce with oral-pharyngeal flora. The available data for 7/8 patients
the amount of bacteria that would be shed into the air by two reported found that antiseptic skin preparation and surgical
to five times, with the exception of methicillin-resistant S. epi- gloves were used, but none of the practitioners wore a surgical
dermidis (MRSE) and MRSE-carriers (86). mask (98-101,54). It has been found that face masks limit the
dispersal of oral-pharyngeal droplets, and therefore, wearing
a face mask by practitioners who may be placing a catheter or
injecting material into a spinal or epidural space, warrants their
Warm-up jackets should be worn in the semi-restricted and use (102,53).
restricted areas of the perioperative suite with cuffs down to the Wearing more than one mask (double) may make it diffi-
wrists to prevent shedding and jacket snapped up to prevent cult to breathe and does not increase the filtering capacity of a
contamination of the sterile field (81,86). surgical mask (96). Masks should be tied snugly and cover the
Cotton fleece jackets should not be worn in the OR. This nose to prevent venting, and not allowed to hang down on the
fabric collects lint which may harbor microbial-laden dust, skin uniform; when removing the mask, use the ties and not
squames, and respiratory droplets. Fleece is made up of a napped the filter part of the mask (83).
surface which has low density, which makes it more flamma- A clean mask is used for every procedure. When the mask
ble (87). Cotton fiber is one of the most flammable fibers. One becomes wet, the filtering capacity is compromised and also con-
hundred percent cotton that does not have fire retardant treat- taminated. One study was done to determine whether the micro-
ment does not meet the federal flammability standard (88). bial barrier was intact using a mask with a 95% filtration capacity.
Blending cotton with 10% to 20% polyester could reduce the Masks were studied at 1-, 2-, 3-, and 4-hour intervals. At the
flammability (88), but this is not always successful (89). 4-hour interval, the mask had decreased efficacy. The research
Chapter 27 • The PtrioperativeSuite 421
also showed all counts of colony fornring units (CFUs) were Sterile SurgiCIJI Gowns
lower than 4 X 102 which could still cause an SSI in patients with
diminished immunity, surgical-wound complications (e.g., isch- Sterile surgical gowns are single use or reusable. The gowns
emia), or a patient having an implant placed (102). may be reinforced for better barrier properties which have
additional layers of the same or different fabrication thus pre-
venting the transfer of microorganisms, particulates, and fluids
Protectifle Eyewear to the HCP or sterile field (11g-115).
Protective eyewear must be worn anytime a splash or splat-
ter with blood, body fluids, or other infectious material could Glwes
occur. Protective eyewear includes goggles, face shields, or
full-face respirators (10g,54). Double gloves help prevent SSis and protect HCPs hands from
blood-borne pathogen exposures (116,117,105,80).
Glwes
LAUNDERING OF PERIOPERATIVE TEXTILES
Gloves should be worn when doing a task that requires protec-
tion from blood or bodily fluids as well as when caring for pa- The AORN does not recommend home laundering due to the
tients who are on Contact Precautions (54). The use of gloves lack of monitored quality, consistency, or safety. Home launder-
does not represent a substitute for hand hygiene. There is a ing may not meet the measures required to achieve a decrease
certain percentage of glove perforation from the manufac- in microbial levels in contaminated surgical attire. To achieve
turer or that occurs during surgical procedures. Gloves, before this, the accreditation standards for processing reusable textiles
worn, have a perforation rate of 1% to 4%, after the surgical in health care facility laundries or in a commercial laundry that
procedure the perforations may increase to 1.2% to 53%. The is accredited by The Healthcare Laundry Accreditation Council
incidence of positive hand cultures after glove use and removal (HLAC) should be met (Table 27.4) (118).
ranges from 2.2% to 34% (10~107).
INSTRUMENT CLEANING,
Protectifle Footwear DECONTAMINATION,
Protective footwear must meet OSHA requirements for safety AND STERILIZATION
where there is a danger of foot injury from falling or rolling
objects or objects that can pierce the sole. OSHA regulations Cleaning, decontamination, disinfection, and packaging are all
mandate that employers perform a workplace hazard risk as- components of the sterilization process.
sessment to ensure that HCP wear protective footwear. Hazards
in a perioperative suite are possible and include needlesticks,
scalpel cuts, and splashing from blood or other possibly infec- TABLE 27.4 The Healthcare Laundry
tious materials (108-109,80). Accreditation Council
Fluid-resistant shoe covers are part of protective footwear Standards
which must be worn during procedures in which there is a pos-
sibility of an exposure to blood or other body fluids. In surgi- • Separation of soiled and contaminated textile areas
cal procedures, such as orthopedics, obstetrics (e.g., caesarian • Negative pressure ventilation in soiled areas
sections), and trauma, HCP are required to wear fluid-resistant • Positive pre55ure ventilation in the clean areas
• Gean textiles stored in an area free of vermin, dust, and lint at
shoe covers to prevent transmission of potentially infectious 68·-7s·F (2o·-25.6•C)
microorganisms entering nonintact skin. Shoe covers should • Storage shelves 1 "-2" from the wall, bottom shelf 6"~" from
be removed and placed in hazardous waste at the end of the the floor, top shelf 12"-18" below the ceiling
procedure (80,110). • Hand washing facilities in all soiled textile areas with antiseptic
Shoes should be clean when worn in the perioperative soap dispensers
suite. A study of outdoor shoes and shoes worn only in the • Working surfaces kept clean and disinfected
perioperative suite showed 98% of the outdoor shoes con- • OSHA Exposure Control Plan in place and PPE available for use
taminated with coagulase-negative staphylococci, coliforms, or • Material Safety Data Sheets available for each chemical in use
Bacillus spp. compared to the shoes only worn in the perioper- • Water quality tested for hardne55, alkalinity, iron content, and
pH routinely
ative suite, which had 56% contamination. The floors studied
• Soiled textiles handled, collected, and transported following
in the OR can contribute up to 15% of CFUs, which are dis-
local, state, and federal regulations
persed into the circulating air by walking. Shoes worn only in • Wash loads recorded to include, cycle, prewa.ili, wash, rinse,
the perioperative area may decrease the contamination of the and final rinse times, water levels and usage, temperatures, and
environment (111,112). chemical usage
• Water extraction and drying performed using methods to main-
tain the integrity of the textiles and minimize microbial growth
SURGICAL AITIRE FOR SCRUBBED • Storage of clean textiles packaged in fluid-resistant bundles or
HEALTH CARE PERSONNEL carts and handled as little as po.!5ible
Surgical attire for scrubbed HCP includes a sterile gown, sterile • Transport cart and vehicles kept clean and separate from
gloves, nonsterile mask, and protective eyewear and foot wear. soiled textiles
• Quality control monitoring and proce55es in place
Mask, protective eyewear, and protective footwear are the same
• Personnel training is provided and documented
as the nonscrubbed HCP.
CLEANING INSTRUMENTS AND Other methods of sterilization include the use of ethylene
DECONTAMINATION OF INSTRUMENTS oxide sterilization, low-temperature hydrogen peroxide gas
plasma, low-temperature hydrogen peroxide vapor steriliza-
During the surgical procedure, instrwnent:ll should be wiped to tion, ozone sterilization, dry heat sterilization, and liquid chem-
remove debris and blood to prevent pitting; lumens should be
ical sterilant instrument processing systems (120,121) (see
irrigated to prevent obstruction with residue; and active elec-
Chapter 20).
trode tips should be cleaned frequently to remove eschar which
impedes the flow of the current.
As soon as the procedure is completed, decontamination ENVIRONMENTAL CLEANING
of instrument:ll should begin. All instrument:ll used and unused
Environmental cleaning requires a collaborative effort between
on the field need to be decontaminated. If decontamination environmental services personnel and the perioperative per-
is delayed, an instrument cleaner approved by a manufac-
sonnel. Environmental services equipment should be dedi-
turer is used. During transport of instrument:ll, they must be cated to the perioperative suite to prevent the transmission
contained in a leak-proof container marked with a biohazard
of microorganisms from other areas the equipment has been
label to prevent exposures to HCP (80). If instrument:ll have used (124). Surgical attire is worn when cleaning to protect the
multiple pieces, they are taken apart, and instrwnent:ll are
environmental services personnel and prevent shedding, expo-
then placed in a mesh tray in preparation for decontamina-
sures, or injuries (83,112,80).
tion. The decontamination area is separated from the clean
area by a door to prevent cross-eontamination where clean
items are kept. Decontamination involves cleaning instrument:ll BETWEEN PROCEDURE CLEANING
with cold running water to remove gross debris, then manual
Booms and spotlight:ll are cleaned at the beginning of the day
or mechanical cleaning through an ultrasonic cleaner, washer and as needed. All horizontal surfaces are cleaned at the be-
decontaminators/disinfectors, or washer sterilizers is done.
ginning of the day and during room turnovers (4). An U.S.
After any of these methods are complete, visual inspection is Environmental Protection Agency (EPA)-registered germicide
performed to determine if cleanliness has been achieved. PPE
should be used that has a claim for elimination of Human
must be worn to prevent blood-borne pathogen exposures: hnmunodeficiency Virus (HIV) and Hepatitis B virus. Alco-
head covering, gown/apron, gloves, and eyewear (80).
hol should not be used as a disinfectant. Spray bottles should
not be used to spray disinfectant (125,126). Microfiber cloths
PACKAGING should be used for damp dusting and cleaning ( 120).
Packing should be done to promote sterilization of the instru- Floors need to be kept clean to prevent dust and debris
mentation. Following the manufacturer's guideline will ensure build-up. The OR should be cleaned after every procedure;
the packaging used is appropriate for the type of sterilization cleaning cannot begin until the patient has been moved out
that will be used (119). The shelf life of a sterile package should of the room. The OR table needs to be unlocked and moved
be considered event related-any compromise of the package to mop. A clean mop head should be used between every pro-
should deem it unsterile which includes: seal breakage or loss cedure, preferably a microfiber mop head (120,125,126). The
of package integrity, moisture penetration, or exposure to air- AHE perioperative checklist for cleaning an OR should be
borne contamination (119). followed (125).
Ultraviolet use in the OR may be limited not only due to
time constraints of rapid room turnover requirement:ll, but also
STERILIZATION
the required surface cleaning that has to precede the use of
Sterilization is the gold standard for killing microorganisms ultraviolet surface disinfection ( 120,127).
that could cause disease. Saturated steam under pressure is the Care should be given to the cleaning and disinfection
sterilization method of choice. It is reliable, consistent, and en- technologies incorporated into the perioperative environment.
sures lethality, besides being inexpensive and has a fairly quick Concerns of microbial transmission related to the presence
process for most porous and nonporous materials (120). of clinical technology are long-standing and can be mitigated
Monitoring the sterilization process includes the use of through effective removal of surface contaminant:ll (128-131).
physical monitors: printouts, digital readings, graphs, gauges, Fluid sensitive electronic devices should be cleaned using a
chemical and biological indicators which are used to ensure the hospital grade disinfectant approved by the manufacturer of
sterilization parameters are met. Documentation of the cycles the device (126). Mobile technologies brought into the surgi-
and monitoring result:ll should be logged which enables track- cal or procedural environment should also be included in rou-
ing of processed items, especially immediate-use steam steril- tine cleaning and disinfection practices to prevent transmission
ization items (121-123). hnmediate-use sterilization should be of microorganisms between patients and clinical care areas
used only in certain clinical situations and follow a prescribed (132-134).
protocol (123).
Manufacturers of autoclaves today have differing cycle times
TERMINAL CLEANING
as well as the use of single wrappers or immediate-use containers
as opposed to unwrapped items. The term "flash sterilization• is Terminal cleaning and disinfection is done at the end of the
no longer in use as it no longer describes different steam ster- scheduled procedures and should be done whether the room
ilization processes for items that are not being stored for later has been used or not. Education should be provided for new
use (121). Immediate use should only be used when the need hires on expectations for terminally cleaning ORs. Reviews are
for the item is immediate, and there is no sufficient time for the done on an on-going basis as new techniques are put in place
preferred method of sterilization (121). or new cleaning products are introduced. There should be a
feedback loop for clarifications, if needed, and support for 25 to 35 cubic feet per minute per square foot (140,57). Con-
the work that is being done. It includes an overview of infec- centration of supply diffusers needs to have the airflow pat-
tion prevention and control, review of the terminal cleaning tern over the patient and surgical team, to be effective (143).
checklist and expectations (135,136), and demonstrations of Ultraviolet light air cleaning in ORs may not be appropriate
the cleaning process for new equipment or equipment which where air exchanges are well above 4 to 6 air exchanges an
has sensitive electronics. A review of steps the environmental hour or in well-designed isolation rooms (144).
services personnel should follow to complete the task should
be done, emphasizing the supervisors availability for clarifi- SINKS
cation. Tenninal cleaning should be monitored. Explanation
of the use of fluorescent gel markers that are used to test/ Individual handwashing sink bowl design should have a slope
monitor the cleaning process should be given. Reinforce the where water coming from the faucet should full to prevent
important role that environmental services personnel provide splashes. This prevents contamination of adjacent surfaces.
for patient safety, and provide on-going education and feed- The sinks should be convenient and accessible, have sensor-
back (126-138). regulated water fixtures or faucets that can be managed with-
Monitoring of terminal cleaning can be accomplished by out contaminating hands (57) . Towel dispensers designed to
each step or in combination by precleaning contamination of be hands-free or dispensers that prevent recontamination of
objects which is done to determine and evaluate the cleaning hands should be provided (146). The scrub sink should be
practices (139). Unobtrusive observation allows for an objective adjacent to the ORs (57). The sink water temperature should
assessment of the cleaning process being done by environmen- be adjustable. A study of water temperatures at 4 •c, 20•c, and
tal services personnel (136). Fluorescent markers can be used 40•c, found that higher temperatures could be associated with
to determine thoroughness of cleaning (138). These mark- skin irritation which can cause skin damage (147).
ers are becoming a routine method for determining the ad-
equacy of cleanliness in health care settings. Cultures obtained FLOORS
by swabbing may be useful for tracking epidemiology of HAI
pathogens in an outbreak, but are not recommended for rou- Floors need to be easily cleaned, devoid of waxing or strip-
tine use (136,139). Agar slide cultures allow for quantitative ping, and be environmentally compatible. Flooring should be
culture of liquids by quantifYing aerobic culture counts per mildew-resistant and have cove fittings from the floor to the
centimeter (135,136,139). wall to prevent water seepage and an increased possibility of
Adenosine triphosphate (ATP) bioluminescence measures the growth of mold (57).
organic ATP on surfaces with the use of a luciferase assay and
luminometer. A special swab is used to sample the surface; swab TRAFFIC PATTERNS
contents are then analyzed using the luminometer which shows
Maintaining positive pressure in ORs is a key element to pre-
microbial and nonmicrobial amount of ATP (139).
venting SSis. Memarzadeh recommends 15 to 20 air exchanges
per hour (ACH) with all fresh air filtrated, as well as keep-
ing temperature and humidity levels within accepted ranges
OPERATING ROOM (Table 27.5) (148).
ENVIRONMENTAL DESIGN
There is an increasing concern for HAis when construction/ TABLE 27.5 Temperature/Humidity/Air
renovation in a perioperative suite is planned and the way it
:&changes
will be executed. The infection control risk assessment (ICRA)
grew out of these concerns. The purpose of the ICRA is to plan Function of Space Operating Room
and manage infection prevention and control before, during,
and after the building phase (140,141). The ICRA recommen- Room temperature 68-75
dations also must provide design components that address its Humidity 20%-60%g
long-range use for infection prevention and how infection con- Exchange per hour 20
trol risk mitigation can be applied in the short-term to projects Pressure relatioruhip to other areas Positive
and the commissioning processes (140,57). Exchange outdoor air per hour 4
There are risks of transmission which can be caused by
Facility Guideline Institute. Guidelines for Dttsignot«J. Cunstruction
Aspergillus spp. outbreaks; a dose of only 1 colony forming
ofHtKJlth CareFruililies. 2010 ed. Chicago, IL; American Society of
unit/m!l is required for an immunocompromised patient to
Healthcare Engineering of the American Hospital Association.
acquire an infection. Several other pathogens can be transmit- Available from; http:/ / www.fgiguidelines.org. AccessedJuly 14, 2012.
ted during construction/renovation; these are Bacillus spp., "The Centers for Medicare & Medicaid Services (CMS) are con-
Legionella, other fungi, Scedosporium, Histoplasma, Mucorales sidering changing the low-end of the humidity range from 35% to
spp. (e.g., Rhir.opus spp.), and molds such as Fusarium spp. and 20%. The 35% CMS uaed was based on the reduction of static
Penicillium spp. (142,143,126). discharge and possible flammable anesthetics by the National
Fire Protection AMociation 99. The American Society of Heating,
Refrigerating and Air-Conditioning Engineers (ASHRAE) now
VENTILATION require at least 20% humidity. Until CMS changes the lower range
to 20%, hospitals with CMS certification are required to provide
OR ventilation systems should be designed with primary non-
humidity leveh at a minimum of :55%. Available at: http://www.
aspirating supply diffusers with airflow in one direction that
ashe.org/advocacy/ advisories/ 2012/ pdf5/ cms-humidity120118.pdf
moves air vertically downward with the average velocity being
Keeping doors closed is important in maintaining positive MONITORING INCIDENCE

pressure in ORs (4). OF PERIOPERATIVE INFECTIONS
SURGICAL CARE IMPROVEMENT PROJECT
MEDICAL WASTE Efforts to reduce SSis and improve patient outcomes are a
primary focus for the Centers for Medicare & Medicaid Ser-
Waste in the perioperative suite includes, but is not limited
vices ( CMS}. Collectively with the CDC, "!]C, and 16 additional
to, materials contaminated with blood or other potentially
organizations, the CMS initiated the Surgical Infection Preven-
infectious material, paper, sharps, glass, plastics, cleaning ma-
tion Project (SIP} in 2002 as part of a national public health
terials, medical devices, and radioactive devices. Appropriate
strategy to reduce antimicrobial resistance (155-156). The SIP
protocols for waste management will prevent exposures to
project culminated in the Surgical Care hnprovement Project
personnel from infectious material (149). The World Health
Organization estimates that over 21 million infections of hepa- (SCIP) collaborative and remains an active component of the
CMS national health care quality improvement plan (157-160).
titis Band C viruses and HIV occur annually due to unsafe in-
jection practices involving reuse of syringes and needles that The SCIP collaborative is a national quality partnership of or-
ganizations committed to improving surgical patient care using
are not sterile (150).
evidence-based practice recommendations, and when imple-
mented into system-wide models of care, contributes to a de-
REDUCE, REUSE, AND RECYCLE crease in SSI-related complications (158-161). Initial studies
conducted on the work of the SCIP collaborative identified:
Red'U&e
Analyzing material usage may result in decreasing waste accord- 1. 31% drop in mortality in surgical procedures by the Veter-
ing to Health Care Without Harm (150). ans Health Administration (158,162),
2. 44% decrease in device-associated and SSI rates by hospi-
tals using the CDC's NNIS system (158,163),
3. 27% reduction in SSis at 56 hospitals reporting through
The reusable products may offer a method to minimize waste. a collaborative of Quality Improvement Organizations
Determine if single-use devices cannot be cleaned, or if sterility (158,164).
of a postprocessed device cannot be demonstrated, the devices
Recommendations for both process and outcome measures
cannot be reprocessed or used. If the integrity and functional-
are developed by a panel of multidisciplinary experts and con-
ity of a reprocessed [single-use] device cannot be demonstrated
tribute to national surveillance and surgical care improvement
and documented as safe for patient care and/or equal to the
efforts (165}. Surgical process measures focus on the
original device specifications, the device cannot be reprocessed
or used. If anything is opened, it should be decontaminated 1. receipt of prophylactic antimicrobials within 1 hour before
before reprocessing (152). making the surgical incision,
2. receipt of prophylactic antimicrobials consistent with cur-
rent CMS recommendations, and
3. discontinuation of prophylactic antimicrobials within
Many items in the perioperative suite may be recycled includ- 24 hours after surgery.
ing sterilization wrap, paper, cardboard, glass, plastic bottles
and aluminum cans. Any item being recycled should be clean, By the end of 2010, the SCIP collaborative predicted out-
free of pathogens, and nonhazardous. Some of the benefits of comes from the measures would
recycling for altemate uses are donations which can be made to
community organizations, such as Project Cure, which can ben- 1. double surgical procedures between SSI occurrences,
efit medical facilities around the world, or donations to veteri- 2. reduce preventable SSis by 25%, and
narian clinics or animal shelters. Recycling can reduce landfill, 3. achieve 100% compliance with appropriate selection
prevent pollution, and conserve energy (153,154). and timing of prophylactic antimicrobial administration
(166,167).
Initial pilots conducted on the work of the SCIP collabora-

SURGICAL CHECKLIST tive identified promising reductions in SSI and mortality rates
(164,168}. While compliance with perioperative antimicrobial
The World Health Organization Surgical Safety Checklist administration has become standard practice across hospital sys-
is applicable to any perioperative or interventional setting. teiDll, SCIP measures, when implemented as isolated practices,
Enlisting the support of administration, surgeons, anesthesi- have minimal effect in patient outcomes at a hospital level. SCIP
ologists, nurses, and surgical technicians is a vital first step in recommendations have greater significance as composite mea-
developing and establishing ownership. Active and equal par- sures providing demonstrated indications for high-quality care
ticipation from everyone will help to facilitate the success of the through multimodal infection prevention practices (166,169).
checklist. The Surgical Checklist is an invaluable tool to assist in SCIP measures evolve as new evidence for practice emerges.
providing the highest quality of care for patients in any surgical The original broad-based measures have been refined to exam-
or procedural setting. The WHO checklist is available at: http:/I ine each of the high impact surgical procedures (i.e., cardiac
whqlibdoc.who.int/publications/2009/9789241598590_eng_ surgery, hip and knee arthroplasty, hysterectomy, colon surgery
Checklist. pdf. and vascular surgery) and clinical practices that can reduce or
Chapter 27 • The Ptrioperative Suite 425
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Candace Friedman and Kathleen H. Petersen
Ambulatory Care Settings

INTRODUCTION GENERAL PREVENTION
Health care ill increasingly provided in ambuJatory care settings. Basic IPC practicea need to be implemented regardle&J of the
These settings include a wide variety of primary and specialty of- setting. Theae include development of an lPC program, assign-
fices and clinic.s, urgent care centen, dental oflicea, and ph}'3ical ment or availability of a trained individual responsible for the
medicine and rehabilitation centers. Treatments once provided program, institution of robust hand hygiene programs, use of
only in a hospital are now offered in outpatient settings, includ.· standard precautions, and development of policies and proce-
ing infusion therapy, dialysis, and endoscopy. In addition, many dures for such activities as cleaning, disinfection, and steriliza·
surgical procedures formerly performed only on inpatient! are tion of medical devices (6,10-13).
now routine practice in ambulatory surgery centers.
Ambulatory care settings present unique challenges for HAND HYGIENE
infection prevention and control (IPC). High volume, com·
plexity of care, increasingly vulnerable patients, and brief Hand hygiene is a comentone of an e:ffeetive IPC program (14)
visits influence the development and recognition ofhealthcare- (see Chapter 3). Soap and an alcohol-based hand sanitizer should
associated infectiom (HAl). There are also risks related to pa· be readily available. Sinks must be conveniently located. Alcohol·
tient placement. communicable disease transmission, and type based hand sanitizers should be placed in waiting areas, exami·
of procedures performed. nation and treatment rooms, and ancillary areas. For invasive
Medical procedures performed in the ambulatory setting procedures, a sw:gical hand scrub is required (see Chapter 36).
may put patients at risk of infections ( 1). Use of intravascular An issue in ambulatory settings is how best to monitor
devices may lead to catheter site infection, bloodstream infec- appropriate hand hygiene. Opportunities for observations
tion, septic thrombophlebitis, or endocarditis. Other invasive by an assigned observer are limited in examination rooms;
procedures, including sw:gical procedures, endoscopies, bron- however it may be possible where multiple health care workers
choscopies, and cystoscopies, pose a riak of infection due to the provide care, such as surgery, open infusion areas, and ph}'3ical
disruption of normal host barriers. There have been reports therapy gyms. A surrogate for observation can be an evaluation
of outbreaks due to inadequate sterilization or disinfection of of the quantity of hand hygiene products used before and after
equipment, absent or inappropriate use of bani.ers, inappro- any intervention designed to increase hand hygiene. A rate of
priate work restrictions for ill health care workers, and poor use can be calculated by using the amount of product divided
hand hygiene practices. There have been several incidents of by the number of visits for a specific time period.
blood-borne pathogen transll:li»ion in ambulatory settings; this
has led to the development ofguidelines on safe injection prac- CLEANING, DISINFECTION, AND STBRILIZATION
tices. However, despite increasingly complex care in ambula-
With recent outbreaks reported in endoscopy areas and rec-
tory settings, overall risb of HAl continue to remain low (2-6).
ognition of the persistence of microorganisms in the environ·
There also is a risk of exposure to communicable diseases in
ment, especially multidrug-resistant organisms (MDRO) (15)
ambulatory settings. Patients with respiratory illneM congregate
and C. diJjicik (16), there has been an increased focus on
with others in waiting areas posing a risk to other patients and
cleaning of the environment and reprocessing (disinfection or
staff (7). This potential for infection transmission, including the
sterilization) of medical devices.
spread of measles and tuberculosis (TB), to patients and staff
Cleaning of the environment and equipment is important
in ambulatory care has long been recognized (6). Additionally,
in any setting. Environmental cleaning can be conveniently
there are concerns about transll:li»ion of antibiotic-resistant
divided into housecleaning of surfaces (e.g., room furniture,
bacteria and the threat of bio-disaster-related infections in
countertops, and examination tables) and patient-care equip-
these settings (8,9). Facilities that manage inpatient! alongside
ment (e.g., blood pressure cuf&, electrollic thermometers, and
outpatients may have additional issues related to management
otoscope handles). Environmental surfaces are considered
and placement of patient!.
noncritical and pose a low risk of transmitting infection.
The ph}'3ical environment in ambulatory care settings poses
Surfaces should be cleaned routinely and when soiled using
a challenge. There ill increased emphasis on the environment.
a low-level disinfectant ( 17). Many ambulatory settings rely on
related to infections such as Clostridium difficik and norovirus.
contractedjanitorial services; to assure that quality cleaning oc-
Janitorial and maintenance services are often contracted; infec-
curs, site management should oversee the contract to specify
tion prevention issues should be considered when developing
environmental cleaning contracts. New products and methods • what items are cleaned;
of cleaning should be evaluated. • the frequency of cleaning;
428
Chapter 28 • Ambulatory Care Settings 429
• that disinfectants approved for use in health care are used; 3. Compare practice with guidelines using a gap analysis.
• that cloths and mops are cleaned and dried daily; 4. Seek to bring policies and practices in line with recom-
• that gloves, gowns or other personal protective mendations. Changes may involve space rearrangement,
equipment (PPE) are available as needed; and switching to a different disinfectant, updating procedures
• that the cleaning staff has adequate training, including for disinfection, sterilization, or monitoring the processes.
the Occupational Safety and Health Administration's For steps to implement required changes, see Figure 28.1.
Bloodborne Pathogen Standard (there may also be state
Written procedures should describe how each device will be
specific requirements).
processed; include the PPE staff need, how to clean the item,
Patient-care items with skin contact also require routine clean- the proper disinfection or sterilization steps, and storage param-
ing (17,18) eters to make the document a practical educational tool. New
Frequency of cleaning depends on the setting, likelihood disinfecting products and methods, such as ultraviolet light (28),
of contamination and susceptibility of the patient population. must be evaluated very carefully to assure that they meet regula-
A general pediatric or oncology clinic may choose to clean tions for efficacy and will not damage devices or equipment.
items more frequently (such as several times per day), whereas Steam autoclaves often are available in ambulatory care
an adult internal medicine clinic may choose to clean less fre- settings. Peel pouches may be used to package small items.
quently (such as once per day). Stethoscopes often are recom- There also may be items, such as vaginal specula, which can be
mended to be cleaned after each patient, easily accomplished steam sterilized unwrapped in place of high-level disinfection.
with a sterile alcohol prep pad. Although there are studies dem- Preventive maintenance is critical to ensure a safe, functional
onstrating contamination of surfaces, spread of infection in an sterilizer. Follow Association for the Advancement of Medical
outpatient setting has not been reported (19). Instrumentation (AAMI) standards (26).
Outbreaks of hepatitis B and C viruses (20,21) have impli- Staff members must be educated on the practices required
cated blood-contaminated glucometers, as well as unsafe injec- for safe and effective processing of items and how to pro-
tion practices, leading to recommendations for disinfection of perly use chemicals and sterilizers. Before allowing new staff
glucometex-3 after each patient. Increases in C. di.fficile infections to perform high-level disinfection or sterilization, they must
and norovirus outbreaks have caused concerns in outpatient set- demonstrate competency, preferably by return demonstration.
tings; these microorganisms are hardy in the environment, not Reassessing competency is needed on a regular basis.
inactivated with standard disinfectants and have been shown When new medical devices are under consideration (pre-
to spread via surfaces contaminated with diarrhea or vomitus ferably before acquisition and use), assessment and education
(16,22,23). Special procedures are required for disinfecting sur- are needed. The reprocessing procedure and products should
faces contaminated with these body fluids; the procedure should be reviewed by the infection control professional/infection
include use of a surface disinfectant shown to be effective for preventionist (ICP /IP) to make sure they are consistent with
these microorganisms (such as 10% bleach). Also recommended the organization's overall high-level disinfection or sterilization
is the use of gloves and gowns for large spills and face protection policies. In most instances the manufacturer of the device will
for cleanup of vomit when suspecting noroviiUll infection. provide the training.
There are many surface disinfectants on the market, liquid Disposable, single-use items must not be reprocessed unless
and wipes; both are effective for surface disinfection. Careful the U.S. Food and Drug Administration (FDA) requirements
consideration is needed before selecting a surface disinfec- are met (29).
tant and an in-use trial is recommended. Factors to consider
for selection: tolerance of the product by the users; ease and
STORAGE
convenience of use; damage to surfaces; customer support
for education and educational materials; and cost. Effective Along with reprocessing, adequate storage space design and
contact time has been controversial; helpful information can location are common concerns. Clean and sterile items must be
be found in the Centers for Disease Control and Prevention stored in a manner to prevent contamination. Sterile supplies
(CDC) guidelines (17). There also are efficacy studies for each should be stored in closed drawers or cupboards, if not in a des-
product, product labels, and results of efficacy testing in vitro. ignated clean supply room. If at all possible, do not store clean
It is probably more important to make sure that surfaces are or sterile items in a soiled utility room. All supplies should be
clean using mechanical action to remove visible blood or body stored in a "first-in, first-out" manner to ensure use of the "old-
fluid and to assure that cleaning actually occurs than the pre- est" items first. How long to keep open bottles of disinfectants,
cise contact time of the disinfectant (24). isopropyl alcohol, povidone iodine, chlorhexidine, hydrogen
Medical devices and instruments that contact mucous mem-
branes are considered semi-critical and need high-level disin-
fection; devices contacting sterile tissue are considered critical • Meet with clinic managers, nurse or medical assistants
and require sterilization (see Chapter 20). There often are bar- • Develop written procedures: have consistent procedures
riers to effective disinfection and sterilization typically facing throughout facility
ambulatory care settings, including lack of resources, expertise, • Develop initial training and competency requirements,
and adequate space. To organize effective and safe reprocess- record keeping, and frequency to repeat, such as annually
ing, here is a suggested strategy: • Implement procedures
1. Evaluate current practice. List all of the devices that con- • Survey site to assess practice: use process surveillance
tact mucous membranes or sterile tissue. • Implement changes and recommendations
2. Gather recommendations from the device manufacturers, • Document and share with relevant staff
relevant professional organizations (25,26), CDC guide-
lines (17), and relevant regulatory agencies (27). Figure 28.1. Disinfection/sterilization of equipment.
peroxide, and other solutions is unknown. A practical ap- TRANSMISSION-BASED PRECAUTIONS

proach is to develop a consistent policy and practice, such as us-
In addition to standard precautions, a method is advisable to
ing manufacturer's outdate and only having one bottle open at
a time in a room or area, relying on state regulations as needed. address airborne or highly communicable infections based on
mode of spread and adaptation of the CDC's Guideline for Iso-
To avoid water contamination and damage, keep clean items
lation Precautions (4) . Early identification can assist with use
away from the splash zone around the sink, and do not place
of appropriate isolation/precautions. A screening tool may be
patient-care items under the sinks. Deny staff food or beverages
useful for assessing diseases such as TB, chickenpox, measles,
in clean storage and utility rooms. In general, the IPC focus is
or pertussis. Screening can be performed at the time of the ap-
on protecting clean and sterile supplies from contamination.
pointment, especially for urgent appointments. Patients meet-
ing screening criteria should be provided a mask, if appropriate,
STANDARD PRECAUTIONS separated from others as much as possible, and not remain in
Use standard precautions for all patients. This includes the use waiting areas. When possible, have patients enter via an alter-
nate door and escort directly to an examination room. When
of PPE (i.e., gloves, gowns, and face protection) as needed to
protect from exposure to blood and body fluid. The type of feasible, patients with rash or fever should be seen at times when
there are fewer patients. During seasons of high influenza or
exposure expected will determine the specific barrier to use.
other respiratory infections, divide the waiting area into those
Barriers should be readily available in examination and treat-
with respiratory symptoms and those with none (Figure 28.2).
ment rooms. Gloves must be worn for vascular access proce-
Transmission-based precautions for MDROs or C. difficile in-
dures, such as phlebotomy, handling contaminated items, and
fections may be implemented, depending on the complexity
performing invasive procedures. Face protection is needed for
of patient care, susceptibility of patient population, and risk of
prevention of splash exposures to the eyes, nose, and mouth.
In addition, safety devices, especially intravenous catheters and spread ( 4,16,30,31).
blood drawing needles, must be accessible. Training regarding
specific practices involved in standard precautions must be pro-
OCCUPATIONAL HEALTH
vided to staff.
Respiratory hygiene/cough etiquette practices should Occupational health programs are important in ambulatory
be implemented by instructing visitors, patients, and staff to care settings. There should be a comprehensive vaccination
"cover their cough". Signs providing instructions should be program for employees for hepatitis B virus, influenza, pertus-
prominently displayed; tissues and masks should be available. sis, and so on (32). Decisions should be made at the administra-
Early reminders to staff in anticipation of influenza season may tive level with input from the ICP/IP about what vaccines are
be helpful to decrease exposure. Reminders to staff during per- mandatory. Note that there may be state, regulatory, or accred-
tussis or other respiratory infection community outbreaks also iting agency requirements for influenza vaccine. A TB screen-
may be beneficial. ing program is also important; it should be more extensive in
For suspected tuberculosis (TB), chicken pox, other airborne-spread or droplet-spread infections, and unidentified rashes:
The nurse will triage the patient phone call and will discuss with the physician or assigned clinician whether or not the patient
must be seen, if the visit can be rescheduled, or if the case can be handled over the telephone.
If the patient will be seen:
1. Advise patient to come to an alternate door and not the main entrance, when available.
2. Determine immune status of staff. Recommend that only staff members who are immune care for patient. All non-immune
staff who must care for the patient must wear masks.
3. At the time of entry to the facility have the patient wear a mask (surgical or isolation).
4. Place the patient into an exam room immediately to avoid time in the waiting room.
5. Keep the exam room door dosed.
6. When the patient leaves, dean surfaces contaminated with blood or body fluid as for any patient, using Standard Precautions.
Patients with suspected active, pulmonary TB must be handled according to Airborne Precautions. Patient is to be moved to a
facility with negative pressure isolation rooms, such as Hospital, as soon as possible or sent home with
appropriate instructions.
If possible exposure occurs, contact _ _ _ _ _ _ _ _ _ or _ _ _ _ _ _ _ __
(Infection Control) (Occupational Health)
Figure 28.2. Sample triage policy.

geographic areas with higher rates of TB. A risk assessment 5. Handle medications safely. Single-dose vials (SDV) are
should be performed to develop the details of the screening intended for one patient only. Prepare medications in
program. There should be a system of follow-up for any body a clean area; disinfect the surface before preparing the
substance or chemical exposure. ff the setting is independent, medications. Store only the medications and new sy-
a contractual arrangement should be made for timely follow-up ringes and needles in the medication preparation area.
of exposures. Work restrictions for specific infections that apply Label according to institutional pharmacy policy; mini-
to all health care workers are also essential to provide consis- mally include the medication, dose, and date and time
tent guidance to managers and staff for staying off work and for of preparation. Once the medication is prepared and
what time period (33). taken to the examination or treatment room, do not
return it to the medication preparation area; discard
the syringes and needles after one use into the sharps
SETIINGS, RISKS, AND PREVENTION container, and discard the used vial according to institu-
tional policy.
Each of the following sections summarizes the application of 6. Clean environmental surfaces, such as examination tables,
IPC principles in various ambulatory care settings. Prevention on a regular basis. Include the surfaces of equipment, such
of infections due to infusion therapy and dialysis is covered as electrocardiogram, endoscopy, or ultrasound machines,
elsewhere (see Chapters 23 and 38). after each use. For specialty equipment, refer to manufac-
turer's recommendations.
PRIMARY AND SPECIALTY CARE MEDICAL 7. Disinfect and sterilize instruments after each patient use.
OFFICES AND CLINICS Use procedures consistent with policies and procedures of
the organization and recommendations or guidelines (such
Services range from noninvasive health maintenance examina-
as the Society for Gastroenterology Nurses and Associates
tions to procedures such as endoscopies, biopsies, and minor
(SGNA) for sigmoidoscopes (25) and CDC (17)). Recog-
surgeries. Risks to patients include exposure to pathogens in
nize that clinics often have special instruments that need
the waiting room and medical devices not effectively repro-
to be reprocessed according to standard procedures, using
cessed. Risks to staff include sharps injuries and exposure to
recommendations from the manufacturer and the Spauld-
communicable infections.
ing classification (see Chapter 20) . Examples include:
The role of toys, computer keyboards, stethoscopes, and
podiatry instruments in podiatry and geriatrics; lenses and
other environmental sources in the spread of communicable
eye exam equipment in ophthalmology; radio frequency
diseases is generally low. Unsafe injection practices and medica-
ablation equipment in pain clinics; biopsy forceps in
tion handling have resulted in transmission of hepatitis B and C
gynecology and obstetrics, urology and gastroenterology;
viruses and Staphylococcus aum.tS (20,21,34). Possible issues with
dilators in gynecology; and so on.
laryngoscopes and outbreaks associated with contaminated ultra-
8. Staff with expertise in infection prevention should assist in
sound gel have led to more stringent recommendations (35-37).
the evaluation of reprocessing before placing new equip-
Reportable diseases diagnosed by the medical office or
mentor devices into use. This is especially important in
clinic must be reported to the local health department. Pri-
specialty clinics such as ophthalmology, infertility or urol-
mary care also can play a major role in promoting community
ogy, where technology is advancing rapidly and new devices
health (e.g., providing immunizations and teaching patients
often are introduced.
about hand hygiene, appropriate use of antimicrobials, and
9. Perform disinfection or sterilization in utility rooms, sepa-
prevention of sexually transmitted infections).
rate from examination or treatment rooms.
Specific measures to prevent infections include the
10. Where laryngoscopes are used, store blades separately and
following:
covered, such as in a sealable plastic bag. The blade needs
1. Triage patients with possible airborne-spread, such as to be high-level disinfected, at a minimum; the handle
chickenpox, or droplet-spread illness, such as pertussis or may be low-level disinfected. Some models can be stored
influenza, to enter an alternate door, where available, or to together in order to test them appropriately.
avoid time in the waiting room (see Figure 28.2). 11. Where ultrasound equipment is used, disinfect probes
2. Immunize patients according to CDC recommenda- between each patient. Probes contacting skin can be
tions (38): store, prepare, and maintain records according cleaned with a low-level disinfectant. High-level disinfect
to immunization labels, state regulations, and institutional probes that contact mucous membranes and nonintact
pharmacy policies. skin, even when probe covers or sheaths are used (41). Re-
3. Practice aseptic technique for minor procedures: pa- fer to manufacturer's guidelines.
tient skin prep, set-up of sterile trays immediately before 12. Consider Use sterile, single-use packets of gel for any mu-
the procedure, adequate hand hygiene and wearing of cous membrane contact (36,42,43). Also consider banning
gloves by the healthcare worker, and draping of patient as the refilling of small containers of gel from large contain-
needed. Where epidural or subdural space injections are ers, allowing only single-use bottles that are filled once and
performed, such as in pain clinics, physicians need to wear then discarded, or purchasing single-use bottles which are
surgical masks and sterile gloves (39). discarded when empty. Use sterile, single-use packets for
4. Perform and teach safe injection practices. Use safety nee- contact with nonintact skin and when performing biopsies,
dles and sharps, including scalpels, except when to do so such as needle aspiration, needle localization, and tissue
is medically contra-indicated. Educate new staff on proper biopsy.
use and the importance of using safety sharps. Needles and 13. Dispose of single-use devices (SUD); in most instances, it
syringes are single-use items and must be used only one is not cost-effective to have a third-party reprocess items
time and for only one patient (40). labeled single-patient use.
DENTAL OFFICES (6,44--47) EMERGENCY DEPARTMENT

Risks of infection due to dental procedures include contami- Services provided in an emergency or urgent care department
nated instruments and equipment, such as ultrasonic scaling, (ED) (6,51-55) focus on the care of critically ill or injured
high speed hand-pieces, and waterlines. In addition, there is a individuals who are having various procedures performed.
risk of postprocedure infection due to microbes in the oral cav- Some of these patients come to the ED with communicable
ity after minor procedures, such as teeth extraction and dental diseases. In addition, individuals seeking treatment after a
implants. Staff exposure to blood and body fluids may occur via biological or chemical attack will be advised to go to an ED.
aerosols and use of sharp devices. Risk of infection to patients arises primarily from invasive
Specific measures to prevent infections include the procedures performed (e.g., bloodstream infections related
following: to intravascular catheter placement). Waiting and other com-
mon areas pose a risk of exposure to communicable diseases
1. Perform a surgical scrub for oral surgical procedures.
for patients, visitors, and staff.
2. Use safety dental syringes/injectors and work practices to
Staff also is at risk from blood and body fluid exposure.
prevent body substance exposures. Wear gloves and fuce
ED staff is at a greater risk of exposure to blood-borne patho-
protection.
gens than other healthcare workers due to their frequent con-
3. Decrease aerosols generated during treatments through
tact with blood; therefore, safe injection practices are important
the use of rubber dams, high-velocity air evacuation, and
in the ED. Exposure protocols for both staff and emergency
proper patient positioning.
response personnel should be available outlining appropriate
4. Sterilize instruments that penetrate soft tissue, including re-
follow-up measures (see Chapter 43).
usable prophylaxis angles, high-speed dental hand-pieces,
and low-speed hand-piece components used intraorally.
following:
5. High-level disinfect instruments that contact oral tissues,
such as the suction tube, or heat-sensitive instruments. If the • Use aseptic practices as in any health care setting for
suction device is labeled single use, discard after one use. If intravascular devices, urinary catheterization, and any
reusable, clean the lumen thoroughly before disinfection. other invasive procedure.
6. Clean hand-pieces thoroughly, both internally and exter- • Assess patients for signs and symptoms of communicable
nally. They must be run to discharge water and air after diseases. A triage screening tool can be used to identify
each patient. potentially contagious patients (Figure 28.3). Mask
7. Flush ultrasonic scalers and air/water syringes for 20 to identified patients with respiratory diseases/ symptoms
30 seconds after each patient. promptly and separate them from others.
8. Use a surfuce disinfectant to clean the following areas after • Implement a system of isolation/ precautions for
each patient: countertops, chair, light handles, dental unit management of potentially infectious patients.
surfaces, aspirator tube, edge of spittoon (if used), and ul- • Implement an emergency response plan that includes
trasonic scaler hand piece. biological threats.
9. Provide hepatitis B virus and influenza vaccines for staff.
10. To protect patients and staff, use safe injection practices,
respiratory hygiene, and cough etiquette (48). OUTPATffiNT SURGERY
Outpatient surgery is performed in traditional hospital settings
or in stand-alone ambulatory surgery centers (ASC). Surgical
PREHOSPITAL-EMERGENCY MEDICAL SERVICES
procedures commonly performed on outpatients include cata-
Emergency response personnel may become exposed to a racts, muscle/tendon procedures, reduction of fractures, lapa-
patient's communicable disease pathogens or may perform roscopic cholecystectomies, tubal ligation, hernia repairs, knee
activities that increase a patient's risk of infection. Providers arthroscopies, podiatry procedures, and many types of plastic
perform procedures ranging from establishing intravascular and oral surgery.
catheters to surgical cricothyrotomy. Primary prevention tech- The risk of surgical site infection (SSI) varies according to
niques include the use of standard precautions, safe injection procedure; however it is reported to be approximately 1% or
practices, and proper cleaning of equipment. There should less overall and certainly less than for inpatient surgery (56,57) ,
be a protocol outlining what emergency response personnel although reported data are limited (58) . Outpatient proce-
should do if exposed to a communicable disease. dures are generally shorter and not as invasive or complicated;
Specific measures to prevent infections include the in general patients have fewer health risks.
following (49): A team approach to prevention of SSis is crucial. Prevention
of postsurgical infections is covered in Chapter 36.
• Wear gloves during assessments and invasive procedures
The strategy for surveillance for SSis in ASCs differs slightly
or treatments.
from inpatient surveillance; however, data are needed to evalu-
• Practice appropriate hand hygiene as soon as possible
ate infection trends, develop rates for new or more complex
before and after performing patient-care.
surgeries, and monitor changes in rates following interven-
• Wear a mask to decrease exposure, if it is suspected the
tions. Surveillance should include the following:
patient has a droplet- or airborne-spread disease.
• Decontaminate used equipment and discard all dispos- 1. Determine which procedures to follow: perform a risk as-
able items. sessment for high-volume, high-risk, problem-prone, and
• Ensure all sterile equipment is, and remains, sterile. historically problematic procedures. Perform a medical lit-
• Practice appropriate environmental cleaning (50). erature search to determine a benchmark.
Emersency Department Alsorithm
Question 1 Question 2 Question 3

Question 4 Question 5
No No No
Does Patient Have
Couah or Other
Respiratory Symptoms
I > Does patient have
abrupt onset of
fever PLUS:
Does patient have
slplllcant diarrhea (3
or more formed or
Does patient haw
acute onset of
nauseafvomltlnB?
l.lntenu headache watery stools In 1Z
No
YES
&mil~ Z. Petechial rash OR hrs)*not caused by
lalllltlve use,
.(l
In Adult Patients:
3. Mental status
chenaes chemotllenpy,
JJYES No
,--A,. I
I
I • Place a recular mask on
l.....T I I • Does patient have fever patient If In waltlnc
entel'lll feeds or other Special
YES medical causes AND
D
>loo•F (past 24 hours] raom lo for transport COnsider Isolation
AT LEAST ONE of the
-
AND cough, COPD, CA- YES NIII'OIIrua 01 Required
pneumo, asthma c:::::) • Place In room with followl"l: Rcltnln!s If In
wrtaln or door Cur1'1!nt or prior
SUSPECT • CONTACT exacerbation, clinical
• Place a DROPLET antibiotic use
CHICICENPOlC/DISS. PRECAUTIONS sip suspicion influenza PRECMI1IONS qn on • Place In room with
5U5PECI' (within 30 days)
ZOSI'ER: on door/curtain • lab confirmed flu the door/ourtaln curtain 01 door
MENNGmS:
• Place a r~~Uiar In Padllltrfc/Aclult BMT • Notify the cha,.e nurse • PIMle patient In
• 51inlllcent • Place CONTACT
htients: abdominal pain, PRECAUTIONS 5i&n
mask on patient roomwltha not caused by
• Promptly place in • Does patient have on door/ourtaln
curtain or door lnclslonal paln,
an Isolation room signs/symptoms of viral • Placi8 a DROPLET dyspepsia, or
set at neptlve resp. illness (with or w/o PRECAIITlOU nausea
pressure fever], including asthma sJ&n on
• Place an exacerbation, CA· • History of C.
door/curtain dt/Jklle
AIRBORfiiE pneuma • Mask on patient
ISOI.AnON sJan on
door
• lab confirmed flu, RSV,
Parainflu, Adenovirus
r--------..., I
SUSPECT111
durlnstransport
*1L of colostomy output, >200ml of watery
• Mask on patient rectal bag output
durlnc transport • Pl1ce a 1'1!gu .. r mask an
~
• Notify chars• .(lNo patient YES
nurse • Promptly place in an
Does patient have and any Isolation room set at
of the following: nqative pressure • SUSPECI' C. IIIII'*
• Blood in sputum • Place an AIRBORNE • Place in room with curtain or
• Night sweats YES ISOLAT10N sian on the door
• +TBTest ... door • Place CONTACT PIIECAIJTIONS
• Weight Loss r-------vJ • Notify the charge nurse 11811 on door/ourtaln
• ExposuretoTB
• HIV/Risk Factors for HIV
Espedelly consider SUSPEa PER1\ISSIS
symptoms In patients with
COUJh >:ZWks • Place a reaular mask on patient If In waltq raom a
fort,..,.,n
[k
YES
~
Does patient have with vomiting post • Place In room with curtain or door
coughing episode or violent coughing • "*-a DROPLET PRECAUTlOWS sian on door
attacks? t- • Notify the cher&e nurse
Especially consider In patients with
COUih>Zwlai
Figure 28.3. Emergency department triage.
"""
~
~
2. Case-finding: develop effective data sources, such as, chart addition to endoscopy centers, endoscopes are used in gy-
review, review of the electronic medical record, phone necology, otolaryngology, urology, speech pathology (where
calls or letters to surgeons or patients, and contact with the swallowing studies are performed), and in primary care or
medical offices where patients receive postsurgery care. gastroenterology specialty clinics. Procedures and devices have
3. Analyze data and determining follow-up: Who will collect become more complex, such as endoscopic retrograde cholan-
data and develop reports; who will receive reports; what is giopancreatography (ERCP) and gastrointestinal endoscopic
the frequency of reports; and who will be responsible for ultrasonography.
follow-up of recommendations or changes in practice. Infections related to endoscopy have been reported, how-
4. Reassess rates after any change in practice. ever infrequently (61,62). Outbreaks of hepatitis C virus related
5. Pitfalls: low numbers of procedures or infections make to reuse of SDVs have occurred (63). Concern for hepatitis C
some SSI rates difficult to interpret. virus and human immunodeficiency virus exposure related to
improper use of the auxiliary water tubing and valve have been
Caring for patients colonized or infected with MDROs, such
reported (62). Numerous exposures to blood-borne pathogens
as methicillin-resistant S. aum.u, or infected with C. difftcile is
related to unsafe injection practices also have been reported
potentially problematic. While the CDC recommendations for
(20,21). Due to these outbreaks and potential exposures, en-
isolation ( 4) are geared toward inpatients, the recommenda-
doscopy centers have come under increased scrutiny by regula-
tions may be used as guiding principles for ASCs. Keep in mind
tory bodies. CMS increased surveys of endoscopy centers under
that many of these patients will not be identified upon admis-
the same umbrella as ASCs.
sion or during the ASC procedure, and that the most impor-
Cross-infection has been traced to failures in practicing
tant preventive practice is standard precautions for all patients.
recommended cleaning and disinfection procedures of the en-
Guidelines should be developed that are applied consistently
doscopes or ancillary equipment. These include Mycobacterium
and may include the following:
tuberculosis related to bronchoscopy, Pseudomonas aeruginosa re-
1. There is no reason to defer a procedure for patients who lated to ERCP and cystoscopy, and Staphylococcal infections
are colonized. related to arthroscopy (6,64). In addition, there have been
2. If a patient has an active infection, regardless of infecting reports of mucous membrane damage (colitis) linked to inad-
microorganism, consider delay of surgery until the infec- equate rinsing of disinfectant, specifically glutaraldehyde from
tion is resolved. An active infection at the time of surgery is sigmoidoscope channels (65) . Endoscopy staff members are at
a risk factor for development of a postsurgery infection. risk of exposure to body fluids during procedures, exposure to
3. Patients whose procedure cannot be deferred and who M. tuberculosis during bronchoscopy, and exposure to chemicals
have active infections with MDROs or C. difftcileare placed during disinfecting procedures.
onto Contact Precautions (CP). Endoscopes are inherently heat-sensitive, complex, and
4. Gowning, gloving, hand hygiene, and postprocedure envi- fragile instruments. Lumens may be long, narrow, and are diffi-
ronmental cleaning are essential to CP procedures. Envi- cult to clean thoroughly (66). Adhering to rigorous procedures
ronmental cleaning with an agent active against C. difficile decreases the risk of infection.
spores, such as 10% bleach, is recommended after caring Specific measures to prevent infections include the
for C. difficile patients. Standard disinfectants can be used following:
for other MDROs.
1. Ensure that all staff responsible for using and reprocessing
5. Patients with MDROs or C. difficile need not have proce-
dures scheduled at the end of the day. endoscopes are trained and competent. Competency dem-
onstration is necessary annually and should be a formal
Following reports of infections, the Centers for Medicare/ part of each employee's records and the in-service training
Medicaid Services (CMS) increased regulations and inspections program (25,59).
of ASCs using stricter standards (59). Categories covered by 2. Reprocess endoscopes consistently after each patient use.
the CMS Quality Assessment and Performance Improvement- Endoscopes with mucous membrane contact should re-
Infection Control Surveyor Worksheet include the following: ceive at least high-level disinfection; endoscopes with ster-
• Infection control program follows national standards, ile tissue contact are generally sterilized. Biopsy devices are
tracks infections, and is directed by an individual quali- either disposable or sterilized after each use. Assure that
fied in IPC; there is adequate work space for cleaning and disinfection,
• Hand hygiene; and perform cleaning and disinfection in a designated re-
• Injection practices; processing/utility room. Do not perform cleaning and dis-
• Sterilization, disinfection, and handling of SUDs; infection in the procedure room.
• Environmental cleaning; and 3. Follow the procedures recommended by the endoscope
• Glucose meters and other point of care devices-use and manufacturer and by professional organizations (25,60,67)
decontamination. including leak testing and a final alcohol flush through
each lumen. Provide manufacturer's instructions as ready
references for staff. Some manufacturers provide illus-
trated posters.
DIAGNOSTIC AND TREATMENT AREAS 4. Assure that gloves, impermeable gowns, and face protec-
tion are available and are worn to prevent exposure during
ENDOSCOPY
procedures and reprocessing.
Endoscopy is among the most common and fastest growing 5. Assure that no food or beverages are in the procedure or
of outpatient procedures (60). Endoscopy areas and ASCs endoscope reprocessing rooms.
routinely perform gastrointestinal, respiratory, urologic, 6. Store endoscopes hanging to promote evaporation of any
arthroscopic, and gynecologic endoscopy procedures. In moisture in the lumen (66).
7. Perform quality control on the entire process, such as reg- Infections are rare after invasive cardiovascular procedures
ular efficacy checking of the high-level disinfectant. and usually are associated with the procedural site or the device
8. Investigate any possible endoscopy-related infections. (77). However, risks for infection have been linked to contami-
9. Follow overall infection prevention practices, such as nated instruments, or solutions, or breaks in technique. When
cleaning of environmental surfaces, as for other diagnostic infection occurs, it is presumed that bacteria are introduced at
and treatment areas. the time of vascular puncture or incision. Infectious complica-
10. Ensure safe injection practices, including disposal of sy- tions include bloodstream infection, endarteritis, pacemaker
ringes, needles, and SDVs after each patient. Use a new and defibrillator infections, coronary stent, and puncture site
needle and syringe for each entry into multi-dose vials. Be- infections. Patients with implants may develop late-onset infec-
fore entry, wipe the top of all medication vials with sterile tions. Skin microorganisms usually cause these infections. Risks
alcohol wipes. for staff are mainly through exposure to blood from sharps in-
11. Follow guidelines from the CDC during bronchoscopy to juries or splashing of blood.
prevent spread of M. tuberculosis (68). Specific measures to prevent infections include the
12. Follow safe ultrasonography practices. following:
1. Prepare the patient: Follow standard vascular access and
RADIOWGY surgery site preparation. Do not remove hair unless it will
interfere with the operation.
Radiology departments provide a number of services, includ- 2. Perform standard surgical hand antisepsis and avoid artifi-
ing diagnostic radiography, computed tomography, fluoros- cial nails, as described in Chapters 3 and 36.
copy, ultrasound, and interventional procedures. Risks of 3. Use aseptic technique.
infection are primarily related to intravascular catheter use 4. Follow Standard Precautions. All cardiac catheterization
or equipment (e.g., ultrasound probes and fluids, contrast procedures must be conducted as if there were a risk of
medium). Because patients suspected of having TB or other infection.
conununicable respiratory illness often are evaluated with di- 5. Prepare staff (74,77):
agnostic radiography, there is a risk of transmission to both • The operator should wear mask, eye protection, cap,
patients and staff. Staff members also are at risk ofblood-bome sterile gloves, and sterile gown.
pathogen exposure due to their contact with blood during • Staff assisting within the sterile field should wear scrub
invasive procedures. suit, cap, mask, and gloves, adding eye protection if
Specific measures to prevent infections include the follow- there is a splash potential during the specific procedure.
ing (6,69-73): • Circulators should wear scrub suits.
1. Follow Standard Precautions. • In procedures where greater wound exposure is neces-
2. Use safety devices, especially intravenous catheters and sary, such as pacemaker implantation or brachial cut-
needle holders/pads, and pass instruments safely. downs, full surgical sterile technique should be used.
3. Use aseptic practices for intravascular devices and other 1. Insert intravascular catheters and maintenance us-
procedures. ing prevention bundles: follow CDC guidelines on
4. Avoid hair removal unless it interferes with the procedure. prevention of catheter-related infections (78).
Clip the site, if necessary. 2. Control intravenous solutions (e.g., dyes, flush
5. Use appropriate techniques during invasive procedures, solutions). Ensure sterility; cold infusates need to
(e.g., insertion of tunneled catheters, surgical scrub), and be cooled without contact with tap water that might
use a sterile field system. Nonporous drapes must cover the contaminate the infusate and then be inadvertently
area surrounding the wound; cover the patient and any injected into vessels.
hardware on the table that might come in contact with a 3. Process equipment: Most supplies used in the unit
long catheter/wire (74). Operators should wear cap, mask, are disposable. However, single-use catheters can be
gown, and gloves. Circulators should wear a scrub suit. reprocessed for reuse, following requirements of the
6. High-level disinfect endocavitary and vaginal ultrasound FDA. Electrophysiology units often use third-party
probes after each use, even when probe covers are used reprocessors for these devices (29).
(41,75). 4. Ensure sterility of implants: any implant removed for
7. Reuse catheters in angiography only per FDA regulations infection must be reported to the FDA. Work with
(29). the institution's risk management department on
8. Implement a protocol on how to manage patients sus- appropriate protocols.
pected of having an airborne conununicable disease (e.g., 5. Control the environment: Air handling is similar to
use of a mask on the patient when an identified patient is that in operating rooms. This includes ensuring that
seen for chest radiography). the room is set at positive pressure with a minimum of
15 air exchanges per hour; make sure construction/
renovation plans follow local health department
specifications (79).
CARDIOWGY: CARDIAC CATHETERIZATION
6. Clean procedure rooms after each patient (79,80).
AND ELECTROPHYSIOWGY
7. Use safety devices and dispose of sharp instruments
Increasingly complex diagnostic and interventional procedures and needles safely. Double gloving has been shown to
are performed on outpatients in the cardiac catheterization reduce the chances of a puncture. Carefully discard
laboratory, including placement of pacemakers, stents and all needles, catheters, sheaths, tubing, and other in-
other implantable devices, angioplasty, and cardiac catheteriza- struments, as well as fluids that come in contact with
tions (74,76). the patient (77).
8. Use prophylactic antibiotics per recommendations protection, and gowns to prevent splashing to the face
(74). and contamination of clothing when caring for large open
9. Develop written policies and procedures for IPC. wounds. During dressing changes, use aseptic technique.
When irrigation, such as pulsatile lavage, is performed
Surveillance for bloodstream infections (BSI) and SSis is diffi-
there is risk of aerosolization; disinfect environmental sur-
cult unless patients return to the clinic affiliated with the cardiac
faces after each treatment (81).
area. However, there should be a system in place for follow-up
8. Perform airway suctioning and intermittent urinary cath-
of patients. Because reported rates of infection are low, any evi-
eterization using aseptic technique. Use new catheters for
dence of an outbreak or cluster should be carefully evaluated.
each patient visit. Discard suction canister and tubing ac-
cording to institutional policy.
PHYSICAL MEDICINE AND REHABILITATION 9. Evaluate whether equipment touches skin, mucous mem-
brane, or sterile tissue. Establish frequency of cleaning and
Rehabilitation services provide a multidisciplinary team
what disinfectants will be used.
approach to treat patients with often complex medical and
10. Perform high-level disinfection of devices that contact mu-
physical conditions. Rehabilitation specialties include physical,
cous membranes, such as endoscopes used for swallowing
occupational and speech and language therapy; orthotics and
studies and vaginal probes used for pelvic floor programs.
prosthetics; recreational, art, and music therapy; and rehabili-
11. Develop regular cleaning protocols for equipment such as
tation engineering. Pet therapy may also be included. Services
mats, walkers, canes, wheelchairs, weights, transfer devices,
may be provided for inpatients and outpatients in the same set-
gait belts, and speech therapy manipulative devices (83).
ting. Programs often target special needs, such as sports or spi-
Provide barriers between patients and equipment such as
nal injuries, traumatic brain injuries, or stroke.
hydrocollators. Standard disinfectants are recommended;
Although services are wide ranging, few involve invasive
consider use of 10% bleach or other disinfectant effective
procedures, and infections related to these services are rarely
for norovirus or C. difftcile to clean-up vomit or diarrhea.
reported. Rehabilitation patients at increased risk of infection
12. Hydrotherapy: drain and disinfect tank and agitator jets af-
include cystic fibrosis (CF) patients who are at risk of devel-
ter each patient. Do not use hydrotherapy for patients with
oping and/ or spreading Pseudomonas sp. or Buikkolderia sp. to
open wounds.
other CF patients; arthritis patients on steroids; patients with
13. Aquatic therapy: follow state laws for chlorination or other wa-
large wounds coming for wound irrigation (81); and diabetic
ter treatment protocols and testing the pool or whirlpool wa-
patients being fitted for orthotics or prosthetics. As in other set-
ter. Restrict patients with open wounds or fecal incontinence.
tings, patients who require intermittent urinary catheterization
14. EMG needles: if disposable, discard carefully after each
or airway suctioning are at risk of developing infection if these
patient. If reusable, sterilize according to manufacturer's
techniques are not performed aseptically. If not adequately re-
recommendations.
processed, devices that are used from patient-to-patient, such as
15. SUDs: discard following single-patient use.
endoscopes, may transmit microorganisms. Speech therapists
16. Pet therapy or service animals: follow standard guide-
or others working with the mouth or items that contact oral
lines (84).
secretions, such as during swallowing studies, may be exposed
17. Where therapy includes activities of daily living, such as
to respiratory infections of the patient.
food preparation or laundry, establish regular cleaning
of surfuces. Assure that food preparation and storage and
following:
refrigerator temperature monitoring are consistent with
1. Use hand hygiene and respiratory hygiene practices to prostate or local regulations. Food supplies can generally
tect staff and patients. be stored as indicated on the label for temperature and
2. Standard Precautions: assess patients for incontinence, expiration date. Food that clients prepare can generally be
open wounds, and increased respiratory secretions to consumed when preparation is completed. Also assure that
evaluate routine need for PPE. With the exception of CF clients clean hands prior to food handling, preparation,
patients, it is not routine to screen patients in this setting and eating (see Chapter 21) .
for MDROs. Thus, use of hand hygiene and Standard Pre-
cautions are the best defense to prevent transmission.
3. Where outpatients and inpatients are treated in the same HOME CARE
space, establish consistent policies for how transmission-
based precautions will be practiced. Many medical procedures are increasingly performed in the
4. CF patients or patients known to have MDROs: apply pre- home; therefore basic IPC practices must be applied in this set-
cautions consistently. When possible, treat CF patients at ting (85). Services provided in a home setting include skilled
the end of the day and individually (no other CF patients nursing care, respiratory therapy, infusion therapy, wound care,
at the same time). dialysis, nutrition therapy, physical and occupational therapy,
5. Clean all equipment after each of these patients, using and hospice care. Home health care is a growing segment of the
standard disinfectants (82). health care delivery system. Many patients cared for at home
6. Develop restrictions for patients with respiratory infections, are immunocompromised, are of advanced age, and/or have
such as colds and influenza, and gastrointestinal/diarrheal a chronic illness. In addition, they may have various types of
illness. Provide information to patients, parents, guardians, devices, including intravascular and urinary catheters, and use
and/or caregivers about these restrictions and expectations. equipment that require management (e.g., ventilators); risks
7. Wound care: dispose of dressings using Standard Precau- for infection are generally associated with these devices, for ex-
tions and follow local health department regulations for ample, BSis due to intravascular devices. Staff may be at risk
medical/regulated/biohazardous waste. Wear gloves, face during contact with patients who have communicable diseases.
Much of the care provided in the home is by someone other 17. Develop a system to manage equipment taken to/from the
than a health care worker (e.g., family members). These inpatient's home (e.g., clean items always placed in a clear
dividuals also play an important role in infection prevention. bag and used items placed into a colored plastic bag).
Education of caregivers in hand hygiene, aseptic practices, care Separate clean and dirty areas and items.
of devices, use ofPPE, disinfection practices, and other aspects
of care are extremely important. Caregivers also should be in-
formed of appropriate signs and symptoms of infection.
Surveillance for infections is a challenge for home care
INFECTION PREVENTION AND
agencies due to the difficulty of obtaining information. Data CONTROL PROGRAM
should be collected for high-risk infections in the populations
served; these may include urinary tract infections, BSI, pneu- INFECTION CONTROL PROFESSIONAL
monia, and skin/soft tissue infections. Definitions on surveil- Responsibility for IPC programs in ambulatory care settings
lance criteria have been published for home care (86). may be designated to a staff member with access to external
Home care agencies should monitor for BSI and catheter IPC experts or an infection control professional/infection pre-
tunnel or exit site infections in their patients who receive home ventionist (ICP/IP) with specialized training. It should be clear
infusion. If patients are on ventilators, they should be moni- who has the designated responsibility.
tored for the development of respiratory infections. Clinical Specific activities include surveillance, data management
home care staff will need to help collect data by identifying pa- and analysis, cluster investigations, quality improvement activi-
tients with clinical signs and symptoms of infection. They can ties, patient and staff education, policy and procedure updates,
then report the information to a central individual responsible product and construction evaluation, site surveys, consultation,
for IPC. That person will then apply the definitions and make and exposure investigations. A staff member may be assigned
recommendations for changes in practice when appropriate. many of these responsibilities. However, if necessary, the services
Specific measures to prevent infections include the follow- of a trained ICP/IP should be obtained as a consultant (89,93) .
ing (87-91): Whoever is assigned the responsibility for IPC, the program
must include both clinical and support teams to ensure success.
1. Use Standard Precautions with attention to hand hygiene. Specific information on designing an IPC program is outlined
Alcohol-based hand sanitizers, soap, and clean paper or in Chapter 5.
cloth towels should be brought to the home by the health
care worker.
2. Protect immune patients to prevent communicable disease SPECIFIC IPC ACTIVITmS IN AMBULATORY
transmission as necessary. CARE/HOME CARE (6,94-100)
3. Transport clean and sterile supplies in a manner to prevent
D11'UJ Mlln~~gement
contamination (e.g., in a travel bag).
4. Setup a clean work surface, (e.g., use of clean paper towel). One of the m~or functions of an IPC program is data manage-
5. Use safety devices and carefully discard sharp items; take a ment. Chapter 6 discusses surveillance; therefore, this section fo-
container to the home, if necessary. cuses on issues pertinent in ambulatory and home care settings.
6. Handle fluids (e.g., sterile water) in a manner to prevent A surveillance plan should be developed. It should outline
contamination. Use small bottles, carefully handle caps, what types of infection will be monitored (outcome surveil-
and store properly. lance) (101-103) or what practices will be routinely evaluated
7. Provide enteral feedings safely: refrigerate; thoroughly (process surveillance) (104,105). In addition, the plan should
clean blender parts, measuring utensils, and other reusable note the methods used to disseminate data to appropriate staff.
items after use. Allow to thoroughly dry. Hang feedings for Healthcare-associated SSis post-runbulatory care surgery or
only recommended time limits. Use clean technique to BSis after infusion therapy or dialysis are appropriate outcome
prepare and administer enteral feedings. measures for settings that perform these procedures. There
8. Follow intravascular device guidelines and ensure proper are no specific definitions for HAis in ambulatory settings. The
handling and storage of medications (78). general definition used for an HAl is the development of an in-
9. Provide sterile solutions for intravenous infusion. fection not present or incubating at the time of the visit or inter-
10. Develop procedures on frequency of ventilator tubing vention. Any definition must include a temporal association with
changes, tracheostomy care, and use of gloves when suc- the visit or care provided. For example, a BSI occurring within 48
tioning and disinfecting suction catheters, canisters, and hours of a visit to an infusion center may be considered an HAl.
tracheostomy cannula. Suctioning is usually performed us- Any surveillance activities measuring outcomes must con-
ing clean rather than sterile technique (92). sider how to obtain information. Patients in these settings may
11. Develop procedures that outline maintenance require- not return to the same provider for follow-up if an infection
ments for respiratory care equipment. occurs. Systems to identify these patients may include coordi-
12. Outline aseptic practices related to urinary catheterization. nation with hospitals, provider offices, or home care services.
Clean technique is appropriate. Disinfect urinary drainage Methods to obtain information may consist of phone calls to
bags per safe protocols. patients or providers, patient mail-back questionnaires, or pro-
13. Use clean technique during wound care. vider surveys; laboratory and radiology reports; risk manage-
14. Teach caregivers methods to prevent pressure ulcers. ment database; and communication with staff.
15. Perform safe injection practices, including use of safety Surveillance of processes may be used to review the care
devices. and maintenance of instruments and equipment and practices.
16. Clean surfaces contaminated with body fluids; the proce- This system focuses on observations using a survey tool to col-
dure should include use of a surface disinfectant and gloves. lect information. Table 28.1 provides an example of questions
Pm......t Silver Spring, MD: U.S. Food and Drug Adminiltration. http://www.fda.gov/
TABLE 28.1 Example of an Ambulatory MedicalDeoicet/Safety/AlertaandNotices/uan305757.htm. Acce&sed May 24. 2013.
6. Friedman C, Pete1:1en KH, ed.o. Infts:#.,. Comrol in AmbaiGior)o C..... Sudbury, MA:Jones and
Care Survey Tool Bartlett Publilhe11; 20M.
7. 1\unberg W, Daniell W, Seixal N, et aL Appraiaal of recommended reopiratory infection
High-level Disinfectant Safely, control practices in primary care and emergency department aettingl. Am] Infoa CofltnJl.
Effectively Used Yes No 2008;!6:26&-275.
8. Matlow AG, MorriJ SK. Control of antibiotic-re1iatant bacteria ill the ofli.ce and clinic.
Are containers: completely covered? Labeled with CM4f c...u.dion Mid &soc]. 2009;180:1021-1024.
chemical name and safety or environmental 9. Rodrigua-Bano J, Ngugro MD. EJ<tellded-tpectrum [beta]-lac:tam3aeo in ambulatory care:
a clinicd pcropective. Clin Micrubiollrif«t. 2008;14(ruppl1) :104-110.
hazard? Oiecked each day for minimum
10. Petersen K. Ambulatory care. Ill: AP1C 1iott ofltlfl&liotl Ctmlrolaruf,~ 3ni eel. Wuh-
effective concentration? Results recorded? illgton, DC: Aaoociation for Profallionah in lllfcction ControllWd Epidenriology; 2009.
Labeled with expiiation date? 11. Buic Infection Control and Prevention Plan for Outpatient Oncology Setting> 2011.
Aie devices thoroughly cleaned before soaking http:/ /www.cdc.gov/hlli/ pdD/guidcline•/basic.mfectioiH:Ontrol-prevention-plan-2011.pdf.
in disinfectant? Acceooed May 24, 2015.
12. Guide to Infection Prevention for Outpatient Setting~: Millinlum hpectatiom for
Are devices completely immersed in Safe Care 2011. http:/ / www.cdc.gov/HAI/ pdfJ/ guidelineo/otandatdJ.<>f"l..IlbulaWry-<:are-
dWnfectant? 7-2011.pdf. Printable guide. http:/ / www.cdc.gov/ HAI/:oettingo/ outpatienVchecklist/
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CHAPTER
29 Nimalie D. Stone and Chesley L. Richards, Jr.
Infections in Long-Tenn Care Facilities

INTRODUCTION for the first time remained in the facility >90 days (7). The
rise in admissions receiving postacute, skilled nursing services
Long·tenn care is broadly defined as "an array of health, per· suggests that nursing facilities are no longer serving as destina·
sonal care, and social services, provided over a rustained period tions, but often are bridging the transition between hospitaliza-
of time to persoWI with chronic conditions and with functional tion and return to home in the community.
limitations" (1). Wbil.e these service& can be provided in the LTCF staffing is lower than staffing in acute care hospitals.
home and community settings, the focus of this review will be Nationally, LTCFs have one-third the number of full. or part·
on infection control issues that are relevant to licensed long· time employees (1.7 million vs. 5.0 million) at acute care hos-
term facilities (LTCFs), mainly certified nursing facilities (nun- pitals (8), even though there are more LTCFs than acute care
ing homes and skilled nursing facilities). In contrast to acute hospitals (15,700 vs. 5,800) and >50% more ll'CF beds. Of
care facilities, LCTF residents generally stay in the facility from the 900,000 nursing staff working in LTCFs, >600,000 are certi-
several weeb to years, and in some instances may represent fied nune's aides (5). Consequently, nune's aides provide the
the final home for many individuals. Consequently, staffing bulk of direct resident care in most LTCFs, while registered
and policies are oriented toward maximizing function, inde- nurses (RNs) and licensed practical nurses (LPNs) supervise
pendence, social function, and resident and family satisfaction. overall care and provide medical services, such as medication
The traditional LTCF resident is a cognitively or functionally di!tribution. Eapecially during evening/night shifts or during
impaired elderly adult. However, recent trends have seen in- weekends, a typical 100-bed LTCF may have only one or two
creases in the number of individuals entering LTCFs to receive RNs or LPNs on duty. Improving the ratio of nursing staff to
postacute care services (e.g., rehabilitation following a surgi- residents and expanding the presence of RNs has been pro-
cal operation or acute illness) or skilled nursing services (e.g., posed as important steps toward improving the quality of care
intravenous antimicrobials, parenteral or enteral nutrition, or in nuning homes (1).
aggressive wound care) following a hospitalization. This chap- Less than 20% ofLTCFs have a phyaic:ian on staff and dire<:t
ter will review LTCF characteristics, selected infections in LTCF medical care rarely is provided by physicians. The mcgority of
residents and facilities, and infection control issues in LTCF. physicians (77%) do not spend time caring for nursing home
residents (9). For physicians who provide nursing home care,
the median effort is 2 hours per week, or approximately 4% of
CHARACTERISTICS OF LTCF the phys:i.c:ians' overall practice time. Very few physicians (3%)
spend >5 hours per week providing medical care in nursing
RESIDENTS, STAFF, AND CLINICIANS homes. Barriers to optimal medical practice in LTCFs by phy-
sicians include inadequate documentation, lack of nursing
LTCF CHAllACTBRISTICS
support, and insufficient reimbursement (10). Consequendy,
In the United States, >40% of adults will reside in an LTCF at nonphysician clinicians provide much of the direct medical
some point during their life (2.~). Of 3.~ million people who care in LTCFs. In a national swvey of LTCFs, 63% reported
spent time in certified nursing facilities in the United States having nurse practitioners with a median of two nurse prac-
in 2009, most were female (65%), age >75 years (69%), and titioners per facility ( 11). On-site nonphysician clinicians can
white (8~%); however, the population of nuning facility resi- reduce hospitalizations of LTCF residents and overall costs
dents is becoming more ethnically diverse and proportion of (12,1!).
people <65 years is increasing ( 4). Additionally, >50% of resi- In addition to practicing clinicians, each nursing home
dent~ in nursing facilities require extensive support with activi· is required to have a medical director who is respoWiible for
ties of daily living, such as toileting, bathing, eating, dressing, providing "oversight and participate in drug utilization review
or transferring. and quality assurance programs and to work with attending
In 2004, the median stay in nuning facilities was 463 days, physicians on appropriate drug therapies and medical care
and most residents came &om a hospital (36%) or private resi- issues" (1). Most medical directors are either internists or
dence (29%) (5). However, a growing proportion of residents family physicians and on average spend 10 to 20 hours per
are entering nursing facilities from hospitals. In a cohort of month performing medical director responsibilities, which in-
2!0,7!0 newly admitted residents in 9,7~8 nursing facilities, clude infection control and resident safety. At a national level,
70% entered the facility following di!charge from hospitals the American Medical Director's Association (AMDA) is the
with Medicare coverage for skilled care (6).In 2005, only 27% primary professional organization for medical directors and
of unique individuals admitted to a certified nursing facility provides training and certification for medical directors (14).
Chapt~ 29 • Infections in Lon~Term Care Facilities 441
LTCFs often have consultant pharmacists on staff or avail- Indeed, with the growth of subacute or postacute care, many
able by contract who evaluate medication prescribing in the LTCFs now have residents receiving medical care (e.g., central
facility and provide consultation regarding drug therapy is- venous catheters, hemodialysis, parenteral antimicrobial or nu-
sues. In most LTCFs, consultant pharmacists perform manda- trition therapy, or mechanical ventilation) equivalent in com-
tory medication reviews and provide feedback to the LTCF plexity to interventions performed in many acute care hospitals.
administrator and medical director. Consultant pharmacists Challenges identifying infections arise because LTCF resi-
may offer an important on-site perspective and expertise in dents may present atypically. A study assessed the clinical signs
improving the management of a wide range of medications, and symptoms of older adults (>75 years) with bacteremic uri-
including antimicrobials, and should be seen as a potential re- nary tract infections and found 10/ 37 (27%) did not mount a
source for clinicians and medical directors regarding antimi- fever >37.9°C and 48.6% failed to report any localizing urinary
crobial management (15). During disease outbreaks in LTCFs, tract symptoms (e.g., dysuria, urgency or frequency) (22). A
consultant pharmacists also may provide valuable resident and large study reviewing clinical presentations of nursing home
family counseling regarding medication side effects or sup- residents with and without radiologic evidence of pneumonia
port regarding the distribution of prophylactic antimicrobials found that cough and sputum production did not discriminate
(e.g., oseltamivir) (16). between residents with and without pneumonia, while new
somnolence or confusion seemed more prevalent among those
with confirmed evidence of pneumonia on X-ray (23). There-
FACTORS THAT IMPACT fore, nonspecific signs and symptoms should prompt further
PREVENTION AND CONTROL investigation for potential infections in this population, and ab-
OF INFECTIONS IN LTCFs sence of typical clinical signs of infection may not reliably rule
out an infection being present.
RESIDENT POPULATION
Many of the residents in LTCFs have underlying risk factors FACILITY ENVIRONMENT AND STRUCTURE
which increase their susceptibility to infections. Age-related Although there are increases in the short-term skilled nurs-
changes to immune functioning (immunosenescence), chronic ing and rehabilitation services being provided, the majority of
diseases, and malnutrition all interact to diminish host defenses LTCFs continue to serve as primary residences for a popula-
to infections and blunt response to preventative measures like tion of frail and aging individuals who are no longer able to
vaccination (17,18). Cognitive deficits, functional impairments reside independently in the community. Culture-change and
(e.g., fecal and urinary incontinence, immobility, diminished resident-centered care movements advocate for the creation of
cough reflex), and frailty also increase vulnerability to infections a "home-like" environment to reduce the institutional feel of
by limiting an individual's ability to maintain personal hygiene these facilities (24). Communal living arrangements, such as
and increasing dependence on caregivers (19) (Table 29.1). a dining hall, resident lounge, and group activities, all foster
Medical interventions, such as indwelling devices and wounds, socialization and enhance relationship building among resi-
have been shown to increase the risk of infection (20,21). dents, staff, and visitors both in and outside the nursing home.
However, the frequent close interactions within large groups
of individuals and use of shared equipment also can facilitate
TABLE 29.1 Individual-Level Risk the spread and acquisition of communicable infectious diseases
Factors for Infection through both direct person-to-person spread and indirect ex-
in LTCF Baidents posure to contaminated surfaces and materials (25,26).
LTCF staffing and other processes of care also may have
• Immunologic senescence
• Lack of vaccination impact on the risk of infections among residents. Studies have
• Influenza, pneumococcal identified turnover among RNs and low staff levels of all levels of
• Malnutrition nursing staff including aides have been associated with increased
• Chronic c!Ueases risk of infection among residents and more frequent receipt of
• Cancer infection control program deficiency citations during facility
• Diabetes mellitus
inspections (27,28). In a study of outbreaks among New York
• Emphysema, chronic bronchitis
• Congestive heart failure LTCFs, institutional risk factors for respiratory or gastrointesti-
• Peripheral vascular c!Uease nal infection outbreaks included larger homes (risk ratio 1. 71
• Medications per 100 bed increase), nursing homes with a single nursing unit,
• Immunosuppressants or with multiple units but shared staff. Risk for outbreaks was
• Central nervous system agents that diminish cough reflex lower in LTCFs with paid employee sick leave (29) .
• Cognitive deficits that may complicate resident compliance with
basic sanitary practices (e.g., hand hygiene)
• Functional impairmenu
• Fecal and urinary incontinence EPIDEMIOLOGY OF SELECT
• Immobility INFECTIONS IN LTCFs
• Diminished cough reflex
• Medical interventions
• Central venous catheters, hemodialysis
GENERAL PRINCIPLES
• Urinary catheters, gastrostomy catheters A study estimated the burden of infections occurring in
• Parenteral antimicrobial or nutrition therapy
LTCFs to range from 1.6 million to 3.8 million annually (30).
• Mechanical ventilation
Data used to calculate these burden estimates were limited
to reports from research studies involving small numbers of ASB from infection contributes to inappropriate antimicrobial
facilities using different methodologies to define infections. use and its related complications. Suspected UTis account for
Additionally, these studies exclusively represent skilled nursing 30% to 60% of antimicrobial prescriptions in the LTCF setting
facilities and nursing homes (SNF/NH) and were conducted (38-40). Antimicrobial use for prevention or treatment of ASB
many years ago. With the rising number of individuals receiv- in LTCF residents, does not confer any long-term benefits in
ing more complex medical care in SNF/NHs, it is possible that prevention of symptomatic UTI or improving mortality, but has
these numbers underestimate the true magnitude of infections been shown to increase the incidence of adverse drug events
in this setting. Data are lacking from other settings, such as as- and result in subsequent infections with antibiotic-resistant
sisted living facilities or senior residential care settings. Most in- pathogens (41).
fection rates are calculated only for endemic infections and fail
to account for the many infections related to outbreaks which
RESPIRATORY TRACT INFECTIONS (RTis)
frequently affect this population. Morbidity and mortality due
to infections in LTCF is substantial. Infections are among the Similar to UTI, RTis are frequently reported and are a maJor
most frequent causes of transfer to acute care hospitals and driver for antimicrobial use. In a 3-year surveillance study of
30-day hospital readmissions from LTCF (31,32). Infections lower respiratory tract infection (LRTI) outbreaks in 5 LTCFs,
also have been associated with increased mortality in this the overall rate ofLRTI was 1.75 per 1,000 resident-days (range
population (33,34). within different nursing homes 1.4 to 2.8), with 43% of those
Providers working in LTCFs face many challenges in iden- infections occurring in the context of an outbreak (42). Anti-
tifying and initiating appropriate management for suspected microbial use for LRTI can be as high as 50% with appropriate-
infections. As outlined above, underlying conditions com- ness ranging from 87% for pneumonia to only 35% for episodes
monly affecting LTCF residents result in atypical manifestation of acute bronchitis (42,43). Morbidity and mortality associated
of infections and difficulties eliciting clinical signs and symp- with outbreaks of LRTis in LTCFs can be significant. Between
toms. Clinical providers are frequently off-site and therefore 2000 and 2002, LRTis were the leading infectious disease cause
make management decisions based on the assessments com- of both hospitalization and death among people >65 years old
municated by front-line staff. The use of surrogate assessments (44). In a cohort study of 353 LTCF residents with LRTI, 22%
and the lack of immediate access to provider follow-up likely were transferred to the hospital and 9% died within 30-days of
drive antimicrobial use and frequent hospital transfers. Many infection ( 45) .
facilities have limited diagnostic testing (e.g., laboratory or ra- The variety of bacterial and viral pathogens which cause
diology) available for febrile or potentially infected residents. LRTis in LTCFs creates a unique set of challenges for preven-
Most laboratory services are contracted out to a local hospital tion and control. The cognitive and functional impairments
or reference laboratory which can lead to delays in obtaining (e.g., difficulty swallowing, impaired cough, limited mobility,
specimens, processing, and reporting results back to providers. oxygen dependence) increase an individual's risk for pneumo-
To address the challenges faced by providers working in LTCF, nia and other LRTis. The impaired immunity of elderly per-
several clinical guidelines outlining the evaluation and criteria sons, allows viral upper respiratory infections (URis) which are
for defining infections in nursing home residents have been generally mild in adult populations to cause significant disease
published (35,36). Implementation of these guidelines could in LTCF residents (46). Clinical presentation of LRTis in
standardize the process for evaluating residents with suspected LTCFs may not discriminate severe viral infections from pneu-
infection to ensure appropriate information is being identified monia, so early implementation of respiratory precautions for
and communicated by nursing staff to clinical providers. residents with cough and fever, until a definitive diagnosis has
been determined, may help reduce transmission of communi-
cable infections.
URINARY TRACT INFECTIONS (UTis)
UTis account for 25% to 30% of all bacterial infections in
INFLUENZA AND OTHER VIRAL
LTFC residents and are among the most common bacterial
RESPIRATORY INFECTIONS
infections in LTCF residents (21,37). Although ordinarily the
bladder is sterile, many older individuals have alterations in Although influenza is the most commonly reported cause of
the functionality of the urinary tract due to medical conditions LRTI outbreaks, many respiratory viruses which are not gener-
(e.g., stroke, diabetic neuropathy, prostate hypertrophy) that ally thought to cause severe infections in adults have emerged
result in incomplete emptying of the bladder, urinary reten- as significant causes of LRTis in LTCFs (47) . Parainfluenza
tion, and chronic bacteriuria. The use of urinary catheters to virus, human metapneumovirus, respiratory syncytial virus,
manage urinary drainage issues also facilitates bacterial entry human adenovirus, and rhinoviruses all have been implicated
into the urinary tract. The prevalence of asymptomatic bacte- in outbreaks of LRTis in nursing home settings, with attack
riuria (ASB), bacteriuria without localizing signs or symptoms rates as high as 50% to 70% (46,48-52). While most commonly
of infection, ranges from 25% to 50% in noncatheterized LTCF occurring in the winter season, influenza and other respira-
residents and 100% among those with long-term urinary cathe- tory viruses can circulate throughout the year, and small off-
ters; ASB is accompanied by pyuria (e.g., ~5 white blood cells/ peak outbreaks can be missed by surveillance programs (42) .
high power field on direct microscopic exam of the urine) in Use of molecular-based respiratory diagnostic testing for viral
>90% of instances (37). Therefore, use of pyuria or bacteri- LRTis (e.g., multiplex polymerase chain reaction assays), could
uria as indicators of UTI in frail elderly patients or catheterized increase the identification of respiratory viruses causing LRTI
patients without clinical symptoms is not recommended. The outbreaks and hasten initiation of appropriate management.
unreliable clinical assessment for infections in LTCF residents However, even before a causative pathogen has been identified,
coupled with the diagnostic uncertainties in differentiating LTCFs should be proactively implementing infection control
measures, such as use of respiratory droplet precautions, co- etiology ofNHAP. Streptococcus pneumoniaewas identified as the
horting of symptomatic residents, and enhanced surveillance bacterial cause in 58% of episodes in one 10-year prospective
for LRTI symptoms among residents, healthcare personnel study of 150 patients with NHAP, while gram-negative bacilli
(HCP), and visitors, to reduce the spread of infection through- (e.g., Haemophilus influenza, Pseudomonas sp. Klebsiella sp.) were
out the facility. more common than S. pneumoniae in a cohort of 115 episodes
Vaccination of residents and HCP is one of the main cor- (65,66). Neither study showed high prevalence of multidrug-
nerstones of preventing influenza outbreaks in LTCFs. Studies resistant organisms causing NHAP, but these episodes often
have demonstrated preventive efficacy rates of influenza vac- were more severe. Although infrequently identified as a cause
cination in elderly residents of LTCFs to be 23% to 43% for of NHAP in prospective studies, Legionella spp. have been
influenza-like illness, 0% to 58% for influenza, 46% for pneu- reported in several outbreaks of pneumonia in LTCFs and
monia, 45% for hospitalization, 42% for death from influenza should be considered as a cause of sporadic NHAP if there is
or pneumonia, and 60% for death from all causes (53,54). Since evidence of Legicnella colonizing the water distribution system
2005, the Centers for Medicare and Medicaid Services (CMS) of a facility (67).
has required that certified nursing homes offer residents an- A multifaceted approach should be taken to assess the risk
nual influenza vaccination and started reporting vaccine cov- of and implement strategies to prevent NHAP in LTCF resi-
erage rates among residents as a quality measure. A recent dents. As outlined previously, identifying and addressing modi-
study of patterns in influenza vaccination coverage in certified fiable risk factors, such has improving oral hygiene, has been
nursing homes showed that although the median coverage was shown to be feasible and effective (68) . A universal approach
73%, there was evidence of significant differences in vaccine to LRTI prevention has been through promotion of both in-
coverage between black and white residents, as high as 10%, at fluenza and pneumococcal vaccination (69). Despite concerns
the state level due to lower vaccination rates in facilities which about decreased vaccine efficacy in the aging population, the
cared for a predominantly black resident population (55). This use of the influenza and the 2g...ya}ent pneumococcal polysac-
finding highlights the importance of culturally appropriate charide vaccines has been shown to confer protection against
strategies for promoting influenza vaccination in LTCFs. Im- invasive pneumococcal disease, pneumonia-related hospitaliza-
proving rates of HCP influenza vaccination in LTCFs also has tions and mortality in nursing home residents (70-72).
been associated with better outcomes among residents during
outbreaks (56-58). In a national survey of clinical nursing as-
GASTROINTESTINAL INFECTIONS
sistants (NA) working in LTCFs, only 37% reported receiving
influenza vaccine. Multivariable analysis showed longer tenure Acute diarrheal infections and gastroenteritis (GE) are the
in the facility, higher numbers of benefits offered by the facil- most common gastrointestinal infections in LTCFs and are asso-
ity, and self-reported feeling of being "respected/ rewarded for ciated with significant morbidity and mortality. In a population
their work" as factors which increased receipt of vaccine (59). level study ofGE episodes from unknown cause, LTCF residents
Facilities which actively work to promote HCP influenza vac- accounted for 17.5% of the deaths, and had the highest death
cination can show improvements in coverage, however, barriers rate compared to any other group (73,74). Among the acute
which must be overcome include individual perceptions of the GE outbreaks entered into the national outbreak reporting
risks and benefits to the vaccine as well as facility-level factors system (NORS) which included information on the setting of
such as staff turnover (60). the outbreak, 80% were reported from LTCFs (75). A variety of
pathogens have been reported in food-borne outbreaks of GE
in LTCFs, including Escherichia coli, Shigella sp., Salmonella spp.,
PNEUMONIA
Campylobactlrspp., and Listeria sp., however, norovirus accounts
Nursing home acquired pneumonia (NHAP) is one of the for the m<J:iority of acute person-to-person GE outbreaks, while
leading infectious causes of hospitalization and death in the Clostridium difftcile is the leading cause of endemic episodes of
LTCF population (61). In a 3 year prospective cohort study in acute diarrheal infection in LTCFs (76,77).
5 LTCFs, the rate of NHAP was 0.7/1,000 resident-days, with
31% requiring hospitalization and 9% dying within 14 days of
Noro11irus
the diagnosis ( 62). Many risk factors for NHAP result from ag-
ing and/ or underlying conditions, such as impaired swallowing Norovirus outbreaks in LTCFs can cause serious disruptions
or cough reflex, advanced dementia, malnutrition, functional in the normal services and care provided. Characterizations of
decline/mobility impairment, and presence of feeding tube. outbreaks in the literature report that predominant symptoms
However, potentially modifiable risk factors include witnessed include vomiting (70%) and diarrhea (80%), with an observed
aspiration events, use of sedating medication, and lack of oral case-hospitalization rate of 3.1% and case-fatality rate of 0.5%
care (63,64). (78). Attack rates among residents and staff can be as high as
Identification of a causative pathogen in episodes of NHAP 55% and 35%, respectively, with a median of 35 residents im-
often is limited by access to diagnostics and quality of speci- pacted during an outbreak and an average duration of 11 days
men collection. In a prospective cohort of patients >65 years (79). Critical control measures identified from outbreaks in-
presenting with either community acquired pneumonia clude rapid identification of clinical episodes with appropriate
(CAP) or NHAP, an etiology was identified in <30% of epi- use of isolation precautions, hand hygiene, and environmental
sodes despite >90% of subjects undergoing diagnostic testing cleaning/disinfection to reduce transmission from person-to-
(65). Similar to a previous study of LRTI in LTCF residents, person. Experience from a large multi-facility outbreak high-
this study showed respiratory viruses were the most com- lighted the role of asymptomatic or mildly symptomatic HCP
monly identified etiology in instances of NHAP (61,65). Data working in several facilities as sources of spread across geo-
are mixed in the literature about the most common bacterial graphically distant facilities (79) . The recommendations in
guidelines for prevention and control of norovirus outbreaks in pathogen transmission in healthcare settings is entirely pr~
the health care settings are applicable to and should be impl~ ventable by adherence to standards of care including appropri-
mented by LTCFs (80). ate staffing and infection control. Staff members who perform
percutaneous procedures should receive appropriate training,
and in particular, hand hygiene and glove use (e.g., changing
Clostridi'Um Difficile
gloves and cleaning hands between patient contacts when per-
C. difficile infection (CDI) is a common and sometimes fatal forming fingersticks) needs to be promoted and monitored in
healthcare-associated infection. Data from a population-based LTCFs (90). Failure to identify new episodes of acute infection
surveillance system showed that 75% of healthcar~sociated and suspect healthcare-associated transmission of blood-borne
CDI had onset among persons not currently hospitalized, in- pathogens can limit the detection of outbreaks in LTC settings.
cluding recently discharged patients, outpatients, and nursing Healthcare providers should consider performing specific sero-
home residents (81). Mandatory CDI reporting from Ohio logic testing for hepatitis B virus (HBV) or HCV infection when
health care facilities in 2006, revealed more than half the total evaluating LTCF residents whose illness includes unexplained
burden of healthcar~sociated CDI patients may have their hepatic dysfunction or substantially elevated aminotransferase
onset in LTCFs, primarily nursing homes (82). The hospital- levels (AST or ALT). Evidence of acute viral hepatitis in any
izations and deaths associated with CDI are disproportionately resident of a nursing home or other LTCF setting should be
higher among people >65 years old, making the population in reported to public health authorities who can provide assis-
LTCFs particularly vulnerable to severe infection and complica- tance in determining the source of the infection (90).
tions from C. difficile (83).
Risk factors for infection and colonization with C. difficik
SKIN AND SOFI' TISSUE INFECTIONS
in LTCF residents include frequent health care exposure,
frequent antimicrobial exposure, reduced gastric acid from Skin and soft tissue infections are the third most common in-
medications or underlying comorbidities, and ag~related im- fection identified in LTCF residents (21). Risk factors for more
pairments in the immune response to the organism (84). The serious or invasive skin infections in LTCF residents include
prolonged survival of C. difficile on surfaces of equipment and presence of wounds from recent surgery or pressure-related
the environment facilitates transmission of this organism in skin breakdown, skin maceration or wetness due to inconti-
the shared living space of LTCFs. Asymptomatic colonization nence and immobility, presence of underlying comorbidities
among residents entering LTCFs from the hospital setting associated with vascular insufficiency and poor wound heal-
also contribute to the reservoir of transmission and increases ing (e.g., diabetes), and poor nutritional status (91). While
risk of relapsing infection in this population. The prevalence presence of a wound will increase risk for more invasive skin
of asymptomatic colonization in LTCFs has ranged from 5% infections, such as cellulitis or osteomyelitis, differentiating in-
in non-outbreak settings to as high as 50% in the setting of a fected wounds from colonized wounds can be challenging in
large outbreak (85,86). Given its strong association with recent the LTCF setting, and inappropriate management of wounds
antimicrobial use, a LTCF resident who develops acute diar- can result in excess antimicrobial exposure and emergence of
rhea, especially during or after completion of a course of an- antibiotic resistant organisms (92,93).
timicrobials, should be suspected of having CDI and undergo S. pyogmes, a common cause of cellulitis and wound infec-
appropriate diagnostic testing, treatment, and implementation tions, can cause outbreaks of severe infections including bac-
of pr~mptive contact isolation precautions. LTCFs should teremia, necrotizing fasciitis, and sepsis in LTCF residents
ensure that infection prevention and control policies are in (94-96). Invasive group A streptococcal (iGAS) infections
place, including judicious use of antimicrobials, CDI surveil- in LTCFs have a substantially higher incidence compared to
lance, consistent hand hygiene practices, appropriate use of older adults living in the community (41.0 vs. 6.9 episodes per
gloves and other infection-control measures, and adequate en- 100,000 population) and are associated with a higher case fatal-
vironmental cleaning and disinfection to prevent both new and ity (97). There is a broad range in the ways that iGAS outbreaks
relapsing CDI in this population (81,84). occur in LTC. Some outbreaks evolve dramatically over a short
few weeks and last 1 to 2 months while others are characterized
by intermittent identification of episodes over several months
Viral Hepatitis
and extend for several months to over a year (98). As outlined
Outbreaks of viral hepatitis B and C in U.S. health care set- in other sections, breaches in basic infection prevention and
tings have renewed awareness of the risks associated with un- control practices including hand hygiene, have been impli-
safe infection practices, specifically highlighting assisted blood cated in the setting of clusters of episodes in an iGAS outbreak,
glucose monitoring practices in diabetes care. LTCFs (nursing but a unique issue frequently highlighted by these events is
homes and assisted living) were the setting for 15/33 (45%) the ability of a LTCF to get information about outcomes, and
of a series of hepatitis B and C outbreaks linked to unsafe causes of infections for residents who are transferred to acute
blood glucose monitoring practices in nonhospital health care facilities before an etiology has been identified. Failures
care settings between 1998 and 2008 (87). As a result of these among referring facilities to communicate identification of
outbreaks, 97 residents were found to have newly acquired serious infectious pathogens, like S. pyogrmes or C. difficile, to
hepatitis B infection among the 900 residents screened of the LTCFs can prevent recognition of transmission and spread of
1,700 residents considered at risk of exposure. Promoting safe these organisms to other vulnerable residents (94,98) .
diabetes care in LTCFs is critically important as the popula- Scabies is an important parasitic skin infection also known
tion of people entering LTCFs with diabetes expands and the to cause outbreaks in LTCFs. Transmission of scabies may oc-
aging cohort of people with chronic hepatitis C virus (HCV) cur by contact with mi~ontaminated inanimate ol!jects (e.g.,
infection starts entering these facilities (88,89). Blood-borne bed linens) or direct person-to-person contact. Outbreaks of
scabies in three Norwegian LTCFs lasted for 5 months and oversight and education about infection prevention in these
involved 27 patients or HCP (99). Initial treatments with per- LTCFs (118,119). As with other sections of this chapter, this dis-
methrin were not successful; however, benzyl benzoate was ef- cussion on infection prevention and control in LTCFs will focus
fective. Ultimately, >600 residents and staff were treated. A key on issues specifically for certified nursing facilities.
observation from these outbreaks was the need for simultane-
ous treatment of residents and staff and disinfection of bed-
INFECTION CONTROL PROGRAM OVERSIGHT
ding, clothing, and the environment. High clinical suspicion
and early identification are critical to prompting the appropri- The guidance for developing and implementing an infection
ate evaluation needed to confirm a diagnosis of scabies, for ex- control program and infection prevention practices in a cer-
ample through dermatologic consultation or skin scraping for tified nursing home are provided by CMS through the inter-
microscopic review. Failure to make the appropriate diagnosis pretive guidance for the federal regulatory tag for infection
can result in large outbreaks impacting both staff and residents control (F-tag 441) (116). The F-tag 441 forms the basis for cita-
and leading to high costs (100). tions when licensure and certification surveys identifY deficient
infection prevention and control practices. A study exploring
national trends in F-tag 441 citations for certified nursing facili-
INFECTIONS WITH MULTIDRUG-RESISTANT
ties from 2000 to 2007 found that the percent of infection con-
ORGANISMS (MDROs)
trol program citations increased from 2000 to 2007 (12.8% to
The health care exposures within the LTCF population, includ- 17.3%) with infection control being the ninth most frequently
ing frequent hospitalization, antimicrobial exposure, use of in- cited deficiency on average across the country (120). The rate
dwelling devices, presence of wounds, and increased caregiver of citations varied by state, and nearly 50% of citations were
dependence for help with daily activities also are risk factors at a severity level of "potential for more than minimal harm."
for colonization and infection with MDROs (101,102). Nursing Multivariable analysis found lower staffing at every level (i.e.,
home residence often is identified as a risk factor for coloni- nurse aides, licensed practical nurses, and registered nurses)
zation and infection with MDROs among patients admitted to was significantly associated with receipt of a higher number of
acute care hospitals (103,104). LTCFs often are described as F-tag 441 citations by a facility. Other studies have identified
"reservoirs" for MDROs because the prevalence of colonization inadequate staff time dedicated to implementation of infection
with antibiotic-resistant bacteria among residents in a LTCF can control program activities and inadequate infection prevention
range from 10% to 20% for vancomycin-resistant Enterococcus training of the infection control program coordinators as ad-
(VRE) and multidrug-resistant gram-negative bacilli (MDR- ditional challenges for LTCFs (121,122).
GNB) to 40% to 50% for methicillin-resistant Staphylococcus Often LTCFs, which are unable to dedicate a full-time per-
aumu (MRSA) (105--109). Among LTCF residents, infections son to manage the infection control program, will rely on the
from MDROs are associated with more severe infection, hos- input from members of a quality assurance or the infection
pitalization, increased risk of death, and increased cost of care control committee to help guide the program activities. In ad-
(65,110,111). dition to having facility administration and clinical leadership
With a growing population of residents transferring between (e.g., medical director or director of nursing) represented on
acute and LTCFs, the risk for MDROs to emerge and spread the committee, it is important to have the input from front-line
within LTCFs has increased. In a study assessing movement nursing staff, housekeeping/facilities management, and if pos-
of patients between health care settings, >50% of individuals sible pharmacy and laboratory services. Infection prevention
identified with a carbapenem-resistant Enterobacteriaceae (CRE) personnel from affiliated acute care hospitals or other LTCFs
during a hospitalization were discharged to postacute care in the community also could serve as resources for ideas and
facilities such as LTCFs (112). Recent reports have highlighted advice on improving and implementing infection prevention
the role of LTCFs in outbreaks of CRE within a community practices.
(113,114). Communication about infection or colonization As demonstrated by the national F-tag 441 citation trends,
with MDROs at the time of transfer is critically important to awareness of the importance of infection prevention programs
controlling these organisms across health care facilities within in LTCFs is growing. Several states have adopted additional
a community. regulations around the oversight and coordination of infection
prevention programs beyond the federal guidance. In 2003,
Maryland began implementing a state regulation for nursing
INFECTION PREVENTION home certification which required employment of a trained
AND CONTROL IN LTCFs infection preventionist (IP) to manage the infection preven-
tion and control program. This regulation was accompanied by
The infrastructure, staffing, and resources available for infec- the creation of an educational initiative to provide basic infec-
tion prevention and control activities are highly variable across tion control training for LTCF providers to meet the training
different LTCF settings. All certified nursing facilities in the expectations for IPs. By 2008, this regulation and accompany-
United States are required to have an infection prevention and ing education had resulted in a 5-fold increase in the number
control program as part of federal regulations for licensure and of LTCFs reporting presence of a trained IP for the infection
certification (115,116); however, many residential care homes control program (123). A separate, small analysis of data from
and small assisted-living facilities (e.g., <50 beds), which are 20 LTCFs reporting outbreaks to the state health department
licensed only at the state level, may not have formal infection found facilities with a trained IP reported outbreaks slightly
prevention programs or training for staff members (117). Out- earlier to the health department compared with facilities
breaks of viral hepatitis among residents in assisted living set- without a trained IP and had smaller numbers of residents af-
tings have raised awareness of the need for more regulatory fected by the outbreak at the time of the report. As evidence of
the impact of dedicated and/or trained IPs in LTCFs increases, practices for these infection control programs. While a com-
additional guidance on the personnel, resources, and train- prehensive review of all the elements of a LTCF infection con-
ing provided for coordination of infection control programs trol program is beyond the scope of this chapter, the following
should be considered. sub-sections highlight activities which have LTCF-specific chal-
lenges to implementation.
KEY ELEMENTS OF INFECTION
CONTROL PROGRAM Infection SurPeilltl.nce
In 2008, the Society for Healthcare Epidemiology of America Performing infection surveillance is one of the primary and
(SHEA) and the Association for Professionals in Infection Con- often most time-intensive activities done by an IP in a LTCF.
trol and Epidemiology (APIC) published an updated guide- Within the CMS interpretive guidance for the F-tag 441, the
line on infection prevention and control in LTCF (26). In section on infection surveillance outlines all the essential fea-
addition to providing background on infections and identify- tures of a program's surveillance plan including: use of stan-
ing challenges to performing infection prevention in LTCFs, dardized definitions and symptom criteria, use of surveillance
this guideline lists the key elements of an infection control tools such as data collection templates, performing a risk as-
program (Table 29.2). Many of the policies and practices for sessment on the resident populations, specifYing processes
infection prevention and control which are implemented by and/or outcomes selected for surveillance, data analysis for
acute care facilities also are relevant in LTCFs. The portfolio trends, and feedback of results to the primary caregivers (116) .
of guidelines for infection prevention and control for health However, the full implementation of this type of surveillance
care settings published by the Centers for Disease Control and plan is highly variable. An in-depth survey of infection surveil-
Prevention (CDC) and the Healthcare Infection Control Prac- lance and prevention programs completed by 488 Canadian
tices Advisory Committee (HICPAC), available at http://www LTCFs (representing -1/g of eligible facilities) quantified all
.cdc.gov/hicpac/pubs.htrnl, address the implementation of possible surveillance activities into an index score (range 0 to
recommendations in LTCFs and other settings outside of hos- 100). The median surveillance index among respondents was
pitals and also are referenced in the CMS interpretive guidance 62.9 and 82% scored <80 leading the authors to conclude that
for the F-tag 441 infection control regulation (116). However, even with full staff and resources, most programs would still
given the communal living environment and other unique as- be conducting <80% of expert suggested surveillance activi-
pects of care delivery in LTCFs, there are challenges to imple- ties (124). A survey of infection prevention programs among
menting these infection control recommendations in facilities U.S. Veterans Affairs nursing home care units, which tend to
while maintaining the "home-like" resident experience that is have better staffing and infrastructure compared to community
increasingly advocated in nursing homes. Research on strate- LTCFs, identified a lack of standardization in the definitions
gies for adapting these guidelines to meet the infection pre- and criteria used to perform infection surveillance across facili-
vention needs of LTCFs will increase the evidence-base for best ties in the system (125).
Elements of a LTCF Infection Prevention and Control Program

Programs Elemen1s Eumples/Activities
Establish and implement infection prevention policies Hand hygiene
and procedures Standard and Thansmission-based precautions
Infection surveillance Defme case definitions, Determine process and outcome measures,
Establish baseline rates
Identification, investigation and control of outbreab Defme outbreak thresholds, Implement control measures, Notification of
public health authorities
Develop organism-11pecific infection prevention and control Tuberculosis (TB), Influenza, Scabies, Multidrug-resistant organisii18,
procedures C. difJicile
Antibiotic stewardship Review antibiotic use, Provide feedback to clinical providers
Monitor resident care practices Aspiration precautions, Pressure ulcer prevention, Use and maintenance
of indwelling devices
Facility management issues Food preparation/ storage, Laundry handling/ cleaning, Infectious waate
collection/ disposal, Disinfection and cleaning of equipment and
environment
Product evaluation and inventory Single use devices, Auto-disabling sharps, Hand hygiene products,
Personal protective equipment
Resident health program TB screening, Immunizations
Health care personnel safety TB screening, Immunizations, Occupational exposure plan
Quality Assurance/Performance hnprovement Represent infection prevention on quality committees, Disseminate
infection prevention data to facility administration and staff
Preparedness planning Develop plans for natural disasters/ pandemics
Adapted from Smith PW, Bennett G, Bradley S, et al. SHEA/APIC Guideline: infection prevention and control in the long-term care facility.
Infect Contr Hasp Epidemiol. 2008;29:78!;.-814, with permission.
A CDC/SHEA guidance published in 2012, reviewed, Tr11nsmission-Based PreMu.tions

revised and updated definitions and criteria for infection
surveillance in LTCFs (126). These definitions built on Although the CDC/HIPCAC guidelines on both isolation and
the foundation of the first set of infection surveillance cri- management of MDROs incorporate reconunendations for use
teria specifically for use by LTCFs published in 1991 (127). in LTCFs and other nonacute settings (133,134), the practical
While the updated surveillance definitions could become implementation of transmission-based precautions in LTCFs
the standard for LTCF surveillance programs, further evalu- has limited evidence-based guidance and remains a challeng-
ation into implementation and validation of the definitions ing issue. A proposed conceptual model for managing trans-
is warranted. Studies have demonstrated that application mission of MDROs in LTCFs suggests shifting the guidance
of surveillance criteria may underestimate the number of from a pathogen-specific precautions model to one based on
nursing-home-associated infections when compared to pro- resident-specific risk factors (135). As previously discussed,
vider diagnosis of infection (128,129). The discrepancy be- presence of wounds and indwelling medical devices have been
tween events identified by applying surveillance definitions identified as risk fuctors for colonization with MDROs. There-
and events based on clinical diagnosis and antimicrobial use fore, one strategy proposed was the preemptive initiation of
highlights the importance of further evaluation of the sen- contact precautions during direct care of residents with these
sitivity and specificity of criteria used to define infections in specific risk fuctors. Another variation on this idea would be a
this setting. The LTCF Component released in 2012 within syndrome-based approach to implementing transmission based
the CDC's National Healthcare Safety Network (http://www precautions (e.g., contact precautions for diarrhea). Rather
.cdc.gov/nhsn/ltc/) could support the implementation of than focusing on precautions for a specific pathogen, now the
the updated LTCF surveillance definitions and provide an facility would be tailoring care to needs of the resident. Given
infrastructure for data collection, reporting, and establish- the limited access to laboratory diagnostics and the frequently
ing national benchmarks for infections in LTCFs. While this poor communication about MDRO history at care transitions,
LTCF-specific reporting infrastructure represents a major op- the resident-centered approach to precautions might be an eas-
portunity for obtaining surveillance data on a national level, ier and more reliable way to ensure precautions are in place for
many of the IP staffing and program resources, such as access high-risk residents compared to waiting for a specific organism
to IT support, will have to be addressed before this system can to be identified. This could be particularly important in the con-
be maximally used by LTCF providers. text of an outbreak. However, in a survey of LTCF staff, >90%
expressed concern about the negative psychosocial impact
contact isolation precautions could have on the LTCF resident
and -15% felt a resident's health could be adversely impacted
H•nll Hygiene (136). An additional challenge to use of contact precautions
The principles of prevention infection transmission through for MDROs in LTCFs is the question of when precautions can
appropriate use of hand hygiene products and adherence to be discontinued. Unlike in acute care facilities where precau-
hand hygiene practices outlined in the CDC/HICPAC guide- tions often remain in place for the duration of the stay, LTCFs
lines for hand hygiene in health care settings (130) should serve as permanent residences for some individuals. Balancing
be applied in LTCFs. However, a survey of 1,143 employees in the goal of reducing spread of organisms by care-givers with the
17 nursing facilities representing six geographically different need to preserve a resident's social and emotional health poses
states found that almost one-third of respondents stated that a significant challenge for LTCFs. Research on identifying the
they would not change their hand hygiene practices, regardless highest risk resident interactions or time-frames for organism
of CDC guidelines' recommendations, and 20% felt that the spread and acquisition should inform best-practices on trans-
guidelines were not practical for LTCFs (131). An additional mission based precaution use in this setting.
barrier to implementing hand hygiene recommendations was
the lack of accessible hand hygiene products, such as alcohol-
Antimicrohi•l StnJ11rdship
based hand rubs (AHBR) and sinks and towels, for hand wash-
ing. Unlike in acute care settings which often have broad use Antimicrobials are among the most frequently prescribed med-
and availability of AHBR throughout a facility, LTCFs have ications in LTCFs and have the second highest rate of adverse
had a slower uptake of AHBR products due to concerns about drug events following antipsychotic medications (137,138). In
mounted AHBRs becoming a fire code violation, accidental in- addition to risk of adverse drug events, antimicrobial exposure
gestion ofAHBR by residents with cognitive impairment, or use also is a well-described risk factor for acquisition, colonization,
of AHBR creating an "institutional" feel to the environment As and infection with C. difficile and MDROs (84,126,139). In a
more evidence becomes available showing the safety and better study of antimicrobial use in 73 SNF/NHs, the pooled mean
efficacy and improved hand hygiene adherence when AHBR rate of antimicrobial use was 4.8 courses/1,000 resident-days
is implemented in LTCFs (132), these barriers may start to de- (range 0.4 to 23.5), and 42% of residents received at least one
crease. A clear challenge to the adoption of infection preven- course of antimicrobials in the &-month study period (38). Fac-
tion guidance by LTCF staff may be the perception that the tors accounting for the facility-level variability in antimicrobial
evidence-base used to form recommendations largely came use may include provider prescribing habits, types of resident
from studies in acute care hospitals and may not reflect the services provided within the facility (e.g., custodial LTCF vs.
culture and needs of a LTCF. A growing body of research of postacute skilled), and resident case-mix index (140-142).
infection prevention practices in LTCFs will hopefully shift the Estimates on the amount of inappropriate antimicrobial use
mindset of staff and providers who are familiar with the hand in LTCFs vary widely depending on how appropriateness is de-
hygiene and other infection prevention guidelines but may not fined (143,144); however, as in acute care, there are many op-
consistently follow them. portunities to optimize and likely reduce antimicrobial use in
this setting. A consensus group of LTCF experts proposed a set 15. Halji\'llll C, L}'iel A. Improved medication use in long-term cano: building on the conoul-
tant pharmaciJt'a drug regimen re-.kw. Am]Mtmapl c-. !002;8:513-3!6.
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SECTION
Endemic and Epidemic

Hospital Infections III
Lennox K. Archibald and William R. Jarvis
Incidence and Nature of Endetnic

and Epidetnic Healthcare-Associated
Infections
Over the past two decades, healthcare systems in the United Although there have been no recent, formal estimates of
States have been evolving from the traditional acute care hos- current costs associated with HAls in the United States, it is
pital into an integrated, extended care model that includes almoat certain that the current financial burden far exceeds
acute care hospital!, outpatient clinics, ambulatory centers, the monetary estimates cited two decades ago. The importance
long-term care facilitie,, and the home. Of the various adverse of surveillance, prevention, and control of HAl within acute
events that affect patients in any of the above levels of care, care hospitals throughout the United States is rendered even
infections acquired in these settings and antimicrobial re,i. more compelling by the fact that during the 1990s, data from
tan.ce in microorganisms that cause these infections continue the Centers for Disease Control and Prevention (CDC) indi-
to be wociated with significant morbidity, mortality, and ris- cated that while the number of general hospital beds have been
ing healthcare costs. The term nosocomial infection has tradi- decreasing across the United States, there has been an inverse,
tionally defined infections acquired in the hoapital inpatient concomitant increase in the number of beds in intensive care
setting (1). However, since infections may be acquired by pa- units (ICUs).
tients at any of the above levels of care, or the actual source The perennial problem of HAls is compounded by the
of infection may be far removed from the healthcare facility- emergence of antimicrobial resistance among the pathogens
case in point: intrinsic contamination of drugs or devices at the that cause these infections in the first place. Antimicrobial
manufacturing facility-the expression healthcare-associated resistance contributes substantially to the higher death rates
infection (HAl) has now largely replaced the term nosocomial. and escalating healthcare coats that currently are attributable
In the United States, most of the HAl surveillance activities to HAis in the United States and increaaingly in economically
since the 1960s have focused on or pertain to the acute care less-developed countries. The financial burden associated with
hospital setting. Thus, except for acute care hospital!, the rela- HAls includes the immediate costs of treating an unexpected
tive importance of outpatient clinics, long-term care facilities, infection; the costs associated with additional inpatient care re-
and home care activities in HAl tranami&ion, acquisition, and quirements and protracted duration of hospital stay; expensive
occurrence remains largely uncharacterized or unknown. For alternative antimicrobial agents necessary for the treatment of
all these reasons, there is a relative paucity of published surveil· antimicrobial-resistant HAl pathogens; the toxicity (e.g., renal
lance data regarding HAl occurrence in freestanding medical or hepatic complications) that may be associated with new, un-
and surgical centers, long-term care facilities, or the home. commonly used agents; the potential costs to the overall commu-
Each year, ....35 million people are hospitalized in the United nity, such as increased prevalence of untreatable infections or
States, accounting for 166 million inpatient-daY~ (2,3). Over a increased insurance premiwns; and loss of earnings and profits
decade ago, HAis were estimated to affect >2 million hoapital due to job loss and reduced productivity, re,pectively. A myriad
patients annually, imposing a financial burden on acute care of published data from single-center studies have characterized
facilities in excess of $4.5 billion (2). The mortality attributed the pathogens commonly associated with HAl in various health-
to these HAh wu estimated at about 100,000 deaths annually. care settings across the United States and Western Europe, and
451
452 Section m • Endemic and Epidemic Hospital Infectiuns
their susceptibility profiles to commonly available antimicrobi- The NHSN network comprises four surveillance compo-
als. Almost 85% of HAis in the United States are associated with nents, each associated with HAl control and prevention-
bacterial pathogens and 33% are thought to be preventable just patient safety, healthcare personnel safety, biovigilance, and
by maintaining infection swveillance and control programs electronic surveillance ( 12). In June 2007, NHSN released its
without even taking individual preventive practices (e.g., cath- first report on device-associated infections (13). The data col-
eter or wound care) into consideration (4). This chapter de- lected and reported by facilities participating in NHSN include
scribes (a) the incidence and prevalence of common HAl risk-adjusted HAl data, adherence to clinical practices and pro-
pathogens in the United States, (b) secular trends in the occur- cedures known to prevent HAis, and incidence and prevalence
rence of some sentinel HAis, (c) the nature of HAl outbreaks in of multidrug-resistant healthcare-associated infection patho-
various healthcare settings, and (d) the implications for patient gens within the respective facilities. The identities of all NHSN
outcome and healthcare providers. facilities are held confidential in accordance with Sections 304,
306, and 308(d) of the Public Health Service Act. This assur-
ance of hospital confidentiality enhances the likelihood that ac-
ENDEMIC HAIS tive surveillance and accurate reporting of HAis occur, because
~name and blame" are removed from the surveillance system.
INFEGI'ION RATES NHSN hospitals collect and report data on all sites of HAl
in ICU patients (13). In addition, ICU-specific denominator
Because of their documented positive impact on HAl preven- data are collected. Thus, site-specific and ICU-specific infection
tion and patient outcomes, smveillance and control programs rates may be calculated and risk-adjusted using as the denomi-
aimed at HAis have become priorities for healthcare provid- nator the number of patients at risk, patient-days, or days of de-
ers across the United States. At its inception, a key objective vice use (e.g., days of indwelling intravascular catheters, urinary
of the managed, integrated care model was to improve patient catheters, or mechanical ventilation). Because NHSN allows for
outcomes through enhancement of the quality of medical care a more uniform collection and analysis of data, several states,
provided by hospitals through reduction of HAl occurrence including California, Colorado, Illinois, Missouri, New York,
while simultaneously controlling costs. To achieve this objec- Oklahoma, Pennsylvania, South Carolina, Tennessee, Vermont,
tive, the key components of the managed care business model Virginia, and West Virginia, require their facilities to report
included substantial downsizing of general hospitals, and directly to the network. Currently, only 21 states require pub-
monitoring the quality of care and the occurrence, effects, and lic reporting of hospital data on surgical site infections (SSis),
outcomes of HAis through the estimation of infection rates and even when disclosure is mandated, the information often is
using approaches that are strikingly similar to the principles not easily accessible to patients. Aggregating institutions, other
and systemic application espoused by Deming for the continu- than CDC, that collect and report HAl rates include the fol-
ous quality improvement process in manufacturing (5) . These lowing: Pennsylvania Cost Care Containment Council (PHC);
principles include the classification of manufacturing errors as the South Carolina Hospital Association; North Carolina Hos-
either "special" or "usual" causes. For both manufacturing and pital Association; and the Duke Infection Control Outreach
healthcare services, the emphasis is on changes at the system Network (DICON)-a collaboration between Duke University
rather than the individual level (6). School of Medicine and a number of community hospitals.
The estimation of HAl rates in the United States began During 1974 to 1983, CDC carried out the seminal Study on
with surveillance studies of the prevalence and incidence of the Efficacy of Nosocomial Infection Control, more commonly
HAis in individual hospitals (7-9). The first systematic effort known as the SENIC project (4). One of the objectives of the
to estimate the magnitude of the problem on a wider scale was SENIC project was to derive a more precise estimate of the na-
made by CDC in a collaborative study of eight community hos- tionwide HAl rate from a statistical sample of US hospitals (14).
pitals known as the Comprehensive Hospital Infections Project The SENIC project was among the first to establish scientifically
(CHIP) (7). Performed in the late 1960s and early 1970s, this that HAl swveillance is an essential element of an effective in-
contract-supported study involved very intensive surveillance ef- fection control program. With 338 randomly selected general
forts to detect both HAis and community-acquired infections. medical and surgical hospitals with ~50 beds taking part, and
At that time, data from these swveillance efforts suggested that examination of over one-third million patient medical records,
-5% of patients in community hospitals acquired ~1 HAl, an the report from the SENIC project estimated that ~2.1 million
estimate that was subsequently widely held to be the national HAis occurred among the 37.7 million admissions to the 6,449
HAl rate. acute care US hospitals during a 12-month period in 1975
In 1970, CDC established the National Nosocomial Infections through 1976 (15). This gave rise to a nationwide overall infec-
Surveillance (NNIS) system, for many years the only source of tion rate of 5.7 HAis per 100 admissions (the infection ratio):
national data on the epidemiology ofHAis in the United States, that is, -4.5% of hospitalized patients experienced -1 HAl (the
the pathogens that cause these HAis, and their respective anti- infection percentage). Other key findings of the SENIC project
microbial susceptibility profiles (10). The participating hospi- included the following ( 4):
tals collected and reported to CDC their HAl data on patients
using standardized protocols, called surveillance components: (i) Hospitals with the lowest HAl rates had both strong sur-
the adult and pediatric ICU, high-risk nursery, and surgical pa- veillance and prevention and control programs.
tient components (10). In 2004, the NNIS system was combined (ii) One-third of HAis involving the four major anatomic
with two other national healthcare swveillance systems-the sites (urinary tract, surgical wounds, respiratory tract, and
National Swveillance System for Healthcare Workers and the bloodstream) that would otherwise occur in the absence
Dialysis Surveillance Network-into a single Internet-based of infection surveillance and control endeavors could be
system-the National Healthcare Safety Network (NHSN) (11) . prevented by well-organized infection control programs.
Chapter 30 • Incidence and Nature ofEndemic and Epidemic Healthcare-Associated Infections 453
(iii) The critical components of an effective HAl preventive categorically stated that such a rate should not be used for
program included a balance between smveillance and interhospital comparison (25).
control efforts, at least one infection control practitio- For surveillance data to be used effectively, infection rates
ner for every 250 hospital beds, and a trained hospital need to be calculated. An infection rate is an expression of
epidemiologist. the probability of the occurrence of an infection during a cer-
(iv) HAl rates increased by an average of 3% annually in fa- tain time interval. The numerator of an infection rate is always
cilities that had not established infection surveillance and the number of infections of a particular type that have been
control programs. acquired by a specific patient population over a defined time
(v) Different categories of HAis required specific control period. The group of patients chosen and the choice of the de-
programs, whose effectiveness were not necessarily trans- nominator used in calculating the infection rates are what sepa-
ferable when applied arbitrarily for control of any class rate comparative rates from those that are not. For HAl rates
of HAl. to be established as the basis for measuring quality of care, they
(vi) Precise determination of the specific methods and sched- must be meaningful for comparison either between healthcare
ules used in performing surveillance was not feasible facilities or within a single facility over time.
largely because most of the participating hospitals were The concept of a comparable rate is one that controls for
performing surveillance for infections at all anatomic variations in the distribution of major risk factors (e.g., expo-
sites across all hospital areas. These data suggested that sure to medical devices, or undergoing a surgical procedure)
hospital-wide HAl surveillance data had significant limita- associated with the event so that the rate could either be
tions that rendered them invalid for benchmarking. monitored and analyzed meaningfully within the facility itself
without reference to an outside standard or rate from another
Subsequently, scientific evidence from various other published facility, or compared with an external standard or benchmark
studies has shown that surveillance activities do indeed reduce rate. Risk factors could be either intrinsic or extrinsic: the for-
HAl rates. For example, the collection, calculation, and dissem- mer includes congenital or hereditary disorders, underlying
ination of surgeon-specific SSI rates to surgeons were shown to acquired conditions such as chronic cardiac or pulmonary
lower SSI rates in several published studies (16-20). Currently, disease, endocrine disorders, immunosuppression, age and
regulatory and accreditation agencies, such as The Joint Com- gender, or high severity of illness scores. Extrinsic risk factors
mission (TJC; formerly the Joint Commission on Accreditation include various forms of medical and surgical therapies, pro-
of Healthcare Organizations ijCAHO]), and the Centers for cedures or interventions, exposure to antimicrobials or inva-
Medicare and Medicaid Services (CMS) use HAl surveillance sive medical devices (e.g., intravascular catheters, mechanical
data to evaluate the quality of care provided by healthcare ser- ventilators, urinary catheters, chest tubes, and ventriculostomy
vices. HAl surveillance activities enable healthcare facilities catheters), receipt of solid organs or allograft tissues, duration
to analyze objectively and follow the trends of their own en- of hospitalization, or exposure to various healthcare personnel.
demic HAl rates over defined time periods, and are now an There are two types of rate comparisons-intrahospital and
integral component of systemic preventive efforts in healthcare interhospital. The primary goals of intrahospital comparison
facilities, including the acute care hospital inpatient setting, are to identifY areas within the hospital where HAis are more
outpatient clinics, freestanding medical and surgical centers, likely to occur and may need attention and targeting of re-
long-term care facilities, and the home setting. sources, and to measure the efficacy of interventional efforts.
The CDC investigators recognized early on that the overall The quantification of baseline HAl rates enables hospitals to
HAl rates, such as those cited, were crude rates (i.e., impre- analyze and follow their HAl trends o~ectively. Intrahospital
cise, meaningless, and not valid unless they were risk-adjusted). monitoring of HAis has the advantage of better control of
A crude overall HAl rate is the total number of HAis at all observer variation, especially for HAl case finding, culturing
sites (e.g., urinary tract infections [UTis], pneumonias, SSis, frequency and technique, and controlling for the case-mix of
bloodstream infections [BSis], and others) divided by a mea- the patient population under study. Unfortunately, sample size
sure of the population at risk (e.g., the number of admissions, comparison within a single facility can be a major problem,
discharges, patient-days, or device-days). Using a crude HAl especially when monitoring HAl rates associated with surgical
rate to characterize a hospital's HAl problem has been seri- procedures. This limitation can be mitigated through participa-
ously questioned or rctiected (21,22). Many investigators and tion in a surveillance system that aggregates data from multiple
organizations, including the Task Force on Infection Control healthcare facilities, thereby enabling interhospital compari-
for the JCAHO, have rctiected this rate as a valid indicator of son of HAl rates.
quality of care (23). The reasons were stated by Dr. Robert Interhospital comparison (or comparison to an external
Haley himself, the task force chair and a principal investiga- standard or benchmark) entails comparing the rates with those
tor in the SENIC project: "A hospital's crude overall nosoco- of other hospitals participating in a multicenter surveillance
mial infection rate was considered to be too time consuming to system. Without external comparisons, hospital infection con-
collect because of the need to do continuous, comprehensive trol departments may not know whether the endemic rates in
surveillance, unlikely to be accurate, and thus misleading to in- their respective facilities are relatively high, or on what area to
terpret, and unusable for interhospital comparison because of focus the limited financial and human resources of their infec-
the lack of a suitable risk index of infection of all types" (24). tion control program. Moreover, since only about 10% ofHAis
Before HAl rates are used for interhospital or intrahospital occur in recognized epidemics, the endemic infection rate in
comparison or as indicators of quality of care, they require a facility may be steady and consistent so that variations that
risk adjustment. As presently derived, a crude overall HAl rate signal an outbreak may be absent (26) .
of a hospital provides no means of adjustment for inpatients' Like intrahospital comparison, one of the key objectives in
intrinsic or extrinsic risks and is meaningless. Thus, CDC has comparing HAl rates of a hospital with those of other similar
facilities is to assess areas or infection control issues (or HAl definition incorporates just laboratory or imaging parameters,
rates) that might need attention. However, the approach is dif- one might not know whether a patient actually acquired a true
ferent. For any healthcare facility, external interhospital com- infection, there may be no clinical relevance to the event since
parisons, while very appealing, may incur more limitations nearly all laboratory tests may have false-negative and false-
than intrahospital comparisons. For example, facilities partici- positive results, or there may be no single laboratory test for di-
pating in a multifacility surveillance system can be audited by agnosing the putative infectious disease event, thereby making
the institution that aggregates the data to ensure that the data confirmation even more difficult. Also, a case definition consist-
being reported is valid and meets the requirements of the sur- ing oflaboratory parameters alone might not reflect the public
veillance system. Moreover, interhospital comparisons work on health relevance of an event. If a case definition consists of clin-
the basis and notion that a large number of hospitals are col- ical parameters only-for example, a doctor's note or clinical
lecting data in the same, consistent manner, and are reporting opinion, or diagnosis-there may be too much subjective varia-
these data in the same way to the aggregating institution. The tion for the event to be useful for surveillance activities across
differences in rates among hospitals are assumed by many to facilities. Finding and documenting events (i.e., case finding),
represent differences in healthcare worker (HCW) or institu- such as mortality or a laboratory-confirmed BSI from an offi-
tional practices and procedures for preventing HAl. Whereas a cial line-listing, can occasionally be straightforward. In general,
relatively low HAl rate may be interpreted as an indication that however, finding and ascertaining HAis require considerable
the facility's infection control program is effective at preventing training before an HCW can reliably and accurately determine
HAl, the converse may also be true if HAl case finding is subop- whether a patient's medical record indicates an existing HAl.
timal, patient census for critically ill patients is relatively low, or Medical record abstractors have consistently performed poorly
there is selection bias in the reporting of rates that make the fa- on HAl case finding when compared with infection prevention-
cility look better, especially if the surveillance system is passive. ist (IP) (29). Limited financial and human resources, including
An HAl rate found to be relatively high compared with that of lack of trained personnel, make it near impossible to monitor
other hospitals may suggest a potential problem in the facil- intensively all hospitalized patients. Therefore, each facility
ity of concern; it does not, however, establish by itself that the must know or be able to identity what group of patients (e.g.,
problem is poor infection control since it may be a reflection of adult or pediatric ICU patients vs. hospital-wide inpatients)
overzealous or inaccurate case finding, inaccurate aggregation should be targeted or monitored. Just as important, the length
of denominator data, or it may be merely a reflection of high of time that the hospital monitors the group must be defined
patient census for a very sick inpatient population requiring and standardized.
critical care management in the ICU-that is, larger numbers Experience at CDC has confirmed that targeted surveillance
of patients requiring invasive medical devices, mechanical ven- is better than hospital-wide surveillance for three main reasons.
tilation, and prescribed antimicrobials. First, case finding is more accurate if targeted in a specific area,
Surveillance data generated from epidemiologic stud- such as a surgical ICU or other specialized ICUs. Second, in
ies may be used to determine the need for clinical or public practical terms, targeting a specialized unit is more efficient for
health action; assess and evaluate the effectiveness of preven- the IP and for allocation of limited resources necessary for pa-
tion, intervention, or control programs, diagnostic algorithms, tient care. And third, risk adjustment is much more feasible for
and prescribing policies; or set priorities for rational and ap- data aggregated in targeted ICUs.
propriate use of limited microbiology resources, planning, and NHSN has HAl surveillance case definitions for 14 m.Yor
research. An understanding of epidemiology is important for anatomic sites, each with one to eight specific site codes to fa-
quantifying and interpreting microbiology and pharmaceutical cilitate data analysis ( 30) . Each site code has ;;;>1 criteria that
data, and for application of these data to clinical practice, qual- may include various combinations of clinical, laboratory, and
ity assurance, hypothesis generation during investigation of out- imaging parameters. Decades of experience with the NNIS sys-
breaks and other adverse events, rational prescribing policies, tem data has confirmed that ICU-targeted surveillance is bet-
and public health. ter than hospital-wide surveillance for three main reasons (31).
HAl comparisons should be used only as an initial guide First, case finding is more accurate if targeted in a specific area:
for setting priorities for further investigation. To be success- for example, a surgical ICU or other specialized units. Second,
ful, multicenter HAl surveillance and monitoring systems must in practical terms, targeting a specialized unit is more efficient
satisfY three requirements (6): (a) the purpose must be dear; for the infection control practitioner and for allocation of re-
(b) the system must use standardized HAl definitions, data sources. And third, risk adjustment is much more feasible for
fields, and protocols; and (c) an aggregating institution must patients in targeted units (28).
be identified to standardize definitions and protocols, receive
the data, assess them for quality, standardize the risk adjust- HAl SURVEILLANCE IN THE
ment of benchmarks, and interpret and disseminate the data OUTPATIENTS AND THE HOME
to those who need to know (6,27,28). CDC has remained the
sentinel aggregating institution for active HAl surveillance in With increasing numbers of patients currently being managed
the United States since the 1960s. at home for malignant neoplasms that require intravenous
chemotherapy, autoimmune conditions that require immuno-
suppressive therapy, surgical wound care following hospital dis-
DBFINffiONS OF HAl
charge, chronic infections (e.g., osteomyelitis or endocarditis)
The importance of integrating clinical medicine, epidemiol- that require long-term antimicrobial therapy, chronic urinary
ogy, and medical microbiology is exemplified by the construct problems or renal fuilure with indwelling urinary catheters or
of HAl surveillance case definitions, which usually incorporate ambulatory peritoneal dialysis, HAis associated with the respec-
clinical, laboratory, and imaging parameters. If a surveillance tive indwelling devices or surgical wounds commonly ensue.
In addition, increasing numbers of long-term care facilities frequencies of HAis involving different sites tend to vary by type
have established high-dependency units to manage critically ill of ICU (35). For example, the rates of CIA-BSI, CA-UTI, and
residents, who inevitably acquire infections once they become VAP in medical-surgical ICUs are 21%, 18.5%, and 26%, respec-
exposed to invasive devices and procedures. Notwithstanding tively (35). The corresponding rates for NHSN medical ICUs
the recognition of an increasing problem with infections asso- are 9%, 8%, and 10%, respectively; for NHSN surgical ICUs: 5%,
ciated with home healthcare, there are still too few guidelines 7%, and 15%, respectively; and for NHSN pediatric ICUs: 5%,
for uniform standards and definitions of infections acquired 2%, and 4%, respectively (35). Moreover, the distribution of in-
in the home and long-term care facilities. Moreover, a formal fection sites and pathogens in pediatric ICU patients differ with
documentation of infections in these settings remains lim- age and from those reported from adult ICUs (36).
ited, largely because few facilities have designated surveillance Unlike ICU HAis where one risk factor (medical devices)
personnel or, if they do, the designated personnel are unsure predominates, the risk of SSis among patients who have un-
about what numerator or denominator data to collect. Infec- dergone surgical procedures is related to a host of factors, in-
tions in outpatient and ambulatory care settings are common. cluding the operative procedure performed, the experience
However, problems that preclude the institution of surveillance of the surgeon, the degree of microbiologic contamination of
activities for infections in these settings include the obvious the operative field, duration of the operation, whether antimi-
queries: What infections to survey? What definitions to use? crobial prophylaxis was administered at the most appropriate
Who would be responsible for surveillance data collection? time before the incision, and the intrinsic risk of the patient
Where should the data be sent for aggregation and analyses? (15,17-19,37). An SSI risk index that effectively adjusts SSI
One of the few successes has been in the area of ambulatory rates for most operations has been developed by CDC (38).
hemodialysis services. In 1999, CDC established the Dialysis This risk index uses a scoring system ranging from 0 to 3 and
Surveillance Network (DSN), a voluntary national system to consists of scoring each operation by counting the number of
monitor and prevent infections in patients undergoing hemo- risk factors present from among the following: (a) a patient
dialysis (32,33). With >100 participating hemodialysis centers, with an American Society of Anesthesiologists (ASA) preopera-
the DSN aggregated data and reported outcome events, in- tive assessment score of 3, 4, or 5; (b) an operation classified
cluding vascular access site infection data. Within the Patient as contaminated or dirty-infected; and (c) an operation lasting
Safety Component of NHSN, the DSN has now been replaced over T hours, where Tis the approximate 75th percentile of
by the device-associated module that includes data collection the duration of surgery for the various operative procedures
of dialysis-related events. Data from the first NHSN dialysis sur- reported to the CDC database and depends upon the operative
veillance report in 2008 showed that pooled mean rates of hos- procedure being performed. The risk index is a better predic-
pitalization among patients with arteriovenous fistulas, grafts, tor of SSI risk than is the traditional wound classification system
permanent and temporary central venous catheters were 7.7, alone and performs well across a broad range of operative pro-
9.2, 15.7, and 34.7 per 100 patient-months, respectively. The cedures. The risk index also predicts varying SSI risks within a
pooled mean rates of BSis were 0.5, 0.9, 4.2, and 27.1 per 100 wound class, suggesting, for example, that all clean operations
patient-months in these groups, respectively (34). do not carry the same risk of wound infection. The SSI rates
should be stratified by risk categories before comparisons are
made among institutions and surgeons or across time. The ex-
RATES BY SITE OF HAl
ceptions are spinal fusion, craniotomy, ventricular shunts, and
HAis involve diverse anatomic sites. However, the relative Caesarean section operations in which SSI risk is not predicted
frequencies of these infections will vary by site and by patho- by the risk index.
gen. The most common HAis reported to NHSN are cen- Healthcare-associated BSis, especially CIA-BSis, cause sub-
tral line--associated bloodstream infections (CIA-BSI), 40%; stantial morbidity and mortality. BSis are either primary or sec-
catheter-associated urinary tract infections (CA-UTI), 27%; ondary. The former are culture-documented BSis in which no
SSis, 23%; and ventilator-associated pneumonia (VAP), 10% other site of infection was found to be seeding the bloodstream
(Figure 30.1) (35). However, the overall HAl rates and relative and usually ensue following direct infection. Of BSis reported
30% S. aureus 21% CoNS*

12% CoNS* SSI CLABSI 18% Enterococcus sp.
12% Enterococcus sp. 15% candida spp.
9% E. coli 12% S. aureus
6% P. aeruginosa 5% Enterobacter sp.
Figure 30.1. Distribution of HAl pathogens re- 4% Enterobactersp. 8% Klebsiella spp.
ported to the National Healthcare Safety Network, 4% Klebsiella spp. 4% E. coli
2009-2010. CoNS, coagulase-negative staphylococ-
cus; SSI, surgical site infection; ClA-BSI, central
line-associated bloodstream infection; CA-UTI,
catheter-associated urinary tract infection; VAP, venti-
lator-associated pneumonia. (From Sievert DM, Ricks P, 24% S. aureus 27% E. coli
Edwards JR, et al. Antimicrobial-resistant pathogens 17% P. aeruginosa 13% candida spp.
associated with healthcare-associated infections: sum- 10% K. pneumoniae 15% Enterococci
mary of data reported to the national healthcare safety 9% Enterobactersp. 11% P. aeruginosa
network at the centen for disease control and preven- 7% Acinetobacter sp. 11% K. pneumoniae
tion, 2009-2010. InfoctControlHospF.pidemiol2013;34:1-14, 6% E. coli 5% Proteus spp.
with pennission.) 5% Serratia spp. 4% Enterobacterspp.
to CDC, -64% are primary. Intravascular catheter me is the ma- cause of SSis (12%) and the second most common came of
jor came of primary BSI. The microbiologic features of primary BSis (35} (Figure 30.1). Although coagulase-negative staphy-
BSI have changed since the early 1980s. In 2004, CDC reported lococC\1!1 remains the most commonly reported cause of HAis
the highest mean rates (number per 1,000 central line-days) of (Figure 30.1}, this rate of occurrence is probably inflated largely
CLA-BSis in trauma ICUs (7.4), followed in descending order because coagulase-negative staphylococcm is a common skin
by bum ICUs (7.0), pediatric ICUs (6.6), and medical ICUs commensal that also is a common blood culture contaminant.
(5.0); the lowest BSI rates (2.7) were found in cardiothoracic In a relatively recent study of positive blood cultures, although
units (39). During 2009 to 2010, NHSN reported the highest coagulase-negative staphylococci were the most common iso-
CLA-BSI rates in medical-surgical ICUs (21 %), followed in late, only 10% were clinically significant ( 46). Not infrequently,
descending order in neonatal ICUs (10.5%), medical ICUs a single blood culture that yields growth of coagulase-negative
(9%), surgical ICUs (5.4%), pediatric ICUs (5.2%), cardiotho- staphylococcm is deemed clinically significant when in fact it
racic (4%), medical-cardiac (4%), trauma (3%), neurosurgery is not. Weinstein and colleagues have shown that when only
(1.5%), bum units (1.4%), and respiratoryiCUs (0.1%) (35). a single blood culture set has been drawn and yields growth
On the basis of its microbiologic features, the pathogenesis of Staphylococcus epidermidis, the culture result almost always is
of secondary BSis (not included in Figure 30.1) appears to be (97.1%} likely to represent contamination (4 7). Tokars et al.
different from primary BSis. The risk of secondary BSI is high- have shown that for blood cultures positive for coagulase-
est after lower respiratory infections (7.8%), SSis (6.6%), or negative staphylococcus, the positive predictive value for clini-
UTis (4.4%). For SSis, the probability of developing a second- cal significance was 55% for one positive culture result of one
ary BSI varies with the primary site of infection-from 3.1% for culture performed, 20% for one positive result of two per-
incisional SSI to 9.5% for organ/space SSI (40). Complications formed, and only 5% for one positive result of three performed
of infection by secondary BSI are most common on the car- ( 48). In addition, he showed that for two positive culture re-
diac surgery service (9.0%), followed by general surgery ser- sults of two cultures performed, the positive predictive value is
vice (6.5%), the high-risk nursery (6.4%), the burn or trauma 98% if both samples were obtained through the vein ( 48). That
service (5.6%), and the urology service (4.9%). Secondary BSI said, coagulase-negative staphylococcal BSis remain one of the
was least likely on the otolaryngology service (2.6%), the or- best markers of intravascular device-related infections in ICUs.
thopedic service (2.5%), and the gynecology service (2.3%). Further studies and improvements in surveillance definitions
Secondary BSis are more likely to occur in teaching hospitals. and laboratory techniques are needed to further clarify the
The organisms most commonly associated with secondary BSis roles of coagulase-negative staphylococci, anaerobic bacteria,
include Staphyloroccus aureus (20.9%), Escherichia CIJli (11.3%), and viruses, whose true roles as causes of HAl have not yet been
Pseudomonas aeruginosa (9.6%), and Enterococcus spp. (9.2%). fully characterized.
Among the variom epidemiologic investigations that have Other data from the Surveillance and Control of Patho-
characterized BSis outside the acute inpatient setting, four have gens of Epidemiological Importance (SCOPE) study, a multi-
implicated the me of needleless devices as risk factors for acquisi- center surveillance system for BSis in the United States, have
tion ofBSis in home healthcare settings (41-44). The associated established that gram-positive organisms are associated with
risk factors included receipt of total parenteral nutrition and me 65% of healthcare-associated BSis in the United States while
ofmultilumen catheters. DSN data from 109 participating hemo- gram-negative organisms and fungi cause 25% and 9.5%, re-
dialysis centers reported that during 1999 through 2001, the vas- spectively (49). The frequencies of bloodstream pathogens in
cular access infection rate per 100 patient-months was 3.2 overall the SCOPE study were as follows: coagulase-negative staphy-
and varied by type of vascular access: 0.6 for native arteriovenous lococC\1!1 (31%), S. aumu (20%), Enterococcu:s spp. (9%), and
fistulas, 1.4 for synthetic arteriovenom grafts, 8.4 for cuffed cath- Candida spp. (9%)-consistent with or similar to CDC NNIS/
eters, and 12.0 for noncuffed catheters (45). NHSN data for NHSN data.
2006 indicate pooled mean rates of hospitalization among di- The increasing role of gram-negative pathogens as impor-
alysis patients with arteriovenom fistulas, grafts, permanent and tant cames of HAl was highlighted in a 2004 editorial (50).
temporary central venom catheters to be 7.7, 9.2, 15.7, and 34.7 For example, gram-negative BSis predominate in patients
per 100 patient-months, respectively (34). For BSI, the pooled with malignancies, bum patients with catheters, and patients
mean rates were 0.5, 0.9, 4.2, and 27.1 per 100 patient-months in with needleless intravascular devices (42). Although S. au:mus
these groups, respectively. The microorganisms most frequently remains the most common (24%} came of VAP in hospitals
identified were common skin contaminants (34). that report data to CDC, the next six most common cames of
VAP are gram-negative microorganisms: P. aeruginosa (17%),
Klebsiella pneumoniae (10%), Enterobacter spp. (9%), Acinetobacter
HAl RATES BY PATIIOGEN
spp. (7%}, E. CIJli (6%), and Serratiaspp. (5%) (Figure 30.1). In
NHSN data indicate that eight pathogen groups account for another analysis of CDC data, Gaynes et al. found that during
-82% of HAis in US hospitals (Table 30.1). The three most 1986 through 2003, although gram-negative microorganisms
commonly reported pathogens areS. au:reus (15.6%), Enterococ- were still commonly associated with HAis in ICUs, especially
cusspp. (13.9%), and E. coli (11.5%). Compounding the issue UTis (71 %) and pneumonia (65%), the percentage of infec-
is the fact that all eight pathogen groups demonstrate antimi- tions associated with gram-negative bacilli in the bloodstream
crobial resistance to one or more commonly med antimicro- and surgical wounds decreased from 33.2% in 1986 to 23.8%
bials (35). Of the microorganisms that predominate among in 2003 and from 56.5% in 1986 to 33.8% in 2003, respec-
the four m~or infection sites-bloodstream, surgical wound, tively. They also noted that although the percentages of
respiratory tract, and urinary tract-S. aumu remains the most pneumonia episodes and UTis associated with gram-negative
common came of SSis and hospital-acquired pneumonia, in- bacilli remained constant during the study period, the pro-
cluding YAPs; and Enterococcus spp. are the third most common portion of Acinetobacter spp. associated with ICU pneumonias
TABLE 30.1 Distribution of Rank Order of Sdectal Pathogens Assocla.ml with Hcalthcarc-.Assoc:iaml
Infec:t:ions (HAis) Reported to the National Hcalthcare Safety Network, by Type of HAl,
2009 to 2010
Overall CLA-BSI CA-UTI VAP SSI
No.(%) of Rani: No. (%)of Rani: No.(%) of Rani: No. (%)of RtmA No.(%) of Rani:
Pathogen ~ pGiho~ ~ pathops pathogeru
Staphylococcus 12,635 (15.6) 1 3,735 (12.3) 2 442 (2.1) 2,G43 (24.1) 1 6,415 (3o.4) 1
aureus
Esclreril;hia coli 9,351 (11.5) 2 1,206 (4.0) 9 5,660 (26.8) 1 504 (5.9 ) 6 1,981 (9.4) 3
CoNS 9,261 (11.4) 3 6,245 (20.5) 1 467 (2.2) 72 (0.9) 2,4 77 (11.7) 2
Klebsiella spp. 6,470 (8.0) 4 2,407 (7.9) 5 2,365 (11.2) 3 854 (10.1 ) 3 844 (4.0) 7
Pseutlorrumas 6,111 (7.5) 5 1,166 (3.8) 10 2,381 (11.3) 2 1,408 (16.6) 2 1,156 (5.5) 5
aeruginosa
Enterococcus 5,484 (6.8) 6 2,680 (8.8) 3 1,519 (7.2) 5 45 (0.5) 1,240 (5.9) 4
faecalis
Candida 4,275 (5.3) 7 1,974 (6.5) 7 1,887 (8.9) 4 147 (I. 7) 267 (1.3)
albicans
EntmJbacter 3,821 (4.7) 8 1,365 (4.5) 8 880 (4.2) 8 727 (8.6) 4 849 (4.0) 6
spp.
Other Can- 3,408 (4.2) 9 2,465 (8.1) 4 811 (3.8) 9 36 (0.4) 96 (0.5)
didaspp.
or NOS
Enterocowus 3,314 (4.1) 10 2,118 (7.0) 6 654 (3.1) 10 25 (0.3) 517 (2.5)
faecium
Enterococcus 2,409 (3.0) 11 703 (2.3) 12 1,010 (4.8) 7 11 (0.1) 685 (3.2) 8
spp.
Protewspp. 2,031 (2.5) 12 232 (0.8) 1,013 (4.8) 6 119 (1.4) 667 (3.2) 9
Serratia spp. 1,737 (2.1) 13 762 (2.5) 11 204 (1.0) 386 (4.6) 7 385 (1.8)
Acinetobacter 1,490 (1.8) 14 629 (2.1) 13 185 (0.9) 557 (6.6) 5 119 (0.6)
baum.annii
Other 9,304 (11.5) 2,762 (9.1) 1,633 (7.7) 1,510 (17.8) 3,399 (16.1)
Total 81,159 (100) 50,454 (100) !1,111 (100) 8,474 (100) 21,100 (100)
CoNS, coagulase-negative staphylococcus; CA-UTI, catheter-associated urinary tract infection; CLA-BSI, central line-associated bloodstream
infection; NOS, not othel'Wi5e specified; SSI, surgical site infection; VAP, ventilator-associated pneumonia. Adapted from Sievert DM, Ricks P,
Edwards JR. et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the national
healthcare safety network at the centers for clliease control and prevention, 2009-2010. Inf«t Control Hosp Epidem.iol. 2013;34:1-14,
with permission.
increased from 4% in 1986 to 7.0% in 2003 (51). More recent which a microorganism interacts with a susceptible patient to
NHSN data show the following changes in antimicrobial resis- cause infection.
tance among pathogens that cause VAP during 2007 through The probability of infection depends on both the microor-
2010: S. aureus resistance to oxacillins (51.9% to 48.4%); ganism and the host: for the former, the intrinsic characteristics
Enterococcus Jaecalis to vancomycin (6.4% to 9.8%); Klebsiella and properties (infectivity, pathogenicity, and virulence) of the
spp. to extended-spectrum cephalosporins (21.5% to 23.8%); microorganism; for the latter, it is increased if the host is im-
E. coli to extended-spectrum cephalosporins (14.2% to 16.3%); munocompromised, nonimmunized, or unvaccinated. Other
multidrug-resistant P. aeruginosa ( 16.6% to 17.7%); Acinetobacter agent fuctors that are important for the development of disease
spp. to carbapenems (56.7% to 61.2%). include the infecting dose, its ability or propensity to produce
toxins, its immunogenicity and ability to resist or overcome
the human immune defense system, and its ability to replicate
RISK FACTORS AND DETERMINANTS
only in certain type of cells, tissues, or patients. Other intrinsic
ASSOCIATED WITH HAIS
and genetically determined properties of a microorganism may
The strongest determinants of HAl risk are the characteristics be important for it to survive in the host or environment. In
and exposures of patients that predispose them to infection and the inpatient setting, these include the organism's response to
the complex interactions of the agent (microorganism causing the effects of heat, drying, disinfection or sterilization, or an-
infection), host (susceptible patient), and environment (hos- timicrobials; its ability to compete with other microorganisms
pital ICU, outpatients, hemodialysis center, surgery or medical within the host or the environment; and its ability to indepen-
centers, or home). The agent, host, and environment make up dently multiply in the environment (52).
a triad that is a useful model for the characterization of infec- For transmission and infection to occur, the microorgan-
tious disease epidemiology in healthcare and other settings ism must remain viable in a reservoir or the environment un-
(52). In this model, the environment is the backdrop against til direct or indirect transfer to a susceptible host and contact
with the host has been sufficiently long enough to cause infec- However, in debilitated populations, such as those with burns,
tion and disease. The entire transmission process constitutes a malignancies, leukemia, critical care patients with multiple in
chain of infection. If this chain of infection remains unbroken, situ invasive medical devices, or children with cystic fibrosis,
the size of the reseiVOir may increase in the continuing chain this pathogen remains a significant cause ofVAP and CLA-BSI
of transmission. Examples of reservoirs that allow the agent to (36,61,62).
survive or multiply include HCW carriage of S. aureus in the Over the past three decades, much epidemiologic and clini-
anterior nares, P. aeruginosa under false fingernails, Serratia cal research have been carried out, either through formal stud-
man:escens in soap preparations or damp areas around sinks, ies or outbreak investigations, to characterize the risk factors
LegioneUa spp. in central humidifiers of air-conditioning sys- associated with the occurrence of HAis in various US health-
tems that disseminate the organism through the air in droplet care settings. However, it has not always been clear whether
nuclei, drug preparations or dialysis fluids that are intrinsically risk fuctors identified in these studies or investigations were the
contaminated at the manufacturer, multidose vials that become true underlying cause of the infection or were merely associ-
contaminated during access with a needle and syringe (this be- ated with the HAl event. Undoubtedly, some risk fuctors are the
comes a major problem if numerous patients receive fluid from direct cause of infection while others are only coincidentally
a single contaminated multidose vial), or sterile infusates that associated with the event because they follow infection or are
become extrinsically contaminated within the acute care set- merely surrogate markers for the intrinsic risk fuctors associ-
ting (e.g., wards or hospital pharmacy) (31,53-58). ated with the patient or the microorganism. Complicating mat-
Indirect contact transmission is the most common mecha- ters further is the fuct that ;;;.:2 independent risk factors often
nism of transfer of the microorganisms that cause HAis, and occur simultaneously in the same patient, sometimes exerting
commonly occurs via the hands of HCWs. Other examples of additive or even synergistic effects. Such risk factors are consid-
indirect contact transmission include contaminated inanimate ered to be strongly intercorrelated.
objects (fomites), work surfaces, and biological fluids (e.g., re- NNIS and NHSN data indicate that HAl occurrence in ICUs
spiratory, salivary, gastrointestinal, or genital secretions, blood, continue to remain unacceptably high (31,13,35,36,61-65).
urine, or stool). Medical devices contaminated with blood- The reasons for this continuing problem are varied and com-
borne pathogens (e.g., hepatitis Band C viruses, cytomegalo- plex and include the following: (a) increased ICU patient
virus, or HIV) are sources of infection for both patients and census due to greater need for intensive care, (b) a greater
HCWs in hospitals, outpatients, long-term care facilities, or the number of susceptible patients (e.g., the very young or elderly,
home. In pediatric populations, fecal-oral spread is an impor- and those with severe underlying disease, burns, malnourish-
tant means of indirect contact transmission of a variety of bac- ment, or immunosuppression) being admitted to ICUs, (c) in-
terial, viral, and parasitic infectious diseases. The mechanisms creased use of invasive medical devices in ICUs, (d) lapses in
are commonly stool-hand-mouth or stool-object-mouth. infection control, (e) crowding or decreased nurse-to-patient
Thus, in the United States, rotavirus and astrovirus are com- ratio in the ICU, or (f) increased presence of HAl pathogens in
monly implicated as the cause of hospital-acquired infectious the environment (66-69).
gastroenteritis in pediatric inpatient populations (59,60). The Environmental fuctors, the third component of the triad,
airborne transfer of droplet nuclei remains the principal route facilitate the transmission and acquisition of HAl through
of transmission of Mycobacterium tubm;ulosis, varicella (chicken three principal modes of interaction with the agent and host
pox), measles, and Legionella spp. that determine infection or disease (i.e., agent-host, agent-
Patient fuctors (e.g., age, state of debilitation, immune or nu- environment, and host-environment interactions). The rela-
tritional status, device usage, invasive procedures, or antimicro- tive contribution of each of these interactions to the acquisition
bial therapy use) play important roles in determining whether and pathogenesis of infection or disease is rendered complex
or not a patient will acquire an HAl. Special units for inten- because of the wide variety of infectious agents, hosts, envi-
sive medical or surgical care and for extensive burns, trauma, ronmental factors, and variability of parameters that make up
transplantation, and cancer chemotherapy frequently house each of these components. For example, CDC data suggest
patients who are susceptible to infection and disease caused that the ICU is the area of highest risk for the transmission of
by endemic organisms. In these patients, reduced inocula of HAis (31). Moreover, methicillin-resistant S. aum£S (MRSA) ,
pathogens may cause infection and disease, and nonpathogenic vancomycin-resistant enterococcus (VRE), and P. aeruginosa al-
agents (e.g., coagulase-negative staphylococcus) may cause se- ready are endemic in the ICUs of many hospitals that report
rious disease or death. Frequent opportunistic infections in HAl data to CDC (31,70). A complex interaction of concomi-
these patients require repeated, broad, and extended therapy tant fuctors, such as a pathogenic microorganism that is already
with multiple antimicrobials, leading to increasingly resistant endemic in the ICU environment, an inpatient population of
resident microbial populations. Commensal microorganisms susceptible patients, inadequate adherence to hand hygiene or
can become opportunistic pathogens under appropriate con- infection control practices among healthcare personnel, fluc-
ditions. Patients with immunosuppression (e.g., patients with tuating staffing levels, unexpected increases in patient census
hematology conditions or HIV infection or who have had solid relative to staffing levels in the ICU, or an unexpected increase
organ or bone marrow transplants or are receiving antineoplas- in the number of severely ill patients with multiple invasive de-
tic drugs) are at high risk of opportunistic bacterial, fungal, or vices might also contribute to HAl acquisition (66,67). Adding
protozoal infections. to the complexity of the entire process is the potential transmis-
Whether an infecting agent produces clinical or subclinical sion of the agent from host to HCW, HCW to HCW, or host to
infections also depends on the agent and certain host factors environment. Thus, acceptable measures for HAl prevention
(e.g., age and immune status.). For example, P. aeruginosa, a and control measures dictate that the hospital epidemiologist
ubiquitous pathogen that thrives in aquatic environments, soil, or IPs identify and analyze the interrelationships among all
and vegetation, seldom causes disease in healthy populations. components of the triad of agent, host, and environment.
It is well known that the social environment is extremely im- expression or detected immune reaction in the host at the time
portant in determining human behavior that affects the direct the microorganism is isolated. In a colonized patient, an infec-
transmission of microorganisms (e.g., artificial nails worn by tious agent may establish itself as part of a patient's flora in mul-
HCWs in ICUs) (53). Equally relevant is the impact of other tiple or specific anatomic sites or may cause low-grade chronic
social factors (e.g., distribution of and access to medical re- disease after an acute infection. Under suitable conditions,
sources), use of preventive services or enforcement of infec- various patient populations colonized with S. aureus are at an
tion control practice recommendations, acceptance of advice increased risk of developing infection and disease (72-74). For
or guidelines on the appropriate use of antimicrobials, or ap- example, nasal colonization with S. aureus may be a risk factor
preciation by relatives, patients, and healthcare personnel alike for SSI in pediatric patients undergoing heart operations or for
that patients who are aged, severely ill, born prematurely, or catheter-related infections in pediatric patients on chronic peri-
have congenital abnormalities, have numerous indwelling med- toneal dialysis (75,76). The HCW's hands, colonized with gram-
ical devices, or have had multiple invasive procedures or sur- negative pathogens, such as S. marcescens or P. aeruginosa, may
gery will be especially susceptible to HAis. Finally, there must become potential sources of outbreaks in neonatal ICUs (53,54).
be a willingness of all involved to appreciate the limitations of
medical technology and antimicrobials when all other clinical
SEVERITY OF ILLNESS
evidence and experience suggest that the condition of the sick
person is irretrievable. In the NNIS/NHSN system, the validity of ICU HAl rates, ad-
To design strategies for preventing HAis, it is important justed for extrinsic risk factors, would be enhanced if they were
to differentiate among coincidental indicators of risk, inde- better acljusted with a direct measurement of patients' severity
pendent causal factors, and synergistic interactions of causal of illness. Otherwise, the hospitals providing care for patients
factors. In a study of 169,526 patients who made up a represen- with a greater severity of illness may appear to have inordi-
tative sample of patients admitted to acute care US hospitals in nately high rates of HAl. Thus, the properties of a severity of
1975 and 1976, population estimates of HAl rates for each of illness score should include specificity for a particular HAl and
the four major types of infection were calculated within each site of infection.
category of exposure to between 10 and 20 separate risk factors The CDC researchers performed a search of the medical
(4,19, 71) . A striking finding was that all of the risk factors were literature to identify a severity of illness scoring system (SISS)
associated with HAl at all four major anatomic sites. At first, this that might be useful for further adjusting ICU HAl rates (77).
seems surprising because one would not expect a direct causal Eleven studies reported use of an SISS; four correlated SISS with
association between mechanical ventilation, for example, and all sites of HAl but did not meet with success; and six showed
acquiring a UTI. The explanation, of course, is that some of the some predictive value between SISS and healthcare-associated
associations indicate direct causal relationships; others indicate pneumonia. The Acute Physiology and Chronic Health Evalua-
partial causal relationships, potentiated or diminished by other tion (APACHE II) score was the most commonly used SISS but
concurrent influences; and others (such as that between res- performed inconsistently and was not routinely used in many
pirators and UTI) represent largely coincidental associations ICUs. The Clinical Pulmonary Infection Score (CPIS) has been
(most patients on respirators also have indwelling urinary cath- evaluated to ascertain its utility as a surrogate tool for diagnos-
eters that predispose them to CA-UTis). ing VAPs (78). The CPIS is calculated on the basis of points
The two factors that appeared to exert the strongest causal assigned for various clinical (e.g., signs and symptoms of pneu-
influences in all four sites of infection were indicators of the de- monia), physiologic (e.g., oxygenation), and radiologic param-
gree of the patient's underlying illness: (a) in surgical patients, eters (78). Although some studies suggest that a CPIS >6 may
the duration of the patient's operation, and (b) an index of the correlate with VAP, most studies indicate that the CPIS has lim-
number and type of distinct diagnoses and surgical procedures ited sensitivity and specificity, and therefore has a limited role
recorded (intrinsic risk index). After these, several factors were in predicting VAPs (79). In summary, although existing SISS
strongly associated with infections at one or two sites but not with scores predict mortality and resource use, none is presently
all four. Having a combined thoracoabdominal operation was available for the prediction of HAl rates. Until such measures
strongly associated with pneumonia and SSI; undergoing a "dirty" are available, comparative HAl rates will be limited in their use
(or contaminated) operation was associated with SSI; having an as definitive indicators of quality of care.
indwelling urinary catheter was an independent risk factor for ac-
quiring a UTI; being on a respirator, with VAPor BSI; and having a
PEDIATRIC/NEONATALPOPULKnONS
previous HAl or receiving immunosuppressive therapy were both
associated with BSI. Examples of risk factors that had weaker asso- The major HAl risk factors in pediatric or neonatal populations
ciations with all four sites were age, gender, previous community- include intrinsic host factors that are important to the develop-
acquired infection, and length of preoperative hospitalization. ment, progression, and severity of infection or disease. These
Multivariate modeling has demonstrated that the risk of include gestational age, gender, birth weight, congenital abnor-
HAl is primarily determined by definable causal factors reflect- malities, age at infection, race, nutritional status, genetically de-
ing the patient's underlying susceptibility to infection or the termined immune status, immunosuppression associated with
degree to which the microorganisms have access to vulnerable other infections, therapy, and vaccination status or previous
body sites. Modification of ~ 1 of these factors can alter a pa- exposure to the relevant microorganism. Extrinsic factors that
tient's risk. Multivariate statistical models based on measurable lead to HAl in pediatric and neonatal populations are similar
risk factors can be developed to predict accurately a patient's to the factors that cause HAl in adults, and include invasive
risk of acquiring an HAl. medical or surgical procedures, use of medical devices (e.g.,
Colonization is the presence of a microorganism in or on a intravenous catheters or mechanical ventilators), duration of
host with growth and multiplication but without any overt clinical hospitalization, or exposure to HCWs (80).
The risk of acquisition and transmission of infectious dis- temperature increase and rates of BSis cawed by Acineto-
eases among pediatric populations in healthcare settings are bacter spp., P. aeruginosa, E. coli, K pneumoniae, and extended-
better characterized if the patients' immune status or immune spectrum beta-lactamase-producing Enterobacteriaceae. Richet
response is known. Immunization is the most effective method also found seasonal variations in the occurrence of SSis, with
of individual and community protection against epidemic dis- winter peaks in the United States and summer peaks in Finland,
eases and plays an important role in the prevention and control CIA-BSis in hematology/ oncology pediatric outpatients, and
of certain HAis acquired by inpatient pediatric populations. As dialysis-associated peritonitis.
the proportion of a population immunized by previous expo- Healthcare-associated viral respiratory infections are com-
sure to the agent or by vaccination increases, the probability mon in hospitalized children, but also occur among adults
and opportunity for transmission of the agent within that popu- and institutionalized persons and are associated with increased
lation declines. VliUses are a frequent cause of HAl, morbid- patient morbidity, mortality, and healthcare costs (91). These
ity, and mortality in pediatric populations (59,60,81-83). Both types of infections occur mostly during the seasons in which
symptomatic and asymptomatic patients with viral infections they occur in the community (e.g., influenza and RSV infec-
can be a source of transmission (84). At present, the influenza tions in the winter and early spring in North America) (82,92).
vaccine is the only vaccine available for the prevention of in- Approximately 20% of patients with healthcare-associated
fection caused by respiratory viruses. Children at high risk for pneumonia have viral respiratory infections, with 70% of these
severe influenza infection who should be vaccinated include infections caused by adenovirus, influenza virus, parainfluenza
those with chronic lung disease, congenital heart disease as- virus, and RSV (91) .
sociated with significant hemodynamic disturbances, hemo- Clostridium difficile-associated diarrhea (CDAD) is currently
globinopathies (e.g., sickle cell disease), and children being the major healthcare-associated gastrointestinal infection in
treated with immunosuppressive agents. Although a vaccine the United States, and is now considered endemic in many gen-
is not available for respiratory syncytial virus (RSV) infection, eral hospitals in the United States (93,94). In fact, data from
palivizumab, a monoclonal antibody, may be considered as it a relatively recent study suggest that C. dif.ficile has replaced
reduces hospitalizations due to RSV infection among children MRSA as the most common cause of HAl in some community
at high risk for severe disease. hospitals in the southeastern United States (95). During 1987
to 2001, CDC demonstrated seasonal variation in the occur-
rence of CDAD in NNIS hospitals, with higher rates observed
SEASONALITY AND SECULAR TRENDS OF HAIS during the winter months Q"anuary to March) versus the non-
winter months (96) . Subsequent studies have documented a
SetuonRJity
winter predominance (97,98). Reasons for seasonal variation
The occurrence of HAis is a dynamic process. Changes are con- include persistence of viable spores during the winter months
stantly occurring in the types of patients admitted to hospitals, and increased patient census or reduced nurse-to-patient ratios
risk factors to which they are exposed, character of the patho- resulting in overcrowding in the ICUs during the winter. Also,
gens predominating in the hospital milieu, quality of patient because hospitals tend to admit higher numbers of patients
care, thrust of infection control efforts, and other important with respiratory infections during winter months, one would
factors. Two indicators of the dynamic nature of the problem naturally expect a parallel rise in antimicrobial use, a major
are the seasonality of certain types of HAl and the long-term risk factor for CDAD, during this time of the year. However, the
secular trends that may occur. Analyses of CDC NNIS data re- magnitude of the difference between winter and non-winter
peatedly have shown seasonal variations in the occurrence of rates varied by year (96). Thus, factors other than climatic con-
HAl involving certain gram-negative bacteria (85-88). There- ditions (e.g., variation in antimicrobial use, staffing, or severity
port of 1980 to 1982 results showed clear seasonal peaks of in- of illness on admission) are almost certainly playing additional
fections in the summer and early fall for KlebsieUa, Enterohacter, roles in the seasonal occurrence of CDAD (96).
Serratia, Acinetobacter sp., and P. aeruginosa; staphylococcal and
streptococcal infections show no significant seasonal variation
Secultlr Trends ofHAI
in the hospital. No seasonal variation has been observed for
infections cawed by other common pathogens, such as E. coli, In prevalence studies performed over several decades, the
Enterococcus spp., Enterobacterspp., or anaerobic microorganisms. relatively small sample sizes have hampered the detection of
Other CDC data have confirmed that the frequency of Acineto- secular changes. An analysis of secular trends in the NNIS sys-
bacterspp. infections is increasing in ICUs in US hospitals and tem from 1970 to 1979 suggested that SSis decreased slightly
is seasonal in nature (78,85). Seasonal variation in the occur- over the decade, BSis might have increased, while other HAl
rence of Acinetobacter spp. HAis is thought to be associated with types remained unchanged (87). NNIS data indicated changes
changes in climate-summer weather increases the number of in the entire distribution of HAl rates following the dissemina-
Acinetobacterspp. in the natural environment and may also affect tion of comparative HAl rates back to clinicians. Since 1987,
the hospital environment, promoting HAl transmission (89). when NNIS began reporting device-associated, device-day rates,
More recently, Richet carried out a comprehensive assess- there has been a 7% to 10% annual reduction in mean rates
ment and literature review of seasonal variations in the oc- for device-associated infections in ICUs (99). During 1980 to
currence of HAis during 1970 through 2012 (90). Seasonality 1989, however, coagulase-negative staphylococci emerged as
was demonstrated mainly for all types of BSis caused by Aci- one of the most frequently occurring BSI pathogens (100).
netobacter spp., E. coli, Enterohacter cloacae, Klebsiella spp., and During 1990 to 1999, the risk-adjusted rates for BSI, VAP, and
P. aeruginosa, with higher rates documented during the sum- UTI decreased significantly in NNIS medical ICUs (101). NNIS
mer months in North America, Europe, the Middle East, adult and pediatric ICU surveillance data from 1987 through
Australia, and Asia (90). He documented correlations between 1996 show a downward trend in the rate of Acinetobacter spp.
infections overall (cf., the increase in ICU pneumonia caused and oncology service (7.0). Lowest rates were found on the pe-
by Acinetobacterspp. from 4% in 1986 to 7% in 2003) (51). The diatric service (3.3) , the well-baby nursery (1.7) , and the oph-
exact reasons for the decreases in risk-adjusted rates for BSI, thalmology service (0.6).
VAP, or UTI have not been well-studied but might be second- In an NNIS report summary covering January 1992
ary to more hospitals participating in organized, surveillance through June 2004, rates were risk-adjusted for device use and
systems that stimulated infection prevention efforts (102). Dur- type of ICU (39). In that report, CA-UTI rates (number per
ing 1980 to 1990, the rate of healthcare-associated fungal in- 1,000 catheter-days) were highest in neurosurgery (6.7) and
fections increased at all four meg or anatomic sites of infection. burn (6.7) ICUs and lowest in cardiothoracic (3.0) ICUs; CIA-
Patients with BSis who had a central intravascular catheter were BSI rates (number per 1,000 line-days) were highest in trauma
more likely to have a fungal pathogen isolated from the blood- (7.4) and burn (7.0) ICUs and lowest in cardiothoracic (2.7)
stream than were other patients with BSI (103). NNIS data dur- units (39). In a more recent report of HAis reported to NHSN,
ing January 1989 through December 1999 show a significant CIA-BSI rates were highest in medical-surgical (20.9) and neo-
decrease in the incidence of Candida albicans BSis; however, natal (10.5) ICUs and lowest in respiratory (0.1) and neurol-
during the same period, the incidence of Candida glabmta BSis ogy (0.4) ICUs (35). CDC data have also shown that medical
increased (104). The decrease in C. albicans BSis was likely a service inpatients appear to be at greater risk of contracting
reflection of the overall decrease in BSI rates associated with CDAD compared with inpatients on the surgical, pediatric, or
bacterial and fungal pathogens in NNIS hospitals over the pre- obstetrics and gynecology services (96).
vious decade and potentially the increased use of antifungal Because of this variability with service, risk adjustment ac-
prophylaxis (105). In 2004, a CDC report confirmed that the cording to service is mandatory when conducting interhospital
incidence of CDAD steadily increased from 1987 through 2001 and intrahospital comparison of HAl rates. The importance
(96). This report also confirmed that the incidence of CDAD of risk adjustment by service is underscored by the disparate
during that 15-year period increased significantly in the ICUs of device-associated infection rates in the urinary tract, blood-
hospitals with >500 beds and that the meg or independent risk stream, and respiratory tract reported in the summary of data
factors were longer duration of patient ICU stay, mechanical reported to NHSN at CDC during 2009-2010 (Table 30.1).
ventilators, intravascular devices, or urinary catheters. This up-
ward trend in CDAD rates was thought to be due to three major
RATES BY HOSPITAL TYPE
factors: increasing antimicrobial use in US hospitals, increasing
AND GEOGRAPHIC REGION
ICU patient census, or increased frequency and sensitivity of di-
agnostic testing. Although there was a general decrease in the It has long been apparent that, overall, HAl rates differ sub-
total number of beds in NNIS hospitals during the 1990s, the stantially from one hospital to another. In the mid-19th cen-
number of ICU beds increased during the same period (31). tury, Sir James Y. Simpson found that the rate of death from
This increase in the numbers of ICU beds would have meant a infection of amputated extremities varied directly with the size
potentially higher number of patients admitted to ICUs, higher of the hospital in which the operation was performed (with
numbers of severely ill patients, and increased antimicrobial larger hospitals having higher rates), a phenomenon he called
use. In 2002, Kyne et al. established that patients who acquired "hospitalism" ( 107). The average HAl rates of NNIS hospitals
CDAD were significantly more likely to have a higher severity were reported to vary from 1.7% in small community hospitals
of illness score at admission (106). The high severity of illness to >11.0% in chronic disease hospitals (108). However, as dis-
score, combined with the obvious prolongation ofiCU stay and cussed earlier in this chapter, the overall HAl rates like these
increase in use of invasive medical devices and antimicrobial are meaningless. Among the numerous NNIS and NHSN data
use that one would expect in the ICU were deemed to be the analyses conducted over the years, characteristics consistently
most plausible risk factors for acquiring CDAD, as was subse- found to be associated with higher HAl rates include affilia-
quently confirmed in the CDC report (96). tion with a medical school (i.e., teaching vs. nonteaching), size
of the hospital and ICU categorized by the number of beds
(large hospitals and larger ICUs generally had higher HAl
RATES BY SERVICE
rates), type of control or ownership of the hospital (municipal,
The rates of HAl differ by service and specialty areas. The ac- nonprofit, investor-owned), and region of the country (109).
curacy of HAl rates would be enhanced if better adjusted with, These relationships were consistent for each of the four ma-
for example, direct measurement of severity of illness or service jor anatomic sites of infection. In addition, within these four
specialty. Previous reports from the SENIC project had shown hospital groups, the rates of UTI, SSI, or BSI were generally
that surgery patients were not only at highest risk of SSI but, higher in the Northeast and North central regions, whereas
compared with the medical service, were also at higher risk VAP rates were higher in the West. Subsequent NNIS data
of pneumonia (four times higher), and for UTI and BSI (one showed increased rates of C. di.fficile or Acinetobacter spp. infec-
and one-half times higher). These results, however, reflected tions in the Northeast (85,96). For C. difficile, the lowest rates
combined data from the ICU and hospital-wide components, were in nonteaching hospitals and intermediate rates were in
were not risk-adjusted, and therefore were not valid for inter- or teaching hospitals with <500 beds; highest rates were observed
intrahospital comparison. By the early 1990s, CDC had begun in teaching hospitals with ;;;.500 beds. More recent NHSN data
to report HAl rates that had been adjusted for service. For ex- indicate that during 2007 to 2010, 88% to 92% of HAl data
ample, NNIS data during 1990 to 1994 showed a stepwise de- were reported by general hospitals; facilities in the East and
crease in HAl rates (calculated as the number of infections per Northeast predominated (40% to 50%); 19% to 24% of HAl
1,000 patient-days) by service as follows: burn or trauma ser- data were reported by hospitals with <200 beds while 35% to
vice (15.0), cardiac surgery service (12.5), neurosurgery service 41% came from hospitals with ;;;.500 beds; and 65% to 75% of
(12.0), high-risk nursery (9.8), general surgery service (9.2), HAis reported occurred in a critical care setting (35) .
Various analyses of the SENIC, NNIS, and NHSN data have problem and recommend control measures, if needed. From
found that indices of patients' risk factors, rather than hospi- these data, it was estimated that one true outbreak occurred
tal type or geographic location, explained the greatest part of for every 10,000 hospital admissions and that HAl outbreaks
the interhospital differences. After controlling for patients' accounted for -2% of all documented HAis. Wenzel et al. es-
risk factors, average length of stay, and measures of the com- timated that 3.7% of HAl in a large, university-affiliated refer-
pleteness of diagnostic workups for infection (e.g., culturing ral hospital actually occurred in outbreaks (111). Although
rates), the differences in the average HAl rates of the various confined to a relatively small number of hospitals, these esti-
hospital groups virtually disappeared. These findings suggest mates confirmed the prevailing view that outbreaks account
that much of the difference in observable HAl rates of various for a fairly small proportion of HAis in healthcare facilities
types of hospitals is due to differences in the intrinsic degree (110,111). Other supporting data indicate that recognized HAl
of illness of their patients, related factors (e.g., age, comorbid outbreaks constitute <10% of overall HAl occurrence (26).
conditions), and whether or not the hospital has a functioning The CHIP investigations also demonstrated that about 40%
HAl surveillance system. For all these reasons, the overall HAl of HAl outbreaks likely resolved spontaneously, whereas the re-
rate per se usually gives little insight into whether the hospital's maining 60% continued until control measures were instituted
infection control efforts are effective. (110). Half of the latter class of HAl outbreaks was controlled
eventually by measures instituted by the facility's own infection
control staff; the other half was terminated only after measures
TRENDS IN HAl RATES VERSUS ANTIMICROBIAL recommended by outside investigators were implemented.
RESISTANCE RATES ASSOCIATED WITH HAl This relatively high rate of spontaneous resolution might ex-
PATHOGENS plain the underlying argument against surveillance expressed
Failure to fully apply infection control precautions may result in by some people. However, if these figures are representative
unmitigated spread of HAl pathogens in ICUs, especially where of community hospitals in general-and it should be borne
there is already heavy invasive device use, blind empiric antimi- in mind that these were hospitals with active infection surveil-
crobial prescribing, a population of critically ill patients who lance systems-then a large number of outbreaks may be going
are more susceptible to overgrowth of endogenous resistant unrecognized and uncontrolled, despite the advanced state of
pathogens, high patient census, and numerous opportunities HAl surveillance and infection control programs that are now
for cross-transmission due to frequent close contacts between available.
the various healthcare personnel who work in such units and
patients. A combination of all these factors with failure to fully HAl OUTBREAKS
identify those patients who are colonized or infected with
antimicrobial-resistant pathogens and the fact that there has The investigation of HAl outbreaks requires a systematic ap-
been a significant increase in numbers of ICUs in the United proach that includes ascertainment that an epidemic does in-
States might be the reason for the upward secular trends in deed exist, formulation of an appropriate case definition, and
antimicrobial resistance among HAl pathogens. Although pa- implementation of epidemiologic methods to identify risk fac-
tients admitted to ICUs in US hospitals are particularly at risk of tors and determine whether the relation between the factor
acquiring HAis, NNIS and NHSN data suggest that the overall and infection is associative or causative---essential for under-
rates of device-associated HAis are decreasing. Moreover, the standing the mechanisms of infection acquisition and transmis-
percentage of MRSA HAis and CLA-BSis reported to NHSN sion, and for implementing appropriate control and preventive
appear to be decreasing. At the same time, however, the rates of measures. This process assumes some previous knowledge of
HAl caused by antimicrobial-resistant gram-negative pathogens the usual or endemic rate of occurrence of the infection or
continue to increase (35). disease under study. Moreover, for this determination to take
place, one must have an understanding of the epidemiology of
the infection or disease-that is, the possible common sources,
putative modes of transmission, usual reservoirs, incubation pe-
EPIDEMIC HAIS
riods, and the microbiology of the microorganism of concern,
including pathogenicity, infectivity, and virulence. This infor-
INCIDENCE, RECOGNITION, AND CONTROL
mation is essential for the formulation of hypotheses and the
Each year, numerous publications describe the investigation of design of relevant epidemiologic, observational, and microbio-
HAl outbreaks at individual institutions, the findings and in- logic studies necessary for confirming the hypothesis.
ferences of these investigations, and the resulting prevention The various factors that influence the HAl outbreaks in-
and control measures that ensue. However, there is a paucity vestigated by CDC include the types of outbreak events (e.g.,
of published data on the frequencies of the underlying causes infections vs. events not associated with infections), the site
of these epidemics or on the comparative nature of HAl out- of occurrence (e.g., hospital inpatient or outpatient setting;
breaks among institutions. The earliest study on this subject was the home; freestanding medical, surgical, or dialysis centers;
described in CDC's CHIP study in the early 1970s (110). Among or long-term care facilities), the expertise of the personnel
the seven community hospitals that participated in CHIP dur- who request CDC's assistance, whether outbreaks are of suf-
ing the 12 months in 1972 to 1973, a computerized threshold ficient potential public health importance (e.g., associated
program screened regularly reported episodes of HAl for clus- with significant attributable morbidity or mortality) to warrant
ters of infection that might indicate an outbreak, and a CDC CDC's involvement in the first place, investigator availability,
medical epidemiologist analyzed the data to eliminate purely or whether a CDC investigation might add to infection control
coincidental clusters. Next, CDC personnel visited the hospi- knowledge to help prevent or control similar outbreaks in the
tals that had putative outbreaks to confirm the nature of the future. Thus, CDC investigations of HAl outbreaks often reflect
problems that are unique, urgent, perplexing to ascertain, or or various surgical and invasive medical procedures. In addition,
difficult to control. many of these outbreaks were associated with gram-negative
HAl outbreaks are, by definition, "special cause" events and pathogens. During the 1970s, outbreaks of BSis in healthcare
often reflect poorly on the infection control and prevention settings were the most common types of investigations carried
practice in a facility ( 112). In general, the mode of transmission out by CDC's Hospital Infections Program {HIP). Also, at that
of outbreak pathogens in healthcare settings can be categorized time, medical epidemiologists in HIP documented increasing
into one of the several groups: {a) common source; {b) human numbers of HAl outbreaks that were associated with anatomic
reservoir (carrier); (c) cross-infection (person to person); sites other than the usual bloodstream, respiratory tract, urinary
(d) airborne; (e) other environmental (e.g., fomites, extrinsic tract, and surgical wounds. These included outbreaks of hepati-
or intrinsic contamination of medications, or introduction of a tis A virus and hepatitis B virus infections; healthcare-associated
new type of medical device); or (f) uncertain modes of trans- Legionnaire's disease; necrotizing enterocolitis in nurseries;
mission. However, the reason why HAl outbreaks occur is more and sternal wound infections after open heart surgery, particu-
complex than the above categorization and opinion would sug- larly those caused by rapidly growing mycobacteria. Also during
gest, especially as the final occurrence of infection and disease this period, HIP recorded increasing numbers of outbreaks as-
involves multifaceted interactions between the patient, the sociated with microorganisms resistant to multiple antimicrobi-
pathogen, and the environment (the healthcare setting). Thus, als, particularly aminoglycoside-resistant Enterobacteriaceae
complex occurrences or fuilure of two or more factors includ- and nonfermentative gram-negative bacilli, and MRSA.
ing unsatisfactory hand washing/hand hygiene and infection During 1980 through 1990, CDC carried out a total of 125
control practices among HCWs; fluctuating staffing levels; an on-site epidemiologic investigations of HAl outbreaks across
unexpected increase in patient census relative to staffing levels the United States (117). Among these 125 outbreaks, 77 (62%)
in the ICUs; an unexpected increase in the number of severely were caused by bacterial pathogens, 11 (9%) by fungi, 10 (8%)
ill patients with multiple invasive devices (e.g., intravascular or by viruses, and five (4%) by mycobacteria; 22 (18%) were
urinary catheters, mechanical ventilators); immunosuppression caused by toxins or other organisms. Overall, Pseudomonas spp.,
caused by illness, therapy, or disease; fuilure to conduct quality Serratia spp., S. aureu.s, and Candida spp. were the most com-
control in the laboratory; fuilure of engineering to maintain mon microorganisms associated with epidemics during this de-
negative-pressure differential in an operating room that should cade (Table 30.2); in fact, gram-negative pathogens accounted
have been kept at positive pressure; inadvertent contamination for more than half of the outbreaks during the first half of the
(intrinsic or extrinsic) of soaps, medications, vials, allograft 1980s in which BSis predominated, followed by SSis and pneu-
tissues, or devices; poor surgical technique; inadvertent bacte- monia. Many of the BSI outbreaks resulted from inadequately
riostasis when conducting quality assurance microbiology cul- disinfected transducers in ICU patients or improper reprocess-
tures; or even misinterpretation of existing infection control ing of dialyzers (11S-120). During this decade, there were no
guidelines could all contribute to the transmission of an organ- epidemics investigated ofUTis and <10% of the outbreaks in-
ism that is already endemic in the healthcare facility, a colo- volved healthcare-associated pneumonia.
nizer of patients, staff, or even relatives, or recently introduced From 1985 through 1990, outbreak investigations increas-
into the fucility (31,54-56,66,67,113-115). ingly involved gram-positive microorganisms, fungi, viruses,
Recently, Archibald and Jarvis reviewed all the on-site in- and mycobacteria (Table 30.2)-rapidly growing mycobacteria
vestigations of HAl outbreaks conducted by CDC during 1946 were increasingly recognized as causes of SSis, chronic otitis
through 2005 (116). During this 60-year study period, CDC media, and hemodialysis-associated infections {121-123) . Sev-
Epidemic Intelligence SeiVice (EIS) Officers conducted a to- eral outbreak investigations implicated noninfectious causes,
tal of 531 on-site investigations in multiple healthcare settings such as E-Ferol toxicity in neonates in a neonatal ICU and py-
across the United States and in 33 facilities in 13 countries. rogenic reactions and chemical toxin exposures in hemodialy-
Initially, during 1949 to 1955, CDC assisted in only two hospi- sis centers (e.g., chloramine, hydrogen peroxide) (124-126).
tal outbreaks: an outbreak of impetigo at an Iowa hospital and The characteristics of the investigations conducted throughout
dysentery in a Georgia hospital. However, during 1956 to 1979, the 1980s reflected the increasing use of invasive procedures
CDC conducted 252 outbreak investigations and in the ensu- and devices and the introduction of an ever-increasing number
ing 16 years through 1995 assisted in another 193 outbreaks. In of products. Approximately 33% of the outbreaks investigated
the early years ( 1956 to 1962), the two most common problems occurred in ICU settings, and nearly 25% involved patients
investigated were epidemics of gastrointestinal disease, primar- who had undergone surgery. Fourteen (11 %) outbreaks were
ily attributable to Salmonella spp. or enteropathogenic E. coli, device-related, 16 (13%) were procedure-related, and 28
or staphylococcal infections; both types of epidemics were (22%) were product-related. The proportion of outbreaks in-
encountered most frequently in neonatal nurseries. During volving products, procedures, or devices increased from 47%
the early 1960s, the investigation of staphylococcal infections during 1980 to 1985 to 67% between 1986 andJuly 1990. For
abruptly decreased and was followed in the 1970s by a decrease example, nine episodes of Yminia enterocolitica sepsis were asso-
in gastrointestinal outbreak investigations in healthcare set- ciated with transfusion of contaminated packed red blood cells
tings. This likely reflected an improved understanding of the (RBCs) (127,128). Each of these independent events was traced
epidemiology and control of such infections or the improved to mildly symptomatic or asymptomatic infection in the blood
ability of hospital infection control personnel to recognize and donor. Prolonged storage of the RBCs allowed proliferation of
control such outbreaks without CDC's assistance. the Y. enterocolitica, which resulted in sepsis or endotoxin shock
From the late 1960s through the 1980s, there was an increase when the blood was transfused ( 127) . In another outbreak in-
in the number of investigations of HAis involving the blood- vestigation, separate episodes of BSI, SSI, or endophthalmitis
stream and surgical wounds; risk factors were increasingly found were traced to extrinsic contamination of a newly introduced
to be associated with being in an ICU, invasive medical devices, anesthetic agent, propofol (129-131). The manufacturer of
fJ,,.
• . §C :) 6 Types of Infections and Pathogens Involved in Epidemic Infections

Epidemic lnveatigatio1111 (%)
} - , 1983-.JtUJ 1,90" } - , 1~»«-.,_.1,~ ] - , 2000-Deannber 2005'
SITE OF INFECTION
Pulmonary 12 15 13
Urinary tract 5 <1 0
Bloodstream 20 39 28
Surgical wound 10 9 18
Central nervous system 5 2 <1
Cutaneous 13 2 15
Gastrointestinal tract 3 0 0
liver (hepatitis) 7 6 8
Other 10 Ill 17
Total 100 100 100
PATHOGENS
Staphylowccus auf!IUS 5 6 20
Escherichia coli <1 <1 0
Coagulase-negative staphylococcus <1 2 0
EnterrJcoccw spp. <1 7 0
Psetl.l.lmnonas spp. 16 <1 0
Enterobacter spp. 4 4 3
Kkbsiella pnetlmtJ'IIiae 2 !I 3
Protewspp. <1 0 0
Group A streptococcus l! <1 l!
Serratia~ 5 5 5
Salmonella spp. 2 <1 0
Hepatitis virus <I 4 8
Candidasp. 5 <1 5
Aspergillus spp. 0 4 3
Mycobacterium spp. 5 11 13
Other gram-negative pathogens 0 Ill 10
Others 48 l!6 27
Total 100 100 100
"Source of data for 1980-1990: Jarvis WR. Nosocomial outbreab: the Centers for Disease Control's Hospital Infections Program experience,
1980-1990. AM] Med.. 1991;91 (suppll!B):l01S.
isource of data for 1990-1999: Jarvis WR. Hospital Infections Program, Centers for Disease Control and Prevention On-Site Outbreak
Investigations, 1990-1999. Seminlnf«tControL 2001;1:74-84.
'Source of data for 2000-2005: Centers for Disease Control and Prevention.
this soybean oil-based product, which did not contain a pre- 114 outbreaks involved the bloodstream, 17 (15%) the respira-
servative, did not recommend refrigeration. Laboratory studies tory tract, 10 (9%) surgical wounds, and 3 (3%) the gastroin-
demonstrated that when contaminated with low numbers of testinal tract; the remaining 34% involved two or more systems.
microorganisms, rapid microbial proliferation ensued (129). Ninety-three (82%) outbreaks were associated with infections
During January 1990 through December 1999, HIP car- caused by bacteria (61; 53%), mycobacteria (12; 11%), fungi
ried out 114 on-site HAl outbreak investigations (132). The (10; 9%), viruses (8; 7%), or parasites (2; 2%) (132). There-
outbreaks of the 1990s were essentially similar to those of the maining 21 (18%) outbreaks were associated with endotoxin
1960s, 1970s, and 1980s (Table 30.2)-BSis predominated as or noninfectious agents. The noninfectious disease outbreaks
before; however, pneumonia moved up to the second place in included aluminum toxicity in dialysis patients, anaphylactic re-
frequency followed in descending order of occurrence by SSis, actions associated with latex hypersensitivity, and carbon mon-
gastrointestinal infections, and meningitis; among the out- oxide poisoning in surgical patients (133-135). Viral infection
breaks associated with procedures, surgery and hemodialysis outbreaks included hepatitis A virus transmitted among HCWs
predominated. These outbreaks occurred in 39 states or ter- in a bone marrow transplant unit, hepatitis B virus infection
ritories and almost certainly reflected the ever-increasing use among nursing home residents or dialysis patients, hepatitis
of invasive procedures and devices, the introduction of an in- C virus transmission associated with intramuscular immune
creased number of products within and outside the traditional globulin, and HN transmitted through inadvertent injection of
acute care hospital setting: 81 (71%) occurred in the hospital HIV-contaminated material or during dialysis (83,132,136,137).
inpatient setting, 15 (12%) in freestanding dialysis centers, Fifty-two ( 46%) of the 114 outbreaks that were investi-
9 (8%) in outpatients, 6 (5%) in long-term care facilities, and gated during the 1990s were associated with either an invasive
5 (4%) in home healthcare settings (41-44). Of the outbreaks device or invasive procedure. Dialyzers (10; 43%) were the
that occurred in the inpatient setting, 23 (28%) occurred in most common invasive devices followed by needleless intra-
ICUs and 58 (72%) in non-ICU areas. Overall, 44 (39%) of the vascular device use among patients in inpatient, outpatient,
or home care settings (7; 29%) (41-44,138,139). The most setting. In addition, outbreaks of bacterial, viral, and fungal in-
common invasive procedures were surgery (21; 50%), dialysis fections associated with hemodialysis continued to have clinical
(16; 37%), or cardiac catheterization (3; 7%). Twenty (17.5%) and public health implications. During 1996 to 2004, there were
of the 114 outbreak investigations were associated with con- several outbreaks of infections associated with implantation of
taminated products, including intravenous anesthetics (9; 8%), cadaveric aortic valves, pericardia! tissue, and musculoskeletal
parenteral solutions (5; 4.4%), or blood products (2; 1.8%). allografts (114,156-158). The findings of these investigations
Twenty-one (28.6%) of the infectious disease outbreaks were led CDC, the Food and Drug Administration (FDA), and the
associated with multidrug-resistant organisms, including American Association of Tissue Banks to improve guidelines
multidrug-resistant M. tuberculosis, Enterococcus spp. resistant for better screening of allograft tissue donors, recovery of tis-
to vancomycin (VRE), S. aureus with reduced susceptibility to sue from cadavers, the processing of recovered tissue by tissue
vancomycin (VISA); vancomycin-resistant S. epidermidis, and banks, and microbiological testing for quality assurance of al-
extended-spectrum beta-lactamase-producing E. coli and K. lograft tissues that had already been processed. The clinical and
pneumoniae (132,140-155). Seminal outbreak investigations public health implications for patient safety were enormous-
during the 1990s heralded the emergence of VRE, and of S. CDC recommended that surgeons who routinely used allograft
aureus resistant to vancomycin (VRSA) (154). tissue in orthopedic procedures should use sterilized tissue
From 2000 through 2005, CDC carried out 40 on-site out- where at all possible, and a Good Tissue Practices document
break investigations of adverse healthcare events. Eight (20%) was published in 2004 (159). The anatomic sites of infection
of these outbreaks reflected the increasing occurrence of com- involved in CDC epidemic investigations differ markedly from
munity-associated MRSA infections and VRSA in the inpatient those involved in endemic infections (Table 30.3).
TABLE 30.3 Comparison of Types of Infections and Pathogens Involval in Bndanic

versus Epidanic Infections
Epidemic Investigations(%)
Endemic Infections (%) 11 , _ , 1981-]u, 199fi' , _ , 1990-December 1999"
SITE OF INFECTION
Pulmonary 29 12 15
Urinary tract 2l! 5 <1
Blood5tream 17 20 l!9
Surgical wound 7 10 9
Central nervous system 0 5 2
Cutaneous 0 Ill 2
Gastrointestinal tract 0 18 l!
Liver (hepatitis) 0 7 6
Other 24 10 13
Total 100 100 100
PATHOGENS
Staphylococcus aumw 13 5 6
Escherichia coli 12 <1 <1
Coagulase-negative 11 <1 2
staphylococcus
Eflttrrococc1ls spp. 10 <1 7
Pseudomonas spp. 9 16 <1
E'llterobacler spp. 6 4 4
Klebsiella /JmumtmiM 5 2 3
Proteus spp. 0 <1 0
Group A streptococcus 0 3 <1
Serratia !IIMC&JMIS 0 5 5
Salmonella spp. <1 2 <1
Hepatitis <1 <1 4
Candidasp. <1 5 <1
Aspergillus spp. <1 0 4
Mycobacterium spp. <1 5 11
Other gram-negative pathogens 0 0 13
Others 34 48 l!6
Total 100 100 100
"Centers for D~ease Control and Prevention, National Nosocomial Infections Surveillance System, 1990-1998.
bsource of data for 1980-1990: Jal'VU WR. NoliOComial outbreaks: The Centers for Disease Control's Hospital Infections Program experience,
1980-1990. Am]Med. 1991;91 (suppll!B):101S.
'Source of data for 1990-1999: Jal'VU WR. Hospital Infections Program, Centers for Disease Control and Prevention On-Site Outbreak Investiga-
tions, 1990-1999. Semin Infect Control. 2001;1:74-84.
OUTBREAKS ASSOCIATED facilities. In the second type of multiple-hospital involvement, a

WITH UNUSUAL MICROORGANISMS widely distributed product used in patient care may cause infec-
tions in many hospitals simultaneously, because of either intrin-
Although the pathogens most commonly implicated in HAl sic contamination of the product in the factory-for example,
outbreaks investigated by CDC were S. aunus, Enterococcus spp.,
hemolysis in hemodialysis patients traced to faulty blood tubing
the Enterobacteriaceae, nonfermentative gram-negative bac-
sets or intrinsic contamination of peritoneal dialysis solution
teria, or yeasts, outbreaks, not uncommonly, involved more
(115)-or design flaws or common usage errors that encourage
unusual organisms, such as multidrug-resistant M. tuberculosis,
in-use contamination in the hospitals (41,168). In-use contami-
EwingeUa americana, 'ISu.luJmurella spp., Rhodococcus bronchia-
nation was a far more common explanation for infections re-
lis, Nocardia Jamnica, EwingtUa Jwrmaechei, Acremonium kiliense,
lated to newly introduced products and devices, and although
Malassezia pachydermatis, Curuularia lunata, Clostridium sordeUii,
intrinsic contamination is still recognized, extrinsic contami-
Ochrobactrum anthropi, and various nontuberculous mycobacte-
nation of products during manipulation remains much more
ria traced to other modes of transmission, including pedicures common (117,132).
or footbaths in nail salons or improper endoscope cleaning
In the 1980s, the widespread use of an unlicensed intrave-
and disinfection (113,114,156,160-167).
nous vitamin E preparation in neonates led to a nationwide
The profile of these outbreaks likely reflected the fact that
problem of unusual illness with high fatality in neonates (124).
HAis vary by service or location (i.e., ICU vs. non-ICU) and that
The recognition of this new syndrome in several neonatal ICUs
clusters of infections caused by unusual organisms, or usual or-
in some states led to the identification of the source and FDA
ganisms with unusual antimicrobial susceptibility profiles are
recall of the product. Similarly, an outbreak of BSis or SSis in
more easily recognized, whereas clusters of infections caused by
five states led to the identification of a newly introduced intra-
common organisms with unremarkable antimicrobial suscep-
venous anesthetic, propofol, as the source (129,130). Although
tibility patterns are less likely to be recognized as significant. only one species of organism was involved in each outbreak,
Also, these differences reflect the fact that unusual outbreaks
different institutions had different pathogens, including S.
are more likely to be investigated, as are outbreaks in which a au:reus, Enterobacter spp., Moraxella sp., and C. afbicans. On-site
common source or personnel carrier is involved, rather than
epidemiologic investigations at each hospital identified con-
the more common problem of direct or indirect contact trans- tamination of the product during preparation by anesthesia
mission of endemic infections in which organisms are com-
personnel. This led the FDA and the manufacturer to alert
monly transferred from patient to patient, patient to HCW, or
users of this product of the need for strict aseptic handling
HCW to patient, via the hands, fomites, or the environment.
during preparation. The outbreaks of BSis in home infusion
therapy patients demonstrated that as new approaches to pa-
tient care (e.g., home infusion) evolved, it became essential
MULTIHOSPITAL EPIDEMICS
that the introduction of new techniques, such as needleless de-
As hospitals became more and more specialized over the past vices to reduce HCW blood contacts, be evaluated for their risk
four decades, the possibility of multiple hospital outbreaks be- of patient complications (41,138). These experiences highlight
came a greater concem and interhospital spread or movement the fact that infection control personnel should remain alert
of patients from long-term care facilities to a variety of acute to the possibility of infections or toxic reactions associated with
care facilities likely caused many HAl outbreaks. Importantly, newly introduced products or procedures. Suspicion of such
though less common, national distribution of contaminated problems should immediately be reported through the state
products were recognized risk factors for HAl. First, a patho- health department to CDC and FDA
gen implicated in an epidemic in one healthcare facility may be
introduced into a patient population at another facility, usually
OUTBREAKS INVOLVING DEVICES
via one of three modes of transmission: (a) transfer of colonized
AND MEDICATIONS
or infected patients, particularly those with burns or decubi-
tus ulcers; (b) transfer or movement of colonized or infected As medical care advanced, an increasing number of compli-
HCWs, including medical house staff and nursing personnel, cated and more invasive devices and therapies were introduced
between facilities; and (c) transient colonization of hands of in the care of patients. In parallel, CDC/HIP investigated out-
HCWs who rotate among different hospitals and other health- breaks of illness associated with a wide variety of these medical
care facilities. Because the transfer of house staff and seriously devices and medications, which can become contaminated with
ill patients occurs primarily among large, university-affiliated, bacteria, fungi, and viruses and thus lead to outbreaks of infec-
tertiary referral hospitals, interhospital spread appears to occur tion (Table 30.4). Organic and inorganic toxins also may be
most frequently in these facilities, and less commonly among contaminants and cause clusters of illness. For devices that are
smaller community hospitals (117,132); in fact, almost two- reusable, inadequate disinfection between uses is one common
thirds of CDC outbreak investigations during 1990 to 1999 in- mechanism in the transmission and spread of infection. Equip-
volved inpatients in acute care hospitals (132). However, the ment intended for use on multiple patients, such as broncho-
blurring of the interface between the acute care hospital, free- scopes, endoscopes, and ventilators, becomes contaminated
standing specialty units, long-term care facilities, and home with microorganisms, and may serve as a reservoir for out-
care, and the increasing trend of "floating" nurses and tech- breaks if not properly reprocessed between uses. Both reusable
nicians, "moonlighting" physicians, and various other ancil- and single-use, disposable items may contribute to outbreaks
lary medical personnel toward working for healthcare systems through misuse, mishandling, or manufacturing defects. For
whose business model includes all of the above facilities in one some devices, a design feature may make in-use contamination
region undoubtedly rendered interfacility spread or transfer unavoidable or adequate disinfection between uses difficult,
of HAl pathogens among patients or residents in any of these if not impossible. Therefore, when clusters of infection are
TABLE 30.4 Features of Selected Outbreaks Associated with Medical Devices
Contaminant Clinical Syndrome Presumed Source

GRAM-NEGATIVE BACTERIA
Aci11etobacter spp. RTI Ventilator equipment
RTI Ventilator circuits/ resuscitation bags
RTI Peal flow meter
BSI Intra-aortic balloon pump
BSI Pressure transducers
RTI Nebulizers
RTI Ventilator temperature probes
CitrobacterJreufldii BSI Needleless N
E~~ BSI Respiratory suction apparatus
Enterobacter cloacae BSI Needleless N
BSI, PR Dialysis machine (waste-handling option)
BSI Pressure transducers
BSI Needleless N
BSI Dialyzers
RTI Ventilator circuits
RTI Respiratory suction tubing
RTI Nebulizers
RTI Bronchoscopes
Endophthalmim Phacoemulsifler
UTI Urodynamic equipment
Salmonella Newprwt Gastroenteritis Endoscope
Serratia liquefaciens UTI Urodynamic equipment
Serratia IIIID'r:&SM'IS BSI Pressure transducers
RTI Bronchoscopes
UTI Urinary drainage pan
BSI, stool colonization Internal tocography leam
Wound, UTI, RTI, BSI Electrocardiogram leads
sphingomtm~JS pauci'IIIIJbilis RTI, UTI Respiratory suction tubing
RTI Ventilator temperature probes
Stenotrophomonas maltophilia BSI Pressure transducers
RTI,BSI Ventilator equipment
Mixed gram-negative BSI Pressure transducers
BSI Dialysis machines
BSI Dialysis machines (WHO)
BSI Dialyzers
BSI Biliary endoscope
GRAM-POSITIVE BACTERIA
Bacillus cem~S RTI Ventilator circuits
Staphylococcus epitlermidis BSI Leaky N tubing connection
Staphylococcus aumu Wound infections Sternal saw/ retractor
MYCOBACTERIA
Mycobacterium chekmae Systemic infection Dialyzers
RTI Bronchoscopes
Skin/soft tWue Jet injector
Mycobacterium tubemdosis RTI Bronchoscope
FUNGI
Candida parapsilosis BSI Pressure transducers
Prosthetic valve endocardim Bypass machine
Multiple Candida spp. BSI Retrograde N system
Curvt.daria lunata Saline-filled silicone breast implants Improperly stored saline bags
VIRUSES
Adenovirus Epidemic keratoconjunctivitis Pneumotonometer
HN 'Ii'ansmission Hemodialysis access needles
HBV 'Ii'ansmission Electroencephalogram leam
Finger-stick blood monitoring devices
HCV 'Ii'ansmission Fmger-5tick blood monitoring devices
TOXINS
Aluminum Elevated serum levels Dialysate
Chloramine Hemolysis Water/ dialysate
Endotoxins PR Dialyzers
Fluoride Pruritus arrhythmia nonspeciflc symptoms Water-treatment system
Hydrogen peroxide Hemolysis Water/ dialysate
Microcystins Hepatic necrosis Water
Sodium azide Hypotension Water
RTI, respiratory tract infection; BSI, bloodstream infection; N, intravenous; PR, pyrogenic reaction; UTI, urinary tract infection; HN, human
immunodeficiency virus; HBV, hepatitis B virus; HCV, hepatiw C virus. Data obtained from the archives of the Centers for Disease Control and
Prevention.
noted, it became important to consider whether any changes substantial morbidity or mortality, all efforts will be made to
of equipment, use protocols, or disinfection procedures might respond; (b) whether the outbreak appears to be caused by an
have preceded the outbreak period. unusual pathogen or a common pathogen with unusual char-
Many different microorganisms and toxins have been im- acteristics (e.g., an unusual or uncommon reservoir or mode of
plicated in device-associated outbreaks (Table 30.4). Among transmission); (c) the availability of trained personnel to travel
bacteria, gram-negative agents are particularly common; tap to the facility; and (d) whether the field of healthcare epidemi-
water contamination may result in infections due to multiple ology can be advanced by the investigation.
gram-negative agents. Atypical mycobacteria also may be associ- All investigations are conducted as collaborative efforts, and
ated with tap water contamination. Items that contact blood close working relationships with local, State, and Federal per-
and/or other body fluids during use may transmit blood-borne sonnel are desirable. These and other selection biases undoubt-
pathogens if not properly reprocessed. edly contribute to the profile of epidemic HAl described in this
The common mechanisms of contamination and transmis- chapter. Of greatest value to infection control is the knowledge
sion of outbreak pathogens include reuse of devices intended gained by an investigation regarding the most common sources
for single use and inadequate disinfection or sterilization of and modes of transmission of various pathogens in outbreaks.
reusable devices. Prevention and control of illness depends These data help infection control personnel focus their pre-
upon adherence to appropriate disinfection or sterilization of ventive interventions on the areas most likely to result in the
devices. Many of the outbreaks have involved medications that containment of ongoing outbreaks.
were contaminated intrinsically (i.e., during the manufacturing In general, the mode of transmission of an outbreak patho-
process) or extrinsically (after the container or vial is opened gen can be categorized into one of the several groups out-
or accessed). Subsequent recommendations for the prevention lined earlier in this chapter: (a) common source; (b) human
of intrinsic contamination include adherence to Good Manu- reservoir (carrier); (c) cross-infection (person to person);
facturing Practices (GMPs) and other applicable FDA regula- (d) airborne; (e) other environmental (e.g., fomites, extrin-
tions by manufacturers. The resulting CDC recommendations sic or intrinsic contamination of medications, or introduction
and guidelines for prevention of extrinsic contamination in- of a new type of medical device); or (f) uncertain modes of
cluded adherence to strict aseptic technique when preparing transmission. In a recent report, Diekema et al. opined that
and administering medications, using single-dose medications outbreaks are, by definition, uspecial cause" events and should
(where possible), and following manufacturers' recommenda- be preventable, and almost always reflects poorly on the infec-
tions pertaining to proper storage and shelf life. tion control and prevention practice in a hospital (146). How-
Although healthcare-associated SalfiiO'Mlla spp. infections ever, the reason why outbreaks occur is more complex than
can be transmitted from person to person, and previous sal- the above categorization and opinion would suggest, espe-
monella outbreaks in healthcare settings have indeed been cially as the final occurrence of infection and disease involves
linked to common-5ource food, CDC/HIP investigations have multifaceted interactions between the patient, the pathogen,
highlighted salmonella infections in ICUs that were traced to and the environment (the healthcare setting). A review of
infection control practices and device use (132). An investiga- CDC outbreaks in healthcare settings suggests that although
tion of a cluster of Pseudmrumas cepacia infections was found to poor infection control almost always plays a role, outbreaks
have been because of a contaminated povidone-iodine solution invariably occur when a series of events (including infection
(169); and other Pseudmrumas spp. infections have been traced to control practices) go wrong at the same time. Thus, complex
other very different sources (e.g., external ventricular devices in occurrences or failure of two or more factors, including unsat-
neurosurgical patients) (170). Outbreaks of gram-negative BSis isfactory hand washing/hand hygiene and infection control
have been traced to myriad causes, including inadequately dis- practices among HCWs; fluctuating staffing levels; an unex-
infected intra-arterial pressure-monitoring transducers, platelet pected increase in patient census relative to staffing levels in
transfusions, soap, contaminated multidose vials, the compound- the ICU; an unexpected increase in the number of severely
ing machine in a hospital pharmacy, and even to staffing levels ill patients with multiple invasive devices; immunosuppression
(54-56,66,118,119,171). caused by illness, therapy, or disease; failure to conduct qual-
A number of selection biases influence which outbreaks are ity control in the laboratory; failure of engineering to main-
investigated by CDC. First, a problem must be recognized at the tain negative-pressure differential in an operating room that
institutional (e.g., hospital, outpatients, home) level. Once an should have been kept at positive pressure; inadvertent con-
outbreak is recognized, the degree of available local expertise tamination (intrinsic or extrinsic) of soaps, medications, vials,
influences whether CDC assistance will be sought or requested. allograft tissues, or devices; poor surgical technique; poorlyI
Second, if a problem at the hospital level is recognized and inadequately trained personnel; inadvertent bacteriostasis
brought to the attention of the state health department, inter- when conducting quality assurance cultures; or even misin-
est or expertise at the state level might determine whether the terpretation of existing infection control guidelines, could all
state concurs with the hospital's request for CDC's assistance. contribute to the transmission of an organism that is already
CDC is not a regulatory agency. Thus, any request for CDC endemic in the healthcare facility, a colonizer of patients,
assistance to conduct an on-site investigation requires an in- staff, or even relatives, or recently introduced into the facil-
vitation by the facility's administration and infection control ity (12,25,50-53,63,147-149). Thus, when outbreaks are clas-
personnel and the local and State Health Department. Finally, sified in terms of mode of transmission, various site-pathogen
if CDC is invited to assist in an on-site epidemiologic investi- combinations, often specific to certain patient groups, will
gation, several factors will determine CDC's response to the almost certainly become apparent, and knowledge of these
invitation: (a) the potential public health importance of the site-pathogen combinations can facilitate initial investigative
problem and its implications for patient safety. For example, if efforts by focusing on the most likely source or modes of trans-
an outbreak is potentially product-related or is associated with mission and hypothesis development.
The danger, of course, is for a hospital epidemiologist to measures of HAl dictate that the hospital epidemiologist looks
make premature inferences regarding association or causation at and analyzes the interrelationships between all components
on the basis of previous knowledge of site-pathogen combina- of the triad of agent, host, and environment. What must be un-
tions. For example, although HAl Sal'fMnella spp. infections derstood to be equally relevant is an appreciation by relatives,
can be transmitted from person to person, and previous salmo- patients, lawyers, administrators, and HCWs alike that patients
nella outbreaks in healthcare settings have indeed been linked who were born very prematurely or are elderly, are debilitated,
to common-source food, salmonella in reus have been traced have severe congenital abnormalities, diabetes, or end-stage
to infection control practices and device use (113). Clusters of respiratory, liver, renal, or cardiac disease, have numerous in-
P. cepacia infections should certainly alert infection control per- dwelling medical devices, or have undergone a major surgical
sonnel to the possibility of contaminated solutions, including procedure or other invasive procedures will be particularly sus-
antiseptics such as povidone-iodine solution (150); however, ceptible to HAl.
Pseudomonas spp. infection has been traced to other very dif-
ferent sources (e.g., external ventricular devices in neurosur-
PSEUDO-EPIDEMICS
gical patients) (151). Although nontuberculous mycobacteria
infection associated with endoscopic procedures should cer- Not all clusters of reported HAl constitute tnle epidemics of
tainly lead one to review endoscope disinfection/sterilization disease. Healthcare-associated pseudo-outbreaks occur when
practices, sources of tap water, and causes of endoscope washer there are an increased number of positive tests in the labora-
reservoir contamination, this class of mycobacteria has been as- tory, which do not correlate with clinical findings, a change in
sociated with other modes of transmission including liposuc- the surveillance system, or an improvement in laboratory meth-
tion and pedicures or footbaths in nail salons (145,152-156). ods (165,166). Weinstein defined pseudo-outbreaks as a real
Similarly, group A streptococcal SSis are almost always traced clustering of false infections or artifactual clustering of real in-
to a personnel carrier, and carriage can involve the rectum, va- fections (167). Of the 181 HAl outbreaks investigated by CDC
gina, scalp, or other sites (157); thus, the underlying reason during 1956 through 1975, 20 (11 %) were pseudo-outbreaks
for transmission must certainly be ascertained. Outbreaks of (167). Approximately one-half of these were attributed to pro-
gram-negative BSis have been traced to myriad causes, includ- cessing errors in the microbiology. The remaining pseudo-
ing inadequately disinfected intra-arterial pressure-monitoring epidemics were traced to systematic errors or changes in the
transducers, platelet transfusions, soap, contaminated multi- definition of infection that resulted in clinical misdiagnosis of
dose vials, the compounding machine in a hospital pharmacy, infection or surveillance artifacts associated with reporting of
and even to staffing levels (12,50-53,99,101,158). Thus, in any infection.
outbreak investigation, the knowledge of site-pathogen com- From 1980 to 1990, 6% of outbreaks investigated by CDC
binations has to be evaluated in context of the epidemiologic were pseudo-epidemics. Of these, 75% were traced to contami-
findings during the investigation. Epidemiologic methods nated products, 12.5% were traced to environmental contami-
should be used to investigate and relate causal factors to an nation, and 12.5% were traced to contamination of the culture
outbreak and are essential for understanding the mechanisms during laboratory processing. From 1990 through 1994, only
of infection acquisition and transmission and identifying puta- one (1.5%) of the epidemics investigated was a pseudo-
tive risk factors. epidemic-this involved Mycobacterium .Jurtuitum contamina-
The above site-pathogen discussion does not lessen the tion of bronchoscopes traced to a contaminated endoscope
importance of using the knowledge of site-pathogen com- washer reservoir (153). In a more recent review of CDC pseudo
binations as a precedent during the conduct of an outbreak outbreak investigations, Manangan and Jarvis reported that of
investigation. For example, clusters of Legionella spp. pulmo- the 104 HAl outbreaks that CDC personnel investigated on-site
nary infections or invasive Aspergillus spp. wound infections, during 1990 to 2000, 11 ( 11%) were pseudo-outbreaks of infec-
especially in immunocompromised patients, should stimulate tions involving Mycobacterium abscessus, TSukamumlla paurometab-
a search for an environmental source for airborne transmis- olum, E. cloacae, P. cepacia, Enterococcus durans, or Mycobacterium
sion (159,160). Clusters of patients with HAl acquisition of grmlonae (166). Among the 20 pseudo-outbreaks that occurred
M. tuberculosis or HCWs with tuberculin skin test conversions during 1956 to 1975 and reviewed by Weinstein and Stamm,
should lead to an evaluation of tuberculosis patient identifica- the most common sites of suspected infection were the blood
tion and isolation practices, pressure differentials in isolations (20%), respiratory tract (20%) , gastrointestinal tract (20%), tis-
rooms, and review of HCW respiratory protective device use sues (15%), liver (10%), or central nervous system (5%) (167).
(122,123,126,128,161,162). Recognition of patients infected or Of the 66 pseudo-outbreaks reviewed by Cunha and Klein dur-
colonized with VRE should lead to an evaluation of infection ing 1976 to 1989, the most common sites of suspected infection
control, hand washing/hand hygiene, isolation practices and were blood (53%), respiratory tract (20%), central nervous sys-
procedures, antimicrobial use, and whether current recom- tem (11 %), or tissues (4%) (168). Manangan and Jarvis found
mendations are being fully implemented (129). that during 1990 through 2000, the most common sites in the
The most common cause of both endemic and epidemic in- 86 pseudo-outbreaks they reviewed were the respiratory tract
fections is cross-infection, whereby organisms are transmitted (37%), multiple sites or sterile fluids (24%), or blood (23%)
from healthcare personnel to patient, healthcare personnel to (166). In the United States, pseudo-outbreaks of respiratory
healthcare personnel, patient to patient, or patient to health- tract infections now exceed pseudo-outbreaks of BSis (166).
care personnel. Although almost any organism can be transmit- The two most common causes of healthcare-associated
ted by cross-infection, gram-negative organisms and S. aureus pseudo-outbreaks of BSis are either intrinsic or extrinsic con-
are the most commonly recognized. HAl viral infections, which tamination of specimens and faulty procedures or misinterpre-
frequently occur in pediatric patients, also often are transmit- tation of laboratory tests (166). Cunha and Klein found that
ted by cross-infection. Thus, acceptable prevention and control the most common microorganisms associated with pseudo-BSis
4 70 Section m • Endemic and Epidemic Hospital Infectiuns
were Bacillus spp., Pseudomonas spp., or Streptococcus spp. (168). and environment triad interact in a variety of ways to produce
Maki described four scenarios when a pseudo-outbreak of BSis HAis. Environmental factors include surroundings (e.g., ICUs,
should be suspected: (a) when there is a cluster of blood cul- outpatient clinics, long-term care facilities, or water reservoirs),
tures that are positive for new or unusual pathogens; (b) when potable water, waste disposal, and healthcare amenities. Clusters
affected patients do not consistently show signs or symptoms of Legitmella spp. pulmonary infections or invasive Aspergillus spp.
consistent with a BSI; (c) when the putative epidemic BSis are wound infections, especially in inununocompromised patients,
primary (i.e., not isolated from likely sites of local infection); stimulated a search for an environmental source for airborne
and (d) when the BSI is inexplicably high-grade (169). transmission (172,173). Clusters of patients with healthcare-
The most common causes of pseudo-outbreaks of respira- associated acquisition of M. tuberculosis or HCWs with tuberculin
tory tract infections have been contaminated equipment and skin test conversions led to an evaluation of tuberculosis isola-
use of automated reprocessing systems for endoscopes or bron- tion practices, measurement of pressure dilferentials in isola-
choscopes (168). In several of these pseudo-outbreaks, the tions rooms, and review of HCW respiratory protective device
underlying cause included user error, washer malfunction, or use (140,141,144,146,174,175). Healthcare-associated outbreaks
contamination of the reservoir or lens (166). Manangan and of measles or varicella have been described when susceptible
Jarvis suggested that the users of these devices should carefully patients and staff were exposed to inappropriately isolated, in-
read the manufacturers' recommendations for use and for dis- fectious persons (176-178). Environmental disturbances of
infection of these machines. In addition, CDC has published ceiling tiles, fireproofing material, hospital construction and
guidelines for cleaning, disinfecting, and inspecting these de- renovation, bird droppings in air ducts, and contaminated car-
vices, and for monitoring unusual clusters of organisms (170). pet have all been associated with outbreaks of fungal infections
All nine reported pseudo-outbreaks of infections in tissues (160,172,173,179,180). The importance of a well-functioning
during 1990 through 2000 occurred in North America. Five of heating ventilation and air-conditioning (HVAC) system in all
these pseudo-outbreaks involved contamination of specimen healthcare facilities was illustrated by an outbreak, which oc-
transport media, specimen tubes, or of solutions used for pro- curred at an ambulatory surgical center and was found related to
cessing the specimens; two involved tuberculin skin testing with the intermittent operation of the HVAC system. Being operated
purified protein derivative (PPD)---one linked to manufactur- on as the first patient of the week, after the HVAC system has
er's error and the other caused by incorrect dose ofPPD (166). been switched back on after being off for 4 days, was a risk fac-
Most of the 21 pseudo-outbreaks of infection at multiple tor for developing A. leilimse endophthalmitis (160). Outbreaks
sites or sterile body fluids reported during 1990 through 2000 of waterborne gram-negative organism such as P. aeruginosa,
involved contamination of blood or cerebrospinal fluid with BurltJwlderia cepacia, Stenotropht:wnonas maltophilia, Ralstonia picket-
wide range of microorganisms. Seven were caused by contami- til, S. man:escens, Acinetobacter spp., or Enterobacter spp. have been
nation of specimen during collection, transport, or processing; linked to direct contact with water, hemodialysis drain ports,
five were associated with malfunctioning of hardware or soft- nebulizers, pressure-monitoring equipment, HVAC systems, as-
ware in the laboratory (166). piration, indirect contact transmission via the hands of HCWs,
Generally, pseudo-epidemics are associated with systematic hand lotions, soap, or mouthwash (180-183). Other investiga-
errors, changes in the definition of infection used for surveil- tions have linked the transmission ofVRE or C. difficile to use of
lance, misdiagnosis of infection, or in the reporting of infec- electronic thermometers (180).
tion by infection surveillance staff. In addition, many can be
traced to contaminated equipment or their processing and
cleaning solutions, contamination of microbiology specimens SELECTED OUTBREAKS LEADING TO OR
during specimen collection, transport, or processing, or other DOCUMENTING THE EFFICACY OF NATIONAL
errors in the microbiology laboratory which could be acciden- Guidelines/IUcommentLJtions
tal, associated with glitches in newly introduced computer soft-
ware and hardware, or linked to quality control problems in From 1990 through 1992, HIP EIS Officers assisted in 11 out-
antimicrobial susceptibility testing. Because of the added costs break investigations of transmission of M. tuberculosis to pa-
(human and financial) and anxiety involved with investigat- tients and/or HCWs in healthcare settings. In each of these
ing pseudo-epidemics, it is imperative that infection control outbreaks, the risk factors for transmission varied and included
practitioners and hospital epidemiologists to be familiar with delayed identification and isolation of infectious tuberculosis
the ascertainment, investigation, control, and prevention of patients; failure to isolate or keep infectious tuberculosis pa-
pseudo-epidemics and to be aware that pseudo-epidemics may tients in their rooms; positive pressure in the isolation rooms;
be due to diagnostic and reporting errors, contaminated equip- recirculation of air from clinics or rooms where infectious
ment, or errors in the microbiology laboratory, as reflected in tuberculosis patients were cared for to other areas, including
the CDC investigations. nurses stations; allowing infectious multidrug-resistant M. tuber-
culosis (MDR-TB) patients out of their isolation rooms for social
events, to go to common bathroom facilities, or after they had
SELBCfED OUTBREAKS ASSOCIATED
been in isolation and received antituberculosis therapy for 48
WITH THE ENVIRONMENT
to 72 hours; failure ofHCWs to report clinical symptoms consis-
HAl outbreaks investigated by CDC have often been traced to tent with tuberculosis; or failure of HCWs to wear appropriate
environmental sources. The environment provides the mutual respiratory protective devices ( 140-146).
background on which host and agent interactions take place Because of these outbreaks, concern was raised as to whether
and contains the factors that influence the spread of infection. the published CDC guidelines for the prevention of transmission
Within the healthcare setting, the components of the agent, host, of M. tuberculosisreallyworked. In three investigations, evaluations
Chapter 30 • Incidence and Nature ofEndemic and Epidemic Healthcare-Associated Infections 4 71
were made of the control measures implemented at MDR-TB out- surveillance and control programs. And second, it has been dif-
break hospitals. In all three, the follow-up studies documented ficult to demonstrate how many HAis are preventable by such
that when the CDC recommendations were fully implemented, programs as well as their cost-effectiveness. Consequently, it has
the transmission of MDR-TB was tenninated or significantly re- been necessary, or at least very helpful, for hospitals to estimate
duced. Since these outbreaks, a variety of studies have shown that the magnitude of adverse effects of HAl on patients to justify
tuberculosis infection control practices have markedly improved the expenditures of mounting and sustaining a preventive pro-
in US hospitals, that HAl outbreaks of drug~usceptible or MDR- gram. The adverse outcomes most often studied are deaths and
TB have been reduced, and that in many if not most geographic costs attributable to infection.
areas, the risk of HCW tuberculin skin test conversion is similar Although CDC data confirm that incidences of HAl involv-
to thatofnon-HCWs in their surrounding community (184,185). ing the four major anatomic sites are decreasing in hospitals
These initial outbreaks investigated resulted in the revision of the across the United States, the looming downside is the concomi-
CDC TB recommendations and led to the current recommen- tant increase in the incidence rates of HAl occurring in long-
dations for longer isolation of infectious TB patients and HCW term care facilities and home care and in rates of infections
respiiatory protection (N95 respirators). associated with antimicrobial-resistant pathogens. Nationwide
In 1993, CDC/HIP investigations of VRE colonization or estimates of the number of deaths attributable to HAis have
infection documented that the m~or risk factors for VRE in- been increasing over the past three decades up from 19,000 re-
fection were severity of illness, underlying disease, receipt of ported in the 1970s (unpublished CDC data) to -100,000 deaths
intravenous vancomycin, and number of hospital-days in which annually at the onset of the new millennium (3) . Despite the
an antimicrobial was received. Subsequent investigations docu- unequivocal evidence for the effectiveness of HAl infection sur-
mented the importance of the clinical microbiology laboratory veillance and control programs, and the increasing body of evi-
in the detection of VRE and how some automated systems at dence in the medical literature that the cost of implementing
the time either misidentified or failed to identify VRE (151). surveillance and infection control programs for problem HAl
Further, it showed that nephrology patients are at increased pathogens is substantially offset by savings involved in the re-
risk ofVRE (149,150). All of these investigations documented ductions of HAl occurrence, healthcare administrations seem
that compliance with CDC contact isolation recommendations loathe to commit fully-both philosophically and financially-
was poor, particularly handwashing by HCWs before and after to the idea of a total preventive package involving screening
contact with a VRE-colonized or infected patient or their envi- and surveillance of HAl pathogens.
ronment. These initial studies provided important data for the Home care is now the fastest growing component of health-
development of the CDC recommendations for preventing the care: -34 million people currently receive home care in the
spread of vancomycin resistance. Because of these outbreaks United States, supported by an increasing outlay of financial re-
and the rapid emergence of VRE as a cause of HAis, several sources ($2 billion in 1988, $20 billion in 1999, and $45 billion
intervention studies were initiated at these outbreak hospitals. in 2001) by the CMS. The movement and dynamic interaction
In the first, an attempt was made to control VRE over the entire of patients and HCWs in the home care, long-term care facili-
institution. In the second intervention, control measures were ties, outpatient services, and the acute care hospital setting,
focused on a high-risk oncology ward where -30% of patients allied with the fuct that few home healthcare companies have
at any one time were VRE-colonized and there were high rates designated surveillance personnel suggest that any significant
of VRE-BSis. The intervention included active surveillance cul- or realistic reduction in HAl rates in the United States is not
tures, patient and HCW education about VRE, respective co- going to be achieved anytime soon unless there is a concerted
horting ofVRE-positive and VRE-negative patients to separate effort by healthcare companies and administrators in hospitals,
areas, and enforced compliance with CDC recommendations. long-term care facilities, and home care to finance evidence-
These interventions resulted in significant decreases in VRE based preventive measures such as those recommended by the
colonization and infection rates. A subsequent, similar inter- CDC, Society ofHealthcare Epidemiology of America (SHEA),
vention in a community hospital resulted in a similar reduction and the Association of Professionals in Infection Control and
of infection and colonization rates (149). Epidemiology, Inc. (APIC) (186,187).
CONSEQUENCESOFEUU CONTROL AND PREVENTION OF EUUS

The reader of the scientific literature on HAl is struck by That endemic and epidemic HAis are preventable has peri-
the disproportionately vast number of articles on the adverse odically been reaffirmed by milestone reports dating from as
consequences-protracted duration of hospital stay, extra far back to Semmelweis; to the myriad of studies published
hospital costs or charges, additional inpatient care require- over the past two decades dealing with the unequivocal effect
ments, costly alternative antimicrobials, potential costs, lost and benefit of hand hygiene with soap and water or waterless
productivity, long-term sequelae, untreatable infections, and agents, proper care of urinary catheters, respirators, intravascu-
death-associated with these HAis. The blurring of the borders lar catheters, and surgical wounds; numerous evidence-based
between the acute hospital setting, long-term care facilities, and infection control guidelines published by CDC; and position
home care has rendered the problem and its solutions even papers issued by SHEA, APIC, and the Infectious Diseases
more complex. The importance of these studies stems from Society of America.
two factors: first, in contrast to most other healthcare provision Although the overall HAl rates at the main anatomic sites
services, hospitals have not traditionally been able to charge have been falling, infections caused by resistant pathogens have
patients or their insurance carriers directly for the costs of HAl been increasing. Thus, control of antimicrobial resistance in
the second decade of the 21st century remains inextricably The tenets of the SHEA guidelines are based on identifica-
linked to the control of transmission of antimicrobial-resistant tion and containment of spread through (a) active surveillance
pathogens in healthcare facilities, and the infections they cawe. cultures/testing to identify the reservoir for spread; (b) routine
The seriousness of the problem was underscored in an edito- hand hygiene practices; (c) barrier precautions for patients
rial by Muto who made the point that "for as long as CDC has known or suspected to be colonized or infected with epidemio-
measured the prevalence ofHAis cawed by multidrug-resistant logically important antimicrobial-resistant pathogens, such as
organisms, it has been increasing" (188). MRSA, VRE, or multidrug-resistant gram-negative pathogens;
So, what do we do? Indeed, there is little doubt that we (d) implementation of an antimicrobial stewardship program;
would not be where we are today had more attention been paid and (e) decolonization or suppression of colonized patients
to the published evidence--based data regarding which inter- (187). Various studies have established that identification of
ventions have been effective in controlling the transmission of MRSA-colonized patients at hospital admission may enhance
healthcare--associated, antimicrobial-resistant pathogens. For ex- the implementation of interventions to decrease infection
ample, the Hospital Infection Control Practices Advisory Com- (193,194). Although there is now growing evidence that active
mittee (HICPAC) guidelines to prevent and control vancomycin surveillance cultures/ testing reduce the incidence of MRSA
resistance were published in 1995 (189). Although the imple- and VRE infections and that programs described in the SHEA
mentation of these guidelines following VRE outbreak investiga- Guidelines are effective and cost-effective, conflicting results
tions played no small part in the resolution of these outbreaks, from other studies allied with differences in acute care facili-
no published outcome studies show how implementation of the ties, surveillance activities, disparate infection control practices
HICPAC guidelines might have resulted in HAl rate reduction and procedures, and varied case--mix and inpatient populations
in healthcare facilities across the nation, especially for those in- suggest that universal screening for MRSA might not be appro-
fections cawed by resistant pathogens (150,190). priate for every healthcare facility (153,194-197). Moreover,
After decades of disCUBsing control of antimicrobial-resistant concerns persist that compliance with the tenets of the prac-
HAl pathogens in the medical literature, there is little evidence tices outlined in the SHEA Guidelines are neither consistent
of control of HAl caused by resistant pathogens, especially nor reliable. This reality led the Institute for Healthcare Im-
among gram-negative microorganisms, in most healthcare fa- provement (IHI) to establish the "5 Million Lives Campaign"
cilities. The myriad articles published have in effect helped for the reduction of MRSA infections (198). The campaign's
explain this fuilure becawe much of the published data on MRSA intervention recommends five key minimum, but neces-
HAl has been carried out in hospitals that had implemented sary, components of care: (a) hand hygiene, (b) decontamina-
untried control programs or already had programs that were tion of the environment and equipment, ( c} active surveillance
substantially ineffective. Moreover, despite all the resources put testing, (d) contact precautions for infected and colonized pa-
into surveillance activities for HAis in facilities across the coun- tients, and (e) device bundles (e.g., central line bundle and
try, there remains substantial variation in surveillance activities ventilator bundle) (198).
from one medical center to another, inconsistent we of effec- In conclusion, active surveillance cultures/testing for resis-
tive control measures (e.g., surveillance cultures/testing not tant pathogens in ICUs followed by isolation of colonized per-
being performed as recommended), or fuilure ofhealthcare fa- sons constitute a highly effective strategy for control of HAis.
cilities to we effective measures due to lack of commitment by However, isolation purely on the basis of history of previous de-
healthcare companies and administrators alike to initiate and tection, at least for VRE or MRSA, appears to be of little bene-
swtain these measures. In addition, there appears to be moder- fit. Standard precautions and isolation of the occasional patient
ate compliance with goals to optimize antimicrobial use, and to recognized to be colonized through routine clinical cultures
detect, report, and control the spread of antimicrobial-resistant are minimally effective. The onus is now on healthcare profes-
pathogens. In 1996, Goldmann et al. found that national guide- sionals and healthcare administrators to invest intelligently in
lines seldom are studied thoroughly by physicians, and, if they prevention programs, to enhance existing surveillance activi-
are read, they rarely are incorporated into everyday practice ties in targeted areas, and to avoid regarding death and mor-
(191). They went on to say that "success depends on the hos- bidity as inevitable. However, hospital epidemiologists and
pital leadership-members of the board, the executive ad- CDC also have a responsibility to evaluate the effectiveness and
ministrative staff, and physician opinion leaders-making the cost-benefit of the programs described in the SHEA Guidelines
campaign against antimicrobial resistance a strategic priority... for gram-positive and gram-negative pathogens and fungi in
under the aegis of the hospital's overall efforts to improve qual- the acute care hospitals. Enormous challenges remain for con-
ity" (191,192). The fuilure to prevent and control HAis contin- trolling transmission of HAl pathogens in acute care hospitals
ues at present; the lack of appreciation of the seriousness of the and conducting similar evaluations and strategies in long-term
problem is reflected in the numerous publications, as recently care facilities and the home setting. These challenges include
as 2013, that continue to document that hand hygiene compli- development of uniform surveillance definitions and protocols
ance rates are commonly <50% among physicians. and a nonpunitive reporting system for HAl in long-term care
Numerous reports presented at the Infection Control Soci- facilities and the home; identification of high-risk infections
ety Annual Meetings and in medical journals have repeatedly (e.g., BSis, pneumonia, or SSis) that need to be focused on in
shown control of endemic or epidemic MRSA and VRE infec- these settings; and determination of relevant numerators and
tions through implementation of the SHEA guidelines with denominators for calculating device-specific rates for infections
more emphasis on active detection and isolation, especially in these settings. These challenges are likely to be tempered by
contact precautions, and less on standard precautions. In fact, the fact that by foCUBing on specific, albeit high-risk infections,
CDC has never provided any evidence--based data that show the true magnitude and epidemiology of HAis acquired in the
standard precautions and passive surveillance activities can home will remain unknown or uncharacterized for some time
control the spread ofMRSAand VRE (193). to come.
Chapter 30 • Incidence and Nature of Endemic and Epidemic Healthc~A.ssociattd Infections 4 73
56. Richards MJ, Edwards JR. Culver DH, et Ill. Nosocomial iDfuction1 In pediatric intenaive
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Chapter 30 • Incidence and Nature ofEndemic and Epidemic Healthcare-Associated Infections 4 75
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Carol E. Chenoweth
Urinary Tract Infections

Urinary tract infection (UTI) is one of the most frequendy re- The microorganisms also enter the catheter intraluminally
ported healthcare-assodated infections (HAill), accounting for when organjsms gain accesJ~ to the internal lumen of the cath-
up to 40% of all HAh (1-5). Most healthcare-associated UTh eter through failure of a dosed drainage system or contamina-
('70%) are associated with urinary catheter~; in intensive care tion of the collection bag (2,18,19). These organisms, usually
units (ICUs), as many as 95% of all UTis are associated with introduced from exogenous sources, often are the result of
urinary catheters (4,5). Urinary catheten are widely used in cross-transmission of organisms on the hands of bealthcare
healthcare today, especially in ICUs, in long-term care facilities, worken (HCWs) (2,19,20). Intraluminal contamination of the
and increasingly in home care patients (4,6,7). Up to 25% of collecting system was recendy found to account for M% of
patients have a ur:iiw:y catheter placed at some time during CA-UTis (18). Once the microorganisms attach and multiply,
their hospital stay (8,9). The Centen for Disease Control and the rerultant sheet of organisms secretes an extracellular ma-
Prevention (CDC) estimates that 139,000 catheter-associated trix of bacterial glycocalyces, imbedding the microorganisms
UTh (CA-UTis) OCCUlTed in US hospitals in 2007 (4). (2,1~1'1,21).
CA-UTis are associated with increased morbidity, mortal- Bacteria within the biofilm grow much more slowly than
ity, and costs. CA-UTh are associated with excesll mortality, planktonic bacteria and secrete chemical signals that mediate
even after controlling for severity of illness and other under- population density-dependent gene expression (2,14-17,21).
lying comorbidities. More significantly, healthcare-associated The migration of the bio&lm over the inner surface of the cath-
bloodstream infection originating &om a urinary source has eter to the bladder occun within 1 to 3 days or more quickly by
a case-fatality rate of 32.8% (10,11). Each episode of CA.-UTI swarming organisms, such as PmiiN..! mimbilis (15,16,21). Most
is estimated to cost approximately $600; if associated with a biofilms are composed of single organisms; however, biofilms
bloodstream infection, costs increase to at least $2,800 (12). may contain a mixture of up to five organisms (2,22). Some
Nationally, CA-UTis rerult in as much as $131 million annual oxganiaiWI, such as Prwidencia stuartii, Ps!~Udcmonas sp., entero-
excess medical costs. cocci, or Prot.tw sp., penist in the urine for up to 10 weeks,
Since October 2008, the Centen for Medicare and Medicaid while other organisms appear to spontaneously cycle in and out
Services (CMS) no longer reimburses for costs associated with (2,22). Several studies suggest that planktonic bacteria found
treatment of hospital-acquired CA-UTis (12). Consequendy, in cultu.res obtained &om the catheter may not reflect the bac-
prevention ofCA-UTis has become a priority for most hospitals, terial population growing within the biofilm (2,22). Proteus sp.,
as 65% to 70% of CA-UTis are potentially preventable (13). .P.seudomoruu anuginost.; KkbsiBlla fmtru;moniM, and P1&vidmcia sp.
This chapter reviews the pathogenesis, epidemiology, and pre- have the ability to hydrolyze urea in the urine to free ammo-
ventive measures for CA-UTis. nia. The resulting increase in local pH allows precipitation of
minerals such as hydroxyapatite or struvite. Mineral deposition
within the catheter biofilm causes encrustations that are unique
PATHOGENESIS to bio:films formed on winary catheters (21,23). Encrustations
Urinary catheters readily develop a biofilm composed of clus-

ters of microbial organisms on the internal and external cath-
eter surface swrounded by an extracellular matrix made up
of primarily polysaccharide materials (2,1~17). The biofihn
allows for microbial attachment and adherence to catheter
surfaces. The microorganisms gain access to the catheter and
attach to the biofihn via one of two routes: extraluminally or in- Entry points for bacteria
traluminally (Figure 31.1). Extraluminal organisms are primar- 1. Urvthral meatus
ily endogenous, originating &om the patient's gastrointestinal (Extraluminal)
tract and colonizing the patient's perineum. The organisiWI a&- 2. Junction between catheter
cend the catheter by direct inoculation at the time of catheter and collection tube
insertion or by migration in the mucous sheath surrounding (Intraluminal)
the external aspect of the catheter (2,18). Approximately 70% 3. Crainage port
(Intraluminal)
of episodes of bacteriuria in catheterized women are felt to oc-
cur through extraluminal entry of organisiWI (18). In a recent 3
prospective study of 1'73 CA-UTis, 115 (66%) were likely ac- Figure 31.1. EntrypointJI for bacteria causing catheter-associated
quired through the extraluminal route (18). urinary tract infection.
476
Chapter 31 • Urinary 1Tact Infections 4 77
on the inner surface of the catheter can build to completely

block catheter flow or act as a nidus for the formation of renal
TABLE 31.1 Miaobial Pathogens
calculi (24,25).
Associated with Catheter-
The urinary biofilm provides a protective environment from Related Urinary Tract
the activity of antimicrobial agents (26,27). First, the extracel- Infections (28,30)
lular matrix may prevent the penetration of antimicrobials into
LTACHs MICUII NHSN
the biofilm. For example, both ciprofloxacin and tobramycin 2009-2010 2009-2010 2009-2012
have poor diffusion into biofilms. Second, organisms grow- %(Rank) %(Rank) %
ing at a slower rate within the biofilm are more resistant to
the effects of antimicrobial agents that require active growth Escherichia coli 14 (3) 20 (2) 26.8
Candida sp. 10 (5) 28 (1) 12.7
(23,26,27). Finally, chemical signaling from organisms growing Enterocacci sp. 14 (3) 15 (3) 10.3
within the biofilm appears to regulate the genes that alter the ~ 19 (1) 11 (4) 11.3
molecular targets of antimicrobials (23). The features of the aerugifiQSa
biofilm as described have important implications for both pre- Klthsiel14 sp. 17 (2) 10 (5) 11.2
vention and treatment of CA-UTis.
LTACH, long-term acute care hospital; MICU, medical intensive
care unit.
EPIDEMIOLOGY
MICROBIAL ETIOLOGY
INCIDENCE OF CATHETER-ASSOCIATED UTI
Enterobacteriaceae, including Escherichia coli, and Klebsiella
sp., are the most common pathogens associated with CA-UTis In hospital-wide data, UTis have accounted for -40% of all
(Table 31.1). Other pathogens, more common in the ICU HAis, but UTis make up a smaller proportion of HAis oc-
setting, include P. aeruginosa, enterococci, and Candida sp. curring in the ICU setting (1,5). With widespread intexven-
(1,11,28). European hospitals report a similar spectrum of tions occurring nationwide, the rates of CA-UTI in ICUs have
bacteria associated with healthcare-associated UTis, except for decreased significantly between 1990 and 2007 (4). In 2010,
Pseudmnunas sp., which were isolated in only 7% of urine cul- the rates of CA-UTis reported to CDC's NHSN ranged from
tures (29). In data reported from the CDC's National Health- 4.7/1,000 catheter-days in burn ICUs to 1.3/1,000 catheter-days
care Safety Network (NHSN) in 2009 to 2010,29.1% and 33.5% in medical/surgical ICUs. The rates of CA-UTI in pediatric
of E. coli CA-UTI isolates from patients in an ICU or non-ICU ICUs were reported at 2.2 to 3.9/1,000 catheter-days (40); how-
settings, respectively, were resistant to fluoroquinolones (30). ever, CA-UTI is infrequently identified in neonatal ICUs (41).
In addition, 24.6% to 29.0% of Klebsiella sp. and 11.5% to Surprisingly, general care wards report rates equivalent to or
13.2% of E. coli isolates from patients with CA-UTis produced higher than ICU settings, with a range from 0.2 to 3.2/1,000
extended-spectrum beta-lactamases. Even more concerning is catheter-days. Among general care wards, rehabilitation units
that during this same time period, 15.2% to 17.0% of all Klebsi- have the highest rates ofCA-UTI (5,40).
ella sp. from patients with CA-UTis were resistant to carbapen-
ems (30). Long-term acute care hospitals (LTACHs) have a
RISK FACTORS FOR CATHETER-ASSOCIATED UTI
prevalence of resistant Enterobacteriaceae in CA-UTI isolates
that is similar to that seen in ICUs in acute care hospitals (28). The most important and consistent risk factor for bacteriuria is
Enterococci emerged as a significant cause of healthcare- the duration of urinary catheterization (odds ratio [OR] = 2.3
associated UTis between 1975 and 1984 (31,32). Enterococcal to 22.4, depending on duration) (42-44). Urinary catheters are
UTis may derive from an endogenous source such as the pa- associated with the vast majority of healthcare-associated UTis;
tient's fecal flora or may be acquired exogenously (33-35). The up to 95% of UTis in ICUs are associated with a urinary cath-
emergence and spread of vancomycin-resistant strains have eter (1,5). Bacteriuria occurs quickly and frequently in cath-
compounded the problem in acute care hospitals and LTACHs eterized patients with an average daily risk of 3% to 10% per
(28,30). Candida spp. are prevalent in the medical ICU setting, day. In patients with a catheter indwelling for 2 to 10 days, 26%
where 28% of UTI are associated with Candida spp. (28). The will develop bacteriuria ( 45-47). Nearly all patients catheter-
risk factors for candiduria include prolonged catheterization ized for a month will have bacteriuria, making this the dividing
and use of broad-spectrum antimicrobials (36). Coagulase- line between short-term and long-term catheterization (2,22).
positive staphylococci (CPS) are an infrequent cause ofCA-UTI Females have a higher risk of bacteriuria than males (rela-
(1,11), but when CPS-UTis occur, secondary bacteremia may tive risk [RR] = 1.7 to 3.7) (42-45). Systemic antibiotics have
result. Conversely, CPS bacteremia or endocarditis may result a protective effect on bacteriuria; therefore, the absence of
in secondary infection of the urinary tract. In one study, 27% systemic antimicrobials increases the risk of bacteriuria (RR =
of CPS bacteremias were associated with secondary bacteriuria 2.0 to 3.9) ( 42-45). Nonadherence to catheter care recommen-
(37). The presence of CPS in the urine should prompt consid- dations has been associated with increased risk of bacteriuria
eration for coinciding bacteremia or endocarditis (37,38). (19,42,43). Other risk factors identified in ;;;.:1 studies include
While 80% of infections associated with short-term indwell- rapidly fatal underlying illness (RR = 2.5) (42); age >50 years
ing urinary catheters are caused by single organisms, infections (RR = 2) (42); nonsurgical disease (RR = 2.2) (42); hospi-
in long-term catheters are frequently polymicrobial. UTis in talization on an orthopedic (RR = 51) or urological service
long-term catheters are associated with ;;;.:2 organisms in 77% (RR = 4) (48); catheter insertion after the sixth day of hospital-
to 95% of episodes, and 10% have >5 species of organisms ization (RR = 8.6) ( 48); catheter inserted outside the operat-
present (1,3,39). ing room (RR = 5.3) (43); diabetes mellitus (OR= 2.3) (43);
long-term indwelling catheters, and are rare in patients whose

TABLE 31.2 Risk Factors Associated
catheterization lasts < 10 days. The signs and symptoms of sepsis,
with the Development including fever, hypotension, mental status changes, or organ
of Catheter-Associated system dysfunction, may be associated with secondary bactere-
Bacteriuria mia, especially those due to gram-negative bacilli (2,5S-60) .
From the short-term clinical perspective, most CA-UTis ap-
Risk Factors
pear to be associated with a benign outcome. Few patients with
Increasing duration of catheterization catheter-associated bacteriuria have undergone localization
Not receiving systemic antibiotic therapy studies, and thus the proportion of patients with bladder, pros-
Female gender
tate, or kidney infections has not been determined. Patients
Diabetes mellitus
Older age with bacteriuria who die have had autopsy findings of acute py-
Rapidly fatal underlying illneM elonephritis, renal calculi, or perinephric abscesses (52,59,60).
Noruurgical di&ease The major systemic complication of catheter-associated bac-
Faulty aseptic management of the indwelling catheter teriuria is secondary BSI, which occurs infrequently (0.4% to
Bacterial colonization of drainage bag 3.9%) (45,52,56,58). Bacteremia is less likely to occur with as-
Azotemia (serum creatinine concentration >2.0 mg/dL)
ymptomatic bacteriuria and is more likely to be associated with
Catheter not connected to a urine meter
Periurethral colonization with uropathogens major underlying disease and comorbidities (56). Nevertheless,
the urinary tract is the source of 11% to 40% of healthcare-
associated BSis (53,61,62).
Healthcare-associated UTI is associated with a mortality rate
or serum creatinine >2 mg/dL at the time of catheterization of 14% to 19% (58,63); patients with UTI are nearly three times
(OR= 2.1) ( 43). Heavy periurethral colonization with bacteria more likely to die during hospitalization than patients without
also has been associated with increased risk of bacteriuria (49). infection (58). UTI-related healthcare-associated BSis have an
The significant risk factors for CA-UTI are summarized in attributable case-fatality rate of 12.7% to 32.8%, with severely
Table 31.2. ill patients at highest risk of death ( 10,52) . The use of a uri-
UTI-related bloodstream infections (BSis) occur infre- nary catheter alone has been independently associated with an
quently ( <4% of patients with catheter-related bacteriuria de- increased risk of death in elderly population residing in long-
velop bacteremia) (10,50-52). In an early prospective study by term care facilities (64,65).
Krieger et al., BSis from a urinary tract origin were found in
2.6% of patients with UTis (51). A more recent study reported
a rate of 1.4 BSis from a urinary tract source per 10,000 patient- DIAGNOSIS AND SURVEILLANCE
days (53). In a case series from an academic medical center,
Enterococcus sp. (28.7%) and Candida sp. (19.6%) were the pre- Clinical diagnosis of CA-UTI can be challenging, as neither py-
dominant microorganisms associated with hospital-acquired uria nor bacteriuria is a reliable indicator of symptomatic UTI
BSI from a urinary source (10). The risk factors for secondary in the setting of catheterization ( 47 ,56,66,67). In the catheter-
healthcare-associated BSI identified in multiple studies include ized patient, pyuria is not strongly correlated with UTI (66,67) .
UTI due to Serratia marascens, compared with other organisms In one study, pyuria was uniformly present with bacteriuria in
(RR = 3.5), male gender, immunosuppression, cigarette use, catheterized men, but pyuria was also present in 30% of cathe-
number of hospital-days before bacteriuria, neutropenia, and terized patients without bacteriuria (66). A prospective study of
renal disease (50,51,54). 761 catheterized patients found that pyuria was most strongly
associated with infection caused by gram-negative bacilli; infec-
tions caused by coagulase-negative staphylococci, enterococci,
CLINICAL MANIFESTATIONS or yeast were less frequently associated with pyuria (67). Uri-
nary white blood cell (WBC) counts >5 per high-power field
CA-UTI presents clinically with a spectrum from asymptomatic had a specificity of 90% for predicting infections, but had a
bacteriuria to urosepsis and death (1,2,55,56). Only 10% to 32% sensitivity of <37% (67).
of patients with catheter-associated bacteriuria experience symp- Bacteriuria in a catheterized patient usually is defined as the
toms attributable to infection; thus, most patients can be classi- growth of~ 102 colony-forming units (CFU) / mL of a predomi-
fied as having asymptomatic bacteriuria (1,2,55,56). In a study nant microorganism (1,47,56,68). The term bacteriuria often is
of 235 patients with healthcare-associated catheter-related bac- used interchangeably with UTI in the published literature, as
teriuria, approximately 90% of infections were asymptomatic. many early studies used bacteriuria to define catheter-associated
Patients, with and without infection, had no significant differ- infection. However, the distinction is clinically important, since
ences in fever, dysuria, urgency, flank pain, or leukocytosis (56). asymptomatic catheter-associated bacteriuria rarely results in
When present, local symptoms of UTI include lower abdomi- adverse outcomes and generally does not require treatment
nal discomfort, dysuria, urgency, frequency, or hematuria (57). (56). Nevertheless, a large proportion of antimicrobial use in
Fever, flank pain, or other clinical manifestations of pyelone- hospitalized patients is prescribed for the treatment of UTI,
phritis develop in <1% of patients with catheter-associated bac- most often, for asymptomatic bacteriuria (69,70).
teriuria (2,5S-60). Clinically recognized infections, including Diagnosis of UTI in patients with long-term urinary cath-
prostatitis, epididymitis, seminal vesiculitis, or renal infection, eters is particularly problematic, since bacteriuria is universally
may arise from bacteriuria originating during catheteriza- present unless antimicrobial therapy is given (1,11,71). Neither
tion, but the frequency of such infections remains ill defined urinalysis nor urine cultures are reliable tests for diagnosing
(2,5S-60). These complications arise primarily in patients with symptomatic UTI in patients with long-term indwelling urinary
Chapter 31 • Urinary 1Tact Infections 4 79
catheters (72). Cultures from these catheters are universally of a specific antimicrobial agent should be guided by the in
positive and may not reflect bladder cultures (22,73). Fever and vitro antimicrobial susceptibilities of the infecting organism(s).
chills are the most consistent symptoms of CA-UTI (59,60,71). Treatment with the catheter in place often results in emer-
UTI in patients with spinal cord lesions may be particularly dif- gence of resistant strains, and eradication of bacteriuria in the
ficult to diagnose because of the inability of the patient to sense presence of an indwelling catheter has been largely unsuc-
localizing symptoms (71). Fever or other systemic symptoms cessful (87,90). A prospective, randomized controlled trial of
may be the only clinical indication of UTI, especially in patients patients with symptomatic UTI found that patients who un-
who have spinal cord injuries (1,11,71). derwent indwelling catheter replacement before the initiation
An essential element of any preventive program is to mea- of antibiotic therapy had a significant decrease in bacteriuria
sure the prevalence of the condition and feedback the results and improved clinical outcome when compared with patients
of interventions to the clinical care providers. The CDC's who had no catheter replacement (90). Their findings support
NHSN surveillance definition for healthcare-associated UTI al- a recommendation that catheters present for at least 1 week
lows for standardization and interhospital comparison of infec- before the onset of catheter-associated infection should be re-
tion rates (74). The NHSN symptomatic CA-UTI rate (UTI per placed (or removed if no longer required) before antimicro-
1,000 urinary catheter-days) is the most widely accepted mea- bial therapy.
sure for infection surveillance, and is endorsed by the CDC,
Infectious Diseases Society of America (IDSA)-Society for
Healthcare Epidemiology of America (SHEA) compendium, PREVENTION
and the Association for Professionals in Infection Control and
Epidemiology (APIC) (75-77). However, a population-based Strict adherence to hand hygiene is recommended for the pre-
measure, in which 10,000 patient-days is used as the denomina- vention of all HAis, including UTis (91). Most UTI outbreaks
tor, may be another measure to assess CA-UTI interventions at have been linked to inadequate employee hand hygiene. The
individual hospitals (78, 79). Other process or proxy measures urinary tract of hospitalized patients represents an important
such as rates of asymptomatic bacteriuria, percentage of pa- reservoir for multidrug-resistant organisms (MDRO). Reduc-
tients with indwelling catheters, percentage of catheterization tion in the use of broad-spectrum antimicrobials, as part of
with accepted indications, and duration of catheter use have an overall antimicrobial stewardship program, is an important
been used in studies and collaboratives with good success (80). strategy to prevent the development of antimicrobial resistance
Surveillance for CA-UTis has not been a priority for most related to urinary catheters (92). Repeated antimicrobial treat-
hospitals previously, frequently due to inadequate resources to ment for bacteriuria during long-term catheterization is a sig-
perform hospital-wide surveillance and the relative low priority nificant risk for colonization with MDRO, yet some of this use
given to CA-UTI, as compared with other HAis (81,82). Since may be inappropriate ( 69,70) . Several specific measures for the
CMS has included CA-UTis as one of the hospital-acquired prevention of CA-UTis are discussed next (Table 31.3).
complications that will not be reimbursed, hospitals have re-
newed interest in CA-UTis (12,83). In addition, beginning in
SPECIFIC STRATEGIES FOR PREVENTION
2012, CMS has required, as a condition of participation, that
hospitals submit ICU-level CA-UTI rates to CDC's NHSN. Several guidelines have been updated recently for the preven-
These external pressures have resulted in increased attention tion of CA-UTI (75-77). Despite the existence and knowledge
to CA-UTI surveillance and prevention, although outcomes do of guidelines for the prevention of CA-UTI, adherence to guide-
not appear to be affected yet (84,85). lines varies among institutions. A 2005 nationwide survey found
that >50% of hospitals did not have a system for monitoring
urinary catheters, three-quarters did not monitor the duration
TREATMENT of catheterization, and one-third did not conduct surveillance
for UTis (82,93). Even after the enactment of the CMS nonpay-
Most patients with catheter-associated bacteriuria are asymp- ment rule in 2009, only one CA-UTI prevention practice, that
tomatic and do not require treatment unless the patient is is, the use of bladder ultrasound, was implemented in >50%
at high risk for complications (e.g., BSI or renal infection) of hospitals (93). Another study showed that only a small pro-
(55,56,86,87) . A recent study revealed that a 1-hour educational portion of ICUs have policies supporting bladder ultrasound
session reduced the inappropriate use of antibiotic therapy for (26%), catheter removal reminders (12%), or nurse-initiated
in patients with positive urine cultures (88). In addition, audit catheter discontinuation (94). The collaborative approach to
and feedback to healthcare providers has potential to decrease
overdiagnosis of CA-UTI and associated inappropriate antibi-
otic use (86).
Treatment of asymptomatic bacteriuria may be useful in pa- TABLE 31.3 Specific Strategies for
tients with neutropenia, pregnancy, if the patient is undergoing Prevention of Catheter-
transurethral resection of the prostate, or other urological pro- .Assodatm Infections (7~77)
cedures likely to induce bleeding (89). In most patients without
such complicating clinical features, bacteriuria often resolves • Avoid catheterization
• Decrease the duration of catheterization
spontaneously with removal of the catheter. After catheter re-
• Insert and care for catheters aseptically
moval, the patient can be observed and subsequently treated if
• Use a closed sterile drainage system
the bacteriuria does not resolve spontaneously after 48 hours • Maintain gravity drainage
(89). Because the antimicrobial susceptibility patterns of strains • Consider anti-infective catheters in selected populations
causing catheter-associated bacteriuria vary widely, the choice
the implementation of prevention measures, as detailed later, the level of training and correlated with inappropriate cath-
has begun to prompt systematic changes in the adoption of pr~ eter use; overall, 22% of interns, 28% of residents, and 38%
vention practices (80,95). of attending physicians were unaware of catheters in their pa-
tients (9). In addition, physician orders for catheter placement
or documentation of presence of catheter occurs in <50% of
LIMITING THE USE OF INDWELLING
catheters (96). Physician orders should be required for inser-
URINARY CATHETERS
tion of any urinary catheter, and institutions should implement
Because as many as 80% of healthcare-associated UTis and a system for documenting the placement of catheters (75, 76).
95% of UTis in ICUs are associated with a urinary catheter, the Nurse-driven interventions have demonstrated effectiveness in
most important prevention strategy is decreasing the use of uri- reducing the duration of catheterization (102,103). A nurse-
nary catheters (1,5,11). Data from NHSN between January and based reminder to physicians to remove unnecessary urinary
December 2010 reveal urinary catheter utilization in partici- catheters in a Taiwanese hospital resulted in a reduction in
pating ICUs ranging from 0.16 to 0.82 urinary catheter-days/ CA-UTI from 11.5 to 8.3 per 1,000 catheter-days (104). A multi-
patient-days. Utilization was highest in neurological and trauma faceted approach, including several types of education, system
ICUs (0.82 and 0.80 catheter-days/patient-days, respectively) and redesign, rewards, and feedback managed by a dedicated nurse,
lowest in pediatric ICUs (0.16 catheter-days/patient-days) (40). resulted in marked decrease in daily prevalence of urinary
Overall, urinary catheters are overutilized, and the documenta- catheter-days ( 105) . Such interventions are easy to implement
tion surrounding catheterization is inconsistent (9,96-98). and may consist of either a written notice or a verbal contact
Decreasing catheter usage may require interventions at sev- with the physician regarding the presence of a urinary catheter
eral stages of the life cycle of a urinary catheter (99). The first and alternative options. The feasibility of this type of interven-
step toward decreasing catheter utilization is limiting the plac~ tion was demonstrated in a statewide effort that resulted in sig-
ment of indwelling urinary catheters; catheters should be in- nificant decrease in catheter use and increase in appropriate
serted only for appropriate indications (Table 31.4). Urinary indications of catheters (80).
catheters are important for patients requiring drainage of ana- However, computerized physician order entry systems may
tomic or physiologic outlet obstruction, patients undergoing offer a more efficient and cost-effective method to reduce both
smgery of the genitourinary tract, patients requiring accurate the placement of catheters and duration of catheterization.
urinary output measurements, and patients with sacral or peri- Cornia et al. found that a computerized reminder reduced the
neal wounds. Despite these recommendations, studies indicate duration of catheterization by 3 days (106). A systematic review
that urinary catheters are placed for inappropriate indications and meta-analysis reports that urinary catheter reminder sys-
in 21% to 50% of catheterized patients (9,97,98,100). Health- tems and stop orders appear to reduce the mean duration of
care institutions should develop written policies and criteria for catheterization by 37% and CA-UTis by 52% (107) .
indwelling urinary catheterization on the basis of these widely ac-
cepted indications (75-77). Interventions for limiting the plac~
PERIOPERATIVE MANAGEMENT
ment of urinary catheters targeted at hospital locations where
OF URINARY CATHETERS
initial placement usually occurs, such as emergency departments
and operating rooms, will have the most impact (101). Specific protocols for the management of postoperative urinary
Once the catheters are placed, strategies for early removal catheters are important for reducing urinary catheterization
become essential. Urinary catheter management based on utilization. Approximately, 85% of patients admitted for ma-
physician orders only may be inadequate as physicians are jor surgical procedures had perioperative indwelling catheters;
frequently unaware or forget that their patient has a urinary patients with duration of catheterization of >2 days were sig-
catheter. A study conducted at four different institutions found nificantly more likely to develop UTis and were less likely to
that 28% of HCWs were unaware that their patient had an in- be discharged (108). Older surgical patients were particularly
dwelling urinary catheter. Lack of awareness increased with at risk for prolonged catheterization; 23% of surgical patients
>65 years of age were discharged to skilled nursing facilities
with an indwelling catheter in place and were substantially more
likely to have rehospitalization or death within 30 days (109).
TABLE 31.4 Appropriate Indications In a large prospective trial of patients undergoing ortho-
for Short-Term Indwclling pedic procedures, a multifaceted protocol for perioperative
Urinary Catheter Use catheter management resulted in a two-third reduction in the
(75-77) incidence of UTI. The protocol consisted of limiting cath-
Monitoring of urine output required: eterization to surgeries > 5 hours or to total hip and knee
• Frequent or urgent monitoring is needed, as for critically ill replacements-removal of urinary catheters on postoperative
patients. day 1 after total knee arthroplasty and postoperative day 2 after
• Patient is unable or unwilling to collect urine. total hip arthroplasty (110).
Urinary incontinence (without obstruction): CMS has now included removal of urinary catheters within
• Patient with an open sacral or perineal wound. 24 hours of surgery as one of the Surgical Care Improvement
• At patient request. Project (SCIP) measures that are reported by all hospitals.
• Patient unable to wear a condom catheter.
Evaluation of patients undergoing one of the SCIP surgeries r~
Bladder oudet obstruction:
vealed that postoperative urinary retention developed in 2.1%
• Temporary relief of anatomical or functional obstruction.
• Longer-term drainage if surgical correction is not indicated. of patients ( 111). This group has significance because they are
Prolonged surgical procedures with general or spinal anesthesia. at risk of requiring recatheterization. Patients who developed
postoperative retention were more likely to be older men,
Chapter 31 • Urinary 1hut Infections 481
undergoing knee, hip, or colon surgery. It will be important to the use of sealed urinary catheter junctions (46,76,120,121}.
focus future studies on interventions to prevent urinary reten- An evaluation of two closed drainage systems compared a com-
tion in this higher-risk group. plex system (including a preattached catheter, antireflux valve,
In addition to preventing CA-UTis, there are other reasons drip chamber, and povidone-iodine-releasing cartridge} with a
to consider limiting indwelling urinary catheter usage; uri- two-chamber system. The authors found no difference in the
nary catheters may be unpleasant and restrictive to patients. rate of bacteriuria between the two systems (121}. Improper
Elderly men at a Veterans Affairs medical center more fre- catheter care and breaches of the closed system remain an im-
quently responded that a condom catheter was comfortable portant risk factor for the development ofbacteriuria (42,122}.
(86%} compared with an indwelling urethral catheter (58%,
p = .04} (112}. Patients also felt that condom catheters were OTHER CATHETER CARE PRACTICES
less painful or restrictive of activities of daily living (24% vs.
61%, p = .0008} (112}. Another sUIVey of patients and family Other interventions such as irrigating the bladder or instill-
of residents in long-term care facilities revealed that 85% pre- ing antibacterial solutions into the urinary collecting bag have
ferred diapers and 77% preferred prompted voiding to indwell- shown no benefit when used on closed urinary collecting sys-
ing urinary catheterization (113}. tems (123,124}. These practices allow for flow of organisms col-
onizing the catheter into the bladder and require opening the
closed system, and therefore are not routinely recommended
ALTERNATIVES TO INDWELLING
(125,126}. In addition, use of meatal lubricants and creams
URINARY CATHETERS
(both antibacterial and nonantibacterial) (127} or urinary
Intermittent urinary catheterization reduces the risk of bacte- catheters that have been coated with heparin (128} or polymer
riuria and UTI when compared with indwelling urinary cath- have not shown benefit for the prevention ofUTis (129}.
eterization. Patients with neurogenic bladder and long-term
urinary catheters, in particular, may benefit from intermittent
USE OF ANTI-INFECTIVE
catheterization (75}. In addition, a meta-analysis reported a re-
URINARY CATHETERS
duced risk of asymptomatic and symptomatic bacteriuria with
use of intermittent catheterization in patients following hip or Several studies support the use of anti-infective (latex-based sil-
knee surgery compared with indwelling catheterization (114}. ver alloy or nitrofurazone-impregnated} urinary catheters as ad-
Combining the use of a portable bladder ultrasound scanner junct to the preceding proven methods of prevention in patients
with intermittent catheterization may reduce the need for in- at high risk for CA-UTI (130-135}. A recent prospective trial ofa
dwelling catheterization (76,115}. silicone-based, silver-eoated urinary catheter, however, showed no
Condom catheters may be considered in place of indwell- effect in preventing UTis when compared with a silicone-based
ing catheters in appropriate male patients without urinary hydrogel catheter (136). Early analysis of the clinical and eco-
retention or obsnuction. A randomized trial demonstrated a nomic consequences of urinary catheters indicates that latex-
decrease in bacteriuria, symptomatic UTI, or death in patients based silver alloy catheters, which cost substantially more than
with condom catheters when compared with those with indwell- standard catheters, may provide both clinical and economic ben-
ing catheters; the benefit was primarily seen in men without de- efits in patient populations receiving indwelling catheterization
mentia (116}. Also, condom catheters may be less painful than for 2 to 10 days, including the critically ill (63,135}.
indwelling catheters in some men (112,116}. More recently, in a large meta-analysis, silver alloy catheters
were found to significantly reduce the incidence of asymptom-
atic bacteriuria in adult patients catheterized for <7 days, but
USE OF ASEPTIC INSERTION
the effect was diminished in those catheterized for >7 days
AND CATHETER CARE TECHNIQUES
(137}. Similarly, antibiotic-impregnated catheters were found
Proper aseptic technique, including aseptic insertion and main- to decrease the rate of asymptomatic bacteriuria in those cath-
tenance of the catheter and drainage bag, is another essential eterized for <7 days but demonstrated no benefit when the
strategy for preventing CA-UTI (19,42,75,76,112,116}. Cleans- duration of catheterization was >7 days (137,138). Few stud-
ing the meatus at urinary catheter insertion has been widely ies have evaluated antiseptic- and antibiotic-coated catheters in
recommended, but has not been well._,tudied. A randomized long-term urinary catheterization; thus, no conclusions can be
study comparing water with 0.1% chlorhexidine cleansing of drawn on the use of anti-infective catheters in this setting (139}.
the periurethral area before catheter insertion revealed no dif- There is no convincing evidence that the use of these
ference in the development of bacteriuria (117}. In addition, catheters prevents CA-UTI, UTI-related BSis, or mortality.
routine meatal cleaning of catheterized patients has shown no Therefore, there is no recommendation for routine use of anti-
benefit (118,119}. The collection bag should always remain be- infective urinary catheters to prevent CA-UTI (75,76). The use
low the level of the bladder to prevent reflux of urine (and of anti-infective catheters may be considered when the rates
bacteria introduced into the bag) into the bladder. Proper of CA-UTI remain high despite the implementation of other
hand hygiene and use of gloves for insertion and manipulation evidence-based practices, or in patients deemed to be at high
of catheters are critical to prevent introduction of exogenous risk for CA-UTI or its complications (139). A nationwide mixed-
pathogens (75,76). methods study revealed that 45% of nonfederal and 22% of
Veterans Affairs hospitals used antimicrobial catheters; hospi-
tals using anti-infective catheters often based their decisions
USE OF CLOSED DRAINAGE SYSTEMS
on hospital._,pecific pilot studies (81,82,93). The CDC Guide-
An important advance in the prevention of CA-UTI was the in- line has made the use of antiseptic-impregnated catheters a 1B
troduction of the closed catheter drainage system that includes recommendation (75}.
USE OF SYSTEMIC ANTIMICROBIALS 9. Saint S, W""" J, Amory JK, et al. Are phyoiciauo aware of which of their patient! have
indwelling catheten? A"']Mill. 2000;109:476-480.
10. Chang 'R, Green MT, Chenoweth CE, et al. Epidemiology of hoopital...,quired uriwuy
Systemic antimicrobial therapy may lower the risk of develop-
tnct-related bloodotn:m> infection at a univellity hoopital Inftl:l Conbol Hasp Epidmoiol.
ing a CA-UTI ( 42,43,48). However, several studies have also 2011;52:1127-1129.
demonstrated that antibiotic prophylaxis increases the rate 11. Shuman EK, Chenoweth CE. Recognition and prevention of healthcare-uoociated uriwuy
tnct infectiouo in the intenoio1: care unit. Grit c- M«l. 2010;58:857~579.
of isolation of antibiotic-resistant organisms in catheterized 12. SaintS, Meddiugl JA, Calfee D, et al. CatheteMioociated urinary tract infection and the
patients (22,140,141). As a result, routine use of prophylactic medicare rule changco. A=mtm. Mrd. 2009;150:877~4.
antibiotics for catheterized patients is not recommended be- 13. Um1heid C, Mitchell M, DoohiJ, et al. Eotimating the proportion ofhealthc:are·alllociated
infectiono that are reasonably pn:ocntable and the related mortality and cost>. bifoct Conbol
cause of cost, potential adverse effects, and potential for selec- Ho.p~ 2011;32:101-114.
tion of antibiotic-resistant organisms (75,76). 14. Donlan RM. Biofiln" and dcvie<>illoociated infectiono. E~bif«t IJV. 2001;7:277-281.
15. Donlan RM. Bio.fihn formation: acliuically relevant microbiological pro<:elll. C/in!nftl:IDV.
2001;55:1!87-1!192.
16. Donlan RM, Cooterton .JW. Bio:filmo: oumval mechanioruo of clinically relevant microor-
USE OF BUNDLES, COLLABORATIVES,
ganionu. C/in Micrubiol &.. 2002;15:167-193.
AND LEADERSHIP 17. Dunne Jr WM. Bacterial adheoion: oeen any good bio:filmo lately'l C/in MimJIJiol &rJ.
2002;15:15,...166.
Recently, "bundles" have been used with success for the imple- 18. Tambyah PA, Halvonon liT, Malri DG. A proopec1ive otudy of pathogeneoil of catheter-
mentation of interventions for several types of HAis. A bun- auociated urinary tnct infectiono. MJI1!0 am Pro<. 1999;74:131-156.
19. Malri DG, Thmbyah PA. Engineering out the riok. of infection with urinary catheter~.~
dle applied to CA-UTI prevention was successfully adopted by inK Inftt:t DU. 2001;7:542-547.
the Michigan Hospital Association Keystone initiative (80,95). 20. Schaberg DR, HaleyRW, Highomith AK, et al. Nooocomial bacteriuria: a proopective otudy
of caoe cluotering and antimicrobial reoiltance. Annmtm. Mill. 1980;95:420-424.
Finally, the essential role of local hospital leadership and fol-
21. Joneo GL, RuRell.AD, Oaliokan Z, eta!. A llr1ilq!y for 1he control of catheter bloc. . by t7)'1td-
lowership for ensuring effective implementation of preventive linel'nJinu.......,..biofilmwingtheantt'bacterialagenttriclooan. Ew[m.I.2005;48(5):83&-M5.
initiatives has been highlighted (142-144). 22. Warren .JW, TenneyJH, Hoopeo JM, et al. A proop~ microbiologic otudy of bacteriuria
in patienta with chronic indwelling urethral cathetero.JbifoctDU. 1982;146: 71~725.
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25. Stickler DJ, ZimakoffJ. Complicationo of urinary tnct infectiono aooociated with derica
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26. Stickler DJ. Susceptibility of antibiotic-resistant gnm..negative bacilli to biocideo: a per-
bidity. CA-UTh are associated with hospital pathogens with a
opecm.. from the omdy of catheter bio:filmo.j.<!ppiM~ 2002;92(ouppl):l65S-170S.
high propensity toward antimicrobial resistance. Despite stud- 27. Donlan RM. Role of bio:filmo iu antimicrobial resistance. 111U!IO]. 2000;46:547-$2.
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and increased attention toward prevention of CA-UTI by CMS Healthcare SafetyNetwori., 2010. htfta ConboiHaspEpiMMid. 2012;55:9"-1000.
and other third-party payers, adoption of evidence-based prac- 29. Bouza E, SanJuan R, Munoz P, et al. A European penp~ on nooociomial urinary tract
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bility (ESGNI.OO! study). ClinMicnJbidlnfoct. 2001;7:52$-551.
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nant risk factor for CA-UTI; preventive measures directed at healthcare-a110ciated infections: •UIIlliWY of data reponed to the National Healthcare
Safety Network at the Centero for Dioeue Control and P==tion, 20W-2010. lnfta Ctm-
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have a significant impact on decreasing CA-UTis. Alternatives 51. Groll PA, Harka"f LM, Barden GE, et al. The epidemiology of nooocomial enterococcal
to indwelling catheters such as intermittent catheterization and urinary tract infection. A"'] Mid St:i. 1976;272:75-81.
52. Morrioon AJ, Wenzel 'RP. Nooocomial uriwuy tnct infection• due to enterococcw. Anh
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ization is appropriate, proper aseptic practices for catheter inser- 55. Groll P, Harkavy L, Barden G, et al. The epidemiology of nooocomial enterococcal urinary
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54. Murray BE. Vancomyciu"<eliotant enterocuccal infections. N &f,!J Mrd. 2000;542:710-721.
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Donald E. Craven, Philip E. Grgurich,
32 Kathleen Steger Craven, and Henri Balaguera
Hospital-Acquired and
Ventilator-Associated Pneuntonia
INTB.ODUCTION fint 5 dafl, 2% per day from days 6 to10, and 1% per day there-
after (13,14). Improved prevention strategies have led to lower
Hospital-acquired pneumonia (HAP) and ventilator-associated rates of HAP and VAP in the past decade (2,15).
pneumonia (VAP) remain important causes of morbidity and
mortality despite recent advances in antimicrobial therapy and
the use of a wide range of prevention measures (1-~). HAP is OUTCOMES: MORTALITY, MORBIDITY,
an infectious disease of lung parenchyma occurring ~48 bout'S LENGTH OF STAY, AND COSTS
after admission that was not incubating at the time ofadmiaaion.
VAP refer~ to pneumonia that occurs >48 hours after endotra- The crude mortality rates for VAP range from 20% to 50%,
cheal intubation. reflecting, in large part, the severity of the patient's underly-
Bacterial pathogens causing HAP and VAP originate from ing disease, presence of organ failure, and infections caused
the host's endogenous nora, other patients, hospital staff, and by MDR pathogen(s) (1,5,10,13,15). In two studies of VAP,
environmental sources. Bacterial entry for VAP may result the mortality rate varied between 4% in patients without prior
from aspiration during intubation, leakage around the endo- antibiotic exposure and 73% in those with VAP due to MDR
tracheal tube cuff, or endotracheal tube colorri:zation (1,4). pathogens (e.g., P. aeruginosaor A. baumDnnu), and attributable
Over the past decade, there has been an increase in HAP and mortality ranged from 6% to 14% (16,1'7).
VAP caused by multidrug-resista:nt (MDR) pathogens, such VAP increases the duration of hospitalization by 12 days, me-
as Ps~ anvginosa, Acintlobacttr baumannii, other resis- chanical ventilation by 10 da:yll, and ICU stay by 6 da:yll, at a cost
tant Enterobacteriaceae, and methicillin-resistant Staphy'Weoecus of $40,000 (13). In a more recent study, when compared with
atmUS (MRSA) (1,5-9). patients without VAP, VAP was associated with a !~longer
This chapter highlights the epidemiology, diagnosis, treat· hospital stay and a similar increase in cost (18). Other analyses
ment, and prevention of HAP and VAP. Our primary focus is have suggested that the morbidity associated with VAP reru.lts
on the wide spectrum of bacterial pathogens causing HAP and in estimated cost per case of nearly $15,000. The discordance
VAP. The readers are referred to other chapter~ for informa- in these cost e~timates refiects the differences in accounting
tion on pulmonary infections caused by mycobacteria, viruses, for patient charge~ w. costs (13,19,20). VAP survivors who have
and fungal pathogens. experienced long-term mechanical ventilation and then W.
charged to chronic care facilities have a significant risk of re-
admission and increased morbidity and healthcare costs. In a
EPIDEMIOLOGY recent study. the average coat per ICU survivor 1 year following
discharge was ....$3.4 million (21). These data underscore the
Each year, there are between 5 and 10 episodes of HAP per importance of preventing HAP and VAP. In addition, there is
1,000 hospital admissions, but the incidence is decreasing a growing trend toward public reporting of institution-specific
(1,5,10). HAP and VAP account for 15% of all healthcare- HAI rates is increasing, which in the future may be linked to
associated infections (HAis) and ....25% of all intensive care reduced hospital reimbunement for care.
unit (ICU) infections (11). HAP and VAP rates and etiology
are infiuenced by underlying host disease, length of hospital
stay, and transfer~ to acute care facilities from other healthcare PAIHOGENESIS
venues. The overall rates of HAP and VAP tend to be higher in
academic vs. nonteaching hospitals. The pathogenesis of HAP and VAP involve~ the direct inter·
The Centers for Disease Control and Prevention's (CDC) action between the invading pathogen(s), risk factors, and
Nati.oual Healthcare Safety Network. (NHSN) data summary host and host defenses (Figure 32.1). Microaspiration in non-
from January through December 2010 reported >~,525 VAPs ventilated patients is the primary route of bacterial entry into
in the United States with an incidence between 0.0 and 5.8 per the lower respiratory tract for HAP (5,10). Patients who are
1,000 ventilatoNiays (12). Crude rates of HAP and VAP vary sedated, postoperative, or have abnormal swallowing are at
by patient population and method of diagnosis (1,5,10). The high risk for aspiration (5,10). Direct inoculation, bacteremic
rates ofVAP increase with the duration of mechanical ventila- spread, and translocation of bacteria from the gastrointestinal
tion, and have been estimated to be -3% per day during the tract (GI) are less well-documented routes of infection.
485
486 St!Ction III • E~ and Epitiemic Hospi:allnftc#itms
The development of biofilm-eucased bacteria increases over

Naopha.ryngNI a Gastric Colonl:rallon time in the endotracheal tube lumen and may result in bacte-
Aspiration or Endotracheal Tube rial embolization to the bronchi and alveoli during suctioning
or bronchoscopy (23).
In contrast to healthy people, critically ill patients and those
with VAP have high rates of oropharyngeal colonization with
bacterial pathogens (5,10). Colonization with gram-negative
bacilli was present in 16% of moderately ill patients vs. 57%
of critically ill patients, and the rates of pneumonia were in-
creased 6-fold in ICU patients with bacterial colonization (24).
Host factors, types of bacteria colonizing the pharynx, and the
use of antimicrobiaLs may alter colollization and adherence
of gram-negative bacilli. Oral epithelial ceUs rich in fibronec-
tin bind gram-positive organisms, such as streptococci and
S. aumc.s. Conversely, those poor in fibronectin preferentially
Flpre 32.1. Pathogenesis of hospital-acquired pneumonia bind gram-negative bacilli such asP. anuginosa (25).
(HAP), ventilator-associated tracheobronchitiJ (VAT), and ventilator- The stomach contents are usually sterile when the pH is <2
associated pneumonia (VAP); early therapy and desired outcomes. due to the potent bactericidal activity of hydrochloric acid, but
increases significandy with increases in gastric pH. The use of
antacids or histamine-2 (H2) antagonists or proton pump in-
In the intubated patient, lower airway colonization may oc- hibitors, commonly prescribed for stress bleeding prophylaxis
cur during intubation, by leakage around the endotracheal in mechanically ventilated patients, increases gastric pH, result-
tube cuff or through the endotracheal tube (Figure !2.2). In ing in bacterial colonization that may exceed 1 million organ-
mechanically ventilated patients, inhalation of aerosols, con· isms per milliliter (Figure 32.2) (10,26-28). Rdlux of bacteria
taminated tubing condensate, and leakage of bacteria and oral from the stomach to the oropharynx and lung may occur when
secretions around the endotracheal cuff are routes of bacterial patients are supine or not kept upright during transport from
entry into the lower respiratory tract (Figure 32.2) (22). In ad- the ICU for X-rays, surgery, or other tests, thw increasing the
dition, local trauma and inflammation from the endotracheal risk of bacterial entry into the lung.
tube increase tracheal colonization and prevent clearance of The reaponse of pulmonary host defenses to invading mi-
organisms and secretions from the lower reapiratory tract. croorganisms plays an integral part in the pathogenesis and
Oropharynx
Orogastric
Tube
Endotracheal Tube
Endotracheal ---...:::;e~~~
Orogastric Tube
Tube
Ventilator-Associated ----r-----T'-,----r.
Tracheobronchitis Trachea
(VAT)
Ventilator-Associated Pooled Secretions

Pneumonia
(VAP)
Esophagus
Colonization
depends on pH
(0-1 06 cfu/ml)
Flpre 32.2. An intubated patient with oropharyngeal and gastric colonization; note the subglottic secretions pooled above the endotracheal
tube cuff and that the endotracheal tube preventiJ mechanical clearance of bacteria and secretions from the trachea; bacteria-encased biofilm
forms in the lumen of the endotracheal tube and increases with duration of intubation. Endotracheal and gastric tube& are in the oropharynx and
are also potential sources for colonization and persistence of multi.drug-resiatant pathogens.
Chapter 32 • Hospital-Acquired and Ventilator-Associated Pneumonia 487
outcome of infection, which may result in HAP, ventilator- STREPTOCOCCUS PNEUMONIAB AND
associated tracheobronchitis (VAT), or VAP, as shown in HABMOPHILUS INFLUENZAB
Figures 32.1 and 32.2 (1,5,29). Mucociliary and mechanical
clearance in the upper airway are important factors in the de- S. pneumoniae and H. injl'Uei'IUJe usually cause early-onset HAP
and VAP. Penicillin or ceftriaxone are the drugs of choice for
fense against infection. The role of bacterial antigens and cyto-
pneumonia due to S. pneumoniae, but resistance may occur (37).
kines that alter the activity and efficacy of ciliary cells in dearing
Generally, patients infected with strains with low or moder-
bacteria from the lower airway should be studied further. The
ate levels of resistance to penicillin have clinically improved
ability of macrophages and polymorphonuclear leukocytes to
when treated with the antibiotic (38). All of the penicillin- and
eliminate bacterial pathogens and the interaction of these cells
ceftriaxone-resistant strains in the United States are currently
with inflammatory cytokines probably play important roles in
the pathogenesis of pneumonia. Cell-mediated immune re- sensitive to vancomycin and linezolid, and many isolates re-
main sensitive to fluoroquinolones. Resistance of H. injluenzae
sponse is controlled by a complex array of lipids, peptides, and
cytokines, including interleukin-1 and -2, interferons, growth to antibiotics other than penicillin and ampicillin is rare.
factors, and chemotactic factors. Leukotrienes, complement
components, and platelet-activating factor also assist in the METHICILLIN-SENSITIVE STAPHYLOCOCCUS
inflammatory response and contribute to the pathogenesis of AUREUS (MSSA)
pneumonia. On the basis of an improved understanding of the
MSSA usually causes early-onset HAP and VAP. Data from the
molecular interaction between bacterial cell walls, toxins, and
SENTRY program revealed that the incidence of MSSA in HAP
host defenses, strategies should be considered to enhance host
has remained remarkably consistent for the past 14 years world-
defenses and supplement current antimicrobial regimens.
wide U~9). In a recent multinational study of HAP and VAP in
patients admitted to ICUs, S. aureuswas documented as a caus-
ative pathogen in 5.5% of cases in Europe and 11.1% of cases
SPECTRUM OF BACTERIAL PATHOGENS in four countries in Latin America, with MSSA being identified
in 63% and 55% of the Staphylococcus isolates, respectively. As in
The wide spectrum of etiologic agents causing HAP and VAP, previous studies, mortality was higher in the MRSA group ( 40).
shown in Table 32.1, varies with time, facility size, geographic In the United States, as in other parts of the world, the inci-
location, type of ICU, patient population, and method of dence of S. aumusis lower among patients with VAP than among
diagnosis (5,9,10,13,30,31). Bacteria causing HAP and VAP patients with HAP ( 19.5% vs. 26.6%) ( 41) .
may originate from various sources, including the patient's
endogenous oropharynx or gastric flora, other patients, medi-
LEGIONELLA PNEUMOPHILA
cal staff, contaminated devices, or the environment (4,32,33).
Gram-negative bacilli have been implicated in most episodes of The rates of HAP due to L. pneumophila vary among hospitals,
HAP and VAP, and S. aureus (often MRSA) accounts for -20% but are increased in immunocompromised patients (e.g., or-
to 40% ofinfections (9,10,34). The overall rates ofMDR patho- gan transplant recipients or patients with HIV disease) and in
gen infections are increasing in the United States (34-36). those with diabetes mellitus, underlying lung disease, or end-
HAP and VAP occurring during the first 5 days of hospital stage renal disease (4,10,42). Serotype 1 is most common and
stay are more likely to be caused by more ~antibiotic-sensitive" can be cultured on special media, but may be more rapidly
bacteria, such as Stmptoroccus pneumoniae, Moraxella catarrhalis, diagnosed by urinary antigen testing. HAP due to ugiooella
Haemophilus injluenz.LJe, methicillin-sensitive S. aureus, or anaero- spp. is more common in hospitals where the organism is pres-
bic bacteria (Table 32.1) (1,5,28). ent in the water supply or may surge during construction.
• JC:if~ffj. Bacterial Pathogens Causing HAP, VAT or VAP

Antibiotic-Sensitive Pathogens Multidrug-Resistant Pathogens
GRAM-POSITIVE COCCI: GRAM-POSITIVE COCCI:
Smptococcus pneumonioe Penicillin-resistant Smptococcus pneumonioe
Methicillin.,eruitive StfJPhylococcw aumu (MSSA) Methicillin-resistant Staflhyloroccus au711US (MRSA)
GRAM-NEGATIVE BACn.LI: GRAM-NEGATIVE BAcn.LI:

ll~huusinfl~ Pseudomonas anuginosa
Escherichia coli Escherichia cdr'
Klebsiella pneumonioe Klebsiella pneumoniai!Ab
Enterobacier aerogmes Enterobacter sp. "'6
Protms species .AciMtobacter sp. G,b,c
Stmotrophomonas mallophU
"ESBI.rpositive (extended.,.pectrum p --lactamase).

bcRE-positive (carbapenemase-resutant Enterobacteriaceae).
'Some isolates sensitive only to polymyxin.
"strairu may be sensitive only to oimethoprim-sulfamethoxazole, or tluoroquiniolones, or ceftazidime.
Owing to the widespread use of Legionella urinary antigen resistance, from 15% at initiation of imipenem treatment for
rather than culture for the diagnosis of Legionella, infection due VAP to 54% during treatment (46). Although currently uncom-
to serotypes other than serotype 1 may be underdiagnosed. De- mon in the United States, there is concern about the acqui-
tailed strategies for the prevention of Legionella spp. infection sition of plasmid-mediated metallofj-lactamases active against
and eradication procedures for LegiQTUJlla spp. in cooling towers carbapenems and antipseudomonal penicillins and cephalo-
and the hospital water supply are outlined in Chapter 44 (10). sporins. Currently, some MDR isolates of P. aeruginosa are sus-
ceptible only to polymyxin B.
MDR PATHOGENS
Klebsiell11, Enteroht:Jtter, 11ntl Serrt:Jti.IJ Species
By comparison, late-onset HAP and VAP are more commonly
caused by MDR pathogens, including MRSA, Klebsiella pneu- Klebsiella spp. are intrinsically resistant to ampicillin and other
moniae, A. baumannii, or P. aeruginosa (Table 32.1) (29,43). aminopenicillins and can acquire resistance to other penicil-
As summarized in the American Thoracic Society (ATS)/ lins and aztreonam by the production of extended-spectrum
Infectious Diseases Society of America (IDSA) guidelines and fl-lactamases (ESBLs) (5). Carbapenem antibiotics have histor-
shown in Figure 32.3, patients who have received prior antibiot- ically been considered the drugs of choice for ESBL-producing
ics, been hospitalized in the past 90 days, resided in a chronic organisms. Plasmids encoding ESBLs often carry resistance
care facility, or have debility or serious underlying diseases to fluoroquinolones, aminoglycosides, and other antibiotics.
or comorbidities are at greater risk of infection due to MDR Enterobacter, Citrobacter, and Serratia spp. as well as Escherichia coli
pathogens (29). Finally, individuals with HAP or VAP, who have can have chromosomal AmpC fl-lactamases with consequent
severe disease, such as septic shock or multiple organ failure, resistance to oxyimino-/3-lactams and a.-methoxy-fl-lactams,
should be given initial broad-spectrum antibiotic therapy as but have susceptibility to carbapenems. Recent reports of in-
shown in Figure 32.3. Specific MDR pathogens causing HAP creasing rates of carbapenemase-producing Enterobacteria-
and VAP are shown in Table 32.1 and discussed below. ceae (CPE) or Klebsiella-producing carbapenemases (KPCs)
have emerged. CPEs and KPCs confer resistance to carbapen-
ems and have been increasingly observed in isolates of K
Psetulomomu Aeruginos11
pneumonia, E. col~ and Enterobacter sp. Treatment options for
P. aeruginosa, the most common MDR gram-negative bacterial CPE infections should be made on the basis of antibiotic-
pathogen causing late-onset HAP and VAP, has intrinsic resis- susceptibility reports.
tance to many antimicrobial agents (5,44). This resistance is
mediated by multiple efflux pumps, which may be expressed
AcinetohtUter BIJum~~nnU, StenotrophomoniU
continuously or may be upregulated by mutation. Resistance to
Mllltophilit:J, 11ntl Burkholtlerit:J Cep1Ui11
piperacillin, ceftazidime, cefepime, other oxyimino-13-lactams,
imipenem and meropenem, aminoglycosides, and fluoroqui- Although generally less virulent than P. aeruginosa, Acinetobacter
nolones is increasing in the United States. Decreased expres- spp. have nonetheless become problematic pathogens because
sion of an outer membrane porin channel (OprD) can cause of their increasing resistance to commonly used antimicrobial
resistance to both imipenem and meropenem or specific resis- agents (4 7). Owing to mechanisms including fl-lactamases, po-
tance to imipenem but not other fl-lactams ( 45) . A systematic rins, and efflux pumps, Acinetobacterspp. can manifest resistance
literature review reported significant increases in imipenem to commonly used antibiotics for treating pneumonia (17,48) .
Resistance to carbapenems through either IMP-type metallo-
enzymes or carbapenemases of the OXA type has increased to
at least 40% of isolates in the United States ( 49). Alternative
I Early, Appropriate Antibiotic Therapy therapies include sulbactam, which is usually employed as an
enzyme inhibitor but has direct antibacterial activity against
I Acinetobacter spp., as well as polymyxins and intravenous and
Assess Risk Factors for Resistant Pathogens: inhaled aminoglycosides as adjuvant agents. Stenotrophomonas
Prior Antibiotics, Hospitalization within 90 days, maltophilia, which shares with Bumholderia cepacia a tendency
Chronic Care, Debility, or Co-morbidities
to colonize the respiratory tract rather than cause invasive dis-
I ease, is uniformly resistant to carbapenems because of a ubiqui-
®-I
LIMIIED &E!ECIBLIM
Severe Disease }---$
BBOAD &E!ECTBUM
tous, metallofj-lactamase. S. maltophilia and B. cepacia are most
likely to be susceptible to trimethoprim/sulfamethoxazole,
ticarcillin/clavulanate, or a fluoroquinolone. B. cepacia usually
Vancomycin or Linam lid is susceptible to ceftazidime and carbapenems.
(Caftrluona +1- Azlthromycln) + Anti·Pseudomonal (AP)
or Qulnolone CephaloiiPOrin .Ill.
AP Carbe.p-m .QJ:
or (Amplclllln/Sulbactam Piperecillin-Tazobactam METHICILLIN-RESISTANT
+1- Azllhromycln) +1- Quinolone or Aminoglycoside STAPHTWCOCCUS AUREUS
HAP and VAP caused by MRSA are associated with significant
Figure 32.3. Algorithm for the choice of initial empiric antibiotic
therapy for patients with HAP and VAP. (Adapted from American morbidity, mortality, and healthcare costs, making it a challenge
Thoracic Society & Infectious Diseases Society of America (ATS/ for infection control (49,50). MRSA produces a penicillin-
IDSA) Guideline Committee. Guidelines for the management of binding protein with reduced affinity for fl-lactam antibiotics
adults with hospital-ru:quired, ventilator-associated, and healthcare- that is encoded by the mecA gene, which is carried by one of a
associated pneumonia [29].) family offour mobile genetic elements (5). Strains of S. au1l!'US
with the mecA gene are resistant to all commercially available or semiquantitative endotracheal aspirates (SQ-EA) having mod-
.,6-lactams and many other antistaphylococcal drugs with con- erate ( + + +) or heavy ( + + + +) growth on agar plates (55).
siderable geographic variability worldwide. Vancomycin and Although clinical and microbiologic criteria are used for the di-
linezolid are the preferred agents for MRSA pneumonia. Treat- agnosis of HAP and VAP, there are m.Yor concerns about lack of
ment with these two agents was studied in a recently published diagnostic specificity and the spectrum of clinical, microbiologic,
multicenter, prospective, randomized, controlled trial that and radiologic criteria used (55). The best available evidence
demonstrated an -10% improvement in clinical response with suggests that clinical signs (i.e., fever, leukocytosis, and purulent
linezolid; however, the lower bound of the 95% confidence in- sputum} often alert physicians to the possibility ofVAP, while a
terval approached zero. There was no difference observed in more definitive diagnosis requires microbiologic and radiologic
mortality (51). Decisions to use vancomycin or linezolid for criteria (with the exception of Legionella jmeumophila that re-
MRSA pneumonia should be made on the basis of patient- quires urine antigen testing or special culture media) (56).
specific criteria, microbiologic data, and relevant considerations Over the past decade, there has been increased interest in
about potential renal toxicity for vancomycin or serotonin syn- VAT, which may be a precursor to VAP and a target for ear-
drome for linezolid. Linezolid therapy should be considered in lier therapy (57-60). The definitions of VAT and VAP are the
patients who are nonresponders to vancomycin or when MRSA same for clinical signs and microbiologic criteria using endo-
isolates have a vancomycin MIC > 1 7Jg/mL (52). tracheal aspirates (Table 32.2), but VAP requires evidence of a
Although vancomycin-intermediate S. aun!W' (VISA) with new infiltrate on chest X-ray or significant growth of a patho-
an MIC of 4 to 8 pg/mL and high-level vancomycin-resistant gen obtained by bronchoscopic bronchoalveolar lavage (BAL)
S. aun!W' (VRSA) with MIC 2:16 pg/mL have been isolated or protected specimen brush (PSB), as shown in Table 32.2.
from clinical specimens, all of these isolates have been sensi- VAT may be a precursor to VAP, and VAT has been suggested
tive to linezolid (53,54). Additionally, some S. aUn!W' isolates as a target for antibiotic therapy to prevent VAP and improve
demonstrating heteroresistance have been associated with poor patient outcomes. (57,61-64).
response to vancomycin. Although linezolid resistance has In HAP and VAP, diagnostic clinical criteria include a com-
emerged in S. aun!W', it is currently rare. Daptomycin resistance bination of temperature elevation, leukocytosis, presence of
also has been reported, but this drug is not indicated for the purulent sputum, and changes in oxygenation (hypoxemia).
treatment of HAP and VAP because of its inactivation by lung If available, sputum gram stain should be examined for bac-
surfactant. Ceftaroline, a broad-spectrum cephalosporin with teria and polymorphonuclear leukocytes (PMNs), and micro-
activity against MRSA, was recently introduced in the United biologic culture criteria should use Q-EA > lo'i or 106 cfu/mL
States, but does not have a Food and Drug Administration or SQ-EA with moderate ( + + +) or heavy ( + + + +) growth on
(FDA) indication for HAP or VAP. agar plates, as summarized in Table 32.2 (29,55,62,64). Some
clinicians use bronchoscopic (B-BAL) or nonbronchoscopic
bronchoalveolar lavage (NB--BAL) or protected brush samples
DIAGNOSIS (PSB) samples for the diagnosis of VAP. VAT, a precursor to
VAP, has similar microbiologic criteria based on Q-EA or SQ-
Accurate data regarding etiologic agents, epidemiology, and EA, but is not associated with a new or persistent infiltrate on
treatment of HAP and VAP are limited by the lack of standard- chest X-ray. There is also considerable variation in criteria and
ized diagnostic criteria and a clinical "gold standard," as shown interpretation of gram stain samples ofEA, BAL, and PSB sam-
in Table 32.2. Two broad strategies exist for the diagnosis ofVAP: ples. Of greater concern is the quality, interpretation, and lack
one depends on clinical and radiologic criteria and the other of specificity for pulmonary infiltrates diagnostic for HAP and
on microbiologic definitions using quantitative endotracheal VAP that are seen on chest X-rays and computer tomographic
aspirates (Q-EA >lOS or 106 colony-forming units [cfu]/mL) scans (29,65). It is often difficult to discriminate between an
TABLE 32.2 Diagnosis of Ventilator-Associated Tracheobronchitis (VAT) and Pneumonia (VAP).

Definitive Diagnosis ofVAP Requires a New Radiographic Infiltrate, or Quantitative
Miaobiologic Criteria from Bronchoscopy with Bronchoalveolar Lavage (BAL) or
Protected Specimen Brush (PSB)
Clinical Signs
mel Clinical Signs0 Radiographic Sign Microbiologic Culture Criteria
VAT At least two clinical signs of No new infiltrate on chest No positive BAL or PSB EA: semiquantitative culture EA:
criteria 1--3: X-ray or Cf scan moderate ( + + +) to heavy
VAP 1. Temperature: New and persistent Positive culture: BAL ( ++ + +) growth or quantitative
2:38°C or 100.4"F infiltrate on chest 2:104 cfu/ mL or PSB EA culture 2:10~ cfu/ mL
2. WBC 2:12,000/mm! or X-ray or cr scan 2:1o!cfu/ mL
S4,000/mm5
3. Purulent sputum
4. Hypoxemia
"Alternative diagnostic criteria: 2:1 of parameters 1-2 and 2:1 of parameters 3--4. VAP may be diagnosed by a CPIS 2:6.
CPIS, clinical pulmonary infection score (28,29); CT scan, computerized tomographic scan; EA, endotracheal aspirate.
infiltrate due to pneumonia vs. atelectasis, pulmonary edema,

pulmonary emboli, neoplastic processes, or some autoimmune
TABLE 32.3 Suggested Empirical
diseases. Chest radiographs consistent with pneumonia are Antibiotic Therapy
difficult to evaluate in patients with preexisting lung diseases, for Hospital-Acquired
such as those with adult respiratory disease syndrome (ARDS) Pneumonia (HAP) and
or congestive heart failure. Ventilator-Associated
Some clinicians use clinical pulmonary infection score Pneumonia (VAP) in Patients
(CPIS), which combines clinical, radiographic, physiologic at Risk for Multidrug-
(Pa02/Fi0 2 ), and microbiologic data into a single numerical Jksistant (MDR.) Bacteria
result (43). When the CPIS score was 2:6, there was good cor-
relation with the presence of pneumonia as defined by quan- MRSA Vancomycin or Linezolid
titative cultures of NB-BAL (66). Singh et al. used a modified Gram-negative bacilli Antipseudomonal cephalosporin
CPIS that did not rely on culture data to guide clinical manage- (e.g., cefepime, ceftalidime)
ment (67). Unfortunately, CPIS has been mainly evaluated in Or
medical and surgical ICUs. Some studies in surgical and trauma Antipseudomona1,6-Iactam/ J'-lacta-
patients suggest CPIS performs poorly, since it cannot reliably mue inhibitor (e.g., piperacillin/
tazobactam)
differentiate VAP from systemic inflammatory response syn-
Or
drome (SIRS) in the face of confounding clinical factors (68). Antipseudomonal carbapenem
(e.g., meropenem, imipenem,
doripenem)
CHANGES IN THE CDC SURVEILLANCE Plus
DEFINITIONS FOR VAP Antipseudomonal aminoglyco!ide (e.g.,
gentamicin, tobramycin, amWu:in)
The CDC, in conjunction with several professional organiza- Or
tions has been working to improve surveillance definitions Fluoroquinolone (e.g., ciprotloxacin,
levofloxacin, moxifloxacin)
for VAP in adult patients. The new definitions are planned for
implementation by NHSN in 2013. VAP rates in many hospitals Adapted from 2005 ATS/ IDSA Guidelines. (29).
have decreased significantly over the past decade, and ranged
from 0 to 5.8 per 1,000 ventilator-days. However, the current
definition involves a wide spectrum of clinical criteria that lack
specificity, and unfortunately, there is no current "gold stan- by K.lompas et al. evaluated 597 patients, and found that 9.3%
dard" for VAP diagnosis. had VAP (8.8 per 1,000 ventilator-days) (69). Compared with
Since the VAP surveillance definition is critical for assess- matched controls, VAP patients had prolonged mechanical
ing and implementing better VAP prevention strategies and ventilation (5.8 vs. 6.0 days) and longer days in the ICU (5.7 vs.
comparing rates between hospitals, the CDC convened a mul- 5.0 days). VAC was associated with increased mortality, but VAP
tidisciplinary working group to develop new surveillance defi- was not. The authors concluded that VAC assessment was fast,
nitions that will be implemented in 2013. All of these events and that objective surveillance definitions that include both
are measured by incidence per 1,000 ventilator-days. The new clinical and quantitative evidence of respiratory deterioration
terms and definitions for VAP include the following with spe- are strongly predictive of increased length of ventilation, ICU
cific details included in Table 32.3. stay, and increased healthcare costs.
• "Ventilator-AIIsociated Condition" (VAC) is associated

with changes in oxygenation, which may be due to either DEFINITIONS FOR VENTILATOR-
an infection or a spectrum of noninfectious causes, such ASSOCIATED PNEUMONIA
as congestive heart failure, adult respiratory distress syn-
drome, pulmonary emboli, or atelectasis. INFEGI'ION-RELATED VENTILATOR-ASSOCIATED
• "Infection-Related Ventilator-Associated Complication" COMPLICATION
(IVAC), which includes temperature criteria, changes in
On or after calendar day 3 of mechanical ventilation and within
white blood cell count, and use of antibiotic therapy.
• "Possible or Probable" VAP includes purulent secretions 2 calendar days before or after the onset of worsening oxygen-
ation measured by and increase in inspired oxygen (FiO~ 2:
and bacterial cultures of sputum, BAL, protected brush
samples, or lung tissue. 0.20) or daily minimal increase in positive end-expiratory pres-
sure (PEEP; ~3 em H 20) for 2 days, the patient should meet
These new CDC surveillance definitions are designed to both of the following criteria:
be suitable for use in internal quality improvement and are
• Temperature >38°C, or white blood cell count ~12,000
scheduled to begin in 2013. Details are available on the CDC
Web site: www.cdc.gov/nhsm/psc_da-vae.html. Note that these cells/mm! or s4,000 cells/mm5•
• A new antimicrobial agent(s)* is started, and is contin-
new surveillance definitions rely on changes in oxygenation,
clinical signs, and microbiologic criteria to define VAP, and ued for 2:4 calendar days.
that chest X-ray criteria for the diagnosis of probable or pos-
sible VAP were not included, because of lack of sensitivity and
"Excludes the following nonpathogens: normal respinto:ry/oral flora; mixed
specificity of new pulmonary infiltrates. A recent multicenter respiratory/oral flora; Candida sp. or yeaat not otherwille specified; coagullue-
evaluation of the above-proposed new surveillance paradigm negative Sta{JhylocrKcus sp.; and E~ sp.
POSSIBLE VENTILATOR-ASSOCIATED PNEUMONIA • Positive culture oflung tissue, 2:104 cfu/g or equivalent
semiquantitative result
• Positive culture of PSB*, 2:10!1 cfu/mL or equivalent
2 calendar days before or after the onset of worsening oxygen- semiquantitative result
ation, om of the following criteria is needed:
Or
1. Purulent respiratory secretions (positive gram stain) 2. One of the following (without requirement for purulent
• Defined as secretions from the lungs, bronchi, or tra- respiratory secretions):
chea that contain 2:25 neutrophils and ::510 squamous • Positive pleural fluid culture (where specimen was ob-
epithelial cells per low-power field (lpf, X 100). tained during thoracentesis or initial placement of chest
• If the laboratory reports semiquantitative results, those tube and not from an indwelling chest tube)
results must be equivalent to the above quantitative • Positive lung histopathology
thresholds. • Positive diagnostic test for Legionella spp.
Or • Positive diagnostic test on respiratory secretions for in-
2. Positive culture for a bacterial pathogen (qualitative, semi- fluenza virus, respiratory syncytial virus, adenovirus,
quantitative (>+++), or quantitative >105 cfu/mL) of parainfluenza virus, rhinovirus, human metapneumovi-
sputum(+++ o)*, endotracheal aspirate(>+++)*, BAL rus, or coronavirus
( > 104 cfu/mL) •, lung tissue, or protected specimen brush-
ing (>lOll cfu/mL)*
PRINCIPLES OF ANTIBIOTIC THERAPY
PROBABLE VENTILATOR-ASSOCIATED
EARLY, APPROPRIATE, AND ADEQUATE
PNEUMONIA
ANTIBIOTIC THERAPY
The 2005 ATS and IDSA Guidelines for Management of HAP
2 calendar days before or after the onset of worsening oxygen-
and VAP emphasized the importance of early, appropriate ini-
ation, one of the following criteria is met:
tial broad-spectrum or limited-spectrum antibiotic therapy based
1. Purulent respiratory secretions (from one or more speci- on an assessment of risk factors for MDR pathogens and the
men collections and defined as for possible VAP) severity of the patient's condition, as shown in Table 32.4 and
and one of the following (see Table 32.2): Figure 32.3. The rates of endemic MDR pathogens present in the
• Positive culture of endotracheal aspirate•, 2:105 cfu/mL hospital or specific ICU are also important. An "appropriate" an-
or equivalent semiquantitative result tibiotic is defined as one that is effective against the likely infect-
• Positive culture of BAC, 2:104 cfu/mL or equivalent ing pathogen(s). Adequate therapy refers to the use of proper
semiquantitative result dosing of the antibiotic(s), as summarized in Table 32.4 (29).
TABLE 32.4 Patients with abnormal renal function should have doses of potentially nephrotolric
antibiotics, such as vancomycin, aminoglycosidcs and trimcthoprim/sulfamcthoxozole
adjusted accordingly.
THERAPY FOR GRAM-POSITIVE PATIIOGENS
Vancomycin Consider an initial loading dose of vancomycin o£25-30 mg/ kg actual
body weight in seriously ill patient.. with sepsis, severe HAP/YAP or
endocarditis.
Linezolid 600 mg IV every 12 hours
THERAPY FOR GRAM-NEGATIVE PATIIOGENS

Antipseudomonal Cephalosporins
Cefepime 2 g IV every 8 hours
Ceftazidime 2 g IV every 8 hours
Antipseudomonal Penicillin
Piperacillin/tazobactam 4.5 g IV every 6 hours
Antipseudomonal Carbapenems
Meropenem 1 g IV every 8 hours
Imipenem 500 mg IV every 6 hours or 1 g IV every 8 hours
F1uoroquinolones
Ciprofloxacin 400 mg IV every 8 hours
Levofloxacin 750 mg IV every 24 hours
Moxifloxacin 400 mg IV every 24 hours
Aminoglycosides
Gentamicin IV: 5-7 mg/kg of dosing weight IV every 24-48 hours
OTHER. ANTIBIOTICS
Trimethoprim/sulfumethoxazole (S. maltophilia only) 5 mg/kg of trimethoprim IV every 6--8 hours
The specific choice of initial antibiotic therapy should be pathogens may vary with the patient's risk factors, medical his-
based on the likelihood of infection with one of the MDR gram- tory, and the prevalence and types of endemic MDR pathogens
negative bacilli or MRSA (29) (Figure 32.3). The risk factors present in the healthcare facility or specific location within the
for MDR pathogens include prior hospitalization, lat~onset hospital. For example, patients with no known risk factors for
infection, prior antibiotic therapy, chronic dialysis, residence MRSA or those in facilities with a low prevalence of MRSA may
in a chronic care facility, and immunocompromi.sed states. Al- not require initial treatment with vancomycin or linezolid. It is
though the ATS/IDSA Guidelines recommend coverage for important to use doses of antibiotics that will achieve adequate
MDR pathogens in the presence of any of these risk factors, concentrations in the lung parenchyma and to consider end-
combinations of >2 risk factors increase the likelihood of in- organ function when dosing antibiotics as outlined in the ATS/
fection due to MDR pathogens. Patients with severe disease, IDSAGuideline (Table 32.4) (5).
such as shock, ARDS, and respiratory failure, also should be
considered for initial broad-spectrum antibiotic coverage until ASSESSING CLINICAL RESPONSE
microbiologic data become available. AND DE-ESCALATING INITIAL THERAPY
The key principles of therapy include the use of initial
timely, empiric, broad-spectrum antibiotic therapy that is effec- While initial antibiotic coverage should be liberal and broad
tive against the infecting pathogen(s) followed by d~escalation enough to cover all suspected pathogens, d~escalation or
or streamlining therapy based on available microbiologic data streamlining of antibiotic therapy based on the patient's clini-
(Figure 32.4). Appropriate dosing of antibiotics, as suggested cal response and microbiologic data is of critical importance
in the 2005 ATS/IDSA Guidelines, is important for optimal to improve patient outcomes by minimizing unnecessary ex-
patient outcomes in patients (Thble 32.4). Therapy should posure to antibiotics and the development of resistance over
generally be limited to 7 to 8 days for patients who respond to time (Figure 32.4) (5,67,72). Patients without evidence of HAP
therapy and are not infected with S. aureus or nonfermenting or VAP, such as those without quantitative microbiologic evi-
gram-negative rods (5). The use of pro calcitonin concentration dence of infection, should have their antibiotics stopped, and
measurements also may help in reducing the duration of anti- if necessary, further workup and treatment for other sources of
biotic therapy (70, 71). fever should be pursued. On the other hand, if a patient fails
Patients with early-onset HAP or VAP who do not have se- to respond to therapy after several days of therapy and an alter-
vere infection or MDR risk factors usually can be treated with native etiology cannot be identified, clinicians should consider
more limited-spectrum antibiotics, such as ceftriaxone, a respi- broadening the antimicrobial coverage.
ratory fluoroquinolone, ampicillin/sulbactam, or ertapenem.
If atypical organisms are a concern, a fluoroquinolone should LIMITING THE DURATION OF THERAPY
be used or a macrolide should be added to one of the other In a landmark trial of patients with VAP, patients randomized to
agents (Figure 32.3) (5). Those patients with severe infection or 8 days of antibiotic therapy had fewer recurrences and less resis-
known risk factors for MDR pathogens need broader initial an- tance overall than those randomized to 15 days of therapy (73) .
tibiotic coverage. The selection of empiric antibiotics for MDR No significant differences were noted in mortality or clinical
response parameters, but the rates of recurrence for those
patients with VAP due to P. aeruginosa infection were higher
in the group treated for 8 rather than 15 days. Approximately
HAP, VAT or VAP Suspected 20% of the patients in this study had VAP due to S. aureus. The
Assess Clinical Signs & Obtain Cultures ATS/IDSA Guidelines recommend 7 to 8 days of therapy for
1 uncomplicated HAP or VAP with close follow-up for any signs
Early Appropriate Antibiotic Therapy of relapse. Given the higher rate of recurrence in patients with
Based on MDR Risk Factors & Severity (Figure 31-3) nonfermenting gram-negative rods, and the limited number of
patients with S. aureus in this study, pneumonia due to these
1 pathogens should be treated for longer than 7 to 8 days (Fig-
Assess Clinical Response & Microbiology ure 32.4) (5). Evaluation ofprocalcitonin kinetics maybe help-
De-Escalate Initial Antibiotic Regimen? ful in identifying patients who may need further therapy, but
1 does not alter mortality (70,71).
1 1
Non-Responders Responders STRATEGIES TO PREVENT
Wrong Bug,
Treat 7-1 Da~s HAPANDVAP
Wrong Drug, if uncomplica ad
wrong Diagnosis Prevention of HAP and VAP is critically important for reducing
patient mortality, morbidity, and associated healthcare costs.
Figure 32.4. Approach to initial antibiotic therapy and man- The core strategies are summarized in Table 32.5 and discussed
agement. Early, appropriate antibiotic therapy ill a&!lociated with
improved outcomes in terms of morbidity, mortality, and reduced below. These interventions need to be constantly monitored
healthcare costs. (Adapted from American Thoracic Society & Infec- and reinforced in an effort to reach a target of "zero VAP."
tious Diseases Society of America (ATS/IDSA) Guideline Committee.
Guidelines for the management of adults with hospital-acquired, HANDHYGffiNE
ventilator-associated, and healthcare-associated pneumonia. Approved
by the ATS Board of Directors and the IDSA Guideline Committee. Microbes causing VAP, particularly S. aureus and gram-negative
Am] Respir Grit Om M«J. 2005;171 :388-416.) bacilli, can be transmitted after colonization of the hands of
legislation in 2004, 14 states and the District of Columbia have

TABLE 32.5 Core Strategies to Prcn:nt
some form of staffing laws or regulations by 2009. In a study
HAPandVAP that measured the impact of mandated hospital nurse staffing
STRATEGIES TO PREVENT HAP AND VAP ratios in California, the lower ratios were associated with lower
• Staff education and appropriate staffing levels mortality and higher staff retention (81) .
• Handwashing and infection control
• Antimicrobial stewardship
• Pneumonia prevention bundle and checklist to remove INFECTION CONTROL
invasive devices Effective targeted surveillance for high-risk patients coupled with
STRATEGIES TO PREVENT VAP staff education, the use of proper isolation techniques, and effec-
• Avoid intubation, if possible tive infection control practices are the cornerstones for prevention
Noninvasive ventilation of HAP (4,10,79). Previous studies have indicated that hospitals
• Silver-i:oated or subglottic secretion drainage endotracheal with effective surveillance and infection control programs have
tubes rates of pneumonia 20% lower than hospitals without such pro-
• Implementation of the VAP infection prevention bundle grams (see Chapters 3 and 5). Infection control programs have
Daily interruption of sedation followed by daily assessment for
repeatedly demonstrated efficacy in reducing infection and colo-
readiness to extubate and trialing spontaneous breathing
nization due to l\IDR organisms (10,32,78,82-84). Unfortunately,
Semirecumbent positioning
Maintain oral hygiene with chlorhexidine
staff compliance with proven infection control measures, such as
Stress bleeding prophylaxis for those who absolutely require it; hand hygiene, remains inconsistent in many facilities. Thus, staff
avoid it if not indicated and discontinue at extubation education on infection control must be inclusive, frequent, and
• Mobilize ventilated patients early reiterative. Special attention should be directed toward house
• Treatment ofVAT staff, stndents, volunteers, and visitors, and compliance should be
monitored periodically.
Surveillance ofiCU infections to identify and quantify endemic
healthcare personnel. Hand hygiene is considered an impor- and new l\IDR organisms with timely feedback of data is critical
tant means of infection control, and adherence has increased (82,85-88). Timely communication of current data among clini-
dramatically in the ICU setting (74). The use of alcohol-based cians, laboratory, pharmacy, and infection control staff is essen-
hand solutions has been associated with increased compliance tial. Organism~pecific strategies for specific MDR pathogens may
with hand hygiene and decreased rates of HAis (75). be appropriate. For MRSA and VISA (or GISA) isolates, active
surveillance testing and isolation are recommended along with
more aggressive eradication methods (53,89,90).
STAFF EDUCATION AND STAFFING LEVELS
Cross<olonization and cross-infection are important mecha-
Reiterative staff education is needed for all clinicians and staff. nisms in the pathogenesis of HAis (4,10,82) (Figure 32.1).
The ICU should be the cornerstone for efforts to reduce the Gram-negative bacilli and S. awms often are present in high
incidence of HAP and VAP. Zack et al. initially reported a suc- concentrations as indigenous flora in critically ill patients, the
cessful VAP educational prevention program carried out in five hospital envirorunent, and on the hands or gloves of hospital per-
ICUs (76). The program, which was developed by a multidis- sonnel (4,91). Hand hygiene before and after patient contact is
ciplinary team, targeted respiratory care providers and ICU an effective means of removing transient bacteria, but because of
nurses who completed a self~tudy module on risk factors for the inadequacy of hand hygiene practices among hospital per-
VAP with evaluation both at baseline and after the program sonnel, some investigators have advocated the use of barrier pre-
interventions. In~ervice teaching programs were coordinated cautions (i.e., gloves and gowns) for contact with all patients. This
with ICU staff meetings, and fact sheets and posters were placed practice has been associated with significantly decreased HAl
in the ICU and Respiratory Care Department. The rates ofVAP rates in pediatric ICUs (5). H gloves are used, care must be taken
dropped nearly 58% to 5.7/1,000 ventilator-days, and cost sav- to change them and perform hand hygiene between patients.
ings were estimated to be between $425,606 and >$4,000,000. Nasal carriage of S. aureus is common among healthcare
Using an extension of this program in an Integrated Health workers (HCWs), and outbreaks are often associated with
Care System involving four hospitals, Babcock et al. reported a HCWs with dermatitis or nasal or rectal colonization (10).
46% reduction in VAP over an 18-month period (77). Bassetti et al. emphasize the importance of viral respiratory tract
Perhaps one of the most important and underappreciated infections in the transfer of airborne MRSA from a physician
prevention strategies is adequate staffing, particularly in ICUs to patients in an ICU (92). Molecular typing was performed
(10,78). Staffing must be sufficient to allow patient care to be to confirm the source of the outbreak, and experimental in-
provided while ensuring that staff are able to comply with es- duction of rhinovirus infection and its role in airborne disper-
sential infection control practices and other prevention strate- sion of bacteria was demonstrated (the "cloud adult"). Without
gies (77,79). In a study of abdominal aortic surgery patients the use of surgical masks, the dispersal of S. aureus increased
by Dang et al., decreased nursing staff was associated with sig- 40-fold. These data underscore the importance of upper respi-
nificantly higher rates of respiratory and cardiac complications ratory tract infection in the dissemination of S. aureus and the
than higher-intensity nursing care (80). importance of masks in preventing transmission.
Currently, this is of critical importance due to severe nursing
shortages and staffing reductions because of budget constraints.
ANTIBIOTIC STEWARDSHIP
Nurse-to-patient ratios should be 1:1 for high-risk, complicated
ICU patients or 2:1 for patients with lower disease acuity. Since Antibiotic stewardship programs play an extremely important
the implementation of California's historic ratio-based staffing role in the overall effort to control HAis, reduce emergence of
MDR organisms, preserve the utility of available antimicrobial during enteral feeding, continues to be strongly recommended
agents, and control spiraling healthcare costs. The rates of un- (5,10,110). However, some studies have not only questioned
necessary antibiotic administration in hospitals range from 30% the results of previous studies, but also suggested that main-
to 50% (93). Various front-end stewardship methods that limit taining semiupright patient position may not be practical,
the initiation of selected antimicrobials as well as back-end ap- at least at the levels currently recommended. A study by van
proaches that minimize overuse of already prescribed antibiotics Nieuwenhoven et al. in which mechanically ventilated patients
have been reported (94). The annual savings from comprehen- were randomly assigned to backrest elevation of 45° vs. the stan-
sive antimicrobial stewardship programs range from $200,000 to dard of 10° demonstrated the barriers to implementing this
$900,000 (95--97). The impact of antimicrobial stewardship pro- strategy (111). Backrest elevation was measured continuously
grams in reducing the emergence of MRSA was demonstrated during the first week of ventilation with a monitoring device.
in a program that reduced the use of fluoroquinolones (98). The targeted backrest elevation of 45o was not reached; the ac-
Antibiotic stewardship is complex and should be focused, tual achieved difference was 28° vs. 10°, which did not reduce
dynamic, and carefully monitored and may vary by type of MDR VAP. Similarly, Grap et al. monitored patient position in ICU
pathogen. For example, control of specific types of MDR gram- patients using a bed frame elevation gauge or electronic bed
negative bacilli may require "squeezing the balloon at multiple readout and found very low compliance with maintaining semi-
sites" to prevent the emergence of other MDR pathogens, as recumbent patient position with a mean backrest elevation of
nicely summarized by Rahal et al. (99,100). Participation of an only 19.2° with 70% of subjects maintained in a supine position
infectious disease pharmacist on the ICU team and computer- (112,113). Perhaps further studies measuring the impact of
ized decision support programs to optimize antimicrobial regi- maintaining ventilated and/or enterally fed patients in a semi-
mens should be considered (5,10). recumbent position may be needed to evaluate more attainable
targets. Until this issue is resolved, prevention guidelines rec-
ommend elevating the head of the bed for ventilated and/ or
ENVIRONMENTAL ISSUES
enterally fed patients.
MDR bacteria are commonly found in the environment (Fig- There are emerging data suggesting that placing a patient
ure 32.1) (53,79). Although it is widely appreciated that the in the lateral horizontal position may be superior to the semi-
environment is swarming with microorganisms, this does not recumbent position to prevent VAP. This approach has been
necessarily directly result in infection; therefore, widespread shown to be feasible and resulted in a greater number of
routine environmental sampling is not recommended. For ex- ventilator-free days observed in an initial study (p = .04) (114).
ample, despite studies showing that ugionella spp. can be recov-
ered from 12% to 70% of hospital water systems, this source of
ENTERAL FEEDING
nosocomial outbreaks remains underappreciated (4).
Studies are beginning to implicate the inanimate environment Enteral nutrition has been suggested as a risk factor for the
as an indirect contributor to pathogen acquisition (79). Special development of HAP, mainly secondary to the increased risk of
interventions, including targeted environmental sampling and aspiration of gastric contents (10,115). However, parenteral nu-
more aggressive environmental disinfection, may be indicated trition is associated with a higher risk of mortality, HAP, intra-
during outbreaks, particularly those involving MDR organisms or vascular device-associated infection, complications from central
organisms that are more resistant to routine cleaning (91). venous catheter insertion, higher costs, and loss of intestinal vil-
lous architecture, which may facilitate enteral microbial trans-
location (10,116,117). Initiating enteral feeding within the first
PATIENT POSITIONING
48 hours oflCU admission may decrease the incidence of infec-
Aspiration, the primary route of bacterial entry into the lung, tion compared with delayed feeding (11S-120).
is commonly increased during hospitalization, especially with The impact of gastric vs. postpyloric feeding on the de-
sedation, neuromuscular blockade, head trauma, intubation, velopment of VAP is controversial. One meta-analysis evalu-
enteral feeding, and following surgery (10,101-105). Supine ated seven studies that assessed the risks for ICU-acquired
patient positioning may facilitate aspiration, which can be HAP in patients randomized to either gastric or postpyloric
decreased by maintaining a semirecumbent patient position. feeding (117). Although significant differences were not
With the use of radioactive-labeled enteral feeding, cumula- demonstrated in any individual study, a meta-analysis showed
tive numbers of endotracheal radioactivity counts were higher that postpyloric feeding was associated with a significant re-
when patients were placed in a completely supine position (0°) duction in ICU-acquired HAP (relative risk [RR], 0.76; 95%
as compared with a semirecumbent position (45°) (106,107). confidence interval [CI], 0.59 to 0.99) (121). A more recent
One randomized trial demonstrated a 3-fold reduction in the meta-analysis, which included 11 randomized controlled tri-
incidence of ICU-acquired VAP in patients kept in a semire- als, failed to find a difference in the incidence of aspiration in
cumbent position vs. supine (108). VAP rates reached 50% critically ill patients (122).
in patients maintained in the supine position while receiving Enteral feeding protocols have been suggested to reduce
enteral nutrition. These data support maintaining patients complications (78,123). Bowman et al. instituted an evidence-
in semirecumbent positions, particularly during enteral feed- based, enteral feeding protocol in which 78% to 85% of patients
ing. In contrast to rotational beds and prone positioning, reached their enteral feeding goal. Aspiration pneumonia rates
semirecumbent patient position is a low-cost, easily accessible decreased from 6.8 to 3.2/1,000 patient-days (123). Such pro-
intervention and may be a more practical and more tolerable tocols should be reviewed by multidisciplinary committees to
approach (109,110). standardize enteral nutrition protocols.
Maintaining mechanically ventilated and/or enterally fed Early gastrostomy for enteral feedings has been suggested
patients in a 30° to 45° semirecumbent position, particularly as a strategy to reduce VAP in patients with head injury and
stroke ( 124). In a small, randomized clinical trial of 20 patients in patients undergoing cardiac surgery and no impact on mor-
with gastrostomyvs. 21 controls, the rates ofVAP were reduced tality was demonstrated (1M). Overall, CHG has the most ro-
(10% vs. ~8%, respectively) and most of the VAP episodes were bust data for preventing HAP as opposed to VAP (133,135,136).
late-onsetVAP (>5 days). Additional studies with higher enroll- Nonetheless, because CHG represents an inexpensive, non-
ment are needed to further assess this strategy in these high- toxic, topically applied modality that has demonstrated efficacy
risk patients. in some populations, it is widely used in ICUs across the United
States.
STRATEGIES TO PREVENT VAP ROUTINE STRESS BLEEDING PROPHYLAXIS-

RISK VS. BENEFIT
INFECTION PREVENTION BUNDLES
AND CHECKLISTS The IHI ventilator care bundle includes the use of pharma-
cologic agents, such as histamine type 2 (H2) antagonists and
Bundles are sets of processes of care that, when instituted as proton pump inhibitors (PPis), to prevent stress-related muco-
a group, provide more robust results than when each process sal disease in mechanically ventilated patients (137). However,
is instituted individually (125). The bwtdle concept was devel- these agents have been identified as potentially independent
oped by the Institute for Healthcare Improvement (IHI) in risk factors for gastric and upper airway bacterial coloniza-
2002 and accepted as a model to reduce VAP in 2005 (126). tion, HAP, and VAP, with PPis appearing to predispose more to
The following practices are part of the IHI ventilator care pneumonia than H2 antagonists (138-141).
bundle to prevent VAP: daily interruption of sedation and The sole consensus guidelines on stress-related mucosal dis-
assessment of readiness to wean, semirecumbent positioning, ease in mechanically ventilated patients state that "prophylaxis
and oral hygiene using chlorhexidine. A recent study in Spain is recommended in patients with coagulopathy or patients re-
demonstrated that despite low compliance ( <~0%) there was a quiring mechanical ventilation for more than 48 hours" (138).
reduction in VAP incidence (15.5% to 11.7%) after the bundle The guidelines also recommend prophylaxis in patients with
was adopted, as well as a reduction in median ICU length of a recent history of GI bleeding or at least two of the follow-
stay from 10 to 6 days and a reduction of duration of mechani- ing risk factors: sepsis, ICU stay > 1 week, occult bleeding
cal ventilation from 8 to 4 days ( 40). for 2:6 days, and use of steroids (>250 mg of hydrocortisone
An ICU checklist serves as a reminder and prompts clinicians daily). Despite this relatively narrow recommendation for use
to evaluate specific medical interventions, prevention measures, of acid-suppressive medications for prophylaxis of stress-related
and processes to enhance medical care and ensure consistency mucosal disease, as much as 73% of PPI use in hospitals is un-
in a complex and stressful ICU environment. Components of necessary (142). Given the potential contribution of H2 an-
the IHI ventilator care bundle and other preventative strategies tagonists and PPis to HAP and VAP, avoidance of overuse and
can be reinforced through the use of a checklist. The use of preferential use of H2 antagonists over PPis may represent cost-
daily ICU checklists has been shown to be beneficial in decreas- effective prevention strategies.
ing the duration of mechanical ventilation. In a randomized
controlled study, checklist-based physician prompting improved
ventilator-free days, 22 (14 to 26) vs. 16 (0 to 21.5) (p = .028),
and lowered ICU and hospital mortality (127). NEW PREVENTION STRATEGIES
TREATING VAT TO PREVENT VAP
ORAL DECONTAMINATION AND CHLORHEXIDINE
Clinical signs of infection trigger microbiologic sampling of
Oropharyngeal colonization is the primary source of pathogens the tracheobronchial tree. BAL with bacteria <::104 cfu/mL
causing HAP and VAP, and thus reducing the levels of coloniza- confirms a diagnosis ofVAP. Meanwhile, a positive EA by either
tion or eliminating potential pathogens is an obvious risk re- quantitative (> 105--6 cfu/mL) or semiquantitative techniques
duction strategy. Oral decontamination, with nonabsorbable (moderate or heavy bacterial growth) drives the diagnosis to-
antibiotics with or without systemic antibiotics, has been stud- ward VAT, unless radiologic findings are present (Table 32.2).
ied and recommended to prevent VAP (128-1~1). In one study, Unfortunately, a chest radiograph in the intubated patient of-
Mori et al. compared the rates of VAP in a nonrandomized ten is of poor quality, may be delayed, and it is difficult for
group compared with historic controls (132). The incidence of clinicians and radiologists to distinguish VAP from congestive
VAP in the oral care group was 3.9 episodes per 1,000 days vs. heart failure or atelectasis ( 143,144) . All clinicians should be
10.4 in the control group. Although there are concerns about aware of the limitations of portable chest X-rays. It is impor-
the study design, oral care has intuitive benefits and limited tant to stress that quantitative cultures obtained by different
cost. However, more randomized controlled studies are needed. methods (EA, BAL, and PSB) seem to be equivalent in VAP
In one of the earliest randomized trials of chlorhexidine diagnosis ( 145).
(CHG), Deriso et al. demonstrated that the use of the oral an- Lower levels of endotracheal bacterial colonization are com-
tiseptic significantly reduced the rates of HAl in patients un- mon in intubated patients. In the absence of clinical signs of
dergoing coronary artery bypass graft surgery (133). Although infection, colonization should not be considered as VAT or be
topical antiseptics, such as CHG, provide an attractive alterna- treated with antibiotics, as they may provide dues to the pres-
tive to antibiotics, the initial reported success in cardiac surgery ence of specific pathogens. The use of periodic surveillance EA
patients has not been consistently demonstrated in other stud- cultures may be helpful in identifying high-risk patients with
ies. A meta-analysis of seven studies fowtd a 30% relative risk re- heavy colonization ( > 1()5-6 bacterial pathogens per milliliter)
duction in VAP with CHG, but this effect was most pronounced and assist in the institution of early infection control measures.
Therapy for VAT has been suggested as an effective strategy AVOIDING INTUBATION WITH NONINVASIVE
to prevent VAP and improve patient outcomes (58,61,146,147). POSITIVE-PRESSURE VENTILATION
Nseir et al. performed a randomized trial of early vs. delayed
Noninvasive positive-pressure ventilation (NPPV) utilizes a
antibiotic therapy for VAT, defined by clinical signs and an
face mask to provide ventilatory support without the need for
endotracheal aspirate with 0!:106 cfu/mL. Patients treated
intubation and can facilitate the earlier removal of the endo-
with early antibiotics developed VAP less often (13% w. 47%,
tracheal tube, consequently reducing complications related
p < .05) and experienced a significant reduction in mortality
to prolonged intubation. NPPV recruits collapsed alveoli
(18% vs. 47%, p < .05) when compared with those with delayed
while treatment of the underlying condition takes place. It is
therapy (57). These data potentially suggest a new paradigm for
an attractive alternative for patients with acute exacerbations
preventing VAP. In addition, treatment of VAT also significantly
of chronic obstructive pulmonary disease (COPD), acute hy-
reduced ventilator-days, ICU length of stay, and crude mortality.
poxemic respiratory failure, cardiogenic pulmonary edema,
Earlier and more liberal antibiotic use raises concerns for
early ARDS, and for some immunosuppressed patients with
the emergence ofMDR pathogens. However, earlier "targeted"
pulmonary infiltrates and respiratory failure (162-165). In
antibiotic therapy, rather than empiric broad-spectrum therapy
a Cochrane review including studies using NPPV mostly for
could reduce antibiotic use, lung damage, and potential com-
COPD exacerbations, Bums et al. reported significant benefits
plications such as empyema or lung abscess ( 67) .
including decreased mortality (RR, 0.55; 95% CI, 0.38 to 0.79),
lower rates ofVAP (RR, 0.29; 95% CI, 0.19 to 0.45), decreased
PROBIOTICS AND SYNBIOTICS length of ICU and shorter hospital stays, and lower duration
of mechanical support (166). The impact of NPPV is greatest
Probiotics, the living organisms of human origin that can sur-
in patients with COPD exacerbations and congestive heart fail-
vive in the lower GI tract and provide health benefits, and syn-
ure. Data also indicate that NPPV may be a good strategy to
biotics, which are probiotics usually combined with soluble
facilitate extubation in some patients with difficulty weaning
fiber, have been associated with interesting data in the preven-
from mechanical ventilation; however, this modality is recom-
tion of HAP and VAP (148). Strains of Lactobacillware the most
mended only in hospitals with staff who are experienced in
commonly studied probiotics in this setting.
this technique ( 167) . When endotracheal intubation and me-
There are multiple ways in which probiotics and synbiotics
chanical ventilation become necessary, unplanned extubation
may prevent HAP. These include attenuation of GI coloniza-
should be avoided, as reintubation significantly increases the
tion with virulent bacteria that can lead to pneumonia, direct
risk ofVAP (168).
antibiotic activity, optimization of local and general immunity,
and minimization of gut mucosal hyperpermeability (149).
Probiotics and synbiotics are generally easy to use, inexpensive, VENTrrATORMANAGEMENT
and are perceived to have a benign adverse-effect profile.
SedR.tion snd Wesning
The studies comparing probiotics and synbiotics in the pre-
vention of HAP have generally been single-<:enter studies and Because excessive use of sedative agents depress cough and
have differed in methodological quality, population studied, other host-protective mechanisms and lengthen the duration
and the way the agents were dosed (150-157). of mechanical ventilation, clinicians should minimize sedative
A recent meta-analysis combined data from several of these exposure and duration of intubation (169). The most compel-
studies of VAP (158). This meta-analysis concluded that the ling intervention to reduce mortality and minimize the dura-
rate ofVAP was significantly lower in patients treated with pro- tion of intubation and sedative exposure was demonstrated
biotics (689 patients; ftxed effect model: odds ratio [OR], 0.61; in the Awakening and Breathing Controlled (ABC) Trial that
95% CI, 0.41 to 0.91; random effects model: OR, 0.55; 95% CI, paired daily awakening trials (commonly called "sedation va-
0.31 to 0.98). Although the lower incidence of VAP persisted cations") with assessment of readiness to extubate through
after exclusion of the one trial that used topical probiotics, this spontaneous breathing trials (SBTs) (170). As compared with
finding has been criticized because of heterogeneity (159). As a standard care with daily SBTs, this paired strategy resulted in
result, the effect of topical vs. enterally administered probiotics a 14% lower 1-year mortality rate, an average reduction in du-
is uncertain. Importantly, two large trials published subsequent ration of intubation by 3 days, and a shorter time to ICU and
to this meta-analysis reported differing results in the incidence hospital discharge without an increased rate of self-extubation
ofVAP (154,157). The one reporting positive results used both requiring reintubation. Other strategies to reduce the dura-
topical application to the oral cavity as well as enteral adminis- tion of mechanical ventilation include improved methods of
tration but suffers from selection bias (157). sedation and the use of protocols to facilitate and accelerate
Owing to episodes of bacteremia associated with probiotics weaning (10,171-174) . Some of these interventions have low-
when used for Clostridium dif.ficik infection, some have been ered VAP rates by 5% to 10% (171,174). These interventions
concerned that probiotics and synbiotics may cause infection clearly depend on adequate ICU staffing and multidisciplinary
when used for VAP; however, no Lactobacillw infections were re- participation (175--178).
ported in any of the studies ofVAP prevention (160). Notably, a
recent study ofprobiotics in pancreatitis revealed a higher rate
Subglottic Secretion Drsinsge
of death (15.7 w. 6.3%, p = .01) and intestinal ischemia in pa-
tients given probiotics (6.3 vs. 0%, p = .004), but the injurious Continuous aspiration of subglottic secretions (CASS) through
mechanism may not be applicable to other patient populations the use of specially designed endotracheal tubes with a wider,
(161). Finally, probiotics are not regulated by the FDA, so the elliptic hole helps facilitate drainage (Figure 32.2), and has sig-
purity and accuracy of the agents in the preparations is less rig- nificantly reduced the incidence of early-onset VAP in several
orously monitored than prescription drugs. studies (5,10). In a meta-analysis, CASS reduced the incidence
of YAP by half (RR, 0.51; 95% CI, 1.7 to 2.3), shortened ICU MULTIDISCIPLINARY TEAM APPROACH
stay by 3 days (95% CI, 2.1 to 3.9), and delayed the onset of
Prevention efforts targeting VAP must be part of an evidence-
YAP by 6 days. CASS also was cost-effective, saving $4,992 per
episode of VAP prevented or $1,872 per patient, but mortal- based, multidisciplinary prevention program that has a core
team with an agenda focused on patient safety and quality
ity was not affected (179). However, when CASS was combined
improvement (190). Optimally, the team should be led by a
with semirecumbent positioning, no clinical benefit was ob-
"champion• and include interested clinicians, respiratory care
served, underscoring the importance of interactive prevention
staff, administrators, risk management staff, and other stake-
strategies (180).
holders as core team members. This group's responsibilities
include setting prevention benchmarks, establishing goals and
Sii'Per-Coa:tetl Entlotruhea.l Tube timelines, providing appropriate education and training, and
performing audits with feedback to the staff, all while continu-
Silver has antibacterial properties. The silver-coated endotra-
cheal tube (EIT) is designed to reduce bacterial colonization ally updating themselves on the relevant clinical and preven-
tion strategies. Prevention programs should be marketed to
and biofihn formation, especially in the EIT lumen. Since there
are concerns about biofilm embolization into the distal airway hospital administrators and others involved in resource alloca-
tion by demonstrating that preventing VAP results in improved
during suctioning or bronchoscopy, the silver-coated tube was
clinical outcomes and significantly reduces costs.
postulated to reduce VAP. A large prospective, randomized,
single-blind controlled study of 2003 patients in 54 medical cen-
ters of North America demonstrated a significant reduction of PREVENTING READMISSION
YAP by BAl. criteria in patients intubated for 2=24 hours with a sil-
The focus of prevention has been on ICU patients while in the
ver-coated E'IT (181). The rates of microbiologically confirmed
ICU, but these patients are also at increased risk for relapse
YAP were 4.8% in the silver-coated EIT group vs. 7.5% in the
or reinfection during rehabilitation. In general, readmissions
control group, with a relative risk reduction in YAP incidence of
are common, with 20% of hospitalized patients readmitted
36%. The silver-coated ETT also delayed the occurrence ofVAP.
within 30 days and 56% within a year, but rates vary consid-
However, there was no statistically significant difference noted in
erably (191). In a study of 11,855,702 Medicare beneficiaries
the duration of intubation, length of stay in the ICU or hospital,
who had been discharged from a hospital from 2003 to 2004,
or mortality. A subsequent study demonstrated that the high cost
147,185 were rehospitalized with a diagnosis of pneumonia or
ofVAP could offset the cost of silver-coated EIT. The estimated
pulmonary infection (192). Currently, no robust data on HAP
number of patients needed to be treated with silver-coated E'ITs
or YAP readmissions are available, but efforts should be di-
to prevent one episode of VAP was -37. The cost-effectiveness
rected at available risk reduction strategies at discharge, such
analysis of silver-coated E'IT showed a saving of $12,800 per epi-
as routine vaccinations and patient education aimed at health
sode ofVAP prevented (19). However, identifying high-risk pa-
promotion, including smoking cessation, exercise, and weight
tients at the time of intubation is difficult.
control. Notwithstanding the type of readmission, inadequate
coordination between the different healthcare providers and
VennlR.tor Circuits and Condensate subsequently poor discharge planning have been identified as
a major component of care lacking at the time of discharge
YAP may also be related to colonization of the ventilator cir-
(193). Instituting targeted care management interventions in
cuit tubing (182). Frequent circuit changes do not prevent
individuals at high risk for relapse, particularly during transi-
YAP (184). Condensate collecting in the ventilator circuit can
tions of care (including transfers and discharges) has reduced
become contaminated from patient secretions or by opening
readmissions in some chronically ill populations and may be
the circuit; therefore, vigilance is needed to prevent inadver-
effective in high-risk patients with HAP or VAP. An example of
tently flushing the condensate into the lower airway (182,184).
such an intervention is the use of "discharge bundles," which
Furthermore, metered dose inhalers (MDI) may be safer for
involve reconciling medications, discharge education, and
the delivery of bronchodilators than nebulizers, which, if con-
postdischarge continuity check by a clinician (193). In order to
taminated, may produce bacterial aerosols (185). High-level
determine the impact of any strategy aimed at reducing read-
disinfection of tubing temperature sensors is recommended to
missions and provide evidence-based recommendations to pre-
prevent cross-contamination between patients (10).
vent HAP and VAP readmissions, more studies targeting these
two populations are urgently needed.
Ellrly Trtuheostomy
Early tracheostomy, historically defined as tracheostomy sooner CONCLUSIONS
than 3 weeks after intubation but more recently considered to
occur within 2 weeks of intubation, has been suggested as a Despite rapid technologic and treatment advances in medicine,
strategy to improve outcomes including weaning from the ven- dramatic reductions in the rates of VAP, and effective use of
tilator, discharge from the ICU, incidence of pneumonia, and complex prevention and management, HAP and YAP remain
mortality. A number of studies have examined the impact of important HAis (5,10). The persistence of resistant gram-
early tracheostomy but found conflicting results (186-188). negative bacilli and MRSA pathogens is troublesome and is
The largest, most recent, rigorously conducted study suggests likely to increase with our aging population. Prevention of HAP
that early tracheostomy improves ventilator weaning and dis- and VAP is directly related to reducing risk, as suggested in
charge from the ICU, but is associated with an increase in Table 32.5. Investing in prevention can pay great dividends in
complications at the stoma site without an improvement in improved quality of life, reduced morbidity and mortality, and
mortality at 1 year (189). lower costs for treatment of HAP and YAP (190). In addition,
adherence to effective prevention strategies can have a huge 29. Guidelineo fur the management of adolto with hoopitakcquired, ventilator....soclated, and
heal~oocialed pneumonia. American thoracic documento. Appnmod bytheATSBoard
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Dick Menzies and Faiz Ahmad Khan
Nosocotnial Tuberculosis
INTRODUCTION TUBERCULOSIS INFECTION
AND DISEASE
The infectious disease tuberculosis (TB) has plagued hu·
mankind for millennia (1). Over the past 130 years, several MICROBIOLOGY
milestone events shaped our understanding of and approach
to TB: Koch's discovery of the etiologic agent in 1892, the cou- Virtually all episodes of human TB are due to infection by
fumatiou of it! airborne tranllmission by Wells and Riley in the M. tubm:uloJis (MTB), a subspecies of the Mjcohact.trium tu!Jer.
mid-20th centu.I'}'; the advent-nearly 60 years ago-of antimi- ctdl>m complex (U). Most of the other subspecies rarely cause
crobial agent! capable of curing TB, and, more recently, the se- human disease; the exception is M. ajrUanum. which accounts
quencing of the organism's entire genome (2~). Largely due for a significant proportion of human TB in part! of Africa
to improvements in general living conditions, public health in- (13). The genus Mycobacterium poase18es certain unique, micro-
terventions, and the availability of effective antimicrobials, TB biologic characteristics. Their lipid-rich cell wall, described by
incidence was declining in many nations through most of the some as "the most complex in all of nature," "resists acid decol·
20th century. In the past 25 years, however, TB has experienced orization of carbo! fuchsin stain," which is why mycobacteria
are tenned "acid-fast bacilli" (14). In addition to being an ob-
a resurgence in many parts of the world, a change attributable to
multiple factors, including the lnV pandemic, increasing preva- ligate aerobe, M. l:uberculosis is slow-growing, and requires 2 to
lence of drug-resistant Mycobactt:rium tubm:uloris. and weakened 6 weeb in culture before colonies are visible (14).
public health infrastructure (the latter related, in some areas,
TRANSMISSION
to structural adjustment programs) (5-'l). Today, TB control re-
mains elusive and challenging. In 2010, there were 8.8 million 'fransmission of M. tuberculmis occun person to person via
incident case& and 1.5 million deaths attributable to TB (8). the airborne route. When an infected person speaks, coughs,
Several characteristics of M. tuberculosis make it an ideal sneezes, or sings, they release "droplet nuclei" into the air.
organism to be tranllmitted in medical facilities. When such Droplet nuclei are small, liquid particles, some ofwhich contain
transmission occurs, the infection is referred to as "nosoco- M. tubemdom organisms ( 15). Infectious droplet! are also gen-
mial" or "healthcare-associated" TB. Under the right circum- erated during certain medical procedures, including sputum
stances, nosocomial TB transmis.sion can lead to nosocomial induction, bronchoscopy, endotracheal intubation, autopsy,
outbreaka, in which large numbers of people are exposed and and drainage of tuberculous abscesses (16). Not all droplet!
infected in facilities providing medical care to patients with TB. transmit M. tuberculosis infection. Most large droplets (>10 1Jlil
Infection conttol measures are critical to prevent nosocomial in diameter) settle to the ground before susceptible hosts can
M. t'Ullerculom tran.mlission. In the United States, inadequate in- inhale them. Those that are inhaled get trapped in the upper
fection control measures contributed to a series of nosocomial airwa)'J where they are expunged into the oropharynx by beat-
TB outbreaks in the late 1980s and early 1990s (9-11). The ing cilia, and subsequently swallowed and sterilized by gastric
widespread implementation of infection conttol measures was acid (15). Droplets <1 1JlD in diameter also are ineffectual at
critical in controlling these outbreaks, and has effectively pre- transmitting infection; the majority evaporate before they can
vented their recurrence. In contrast to the United States and be inhaled by susceptible host!, and those that manage to enter
other high-income nations, nosocomial M tubm:uloJis 1ra.n5- the respiratory tract are typically e:xhaled during subsequent
missi.on and outbreaks continue to pose a significant threat to breaths. Droplet nuclei between 1 and 5 'JII'tl in diameter cany
public health in low- and middle-income countries. There is an the greatest risk of transmitting infection. In this size range,
urgent need to strengthen TB infection couttol measures in droplets can remain suspended in the air for prolonged periods
resource-constrained areas, particularly those burdened with a of time and be transported long distances via air currents and
high prevalence of both lnV and TB (12). ventilation systems. Furthermore, these droplet! are more likely
Our chapter begins by reviewing the basic microbiologic, to reach and settle in the alveolar ainpaces once inhaled (16).
pathogenic, and clinical aspects of TB infection. We then pro- The droplet! need can:y only one viable M. rubm:ulosis organ-
vide the reader with an overview of the epidemiology of nosoco- ism to transmit infection (1'7). Several factors determine the
mial TB transmission. The last portion of the chapter provides probability that an individual who is exposed to a patient with
a detailed discwsion ofinfection control measures and current TB will inhale infectious droplets and develop TB infection
recommendations regarding their implementation. (Table 3lH) (18).
501
the bacilli are near-dormant and confined to the granuloma,

TABLE 33.1 Determinants of Infection LTBI is an asymptomatic state in which individuals cannot
Given Exposure to a Patient transmit M. tuberculosis to others. Of the immunocompetent in-
with Active TB (16,18) dividuals with LTBI, 95% remain asymptomatic and noninfec-
CONCENTRATION OF INFECTIOUS DROPLETS tious throughout their lives and 5% develop "postprimary TB"
IN THE AIR WDA. BE DETERMINED BY: (also known as "reactivation" TB).
A Number of infectious droplet& released by the patient, which is
determined by:
LATENT VS. ACTIVE TB INFECTION
Location ofTB disease (upper airways and lungs)
Actions (e.g., coughing, singing, speaking, and failure to cover It is important to have a clear understanding of the distinc-
mouth and nose during these activities) tion between the two forms of TB-LTBI and active TB (the
Duration of TB treatment (initiation of adequate TB treatment latter is often called "tuberculosis disease," or even simply,
rapidly reduces the number of organisms released by a patient)
"tuberculosis~)-as the two differ in their epidemiology, impli-
B. Characteristia of the environment in which exposure occurs,
which is determined by: cations for public health, clinical manifestations, and treatment.
Levels of ventilation As described above, LTBI is a nontransmittable, asymptom-
Size of room in which exposure occurs atic infection by dormant, essentially nonreplicating M. tuber-
Recirculation of air containing infectious droplets culosis. One-third of the world's population has LTBI. In 5%
of people with LTBI, the bacilli will exit the dormant state and
CHARACTERISTICS OF THE EXPOSED INDIVIDUAL
multiply, causing inflammation and local tissue destruction,
Previous TB infection may lower the risk of subsequent TB
infection and rendering the carrier capable of transmitting infection to
Inadequate infection control measures others. This is known as "postprimary" or "reactivation" TB.
Nonuse of personal protective measures The risk factors for reactivation TB are discussed in the next
Use of inadequate personal protective measures subsection. Both reactivation and primary progressive TB are
forms of "active TB." Bacterial replication, inflammation, and
tissue destruction characterize active TB, which is the conta-
gious form of TB infection. Active TB develops in sites that
PATHOGENESIS
were seeded during the hematogenous phase of primary TB
Once droplet nuclei settle in the distal puhnonary airspaces (or infection, and hence active TB can be pulmonary, extrapul-
"alveoli~), the bacilli within them are phagocytosed by macro- monary, or both, and can present with a myriad of symptoms.
phages. However, the macrophage's antibacterial mechanisms As nearly all M. tubtm:ulosis transmission is airborne, the prob-
are only partially effective at killing M. tuberculosis. Persistent ability that a TB patient will transmit infection to others is, in
intracellular replication leads to macrophage death and fuels part, dependent on the organ systems involved (Table 33.1) .
the local immune response, which carries organisms to hilar The risk of transmission is highest in patients with pulmonary
and mediastinal lymph nodes (17,19). Caseating granulomas (parenchymal or endobronchial) or upper airway TB, with
are the hallmark histologic lesion arising from host immune re- laryngeal disease being the most contagious form. In low-
sponses toM. tuberculosis infection (20). The intraparenchymal burden settings, most episodes of active TB are likely due to
granuloma at the initial nidus of infection is called the "Ghon reactivation of LTBI. In contrast, primary progressive disease
focus," and the combination of this lesion and locally enlarged accounts for a greater proportion of episodes of active TB in
hilar or mediastinal lymph nodes is referred to as the "Ranke high-burden settings (15).
complex" (20). The host eventually develops cell-mediated im-
munity and delayed-type hypersensitivity, resulting in a positive
RISK FACTORS FOR REACTIVATION
tuberculin skin test (TST) within 2 to 8 weeks of primary infec-
tion (19,21). It is during this minimally symptomatic period of While the average risk of developing active TB among individu-
primary TB infection that a critical event occurs: bacilli enter als with LTBI is -5% over a lifetime, many factors increase the
the bloodstream and seed other parts of the body (including risk of progression (Table 33.2). The important risk factors for
the lung apices) through hematogenous spread (22). reactivation include HIV infection, other causes of severe im-
What happens next depends on the effectiveness of the munosuppression, and recently acquired LTBI (25).
host's immune response to M. tuberculosis. ff the immune system Treatment of LTBI significantly lowers the risk of progres-
is unable to control the primary infection, bacterial replication sion from LTBI to active TB, but also carries risks of adverse
continues, with increasing inflammation and tissue destruction effects; thus, it is important to offer treatment to individuals
(either at the site of the initial pulmonary infection or at the whose risk of progressing from LTBI to active TB is greater
metastatic loci) (23). This condition, termed "primary progres- than the risks associated with LTBI treatment (26).
sive TB, ~ manifests within 2 years of the initial exposure. Only
5% of immunocompetent individuals develop primary pro-
DIAGNOSIS AND TREATMENT
gressive TB. Among the other 95%, the immune system halts
bacterial replication, effectively controlling M. tuberculosis infec- Different diagnostic approaches apply to LTBI and to active TB.
tion. This process leaves multiple granulomatous lesions in the Diagnosis of the former is based on eliciting immune reactions
organs and lymph nodes where the bacilli spread. While the to M. tubtm:ulosis antigens, and necessitates accounting for the
infection is controlled, it is not entirely eliminated-bacilli sur- probabilities of false-positive and negative test results, as well
vive in a near-dormant state for several years within the granu- as the probability of progression to active disease. In contrast,
lomatous lesions (24). Individuals who harbor these dormant active disease is confirmed through the visualization of acid-fast
bacilli are said to have "latent TB infection" (LTBI). Because bacilli (AFB} on smear microscopy, the growth of M. tuberculosis
Chapttr 33 • Nosocomial Th.berculosis 503
by injecting 0.1 mL of 5-tuberculin units of purified protein de-

TABLE 33.2 Risk Factors for the
rivative (PPD) in the dermis of the volar aspect of the forearm
Development of Active TB (29). The test is read 48 to 72 hours following implantation, by
Among Persons with Latent measuring the diameter of induration transverse to the long
TB Infection (25) axis of the forearm. The "ballpointn method is recommended
Estimated Risk of TB
to reduce interobserver variability. Interpretation outside the
Relative to Persons recommended postimplantation period may underestimate the
with No Known Risk extent of induration. The dose, lot number, manufacturer date,
Risk Factor Factor and expiry date of the PPD vial should be recorded in addi-
tion to the dates of implantation and interpretation, the size
InGHRISK
Acquired immunodeficiency syndrome 110-170
of the induration, any adverse reactions, and the name of the
(AIDS) interpreter. The only absolute contraindication to TST is a his-
HIV infection 50-110 tory of serious adverse reaction to a previous TST. The test does
Thamplantation (related to 20-74 not provide clinically useful information in individuals with a
immunosuppressants) documented history of active TB, previously documented posi-
Silicosis !10 tive TST reaction (with the size recorded), and those with a
Chronic renal failure requiring 10-25 documented history of adequate TB treatment.
hemodialysis
TST interpretation often is challenging, and a systematic ap-
Carcinoma of head and neck 16
Recent TB infection (""2 yean) 15 proach can help clinicians avoid misdiagnosis. Three dimen-
Abnormal chest X-ray-fibronodular 6--19 sions must be considered when interpreting TST results: size,
llliease positive predictive value (PPV), and risk of progression to ac-
tive TB. The minimum size of induration required to classifY a
INTERMEDIATE RISK
TST as positive depends on the risk of progression to active TB.
Theatment with glucocorticoid! 4.9
The U.S. Centers for Disease Control and Prevention (CDC)
Tumor necrosis factor (TNF)-alpha 1.5-4 recommends cutoffs of 5, 10, and 15 mm for patients at high,
inhibitors
intermediate, and low risk, respectively (Table 33.3) (28,29).
Diabetes mellitus (all types) 2.0-!1.6
Underweight (<90% ideal body 2-!1 In areas where prevalence of nontuberculous mycobacteria is
weight; for most persons this is a low, it is reasonable to use a cutoff of 10 mm even for indi-
body mass index ""20 kg/m2) viduals at low risk of reactivation to increase sensitivity without
Young age when infected (0-4 yean) 2.2-5.0 compromising specificity. When the induration diameter is suf-
Cigarette smoker (one pack/day) 2-!1 ficiently large to be declared positive, one must consider the
Abnormal chest X-ray-granuloma 2 next dimension of TST interpretation, the PPV. The PPV is the
LOW RISK probability that a positive TST result is truly due to the pres-
Infected person, no known risk
1 ence of LTBI. This can be the most challenging step in TST in-
factor, normal chest X-ray ("low terpretation as several factors affect the PPY, including the TST
risk reactor") reaction size, country of origin (and the state, if U.S.-bom),
current age, age at immigration, BCG vaccination status, and
Adapted from Canadian Thbemdosis Standanls, 6th ed. Ottawa,
history of contact with TB (31,32). Nontuberculous mycobac-
Canada: Public Health Agency of Canada; 2007. Reproduced with
permission from the Minister of Health, 2012.
terial (NTM) infection and childhood BCG vaccination are
common causes of false-positive TST (31,32). The latter can
be ignored as a cause of false-positive TST in the following
in culture, the identification of M. tuberculosis DNA through circumstances: (a} if the vaccination was received in the first
nucleic acid amplification, or seeing typical histopathological year of life and the individual being tested is at least 10 years
changes consistent with TB (caseating granulomas) in tissue old, (b) when the probability of true infection is high (e.g., in
specimens. When the presence of active TB cannot be con- contacts of active TB cases, or individuals from high-incidence
firmed through these methods, a presumptive diagnosis can be settings}, or (c) when the risk of progression to TB is high. The
made on the basis of radiologic and clinical features (such as last dimension of TST interpretation-the probability of pro-
response to antituberculosis treatment). gression to active disease if the patient truly has LTBI-is deter-
mined by the presence of risk fuctors for developing active TB
(Th.ble 33.2). An online tool is available to assist practitioners
Diagnosis antl Treatment of LTBI
with TST interpretation (www.tstin3d.com) .
Two tests can be used to diagnose LTBI: the TST and the in- TST "conversion" is said to have occurred when an individ-
terferon gamma-release assays (IGRAs). The TST is an inex- ual who previously tested negative becomes TST-positive. Cau-
pensive, reliable, and widely available test that has been used to tion should be applied when interpreting repeated TSTs, as
diagnose LTBI since the early 20th century. Some practitioners induration measurement is subject to substantial inter- and in-
prefer using IGRAs to diagnose LTBI because they are easier to trareader variability (21). Different approaches can be taken to
interpret, have a lower false-positive rate, and require only one address this issue (21) . The CDC recommends that increases in
patient visit (TST requires at least two visits). Different guide- induration diameter of 10 mm or more, within a 2-year period,
lines identify different tests as the preferred method for diag- be considered as conversion.
nosing LTBI (27). For individuals who will have multiple TSTs (such as health-
The Mantoux test is the most reliable and widely used tech- care workers), it is recommended that the first TST be a "two-
nique for performing the TST (2S-30). The test is performed step TST." In the first step, the test is performed as described
TABLE 33.3 Criteria for Tuberculin Skin Test Positivity (U.S. Centers for Disease Control
and Prevention) (28,29)
Diameter of Reaction Groups in Whom this Diameter of Reaction is Recommended to be Interpreted as Positive"'"
;;..Smm People living with HIV
Individuals in recent contact with cases of active TB
Individuals with fibrotic changes on chest radiography that are consistent with TB
Immunosuppressed (e.g., organ transplant recipients; persons taking ... 15 mg/ day prednisone for at least
1 month [or equivalent doses of other corticosteroids]; persons on TNF-alpha inhibiwrs)
;;..10mm Individuals at increased risk of reactivation of TB due w medical conditions other than those listed above
(e.g., silicosis,' diabetes mellitus, head and neck carcinoma, end~tage renal disease', hematologic
conditions associated with impaired immunity [leukemia and lymphomas])
Individuals employed11 or residing in group settings (e.g., prisons or jails, long-term care facilities
[including nursing homes, mental health residential facilities, and facilities for individuals with
acquired immunodeficiency syndrome], hospitals or other healthcare facilities, homeless shelters)
Individuals employed in mycobacteriology laborawries
Immigrants who have recently arrived from countries with high TB prevalence
Users of intravenous drugs
;;..}5mm Individuals who are otherwise healthy and carry no risk facwrs for reactivation
"Modified from Centers for Disease Control and Prevention. Screening for tuberculosis and tuberculosis infection in high-risk populations.
Recommendations of the Advisory Council for the elimination of tuberculosis. MMWR Recomm &p. 1995;44(RR-11) :19-34 and Centers for
Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR Reromm Rep.
2000;49(RR~) :1-51.
Drhe lists in this table are truncated versions oflists in the recommendations by the Centers for Disease Control and Prevention (CDC).
A version of this table with the complete listing of groups that fall inw each of the three categories can be found in the references cited above.
'Owing w elevated risk of reactivation, it may be reasonable w use cutoffi of 5 mm in these groups (not part of current CDC
recommendations).
tlA cutoff of 15 mm should be applied w low-risk individuals being tested at the start of employment.
above. The second step is performed only if the first reaction tests perform better than serial TST (35). Furthermore, several
was negative. The second step involves repeating the TST 1 to studies have documented high rates of spontaneous reversion
3 weeks after the first TST was performed. If the second TST is when using I GRAs for serial testing (20% to 30% of those with
positive, this is termed a "booster response" (or "booster phe- initially positive tests have reverted) (35,36). These studies also
nomenon"). Infection by NfM, BCG vaccination, and the pres- reported very high rates of IGRA conversion-much higher
ence of true LTBI are all causes of the booster reaction (21) . than with tuberculin testing (35) . This makes it difficult to in-
The PPV of a booster response can be estimated with the help terpret and manage an individual with an apparent IGRA con-
of the same factors that help us interpret positive TSTs. The version. In view of this, and until this phenomenon is better
purpose of the two-step TST is to identify those individuals in understood, it is difficult to recommend serial testing of health-
whom a positive TST on repeat tests may be due to boosting care workers with !GRAs as part of an institutional TB infection
rather than conversion from a negative to positive TST. It is im- control program.
portant to note that the risk of progression to active TB among Under certain circumstances, performing both a TST and
individuals with a booster response is roughly half the risk an IGRA can be useful. In situations where it might be pref-
among individuals with the same size induration on the first erable to maximize the sensitivity for LTBI diagnosis (e.g., in
TST (21). Two-step testing should only be performed once, persons with a high risk of progressing to or dying from active
and only when there has been no contact with persons with ac- TB), if the initial test for LTBI is negative, one can increase the
tive TB in the preceding 1 to 5 weeks ( 21) . Increases in TST size sensitivity by performing the alternative test and interpreting a
should not be interpreted as booster phenomena if there has positive result as sufficient evidence of LTBI. Another circum-
been recent contact with a person with active TB. stance where one can consider using both TST and IGRA is
The !GRAs are an alternative to TST for the diagnosis of when there is a strong suspicion of a false-positive TST. In this
LTBI. These assays measure the release of interferon gamma situation, an IGRA can be done to either confirm or refute the
in blood samples exposed to M. tuberculosis antigens. While TST result. It is important to note, however, that there is no
they are as sensitive as the TST, their specificity is greater for evidence to guide the correct interpretation of discordant TST
M. tuberculosis, as IGRA results are not affected by BCG vac- and IGRA tests.
cination status or exposure to NTM (33). Persons with a his- Multiple regimens can be used to treat LTBI, the most com-
tory of BCG vaccination and those unlikely to return. for the mon being isoniazid monotherapy for 9 months. If there is any
TST-interpretation visit are groups in whom !GRAs are the pre- suspicion of active TB (based on symptoms, exposure history,
ferred test for the diagnosis ofLTBI (34). clinical findings, or radiographic abnormalities), treatment for
TST is the preferred test for groups in whom serial testing LTBI should not be initiated until active disease has been ruled
for LTBI is likely (such as healthcare workers). A recent system- out. This is because the administration of only one anti-TB
atic review and meta-analysis on the use of I GRAs in serial test- medication to someone with active disease rapidly leads to the
ing of healthcare workers found no data to suggest that these development of drug-resistant organisms.
Dillgnosis snd Treatment of Acti'pe TB abuse, and underfunding of TB control programs) (10,39),
(b) inadequate TB infection control measures in many health-
In general, TST and IGRA do not provide useful information care facilities (9), and (c) inadequate treatment of drug-
when investigating someone for active TB (the exception is in resistant TB patients due to delays in susceptibility testing (9).
young children, where these tests are still used to diagnose ac- Infection control measures played a central role in terminating
tive disease). VISualization of AFB on microscopic examination these nosocomial outbreaks, and remain critical for preventing
of specimens, growth of M. tuberculosis in culture, and identi- their recurrence (9,40-42).
fication of M. tuberculosis DNA are the preferred methods to Today, nosocomial M. tuberculosis transmission is much
diagnose active TB. The ease of obtaining specimens for mi- less common in the United States, but remains an important
croscopy and culture, and the sensitivity of tests for the de- concern in low- and middle-income countries, where it is con-
tection of active TB depend, in part, on the site of infection. tributing to the propagation of drug-resistant M. tuberculosis
When pulmonary TB is suspected, microscopy and culture of (12,43--48). One particularly alarming investigation impli-
three sputa, collected through cough induction with nebulized cated nosocomial transmission in the spread of extensive
hypertonic saline, provides a sensitive and noninvasive initial drug-resistant TB (XDR-TB) in a South African hospital (49).
investigation. In contrast, the sensitivity of microscopy and Several findings suggested that primary nosocomial trans-
culture is low for pleural, peritoneal, pericardia(, and spinal mission of resistant strains, rather than acquisition of drug
fluid. Molecular tests-such as nucleic acid amplification and resistance during TB treatment, was responsible for XDR-TB
adenosine deaminase levels-also have a low sensitivity for di- infection: 55% of patients had never been treated for TB in
agnosis of TB in these locations; however, their high specificity the past, only 15% had a history ofTB treatment failure or de-
can help in ruling in disease. fault, and 67% had previously been admitted to hospital (49).
A new generation of nucleic acid test, the Xpert MTB/RIF A follow-up study used molecular fingerprinting to investigate
assay, is highly sensitive for the diagnosis of pulmonary TB, and patients in whom MDR- and XDR-TB developed following the
provides results faster than smear microscopy and culture. In initiation of treatment for TB (43). Again, the findings pointed
an international, multicenter study, the assay identified 98% of toward nosocomial transmission as the culprit: DNA finger-
sputum smear and culture-positive patients, and 70% of spu- printing revealed that all cases were caused by exogenous re-
tum smear-negative but culture-positive patients (37). The test infection by MDR and XDR-TB and all patients had previously
has an additional advantage in that it provides rapid identifica- been hospitalized (43). These studies underscore the urgent
tion of rifampin-resistant M. tuberculosis, a process that would need to scale up resources for TB infection control in low- and
otherwise take at least 4 weeks. The disadvantages include its middle-income countries, particularly in settings with a high
high cost, and that it does not provide information regarding burden ofboth HIVand TB (44).
the infectivity of the patient. This test is likely to start playing a The most studied form of nosocomial transmission is from
greater role in the diagnosis of active TB ( 38). patient to healthcare worker, and several studies suggest the risk
The treatment of active disease lasts at least 6 months. In or- is greatest for healthcare workers in low- and middle-income
der to prevent the organism from acquiring resistance to anti- countries. In a recent systematic review and meta-analysis, the
TB medications, active TB treatment requires the use of at least median annual incidence of TB infection attributable to work
three drugs to which the isolate is sensitive. Effective treatment in healthcare was 5.8% in low- and middle-income countries
rapidly reduces the number of bacilli in the smear, and in so and 1.1% in high-income countries (50). The median preva-
doing lowers both the magnitude and duration of infectivity. lence of LTBI among healthcare workers in low- and middle-
While the confirmation of active TB is preferable, in cer- income countries was 63%, compared to 24% in high-income
tain situations empiric treatment for active disease may be countries (50) . Another review by the same group found an
the best option. Factors that affect the decision to initiate and annual risk of TST conversion for healthcare workers in low-
continue empiric treatment include (a) the pretest probabil- and middle-income settings between 3.9% and 14.3%, after ac-
ity of active TB (determined by exposure history, risk factors counting for the local incidence of TB infection in the general
for reactivation of LTBI, and clinical and radiologic manifesta- population (51). Work in healthcare also increased the risk of
tions), (b) the ability to obtain specimens for diagnostic test- developing active TB, an association seen regardless of country-
ing, (c) the sensitivity of microbiologic testing for active TB income category (51). Other studies have demonstrated that in
(determined by the type of specimen), (d) the risks associated settings with a high prevalence of drug-resistant TB, healthcare
with delayed treatment (both to the patient and to others), and workers are at an increased risk of acquiring drug-resistant dis-
(e) the risks of serious adverse reactions to TB treatment. ease compared to nonhealthcare workers (52) .
It is difficult to estimate the TB risk attributable to transmis-
sion from patient to patient or healthcare worker to patient.
EPIDEMIOLOGIC OVERVIEW The former has been studied mostly in the context of noso-
OF NOSOCOMIAL TRANSMISSION comial outbreaks. However, it is likely that the frequency of
patient-to-patient transmission approximates that of patient-to-
In facilities taking care of patients with active TB, work- healthcare worker transmission. While the least common form
ers, patients, and visitors are at risk of acquiring nosocomial of nosocomial transmission is from healthcare worker to pa-
M. tuberculosis infection. In the United States, nosocomial out- tient, there exist published case reports of healthcare workers
breaks of TB and multidrug-resistant (MDR)-TB increased in propagating nosocomial outbreaks and of healthcare workers
frequency in the late 1980s and early 1990s. Multiple factors with active TB infecting patients and coworkers (53,54). Be-
contributed to this increase, including (a) the resurgence of cause they are frequently in contact with patients at increased
TB in the United States (attributable to the emergence ofHIV, risk of progressing to active TB, it is important that healthcare
increases in the prevalence of homelessness and substance workers are assessed and, if appropriate, treated for LTBI (55).
506 Section m • Endemic and Epidemic Hospital lnfectiuns
RISK FACTORS FOR NOSOCOMIAL TRANSMISSION Rapid isolation and treatment of TB patient!! is critical to
prevent nosocomial transmission. Because delayed identifi-
Both institutional and individual characteristics affect the likeli-
cation of patient!! with active TB increases the risk of noso-
hood that healthcare workers and patient!! will be exposed to comial transmission (60), it is imperative that clinicians and
M. tuberculosis (Table 33.4). Institutional characteristics include
infection control personnel recognize the multiple clinical
the annual number of TB admissions and the efficacy of TB
manifestations of TB, and the patient groups at risk for TB
infection control measures (50). A systematic review of occu-
in their community. TB patients with the following charac-
pational TB risk amongst healthcare workers found that the
teristics may be at increased risk of delayed diagnosis and
annual risk of TB infection was highest for workers in facilities
treatment initiation: older age, HIV infection, absence of
with substantial numbers of TB admissions (56 to 269 annu-
cavitary disease on chest radiographs, and absence of "clas-
ally) and inadequate TB infection control (50). Under these sic" TB symptoms (i.e., cough, fe-ver, night sweats, or weight
circumstances, the reported annual risk of infection was as high
loss) (61-66).
as 7.2% (50). Inadequate infection control measures increase Several occupational characteristics influence a healthcare
the risk of occupational M. tuberculosis infection even in settings
worker's risk of nosocomial M. tuberculosis infection. In the
with a low burden ofTB (56).It is important to note that infec-
croswectional study of hospital ventilation and TST conversion
tion control measures can substantially lower the risk of noso-
amongst healthcare workers, employment at a hospital admit-
comial M. tuberculosis transmission, even in facilities with a high
ting at least six patient!! with active TB annually and occupations
volume of TB patient!! (56-58). In a Brazilian study, the risk
that required direct patient contact (i.e., nursing, respiratory
of TST conversion was twice as high among healthcare work-
therapy, physiotherapy, and housekeeping) were associated with
ers at hospitals without infection control policies compared to
increased risk ofTST conversion (60). Studies in low-, middle-,
healthcare workers at hospitals with policies in place (59).
and high-income countries also have demonstrated increased
The level of ventilation in an institution also modifies the risk of LTBI among nurses, physicians (in particular internal
risk of nosocomial transmission. Ventilation can be measured
medicine, anesthesia, and respiratory medicine specialties),
in air changes per hour, which is the proportion of the total and healthcare worker trainees (i.e., medical student!!, resident
volume of air in a room that is replaced by air external to the
physicians, and nursing students) (50). Longer duration of
room in 1 hour. As discussed in further detail below, healthcare employment (in other words, greater cumulative risk), employ-
workers-including laboratory and autopsy personnel-are at
ment in department!! or wards with a greater number of TB
increased risk of acquiring nosocomial TB in hospitals with
patients, and participation in sputum collection and autopsies
inadequate levels of ventilation.
increase the risk of LTBI in healthcare workers. The risk of ac-
tive TB is highest amongst workers on TB wards (incidence rate
TABLE 33.4 Factors Associated with ratio [IRR] compared to the general population ranges from
Increased Risk of Nosocomial 14.6 to 99.0), general medicine wards (IRR, 3.9 to 36.6), and
M. tldlerc.UOSU Transmission emergency rooms (IRR, 26.6 to 31.9) (51). The lowest risk is
seen among workers in surgical, obstetric, and administrative
INSTITUTION LEVEL department!!.
Number of patients admitted with active TB annually Information on patient characteristics that increase the
Inadequate or absent TB infection control policies. .
risk of acquiring nosocomial M. tuberculosis is mostly derived
Delayed recognition, uolation, or treatment of pauents With TB
Insufficient ventilation in general and nonuolation patient roozm from report!! of the nosocomial outbreaks that occurred in the
Insufficient ventilation in microbiology and pathology laboratories United States in the early 1990s, and thus may not be generaliz-
able to other settings. In these outbreaks, the risk factors for
INDIVIDUAL LEVEL
nosocomial M. tuberculosis infection among patients included
Healthcare workers
Years of employment as a healthcare worker exposure to a patient with TB, prolonged admission to a room
Type of work (e.g., respiratory therapy, nursing) less than three rooms away from a TB patient, HIV infection,
Location of employment in healthcare facility and lower CD4 cell count (67,68).
TB or general medicine ward, emergency department, intensive The likelihood of exposure to M. tuberculosis-containing
care unit, general laboratory, combined inpatient and outpa- droplet particles is the fundamental determinant of the risk
tient TB facility of nosocomial TB transmission. Thus, the characteristics of
Direct patient interaction
institutions, healthcare workers, and patients that increase the
Work in microbiology or pathology laboratories, or in autopsy
suites risk of nosocomial M. tuberculosis infection do so by affecting
Involved in sputum collection or other cough-inducing procedures the likelihood of exposure to cases of active TB and to the in-
fectious droplets they generate. Conversely, infection control
PATIENTS•
measures lower the risk of nosocomial TB by decreasing the
Exposure to TB patient
Admission to a room less than three rooms away from that of
likelihood of exposure. The remainder of this chapter focuses
a TB patient on infection control measures that can be applied to prevent
HIV infection nosocomial M. tuberculosis transmission.
Lower CD4 cell count
·Individual-level mk factors that place patients at risk of acquiring PREVENTION OF NOSOCOMIAL M. TUBERCUWSIS
nosocomial M. tuberculosis are taken from two single-<:enter studies TRANSMISSION IN HEALTIICARE FACILITIES
reporting on nosocomial outbreaks of M. t'ullemllosis that took
Programs to prevent nosocomial M. tuberculosis transmission
place in the United States between 1989 and 1990, and may not be
in healthcare facilities have two major aims-to prevent trans-
generalizable to other settings (67,68).
mission to all persons within the facilities and to protect the
healthcare workers. These programs involve multiple differ- "low risk" and "moderate risk," although "low risk" and "not
ent interventions, which can be categorized into three major low risk" might be better terms. This classification is based on
groups: administrative, environmental, and personal. Admin- the number of beds and the average number of TB patients
istrative and environmental measures act to reduce the risk of admitted annually in the last 3 years, as summarized in the
transmission to all persons in the hospital including patients, table below.
workers, and visitors. Administrative measures are those poli- Healthcare workers' activities also are classified into high,
cies and procedures that seek to limit exposure to undiagnosed intermediate, or low risk as below (Table 33.5).
and potentially contagious patients through rapid identifica- Some occupations, such as housekeeping, despite having
tion, separation, diagnosis, and institution of effective ther- relative little direct patient contact have been described as
apy. Administrative measures also include policies to place high-risk occupations (50,51,73). Whether this is related to
such patients in airborne respiratory isolation. Environmental their frequent entry into patients' rooms or the cleaning activi-
measures include ventilation, ultraviolet germicidal irradia- ties themselves is unclear. This finding illustrates that all work-
tion (UVGI), and portable air-cleaning devices. A third set of ers on inpatient and outpatient units should be considered at
measures seeks to protect the workers--either by reducing the risk if the population they serve sometimes includes patients
risk of transmission to them or reducing the risk of disease if with active TB that is unsuspected and undiagnosed.
infection has occurred. Measures to reduce the risk of work-
ers becoming infected include education of workers and use
Tr11ining He11lthuJre Workers
of personal respirators (or masks), while BCG vaccination and
diagnosis and treatment of latent TB infection act to reduce An important component of administrative controls is the train-
the risk of development of disease, if infected. ing of healthcare workers about TB diagnosis and treatment.
The measures that have been recommended by different au- The objective is to miss fewer patients and to shorten delays
thoritative agencies, including the World Health Organization in diagnosis. A second objective is to improve the understand-
(69), the CDC (70), the American Society of Heating Refrig- ing about M. tuberculosis transmission and the importance of
eration and Air-conditioning Engineers (ASHRAE) (71), and personal protective measures. The hope is that better-informed
the Canadian Thoracic Society (72), are summarized below, healthcare workers will be more compliant with policies regard-
along with selected supportive evidence. Interested readers are ing respiratory airborne isolation and use of personal protec-
referred to the documents produced by these agencies for fur- tive measures, including respirators and LTBI screening and
ther reading. treatment.
ADMINISTRATIVE MEASURES
TB Prnention Progr11m TABLE 33.5 RiBk Classification for
The first and most fundamental administrative measure that Hospitals and Workers
every healthcare facility should have in place is a written TB
Hospitals
prevention program that contains all policies and procedures
related to the prevention of nosocomial M. tuben;ulosis trans- Low .Ria Not Low .Ria
mission in that facility. This program should include the infor- <200 beds and <3 TB <200 beds and 2:3 TB
mation necessary for risk classification of the facility as well as patients/year patients/year
identification of workers considered at high, intermediate, or ~200berhand <6TB ~200 beds and ~6 TB
low risk of exposure. This should clearly identify who is respon- patients/year patients/year
sible for implementing policies and procedures, and contain
policies regarding triage, identification, and placement in air- Healtbcare Workers
borne isolation of patients suspected of contagious active TB Low .Ria
disease. Little or no direct Direct patient Aerosol-producing
The TB prevention program should be reviewed regularly patient contact contact activities
to ascertain the number of patients admitted with TB and the • Administration • Inpatient unit! • Bronchoscopy
number of potential exposure episodes per year. Exposure epi- • Archives • Intensive care • Sputum
sodes are defined as instances when a patient with active conta- • Other support units induction
gious TB is admitted or is seen in the hospital (i.e., emergency staff • Pediatric units • Aerorol
room, outpatient department, or admitted as an inpatient) • Emergency administration
rooiiU • Autopsies
while the active TB is undiagnosed and untreated.
• Outpatient • Morbid
units pathology
Risk Cltusi.{iclltion of He11lthcllre F~~eilities • Microbiology/ TB
11ntl Workers~ Acti:11ities laboratory
Risk classification is imprecise but accounts for the number Adapted from jensen PA, Lambert LA, Iademarco MF, et al. Guide-
of patients with active TB diagnosed annually in the hospital lines for preventing the transmission of Mycobaamum tuberculosis in
health~are settings, 2005. MMWR Recomm Rep. 2005;54 (RR-17):
as well as the number of workers per patient. Obviously, in
a large hospital with many workers, the risk of exposure to 1-141 and Canadian Thbemdosis Standards. 6th ed. Toronto,
Canada: Canadian Lung Association, Public Health Agency of
an individual patient is less. For pragmatic reasons and sim-
Canada, Tuberculosis Prevention and Control; 2007.
plicity, current risk classification divides health facilities into
guests or visitors at home, and will not visit other people's

homes. If the patient has to leave their home and enter
In almost all outbreak reports and population-based studies, other buildings, they will wear a mask.
delayed and missed diagnoses of patients with active contagious 4. There are no susceptible contacts in the home. This means
TB has been the most common and important risk factor for that all contacts have been investigated and are either al-
nosocomial transmission (51,73). In several studies where mul- ready on LTBI therapy or are judged at low risk of develop-
tiple interventions were used, but sequentially, these simple ad- ment of disease. Persons who are healthy but do not have
ministrative measures had the greatest impact in reducing the evidence of LTBI must be aware of the potential risk of
indicators of transmission (74-76). Hence, early identification acquiring infection before patients are discharged home.
of TB suspects and rapid triage of those suspects with place- 5. Patients must not live in a congregate setting.
ment in airborne isolation rooms are the key components of
administrative controls. Early identification depends upon the To discontinue respiratory airborne isolation for patients
knowledge of the epidemiologic profile of TB patients in the who remain hospitalized, the following conditions must be met:
community served by the healthcare facility. Tiris varies con- 1. If the patient is initially AFB smear-negative but culture-
siderably in different parts of North America so that facilities positive, the patient must have drug-susceptible isolates, or
may serve aboriginal populations, inner-city poor and home- drug resistance must be judged very unlikely on the basis
less, or immigrant or foreign-hom populations. In addition, it of clinical and epidemiologic risk factors. At least 2 weeks
is important for workers to know the typical and atypical clini- of multidrug M. tuberculosis therapy must be completed
cal features of TB, especially if the population served by the with evidence of clinical improvement.
healthcare facility has a high prevalence of immunosuppressive 2. If the patient is initially AFB smear-positive, all of the above
conditions, such as HIV infection or transplantation, as clinical conditions must be met, plus at least 2 weeks ofmultidrug-
features of TB often are atypical in such patients. resistant M. tuberculosis therapy are completed and there is
evidence of clinical improvement The patient must have
ER.rly Institution ofEffoaive Tre11tment two consecutive sputum smears negative for AFB on direct
smear microscopy.
A number of studies have shown that contagiousness is reduced
These recommendations are conservative and are not based
rapidly by institution of effective treatment (77). In the late
on extensive evidence. Indeed, much of the available evidence
1980s, there were a number of nosocomial outbreaks related to
suggests that patients are rapidly rendered noninfectious (re-
MDR-TB. In these outbreaks, patients had been started on ther-
viewed in (77, 78)), although a recent study questioned this (79).
apy with first-line drugs that were completely ineffective and
Much of this evidence is based on observational studies in set-
therefore they remained contagious and important sources for
tings where there was a high burden of TB and the uninfected
weeks until the drug-resistant isolates were recognized (73).
contacts exposed to patients on treatment had already been
Hence, it is important to ensure that patients are on therapy
exposed for months before the treatment began. The situation
promptly ifTB is strongly suspected as soon as appropriate spec-
is very different in modem healthcare facilities in high-income
imens have been collected for microbiologic confirmation. Pa-
countries, where the m.Yority of patients and workers do not
tients with risk factors for drug resistance should be considered
have LTBI and the great m.Yority of hospitalized patients are
for additional second-line therapy or rapid drug-susceptibility
seriously immunocompromised. In the absence of incontrovert-
tests should be performed. In addition, it is important to moni-
ible evidence that patients on therapy are noncontagious, it is
tor patients closely for clinical response to therapy until the re-
prudent to adopt the conservative approach outlined above be-
sults for drug-susceptibility tests are available.
fore discontinuing isolation precautions in hospitalized patients.
Disr:ontinHt:Jtion ofRespi.r11tory Airborne Isollltion

En'Pironment:t:Jl Controls
One of the most common questions in healthcare facilities is
when can respiratory airborne isolation be discontinued. There
Ventilation The primary objective ofventilation is to exchange
contaminated air with clean air to reduce the concentration of
are two considerations. Can the patient be discharged to share
airborne M. tuberculosis organisms and thereby reduce risk of
a room with one or more patients in the hospital? Or can the
exposure. Increasing air changes per hour (ACH) from 1 to
patient be discharged home? The criteria for discharge for
6 will result in four to five times more rapid dearing of infec-
these two situations are different.
tious microorganisms from the air within the room (71,80).
Discharge of patients to their homes has many advantages
However, further increases >6 ACH will have less effect and
and should be considered even when patients are still AFB
increases> 12 ACH will be of very little added benefit (80,81).
smear-positive. For discharge home, the patient should meet
Recommendations for the levels of ventilation or ACH
the following criteria:
in different areas of healthcare facilities vary widely between
1. Evidence of clinical improvement on therapy, and drug different authoritative agencies. Unfortunately, almost none
susceptibility is confirmed, or drug resistance is deemed of these recommendations are based on any evidence. Not
unlikely, based on epidemiologic risk factors and clinical surprisingly, there are no randomized trials. There is only a
history. single observational study of 17 Canadian hospitals that corre-
2. There are no other major medical conditions or complica- lated detailed measures of air change rates with documented
tions of the disease that necessitate hospitalization. TST conversion (82). In this study, ventilation levels in air-
3. It is judged that the patient will be compliant with home borne isolation rooms were not associated with indicators of
isolation precautions. This means that the patient will not M. tuberculosis transmission to healthcare workers. However,
return to work or school or social activities, will not receive ventilation levels of general patient areas, where undiagnosed
TB patients are most likely found, were significantly associated However, very few airborne isolation rooms will be needed
with M. tuberculosis transmission to healthcare workers working in a low-risk facility (maybe as few as one), particularly if the
there. Ventilation levels in their work areas also were associated facility adopts a "transfer out" policy. This policy implies that
with TST conversion in microbiology and pathology techni- the facility elects to transfer any patient with strongly suspected
cians in the same study (60). or confirmed active TB to another designated facility that has
Areas where patients with confirmed or strongly suspected more adequate facilities for airborne isolation.
TB are housed, and areas where there may be generation of When can a room be used after a patient with active TB has
aerosols from TB suspects should have higher air exchange been present? A common question is when can a sputum in-
rates and directional airflow (70-72). Directional airflow is duction or bronchoscopy room be used, or an airborne isola-
achieved by creating "negative pressure" within the occupied tion room occupied by a new patient, after a TB patient has
space-meaning the air pressure is less than the pressure in been in that space. The time needed to remove airborne organ-
the hallway outside. This ensures that air always flows from the isms depends upon the ACH rate, as seen in the table below
adjacent rooms into the potentially contaminated space. The (Table 3!t 7).
table below summarizes the recommendations by three differ-
ent agencies-the CDC (70), ASHRAE (71), and the Canadian Ultraviolet germicidal irradiation (UVGI) There is ex-
Thoracic Society (72) (Table 33.6). cellent in vitro evidence that UVGI is highly efficacious in
Note that the costs associated with high rates of air ex- eradicating airborne viable TB bacilli (83). There is experi-
changes is considerable-for initial construction and mainte- mental evidence that upper-room UVGI radiation can pre-
nance, plus the energy costs to heat or cool the air to maintain vent transmission of measles (84), and animal evidence that
comfort for the occupants. It is unclear whether these costs UVGI radiation of air exhausted from a TB ward will prevent
have been considered by authoritative agencies when making M. tuberculosis infection in guinea pigs exposed to that air (85).
the recommendations above. No study has demonstrated the However, there is no evidence that these measures will actually
cost-effectiveness of these measures. prevent M. tuberculosis infections among workers or patients in
It is important to note that the recommendations for proce- healthcare facilities. However, the theoretical considerations
dure rooms, such as sputum induction or bronchoscopy or au- are strong and this technology is much less expensive than
topsy, apply to all facilities, regardless of their risk classification. ventilation systems to achieve the high rates of ACH recom-
In part, this is because airborne isolation procedures may be use- mended (81). At present, however, UVGI remains widely un-
ful for the prevention of transmission of other organisms such derutilized. This is largely the result of unwarranted concerns
as avian influenza or severe acute respiratory syndrome (SARS). over potential risks of skin cancer (which are completely un-
Inevitably, TB patients are seen in low-risk facilities, where they founded (86)) and eye irritation (which are warranted, but
are more likely to undergo invasive procedures (or unfortu- easily avoided through proper installation and maintenance of
nately autopsy). This is because the likelihood, for an individual the UVGI lamps). This technology appears to offer an excel-
patient, that the diagnosis will be delayed or missed is greater in lent alternative or adjunct to mechanical ventilation systems,
facilities with fewer TB patients admitted each year (63). but remains underutilized.
Air Exchange Rates Ra:omm.cndcd for Selected Areas in Hcalthcarc Facilities

Number of Mechanical Air Changes
per Hour (ACH) Recommending Agency
Direction of Air Movement
Area CTS CDC ASllRAE (All Agencie.1) 11
Autopsy suite 12 12 12 Inward
Bronchoscopy room 6--12b 12 12 Inward
Sputum induction/ pentamidine
aerosol
Emergency departments 2 12-15 12 Inward
Trauma 12 or 15
Radiology waiting room 2 12-15 12 Inward
Operating room or surgical room 15 15 25 Outward
Airborne isolation rooms'
Existing buildings 6 6 NS Inward
New buildings 9 12 12
General patient care, and nonisolation 2 NS 4d NS
rooms
Ambulatory care
Exam/treatment/patient rooms
"Direction of airflow from hallway or corridor relative to space (inward means from hallway into room).
hSix ACH for existing room and 12 ASH for new constructions.
<Air-cleaning devices may be wed to increase the equivalent ACH.
"Recommendation is for patient corridors.
GIS, Canadian Thoracic Society; CDC, Centers for Disease Control and Prevention; ASHRAE, American Society of Heating Refrigeration and
Air-conditioning Engineers; NS, not stated, no recommendation made specific to these areas.
respirators for patients, as these fit more tightly and result in

TABLE 33.7 Time Needed to Ranove less leakage. However, these masks could cause respiratory dis-
Airborne Microorganisms comfort to patients, particularly patients with limited pulmo-
After the Generation of nary reserve due to advanced TB.
Infectious Droplet Nuclei
Has Ended Fit testing Many jurisdictions require that healthcare workers
undergo fit testing to ensure that the respirator they wear does
Minutes to Remove
Airborne Orgaoisou not leak more than 10%. However, studies have shown that fit
testing is unreliable and poorly reproducible, and there is no
Air Changes per Hour By 99% By 99.9%
evidence that this will add protection for healthcare workers.
2 1!18 207 Hence, it is difficult to recommend. We suggest that a more
4 69 104 useful measure is training healthcare workers how to wear the
6 46 69
respirators, plus why it is important to wear respirators every
12 23 35
15 18 28 time there is a potential exposure.
20 14 21
Preventing TB disease in infected healtlu:are workers All
Adapted from jensen PA, Lambert LA, Iademarco MF, et al. of the preceding infection control measures are designed to
Guidelines for preventing the transmission of M~um prevent transmission and acquisition of M . tuberculosis infec-
tvberr;u/o.m in health<are settings, 2005. ~ Recomm Rep. tion by healthcare workers. However, if infection occurs, then
2005;54(RR-17):1-141.
measures are needed to reduce the risk of disease. The risk of
reactivation once infected is strongly affected by illnesses that
suppress the immune system, such as HIV infection, cancer che-
Portabk units Portable air-cleaning units that incorporate motherapy, transplant rejection drugs, tumor necrosis factor
high-efficiency particulate air (HEPA) filters or UVGI to de- (TNF) -alpha inhibitors, and corticosteroids (Table 33.2) . Work-
contaminate the air are helpful in emergency situations when ers with these conditions or taking these medications should be
no airborne isolation rooms are available. However, these are counseled to avoid high-risk activities to prevent acquisition of
not practical for long-term installation for several reasons. First, infection. If they have evidence of M. tuberculosis infection, they
they may recirculate air locally and not achieve clearance of air- should be strongly encouraged to take LTBI therapy.
home TB bacilli in air throughout the room. Second, they may For other workers, regular testing to identifY new M . tuber-
be covered or blocked by patients inadvertently. Third, they culosis infection is an important method to detect workers with
do not create directional airflow, allowing contaminated air to new infection. This is because the risk of development of dis-
flow out of the room into the corridor and beyond, thereby ease is highest soon after infection; hence, these workers would
exposing other patients and workers. benefit from therapy for LTBI.
PersomU ProtectiJie MetuUres

Testing for latent TB in healthcare workers Two tests are
now available for the diagnosis of LTBI in healthcare workers.
Personal protective measures for healthcare workers include The traditional test is the TST. As reviewed earlier, this is a
measures to prevent acquisition of infection and measures to test with a long track record of use in healthcare workers, but
prevent the development of disease once infected. has problems of poor specificity and requires multiple visits.
However, once a baseline is established, significant increases
Measures to prevent acquisitiun ofinfection-respirators in size, in the absence of new TB infection, are rare (21,88,89).
(masks) The current standard for personal respiratory pro- Preemployment, workers should undergo two.,tep tuberculin
tection is N95 respirators. These are respirators that are certi- testing. Those that are found positive on either test should
fied to filter at least 95% of particles of 1 1m1 or greater and undergo medical evaluation and should not undergo further
have less than 10% leakage. They provide protection against testing. If they are reexposed, the most important strategy
breathing in airborne TB droplet nuclei that are typically 3 to is to question them regarding symptoms suggestive of active
6 1m1 in size and may contain one or more viable TB bacilli disease. In some facilities, postexposure chest X-rays are per-
(see "Transmission" section above). Hence, these are to be formed; the yield of this screening is low, in the absence of
worn by healthcare workers. symptoms.
Surgical masks are designed to protect against breathing Workers who are initially negative may be retested following
out large droplets and have only 50% efficiency in filtering par- exposure episodes, or regularly; this depends upon the risk of
ticles of 1 llffi· Hence, they are useful for TB patients to prevent exposure. Workers involved in high-risk activities should un-
them from expelling larger droplets into the air. A problem dergo periodic TST, usually annually. If previously TST-negative
with surgical masks is that they are very loose-fitting. In a pa- workers have positive tests following exposure or on periodic
tient who is coughing, there may be substantial aerosolization testing, then they should be referred for medical evaluation,
around the mask, and the mask can quickly become saturated chest radiograph, and consideration for LTBI therapy. This eval-
at which point it is simply a wet membrane from which droplet uation and discussion regarding therapy should be with a physi-
nuclei are generated. In one study, airborne transmission was cian who is experienced in LTBI diagnosis and management.
reduced by 50% when patients wore surgical masks (87). The Owing to the difficulties in interpreting conversion and re-
optimist will say that 50% reduction is good, but the pessimist version reactions with IGRAs (discussed earlier), it is difficult
will observe that these masks still allow an unacceptably high to recommend the use ofiGRAs for serial testing ofhealthcare
level of transmission! Some experts recommend the use ofN95 workers as part of an institutional TB infection control program.
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be applied with particular caution in low- and middle-income latent tubercul.ooia infection. MMWR RlcotMI &p. 2000;49(II.R.-0) :1-51 .
countries. In resource-poor settings, emphasis should be placed 30. Huebner RE, Schein MF, llaaa]BJr. The tuberculin akin teot. Clini..p.tDis. 199S;17(6):
968--975.
on administrative controls, particularly the rapid identification, 51. Farl>at M, Greenaway C, Pai M, et al. Faloepooitive tuberculin akin teota: what il the abao-
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tion of effective therapy. Environmental controls in low- and 1192--1204.
52. Menzie• D, Gardiner G, Farhat M, et al. Thinking in three dimenoi.ono: a web-baoed algu-
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L. Clifford McDonald and Benjamin A. Lopman
Infectious Gastroenteritis
INTRODUCTION were fulfilled, establishing it as the cause of pseudomembra·
nous colitis (4,5). Pseudomembranous colitis, meanwhile, bad
Infectious gastroenteritis (IG) is manifest most commonly by been first described in the late 1800s (6), but became much
diarrhea and variable degrees of nausea and vomiting. & a more common in the antibiotic era and recognized as a partic-
healthcare-associated infection (HAl), IG is umque from other ular threat following the use of clindamycin in the 1970s to the
HA.Is such as surgical site infections, ur:Wary tract infections, point that it was commonly known as "clindamycin colitis" (7).
pneumonia, and bloodstream infection, with no direct role for In retrospect, this was likely due to early emergence of highly
invasive devices or procedures in pathogenesis. In addition, clindamycin-resistant strains of C. diJJicile, foreshadowing how
the main manifestations are more commonly due to noninfec- years later, acquired resistance to commonly used antibiotics
tious rather than infectious causes. DiaiThea, defined as three would facilitate the emergence of epidemic st:raiJ:IJ (8,9).
or more unformed stools in a 24-hour period, i5 the principal The main virulence factors of C. di.fficil8 are the two large
symptom of IG with nausea and vomiting playing a more prom- clostridial toxins A and B (10,11). Both toxins have high
inent secondary role in certain etiologies such as norovinu. sequence homology, suggesting evolutionary origins via a gene
Healthcare-associated diarrhea, defined as diarrhea with onset replication event. Both have carboxy-terminal binding do-
<::3 da)l3 after admission is common (1). In one recent preva- mains, amino-terminal biologically active domains, and a small
lence study, healthcare-aaaociated dianhea was found in 12% of hydrophobic intermediate domain, possibly active in transloca-
patients overall and in 27% of patients who had been hospital- tion. The main biologic activity is via glycoaylation of Rho pro-
ized for>~ weeks (2). teins, disrupting the cell cytoskeleton. Whereas toxin A targets
Instead of IG, medications and enteral feedings are the most only cells of the gastrointestinal endothelium, toxin B targets
common came of healthcare-associated diarrhea (1). Among a broad range of cells. While it was initially believed that toxin
causes of IG, pathogens may be categorized on the basis of A was the main virulence factor in humans, over and above
whether symptoms are associated with antibiotics or not An- toxin B, this was called into question in the early 1990s with
tibiotics, because they disrupt the lower intestinal microbiota, the emergence of toxin A- B+ strains that could cause even
are responsible for 25% of all episodes of healthcan>a5SOciated severe disease (12). More recent laboratory work with isogenic
diarrhea even without a recognized pathogen playing a dis- C. difjici'U isolates suggests that toxin B may be more impor-
tinct role. When IG is found in antibiotic-associated diarrhea tant or that, at the very least, either toxin individually can cause
(AAD), it i5 most often due to Clostridium diJ!icik, the most com- disease (13,14). Both toxin genes and sUITounding regulatory
mon healthcare-aaaociated IG and recogllized cause of AAD. genes are located in a 19.6-Kb region of the C. di.f.ficikgenome
The next most common IG cause of AAD is Klehsiilla o~UJca, known as the pathogenicity locus (11). In addition to toxins
which causes a distinctly hemorrhagic colitis and commonly A and B, a third toxin, known as binary toxin, was historically
resolves with cessation of the antibiotics. Clostridium perjrin- found in <10% of isolates. The gene encoding binary toxin is
pu and Staplrjk>coccw aumu are two even less prominent IG not located in the pathogenicity locus, and although its exact
causes of ADD. Meanwhile, the most prominent IG cause of role in pathogenesis is not known, it has increased in preva-
healthcare-a.ssociated diarrhea not aaaociated with antibiotics is lence as it is present in hypervirulent strains that have recently
norovirus. The primary focus of this chapter is on the two most emerged (15).
well-recognized healthcare-essociated IGs, C. di.fficile and nom-
virus infections, but also includes a brief discussion of other vi- PATHOGENESIS AND CLINICAL PRESENTATION
ral causes of IG that may be transmitted in healthcare settings.
C diJjicile is not part of the normal lower-intestinal microbiota,
but is acquired following transmission via the fecal-oral route
CLOSTRIDIUM DIFFICILB from other patients (16). The spore is the transmissible form
that is ingested and, owing to its relative acid resistance, passes
INFECTION (CDI) easily through the stomach and into the small bowel where it
germinates into the active growing vegetative form and then
THE ORGANISM AND ITS VlllULENCE FACTORS
passes into the large intestine. Following acquisition, the
C. difJicillt is an anaerobic, gram-positive, spore-forming ba- human host may either become asymptomatically colonized,
cillus. It was first isolated from a healthy infant in 19~5 and develop infection, or resist either colonization or i.nfe<:tion.
named difficile because, as an obligate anaerobe, it can be dif- The main human host defense mechanisms that detennine
ficult to cultivate in the laboratory (~). It was first associated outcome following transmission are an intact lower-intestinal
with human disease in the late 1970s when Koch's postulates microbiome (i.e., the collective genome of the microbiota
513
reOecting both atrain and species composition) and humoral of recent symptomatic infection are at decreased rather than
im.mUDity or responsiveness (17). An intact intestinal mi.crobi- increased risk for developing CDI during aubsequeut hospi-
ome prevents both colonization and infection; antibiotic expo- talization (29). 'Th.ia paradox, relative to colonization by other
mres that commonly perturb the microbiome are the principal multidrug-resistant organisms (:MDROs) that generally in-
modifiable risk factor for both infection and colonization. crease the ruk for subsequent infection, reflects the increased
Asymptomatic colonization occurs in two major patient groupa: leveb of antitoxin antibodies that appear in patients with as-
infants who have not yet established a mature microbiome and ymptomatic colonization (17). Available data suggest that the
adults who have a perturbed microbiome following antibiotic incubation period of CDI following tranm~iniou/acquisition is
exposure. Colonization rates may easily exceed 50% in either <3 days (17,30-32), suggesting that persons found asymptom-
of these groups (18-20), depending upon the opportunity atically colonized have either bad preexisting protective levels
for tran.smiuion from other colonized or infected individuals of antibodies or quickly boosted their antibody levels on the ba-
(Figure 34.1). Meanwhile, rates of detectable C. tU.fficile car- sis of an anamnestic immune reaponae. In a similar vein, recur-
riage in healthy adults who have not recently received antibiot- rent CDI, defined for surveillance pwposes aa a aecond episode
ics are <5%, and even among these persoDll the organism may of symptoms within 8 weeka of initial infection (33), occurs in
be only passing through the gastrointestinal tract following -20% of patients with an initial episode of CDI and is ;woci-
environmental exposure (21-23). ated with a poor antitoxin antibody response to initial infection
In contrast to adults, C. tUJjicikdoes not have a dear etiologic (27,28). Key evidence confirming the centtal role of antitoxin
role for cawing 3)'1Dptomatic infection among infants, eape- antibody levels protecting against reCUITence ill the recently re-
ciallyneonates (18,19). Although the exact reason forthiJJu un- ported 72% reduction in recurrencea observed among patients
known, it may be related to a specieHpecific innate resistance administered a cocktail of antitoxin A and antitoxin B mono-
to infection in early life; while the enterocytes of immature rab- clonal antibodies (34).
bits do not bind toxin A (24), the enterocyte.s of neonatal piga The main symptom of CDI is diarrhea, which may be severe
do bind the toxin and internalize it (25,26), reOecting the riak and accompanied by abdominal tendernesa, fever, and, in ami-
of symptomatic infection in one but not the other immature nority of patients, blood in the stool. Important early indicaton
animal population. Regardless, human adults are definitely at of more severe diaease that may be more likely to progress to
risk for symptomatic infection as well as colonization. Humoral complicated disease include leukocytosis ;a:15,000/mms and an
immunity is an important detenninant of whether an individual elevated serum creatinine over baseline (35,36). Leukocytosis
with a perturbed microbiome developa infection or only colo- to various degreea is quite common, a:nd severe CDI is one of
nization following C. ~acquisition (17); likew:Ue, immune the relatively few infectious causes of white blood cell counts
respomivenesa plays an important role in whether a previowly >50,000/uuns (37,38). While such extreme values ca:n be a
infected patient will develop recurrence (27,28). poor prognostic sign and ilew can occur in severe diaease, CDI
Supporting the role of humoral immunity in CDI is the find- is uncommonly an occult cau.se of leukocytosis in the patient
ing that patients with asymptomatic colonization and no history not experiencing diarrhea; leukocytosis alone should notjwtify
Unestablished Antibiotic per turbed-

Microbiome, Microbiome,
Waning im munity,
Disease susceptibility
1
I
I . \.
....····...
:·:· ···...
. -··-·· ......... ..
'
... .. /
/
' .:\ ..,..·····
X / / . . . . . . . . . . . .···············
\
. ._.,;
.....
···························································
65
0 3
A ge in years
Figure 34.1. Depiction of the prevalence of colonization by C. diffoik a:nd evidence of humoral immunity to infe<:tion at
di1ferent stages of life.
Chapter 34 • Infectious Gastroenteritis 515
routine C. difficile diagnostic testing in patient!! with formed doubled from 139,000 in 2000 to 347,000 in 2010 (Figure 34.2).
stool (16). Pseudomembranous colitis is the classic lesion de- Death certificate data during this period reflect an even more
scribed in CDI, and can be visualized as white plaques seen on startling 4fold increase from an estimated 3,000 deaths with
endoscopy or the eruption of cellular debris and pus cells from CD! listed as a cause of death in 1999 to 2000 to 14,000 in
the mucosa's deep crypt!! seen under the microscope. Other 2006 to 2007 (51). While hospital discharge and death certifi-
histopathologic findings include disruption of the basement cate data suggest a plateauing of historically high rates in the
membrane with intense infiltration of the mucosa and lamina United States, some countries in Europe have seen a decline
propria by neutrophils and histiocytes. Not all patients with CDI in their rates, coincident with a reduction in the proportion of
will have pseudomembranous colitis observable by endoscopy; infections caused by NAPI (53,54).
however, virtually all have diarrhea as their initial and principal Estimations of the current U.S. burden of CDI are compli-
manifestation, and this should be the key factor in consider- cated by the impact of different definitions, settings of onset,
ing the diagnosis, especially as more sensitive diagnostics are and the different diagnostic testing methods discussed below.
introduced. However, interpolation of existing data suggests the U.S. bur-
Complicated disease often involves a progression of se- den of incident HO-CDI episodes in 2009 to be -140,000
vere disease with a thickened edematous colon that may be (52,55). Because HO-CDI represents only 20% to 25% of all
observed on an abdominal CT scan and may dilate into a con- CDI (56), it is likely the total U.S. burden for CDI is within
dition known as toxic megacolon (39). Meanwhile, the patient range of 500,000 episodes annually. Meanwhile, the attribut-
may experience a paradoxical slowing of the diarrhea and able costs over 180 days offollow-up for an episode ofHO-CDI
development of sepsis that presumably reflects translocation lie in the range of $5,000 to $7,000, and the attributable excess
of resident bacterial toxins. Although uncommon, perforation hospital days are 2.8 days, which, if extrapolated to the above
can occur and, whether via this mechanism or overwhelming HO-CDI burden estimate, suggests excess U.S. hospital cost!! of
sepsis, death may ensue. Recent carefully performed studies $700 million to nearly $1 billion and nearly 400,000 excess days
that account for the confounding from patient!! with CDI of- of hospitalization annually (40,57). However, not only does
ten having more severe underlying disease indicate that the HO-CDI represent only a fraction of all CD!, there are other
attributable mortality of hospital-onset (HO) CDI is between outcomes from HO-CDI not reflected in these numbers, such
3% and 5% (40). However, observed mortality in recent out- as the proportion of patients who are discharged to a skilled
breaks involving hypervirulent strains has ranged as high as nursing facility instead of to their home-an outcome that is
10% to 15% (41,42). 62% more likely if a patient develops HO-CDI (40).
While the precise molecular factors responsible remain un-
certain, there is evidence that, controlling for other factors,
EPIDEMIOWGY
NAP1 is responsible for higher rates of disease and more se-
The epidemiology of CDI changed dramatically with the emer- vere disease. In addition to population-based data where the
gence of the North American Pulsed Field type 1 (NAPl) prevalence of NAP1 is associated with higher rates and more
strain, also known as the restriction endonuclease analysis severe outcomes in different regions (58), and reductions in
(REA) BI strain and PCR ribotype 027 strain (9,41). Although these outcomes are temporally associated with decreases in
there were previously reported outbreak strains that spread the proportion of CDis caused by NAP1 (53), result!! of recent
to multiple hospitals, such as the highly clindamycin-resistant randomized controlled drug treatment trials confirm greater
REAJ-strain responsible for hospital outbreaks in the late 1980s disease severity and likelihood of treatment failure with NAP1
and early 1990s (8,43), none were associated with such sweep- (59). Likewise, recent natural history studies suggest the ratio
ing epidemiologic impact as has been noted with NAPI over of symptomatic infections to asymptomatic colonization caused
the past 12 years ( 44). It is likely that factors other than strain by NAP1 in a population is greater than with other strains (60).
hypervirulence, such as the aging of Western nation popula- Early on in descriptions of NAP1, it was suggested that
tions and evolving antibiotic usage practices, also have played increased virulence might be due to increased toxin A and B
a role in this changing epidemiology. Although the large out- production resulting from an 18-bp deletion in tcdC, a negative
break of 2003-4 that affected over a dozen hospitals in Mon- regulator for toxin production within the pathogenicity locus
treal and surrounding environs was the first to make national (61). Although an associated upstream frameshift mutation in
and international headlines (41), the first known outbreaks talC has been identified as the responsible genetic change lead-
caused by NAP1 actually occurred in Pittsburgh in 1999-2000 ing to a loss of function (62) and the exact role of tcdChas only
(45,46) and Atlanta in 2001-2 (47) but were only retrospec- grown more controversial (63,64), increased toxin production
tively linked to this emerging strain (9). While outbreaks at remains a possible mechanism for hypervirulence (63,65--67).
some centers were clearly associated with increased disease se- The concept of increased sporulation as the main driver for
verity (41,45,46), other centers noted no such increase (47). hypervirulence has been refuted (67,68). While binary toxin in
This is most likely due to many confounding factors, such as NAP1 represents another possible virulence factor that some-
the median age, underlying severity of illness in the popula- how works in concert with toxins A and B ( 15), polymorphisms
tion, and local diagnostic and treatment practices. in the binding domain of toxin B have also been suggested as
Before and early in the emergence of NAP1, only limited a possible virulence factor (69). Moreover, comparative whole
surveillance data for CDI from relatively few hospitals in North genomic sequencing has identified a number of genes that are
America and Europe were available (48) . However, hospital dis- unique in current NAPI strains compared to historic NAP1
charge and death certificate data provide insight into global strains (dating back to the early 1980s) and many more genes
increases in CD!, first in the United States and Quebec, and that are unique from a standard reference strain (70). Finally,
later in Europe (49-52). In the United States, the number of fluoroquinolone resistance in NAP1 appeared coincident
hospitalizations with a discharge diagnosis for CDI more than to it becoming a cause of outbreaks, and it is likely that the
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E F
Fipre 34:.2. Rates of U.S. acute care hospital discharges coded for C. diJiieile infection (CDI: an ICDS-CM: code of 00845 as primary or
secondary diagnosis) for years 2000 to 2010, (A) overall and stratified by: (B) patient age category, (C) hospital teaching status, (D) hospital
location, (E) hwpital size (bed-size criteria vuybyregion,locati.on, and teaching statw), and (F) region. Compiled from the National Inpatient
Sample, downloaded at the Healthcare Cost and Utilization ~ect (available at http:/ /www.hcup-w.ahrq.gov/overviewJsp).
widespread use of respiratory fluoroquinolones in older adulm, suggesting that factors other than antibiotia may diarupt the
a trend that began in the late 1990s, conferred a selective ad· microbiome to render a patient susceptible to CDI. In contrast,
vantage to this strain, leading to im emergence and spread (9). 90% to 100% of hospitalized patients who develop CDI have
Around the same time increases were noted in CDI among received recent antibiotics, and those who have appeared unex-
hospitalized patients the important role of CDI in the composed have been thought by some, at least in the past, to have
munity became clearer (71). Approximately 25% to 35% of all had occult antibiotic exposures (75, 76). The straim respous:ible
CDh appear to be commumty-associated (CA)-CDI, meaning for CA-CDI are largely similar to those causing HQ.CDI (77, 78)
that they occur in patients who have had no overnight stay in except in the Netherlands where another hypervirulent strain,
an inpatient care facility in the previous 12 weeks (56,72). Most PCR ribotype 078 (NAP 7 and 8), has been found prevalent
remarkable about these patients is that as many as 30% to 40% in rural areas (79). PCR ribotype 0'78 is of particular interest
have not received antibiotia in the previous 12 weeks (73,74), because it ill a common, widespread (e.g., Europe and North
CMjMr 34 • InftaitNs GasfromUriti.s 517
America) cause of sometimes severe em in neonatal pigs, rai9- No bealtbcare

ing concem that pathogenic C. di.fficil8 could be transmitted via
the food supply (79-81). However, considering the overall Hospital-onset
23%
results of recent retail meat studies suggesting little or no con· Communi ty· onset,
tamination and a geographic distribution of human PCR ribo- recent ouq;tatie,nt ~
type 078 infections in the Netherlands inconsistent with food exposure 26%
distribution patterns (i.e., predominantly rural), available evi-
dence points toward little or no role for foodbome transmiasion
in the epidemiology of human CDis ('79,82-84). Nonetheless,
there may be a role for amplification in animals of emerging
hypervirulent strains such as ribotype 078 with transmission
between animal!J and humans via the environment (79,81,8&).
In addition to patients with CA.-CDI, who are often younger
Nuning hom~
and have leu severe underlying disease than patients with -onset 26%
HO-CDI or nuning home-onset CDI (74), episodes of severe recent inpatient
em and deaths among generally healthy pregnantwomen have exposure 19"/o
been reported (71,86). However, although there are immuno- Pigue 34.3. Percentage of C dilfia18infection (CDI) cues
logic reasons to expect that severe CDI could occur in preg- (N = 1O,M2), by inpatient or outpatient statu.! at time of stool collec-
nancy and there bas been increased antibiotic use associated tion and type/location of ez:posures in the previous 12 week&, United
with prophylaxis for Group B streptococcus, available evidence States, Emerging Infections Pro~, 2010. (Adapted from~
does not suggest that increases in pregnancy-associated CDI are Morb.Mtnt4l'W1tq&p. 2012;61:157-162).
out of proportion to disease in other populations (87). em
has also increasingly been recognized among children with on-
set both inside and outside the hospital Marked increases in encoding interleukin-8 is wociated with a deficient humoral
hospital discharge diagnoses for CDI have been noted in the immune response to C. dijficile toxin A and increased risk. for
pediatric population as they have in adult patients (88). TbiJJ recurrent CDI may constitute the most advanced understand-
includes increases in infants, suggesting that even though there ing of a genetic susceptibility to any HAl pathogen (90,91).
is no good evidence to indicate that C. dijficile is etiologic for Similarly, certain cancer patients, patients receiving steroids,
disease in human infants (89), many clini.ci.ans are at least con- and HIV-infected patients are all at increased risk for CDI or se-
sidering the diagnosis and posaibly testing and treating for CDI. vere outcomes independent of antibiotic exposures, most likely
Above 1 to 2 years of age, C. diJficiJe does appear to cause dis- via an acquired immune deficiency (75,92,93).
ease, suggesting that observed increases in children above this Now with the dawning of the metagenomics era, it is be-
age represent increases in true disease similar to that observed coming apparent that the disruption of the lower-intestinal
in adults (89). microbiome wrought hy antibiotics is both profound and long-
While there is increased recognition of em episodes oc- lasting (94,9&). It bas long been recognized that virtually every
curring in persons without recent inpatient bealthcare expo- antibiotic, except perhaps the aminoglycosides, predispoae1
sure (71,72), another way to asseu the epidemiology iJJ the patients to CDI. It is difficult to preci!ely rank the CDI risk. of
proportion of all patients who have had any recent healthcare different antibiotics because several factors confound the rela-
exposure. Thking this perspective, a recent report from the tionship between antibiotic and em, including the charactel:"'
Centers for Disease Control and Prevention's (CDC's) Emerg- istics of prevalent strains such as bypervirulence or resistance
ing Infections Program (EIP) population-based surveillance to the antibiotic in question (9), the prevailing "colonization
in the United States indicates that 94% of all patients with pressure" indicating bow likely a patient may newly acquire
CDI have bad some healthcare exposure within the previous C. difficik after exposure to the antibiotic (7&), and other host
12 weeks, even if only a recent outpatient exposure (56). Thus, factors already mentioned. Given these limitations, it still ap-
the main focus for preventing CDI across a community should pears safe to say that broadeMpectrum antibiotics, especially
remain focused on healthcare delivery (Figure 34.3). However, those with anaerobic activity and/or against which prevailing
because data from the EIP also indicate that 75% of all CDa strains are highly resilltant, all appear to have higher risk. than
related to recent healthcare have their onset outside an acute other narrower-apectrum drugs with activity against C. diJfo;ile.
care hospital, including in nuning homes, rehabilitation facili· Thus, advanced-generation cephalosporins, fluoroquinolones,
ties, and the community, em prevention needs to occur acrosa carbapenems, and penicillin:JUactamase inhibitor combina-
the continuum of healthcare, suggesting a possibly unique and tions appear, somewhat in decreasing order, to be the antibiot-
important role for coordination by state and local public health ics currently in use that place patients at greatest risk per unit
departments that have relationships with all care settings (56). of exposure. Overall, antibiotics increase the risk of CDI 7- to
All epidemiologic risk factors can be categorized accord- 10-fold while a patient is receiving the drug and the month
ing to the three main prerequisites in pathogenesis of CDI: thereafter, and 2- to Mold for the 2 months following that (96).
deficient or waning immunity, microbiome disruption, and In addition, the receipt of multiple antibiotics and cumulative
transmission leading to new acquisition. Both the incidence antibiotic exposures over 2 to 3 months increases the risk of
of initial em and the proportion of patients who experience em more than a single antibiotic administered for a single,
recurrence are more common with advanced age, moat likely short coune (97). Similarly, patients who have bad a recent
related to, among other factors, an age-related lou in ability to episode of CDI and were sw:ceufully treated are more likely to
mount an anamnestic immune response (27). Recent evidence have a recurrence if they are again exposed to antibiotics for
that a common human genetic polymorphism in the gene other reasons (98).
Proton pump inhibitors (PPis) used in the treatment Historically, the cell cytotoxin neutralization assay (eeNA),
of peptic ulcer disease and gastric reflux disease, as well as a functional assay in which the cytotoxic effect of stool
histamine--2 receptor (H2) blockers used for a similar purpose, supernatant is demonstrated on a tissue culture cell monolayer
are risk factors that have only begun to be identified in the past and proven due to toxin B via blocking of cytopathic effect
10 years (99,100). Although there have been several studies by antitoxin B antibodies, was the gold standard for diagno-
that have failed to find an association between these drugs and sis (4,5). However, this is a complex test to perform and inter-
em (73,74), many others have identified this risk, and follow- pret, requires tissue culture capabilities, and has a 2- to 3--d.ay
ing several recent meta-analyses all confirming an association, turnaround. These shortcomings led to the development of
the U.S. Food and Drug Administration (FDA) recently issued rapid and simpler-to-perform enzyme immunoassays (EIAs)
a clinician warning about the association (101). Because the for toxin A that are relatively inexpensive and have less than
spores of C. difficile are quite resistant to the effects of stom- a 1- to 2-hour turnaround. Owing to the emergence of toxin
ach acid and the spore is the predominant infective form, the A- B+ positive strains, these early-generation EIAs have been
depletion of stomach acid by PPis or H2 blockers leading to replaced with more sensitive toxin A and B tests. However,
increased passage of viable organism into the intestine is not a even when compared to eeNA, toxin A and B EIAs are insen-
likely mechanism for these drugs to increase eDI risk. Instead, sitive (i.e., :580%) although they have fairly high specificity
recent data indicate important effect modification between (107,108). Meanwhile, another approach long used in Europe
antibiotics and these drugs with larger strength of association is to culture for the C. difficile organism and, because there are
for PPis and H2 blockers and CDI in patients with less intense many strains of C. difficile that do not carry toxins A or B and
antibiotic exposures (102). Moreover, PPis have been dem- are therefore not pathogenic, a toxin test (i.e., either tissue cy-
onstrated to impact the lower-intestinal microbiome of dogs totoxin or EIA} is performed on the isolate (109}. While this
(103), suggesting that increased CDI risk from PPis may result is much more sensitive in detecting the presence of toxigenic
from a perturbation of the lower-intestinal human microbiome C. difficile, the turnaround time (i.e., 4 to 5 days) makes it less
in a manner similar to how antibiotics work. clinically useful, and there are concerns over the detection
Other epidemiologic risk factors for CDI reflect increas- of asymptomatic carriage if not used in the right population.
ing risk of a patient newly acquiring C. difficile. These include Nonetheless, toxigenic culture has been proposed as the new
increasing length of stay in an inpatient facility in proximity gold standard against which to compare the sensitivity of other
to source patients who are either colonized or infected with testing modalities (16).
C. difficile (75). In general, it is likely that colonization and The past 5 years have witnessed the FDA approval of eight
infection rates mirror each other across settings such that the commercial nucleic acid amplification tests (NAATs) (110}
incidence of infection in a setting might be an adequate sur- each with sensitivities approaching toxigenic culture and
rogate for "colonization pressure." Thus, a given patient with turnaround times of a few hours (111}. Although these newer
a given underlying risk of developing em is at higher risk if technologies are on the whole more expensive than EIAs, with
admitted to a ward or unit with a higher incidence of eDI than increasing availability of competing platforms, it is anticipated
a low-incidence setting. Another variation on this risk is the that the cost should become more competitive over time.
prevalence of active eDI on admission (1 04). At facilities where Meanwhile, use of less-expensive, highly sensitive but nonspe-
a higher proportion of admitted patients have active em, cific EIAs for the glutamate dehydrogenase antigen (GDH} has
whether related to previous care at the same facility or another been proposed as a screening test for stools, to be followed by
facility, the risk of other patients acquiring C. difficile from these a second confirmatory test (112,113) . While a toxin EIA may
prevalent patients (and/or the unmeasured number of asymp- confirm the diagnosis in many instances, to overcome the poor
tomatically colonized for which they serve as sentinels) will be sensitivity of the toxin EIA, another sensitive method such as a
greater. The importance of adjusting for this risk in presenting NAAT or CeNA should be used for GDH (+}/EIA (-)sam-
surveillance data will be discussed below. Finally, certain care ples (i.e., three--step algorithm) (112} . Alternatively, a two-step
practices, such as the use of feeding or nasogastric tubes, also algorithm of GDH with NAAT or eeNA performed on all GDH
increase the risk of CDI (105). While this risk factor may result (+) specimens can be used (113). Including NAAT in such a
from increased hand contact by healthcare providers providing multistep GDH paradigm may be preferable as the NAAT can
increased opportunity for C. difficile transmission, it has been be periodically performed in parallel with the GDH to assure
recently suggested that this may reflect the deleterious effects the test is performing with desired high sensitivity; there are
of an elemental diet on the lower-intestinal microbiota (106). unconfirmed reports of lower GDH sensitivity that may be
strain-specific (114,115). Especially where there is significant
delay to final results in a subset of patients (i.e., three--step al-
DIAGNOSIS
gorithm}, care must be taken in reporting interim results to
Currently, there is no test available that can make the diagnosis clinicians in an understandable way.
of em but only tests that, combined with a consistent clinical With the rise in the widespread use of the toxin EIAs, the
scenario, raise the pretest probability to make a likely diagnosis. insensitivity of tests for CDI became well known, leading to re-
While the visualization of pseudomembranes on endoscopy is ports that repeat testing might bolster sensitivity and widespread
highly specific for eDI, it is an invasive procedure that is not adoption of this practice (116). It is now well documented how
very sensitive for many patients both because the entire colon such repeat testing and other poor test-ordering practices have
may not be visualized (as in flexible sigmoidoscopy) and be- led to routine testing in populations with very low overall preva-
cause many episodes of eDI will not manifest grossly visible lence (i.e., <5%) of true disease. In those patients with a first
pseudomembranes early in their course. Likewise, a biopsy with negative toxin EIA result, the prevalence of true disease is even
histopathology that is consistent with pseudomembranous coli- lower. At such low prevalence, even toxin EIAs with a specificity
tis is highly specific but not practical or sensitive. of98% can have a positive predictive value of <80%, and repeat
test results quickly approach a positive predictive value as low as and serum creatinine > 1 mg/dL over baseline on the date of
50% (117). diagnosis (16).
Given such scenarios, it has been recommended that all Fidaxomicin is the most recently FDA-approved therapy for
laboratories migrate toward the use of more sensitive assays CDI. Like oral vancomycin, fidaxomicin is not systemically ab-
while improving the selection of the population in which they sorbed and has favorable activity against C. difficile at concentra-
are used. It is the opinion of this author that target laboratory tions easily achieved in the stool (123). In addition, this drug
positivity rates (i.e., surrogate for prevalence in tested popula- is thought to cause less disruption to the microbiome (124),
tion) should be 7% to 12% if a toxin EIA is still being used, or and this, along with a demonstrated inhibition of sporulation
if, as recommended, a testing paradigm that is more sensitive (125), may be responsible for it being the first approved anti-
with a clinically useful turnaround time is used (i.e., two- or CDI therapy associated with a lower recurrence rate (126,127).
three-step GDH algorithm or routine NAAT in all patients), a In two recent pivotal phase III studies, fidaxomicin had a signif-
laboratory positivity rate of 15% to 20% should be targeted. icantly higher overall 30-day "sustained clinical response" com-
Such positivity rates can be achieved through clinician edu- pared to oral vancomycin (128) . This clinical response is the
cation regarding the strength (i.e., high negative predictive combined sequential outcomes ofresponding to initial therapy
value) and limitation (i.e., inability of any diagnostic to make with resolution of symptoms followed by 30-day recurrence-free
the diagnosis of CDI apart from clinical correlation) of the survival. Although these phase III studies showed unequivocally
more sensitive approach, education on the appropriate popu- that the BI/NAP1/027 strain was associated with a lower initial
lation in which to test (i.e., >3 unformed stools in a 24-hour therapeutic response and recurrence rates, the benefit offidax-
period) and why not to perform a test for cure (i.e., patients omicin for sustained clinical response was only seen in patients
routinely remain colonized following resolution of CDI) (16), with non-BI/NAP1/027 strains (59,126,127) . Despite these fa-
and strictly enforced laboratory rejection policies for formed vorable outcomes with fidaxomicin, because it is much more
stool and repeat testing within a 5- or 7-day time frame ( 118). expensive than oral metronidazole or vancomycin, and because
there is much less clinical experience with the drug, the precise
role of fidaxomicin in routine clinical management of CDI has
TREATMENT
not been determined.
General recommendations for the management of patients The management of recurrent disease, especially multiply
with CDI include stopping any other antibiotics when possible recurrent disease, remains a challenge. Although a first re-
(whether stopping PPis makes a difference in clinical outcome currence can generally be managed using the same agent as
is not known), using oral therapy whenever possible, treating used to treat the original episode as long as the recurrence is
for a minimum of 10 days, avoiding antiperistaltics, assuring of similar severity, subsequent recurrences should be managed
that anti-C. difficile therapy is reaching the colon in patients using alternative strategies (16) . If a patient was treated using
with severe disease, and involving surgeons early in the care of metronidazole for the first two episodes, oral vancomycin or
patients with complicated disease. Drugs with an FDA-approved fidaxomicin should be used to treat a subsequent episode. If
indication for CDI include oral vancomycin and fidaxomicin. the patient has already received oral vancomycin or fidaxomi-
Meanwhile, metronidazole, although not FDA-approved for cin in treatment of an episode, an oral vancomycin 6-week ta-
CDI, has been a recommended treatment for many years (16). per has been the traditionally recommended approach (129).
Of these three agents, only metronidazole is orally absorbed Metronidazole is not recommended for this purpose because
and in fact this absorption is quite high in the absence of di- absorption increases and stool concentrations decrease with
arrhea, resulting in low stool concentrations in asymptomatic the cessation of diarrhea; prolonged systemic exposure to met-
patients. Because of its absorption, systemic toxicity in the form ronidazole can lead to toxicities such as peripheral neuropa-
of peripheral neuropathy can occur if administered for a pro- thy (16). While a vancomycin taper is intended to suppress
longed period. However, the advantages of metronidazole are C. difficile germination and growth while allowing the micro-
its lower cost per course (i.e., owing to its widespread generic biome to restore, unfortunately some patients will fail this and
availability) and the perhaps mistaken perception that expo- develop a pattern of multiple recurrences whenever vanco-
sure to it vs. oral vancomycin results in less selective pressure mycin is discontinued, regardless of taper. Because these pa-
for vancomycin-resistant enterococci (VRE) (119). tients are likely not developing an immune response and have
Oral vancomycin, meanwhile, is not absorbed systemically a deeply disturbed microbiome, more experimental therapies
and has a favorable peak stool concentration relative to mini- are often needed. One of these showing great promise is fecal
mum inhibitory concentration for C. difficik. In addition to the microbiota transplant in which the stool of a family member or
concern about selecting for VRE, oral vancomycin has always other screened donor is administered via either lower endos-
been much more expensive than metronidazole. However, this copy or nasogastric tube to reconstitute the microbiome of the
difference in price may change appreciably with the approval patient with multiply recurrent CDI (130). Other agents that
of generic oral vancomycin. Previously, many inpatient settings remain experimental for both prevention and therapy include
circumvented the higher price of oral vancomycin by admin- rifaximin (131), monoclonal antibodies to toxins A and B (34),
istering generic IV vancomycin via the oral route. However, and probiotics (132).
this practice was less amenable to use in the outpatient setting.
Although the equivalence of oral metronidazole and vancomy-
PREVENTION
cin was asserted in many previous guidelines, recent trials have
shown more favorable outcomes with vancomycin, especially in Keys to interrupting C. difficile transmission in healthcare set-
more severe disease (16,120-122). Vancomycin is currently rec- tings include early detection and institution of Contact Precau-
ommended for initial treatment of CDI in patients with early tions for patients with CDI (16,133). This requires a proactive
indicators of severe disease, including a WBC > 15,000/mm3 approach by clinicians in asking patients at high risk about
their stool patterns and educating them to alert staff when diar- Another area of some uncertainty is the duration of Contact
rhea first has its onset. In high-risk patients (i.e., hospitalized Precautions. Although patients are likely most contagious while
patients with recent receipt of antibiotics), and especially in they have active diarrhea, and current evidence-based guide-
those at highest risk (i.e., those with a previous recent episode lines recommend precautions only while patients are symptom-
ofCDI), one should consider presumptive Contact Precautions atic (16,133), it is clear that patients continue to shed organism
once the history of clinically significant diarrhea has been elic- for several weeks following resolution of symptoms (139), lead-
ited, before the diagnosis is confirmed with a positive diagnosing to ongoing contamination of their skin and nearby envi-
tic assay. In some hospitals, presumptive Contact Precautions ronmental surfaces with C. difficile spores. Also, during the
are routinely instituted in all patients undergoing testing for time soon after resolution of symptoms and discontinuation
CDI. The use of sensitive diagnostics with high negative pre- of therapy, patients are at maximum risk of recurrence, lead-
dictive value is important for either deciding not to isolate or ing to higher degrees of environmental contamination. This
discontinuing isolation despite continued diarrhea. The im- has led some experts to recommend continuation of Contact
portant performance measures in this area include the average Precautions for 72 hours after cessation of therapy (assuming
time from onset of symptoms to institution of Contact Precau- the symptoms resolved by the time therapy was discontinued),
tions, collection of a specimen for testing, availability of results, whereas others recommend continuation through the remain-
and, because early effective therapy will render patients less der of an acute care hospitalization. Given the relatively short
contagious, initiation of treatment. length of stay in most acute care facilities, maintaining precau-
Important in implementing Contact Precautions is the tions for the remainder of hospitalization may be more fea-
placement of the patient in a single-patient room with a dedi- sible than maintaining precautions in long-term care facilities
cated bathroom. If a single-patient room is not available, then (LTCFs) for an indefinite period. However, it may be that in
priority should be given to dedicating a bathroom or bedside LTCFs, where there is a higher ratio of recurrent-to-initial CDI
commode for the use of the patient with CDI. If a bedside com- patients (140), there is a more prominent role for transmis-
mode is used for the patient with CDI, care should be taken sion of C. diJ.ficilefrom patients who are status-post symptomatic
in emptying contents so as not to contaminate a shared toi- CDI. If further evidence accumulates to support the duration
let and a low threshold should be used for deciding when to of precautions lasting beyond symptoms to the duration of
clean the bathroom when contamination may have occurred. acute care hospitalization, new criteria will be needed to better
Gloves should be worn by all healthcare personnel (HCP) en- delineate the period of greatest transmission risk following an
tering the room to prevent contamination of the hands with episode of CDI in long-term care patients.
C. difficile spores contaminating the patient's skin or surround- Although the role for contamination of environmental sur-
ing environment (16,133,134). Although not as well proven in faces in transmission is better defined for C. difficile than any
preventing C. difficile transmission as gloves are, gowns have other HAl pathogen with the exception possibly of VRE, it re-
been proven to have an incremental impact on preventing mains controversial exactly what steps for environmental disin-
transmission of other pathogens found in the stool, such as fection should be routinely recommended (16,133,141-143).
VRE, and therefore are recommended in addition to gloves Just as alcohol is not effective for inactivating C. difficile spores on
(135). The important performance measures include the pro- the hands, so commonly used disinfectants, such as the quater-
portion of visits by HCP in which there is compliance with nary ammonium compounds, are not effective for inactivating
glove and gown use. these spores on high-touch environmental surfaces (144). How-
Of less certain importance is the use of soap and water ever, good environmental cleaning, as part of a recommended
handwashing over alcohol-based hand sanitizers for hand ~tep cleaning and disinfection strategy, does remove a sig-
hygiene after glove removal. Although alcohol has negligible nificant number of these spores (141). Therefore, the founda-
activity against C. difftcile spores and handwashing is superior tion of any environmental strategy for C. difficile is assessment
to alcohol-based hand sanitizers in removing spores, it is not of the adequacy of cleaning using standardized methods (145) .
clear whether the improved efficacy of handwashing translates The various strengths and weaknesses of the different assess-
into reduced transmission (136,137). Achievable C. difftcile ment methods available is beyond the scope of this chapter,
spore-count reductions on hands using soap and water are 1 to but suffice it to say that direct observation may be too prone to
2 logs below the achievable reductions observed with other the Hawthorne effect to be a useful method of assessment. The
common vegetative microorganisms, whether using soap and reader is referred to a CDC toolkit and Chapter 20 of this text
water or alcohol-based hand sanitizers. Thus, it appears that for the purpose of assessing the adequacy of cleaning (146).
glove use, and not a particular form of hand hygiene, should Until recently, the mainstay C. difficile sporicide was a 1:10
be the principal recommendation for preventing the transmis- dilution of household bleach (final concentration of sodium
sion of C. difficile via the hands of HCP. Moreover, the spore hypochlorite of 5,000 ppm) prepared fresh daily. However, the
burden on hands following glove removal is likely to be low, Environmental Protection Agency (EPA) has now established
assuming care is taken in glove removal. A different application registration criteria for a C. difftcile sporicidal label claim that
where improved hand hygiene might be more likely to impact requires a 6-log reduction in spore counts following the manu-
transmission would be routine use on wards with high rates of facturer recommended contact time (147), and there are now
asymptomatic carriage (e.g., wards with longer lengths of stay over a dozen products with a C. difftcile sporicidal EPA claim
and high rates of antibiotic use and CDI incidence). However, for surface disinfection (148). Although most are sodium
before--after studies of hospital-wide transition from handwash- hypochlorite-based, some are not Some are available in final
ing to alcohol-based sanitizers have failed to demonstrate an working concentrations as cleaner-disinfectants (i.e., sodium
impact on CDI rates (138); thus, it would seem more reason- hypochlorite alone does not have detergent action), and while
able to trial universal gloving in such settings with high risk for most require a 10-minute contact time, some have shorter con-
asymptomatic carriage (134). tact times.
Although there have been a few studies that associated the a minority of intrahospital C. difficile transmission events could
use of a C. difficile sporicidal disinfectant (i.e., various con- be attributed to another patient from anywhere in the hospi-
centrations of bleach) with lower rates of CDI (142,143,149), tal infected with the same or similar strain in the recent past
these were largely uncontrolled studies or studies in settings (154). One possible conclusion was that asymptomatic carriers
with hyperendemic rates. Therefore, the use of a C. dif.ficile must be playing a larger role in transmission (i.e., the authors
sporicidal disinfectant remains a supplementary measure for did not dispute the evidence for a very short incubation period
considered use in outbreak situations or when endemic rates indicating that carriage of an infecting strain into the hospital
remain elevated despite the implementation of other preven- would be unlikely). However, the method used to diagnose CDI
tion strategies (16,133). However, several prevention initia- in the study was EIA, allowing the prospect that a large pro-
tives have been successful in reducing endemic rates in either portion of patients with diarrhea and C. difficile in their stool
individual or small groups of hospitals by implementing, in were not identified leading to many occult transmission events
addition to other transmission prevention strategies, environ- between patients. Moreover, it is clear that increasing numbers
mental interventions that included improved cleaning and use of U.S. acute care hospitals have experienced at least modest
of a C. difficile sporicidal disinfectant (56). Although C. dif.ficile reductions in their CDI rates through a focus on containing
sporicidal disinfectants have been used primarily during termi- transmission from symptomatic patients (56).
nal room disinfection between patients (142,143), with the ad- Though dealt with last in terms of prevention, antibiotic
vent of disposable wipes impregnated with these disinfectants, stewardship has the potential to be the most effective means
this intervention may be now more easily applied on a daily of preventing CDI. Of any prevention measure, it has some
basis (149). of the best evidence in preventing both endemic (155,156)
Other innovative methods for applying a sporicidal disinfec- and outbreak-related infections (157-159), whereas most of
tion step in terminal cleaning are the "no-touch disinfection" the best evidence for interventions to reduce C. difftcile trans-
(NTD) methods, the most developed ofwhich are vaporized hy- mission is drawn from observed reductions in hyperendemic
drogen peroxide and UV light irradiation (150-152). Although settings (16,133). The challenge is to effectivelyimplementan-
an in-depth discussion of the pros and cons of NTD methods tibiotic stewardship in a manner that results in real decreases
is beyond the scope of this chapter, strengths include the auto- in the total number of antibiotic-days, average number of an-
mated nature of the application with feedback mechanisms to tibiotics prescribed to a patient, or narrower-spectrum anti-
assure the adequacy of the application, leading to an overall biotics. The reader is referred to the chapter on antibiotic
unequaled efficacy in reducing bioburden (see Chapters 20 stewardship regarding how improvement in these metrics may
and 21). Weaknesses include that NTD methods can generally be achieved (see Chapter 14). However, when such metrics
be applied only for terminal disinfection of patient rooms. One are achieved, a reduction in CDI rates is probably the first
particularly attractive application of NTD methods is for dis- and most readily measured patient outcome likely to improve,
infection of noncritical, reusable medical equipment between making the reduction of CDI an important target for antibi-
patients (153). otic stewardship (156).
Another outstanding question is the role of asymptomatic In addition to generally narrowing the spectrum of antibiot-
carriers in the overall transmission of C. difficile and whether ics and reducing days of unnecessary therapy, there have been
any special measures should be taken to prevent this transmis- more tailored approaches to stewardship shown successful in
sion. It is well recognized that the number of asymptomatic car- outbreak situations. This involves conducting a case-control
riers with C. dif.ficileamong inpatient populations with common study of CDI patients to determine which antibiotic exposures
antibiotic exposures well exceeds the number of patients with are most closely associated with infection in a particular facility
current or recent active infection and that the cumulative risk experiencing an outbreak (157-159) . In some instances, such
for becoming a carrier, like active infection, increases with the as clindamycin associated with outbreaks in the 1990s and fluo-
length of hospitalization (20,30,60). In some long-term care roquinolones in the past decade, this approach identifies a role
settings, the proportion of asymptomatic C. difficile carriers for acquired resistance in the outbreak strain, and focusing
may exceed 50% (20). Nonetheless, it has been generally ac- better stewardship. Moreover, in these outbreaks, the outright
cepted that asymptomatic carriers play a minor role in overall restriction or removal from the formulary of a particular an-
C. dif.ficile transmission (16,133). More recent data suggest that tibiotic or antibiotic class has led to the cessation of the out-
while patients with active infection contaminate the environ- break (159). Given the continued prominent role of the BI/
ment and hands of HCP to a greater degree, contamination NAP1/027 strain in the United States as of this writing, and the
from asymptomatic carriers is also significant (20). It is likely fact this strain is highly fluoroquinolone-resistant, particular
the contribution of transmission from asymptomatic carriers is focus on fluoroquinolone stewardship would appear to remain
inversely proportionate to the overall rate of C. dif.ficile infec- warranted. In the United Kingdom where CDI rates have been
tions in a particular setting. In settings with poor containment reduced markedly from historic highs of -5 years ago, there
of transmission from actively infected patients, the proportion is evidence to suggest that there has been not only improved
of all transmission events resulting from symptomatic patients infection control leading to reduced transmission, but impor-
will be higher, leading to overall higher rates, and in such set- tant shifts in prescribing so that whereas once most episodes
tings, improved containment will have its greatest impact on were associated with recent fluoroquinolone or cephalosporin
reducing overall rates. If this is true, there may be an increas- exposures, now most episodes are associated with extended-
ing need to reduce transmission from asymptomatic carriers as spectrum penicillin exposures (53). This is coincident with a
facilities reduce endemic rates of CDI to very low levels. shift from BI/NAP1/027 to other less virulent strains. From
In a recent study from a hospital in England, where there among U.S. hospitals where the fluoroquinolones continue
has been a longer-standing national program to reduce CDI to account for a major, if not leading, proportion of total an-
rates, it was found, using advanced molecular analysis, that only tibiotic days, there is only one report of a hospital taking the
dramatic action of removing all fluoroquinolones from their taking the shape of a container) in a 24-hour period should be
formulary in the midst of a difficult-to-control outbreak with used to determine whether a stool sample should be sent for
BI/NAPl/027 (159). What was most remarkable from this re- diagnostic testing and whether a patient should be treated, for
port was that not only did the rates of CDI quickly fall, but the surveillance purposes, the focus has shifted toward metrics that
overall antibiotic days were reduced by 22%--11uggesting that may be easily captured electronically.
these antibiotic days were probably unnecessary as there was no This has led to the development of the LabiD event measure
evidence of increased patient morbidity or mortality due to unin the CDI module for hospital-based reporting to the CDC's
treated infections. National Healthcare Safety Network (NHSN) (165). On the ba-
Another area of prescribing stewardship that has not been sis of the premise that clinicians, laboratories, and healthcare
formally studied as a CDI prevention strategy is PPI prescribing. facilities are ultimately responsible for selecting an appropri-
Although, as mentioned earlier, there is now growing consen- ate population to test, assure specimen quality, and use recom-
sus that PPI exposures are a risk factor for CDI, a program of mended tests, a positive result for a C. difficile diagnostic assay
reducing unnecessary PPI prescribing leading to a reduction is counted as a LabiD event. Because time stamps for both the
of PPI has not thus far been described. While it appears that a admission of a patient to a hospital and the collection of the
large proportion of "PPI-daysw both among inpatients and out- stool sample may be unreliable and are not captured in a con-
patients are unnecessary and could probably be reduced (160), sistent fashion across hospitals, NHSN substitutes a calendar-
the impact of such an intervention is unknown. day algorithm for the 48 hours between admission and onset of
A final area of growing interest in prevention is in the use symptoms. Using the date of admission as day 1, a stool yield-
of probiotics to prevent CDI. Currently, all of the probiotics ing a positive result for C. diffici/e collected on or after day 4 is
sold in the United States are registered by the FDA as nutri- considered an HO-CDI LabiD event. All positive results from
tional supplements, and none have a therapeutic chug claim before this day are considered community-onset (CO) CDI
for the prevention of CDI. As such, they do not undergo the LabiD events. CO cases are further categorized as to whether
same regulatory review to assure potency and safety as drugs they occurred in patients who have been discharged from the
with therapeutic or preventative claims. Nonetheless, there reporting hospital in the previous 4 weeks (hospital-associated) .
are numerous studies suggesting preventive efficacy of certain Along with the information that defines and categorizes a case,
probiotics in preventing both AAD and, increasingly, CDI in NHSN captures patient-day information from the areas of the
particular (132,161). The probiotics with the most data in- hospital where surveillance is being conducted, and the main
clude LactobaciUus spp. and Saccharomyces boulardii, along with metric for tracking and comparison to other rates is the rate of
combinations of Bift.dobacteria spp. with other organisms, often HO-CDI LabiD events per 10,000 patient-days.
LactobaciUus spp. Although the most recent U.S. treatment and It is becoming increasingly clear that HO-CDI rates are sen-
prevention guidelines indicated insufficient data for recom- sitive to factors beyond a hospital's control or, if under their
mending probiotics for prevention of CDI (16), recent sys- control, are associated with improved case finding. Chief
tematic reviews and meta-analysis suggest benefit (132,161). among these is the use of more sensitive diagnostic assays,
However, these reviews also highlight the tremendous heten>- particularly the NAATs, and HO LabiD event rates need to be
geneity of the studies to date in terms of dosages and formula- adjusted by the diagnostic test used to facilitate interhospital
tions used, when the probiotics are started, and how long they comparisons (166) . Another factor is the "prevalence on ad-
are continued in relation to a course of antibiotics, as well as mission" of C. difficile that cannot be reasonably linked in any
the duration of patient follow-up. Finally, there may be adverse way to the care delivered in the hospital (104) . While the true
outcomes from probiotics with rare reports of bacteremia and prevalence of C. diffici/e colonization or infection among all ad-
fungemia among immunocompromised patients with muco- mitted patients is unknown, the rate of CO LabiD events per
sal or bowel wall injury (162,163). Overall, probiotics remain 1,000 admissions should correlate with the prevalence of colo-
a promising approach to prevention although the science re- nization or infection among all admissions (30,60). Because
mains in its infancy. If probiotics are used for prevention, they hospital-associated CO cases, even if previously discharged to
should probably be avoided in patients with very low absolute skilled nursing or other healthcare facility, may reflect the care
neutrophil counts, mucositis, or other bowel injury. previously provided in the hospital (i.e., including possibly un-
necessary antibiotic use), only those CO LabiD events that are
not hospital-associated should be used to adjust a hospital's HO
SURVEILLANCE
rates.
With the rise in the importance of CDI as an HAl in the past An early look at NHSN data from >700 hospitals report-
10 years, there have been several advances in surveillance and ing in 2010 from 28 states overall (but predominantly three
increased understanding of limitations of existing administra- with reporting mandates) showed a pooled rate of 7.4 cases
tive data sources. While hospital discharges for CDI (i.e., ICD9- of HO-CDI (i.e., LabiD events) per 10,000 patient-days (56).
CM 00845) have been helpful for understanding the overall, While this was noted to be twice that of contemporary pooled
hospital characteristic, and regional trends (see Figure 34.2), it rates in England and attributed, at least in part, to their more
is clear that there is too much variation in coding practices and mature national reporting and prevention efforts, -30% ofU.S.
other factors to preclude their use for hospital or even local hospitals had already switched to a NAAT, while very few hos-
and state benchmarking (55,164). Meanwhile, surveillance ad- pitals in England appeared to have done so (117), suggesting
vances include the development of definitions for "cases" of that such an intercountry comparison may be limited without
CDI, including more commonly used laboratory surrogates, risk adjustment. To facilitate both interhospital and eventually
and categorizing them with regard to place of onset and re- interregional comparisons within the United States, a standard-
cent inpatient healthcare exposures (Figure 34.4) (33). While ized infection ratio (SIR) for HO-CDI is under development
a clinical definition such as 2:3 unformed stools (defined as by the CDC at the time of this writing. An SIR is similar to
CMjMr 34 • lnftaitNs GasfromUriti.s 5.23
Admissjon Discharge
+....hours
48 --.
·~ 4
weeks
... 8
weeks
A( I
* I HCFO I CO-HCFA I Indeterminate CA
)
Admission
Discharge
(day 1) (day 4)
+._:: 2J
days ·~ 4
weeks
..
( )
I 1\ I HO I CO-HA I NHA
8 Time
Figure 34.4. Comparison of surveillance definitions for C. diJ!iciltt infection, including (A) a definition for population-
hued surveillance (Adapted &om McDonald LC, Coignard B, Dubberke E, et al. Recommendations for surveillance of
Clostridium dtffic:ilHasociated disease.lnftd OmtrolHosp.EpidntwiL 2007;28:140-145) and (B) a de&nition for hospital-baaed
reponing (Adapted from CDC. NalWMZH«<llAtxmSaftltJ Nttwori (NHSN): M~m Otganism and Clostridium~
lfl:foctilm (MDRO/CDI) Module. Allanta, GA.: CDC; 2011. Available at: http://www.cdc.gov/nhsD/mdro_cdad.html. Acce&Sed
December 15, 2012).
Key for (A): HCFO, healthc:are hdllty-onset (e.g., hoapital- or nursing home-onset); C~CFA, community-onset. healthcare fadlltT-
aiiOdated; CA. comm.unlty4110dated; *, calet with onset dw:iDg th1l period are either CO-HCFA, indeterminate, or CA. depeD.dlng upon time
Iince Jut overnight stay in any healthcare fadllty.
Key for (8}: HO, ho.pital-oruet; CO-HA, community-onset. ha.pital-aNOciated; NHA. not hoipi~ 4 , c:.uea with a C. t.lij]it:i.r.paorllive
rtool aample co11ected during thia period are either CO-HA or NHA. depending upon time Iince Jut overnight stay in the index ha.pital.
a standardized mortality ratio and compares the number of ob- rurgical site infections in 2012 under the same IPPS program, it
served infectious events to the number expected in a particular is anticipated that the number of acute care hospitals reporting
hospital or region on the basis of underlying risk (167). This CDis to NHSN will grow to several thousand and encompass
expected number is modeled from baseline data, and in the the majority of all U.S. acute care hospitals. Hopefully, such
inatance of an initial SIR for CDI, this baseline data will be the national public reporting of hospital CDI rates will spur real
combined data from 2010to 2011. Thus, an SIRof1.0suggests prevention similar to the national program in England where
that a hospital or hospitals in a region performed similarly with HO rates have declined over '75% since 200'7-8 (1'70).
regard to prevention to similar-risk hospitals during the base-
line period, whereas an SIR below or above 1.0 suggests bet-
ter or worse performance. The CUITent risk. adjustment model NOROVIRUSES
under development for use in the SIR will include both of the
important factors mentioned above, along with other factors Norovirwes are a genera of single-stta:nded RNA viruses in
independently associated with higher rates and yet beyond the the Coliciviridoe family. Across all age groups in the commu-
control of the reporting hospital. nity, noroviruses are the leading cause of acute gastroenteri-
By early 2012, there were six states that had mandated pub- tis (AGE) and are the most common cause of gastroenteritis
lic reporting of hospital-wide CDI LabiD events using the CDI outbreaks, including those tr'aD3rnitted from person to person
module of NHSN (i.e., California, lllinois, New York, Oregon, and food.
Thnnessee, and Utah). However, beginning in 2013, reporting Noroviruses were discovered in 19'72 by Kapikian and
of CDis is expected to increase dramatically as m.ch hospital- colleagues from stools collected in 1968 during an outbreak
wide reporting will be incentivized as part of the Center for of gastroenteritis in an elementary school in Norwalk, Ohio.
Medicare Services (CMS) "pay for reporting" program under Formerly referred to as "Norwalk-like viruses" or "small, round-
the Inpatient Prospective Payment Syatem (IPPS) (168). In or- structured viruses," noroviruses are nonenveloped, icosahedral,
der for acute care hospitals nonnally reimbuned by IPPS to re- and small (-!0 nm in diameter). They are genetically diverse
ceive their annu.al payment update, they must begin reporting and have been identified in both humans and animals. Norovi-
these events to NHSN. CDC will rul»equendy send data to CMS ruses have been classified into several different genogroups, GI
Hospital Compare for public posting of HO-CDI SIRs by hospi- to GV, which can be further divided into >25 genetic clusters
tal (169). On the basis of ol»ervatiom from reporting of cen- through sequencing. Only strains within genogroups GI, Gn,
tral line-as.sociated bloodstream infection reponing in 2011 and GN are known to affect humans. Worldwide, Gn viruses
and catheter-associated urinary tract infections and certain cause -75% of all disease in the community (1'71).
N oroviruses are highly infectious agents transmitted through In Europe, approximately one-third of reported outbreaks
a variety of routes, including person-to-person, contaminated occur in hospitals compared with 4% in the United States
food, water, or environmental surfaces, or possibly via airborne (186). It is not known whether this difference in reported out-
droplets. Inununity is complex and incompletely understood, breaks represents a real difference in the epidemiology of out-
but generally regarded to be short-lived, resulting in high rates breaks, an underreporting of hospital outbreaks in the United
of disease across the age range (172). States, or differences in infection control practices in hospitals.
In healthcare settings, outbreaks are largely driven by a
single genotype, GII.4, which causes in the range of 90% of
EPIDEMIOWGY
nosocomial outbreaks. Most studies to date have only quanti-
Noroviruses are now recognized as the most common cause of fied the cost of outbreaks, as opposed to endemic disease,
AGE in the community, the most common cause of outbreaks which is much greater. For example, an outbreak in a single
of gastroenteritis (including foodbome disease), and a key 946-bed U.S. hospital cost an estimated $650,000 (187). Dur-
healthcare-acquired infection in the United States and other ining the 2002 to 2003 season, the cost to the English National
dustrialized countries. In the United States, norovirus causes an Health Service of nosocomial AGE outbreaks was estimated at
estimated 21 million cases of AGE (173), 1.7 million outpatient $184 million (188).
visits (174), 400,000 emergency care visits, 70,000 hospitaliza-
tions (175), and 800 deaths annually across all age groups (51).
CLINICAL PRESENTATION
Globally, norovirus is estimated to account for 12% of all
community- or clinic-based gastroenteritis cases, and 11% of Noroviruses cause AGE in persons of all ages. The illness typi-
emergency department- or hospital-based cases ( 176). Similar cally begins after an incubation period of 12 to 48 hours and
to the influenza virus, antigenic shift of norovirus periodically is characterized by acute-onset, nonbloody diarrhea, vomiting,
occurs, and the burden of disease sometimes increases consid- nausea, and abdominal cramps. Some individuals may experi-
erably in years where novel genogroup II genotype 4 variants ence only vomiting or diarrhea. Low-grade fever and body aches
emerge. For example, in 2002 to 2003 and 2006 to 2007, may also be associated with infection; thus the term "stomach
hospitalizations increased by -50% (177-179). flu" is often used to describe the illness, although there is no
The high incidence of noroviruses is, in part, explained connection to influenza. While symptoms may be severe, they
by their extreme infectiousness and levels of shedding. The typically resolve without treatment after 1 to 3 days in otherwise
infectious dose (ID50 ) is estimated at 18 to 1,000 viral particles, healthy individuals. However, more prolonged courses of ill-
whereas at peak shedding (180), there may be> 109 particles/g ness lasting 4 to 6 days can occur, particularly among children,
of stool (181). Humans are the only known reservoir for human the elderly, and hospitalized patients (188,189).
norovirus infections, and transmission occurs via fecal-oral and Norovirus is shed primarily in the stool but can also be
vomit-oral pathways. This occurs by four general routes: direct found in the vomitus of infected individuals. The virus can be
person-to-person, foodbome, waterborne, or through environ- detected in stool for an average of 4 weeks following infection,
mental fomites. The ability of noroviruses to cause infection in although peak viral shedding occurs 2 to 5 days after infec-
persons exposed to a tiny amount of virus with a short incubation with viral load of -100 billion viral particles per gram of
tion period of <2 days allows this virus to rapidly cause wide- feces (181). However, given the lack of a cell culture system
spread outbreaks with high attack rates. or small animal model for human norovirus, it is not known
Direct person-to-person transmission is believed to be the whether these viruses represent infectious virus and, therefore,
primary mode of spread in most outbreaks (182,183) as well the time after illness at which an infected person is no longer
as sporadic disease (184,185). Person-to-person transmission contagious is unknown. Furthermore, up to 30% of norovirus
may occur directly through the fecal-oral route, by ingestion of infections are asymptomatic, and asymptomatic individuals can
aerosolized vomitus, or by indirect exposure via fomites or con- shed virus, albeit less at lower titer than symptomatic persons
taminated environmental surfaces. The proportion of outbreak (181,190,191). The role of asymptomatic infection in transmis-
spread primarily by person-to-person transmission is highest in sion and outbreaks of norovirus remains unclear.
settings with close contacts, especially healthcare institutions. Although norovirus AGE is typically a mild self-resolving
Direct person-to-person transmission is reported as the primary illness in healthy adults, it can lead to severe dehydration, hos-
route in >90% of norovirus outbreaks in hospitals, LTCFs, and pitalization, and in rare cases, death. These severe outcomes are
schools (182). Infection can occur year-round, but has been re- more common in vulnerable populations such as young chil-
ferred to as the "winter-vomiting" disease because of its winter dren and the elderly residing in LTCFs or hospitals (192,193) .
predilection and number of patients who present with vomiting. In nearly all instances of norovirus-associated death reported
N orovirus outbreaks in LTCFs, hospitals, camps, cruise in the literature, the decedents had other serious underlying
ships, and other areas where crowding occurs are frequently heath conditions, such as immunosuppression (194-197). Data
reported. The most conunon setting for norovirus outbreaks from passive surveillance systems and outbreak investigations
is healthcare facilities. These outbreaks affect both patients/ provide estimates of norovirus case-hospitalization in the range
residents and staff. As such, vulnerable groups of individuals of 0.1 to 5.0 per 1,000 cases (182,193,19S-200). A large system-
are affected, while staff illness leading to absence can result atic review of published outbreak reports estimated norovirus-
in compromised provision of healthcare. Relatively few docu- associated hospitalization and morality rates at 7.0 and 0.7 per
mented acute care hospital-associated outbreaks of norovirus 1,000 cases, respectively ( 192) . The relatively high hospitaliza-
have been reported in the United States; however, data from tion rates in LTCFs and mortality in all healthcare settings un-
other regions that conduct surveillance for these events, such derscore the vulnerability of populations affected by outbreaks
as Europe and Australia, indicate that norovirus is the most in these settings. In addition, data from studies suggest that
common agent causing hospital-associated outbreaks of AGE. GII.4 viruses, which are more common in healthcare facilities,
also result in more severe disease, even after accounting for are not recommended for clinical diagnosis of norovirus infec-
case-mix. tion in sporadic cases of gastroenteritis. However, EIA kits may
Approximately 10% to 12% of individuals with norovirus gas- be of value for screening of multiple fecal samples associated
troen teritis seek medical attention, which may include hospital- with an outbreak of AGE. It is recommended that negative
ization and treatment for dehydration with oral or intravenous samples are confirmed by a second technique such as RT-qPCR.
fluid therapy (201-203). Necrotizing enterocolitis in neonates, In the absence of laboratory confirmation, preliminary
chronic diarrhea in immunosuppressed patients, and postin- ascertainment of norovirus outbreaks can be made on clini-
fectious irritable bowel syndrome have also been reported in cal and epidemiologic characteristics. N orovirus outbreaks are
association with norovirus infection (204-206); however, more characterized by high frequency of vomiting (>50% of affected
data are needed to confirm a causal link with these conditions. persons), median incubation period of 24 to 48 hours, median
Protective immunity to norovirus appears to be different duration of illness lasting from 12 to 60 hours, and no other
from other enteric viral pathogens and is incompletely un- bacterial or parasitic agents identified in stool specimen (212).
derstood. Although seroepidemiologic studies have shown an These criteria, originally proposed by Kaplan et al. in 1982, are
antibody prevalence to norovirus of >80% by age 20, adults reasonably sensitive ( 68%) and highly specific in identifying
consistently demonstrate a high degree of susceptibility to both norovirus outbreaks, and are therefore of use where laboratory
naturally occurring and experimentally administered norovi- tests are not widely available (213).
ruses. Both innate host factors and acquired immunity likely
contribute to the susceptibility to infection (207). Human
SURVEILLANCE
volunteer studies suggest that -50% of individuals develop ill-
ness after challenge, and infected volunteers were susceptible CDC has recently implemented the National Outbreak Re-
to reinfection with the same strain as well as to infection with porting System (NORS) as an integrated national surveillance
heterologous strains, suggesting short-lived and homotypic system for enteric disease outbreaks (214). Launched in Feb-
immunity (207-210). However, it should be noted that the ruary 2009, NORS provides the framework through which all
infectious dose of virus given to volunteers in these challenge outbreaks of enteric disease, regardless of transmission mode,
studies was several thousand-fold greater than the small dose may be reported from state and local health department!! to
of virus capable of causing human illness, and thus immunity the CDC. CDC also coordinates a molecular epidemiologic out-
to a lower, more natural challenge dose might be greater and break surveillance network known as CaliciNet, also launched
more cross-protective. in 2009 (215). State and local public health and food regula-
Histo-blood group antigens (HBGAs), including H type, tory agency laboratories upload norovirus sequences to allow
ABO blood group, and Lewis antigens, are a diverse family of rapid comparison of norovirus sequences with the aim of po-
carbohydrates expressed on mucosal surfaces. Several studies tentially linking outbreaks with a common (e.g., food) source
indicate that they act as putative receptors or coreceptors for as well as to identify emerging norovirus strains.
noroviruses, and there is a strong correlation between poly-
morphic expression of HBGA and human susceptibility to
TREATMENT
norovirus infection (211). However, no single norovirus strain
may be able to cover the whole spectrum of human HBGAs di- No specific treatment exists for calicivirus gastroenteritis, so
versity, although collectively, they are likely to be able to infect treatment is supportive and includes therapy for dehydration
nearly everyone. and electrolyte imbalances. First-line treatment should be oral
rehydration solutions, while severe dehydration or shock may
warrant intravenous fluid therapy. Antiemetics, antimotility
DIAGNOSIS
agents, and antibiotics are generally not recommended (216).
Diagnosis of norovirus is typically by detection of viral nucleic Certain compounds with antiviral properties have shown prom-
acid or, less commonly, of antigen from stool (preferred) and/ ise in laboratory studies, but their value in the clinic remains
or vomitus samples. Whole stools should be collected ideally uncertain, given the short and acute infection caused by cali-
within 72 hours after the onset of symptoms. Most clinical vi- civiruses. No vaccines are currently available, but a number of
rology laboratories presently perform TaqMan-based real-time norovirus vaccines are at various stages of development. The
reverse transcription polymerase chain reaction (RT-PCR) as- product furthest developed is based on recombinant virus-like
says for norovirus detection. Positive samples can subsequently particles (VLPs) and was shown to be safe and immunogenic in
be typed by DNA sequencing of conventional RT-PCR product!!. phase 1 and 2 trials (217) . In a challenge study, where partici-
The samples can then be sequenced at standardized regions pants were vaccinated and subsequently exposed to homotypic
of the viral genome to allow for typing of isolates. Genotyping Norwalk virus, the vaccine was shown to be effective against dis-
information can be useful for establishing links between unease and, to a lesser extent, infection (218).
recognized transmission events or common exposures and for
detecting trends in viral diversity, including the emergence of
PREVENTION AND CONTROL
new strains.
EIAs, given their ease of use and rapid processing time, offer Humans are the only known host of human caliciviruses, so ef-
an attractive alternative to molecular detection assays. However, forts to prevent disease are directed at interrupting the person-
the development of a broadly reactive EIA for noroviruses has to-person transmission cycle, even in the case of contaminated
been challenging because of the number of antigenically dis- food or water. Agents of viral gastroenteritis are essentially
tinct norovirus strains and the high viral load required for a transmitted via the ingestion of infectious fecal (or, less com-
positive signal by these assays. Given the modest performance monly, vomitus) material, so standard sanitation and hygienic
of these commercial kits, particularly their poor sensitivity, they precautions are crucial. These include frequent hand hygiene,
environmental disinfection, proper disposal of fecal or vomit- be transmitted by the same wide variety of transmission routes
soiled materials, and limited contact with ill persons. Even when as the noroviruses. The sapovirus were previously referred
these precautions are put finnly in place, the ability to control to as the "classic caliciviruses" because of their characteristic
outbreaks remains limited (219). morphology; their current name derives from the prototype
The single most important method to prevent norovirus Sapporo viruses, based on the city in Japan of initial discovery.
infection and control transmission is appropriate hand hy- Sapoviruses are divided into at least seven different phyloge-
giene (220,221). Washing with soap and water is the preferred netic clusters, four (GI, Gil, GIV, and GV) of which include
method, with alcohol-based hand sanitizers useful only as an viruses that infect humans, whereas Gill, GVI, and GVII have
adjunct when hands are not visibly soiled (222). The use of only been found in swine (236). Two of these viruses, GI.2 and
alcohol-based hand sanitizers remains controversial, due to GIV, have been most commonly associated with outbreaks in
both inconclusive in vitro finger pad studies (221,223,224) Europe, Asia, and North America, primarily affecting older
and epidemiologic studies where higher outbreak rates have adults (237-239). Additional sapovirus genogroups have been
been detected in LTCFs that use alcohol-based hand sanitizers detected in mink and recently in bats, which illustrates the con-
(225), though the reasons for association in this one study are siderable genetic variability and host range of viruses within the
debated (226). sapovirus genus.
In healthcare fucilities, ill patients may be cohorted together Outbreaks of sapoviru.s-associated AGE have been reported
in an isolatable unit, with the same dedicated nursing staff pro- in settings similar to those ofnoroviruses-schools (240), child
viding care for infected individuals (222). ill patients should not care facilities (241), hospitals (242), LTCFs, and occasional
generally be transferred to unaffected units in the facility-except foodborne outbreaks (243,244). The broad age range of indi-
in the case of medical necessity and after consultation with infec- viduals affected in these outbreaks demonstrates that sapovirus
tion control staff. To minimize the risk of spread from incubat- infection is not restricted to young children, as was previously
ing or asymptomatically infected patients and staff in healthcare thought. Relatively little is known regarding the community
facilities, such individuals should not be transferred to or work in burden of sapoviruses; but the few larger studies performed es-
unaffected areas, typically for 48 hours after exposure. In certain timate the incidence of sapovirus-associated illness in the com-
situations, units in a healthcare facility may be closed to new ad- munity at 1% to 2.6% per year (174). A prospective study of
missions to prevent the introduction of new susceptible patients, Finnish children <2 years of age reported sapoviruses in 9%
though guidelines differ on this point (222,227-229). m
staff of sporadic gastrointestinal illness, compared with rotavirus in
members in healthcare facilities as well as infected food handlers 29% and norovirus in 20% (245).
should be excluded during their illness and for 48 to 72 hours
following resolution of symptoms (214). ill HCWs involved in di- R.OTAVIR.US
rect patient care and handling of hospital food should refrain
from working until24 to 48 hours after symptoms resolve (214). Rotavirus is the leading cause of severe diarrhea in children
Use of proper personal equipment such as gowns, masks, and under the age of 5 years, accounting for one-third to one-half
gloves when cleaning up body fluid spills and disinfecting con- of diarrhea hospitalizations in countries of all income strata
taminated surfaces/fomites is recommended (222). (246). In lower-income countries with suboptimal access to
Other interventions to reduce secondary transmission healthcare, rotavirus is an important cause of childhood mor-
include educating of HCWs and patients regarding the risks tality and was estimated to cause -450,000 deaths in 2008, or
related to and prevention of norovirus transmission, reinforc- about 5% of all child deaths (247,248). In high-income set-
ing appropriate hand hygiene measures, and promptly cleaning tings, deaths from rotavirus are uncommon, but the disease
and containing body fluid spills. Chemical disinfection is an- causes substantial morbidity. In the United States, rotavirus in-
other central approach to interrupt the chain of norovirus trans- fection was responsible for an estimated 55,000 to 70,000 hos-
mission (230,231). The U.S. Environmental Protection Agency pitalizations per year and half a million emergency room and
maintains a list of approved products for norovirus disinfec- outpatient clinic visits before vaccine introduction (249).
tion (232). Largely due to the uncertainty from in vitro studies, Two rotavirus vaccines, a monovalent rotavirus vaccine
chlorine bleach solution is recommended at a concentration (RV1, Rotarix®, GlaxoSmithKline Biologicals) and a pentava-
of 1,000 to 5,000 ppm (5 to 25 tablespoons household bleach lent rotavirus vaccine (RV5, RotaTeq®, Merck Vaccines) are
[5.25%] per gallon of water) for disinfection of hard, nonpo- recommended by the World Health Organization (WHO) for
rous, environmental smfaces whenever feasible (214,233). children in all regions. As of 2011, RV1 and RV5 had been
In healthcare settings, the cleaning products and disinfec- introduced into 27 and 7 programs, respectively, either nation-
tants used should be EPA-registered and have label claims for ally or regionally, with both vaccines being available as part of
use in healthcare settings (214). Hand hygiene is also a key part the national program in some countries.
of the environmental transmission cycle since contaminated In many countries, substantial declines in rotavirus and/ or
hands can transfer virus to touched surfaces, and hands may diarrhea-related hospitalization have been documented follow-
be a vehicle for transferring virus from contaminated surfaces ing vaccine implementation. In the United States, where vac-
back to humans (234). cine was introduced in 2006, a 46% decline in all-cause diarrhea
hospitalizations in children under 5 years of age was observed,
equating to an estimated 40,000 to 60,000 fewer hospitalizations
in 2008 (250). Perhaps most compelling, though, has been the
OTHER VIRAL INFECTIONS observation of decreased gastroenteritis mortality following the
introduction of rotavirus vaccination, an outcome that was not
SAPOVIR.US
evaluated in prelicensure trials. In Mexico, where nationwide
Sapoviruses, like the noroviruses, are a genera of the Caliciviri- rotavirus vaccination was implemented in 2007, mortality de-
dae fumily (235). They share a similar genetic makeup and may clined by 35% in 2008 compared with prevaccine years from
2003 to 2006, with the most pronounced decreases in the vac- 20. Riggi MM, Sethi AK, Zabanky TF, et al. Alymptomatic carn..n are a potential oource fur
tranlllliooion of epidemic and nonepidemic Closlridi1m& dif!irillotraino among long-term
cinated age groups ( <1 year), and during the historic rotavirus care f;ocility reoidenll. Clmlllfocl DiJ. 2007;45:992-998.
season (251). 21. Mi~ima 1', Roberto P, Swale A, et al. Chancteriwion and carriage ratio of C1onridillm dO$
Vaccines also appear to have changed the epidemiology t.Wotraino ioolated from a community-dwelling elderly populatinn in the United Kingdom.
PloS 0.... 2011;6:e22804.
of rotavirus by affecting the transmission dynamics of natural 22. V!Ocidi R, Willey S, BartlettJC. Ioolation rateo and toxigenic potential of CloJtridi""' rJOJjidk
infection. First, indirect benefits appear to have occurred in ioolateo from nrio1u patient populationo. Gtulromlmllltt:J. 1981;81:~.
23. Arono•on B, Mollby R, Nord CE. Anlinlicrobial agents and Clmtridium dijJi<ilc in acute en-
that unvaccinated children have also experienced reduced risk teric dioeaoc: epidemiological data from Sweden,198()..1982.]Jnfoc1Dis. 1985;151 :476--481.
of disease in partially vaccinated populations (250,252,253). 24. Eglow R, Pothoul:alio C, Itzkowitz S, et a!. Diminiohed Cllmridi..., riiffici~ toxin A oemitivity
These indirect benefits may even extend to older children and in newborn rabbit ileum iJ associated with decreased tol:in A receptor. j C1in Invm. 1992;
90:822-329.
adults, groups not previously well recognized to have substan- 25. Keel MK, SongerJG. The attachmcn~ internalization, and tim<>-dependen~ intracellulardiJtri-
tial rotavirus burden. blltion of UoRridium diJ!icil<IDxin A in pon:inc: inlcltinal explant>. lit PutJwL 2011;48:!169-,!80.
Immunity to rotavirus gastroenteritis is generally believed 26. Keel MK, SongerJG. The diJtriblltion and denoity of Clollridill"' rJOffi<Wtolrin recepton on
the inteotinal mucooa of neonatal pig!. lk Padwl. 2007;44:814-822.
to be long-lasting, so disease appears less common-or at 27. Kyne L, Warny M, Qamar A, et al. Aooociation betwtoen antibody "''Ponae to toxin A and
least less frequently requires medical attention-compared protectinn againot recurrent Clmtridium riifficikdianhoea. Llmat. 2001;ll57:189-19ll.
28. Leav BA, Blair B, Leney M, et ill. Serum anti.wrin B antibody correlateo with protection
with children (254). However, outbreaks in LTCFs and acute from recurrent Clollridiwa dif.li<ilcinii:ction (CD I). ~. 2010;28:965-009.
care have been reported with some frequency. In one study in 29. ShimJR,Johnoon S, Samoll' MH, et al. Primary oymptomleu colonioation by CIIJJtridiiiJII
Australia, rotavirus was detected in 13% of gastroenteritis out- riifficikand decrcaoc:d riak of subocquent dianhoca. Llmat. 1998;ll51:6ll!--636.
50. McFarland LV, Mulligan ME, Kwok RY, et ill. Nooocomial acquilition of CloJiri&,.... dOJJidk
breaks in LTCFs (compared to 42% for norovirus) (255). In infection. N Eng!]Ma-L 1989;!20:204--210.
some countries, reducing the burden of nosocomial rotavirus, 51. Johnoon S, Claboll CR, Linn Pv, et al. No1ocomial CllmridiiiJII dif.li<1U colonioation and
dioeaoe. Lancot. 1990;!36:97-100.
primarily in children, was an important factor when consider-
52. Samore MH, DeCimlami PC, Tiucko A, et al. Clorlridi!IJII rJOJjidkcolonization and dianhea
ing whether to introduce rotavirus vaccination (256,257). Nos- at a tertiary care hospital. ClmlnfiCllJiJ. 1994;18:181-187.
ocomial infections are common, especially in children under llll. McDonald LC, Coignard B, Dubberke E, et ill. Recom:mendationo fur ourveillance of C,.,_
lritJiwa d~oociated diaeaoe. Infocl ConlroiHospEpi4fttiol. 2007;28:146-145.
the age of 2 years and in the winter months (258). M. Lowy I, Molrine DC, Lcav BA, et a!. 'lh:atment with monoclonal antibodico against CW..
ll'i.W.. diffirilltoxino. N Eng!]Ma-L 2010;!62:197-205.
55. Pant C, Madonia P, Minocha A, et al. Laboratory marker> ao predictor> of mortality in
patienll with Clmtridium tlq}'icillinfection. j InwnMIIL 2010;58:4!--45.
ACKNOWLEDGMENTS 36. Bauer MP, Henogcno MP, Miller MA, et al Renal :lililure and leukoc:ytooio arc predictors of
a complicated course of Closlridi1m& riiffici/1 infection if measured on day of diagnooio. am
Illfocl DiJ. 2012;55 (mpp12):S149-S153.
We wish to thank Dr. Erik Dubberke, who assisted with the 57. Wanahita A, Goldomith EA, Marino BJ, et al. Clollridium diJfi<Winfection in patienta with
collation of data for Figure 34.2. unexplained lculr.oc:ytooio. Am] MINi 200ll;115:54!--546.
58. Wanahita A, Goldomith EA, Musher DM. Condition• auociated with leukocytooio in a ter-
tiary care ho•pital, with particular att<:ntion to the role of infection cawed by CIIJJtridiiiJII
riifficik Clinlllfocll>os. 2002;34:158&-1592.
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Jeffrey M. Tessier and W. Michael Scheid
Central Nervous Systetn Infections

Healthcare-associated infections (HAis) of the central nervous spinal fusions, and ~.85/100 ventricular shunts (11). From
sy;stem (CNS) are a rare but serious occurrence in the modem 2006 to 2008, as per CDC's National Healthcare Safety Network
hospital. Az. with other types ofHAia, infection of the CNS most (NHSN) report, pooled mean SSI rates for spinal fusions of risk
often follows a procedure that provide& access for microbes index 0 was 0.70 (median 0.74), risk index 1.0 was 1.84 (median
to bypass normal host barriers. While a m,Yority of episodes 1.70), and risk index of 2.0 or 3.0 was 4.15 (median 3.35)
follow neurorurgery (NS), other neuroinvasive procedures (http://www.cdc.gov/nbm/PDFs/dataStat/2009NHSNReport.
(e.g., lumbar puncture or placement of an epidural catheter) PDF). Among patients with higher ASA scores (ie., greater
can occasionally lead to infection of the CNS (1,2). Healthcare- severity of underlying illnesses), longer durations of the proce-
associated CNS infections that are not due to microbial contam- dure, and/or contamination of the wound, higher rates were
ination during procedures generally affect immunosuppressed observed (11). The most conunon infection following NS pro-
patients or neonates who possess an immature blood-brain cedures has been superficial SSI, accounting for 60% of SSis
barrier that may be more easily crossed during bacteremia. after craniotomy and 75% after laminectomy, according to
Healthcare-a.ssociated CNS infections range from superficial NNIS data (4). According to updated NNIS data from january
sw:gical site infections (SSis) as the result of neurosurgery to 1992 through June 2004, the rate of SSI after craniotomy was
meningitis, meningoencephalitis, or focal suppurations in- 2.40/100 operations when patients had a risk index category
cluding brain abscess, rubdural empyema, or epidural abscess. of 2 or 3. 'I1Ws rate was reduced to 1.72/100 operations and
A recent review of healthcare-associated bacterial meningitis 0.91/100 operations when the risk index. category was 1 or 0,
provides the reader with an excellent additional reference to respectively. From 2006 to 2008, the craniotomy SSI pooled
this chapter(~). mean rate for risk index 0 or 1.0 was 2.15 (median, 1.51) and
for risk index 2.0 or 3.0 was 4.66 (http://www.cdc.gov/nhsn/
PDFs/dataStat/2009NHSNReportPDF). Ventricular shunt
INCIDENCE placement resulted in SSI in 5.35/100 operations with a risk
factor index of 1 to 3 compared to 4.42/100 operations with a
Data from the Centers for Disease Control and Prevention's risk factor index of 0 (12). From 2006 to 2008, for ventricular
(CDC) National Nosocomial Infections Surveillance (NNIS) shunts, the pooled mean SSI rate was 4.04 for risk index 0 pa·
program, which were collected in 16~ U.S. hospitals between tients and 5.9~ for risk index 1.0, 2.0, or ~.0 patients (http:/I
1986 and 1993, document 5.6 NS healthcare-associated CNS www.cdc.gov/nhsn/PDFs/dataStat/2009NHSNReport.PDF).
infections for every 100,000 patients discharged (4). This rate Meningitis is the second most common CNS infection after
is approximately half of what it was a quarter of a century ago craniotomy, accounting for 22% of episodes, and it is the most
(1!10,000 discharges) (5). Meningitis is the most conunon common form of CNS infection after ventricular shunt place-
CNS infection, accounting for 91% of the total, followed by ment, accounting for 76% of episodes.
intracranial abscesses in 8% and spinal abscesses in only 1%.
Somewhat higher rates of CNS infection have been observed
among the immunosuppressed, ranging from 20 per 100,000 RISK FACI'ORS
discharges for cancer patient! (6,7) to 2.5 per 100 among heart
transplant patients (8). Meningitis has constituted 71% of CNS The most obvious risk factor for healthcare-associated CNS
infections among cancer patienta, followed by brain abscess infection bas been NS. Skin flora, which usually cannot be
and encephalitis (making up 27% and 2% of episodes, respec- cultured from the operative site immediately after antiseptic
tively) (6). Brain abscess appears to be more common among preparation, regrow during the operation and can be cultured
transplant patient! (see Chapter 45), accounting for -40% from a majority of operative sites just before closure (13). Ju
of CNS infections after heart and heart-lung transplants (9). with other types of surgery, it is thus likely that most infec-
The highest rate of infection for a hospital service has been 45 tions occur during the procedure while the wound is open,
per 100,000 discharges for the newborn nursery, according to becoming contaminated from regrowth of the patient's own
NNIS data collected between 1986 and 1990 (10). skin flora at the margins of the wound or occasionally by or-
The incidence of CNS infection is relatively high among ganisms from the operative team introduced on contami-
NS patients compared with other groups of patients. Among nated gloves or instruments or settling from the air into the
patients with American Society of Anesthesiology (ASA) scores wound. Infection at another body site also is a risk factor for
<~, an operative duration <75th percentile, and a wound clas- infection of the NS wound. In an outbreak of meningitis due
sification of"clean" or "clean contaminated," infection rates in to Klebsiella spp., for example, colonization and/or infection
the NNIS program have been 0.56/100 craniotomies, 0.70/100 of the respiratory or urinary tracts appeared to precede CNS
531
infection (14). Another study found that in 70% of NS patients occurred at a rate of 2.1 episodes per 1,000 procedures. On
with meningitis, there was antecedent or simultaneous isola- multivariate modeling, the use of a positioner was significantly
tion of the same organism from another body site (15). Are- associated with meningitis (OR, 4.5; 95% CI, 1.3 to 17.9), as was
view of 15,200 NS procedures performed at one tertiary care inner-ear malformation with a CSF leak (OR, 9.3; 95% CI, 1.2
center from January 1986 to December 2001 revealed an in- to 94.5) (25).
fection rate of 0.28% (35/12,980) after craniotomy and 1.20% Gliadel® wafers are approved for the treatment of malignant
(27 /2,220) after ventriculostomy or ventriculoperitoneal shunt gliomas. These dime-sized disks contain carmustine (1,3-bis(2-
insertion, with an overall infection rate of0.40% (16). Another chloroethyl)-l-nitrosourea), the primary chemotherapeutic
comprehensive review of 51,133 patients admitted to an NS agent used to treat glioblastoma multiforme. Initial studies re-
service from 1993 to 2002 revealed 51 episodes of healthcare- ported an SSI rate of <5% with wafer insertion, but subsequent
associated meningitis, all of which were associated with NS reports revealed infection rates of 15% to 23%. A 2003 review
intervention. Ventriculoperitoneal shunt procedures, either of 32 patients who received a Gliadel® wafer identified nine pa-
insertion or revision, accounted for 26% of the episodes. The tients who developed an SSI. Among these nine patients, there
next largest group consisted of patients undergoing surgery for were four episodes of brain abscess, four of bone flap osteitis,
an intracranial mass (17). A total of74% of bacterial meningitis two of epidural abscess, and one each of cellulitis and subgaleal
in 61 patients aged 17 to 40 years identified in Taiwan had a abscess associated with wafer insertion (26).
postneurosurgical state as an underlying condition (18). Patients with head trauma are at increased risk of CNS infec-
The factors that amplify the risk of postcraniotomy infection tion, especially meningitis. CSF fistula raises the risk of infec-
have included duration of the operation, external drainage, re- tion in this population. A CSF leak was found to be present in
exploration, and operation through a paranasal sinus (19). The 13% of episodes of healthcare-ru~sociated meningitis after head
risk factors contributing to the development of meningitis/ trauma in one series (27). Infection of the paranasal sinuses
ventriculitis after placement of a ventriculostomy catheter may be followed by CNS infection in these patients (28).
have included intracerebral hemorrhage, other NS operations, A rare but important risk factor for healthcare-associated
drainage for >5 days, an air-vented system, irrigation of the sys- bacterial meningitis to consider is the diagnosis of acute bac-
tem, and intracranial pressure >20 mm Hg (19,20). The risk terial meningitis (ABM) itself. This phenomenon of "super-
for infection of cerebrospinal fluid (CSF) shunts is increased infection" has been studied by Huang et al., who reported
by the duration of the procedure, thrombosis of the catheter, 21 patients with 27 episodes of healthcare-associated menin-
externalization of the shunt, inexperience on the part of the gitis after being diagnosed with ABM over a 9.5-year period
surgeon, and type of shunt (ventriculoatrial carrying a higher in Taiwan (29). Superinfection was identified in this study as
risk than ventriculoperitoneal shunting) (19). A persistent CSF growth of a new pathogen from the CSF during the therapeu-
leak after surgery heightened the risk of infection Ul-fold in tic course of existing meningitis. All 21 patients underwent a
one study (21); concurrent infection at a remote site increased neurosurgical procedure/device (External ventricular drains
the risk of CNS infection &.fold. (EVD), VP shunt, or Ommaya reservoir) temporally associated
Korinek et al. prospectively evaluated every adult patient with the superinfection. Recurrent fever was the most common
undergoing craniotomy in 10 NS units during a 15-month clinical finding, and the recovered CSF pathogens implicated
period. Of the 2,944 patients studied, 117 patients developed in the superinfections were predominantly drug-resistant gram-
SSis. Independent SSI risk factors were postoperative CSF leak- negative bacilli. Superinfections were associated with a high
age (odds ratio [OR], 145; 95% confidence interval [CI], 72 to mortality rate (33.3%) .
293) and subsequent operation (OR, 7; 95% CI, 4 to 12). Inde- Premature birth also appears to be an important risk fac-
pendent predictive risk factors were emergency surgery, clean- tor for CNS infection because neonates cared for in neonatal
contaminated and dirty surgery, an operative time >4 hours, intensive care units (NICUs) have had the highest rates ofCNS
and recent NS. Absence of antibiotic prophylaxis was not a risk infection according to NNIS data (1 0) . This finding seems to be
factor. The investigators also found that the NNIS risk index related to the high risk of bacteremia from critical care instru-
was effective in identifying at-risk patients (22). mentation coupled with an increased risk of secondary menin-
Placement of an intracranial pressure monitor is associated gitis from bacteremia stemming from the neonate's immature
with different rates of infection, depending on where the moni- blood-brain barrier. Immunosuppression is another important
tor is positioned. One study found a 7.5% infection rate with a risk factor for nonsurgical CNS infection, usually due to hema-
subarachnoid screw, a 14.9% rate with a subdural cup catheter, togenous spread.
and a 21.9% rate for a ventriculostomy catheter (23). Another
study found a 0.6% rate for epidural monitors, a 3.0% rate for a
subdural bolt, and a 4.0% rate for intraventricular or parenchy- ETIOWGIC AGENTS
mal brain monitors (24).
In June 2002, a manufacturer of cochlear implants used to Staphylococci and gram-negative bacilli accounted for almost
enhance the perception of sounds in patients with severe to 70% of CNS infections documented in NNIS hospitals between
profound hearing lOllS notified the Food and Drug Administra- 1986 and 1992 (4). During this time, Staphylococcus aunous was
tion (FDA) of 15 reports of postimplantation bacterial meningi- the most common pathogen after both craniotomy and lami-
tis in patients who received these implants. This led to a cohort nectomy, followed by coagulase-negative staphylococci. These
study to determine the incidence of bacterial meningitis among organisms were followed by enterococci, Streptococcus spp., Pseu-
children with cochlear implants and a nested case-control study domrmas aeruginosa, Acinetobacter spp., Citrobacter spp., Entero-
to examine the risk factors for meningitis. The incidence of bacter spp., Kkbsiella pneumoniae, Escherichia coli, miscellaneous
all episodes of meningitis in the cohort was 239.3/100,000 other gram-negative bacilli, and yeast, each of which accounted
person-years (95% CI, 156.4 to 350.6). Perioperative meningitis for <10% of episodes. Mter shunt procedures, S. aunous
Chapter 35 • Central Nervous System Infections 533
remained the most common pathogen causing superficial SSis, neurosurgery (45%), CSF leaks (17%), and head trauma
but coagulase-negative staphylococci were more typical causes (12%). MRSA meningitis in this study carried a 30-d.ay mortal-
of deeper SSis; gram-negative bacilli were responsible for 19% ity of31 %, and multivariate analysis identified spontaneous ori-
of deeper SSis related to shunts (4). Streptococcus pneumcmiae was gin (i.e., not identified as healthcare-associated in origin; OR,
the predominant pathogen in the cohort of children with bacte- 21.4; 95% CI, 2.3 to 195.4; p = .007) and development of coma
rial meningitis as a complication of cochlear implants (15/24), (OR, 9.7; 95% CI, 2.2 to 42.3; p = .002) as independent predic-
and Staphylococcus spp. were predominantly isolated after infec- tors of death.
tious complications of GliadeJ® wafer insertion (25,26). A. baumannii has become a more commonly reported patho-
If all CNS infections are considered, coagulase-negative gen in episodes ofhealthcare-associated meningitis throughout
staphylococci were the most frequent pathogens, making up the world, a phenomenon attributed to the use of broad-
31% of episodes compared with 27% for gram-negative bacilli, spectrum antimicrobials, especially carbapenems, and the
11% for Staphyloroccus aumt.S, 18% for Streptococcus spp., 4% emergence of carbapenem-resistant A. baumannii strains. The
for yeast, and 9% for others ( 4). For meningitis, the most fre- mortality of A. baumannii meningitis (ABM) reported in pub-
quently encountered CNS infection, coagulase-negative staphy- lished studies is high, in the range of 30% to 70%, depending
lococci accounted for 32%, followed by gram-negative bacilli on the report ( 32-34), and appears related to the antimicrobial
(29%), Streptococcus spp. (18%), S. aureus (10%), yeast (4%), activity of empiric drug selection.
and others (9%) ( 4). For intracranial infections, gram-negative Candida spp. are infrequently implicated as causative agents
bacilli were the cause of 23% of episodes, followed by S. aumt.S in healthcare-associated CNS HAis. O'Brien et al. performed
(19%), coagulase-negative staphylococci (17%), anaerobes a retrospective, single-center study of Candida CNS infections
(11%), fungi (8%), Streptococcusspp. (8%), viruses (4%), yeast after NS over an 11-year period (1998 to 2009) (35) . They iden-
(3%), and others (8%). Spinal abscess displayed a dramatically tified 11 episodes via laboratory review of positive cultures from
different distribution of etiologic agents: 67% were due to S. au- CNS specimens. Candida albicans was the most commonly iden-
reus and 33% were due to coagulase-negative staphylococci ( 4). tified yeast (73%), and all of the episodes were associated with
The largest study of healthcare-associated meningitis from a the presence of foreign material in the CNS (nine EVD, one VP
single hospital was conducted by Durand et al., who reviewed shunt, one lumbar drain, one Gliadel® wafer).
197 episodes among 151 adult patients at Massachusetts Gen- Although large outbreaks of fungal meningitis are very rare,
eral Hospital during a 27-year period (27). These healthcare- in 2012 to 2013, there was a very large outbreak of fungal men-
associated episodes accounted for 40% of the total of 493 ingitis and spinal epidural abscesses traced to epidural or para-
episodes of bacterial meningitis observed during the study pe- spinal glucocorticoid injections of intrinsically contaminated
riod. The proportion of episodes that were HAis increased dur- preservative-free methylprednisolone acetate prepared by a
ing the 27-year period. In this study, gram-negative bacilli were single compounding pharmacy (36).
most common, accounting for 38% of episodes, followed by Pathogens most frequently isolated from brain abscesses have
S. aureus (9%), coagulase-negative staphylococci (9%), Streptococ- traditionally been streptococci, Enterobacteriaceae, and anaer-
cus spp. (9%), Haemophilus influenzae (4%), Listeria monocytogrmes obes. However, a recent prospective study of bacteria associated
(3%), andEnterococcusspp. (3%) (27). The microbesresponsible with 20 brain abscesses in Marseilles, France, utilized 16S rRNA
for healthcare-associated gram-negative meningitis in this study sequencing to identifY fastidious organisms (37). Tiris study
were E. coli (30%), Klebsiella (23%), Pseudmnnnas (11 %), Acineto- found an extremely broad array of bacteria in brain abscesses,
bacter (11%), Enterobacter (9%), Serratia (9%), Citrobacter (4%), including several new organisms not previously described, and
Proteus (2%), coliform types (2%), and nonenteric types (2%) confirmed the polymicrobial nature of these infections. Con-
(27). The higher proportion of gram-negative and lower pro- ventional culture techniques identified a total of 22 species
portion of staphylococcal isolates in this study than in the more of bacteria in this study, whereas multiple sequencing of 16S
recent NNIS data could be due to the fact that there were only rRNA identified 72 species. Importantly, Mycoplasma spp. were
2 years of overlap between the 27-year study and the NNIS data. commonly identified in brain abscesses (25% of specimens);
In Wang's review of 15,200 operative NS procedures from this genus has not traditionally been considered when design-
1986 to 2001, the most frequently isolated pathogen was S. aumu ing empiric antimicrobial regimens to treat brain abscesses.
(13/62, 21 %); 91% of episodes involved a single pathogen with Among immunocompromised patients, the frequency distri-
coagulase-negative Staphylococcus (7/62, 11%), P. aeruginosa bution of etiologic agents is somewhat different; To"oplasma
(5/62, 8%), E. coli (5/62, 8%), and Acinetobacter haumannii grmdii and Cryptococcus neoformans are most frequent in patients
(4/62, 6%) following S. aumu in frequency (16). A review of with the acquired immunodeficiency syndrome, Aspergillus
S. aumuCNS infections in Denmark over a 16-year period (1984 spp. and T. grmdii are the most common after heart and
to 1999) identified 45 episodes of meningitis and 5 episodes of heart-lung transplants, and Aspergillus spp. and C. neoformans
brain abscess. Forty-four of these episodes were HAis, and only are the most typical after kidney and liver transplants (38).
six were community-acquired. None of the isolates was methicil- Among bone marrow transplant recipients, fungi accounted
lin- resistant, and six were penicillin-susceptible (30). for 92% of episodes in a comprehensive study: Aspergillus spp.
Methicillin-resistant Staphylococcus aumt.S (MRSA) now rep- in 58% of episodes and Candida spp. in 33% (38). A South
resents a substantial percentage of S. aumu isolates in most African, single-center, retrospective study of brain abscesses re-
hospitals in the United States and other countries around the quiring surgical intervention (N = 121) found Nocardia spp.
world. A recent multi-institutional study from Spain examined in 2.5% of patients (39); these organisms are well-described
86 episodes of MRSA meningitis, with 80 of these being identi- causes of community-acquired infections in immunocompro-
fied as healthcare-associated (93%) (31). The vast majority of mised patients. A retrospective hospital-based epidemiologic
healthcare-associated episodes (78/80, 97.5%) were postopera- study identified 153 patients with brain abscess over a 15-year
tive complications, mainly associated with CSF devices (74%), period ( 1986 to 2000) . There were 103 community-acquired
infections and 20 HAis. Of the HAis, 17 occurred in a post- Because the clinical picture often is more difficult to inter-
neurosurgical state. Overall, K pneumoniati and vi.ridans strepto- pret for healthcare-associated than for community-acquired
cocci were the two most prevalent pathogens, and the addition meningitis, CSF analysis is correspondingly more important
of S. aurew accounted for 4 7% of post-NS brain abscesses ( 40). for confirming the diagnosis. Unfortunately, CSF abnormali-
Outbreaks of CNS infection among neonates or in NS ties due to underlying disease, nonsurgical interventions (e.g.,
patients most often have involved aerobic gram-negative bacilli drug therapy), and/or aseptic inflammation after NS can result
(12,41-45). Such outbreaks sometimes have been linked to a in confusion, especially very early after surgery (61). Adminis-
healthcare provider carrying the organism (46) and at other tration of OKT3 (muromonab-CD3) has been associated with
times to contaminated equipment, such as respirators ( 47) or the development of aseptic meningitis in transplant patients
a shaving brush used for preoperative hair removal (45). A re- with negative culture results for bacteria, fungi, or viruses (62).
view of 30 adult patients with gram-negative bacillary meningitis The CSF findings most predictive of healthcare-associated bac-
found that the majority of episodes occurred in men and that terial meningitis have been neutrophilic pleocytosis, with most
E. coli was isolated most frequently ( 48). Outbreaks due to gram- who are affected having a CSF white blood cell (WBC) con-
positive bacteria, such as Streptoroccus spp. (both groups A and B), centration > 1,000/mm5 (and almost all having a CSF WBC
S. aurew, and L. monocytogmes, also have been reported ( 49-57). concentration >100/mm5), >50% neutrophils, and hypogly-
Secondary spread of Neisseria meningitidis or H. injl'I.Ufi'IUJe within corrhachia (usually <40 mg/dL). Hypoglycorrhachia appears
the hospital setting appears to be rare (56-58). to be the most reliable indicator of infection in the absence
Insofar as drug therapies can be considered "healthcare- of positive results on Gram's stain or culture (15). CSF lactate
associatedw causes of disease, drug-induced aseptic meningitis has shown some promise as a marker of bacterial meningitis
(DIAM) must be considered in the differential diagnosis of poin post-NS patients. When a CSF concentration of 4.0 mmoi/L
tential CNS infections. A very broad array of drugs, biological was used as a cutoff value for the diagnosis, the sensitivity was
therapeutics, and medical devices have been associated with 88%, the specificity was 98%, the positive predictive value was
DIAM. Hopkins andjolles provide an excellent comprehensive 96%, and the negative predictive value was 94% (63). Recent
review of drugs and other therapies implicated in DIAM (59). guidelines for the management of bacterial meningitis have
suggested that empiric antibiotic therapy should be initiated
when CSF lactate concentrations are 2:4.0 mmol/L. However,
CLINICAL MANIFESTATIONS it must be realized that there are many other reasons for an
elevated CSF lactate concentration, including cerebral hypoxia
AND DIAGNOSIS
or ischemia, anaerobic glycolysis, vascular compromise, and
metabolism ofCSF leukocytes (64).
MENINGffiS
Other CSF biomarkers have been investigated as adjuncts in
The typical manifestations of meningitis-fever, headache, the diagnosis of meningitis due to a variety of pathogens. CSF
neck stiffness, and depressed level of consciousness-usually matrix metalloprotease (MMP) concentrations may become
are present with healthcare-associated CNS infection, but the useful markers to differentiate meningitis due to bacteria from
last three of these symptoms and signs are also frequently pres- other etiologies. Green et al. examined CSF MMP concentra-
ent in post-NS patients who do not have meningitis. These find- tions in Vietnamese patients presenting with meningitis due to
ings may stem from the underlying disease or the surgery. For various etiologies and found significant elevations in the CSF
this reason, changes in the degree of these symptoms and signs concentrations of MMP-1, -3, -8, and -9 in patients with bacte-
over time may be more important indications than their mere rial meningitis when compared to those with meningitis from
presence. Meningitis usually begins within 10 days of NS and other infectious etiologies or noninfected controls (65). Serum
almost always within a month. Fever is the most reliable single procalcitonin (PCT) level has been investigated as a marker to
sign because usually it is not seen in postsurgical patients and differentiate bacterial from aseptic meningitis in children and
because it is a component of almost all healthcare-associated maybe useful as an adjunct in the triage of pediatric patients in
meningitis episodes; 94% of patients with meningitis after NS an emergency setting, but PCT has not been studied as a diag-
had fever within the first day of illness in one study ( 15). In nostic tool in other populations such as post-NS patients (66).
Wang's review of 15,200 patients undergoing NS, 62 episodes Gram's stain confinned the presence of a pathogen in
of postsurgical meningitis occurred. Fever occurred in 54 of ~50% and culture in 83% of healthcare-associated meningitis
these patients, and all but 13 patients had a disturbance of episodes in one large study (27). Mter NS, Gram's stain in-
conscious state (16). Fever was also a prominent finding in dicated Candida spp. to be the causative agent in 36% of 18
a review of 30 episodes of gram-negative bacillary meningitis reported episodes; it is worth noting that Candida spp. men-
(27/30) (48). ingitis resulted in neutrophilic pleocytosis in 62%, with CSF
These usual clinical manifestations are more diagnostically WBC counts ranging from 13 to 8,000/mm! and a CSF glucose
useful indicators in nonsurgical patients with some exceptions, level of <40 mg/dL in only 12% (67). False-positive results of
such as neonates and the immunosuppressed. Neonates with Gram's stains reportedly have been due to organisms in stain
meningitis usually have fever, but may fail to manifest other reagents, on glass slides, in media used for swabs, or in tubes
classic findings of meningitis, such as nuchal rigidity or a bulg- used to centrifuge the CSF (68,69,70). Culture results often
ing fontanelle. Instead, there may be a weak cry, decreased will be rendered negative within 24 hours of starting antibiotic
muscle tone, lack of movement, poor suck, diarrhea, vomiting, therapy, but changes in glucose, protein, and WBCs usually take
dyspnea, or apnea (59). Likewise, the geriatric patient may not days to detect (71). Antigen detection testing is seldom help-
show the classic symptoms or signs of meningitis. High-dose ful in healthcare-associated meningitis, but may be useful for
corticosteroid therapy or severe neutropenia also may signifi- detecting C. neofurmans (cryptococcal antigen), AspergiUus spp.
cantly alter the clinical presentation of meningitis (8,60). (galactomannan, _,8.D-glucan), Candida spp. (,8-D-glucan), and
Histoplasma capsulatum or Blastomyces dermatitidis (Histoplasma an increase in seizure activity, and no symptoms suggestive of
and/or Blastomyces antigens) in select patient populations. infection (26).
FOREIGN BODY-ASSOCIATED INFECTION BRAIN ABSCESS

Infection of a shunt is classified by the CDC as an HAI ifit occurs Brain abscess can occur after NS, paracranial infections
< 1 year of placement, although most episodes occur within the (sinuses, ears, dental), sinus surgery, bloodstream infection,
first 2 months. Pathogens such as S. aureus are associated with or penetrating head trauma (e.g., gunshot wounds) (78-82).
early-onset infections, whereas coagulase-negative staphylo- Headache, fever, and focal neurologic abnormalities are the
cocci are associated with a later-onset infection (72,73). Fever most typical findings while seizures, nuchal rigidity, nausea,
is the most reliable symptom (74). Infection of the proximal vomiting, and papilledema can each be seen in up to half of
end of a ventricular shunt often results in symptoms of shunt the patients. Magnetic resonance imaging (MRI) is more useful
obstruction (e.g., nausea, vomiting, or headache). Nuchal ri- than computerized tomography (CT), and is the imaging pro-
gidity is present in one-third (72) of episodes. The symptoms cedure of choice, in confirming the anatomic location and size
and signs of distal infection of a shunt depend on the location oflesions. Stereotactic aspiration with CT guidance can be used
of the tip. With ventriculoperitoneal shunts, peritonitis is the for therapeutic drainage and for obtaining fluid for cytologic
usual manifestation, but intestinal obstruction, intestinal perfo- and microbiologic stains and cultures to guide therapy.
ration, and intra-abdominal abscesses have each been reported.
Aseptic inflammation around the distal end has resulted in the
~GOENCEPHALnnS
development of a peritoneal pseudocyst (75). A tunnel infec-
tion with inflammation along the catheter may be seen. Meningoencephalitis involves inflammation of brain paren-
Ventriculopleural shunts may result in empyema with distal chyma and the meninges. Meningoencephalitis has occurred in
infection, whereas ventriculoatrial catheters can be character- rare episodes as an HAI after comeal or dural transplants taken
ized by symptoms of endocarditis (e.g., lethargy and fever of from cadavers and after NS using contaminated instruments
several weeks' duration). In these instances, blood cultures usu- or electrodes. Both rabies virus and the agent of Creutzfeldt-
ally are positive, and nephritis may be detected by urinalysis Jakob disease (CJD) have been transmitted in this manner.
and serum creatinine measurement. When a shunt infection The incubation period for rabies following transplantation was
is suspected, aspiration of shunt fluid is indicated for cytology, 1 month; for CJD, it was about 18 months (19).
Gram's stain, and culture. The sensitivity of the Gram's stain CJD is a rapidly dementing illness with prominent myoc-
of such aspirates is -50% and of culture -80% ( 4). Nine of lonus. Hypokinesia, rigidity, nystagmus, tremor, or ataxia may
10 patients with shunt infection will have > 100 WBCs/mm!l of each be present in >50% of patients. Seizures occur in 10%
CSF. Glucose and protein determinations on CSF from a shunt to 20% of patients. The disease generally ends with coma and
have not proved useful (76). Most studies of CSF shunt infec- death after 7 to 9 months. Rabies begins with a prodrome of
tions have focused on pediatric populations; the limited data nonspecific symptoms (e.g., fever, headache, malaise, anorexia,
available on these infections in adults were extended by Conen nausea, vomiting, or diarrhea). The prodrome is followed after
et al. (77). These investigators performed a retrospective, 2 to 20 days by an acute neurologic phase, which may be char-
single-center study of patients aged> 12 years (median age, 50) acterized by hyperactivity and disorientation (furious rabies) or
who were diagnosed with CSF shunt infections (N = 78 infec- by paralysis. Coma usually supervenes within 10 days of the on-
tion episodes) between 1996 and 2006. Fever was present in set of neurologic symptoms and may last for hours in untreated
78%, neck stiffness in 45%, and local signs of infections in 49%. patients to months in treated patients. The average duration
CSF WBC counts were >5,000/mms in 80% of patients, and of coma is 7 days in untreated patients and 13 days in patients
CSF lactate concentrations were > 1.9 mmol/L in 81%. receiving intensive care. Until 2005, only three recoveries
In the study of children with cochlear implants, episodes of from rabies had been reported. A fourth recovery was recently
possible meningitis were associated with a CSF WBC concen- documented after a phenobarbital coma was induced and the
tration of 300 to 6,115/mm3 , and in all but one patient, there patient was treated with ketamine, midazolam, ribavirin, and
was a predominance of neutrophils. Nine episodes of bacterial amantadine (83).
meningitis were perioperative (occurring :530 days after sur- Several pathogens associated with meningoencephalitis
gery); 20 episodes were sporadic and occurred 2:30 days after have been transmitted via organ transplantation and need to
surgery. Eight of these 20 patients had evidence of otitis media be considered when evaluating transplant recipients with signs
at presentation. In 11 out of the 15 patients with S. Jmeumoniae or symptoms of meningitis and/ or encephalitis. West Nile virus
infection, meningitis was associated with bacteremia, and one (WNV) has been transmitted via solid organ transplantation,
patient had pneumonia. Two patients had received one dose of blood transfusion, and granulocyte infusion (84-86). Lympho-
7-valent pneumococcal conjugate vaccine. One other child had cytic choriomeningitis virus (LCMV) also has been transmitted
received two doses of the same vaccine and had S. Jmeumoniae via organ transplantation and was associated with a very high
meningitis caused by serotype 1OA, which is not included in the mortality, with seven of the eight organ recipients dying from
vaccine. Two children had meningitis caused by H. injluenzae LCMV infection (87). C. neoformans has been transmitted via
type b (Hib). One child was fully vaccinated against Hib, and transplantation of liver and kidneys from a donor who died
the other had received three of the four recommended doses with an undiagnosed neurologic condition, later confirmed at
of Hib vaccine (25). In the four patients who developed brain autopsy to be cryptococcal meningitis (88). Interestingly, only
abscess after GliadeJ® wafer insertion, the abscesses were diag- one of the three organ recipients from this donor developed
nosed 22 to 159 days after implantation. One patient had an un- cryptococcal meningitis (kidney recipient), while the other two
usual presentation that included focal neurological symptoms, developed pneumonia syndromes (one kidney recipient, one
liver recipient). Finally, Balamuthia mandrillaris, a free-living CSF shunt infections were associated with an attributable
amoeba associated with highly fatal meningoencephalitis, has mortality rate of 23% in a study by Schoenbaum et al. (72).
been transmitted by transplantation of heart, liver, and kidneys Walters et al. confirmed the mortality associated with shunt in-
into four recipients (89). Remarkably, three of the four (recipi- fections and found a doubling of the case-fatality rate, a tripling
ents of heart, liver, and one kidney) were alive at the time of of the number of additional surgical procedures, and signifi-
the CDC Morbidity and Mortality Report (MMWR), with only cant prolongation of hospital stay among survivors (91). The
one of these suffering residual neurologic sequelae; one of the type of therapy appears to have an important effect on the out-
kidney recipients died from amoebic encephalitis on posttrans- come. Antimicrobial therapy alone had a 36% success rate in
plant day 75. treating shunt infections in one study compared with 65% for
antimicrobial therapy and immediate shunt removal and 96%
for shunt removal, antibiotic therapy, and ventricular aspirates
SPINAL EPIDURAL ABSCESS
or external drainage (92). Mayhall et al. found a case-fatality
The classic stages of an epidural abscess are back pain, radicular rate of 100% among untreated patients with ventriculostomy
pain, radicular weakness, and then paralysis. Other symptoms infection (20). A decline in cognitive ability has been docu-
may include bowel and/or bladder dysfunction, sensory defi- mented following shunt infections (93). One of the children
cits, stiff neck, and altered mental status. Fever usually is pres- with cochlear implant-associated meningitis died, and three
ent at the time of diagnosis. Laboratory evaluation of peripheral required removal of the implant (25).
blood usually demonstrates leukocytosis and an elevated eryth- Brain abscess is associated with a case-fatality rate of -10%
rocyte sedimentation rate. MRl with gadolinium-DTPA contrast (78,80) and permanent neurologic side effects in almost 50%
allows the best delineation of an abscess in preparation for sur- of the survivors (79,81). Adverse prognostic factors include
gery, which is done rapidly to preserve or salvage cord function. very young or very old age, ventricular rupture, delay of anti-
microbial therapy, altered mental status at diagnosis, larger size
and greater number of abscesses, or fungal or gram-negative
SUBDURAL EMPYEMA
bacillary pathogens (79,81-82). Spinal epidural abscess was as-
Cranial subdural empyema can follow paranasal sinusitis, otitis sociated with a case-fatality rate of 13% in a review of seven
media, penetrating trauma, or an NS procedure. The symptoms case-series including 188 patients (94), but a more recent study
generally begin with fever and headache followed by seizures, of 43 patients reported only two deaths (5%) (95). Paralysis
altered mental status, focal neurologic symptoms, nausea, and was observed in 22% of patients in the review (94) and 20%
vomiting. CT scan or MRl can be used to differentiate empy- of patients in the more recent series (95). Intracranial subdu-
ema from brain abscess. Spinal subdural empyemas have oc- ral empyema is associated with a case-fatality rate of 20% to
curred very rarely and show symptoms similar to spinal epidural 30% and a high incidence of seizures and other side effects in
abscess, but tenderness may be absent on physical exam (4). survivors (96). The most common CNS infection after NS-
superficial SSI-has little effect on mortality, but does prolong
hospital stay (4).
PROGNOSIS Prognosis often is related to the specific cause of the CNS
infection. In the study by Durand et al., case-fatality rates for
CNS infections are regarded as being among the most serious the three most common HAl pathogen groups were 36%
because of the potentially disabling morbidity and mortality. for gram-negative bacilli, 39% for S. aureus, and 0% (0/16)
Of the 53 deaths among patients with CNS infection in NNIS for coagulase-negative staphylococci (27). The etiologic agent
hospitals between 1988 and 1993,49 (92%) of the deaths were has an important effect on prognosis among the immunosup-
either caused or contributed to by the infection rather than pressed, with case-fatality rates of 84% for gram-negative bacilli,
a preexisting illness ( 4). The case-fatality rate for healthcare- 24% for S. aureus, and 37% for L. monocytogmes (8,97). The use
associated bacterial meningitis in the study by Durand et al. of voriconazole has improved survival in the setting of invasive
was 35% compared with 25% for community-acquired bacte- aspergillosis. In one study, voriconazole improved survival at
rial meningitis in adults (27). In the comprehensive review of 12 weeks from 57.9% with amphotericin B treatment to 70.8%
15,200 NS patients, the overall mortality of the 62 patients with (98). The type of underlying illness also affects prognosis in
meningitis was -34% (21/62). Death most often was associ- immunosuppressed patients with CNS infection. Case-fatality
ated with sepsis (14/21). Of the 41 surviving patients, 19 were rates of 90% have been observed among patients with leuke-
vegetative or had severe neurologic deficits (16). In the study mia, compared with 77% for lymphoma and 59% for solid tu-
of 30 gram-negative bacillary meningitis patients, death oc- mors of the head or spine ( 6,97).
curred in 11 patients. Inappropriate antibiotics were given to
8 patients, and all8 patients died (48).
The mortality for post-NS bacterial meningitis caused by PREVENTION
gram-negative pathogens may be directly related to the empiric
antimicrobial regimen used for initial therapy. In a retrospec- Because most healthcare-associated CNS infections are related
tive study of A. baumannii meningitis, Tuon et al. found that to surgery, efforts to prevent these infections prominently in-
inappropriate antimicrobial therapy within 5 days of CSF col- dude general measures for the prevention of SSI, which is dis-
lection was an independent predictor of mortality from this cussed in detail in Chapter 36. Such measures include strict
infection (34). A Taiwanese study of post-NS bacterial men- attention to antiseptic preparation of the skin and aseptic
ingitis identified gram-negative resistance to third-generation technique, hair removal by depilatory or clipping rather than
cephalosporins (ceftriaxone, ceftazidime) as a risk factor for shaving, and minimizing the duration of operation while avoid-
mortality, with an adjusted OR of 33.65 (p = .047) (90). ing hemorrhage or creation of a CSF fistula, both of which can
promote infection. Prophylactic antibiotics reduce the risk of catheter placed with systemic antimicrobials for EVD dura-
HAl with craniotomy at least 3-fold. However, a large study by tion and found no difference in the rate of HAis between the
Korinek et al. provides evidence that most of the prevented in- groups (57% vs. 51%), suggesting that the use of the antibiotic-
fections are incisional, and not meningitis, at least for antibiotic impregnated EVD catheter was as effective as systemic antimi-
prophylaxis used in craniotomy patients (99). Either cefazolin crobials for the prevention ofEVD-related HAis (115) . A more
or vancomycin is acceptable because most infections are caused recent trial prospectively evaluated a silver-impregnated EVD
by staphylococci (100). Cefazolin would be preferred for hospi- catheter compared to a plain catheter. This study was done as
tals with low rates ofMRSA infection (see Chapter 41) because a blinded, randomized controlled trial at two hospitals in the
high usage of vancomycin appears to select for vancomycin- United Kingdom between 2005 and 2009 (116). There was
resistant enterococci (see Chapter 41) within an institution a significantly lower rate (p = .0427) of CSF infection in the
(101). In hospitals with high rates ofMRSA infection, however, silver catheter arm (12.3%, 17 of 138) compared to the plain
vancomycin would be the preferred agent. Owing to the con- catheter group (21.4%, 30 of 140), supporting the use of the
cern for staphylococcal infection, current guidelines recom- silver-impregnated EVD catheters for the prevention of CSF
mend the use of either cefazolin or vancomycin for a patient infection. A meta-analysis of mainly observational studies sug-
undergoing craniotomy (102). Prevention ofMRSA and meth- gests that antimicrobial-impregnated catheters may be an effec-
icillin-sensitive S. aureus infections in NS implant patients is en- tive way of reducing the incidence of shunt and EVD infections.
hanced with preoperative screening and decolonization before Well-designed multicenter randomized controlled trials are
the surgical procedure. urgently needed ( 117) .
For spinal surgery, antibiotic prophylaxis has not been Respiratory isolation of patients with suspected meningo-
standard because of the perception that infection rates are coccal meningitis in a private room (with clinicians wearing
low without antibiotic prophylaxis. While some studies have masks) until 24 hours after the start of effective therapy has
documented rates <1% (103-106), others have observed rates been associated with only very rare episodes of transmission to
from 2.3% to 5.0% (107-110). One study has shown significant other patients (58) or to healthcare personnel; usually the lat-
prevention with antibiotic prophylaxis for patients undergoing ter form of transmission has been due to exceptional exposure
lumbar laminectomy (111). It is likely that large, randomized to the patient's respiratory secretions (e.g., mouth-to-mouth
trials with adequate statistical power would document benefit resuscitation) (118-120). Chemoprophylaxis of household or
as has been demonstrated recently for two other dean surgi- other very dose contacts of patients with meningitis due to
cal procedures with generally low infection rates, herniorrha- N. meningitidis or H. injluem.aeis indicated and may be arranged
phy, and breast surgery (112). Gantz and Godofsky suggested by the local public health department, which should be con-
that prophylactic antibiotics are already being used routinely tacted promptly after admission of a patient with this disease.
for high-risk situations (e.g., spinal procedures involving fusion Eradication of the organism from the index patient before dis-
or prolonged operations, immunosuppressed patients, and charge may require additional therapy with rifampin because
implantation ofhardware) (4). many regimens used for therapy of meningitis do not eliminate
Prevention of infection of a CSF shunt using antibiotic pro- carriage ( 10).
phylaxis has been difficult to confirm despite 12 randomized
trials. Only one of the 12 trials showed significant prevention,
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61~22. EVD randomized trial): a double-blind, proopectivc, randomized, controlled trial of an
104. El-GiudiS,ArefS, Salama M, etal.lnkctiouo of intervertebral dioca after operation.I B.,.. intervention to reduce the rate of external ventricular drain infection. N,..,...,.,.,. 2012;
Joint SU1g JJr. 1965;58:114-116. 71:~4.
105. Odum G, HartD,Jobnoon Smith W, etal. Aaeventeen'1""" ourvey of the uoe of ultraviolet 117. Thomao R, Lee S, Patole S, Rao S. Antibiotic-impregnated catheter. for the preven-
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106. Puranc:n J, Malu:la J, Lande S. Pootoperative intervertebral dDcitio. &Ia onJwp Scam!.. 118. Feldman HA. Recent W:velopmenta in the therapy and amtrol of meningococcal infec-
1984;56:461--465. tiono. DU Moll. 1966:1--SO.
107. Savitz MH, Katz SS. Prevention of prinwy wound infection in neuroourgical patienta: a 119. Center> for Dileaoe Control. Nooocomial meningococcemia-Wucomin. MMWR. 19'78;
10'1"aJ' otudy. Novtruut-pry. 1986;18:685-lXlS. 27:558.
108. Green JR. Kanobepobky J, Thrkian B. Incidence and oignificance of central nervouJ 120. Arten1tein MD, Ellil RE. The riok of exporure to a patient with meningococcalmeningi-
')"tern infection in neuroourgical patiena. Adu Newrol. 1974;6:2U-228. tio. MilMa. 1968;153:474.
Teena Chopra, DeverickJ. Anderson, and Keith S. Kaye
Surgical Site Infections

HISTORICAL BACKGROUND demonstrating dinicaUy and statistically significant effects in
human patients undergoing scheduled operative procedures,
The role of the surgeon's hands in introducing bacteria into first by Bernard and Cole (5) and then by Polk and Lopez-
wounds was slow to be recognized despite the work of Semmel· Mayor (6) in the 1960s. Work on prophylactic antibiotic.s since
weis in 1847. Although rubber gloves were first developed for that time has focused on defining those procedures and cir-
the use of Halsted's scrub nurse in 1889 to protect her hands cumstances most likely to benefit from the use of prophylactic
from harsh antiseptics, widespread use of rubber gloves in sur- antibiotics and on examining the relative efficacy of different
gical procedures did not become established until weU into the drugs and different routes and regimens of administration.
20th century. As improvements in anesthetic care and understanding
In the 20th century, the standardization of aseptic practices of surgical physiology permitted more aggressive and wide-
in the operating room greatly improved the safety of clean op- spread rurgical interventiom during the second half of the
erative procedures, but operatiom involving anatomic struc- 20th century, the importance of surveillance for infectious
tures with dense endogenous flora that cannot be eliiWnated. complications became more evident. In the 1970s, the Cen-
before the operation, such as of the colon or rectum, contin- ters for Disease Control and Prevention (CDC) began the
ued to carry a very high risk of infection. A m~or collabora- NationalNosocomiallnfectionsSurveillance (NNIS) system (7).
tive study organized by the National Research Council (NRC) Although it included all healthcare-associated infections (HAis),
in 1964 documented the rate of surgical site infection (SSI) one component emphasized from the beginning was the col-
following 15,615 operatiom carried out over 27 months from lection of data on postoperative infections. Data from the NNIS
1959to 1962in 16operatingroomsoffiveuuiversityhospitalJJ (1). sy3tem provide a rich source of information about the relative
The NRC study was one of the earliest and certainly one of occurrence of infections at aU sites in hospitalized mrgical pa·
the most convincing to document the importance of endog- tients (8). Also, in the 1970s, surgical groups' reports of surveil-
enous bacteria as the primary etiologic agent of SSis. This re- lance of large numbers of procedures validated the relationship
port also introduced a syatem for classifYing wounds according between wound class and different risks of infection as well as
to the risk. of endogenous contamination (and thus of post- the beneficial effect of reporting SSI rate data to the operating
operative wound infection), which provided a basis for com- surgeons on reducing the incidence ofSSI (9).
paring SSI statistics and was a harbinger to the currently used Recently, SSI has taken on an increasingly visible role as a
metric of "wound class." Although more sensitive and specific potentially preventable, publicly reported condition. Occur-
wound classification sy3tems employing additional risk factors rences of SSI and measurements of compliance with processes
for wound infection have been developed since the NRC study to prevent SSI can now impact a hospital's accreditation by or-
(2.~). aU systerru continue to incorporate elements of this origi- ganizations such as The joint Commission (10) and payments
nal scheme. The NRC report contained result:J from the largest from the Center for Medicare and Medicaid Services (CMS)
and most carefully conducted study in its day to examine a host and insurance carriers (11).
ofother factors related to the patient and the environment that
influenced the risk of postoperative wound infections. Multi-
variate analysis of this large body of data provided convincing THE IMPACT OF SURGICAL
evidence of changes in the risk of developing postoperative INFECTIONS
infections influenced by the patient's age, obesity, steroid ad-
ministration, malnutrition, presence of remote infection, use Postoperative infections in surgical patients can prolong the
of drains, duration of the operation, and duration of preopera- length of hospitalization for substantial periods, depending
tive hospitalization. on the type of operation (estimated at 1 million additional
Although antibiotics were introduced near the end ofWorld inpatient-days in a recent study, and thereby incurring $1.6
War II, their effective use for preventing postoperative infec- billion in excess costs) (12). Cardiothoracic, orthopedic, and
tion ultimately was made possible by the pioneering studies gastrointestinal operations are especially costly in this regard as
of Dr. John Burke, who used an animal model to demonstrate the result of both pulmonary and operative site infections (12).
the critical importance of the timing of prophylactic antibiotic In addition to the higher direct costs of care, indirect costs
administration (4). He showed via a guinea pig model that should be considered in calculating the consequences of post·
the appropriate antibiotics given before bacterial contamina- operative infection. These costs include the time the patient
tion could significantly reduce the risk. of infection, whereas loses from gainful employment and the possible medicolegal
the same antibiotic given after bacterial contamination was actions that the patient could take against a hospital or the sur-
much less effective. 'Ibis information was translated into trials gical staff (see Chapter 17).
540
Chapter 36 • Surgical Site Infections 541
DEFINITION AND PATHOGENESIS and (b) infection involves either the skin or soft tissue (inci-
OF SURGICAL SITE INFECfiONS sional SSI) or an organ/space that was operated on or manipu-
lated during the surgical procedure (organ/space SSI) (13)
Diagnosis of SSis depends on following two criteria: (a) infec- (Table 36.1) . The occurrence of SSI is an interplay among vari-
tion occurs within 30 days after an operative procedure if no ous factors, including the type and inoculum of bacterial con-
implant is left in place, or within 1 year if an implant is in place tamination of the operative site; complicating intraoperative
TABLE 36.1 Centers for Disease Control and Prevention's (CDC) Definitions
of Nosocomial Surgical Site Infections (SSis), 1992
Superfo;ial tnci.Mnal SSis: Infection occurs within 30 days after the operative procedure and involves only skin or subcutaneous tissue of the
incision, and at least rmt~ of the following signs or symptoms is present
• Purulent drainage from the superficial incision
• Organisms isolated from an aseptically obtained culture of fluid or tissue from the superficial incision
• At least one of the following .signs or symptoms of infection: pain or tenderness, localized .swelling, redness, or heat; and superficial
incision deliberately opened by the surgeon or attending physician
• Diagnosis of superficial incisional SSI by the surgeon or attending physician
• The following are not reported as superficial incisional SSis: stitch abscess (minimal inflammation and discharge confmed to the points
of suture penetration), infection of an episiotomy or a neonate's circumcision site, • infected bum wound, a and incisional SSI that extends
into the fascial and mwcle layen (see "Deep incisional SSis' below).
Deep incisional SSis: Infection occurs within 30 days after the operative procedure if no implantb is left in place or within 1 year if implant is in
place and the infection appears to be related to the operative procedure and involves deep soft tissues (e.g., fa&cial and muscle layen) of
the incision and at least omr of the following signs or symptoms is present:
• Purulent drainage from the deep incision but not from the organ/space component of the surgical site
• A deep incision spontaneously dehisced or deliberately opened by a surgeon when the patient has at least one of the following .signs or
symptoms: fever (>38°C),localized pain, and tenderness unless culture of the incision gives negative results
• An abscess or other evidence of infection involving the deep incision found on direct examination, during reoperation, or by
histopathologic or radiologic examination
• Diagnosis of a deep inci.sional SSI by a surgeon or attending physician
Organ/space SSis: An organ/space SSI involves any part of the anatomy (e.g., organs or spaces) other than the incision opened or manipulated
during the operative procedure. Specific sites are assigned to organ/space SSis to identify the location of the infection. The specific sites
that must be used to differentiate organ/ space SSis are listed here. An example is appendectomy with subsequent subdiaphragmatic
abscess, which would be reported as an organ/space SSI at the intra-abdominal site. Organ/ space SSis must meet the following criteria:
Infection occun within 30 days after the operative procedure if no implant is in place and the infection appean to be related to the
operative procedure and infection involves any part of the anatomy (e.g., organs or space) other than the incision opened or manipulated
during the operative procedure and at least rmt~ of the following is present:
• Purulent drainage from a drain placed through a stab wound' into the organ/space
• Organisms isolated from an aseptically obtained culture of fluid or tissue in the organ/ space
• An abscess or other evidence of infection involving the organ/space on direct examination, during reoperation, or by histopathologic or
radiologic examination
SSis involving more than one site:
• Infection that involves both superficial and deep incision .sites is classified as deep incisional SSI
• Occasional organ/space infection draining through the incision generally not requiring reoperation and considered a complication of the
incision is classified as a deep incisional SSI
Specific sites of organ/space SSis:
• Arterial or venous infection • Breast abscess or mastitis
• Diskspace • Ear, mastoid
• Endocarditis • Endometritis
• Eye, other than conjunctivitis • Gastrointestinal tract
• Intra-abdominal, not specified elsewhere • Intracranial, brain abscess or dural infections
• Joint or bursa •Mediastinitis
• Meningitis or ventriculitis • Myocarditis or pericarditis
• Oral cavity (mouth, tongue, or gums) • Osteomyelitis
• Other infections of the lower respiratory tract • Other infections of the urinary tract
• Other male or female reproductive tract • Spinal abscess without meningitis
• Sinusitis • Upper respiratory tract, pharyngitis
• Vaginal cuff
"Specific criteria are used for infected episiotomy and circumcision sites and for bum wounds.
~mplant is defined as a nonhuman~erived implantable foreign body (e.g., prosthetic heart valve, nonhuman vascular graft, mechanical heart,
or hip prosthesis) that is permanendy placed in a patient during an operation.
'If the area around a stab wound becomes infected, it is not an SSI but is considered a skin or soft-tissue infection, depending on its depth.
Modified from Horan TC, Gaynes RP, Martone WJ, et al. CDC definitions of nosocomial surgical site infections, 1992: a modification of CDC
definitions of surgical wound infections. Infect Control Hosp Epidemjol. 1992;13:606--608, with permission.
factors, such as a technique that results in vascular compromise, 5. Dirty: Presence of pus, perforated viscus, or traumatic
devitalized tissue, and/or dead space after wound closure; and wound that is old or from a dirty source.
host factors. By and large, SSis are caused by endogenous bac-
teria that contaminate the operative site, and in the absence Subsequent reports have condensed this system into four
of bacteria, they do not occur. However, surgeons have known groups, combining refined-dean and other (clean) into the
for years that many other factors also influence the risk of in- one category of clean. Although the risk for SSI generally in-
fection. Burke demonstrated in 1963 that all (50/50) clean creased as procedures move from clean, to clean-contaminated,
surgical incisions contain bacteria at the end of an operation, to contaminated and infected, subsequent reports indicate a
but only a small number (4% in that report) become infected general consistency of the trends toward decreased overall SSI
(14). An animal study of the relationship between bacterial in- rates over time that is most marked in the contaminated and
oculum and SSI risk showed an increasing danger of infection dirty classes ofwounds (Table 36.1) (9,16). These rates could
with increasing numbers of bacteria. This risk was described have been influenced by a variety of factors, including a better
by a typical sigmoid, biologic curve when inoculum size was understanding of the effective use of prophylactic antibiotics
graphed against SSI incidence. However, there was no inocu- and of the bacteriology of dirty operative procedures and a re-
lum in that study of 1,028 incisions that resulted in either a 0 or duction in the practice of closing the skin in dirty procedures.
a 100% risk of infection (15). The authors concluded that the Since the NRC study, much effort has focused on under-
development of infection in a surgical incision is udependent standing which factors other than wound class affect the SSI
on many factors other than the presence of bacteria." They risk. This trend began with the original analysis of additional
further predicted that reductions in the incidence of postop- risk factors performed with the NRC study. The earliest efforts
erative infection could be achieved both by using techniques to control SSI focused on lowering infection rates for dean
to reduce the numbers of bacteria that gain access to surgical wounds, because these wounds should theoretically have a zero
wounds and by focusing on methods to increase the efficiency SSI rate if all bacteria could be eliminated from the wound.
of host defenses in resisting those bacteria that do gain access Thus, efforts focused on aseptic technique for the preven-
to the wound. Modern surgical surveillance and surgical infection of SSI. Subsequent work found that even clean wounds
tion control must acknowledge both of these areas to achieve become contaminated with some bacteria, and evaluation of
the goals of minimum postoperative infection rates (13). historical data discovered potential interventions for reducing
The types of bacteria that cause SSis are a function, in part, SSI rates even in high-risk wounds. This provided an incen-
of the anatomic location where the surgery took place. The most tive to understand the underlying SSI risk in order to sensibly
common SSI pathogens include staphylococci (Staphylococcus au- compare inter- or intrafacility SSI rates.
musand coagulase-negative staphylococcus), Streptococcus spp., and The CDC developed a simplified risk index on the basis of
Enterococcus spp. Staphylococci are particularly important patho- analyses of NNIS SSI data that includes three components: the
gens complicating smgeries that involve implants. Gram-negative physical status index of the American Society ofAnesthesiology
bacilli, both aerobic and anaerobic, are more common pathogens (ASA) (14), surgical duration, and wound class (3). The ASA
in smgery involving the gastrointestinal or genitourinary tracts. index assigns one point for a preoperative assessment score
of 3, 4, or 5. In addition, a cut point was developed using the
75th percentile for operative duration for most operative pro-
SURGICAL INFECTION SURVEILLANCE cedures. A point is assigned for operative duration >75th per-
AND CLASSIFICATION OF SURGICAL centile. The wound classification of contaminated or dirty adds
one point to the risk score. Thus, the NNIS SSI risk index has a
WOUNDS
possible range from 0 to 3.
A comparison of the predictive accuracy of the NNIS SSI
As indicated earlier, the oldest and best-established definitions
risk index with the old NRC classification shows that this sim-
of surgical wound classes originated with the NRC study of the
pler index retains the increased accuracy and consistency while
efficacy of ultraviolet light for reducing wound infections. That
being easier to apply (Table 36.2) . The ratio of risks within
study placed all wounds into one of five classes (2) :
single NRC wound classes range between 3.9 and 5.4, whereas
1. Refined-dean: Clean elective operations, not drained, and all risk ratios within single NNIS risk strata fall between 1.0 and
primarily closed. 2.1. For surveillance programs with limited resources, surveil-
2. Other (clean): Operations that encountered no inflamma- lance of the 53% of patients with 2: 1 SSI risk factors would yield
tion and experienced no lapse in technique. In addition, data on 75% of all SSis, thus increasing the efficiency of surveil-
there was no entry into the gastrointestinal or respiratory lance efforts (4).
tract except for incidental appendectomy or transection Despite its advantages over the NRC wound classification
of the cystic duct in the absence of signs of inflammation. system with regard to estimating SSI risk, the NNIS index, as
Entrance into the genitourinary tract or biliary tract was with all indexes, is not effective in predicting outcomes for
considered clean if the urine and/or bile were sterile. individual patients. In addition, the NNIS index lacks predic-
3. Clean-contaminated: Gastrointestinal tract or respiratory tive power for certain highly standardized procedures, such as
tract entered without significant spill. Minor lapse in tech- coronary artery bypass grafting (CABG) (17), Cesarean section
nique. Entry into the genitourinary tract or biliary tract in (16), and craniotomy (18), where the m<~Jority of patients have
the presence of infected urine or bile. the same or similar NNIS index score. Although the NNIS in-
4. Contaminated: M<~Jor lapse in technique (such as emer- dex can accurately distinguish the risk of procedures from dif-
gency open cardiac massage), acute bacterial inflamma- ferent categories of operative procedures, it does a poor job
tion without pus, spillage from the gastrointestinal tract, or of distinguishing higher- and lower-risk procedures among all
fresh traumatic wound from relatively clean source. patients undergoing the same procedure. In these instances,
TABLE 36.2 Comparison of Centers for Disease Control and Prcw:ntion's (CDC) National
Nosocomial Infection Surveillance (NNIS) System and National Jksearch
Council (NRC) Risk Predictions for Surgical Wound Infection
NNIS Risk Index
NRC Class 0 1 z J AU MaimumB.alid'
Clean 1.0 2.3 5.4 2.1 5 .4
Clean-contaminated 2.1 4.0 9.5 3 .!1 4.5
Contaminated 3.4 6.8 13.2 6 .4 3.9
Dirty !1.1 8.1 12.8 7.1 4.1
All 1.5 2.9 6.8 1!1.0 2 .8
Maximum ratio" 2.1 1.7 1.8 1.0
"Ratio of the lowest to the highest infection rate in wound class or in risk index.
different risk factors specific to the procedure and to the pop- or to inoculation of the surgical wound by bacteremia (23).
ulation become more important. Another potential problem Data from human wounds suggest that the risk of postoperative
with the NNIS system is inconsistency in the assignment of ASA infection is very great whenever the wound inoculum is > 105
scores (19). A comparison of the sensitivity and specificity of bacteria (24). Although lymphatics have been suspected as a
ASA scores compared with the presence of 2:3 discharge di- route of infection in patients with distal infections, evidence is
agnoses would be of interest. This comparison could probably lacking (25). Patients who have been shaved at the surgical site
be carried out on the original data sets used in the studies by before the time of operation theoretically have a higher risk of
Haley et al. (2) and Culver et al. (3). infection because of abrasions caused by the razor and subse-
The CDC recently introduced the use of the Standardized quent bacterial proliferation and inflammation in those inju-
Infection Ratio (SIR) for surveillance of several HAis includ- ries (26). In vascular surgery, similar operations have a higher
ing SSis. The SSI SIR is more specific and is a result of logistic risk of postoperative infection in the groin region than in the
regression modeling of all procedure-level data collected by arm or neck (27). This could stem from local vascularity, local
the CDC's National Healthcare Safety Network (NHSN; the differences in bacterial number and type, or both.
updated version of NNIS) facilities as compared to the tradi-
tional NNIS risk index. The SSI SIR will provide improved risk
adjustment and will replace the current risk-stratified SSI rates INTRAOPERATIVE EVENTS THAT
(20). The SSI SIR, however, does not account for many patient-
specific factors, such as obesity, diabetes, smoking, or redo
INFLUENCE INFECTION RISK, AND
procedures, and compares the SSI rate to the past SSI rate.
METHODS FOR PREVENTION
Other organizations, including the National Surgical Quality
DURATION OF OPERATION (28,29)
Improvement Program (NSQP) and The Society of Thoracic
Surgeons (STS), use different types of risk adjustment models One of the most consistently reported factors in SSI is the du-
that include additional variables (20,21). ration of the operative procedure. The precise connection be-
tween duration and SSI risk is not known. It is plausible that a
prolonged operation results in more desiccation of tissues, po-
HOST FACTORS THAT INFLUENCE tential for hypothermia of the patient, and increased exposure
INFECTION RISK of the wound to bacteria. It is also possible, however, that a lon-
ger operative duration is a marker for other, unmeasured fac-
Many individual host factors influence SSI risk. In most in- tors, such as the underlying difficulty of the procedure, more
stances, the precise mechanism of action that links the risk scarring, larger tumor, patient obesity, difficulty in exposure
factor and the infectious outcome are not known, although (30), or the skill or experience of the surgeon. An operation
plausible explanations have often been provided based on that is rushed could heighten the risk of intraoperative contam-
logical reasoning. Thus, the increased SSI rates observed with ination or of imperfect hemostasis with subsequent increased
advanced age, morbid obesity, weight loss, hypoalbuminemia, SSI risk. Operations should not be prolonged unnecessarily,
impaired functional status, immunosuppression, and diabetes but emphasis on the speed of operation can be misleading.
mellitus have been attributed, in part, to nonspecific defects
in host defenses. The increased SSI risk observed in patients
TRANSFUSION AND FLUID MANAGEMENT
with anergy is not easily related to other measurable immune
functions. It is well established, however, that cigarette smok- Repeated blood transfusions can lead to increased risk of in-
ing decreases wound healing by causing vasoconstriction and fections by altering the body's immune response, especially
decreased tissue oxygenation (22). macrophage functions. There is dose-dependent correlation
Patients who have an active infection at another body site between blood product transfusion and increased mortality
are at increased risk of postoperative SSI ( 1). This finding and infections in trauma patients. Additionally, crystalloids
could relate to the increased risk that significant numbers of have shown to reduce tissue oxygen supply and hence should
bacteria will gain access to the wound during the procedure be avoided (30).
HYPERGLYCEMIA and robotic procedures may reduce tissue trauma, shorten

the duration of surgery, and result in lower SSI rates for these
High blood sugar (~140 mg/dL), irrespective of having dia-
procedures.
betes, increases the risk of SSI (31). However, a very aggres-
sive approach can cause hypoglycemia, and hence monitoring
TYPE OF SUTURE
serum glucose during the perioperative period is essential.
Maintaining serum glucose <200 mg/dL has been demon- Monofilament and braided sutures, like silk sutures, have
strated to reduce SSI following some procedures, including been demonstrated to decrease the risk of SSis (30). The
in adult but not pediatric cardiothoracic surgery. Ata et al. role of antimicrobial sutures in reducing SSI risk remains un-
showed that basal-bolus insulin regimen is preferable over clear. It has been proposed that antimicrobial-impregnated
sliding scale insulin as it reduces SSis and provides good gly- sutures (such as suture impregnated with tridosan) could be
cemic control in adult general surgery patients with Type 2 of some benefit in reducing SSis; however, it has not yet been
diabetes (32). proven (35).
DELAYED PRIMARY CLOSURE PREPARATION OF THE PATIENT

AND OPERATIVE SITE (22)
Delayed primary closure is recommended in patients who have
highly contaminated wounds, as this approach leads to im- Preoper~r.ti:ve Bllthing with Antiseptic Agents
proved blood flow at the wound edges and hence better de-
There is a marked reduction in surface bacterial load with
livery of functional phagocytes, resulting in increased defense
preoperative bathing using chlorhexidine as compared with
against infections, especially through the first 5 to 6 postopera-
povidone-iodine or soap and water. Showering the evening
tive days (33). before and the morning of the surgery is more effective than
a single shower in the morning or the night before the sur-
INTRAOPERATIVE HYPOTHERMIA gery. Also, cleaning the body with a chlorhexidine-impregnated
cloth has been shown to decrease colony count more effectively
The risk of SSI may also be decreased by maintaining intraop- than simple showering (30). The role of preoperative bathing
erative normothermia (34), particularly in colorectal surgery.
with chlorhexidine, however, remains unclear. Despite a recent
Intraoperative hypothermia impairs various aspects of the im- review that demonstrated no protective effect (37), routine
mune system because of generalized vasoconstriction leading
preoperative chlorhexidine bathing is frequently practiced. If
to decreased subcutaneous blood flow and low 0 2 tension and
done appropriately, it may decrease SSI risk (30).
delay in wound healing (30).
Skin Deconmmin~r.tion of the Surgiud
DRAINS (30,35) Tmm ~r.nd of the P~r.tient
Drains are a potential source of wound contamination leading Chlorhexidine in combination with alcohol has been found to
to SSI. Although closed suction drains have been preferred be more effective as hand scrubs in reducing skin bacteria com-
over open drains, Rao et al. demonstrated that SSI is strongly pared with povidone-iodine. For preoperative skin preparation
associated with dosed suction drains when left for longer dura- of the patient, chlorhexidine/alcohol and iodine povacrylex/
tions (36). Hence, if the use of a drain is necessary, it should alcohol-based products have the most demonstrated efficacy
be positioned through a separate incision and for the shortest in microbial reduction. In a randomized controlled trial,
duration possible (30). chlorhexidine with alcohol as a skin prep significantly reduced
SSis compared with povidone-iodine (38).
INTRAOPERATIVE TEAMWORK
AND COMMUNICATION
Poor surgical teamwork and communications is associated with Not removing hair at the operative site is associated with a
adverse postsurgical outcomes, including SSI, sepsis, and even lower SSI risk compared with hair removal by any means. How-
death. Hence, good collaboration among the operative team ever, when necessary, surgeons should preferentially clip hair
members is important for optimizing clinical outcomes for the or use a depilatory method as opposed to shaving the operative
patient (28). Perforated surgical gloves have been shown to in- site (39).
crease SSis (29).
SURGEON SKILL AND TECHNIQUE

The use of antimicrobial adhesive drapes may decrease SSis
The skill of the surgeon has long been considered to be one of depending on the type and technique of drape application
the most important factors in determining SSI risk. However, ( 4Q). The newly available cyanoacrylate-based "microbial seal-
it has been very difficult to effectively measure the association ant," a variant of adhesive antimicrobial incise drape, reduces
between surgical skill and SSI risk. Certain surgical techniques wound colonization by 99.9% (41). This microbial sealant has
have been associated with increased SSI risk. For example, in- also been shown to enhance the effect of povidone-iodine
terrupted sutures increase SSI risk compared to continuous skin prep by fixing it to the skin and hence avoiding wash-
sutures owing to more tissue necrosis at suture sites and more ing it off. However, drape type has not been demonstrated to
suture material left in the wound. The advent of laparoscopic reduce SSI risk.
ANTIMICROBIAL PROPHYLAXIS increased risk of postoperative infection; thus, prophylaxis

is recommended for these types of surgery. Prophylaxis is
Numerous articles have demonstrated the effectiveness of peri- also recommended for gastric operations on morbidly obese
operative prophylactic antimicrobial administration (5,6). The patients (42-44).
recommendations from a recent review on antimicrobial pro- The biliary tract is sterile in healthy persons, and coloniza-
phylaxis are summarized in Thble 36.3. tion rates are low during elective operations for symptomatic
Several controversial topics regarding antibiotic prophylaxis stone disease. Higher rates of colonization and of postopera-
remain, including the use of prophylaxis for some dean operative infection are encountered in patients >60 years old or
tive procedures, the specific agent used in some procedures, who have common duct stones, bile duct obstruction, recent
the duration of antimicrobial administration, and the relative episodes of acute cholecystitis, or previous operations on the
merits of oral antimicrobial agents, parenteral antimicrobial biliary tract. Antimicrobial prophylaxis is recommended for pa-
agents, or both for prophylaxis in colorectal procedures. Most tients in these high-risk categories ( 42-44,45).
practitioners agree that antimicrobial prophylaxis is beneficial Elective colon and rectal procedures are followed by very
for procedures that involve entry into the gastrointestinal tract high SSI rates in the absence of antimicrobial prophylaxis, and
with resulting exposure of the surgical site to endogenous in- such prophylaxis is widely practiced (44,46). For procedures
testinal bacteria. other than colorectal operations, parenteral administration of
In gastric operations, the highly acid gastric contents keep the antimicrobial agent is standard. For colorectal procedures,
endogenous bacterial numbers very low in patients undergo- oral (luminal) agents may be used to lower the endogenous
ing elective peptic ulcer operations, and antimicrobial prophy- bacterial load before operation. Both routes of antimicrobial
laxis is not considered necessary. With the understanding of administration have been found to reduce SSis when compared
the role of Helicobacter pylori in the pathogenesis of peptic ulcer with those of a placebo, but the additional benefit of using both
disease, elective operations for this condition have essentially together has not been firmly established (46) . A recent study
ceased. Procedures on the stomach for cancer, gastric ulcer, demonstrated that an oral antimicrobial preparation before
bleeding, obstruction, or perforation are considered high risk colorectal surgery reduced SSI risk (4 7). The most common
because of the higher bacterial densities encountered and the practice in the United States is to achieve mechanical cleansing
• . ftC :If l@. Antibiotic Prophyluis for Various Surgical Procedures

Type of Surgery Common Pathogens Recommended Antibiotics
Gastrointestinal:
Esophageal, gastroduodenal Enteric gram-negative bacilli, Cefazolin 4 Clindamycin and gentamicin or
gram-positive cocci levofloxacin or ciprofloxacin
Biliary tract Enteric gram-negative bacilli, Cefazolin6 Levofloxacin or ciprofloxacin
enterococci, clostridia
Colorectal Enteric gram-negative bacilli, Cefazolin and metronidazole Clindamycin and gentamicin or
enterococci, anaerobes cefoxitin
Gynecologic and obstetric:
Hysterectomy Enteric gram-negative bacilli, Cefoxitin or cefazolin Clindamycin and gentamicin
enterococci, group B
streptococci, anaerobes
Cesarean section Enteric gram-negative bacilli, Cefazolin Clindamycin or vancomycin
enterococci, group B
streptococci, anaerobes
Genitourinary Enteric gram-negative bacilli, Cefazolin4 or trimethoprim/ Clindamycin or vancomycin or
enterococci sulflunet hoxazole 4 ciprofloxacin
Neurosurgery Staphyllx:oaw autW&, coagulase- Cefazolin and vancomycin Vancomycin
negative staphylococci
Cardiac surgery S. au~,coagul~negative Cefazolin and vancomycin or Clindamycin or vancomycin
staphylococci cefuroxime
Orthopedic S. au~,S.~uus Cefazolin and vancomycinb Clindamycin or vancomycin
orcefuroxime
Vascular (prosthetic graft) S.au~,coagulase-negative Cefazolin or vancomycin6 Clindamycin or vancomycin
staphylococci
Ophthalmic S. au~,coagul~negativestaph Gentamicin or tobramycin or cip-
ylococci, enteric gram-negative rofloxacin or gatifloxacin or
bacilli, PseuOOmonas sp. levofloxacin or moxifloxacin
Thoracic (noncardiac) S. au~, coagulase-negative staph- Cefazolin or cefuroxime or Clindamycin or vancomycin
ylococci, enteric gram-negative vancomycin
bacilli
"High-risk cases such as morbid obesity, esophageal obstruction, decreased gastric acidity, or gastrointestinal motility.
bffigh-risk cases such as age > 70 years, acute cholecystitis, nonfunctioning gall bladder, obstructive jaundice, or common duct stones.
'Patients allergic to penicillins and cephalosporins.
Adapted from Enzler 1\g", Berbari E, Osmon DR. Antimicrobial prophylaxis in adults. Mayo Clin Proc. 2011;86:686-701.
of the bowel combined with oral administration of antimicro- the operating room (6). Before then, the practice had been to
bial agents designed to reduce the luminal bacterial load on begin antibiotic therapy in the recovery room after the com-
the day before the scheduled procedure and to administer par- pletion of the procedure. This later approach was ineffective.
enteral agents in the operating room immediately before the Recent reports have confirmed the importance of administer-
operation ( 46,48). The oral regimen that has the best support ing prophylactic agents in the immediate preoperative period,
is the administration of 1 g each of neomycin and erythromy- usually within 30 to 60 minutes of the incision (unless vanco-
cin base at 19, 18, and 9 hours before the scheduled time for mycin or quinolones are used, in which instance administra-
the colon procedure (49). Some procedures do not enter the tion should occur 1 to 2 hours before the incision) (55,56).
gastrointestinal tract, but nevertheless have a high rate of post- Unfortunately, postoperative initiation of "prophylaxis" is still
operative infection without prophylaxis. They include lower- relatively common (55,57,58). For surgeries lasting >3 hours,
extremity vascular procedures, hysterectomy, primary Cesarean short-acting antibiotics, such as cefazolin, should be redosed
section, and craniotomy. Some other procedures do not have (after making adjustment for renal function and rate of drug
excessive SSI rates, but any SSis that do occur have devastating elimination) 3 hours after the incision has been made (30).
consequences. These operations include joint replacement or The necessary duration of antimicrobial prophylaxis has
placement of other prosthetic devices, cardiac procedures, and not been established, although analysis of data from some pub-
aortic graft placements. These procedures benefit from pro- lished reports suggests that antimicrobial activity should be
phylactic antimicrobial administration (42,44,45). present in blood and wound fluids at the time of closure for
The use of prophylactic antimicrobial agents for clean maximal effectiveness. Most early trials employed administra-
operations in which the SSI risk is relatively low and the con- tion on a schedule that gave the third and last dose 12 hours af-
sequences of infection are considered mild is controversial ter the first preoperative dose. Numerous reports indicate that
(50,51). When SSI rates are low and the consequences small, longer durations and prolonged administration of prophylactic
the use of antimicrobial agents could expose patients to a drug agents are common in clinical practice (55,57,58). Although a
to prevent a single infection, which could predispose to the de- single report suggests better results with longer use of prophy-
velopment of bacterial resistance and/or an increase in adverse lactic therapy in certain high-risk patients undergoing periph-
drug reactions in the population being treated. eral vascular procedures (59), most published articles support
Many agents have been found to be effective for periop- a short duration of antimicrobial prophylaxis (60,61).
erative prophylaxis. In recent years, most new antimicrobial The Surgical Care Improvement Project (SCIP) recom-
agents with any potential for surgical use have been licensed mends that an appropriate prophylactic antimicrobial agent be
with one or more prophylaxis indications. The primary require- administered within 60 minutes before the incision (120 min-
ment for a prophylactic antimicrobial agent is that it be active utes are allowed for some agents including vancomycin) and
against the pathogens known to be present at the operative site that, for most procedures, the prophylactic agent be stopped
and those typically recovered from SSis. The agent most com- within 24 hours of surgery end (54).
monly recommended for procedures that do not involve the An area of controversy is the prevention of SSI after trau-
distal ileum, colon, rectum, or appendix, and that, therefore, matic injuries that expose the patient to bacterial contamination
do not entail much risk of exposure to colonic anaerobes, is before antimicrobial treatment can be initiated. Because pro-
cefuzolin ( 42,44,45). Procedures that do involve these sites phylactic agents cannot be administered before contamination,
require an antimicrobial agent with activity against Bacteroides some clinicians have termed their use therapeutic rather than
fragilis and other colonic anaerobes and the Enterobacteria- prophylactic. A number of recent studies have established the
ceae (46). Cefoxitin is one of the most commonly recom- fact that even in this context, a short duration of antibiotic
mended agents. Newer, so-called advanced-generation agents, treatment is as effective as a prolonged one and probably is
including ertapenem, have not been confirmed to be superior preferable (60-62).
to cefuzolin, cefoxitin, or cefotetan for the prophylactic indi-
cations for which these three drugs have been recommended
PROPHYLACTIC TOPICAL ANTIMICROBIALS (30)
(52). Regimens with specific activity against Enterococcus spp.
have not been shown to achieve superior results in colorectal The role of preoperative, prophylactic, topical antibiotics has
procedures. Such regimens (e.g., ampicillin, amoxicillin, and been shown to be beneficial in specific types of surgeries, in-
vancomycin combined with gentamicin) are recommended for cluding joint arthroplasty, cataract surgery, and, possibly, breast
prophylaxis against bacterial endocarditis when gastrointes- augmentation and also in obese patients undergoing abdomi-
tinal or genitourinary procedures are performed on patients nal surgery (62). However, antimicrobial prophylaxis using sys-
with high-risk cardiac conditions (53). A patient's body mass temic agents remains a critical component of SSI prevention,
index should be taken into consideration when dosing prophy- and the role of topical antimicrobials remains unclear. Topical
lactic antimicrobials, particularly for morbidly obese patients antimicrobials should not be used alone for prophylaxis.
(54). For example, in such patients, increasing the dose of ce-
fazolin from 1 to 2 g is recommended.
SELECTIVE DIGESTIVE DECONTAMINATION
More than 10 years ago, Stoutenbeek et al. proposed a method
TIMING OF ADMINISTRATION
of selective digestive decontamination (SDD) to lower the in-
The timing of antimicrobial administration for prophylaxis is fection rate in posttraumatic surgical patients in the intensive
important. For maximum effectiveness, the agent must have care unit (ICU) ( 63) . The concept holds that potentially patho-
high concentrations in blood and body fluids before an inci- genic bacilli reside in an intestinal reservoir and serve as the
sion is made. The original successful reports of prophylaxis source for many HAis. The proposed regimen-tobramycin,
specified that drugs were administered to patients "on call" to polymyxin B, and amphotericin B by nasogastric tube and oral
paste for the duration of ICU stay and parenteral cefotaxime not lead to the outcomes just cited and that are readily treated
for the first 5 days-is supposed to suppress potentially patho- on an ambulatory basis without a major increase in therapeutic
genic microorganisms in the gastrointestinal tract while pre- costs or delay in the patient's retum to regular activities. SSis
serving the useful anaerobic flora that promote colonization (especially ones classified as deep and organ/space per CDC
resistance. Despite years of study and numerous publications, definitions (Figure 36.1); and those that complicate operations
the concept is still the su~ect of much controversy. It has many involving cardiac, vascular, and neurologic structures; bones;
proponents in Europe, but has failed to garner much enthu- joints; stomach; bowel; or rectum) are more likely to compro-
siasm or be put into wide practice in the United States except mise a patient's well-being than are similar SSis complicating
among some solid-organ transplant groups (64). hemia repair or uterus, gall bladder, or thyroid operations.
Some SDD regimens also include intravenous antimicrobials Postoperative infections beyond the operative site may bring
in addition to oral agents. While many articles report a reduc- about considerable morbidity and may be included in routine
tion in healthcare-associated lower respiratory tract infections, S}'5tematic surveillance. This is particularly true for pneumonia
few cite any important differences in mortality rates or dura- (see Chapter 32). In special-care surgical units, surveillance of
tion of ICU stay, and the suspicion arises that what has changed various infections caused by multidrug-resistant bacteria can be
is the diagnosis of pneumonia, a notoriously difficult task in especially useful in providing information to surgeons about
ICU patients (see Chapter 32). A recent European study dem- possible inappropriate antimicrobial use and could indicate per-
onstrated a reduction in mortality among patients undergoing sonnel or environmental transmission ofbacteria. Hospital-wide
SDD in an ICU setting (65). However, the role of SDD in set- outbreaks of infections due to methicillin-resistant S. auf"eUS
tings where rates of antimicrobial resistance are relatively high (MRSA) or vancomycin-resistant enterococci (VRE) and dus-
(such as in the United States) remains unclear, and whether or ters of diarrhea or colitis due to Clostridium difficile can manifest
not SDD is as effective as oral topical antiseptics in infection first among postoperative patients (see Chapter 15). Surveil-
prevention remains unclear. The emergence of antimicrobial lance activities should identifY such infections.
resistance is a concem with SDD (66,67), and its role in preop- Hospital episodes of SSis should be identified and classified
erative prophylaxis remains undetermined. by the different NHSN/NNIS risk index categories (0 to 3).
Whereas patients having dirty operations could acquire a new
infection as a complication of the operative procedure, often
PREVENTION OF SSI
it is difficult to separate this event from the extension of the
SSI prevention focuses mostly on optimizing preventive care infection already present at the time of operation. As the sur-
during the perioperative period, and, in particular, during the veillance findings from patients undergoing specific types or
intraoperative period. Preparation of the surgical team and groups of operations become large enough for meaningful
patient, hair removal, antimicrobial prophylaxis, glucose con- interpretation, SSI rates for various procedures can be estab-
trol, and intraoperative warming are all important factors in lished as a baseline and to reflect the specific populations of
preventing SSI. Formal prevention guidelines are discussed in patients being treated. Mter a database has been established,
detail in the published literature (68). duster definitions and threshold levels for outbreak investiga-
tion could be defined.
SURVEILLANCE OF
POSTOPERATIVE INFECTION
The basic elements of a successful infection surveillance pro-
gram include a definition of specific types of postoperative
Superficial
infections, a method for screening patients at risk, and a re-
incisional
liable means of recording and retrieving information (see SSI
Chapter 6). The observer who records the presence or absence
of infection (infection preventionist [IP] or hospital epidemi-
ologist) should have no conflict of interest in performing these
duties. The surgical staff should be aware of the methodology
for screening and recording SSis and should accept the SSI def-
Deep incisional
inition criteria. It is useful for the observer to make rounds with
SSI
several surgeons to ensure agreement on the use of definitions.
The general criteria put forth by the CDC (13) are available
(Table 36.1). A common definition error is to equate infection
with recovery of bacteria from the wound site. Bacteriologic
findings do not distinguish between colonization and infection,
and SSI can occur without recovery of bacteria from culture.
Surveillance objectives should be defined. All SSis are not
necessarily equally important to identify. Highest priority is
Figure 36.1. Classification of SSh according to Centers for Disease
given to detecting SSis that lead to death, reoperation, in- Control and Prevention's National Nosocomial Surveillance System
creased intensity of services, or special diagnostic or therapeutic (CDC.NNIS). (Reprinted from Horan TC, Gaynea RP, Martone~. et al.
measures (including parenteral administration of antimicro- CDC definitions ofnosocomialsurgicalsite infections, 1992: a modi-
bials, prolongation of hospital stay, or hospital readmission). fication of CDC definitions of surgical wound infections. Infect Control
Lower priority is assigned to finding superficial SSis that do HospEpidnniol. 1992;13:606-608.)
A positive culture is not by itself a sign of infection. Instead, The goal of surgeon-specific surveillance is to lower the SSI
the fact that a culture was sent alerts the Infection Control rate by making individual surgeons aware of excesses in SSI
Practitioner (ICP) that the wound was regarded as suspicious rates and anonymously comparing SSI rates among other sur-
and prompts the IP to inspect the wound personally. This sys- geons as well as to national benchmarks. Such practices can
tem allows the IP to focus his/her efforts on only the most sus- promote adherence to accepted principles of operative care.
picious wounds and provides a complete microbiologic record One approach to SSI surveillance decreases the focus on ab-
for those wounds that are determined to be infected (69). solute SSI rates, and concentrates on classifying each SSI into
Most SSis occur -1 to 3 weeks after surgery. Up to 50% of the dichotomous classes of potentially avoidable and apparently
SSis occur after discharge, and many are identified at the time unavoidable infections (69) . A potentially avoidable SSI is an in-
of hospital readmission. Postdischarge surveillance for SSI is fection that occurs under circumstances in which any indicated
a critical component of SSI. Most patients who develop seri- infection-reducing a!ljuncts were omitted. Such adjuncts would
ous SSis (i.e., deep incisional or organ/space) after hospital include appropriate use of prophylactic antibiotics (i.e., agent,
discharge will require readmission to the hospital for debride- timing, and discontinuing) , avoidance of razor shaving on the
ment and intravenous antimicrobials. Screening operative pa- day before operation, appropriate skin preparation at the opera-
tients who are readmitted to the hospital or who are prescribed tive site, avoiding elective operations in the presence of distant
antibiotics can help to target surveillance toward patients who site and active infections, and so on. An apparently unavoidable
have an increased likelihood of having SSis (70). Patients who SSI is one that occurs despite the application of all known appro-
have postdischarge SSis that are categorized as superficial in- priate infection-reducing measures. The goal of an SSI surveil-
cisional often are managed in the outpatient setting. Tools to lance program should be zero avoidable SSis. When a particular
identify postdischarge infections include questionnaires sent infection-reducing strategy is well accepted but not always reli-
to surgeons or to patients, telephone follow-up with surgeons ably applied, such as the indicated use of perioperative prophy-
or patients, and systems to detect readmission of patients to lactic antibiotics, a quality assurance program designed to ensure
hospitals and postoperative antibiotic prescriptions. The best the reliable application of this method could have a greater ef-
method for accomplishing postdischarge outpatient surveil- fect on SSI rates than could feedback on SSI rates alone (45,39) .
lance is not known and may well vary from one type of proce-
dure to the next.
A growing area of importance is surveillance of outpatient INVESTIGATIONS OF
operative procedures, often in ambulatory surgery centers. OUTBREAKS AND CLUSTERS
An increasing number of operative procedures are being per-
formed on patients who are not admitted to a hospital. Once baseline SSI rates are established, increases in the fre-
A surveillance worksheet indicating the criteria used for SSI quency of SSI above the baseline for a particular type of sur-
definitions is useful to record important details about an in- gery can trigger an outbreak investigation. When potential
fected patient. In general, the CDC NHSN SSI definitions are outbreaks are being investigated, it is important to notify the
used (13) (Table 36.1). Only the minimum information nec- involved surgeons, and when appropriate, hospital administra-
essary for further tabulation to identify dusters or outbreaks tion. However, sharing of crude surveillance data widely with
should be included, including mostly perioperative variables uncritical audiences should be avoided, until sufficient data
(e.g., procedure type, NHSN/NNIS risk index variables, and are collected, analyzed, and interpreted. Failure to identify po-
so on). On infrequent occasions when SSI dusters are found, tential limitations in interpreting crude data and possible sam-
additional information about host risk factors, technical as- pling errors in small dusters can result in a loss of credibility
pects of surgical procedure, and environmental details con- of the surveillance program, create a climate of suspicion and
cerning the patient's care can be important for stratification animosity among the surgical staff, and jeopardize the success
during analysis. Analysis of surveillance data is helpful only to of any future efforts. Thus, sound epidemiologic methods and
the extent that the data output is consonant with the previously strict confidentiality of records are central to an effective pro-
determined objectives (see Chapter 6). gram. However, legislation requiring mandatory reporting of
hospital-specific HAl rates, although publicized as beneficial,
could lead to efforts to minimize SSI rates and not ultimately
SURGEON-SPECIFIC SURVEILLANCE
lead to reduction of HAis. There should also be constant con-
Providing SSI rates to the surgical staff has been shown to de- cern about disseminating interpretations of a single set of data
crease SSis. These findings are consonant with the results of indicating highly unusual findings because of possible sam-
the Study of the Efficacy of Infection Control (SENIC) study pling or other biases and for type 1 error due to inadequate
(70), in which reduction of SSis was found to be associated with sample size (see Chapter Epi methods).
a strong infection control program that included an effective In the early stages, using statistics to determine whether or
hospital epidemiologist and a system for reporting specific SSI not an increase in SSI frequency compared to baseline is signif-
rates to the specific surgeon. Surgeon-specific SSI rates can be icant can be very useful. In situations where the denominator
readily determined. In order to provide risk-adjusted, surgeon- of procedures being performed is low, SSI rates might appear
specific SSI infection rates, all components of the NHSN/NNIS to be much greater compared to baseline, but these differences
risk index must be collected for all of a surgeon's procedures, might not be statistically significant, and might have occurred
those that result in SSI as well as those that do not. It can by chance alone. Using case-control analysis can be useful in
be time-consuming for IPs to collect these variables on all op- determining the cause or source of an SSI duster. If SSI iso-
erative patients. Using automated data generated by operative lates from a duster are available, molecular diagnostics can be
databases can greatly facilitate collection of these NHSNINNIS used to determine the genetic similarity of the strains. Strains
risk variables and of risk-adjusted, surgeon-specific rates. that are the same or similar might indicate the presence of a
common source, such as an environmental reservoir or colo- Decolonizing known carriers of S. aureus preoperatively, partic-
nized member of the operative team as a cause. ularly if the surgery involves an implant, is a preventive strategy
SSI clusters can be sought by grouping infected patients ac- that might be appropriate in some settings, such as when the in-
cording to characteristics such as time, place, person, infect- cidence of SSI due to S. aureus and/or MRSA is relatively high.
ing organisms, surgeons, types of operations, preoperative host The role for preoperative screening for S. aufln~S carriage, via
and surgical risk factors, use of various devices, characteristics intranasal culture or PCR, and decolonizing carriers needs to
of critical care, preoperative duration of hospitalization, and be better elucidated, but is an approach that is being increas-
postoperative intervals until onset of infection. In stratifica- ingly studied for surgeries involving implants.
tion, the analyst seeks to identify possible commonality in SSI MRSA has become the single most common SSI pathogen
sources. For example, a lengthy preoperative period of hos- in some settings, surpassing methicillin-susceptible S. aureus.
pitalization could indicate patients with unusual or complex Routine preoperative antimicrobial prophylaxis regimens are
manifestations of disease. Recent changes in operative practice Jl-lactam-based. Because jl-lactams do not cover MRSA, patients
might be implicated in an outbreak, as might a specific mem- who are known carriers of MRSA should be either identified
ber of the surgical team. Many times, no single "smoking gun" and decolonized before surgery or prophylaxed with an agent
will be identified as a cause of an increase in SSI rates, but im- active against MRSA, such as vancomycin.
proving adherence with a variety of factors such as minimizing Recent studies suggest that if vancomycin is used for antimi-
traffic in the operating room, improving preoperative patient crobial prophylaxis before surgery involving implants in place
preparation, and minimizing crowding in the operating room of jl-lactams, that although decreases in the frequency of SSI
can improve SSI rates. An increase in the incidence of postop- due to MRSA might occur, increases in SSI due to MSSA and,
erative infection could result from a change in risk characteris- in some instances, gram-negative bacilli might occur. Thus, one
tics of the patients with the introduction of a population having approach might be to add vancomycin to the jl-lactam agent for
an increased susceptibility to infection. known MRSA carriers (76).
Oxygen is a key component of wound healing and proper
immune function (77). In fact, tissue hypoxia is a proven risk
VIRAL INFECTIONS
factor for SSI and is probably the primary reason that cigarette
Studies of patients receiving transplants have confirmed that smoking is associated with increased risk of SSI (68).
viral infection is a surgical complication in this context (see Several randomized controlled trials compared high in-
Chapter 45). The principal agents are transferred by human spired oxygen fraction (Fi0 2 of 80%) to "standard caren (Fi02
tissue organs and blood. Cytomegalovirus, herpesvirus, hepatitis B, of 30%) in surgical patients (78--82). While most studies dem-
hepatitis C, HIV, and varicella zoster are the viruses most fre- onstrated that patients who received Fi0 2 of 80% had lower
quently identified (see Chapter 42). rates of SSI than patients who received Fi02 of 30% (78,80,82),
one study demonstrated that general surgery patients who re-
ceived Fi02 of 80% had higher rates of SSI (79), and one study
FUNGAL INFECTIONS
showed no difference between the two groups (81). A meta-
Candida spp. are gaining prominence in consideration as causes analysis of five of these trials that included the one negative
of SSI. This is particularly true in the surgical treatment of trans- trial concluded that the use of high inspired oxygen led to a
plant patients, bum patients, and patients with prosthetic devices 25% relative risk reduction in SSI (RR, 0.74; 95% CI, 0.60 to
(see Chapter 44). Intravenous catheter and urine cultures can 0.92) (83). Importantly, high inspired Fi02 is not associated
yield fungi before systemic involvement, and it is likely that pa- with a higher frequency of respiratory adverse events (81).
tients are infected from such sources by hematogenous spread. The CMS has initiated a national SSI prevention initiative
Improved methods to identify and control such infections will (73,84,85). This effort has focused on the appropriate use of
become more important as technical advances in surgery lead to prophylactic antibiotics as well as control of postoperative glu-
treatment of more immunocompromised subjects (69). cose and appropriate hair removal in selected surgical patients.
Hospitals are required to report compliance with these metrics
to CMS. In addition, SSJs occurring among patients undergo-
NEW DIRECfiONS IN PREVENTING ing certain surgical procedures (such as colorectal surgery, to-
POSTOPERATIVE INFECTION tal abdominal hysterectomy, CABG, total knee arthroplasty, and
total hip arthroplasty procedures) also are being reported to
As the incidence of SSis progressively declines, new thinking is CMS. These process measures and SSI occurrences can impact
required to define the next step in improving the care of pa- a hospital's reimbursement from CMS. Those who have high
tients in relation to controlling postoperative infection. Periop- compliance with performance indicators will be paid more, and
erative colonization with virulent bacteria can be a source of those who have lower rates will be paid less.
both endogenous infection and cross-infection. The association
between nasal carriage of S. aureus (or MRSA) and postoperative
infection is well known ( 71-73). An increasing body of evidence, REFERENCES
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14. Burie JF. Identification of the oourcco of staphylococci contalllinating the surgical wound 10) :S869-3875.
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15. Morrio PJ, Barneo RA. Burke JF. The nature of the "irreducible minimum" rate of inci- on Therapeutia. Clin1'fumri.1992;11:48HIS.
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16. Olaon MM, Lee JT Jr. Continuona, 10.,..ar ""und infection mrveillanee. Ri:&ulb, advan- dation& by the American HeartA11ociation.]AMA. 1990;264:291~2922.
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17. Denio•Torreo SI, Mu Y, Edwardo JR. et al. lmp"""d riot a<ljumnent in public reponing: tion of national quality meuureo. Svrg111/«1 (LarcloMl). 2006;9:579-584.
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46!.-469. antibiotic• and the riok. of mrgi.cal-wound infection. N E..,;l1 MML 1992;526:281-286.
18. Cha KS, Cho OH, Yoo SY. [Risk fa<:ton for surgical lite infectiono in patienb undergoing 56. DiPiro JT, Vallnerlf, Bowden TAJr, etal.lotraoperatmo oerum and tiooue activity of cefiw>.
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19. Salemi C, Andenon D, Thm:o D. American SocietyofAneatheoiologyacoriog diocrepauciea 57. Crollley K, Gardru:r LC. Antimicrobial prophyl.W. in mrgical patienb. JAMA. 1981;245:
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risk. index ratea. Infra Ctmtro!Ho.p EpUIImiDL 1997;18:24&-247. 58. Cunier JS, Campbell H, Platt R, et al. Perioperatmo antinW:robial prophyl;W• in middle
20. Henderoon WG, DaleyJ. Oelign and Ratiotical methodology of the National Surgical Qual- Thnne11ee, 1~1990. &v Infr<tDis. 1991;15(ouppi10):S8'l4-S878.
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26S-279. 62. McHugh SM, Collim CJ, Corrigan MA, et al. The role of topical antihiotico wed ao propby-
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24. Roboon MC, Krizek 'IJ, HeggenJP. Biologyofmrgical infection. Cvrrl'roiJIS"'f.l97ll:l-62. tion of the digeotmo tract on coloniJation and infection rate in multiple trauma patienb.
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59. Tanner J, Norrie P, Melcn K. Preoperatmo hair relllrmol to reduce mrgical lite infection. 78. Go-cif R, ~ 0 , Horn EP, et al. Supplenl.ental periopentive oxygen to reduce the inci-
C/JchnmolJatoJHJs.s,..t &v. 20ll:CD004122. dence ofaurgical-wound infection. N Englf MMl. 2000;M2:161-167.
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rilk of ourgi<:al wound infection: a randomized controlled trial ]AMA 2005;294:205!>-204!. cal site infection: a meta-=alym of randomized controlled trialo. An/1 Surg. 2009;1 44:359-
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David W. Mozingo and Basil A. Pruitt, Jr.
Infections of Burn Wounds

Infection, the risk. of which is proportional to the extent of in· typical cause of morbidity and death in these severely injured
jury, continues to be the predominant determinant ofoutcome patients (Figure 37.1).
in thei1D.ally injured patients de&pite improvements in overall
care in general and wound care in particular. The control of
invasive bum wound infection through the use of effective topi· HOST IMMUNE FUNCTION
cal chemotherapy, prompt mrgical excision, and timely closure
of the burn wound has resulted in unsurpassed survival rates. Thermal injury initiates a deleterious pathophysiologic re-
Even so, infection remains the most common cause of death in sponse in every organ system with the extent and duration
these severely injured patients. of organ dysfunction proportionate to the size of the bum.
Direct cellular damage is manifested by coagulation necrosis
with the depth of tissue destruction determined by the dura·
ETIOLOGY OF BURN INJURY tion of contact and the temperature to which the tissue is ex-
poaed. Following a bum, the noimal skin barrier to microbial
Bums are estimated to affect 450,000 people in the United penetration is lost, and the moist, protein-rich avascular eschar
States annually (1). Of this number, -45,000 patients require of the bum wound provides an excellent culture medium for
hospital admission, 20,000 to 25,000 of whom have injuries of microorganisms. While destruction of the mechanical barrier
such significance that care is best undertaken in a burn cen· of the skin contributes to the increased susceptibility to infec·
ter. Howse and structure fires are responsible for >70% of the tion, postbum alterations in immune function also could be of
yearly 3,500 bum-related deaths, 75% of which result from significant importance. Every component of the humoral and
smoke inhalation or asphyxiation and 25% of which are due cellular limbs of the immune system appears to be a.ffected af-
to burns. However, these fires are responsible for only 4% to ter thermal injury; the magnitude and duration of dysfunction
5% of burn admissions. Injuries due to contact with flame or are proportional to the extent of injury.
ignition of clothing are the most common cause of burns in During the lint weeks after injury, the total white blood ceil
adults, whereas scald burns are most common in children. The count is elevated, but peripheral blood lymphocyte counts de-
m,Yority of patients sustain burns of such limited severity and crease. Alterations in lymphocyte subpopulations, including re-
extent (>80% of burns involve <20% of the body surface) versal of the nonnal ratio ofT helper cells to T suppressor cells,
that they can be treated on an outpatient basis. Approximately have been described (3,4). Delayed hypersensitivity reactions
170 to 230 patients per million population per year require and peripheral blood lymphocyte proliferation in the mixed
hospital admission owing to the extent of their bums or to lymphocyte reaction are both inhibited following burns. Altera·
other complicating factors. Approximately 33% of patients who tiona in interleuk.in-2 (ll.r2) production and n.-2 receptor ex-
require in-hospital care have a major burn injury-as defined pression by lymphocytes have been observed with burn injury;
by the American Bum Association on the basis of bum size, a direct correlation has been established between the extent
causative agent, preexisting disease, and associated injuries-- of the bum and the decline of n.-2 production by peripheral
and should be treated in a tertiary care bum center (2). lymphocytes (5).
Changes in wound care over the past 40 years, including the Increased numbers of circulating B lymphocytes are evi-
use of effective topical antimicrob:i.al chemotherapy and exci- dent early in the postbum coune; however, serum immuno-
sion of the burned tissue to achieve timely closure of the bum globulin G (IgG) levels decline after bum injury and gradually
wound, have significantly reduced the occurrence of invasive return to normal over the succeeding 2 to 4 weeks. The asso-
burn wound infection and its related morbidity and mortality. ciation of higher numbers of circulating B cells but reduced
Regular collection of cultures from patients permits early iden· serum levels of IgG suggests a defect in the ability of B cells
tification of the causative pathogens of those infections that do to generate a normal response after bum injury (6). Similar
arise. Moreover, infection control procedures, including strict findings have been observed in IgM-producing cells isolated
enforcement of patient and staff hygiene and use of patient from murine mesenteric lymph nodes and spleens following
isolation precautions, have been effective in controlling the burns ('1). Exogenous administration of IgG to bum patients
spread of multidrug-resistant organisms and eliminating them has been shown to promptly restore normallgG levels, but ex·
from the bum center. These advances and the improvements erts no demonstrable effect on the incidence or outcome of
in the general care of critically ill bum patients have resulted in infections (8).
markedly improved survival rates. However, as a marrifestation Bum injury induces a severity-related shift in the maturity of
of the systemic immunosuppressive effects of bum injury, infec- circulating granulocytes that continues for several weeks after
tion at other sites, predominantly the lungs, remains the most injury. Alterations in granulocyte function, including those of
552
Chapttr 37 • Infections of Bum Wounds 553
FREQUENCY OF INFECTION IN BURN PATIENTS and invasiveness of the microorganisms exceed the host's de-
fense capacity, proliferating organisms in the subeschar space
BRONCHITIS can invade the underlying viable tissue, leading to invasive
11 burn wound infection and even systemic spread to remote tis-
WOUND sues and organs. Bacterial invasion is uncommon unless the
number of microorganisms exceeds 105I g of biopsy tissue.
Certain strain-specific factors also appear to be important
in the pathogenesis of invasive bum wound infection. The
production of enzymes, such as collagenase, elastase, protease,
and lipase, can enhance the organisms' ability to penetrate the
eschar. Moreover, bacterial motility and antibiotic resistance
appear to be important in the development of invasive infec-
tion. Effective topical antimicrobial chemotherapy limits intra-
eschar bacterial proliferation and the attendant risk of invasive
infection.
Figure 37.1. The frequency of infection by site expressed as
a percentage of all infections complicating thermal injury. (From
United States Army Institute of Surgical Research, 1991-1995.) IDSTOLOGIC STAGING OF BURN
WOUND COLONIZATION AND
INFECTION
chemotaxis, adherence, degranulation, oxygen radical produc-
tion, and complement receptor expression, have been iden- The presence of microorganisms in the nonviable burned tis-
tified (9). Granulocytes isolated from bum patients exhibit sue, termed colonization, is a distinctly different entity from
increased cytosolic oxidase activity and greater-than-normal the presence of microorganisms in viable tissue beneath the
oxidase activity after in vitro stimulation, suggesting that these burn eschar, termed invasive bum wound infection. Histologic
neutrophils are primed and capable of producing more tissue examination of a biopsy of the burn wound and underlying vi-
and organ injury (10). Recent investigations have verified el- able tissue is the most rapid and reliable method for differenti-
evations of F-actin content and impaired ability to polymerize ating microbial colonization from invasive infection (12). Burn
F-actin in the granulocytes of bum patients when compared wound biopsy is performed as an intensive care unit or ward
with those of controls (11). These alterations can, in part, be procedure. An elliptical biopsy (0.5 X 1.0 em), which includes
responsible for the observed changes in chemotaxis and migra- the subjacent unburned viable tissue, is obtained by scalpel
tion after thermal injury. dissection from an area of burn wound suspected of being in-
fected. Hemostasis is easily achieved by the application of direct
pressure or by electrocoagulation. One-half of the specimen is
ETIOLOGY OF BURN WOUND cultured to identify microorganisms and their antimicrobial
INFECTION sensitivities. The remaining half is submitted to the pathology
laboratory for histologic examination. Using the rapid sec-
Both the nature of the bum wound and microorganism-specific tion technique, results are available in 3 to 4 hours, whereas a
factors influence the rate of microbial proliferation in and pen- frozen-section technique can yield a diagnosis in 30 minutes,
etration of the bum eschar. Bum tissue, rich in coagulated pro- albeit with an attendant 4% falsely negative diagnosis rate (13).
tein and well hydrated by the trans-eschar movement of fluid The presence of microorganisms in viable tissue confirms the
and serum, creates an excellent microbial culture medium. diagnosis of invasive bum wound infection (Figure 37.2). When
The eschar is avascular owing to thermal thrombosis of nutri- the organisms are confined to the necrotic eschar or there is
ent vessels, limiting both the delivery of systemically adminis- suppuration in the subeschar space separating nonviable from
tered antibiotics and the migration of phagocytic cells into the viable tissue, the wound is considered to be colonized, not in-
burned tissue. Bacterial proliferation in the wound can also be fected (Figure 37.3). Table 37.1 presents a histologic staging
enhanced by such factors as wound maceration, pressure scheme for burn wound colonization and infection.
necrosis, and wound desiccation with neo-eschar formation. In Surface cultures of the burn eschar cannot distinguish
addition, secondary impairment of blood flow to the wound colonization from invasive infection. Although commonly
could further predispose the patient to invasive infection by used in clinical practice, quantitative bacteriologic cultures
curtailing the delivery of oxygen, nutrients, and phagocytic of the bum wound correlate poorly with the presence of in-
cells to the viable subeschar tissue. vasive bum wound infection. When bacteriologic counts are
The character of the microbial flora of the bum wound < 105I g of biopsy tissue, invasive bum wound infection is rarely
changes with time. The gram-positive organisms that predomi- present; however, even when quantitative counts exceed 105
nate in the early postbum period are replaced by gram-negative organisms/g, histologic examination confirms the presence of
organisms by the second week. Without the application of invasive infection in <50% of such specimens. Burn wound bi-
topical antimicrobial agents, the density of bacteria groWl! pro- opsies can at times yield misleading results, but less commonly
gressively, and the microorganisms penetrate the eschar by mi- than wound cultures. Failing to include viable subeschar tissue
gration along sweat glands and hair follicles until they reach in the biopsy specimen or sampling of a noninfected area can
the eschar/nonviable tissue interface. Additional microbial limit the usefulness of this technique. Negative biopsy results
proliferation occurs in the subeschar space, enhancing the lysis in the presence of clinical deterioration necessitate reexamina-
of denatured collagen and sloughing the eschar. If the density tion of the bum wound and procurement of biopsy material
554 St!Ction III • E~ and Epitiemic Hospi:allnftc#itms
TABLE 37.1 Histologic Staging of Bum

Wound Colonization and
ID:vuion
S'L\GE I; COIDNJZAl'ION
Superficial: sparse microbial population on the sur&ce of bum
wound
Penetration: microorganisms present in variable thickness of
eschar
Proliferation: dense population of microorganism at the inter-
face of viable and nonviable tiuue
S'L\GE D: INVASION
Microilmuion: microscopic fod of organisms in viable tissue
immediately su~acent to subeschar space
Generaliud: widespread penetration of microorganisms deep
into viable subcutaneous tiuuea
Microvaacular: involvement of lymphatics and micrcnuculature
from other areas when other sources of systemic infection have

been cllicounted.
BURN WOUND MICROBIAL FLORA

Over the past 20 years, significant changes in the microbial
Figure 37.2. Photomicrograph of a burn wound biopsy specimen
showing hyphae typical of .&pergillus spp. present in unburned timle. ecology of the burn wound have been noted. The recovery of
The periVli!CUlar location of the hyphal element indicates stage nc Pl~ spp. and other gram-negative bacteria, which were
invasion. once the most common organisms causing bum wound infec-
tion, has markedly declined with improvements in the isola-
tion of patients (14). Consequently, invasive Pltudl.mwno.s spp.
burn wound infection has essentially disappeared as a compli-
cation of bum patients treated in tertiary bum centers (15).
Tables 37.2 and 37.3 review all burn wound biopsy remits in
general and those demonstrating invasive bum wound infec-
tion in particular, respectively, during a recent 5-year period at
the U.S. Army Institute of Surgical Research and confirm this
fact. Patients who have received broad-spectrum antimicrobials
for perioperative coverage or treatment of septic complications
and whose wounds remain open for many days owing to the
extent of the bum are at increased risk of bum wound coloni-
zation and infection by yeast!, fungi, and multiple antibiotic-
resistant bacteria. The ttue fungi have replaced bacteria as the
most common microbes causing burn wound infection in re-
cent years (16). This predominance of fungal wound infections
must be viewed in the context of the marked overall decline
in wound infections. Moreover, improperly cared for and ne-
glected bum wounds have the same high risk of bacterial infec-
tion as was conunon in this country several decades ago.
TABLE 37.2 Miaoorganism• Causing

Burn WOllDd IDfection
No.
~'PP· 12
Mucorspp. 5
EntmJIHJelfr eloGet.w 1
Alnmlorw A,.,.tla 1
F.igure 37.3. Photomicrograph of a burn wound biopsy specimen Entmcoccus jalcalis 1
showing deme inflammatory cell accumulation at the interface of Thtal 18
the viable tiuue to the right and the nonYiable tiuue to the left.
Branched hyphal elements are localized in this area, indicating stage From U.S. Army Jmdtute ofSurgical Research, 1991-1995.
IC colonization (arrow).
Effective infection control programs for burn centers should

TABLE 37.3 Organisms Isolated from include scheduled microbial surveillance of colonization of
Burn Wound Biopsy patients, environmental hygiene-monitoring procedures (see
Spedmals Chapter 20), biopsy assessment of the microbial status of the
GRAM-NEGATIVE SPECIES bum wound as necessary, monitoring of the incidence and
Pseu.tlomonas aeruginosa 174 causes of infection, and timely review of culture and clinical
Other species 270 data by the infection control team (see Chapter 5). The pa-
Total 444 (29.1%) tient colonization surveillance program typically includes
thrice-weekly cultures of sputum and the bum wound surface
GRAM-POSITIVE SPECIES and twice-weekly cultures of urine and stool. The determina-
Staphylococcus aunms 157 tion of a panel of antibiotic sensitivities for the predominant
Other species 271
Total 428 (28.0%) isolated organisms or targeted organisms aids in the recogni-
tion of problems with cross-contamination and introduction
NONBACTEKIAL PATHOGENS of multiply resistant bacterial strains into the unit's usual flora.
Mold species (principally 557 Strict criteria for the definition and identification of infections
Aspergillw spp.) that occur in bum patients are necessary to avoid nonessential
Candida alhicans 71 and inappropriate antibiotic use. To minimize the emergence
Other yeasts 26 of microbial resistance, antibiotics are used in general only for
Total 654 (42.9%)
specific indications. Effective infection control policies require
Total 1,526
continual reevaluation of surveillance culture results and cor-
From U.S. Army lrutitute of Surgical Research, 1991-1995. relation with the sites and treatment of infections. Prompt insti-
tution of effective infection control practices is required when
cross-contamination and/or other breaches in infection con-
trol are identified through these surveillance programs.
Viral burn wound infections are relatively uncommon Patient isolation in single-bed rooms has been shown to
and are usually caused by herpes simplex virus type 1 (see lower the incidence of cross-contamination and subsequent in-
Chapter 42) (17). Recently healed or healing partial-thickness fections complicating the hospital course of bum patients (19).
burns, particularly those in the nasolabial area, are most fre- In general, the airflow patterns of the isolation rooms are prob-
quently affected. The appearance of serrated crusted lesions, ably not as important as the prevention of patient-to-patient
particularly on the lips, is characteristic of viral infection. contact. However, positive airflow design can delay colonization
Diagnosis is made by histologically examining biopsy material by HAl flora. Negative airflow rooms in bum centers are gener-
or scrapings from the cutaneous lesions. Applications of topi- ally reserved for patients with infections spread by the airborne
cal5% acyclovir ointment every 3 hours for 1 week have been route (e.g., Mycobacterium tuberculosis) that could be hazardous
reported to shorten the time to heal these lesions, the duration to other patients and hospital staff members (see Chapter 33).
of associated pain, and the duration of viral shedding. Even
without treatment, these infections are usually self-limited and
of little or no systemic consequence. However, if systemic signs BURN WOUND HYGIENE AND
and symptoms of disseminated infection are present, such as TOPICAL ANTIMICROBIAL THERAPY
unexplained sepsis and/or unrelenting fever, the diagnosis of
disseminated viral infection should be entertained. Care of the burn wound begins at the accident scene by cover-
ing it with clean sheets or blankets to preserve body tempera-
ture and prevent continued environmental exposure. In the
PREVENTION OF BURN absence of gross contamination, bum wounds can be treated
WOUND INFECTION safely without topical antimicrobial agents for the first 24 to
48 hours. When a bum patient arrives at the definitive care fa-
Progress in the general care of the critically burned patient cility, initial burn wound debridement should be performed.
emphasizes preventing infectious complications. These efforts General anesthesia is not necessary; intravenous analgesia is
have focused mainly on the areas of environmental control sufficient for pain control during this procedure. The bums are
(through single-bed rooms and other forms of patient isola- gently cleansed with a surgical detergent antiseptic, and nonvi-
tion) and topical antimicrobial prophylaxis of the burn wound. able epidermis is debrided. Bullae should be excised and body
Effective infection control programs are essential to reduce hair shaved from the area of thermal injury beyond the margin
the exposure of patients in critical care units to healthcare- of normal skin. The patient is placed in a dean bed, and bulky
associated infection (HAl) pathogens. Such control includes dressings can be positioned beneath the burned parts to absorb
strictly enforced hand hygiene, gowning, and gloving policies. the often copious serous exudate. These dressings should be
When new endemic microbial strains are identified, preven- changed when they become saturated or soiled, and patients
tion of patient-to-patient spread and unit environmental con- should be turned frequently to prevent maceration of burned
tamination can be accomplished using patient cohorting (see and unburned skin. The initial debridement and daily cleans-
Chapters 13 and 25). Cohorting, which entails the assignment ing with an antimicrobial-containing surgical scrub is best per-
of patient-care personnel in teams to provide care for only a formed in a shower area using a handheld shower head with
specific patient or only patients colonized or infected with a the patient lying on a disposable plastic sheet-covered litter or
targeted organism, limits the spread of and can even eliminate specially designed shower cart. Alternatively, the patient can be
antibiotic-resistant endemic organisms (18). placed on a slanted plinth suspended over a physical therapy
tank. Immersion hydrotherapy is not necessary and can serve not penetrate the eschar because the silver ions are rapidly
only to disseminate the fecal flora or other contaminating precipitated on contact with any protein or cationic material.
organisms over the entirety of the bwn wound. For patients Use of this agent is not associated with more intense wound
whose general condition is too critical to permit movement to pain except from the mechanical action required for dress-
a shower area, daily wound care can be carried out at the bed- ing changes. The dressings, which are changed twice daily,
side. Following cleansing and debridement, the topical antimi- are moistened every 2 hours with the silver nitrate solution to
crobial agent of choice is applied. prevent evaporation from increasing the silver nitrate concen-
Mafenide acetate (Sulfamylon), silver sulfadiazine (Silvadene), tration to cytotoxic levels within the dressings. Trans-eschar
and silver nitrate are the three most commonly employed topi- leaching of sodium, potassium, chloride, and calcium should
cal antimicrobial agents for bum wound care. Each agent has be anticipated, and these chemical constituents should be ap-
specific limitations and advantages with which the physician propriately replaced. Hypersensitivity to silver nitrate has not
must be familiar to ensure the patient's safety and optimal bene- been described. Mafenide acetate, silver sulfadiazine, and 0.5%
fit. Mafenide acetate and silver sulfadiazine are available as topi- silver nitrate are effective in preventing invasive bum wound
cal creams to be applied directly to the bum wound, whereas infection; however, because of their lack of eschar penetration,
silver nitrate is applied as a 0.5% solution in occlusive dressings. silver nitrate soaks and silver sulfadiazine bum cream are most
Either cream is applied in a 1/8-inch layer to the entire bum effective when applied soon after bum injury.
wound in an aseptic manner after initial debridement and reap- Recently, many silver-containing dressings have become
plied at 12-hour intervals or as required to maintain continuous available and are marketed as antimicrobial barrier dressings.
topical coverage. Once daily, all of the topical agents should be Some have the indication to be used on second-degree bums.
cleansed from the patient using a surgical detergent antiseptic Also, most of these dressings can be left on the wounds for
solution and the bum wounds examined by the attending phy- several days. Like silver nitrate, the bacteriocidal properties of
sician. Silver nitrate is applied as a 0.5% solution in multilay- silver are responsible for the antimicrobial nature of these dress-
ered occlusive dressings that are changed twice each day. ings, but are not indicated for use on full-thickness bums. Free
Mafenide acetate bum cream is a 11.1 % suspension in a silver cations have a potent antimicrobial effect that destroys
water-tioluble base. This compound diffuses freely into the eschar microorganisms immediately by blocking cellular respiration
owing to its high degree of water solubility. Sulfamylon is the and disrupting the fwlction of the bacterial cell membranes.
preferred agent if the patient has heavily contaminated bwn This occurs when silver cations bind to tissue proteins, causing
wounds or has had bum wound care delayed by several days. structural changes in the bacterial cell membranes, which, in
Sulfamylon has the added advantage of being highly effective twn, cause cell death. Silver cations also bind and denature the
against gram-negative organisms, including most Pseudmnonas bacterial DNA and RNA, thus inviting cell replication. There is
spp. Physicians using this agent must be aware of several poten- no indication that silver is absorbed significantly into the bum,
tial clinical limitations associated with its use. Hypersensitivity but an increase in serum levels has been described in case re-
reactions occur in 7% of patients, and pain or discomfort of ports (21). When using dressings that can be left in place for
20 to 30 minutes' duration is common when it is applied to > 1 to 2 days, it is essential to ascertain that the wounds indeed
partial-thickness bwn wounds. This agent also inhibits carbonic are partial-thickness in nature and that healing would be ex-
anhydrase, and a diuresis of bicarbonate is often observed after pected to occur within 1 to 3 weeks. A serious bum wound in-
its use. The resultant metabolic acidosis could accentuate post- fection could occur beneath an occlusive dressing left in place
bum hyperventilation, and significant acidemia could develop for an extended period on a full-thickness bwn. Since these
if compensatory hyperventilation is impaired. Inhibition of this dressings may be left in place for several days, the pain associ-
enzyme rarely persists for >7 to 10 days, and the severity of ated with frequent dressing changes is minimized and the costs
the acidosis can be minimized by alternating applications of associated with more frequent dressing changes are reduced.
Sulfamylon with silver sulfadiazine cream every 12 hours. The acceptance and widespread appliance of prompt bum
Silver sulfadiazine bwn cream is a 1% suspension in a water- wound excision in the early care of bum patients also has con-
miscible base. Unlike Sulfamylon, Silvadene has limited solu- tributed to the decreased incidence of bacterial bum wound
bility in water and, therefore, limited ability to penetrate into infection. Surgical excision and split-thickness skin grafting
the eschar. The agent is most effective when applied to bwns of burns diminish the time during which the wound is at risk
soon after injury to minimize bacterial proliferation on the of invasive infection. In patients with bums <40% of the total
wound's surface. This agent is painless upon application, and body surface, excision is associated with shorter hospital stays,
its use does not affect serum electrolytes and the acid-base bal- and the bwn wounds can be definitively grafted in one or two
ance. Hypersensitivity reactions are uncommon; an erythema- surgical procedures (22). In patients with bwns 2:40% of the
tous maculopapular rash subsides on discontinuation of the total body surface, bum wound excision can shorten the du-
agent. Silver sulfadiazine occasionally induces neutropenia by ration and magnitude of injury-related physiologic stress and
a mechanism thought to involve direct bone marrow suppres- the subsequent degree of immunologic impairment. As soon
sion; white blood cell counts usually retwn to normal follow- as the initial bwn resuscitation is complete and the patient is
ing discontinuation (20). With continual use, resistance to the physiologically stable, bwn wound excision can be initiated in
sulfonamide component of silver sulfadiazine is common, par- staged procedures so that the entirety of the full-thickness or
ticularly in certain strains of Pseudomonas and many Enterobacter deep partial-thickness wounds can be removed within several
spp. However, the continued sensitivity of microorganisms to weeks. When skin donor sites are not available for complete
the silver ion of this compound has maintained its effectiveness grafting of these wounds, a variety of skin substitutes and
as a topical antimicrobial agent. biologic dressings can be used as a bridge to complete wound
A 0.5% silver nitrate solution has a broad spectrum of an- coverage. The exact contribution of surgical treatment to the
tibacterial activity imparted by the silver ion. This agent does decline in incidence of invasive bacterial bum wound infection
CMfMr J7 • Inftdi<ms ofBwm Wounds 557
has not been well documented; however, the temporal relation-

ship cannot be ignored.
CLINICAL DIAGNOSIS OF BURN

WOUND INFECTION
Bum wound infection occurs most commollly in patients in
whom the extent of bum exceeds 30% of the body surface
and in those who have suffered skin graft failure that left an
open wound. Succes.sful treatment of burn wound infection
requires early detection; therefore, it is mandatory that the en-
tire wound be examined daily to detect change& in appearance.
The clinical signs of invasive burn wound infection are often
indistingtilihable from those observed in uninfected hyper-
metabolic burn patients or in burn patients with other forms
of sep.sis. These findings can include hypel"' or hypothermia,
tachycardia, tachypnea, ileus, glucose intolerance, and disori-
entation. Physical and tinctorial changes in the appearance
of the burn wounds are more reliable signs of invasive burn Figure 37.4. Multiple areas of dark discoloration on the thigh and
wound infection (Thble 3'7.4). Convenion of an area of partial- buuocb of this patient, accompanied by unexpectedly rapid e&char
thickness burn to full-thickness necrosis and the appearance of separation, characteristic of bum wound infection.
focal areas of dark hemorrhagic or black discoloration are the
most commollly noted changes indicative of burn wound infec-
tion (Figure 37.4). The development ofclinical signs and symp- texture, appearing in a skin graft interstice or an area of open
toms of sepsis in the thermally injured patient should prompt wound. This rurface appearance is often accompanied by sub-
a thorough examination of the burn wound to identify areas cutaneous burrowing tunnels filled with the invading fungus
suspected of harboring invasive infection. Confumation of the and detected at the time of surgical debridement.
diagnosis of bum wound infection is made by histologic exami- The phycomycetes are typically aggressive, spreading rapidly
nation of a biopsy specimen as previously described. along tissue plains, traversing fascia, and invading blood vessels
The emergence of nonbacterial opportunists as the major and lymphatics (23). Infectiom caused by these organisms are
pathogem invading the burn wound has rerulted in changes characterized by expanding soft-tissue ischemic necrosis with a
in the classic clinical presentation of bum wound infection. peripheral edematous rim and, frequendy, hematogenous dis-
Candida spp. rarely invade the wound to cause systemic infec- semination to remote sites. The diagnosis is confumed, as with
tion. However, Candida spp. infection can arise in the inter- bacterial bum wound infection, by histologic examination of a
stices of a meshed skin graft and in an excised bum wound that biopsy specimen.
remains unclosed as a consequence of the loss of a skin graft
or a biologic dressing. Filamentous fungi are more aggres.sive
invaders of the bum wound and could cause severe infection. TREATMENT OF BURN
These fungi rarely traverse fascial planes and remain confined WOUND INFECTION
to the subcutaneous tissues. AsptrtgiUw spp. can be detected as
colonizers and occasionally as invaders of the bwn eschar by The treatment of bum wound infection is initiated upon histo-
histopathologic examination of burn wounds at the time of ex- logic confumation of the presence of microorganisms in viable
cision and skin grafting. The clinically relevant infections oc· tissue. If only colonization (stage lA-c) is present, no specific
cur, however, relatively late in the hospital course of patients change in antimicrobial therapy is indicated unless serially ob-
with extensive burns who have already undergone multiple op- tained biopsy specimens document progression of the coloniza-
erative procedures (for which they have received perioperative tion stage. If stage 2 (invasion) is observed, prompt treatment
broad-l!lpecttum antimicrobials) and still have unexcised eschar for invasive burn wound infection should begin. In the case of
or previously excised, ungrafted open wounds. These infec· bacterial burn wound invasion, topical twice-daily applications
tions often resemble a colony of mold with a somewhat fuzzy of mafenide acetate should be used. The eschar-penetrating
ability of this agent extends the antimicrobial activity through-
out the depth of the bum eschar. Systemic antibiotic therapy
TABLE37.4 CliDical Sips of Bum is initiated on the basis of previous burn wound surveillance
Wound Infection cultures and bum center organism prevalence. Additional re-
finements in antibiotic treatment are based on the individual
• Focal dark brown or black discoloration of wound patient's wound culture and sensitivity results. Supportive criti-
• Con~nion of leCOild4egree bum to ~thicknal necrosis cal care is employed to maintain hemodynamic and respiratory
• Depneralion of wound with neoachar formation
stability, as it is for other severely ill patients.
• Unexpectedly mpid eachar aeparalion
Injection of an antibiotic solution into the subcutaneous tis-
• Hemorrhagic dUcoloralion of suheachar fat
• Violaceous or erythematous edematous wound IJial1in sue beneath the eschar (subeschar clysis) is recommended be-
• Metastatic leptic lesions in unburned skin or distant orpm fore surgical excision of an infected bum wound to minimize
the risk of hematogenous seeding and precipitation of florid
septic shock (24). Half of the daily dose of a broad-spectrum exotoxin. The usual dose is 3,000 to 6,000 (u) given intramus-
antipseudomonal penicillin, such as piperacillin or ticarcillin, cularly. Intravenous penicillin G (10 to 40 million u per day)
delivered in 1 L of normal saline is infused into the subeschar should be given to eradicate the Clostridium spp. organisms.
tissues using a no. 20 spinal needle to minimize the number of Uncontrolled muscle spasms can lead to rhabdomyolysis and
injection sites. The patient is prepared and scheduled for surgi- skeletal fractures. Morphine, magnesium sulfate, and epidural
cal excision of the infected tissue within the next 6 to 12 hours, anesthesia all have been used to reduce muscle spasticity.
and the subeschar clysis is repeated immediately before surgery. Sedation with benzodiazepines or barbiturates could be neces-
Excision of the burn wound to the level of the investing sary, and, in severe episodes, neuromuscular blockade could be
muscle fascia ensures complete removal of all nonviable in- required.
fected tissue. After excision of the bum, the wound is treated Fortunately, tetanus is readily prevented. During the initial
with moist dressings containing an antimicrobial agent, such as care of the burn patient, the patient's tetanus immunization
0.5% silver nitrate solution (the authors use a 5% mafenide ac- status should be determined. The bum patient who has been
etate solution, which is not generally available). Alternatively, a immunized against tetanus should be given a booster dose of
biologic dressing can be applied if all nonviable tissue has been tetanus toxoid if the last dose was administered > 5 years ear-
removed and the exposed tissue appears to be uninfected. The lier. Patients with no history or an uncertain history of active
patient is returned to the operating room in 24 to 48 hours; at immunization should receive tetanus immune globulin in ad-
that time, the wound is inspected, and redebridement or split- dition to the initial dose of tetanus toxoid. Active immuniza-
thickness skin grafting can be performed as needed. tion is subsequently completed according to the routine dosage
The treatment for candida( or fungal bum wound infection schedule.
is similar to that of invasive bacterial infection. Infection or new
colonization of previously excised or grafted wounds requires STAPHYLOCOCCUS AURBUS
treatment by twice-daily application of a topical antifungal
agent, such as clotrimazole cream or ciclopirox olamine cream. Toxin-producing Staphylococcus spp. have been isolated from
Such treatment usually controls surface colonization. However, both colonized and infected bum wounds and other sites of
if the superficial infection continues to extend or the fungal infection (25,26) (see Chapter 41). The emergence of gram-
infection is shown to involve deep tissue, such as fascia or muscle, positive organisms as the predominant flora in bum patients
if it has invaded the microvasculature of underlying viable tis- has contributed to a lessening in the impact of infection; the
sue, or if it is associated with systemic signs of sepsis, parenteral virulence of Staphylococcus aurew can be strain-specific, and
administration of amphotericin B should be initiated. The in- bacteremia resulting from strains possessing the gene for the
fected tissue must be widely debrided and treated with a topi- production of toxic shock syndrome toxin has been associated
cal antifungal agent applied beneath occlusive dressings, which with episodes of unexplained profound hemodynamic instabil-
should be changed two to three times daily. The patient is re- ity. This gene, however, has been identified in staphylococcal
turned to the operating room 24 to 48 hours later for further strains recovered from patients with wound colonization,
debridement and closure of the bum wound by autografting or bacteremia, and other infections without evidence of profound
applying a biologic dressing as dictated by the adequacy of the physiologic disturbance.
initial debridement The diagnosis of a variant of the toxic shock syndrome should
be considered in thermally injured patients with Staphylococcus
spp. infections who manifest hemodynamic instability that re-
sponds poorly to treatment and that is out of proportion to
INFECTIONS OF SPECIAL CONCERN
what is usually encountered in gram-positive infections. The
initial treatment requires aggressive intravenous fluid resuscita-
CLOSTRIDIUM TETANI
tion to restore hemodynamic stability. Vancomycin should be
Tetanus, caused by the neurotoxin of Clostridium tetani, an an- administered intravenously unless the organism is known to be
aerobic, gram-positive, spore-forming rod ubiquitous in soil sensitive to methicillin when a J-lactamase-resistant antistaphy-
and the gastrointestinal tracts of humans and animals, has lococcal antibiotic, such as nafcillin, can be given.
been reported as a rare complication of thermal injury. This or- At present, an antitoxin to the toxic shock syndrome toxin
ganism thrives in hypoxic wounds and necrotic tissue, both of 1 is not available. Approximately 90% of the general popula-
which exist in the full-thickness bum. The diagnosis of tetanus tion has antibodies against the toxin, but nearly all patients
is based on characteristic physical findings because wound cul- with toxic shock syndrome related to menstruation have had
tures often fail to detect the causative organism. The usual ini- undetectable antibodies at the onset of the disease. Although
tial signs and symptoms are severe trismus with stiffness of the this relationship has not been confirmed in thermally injured
paraspinous and abdominal musculature. Localized or general- patients thought to have the variant toxic shock syndrome, the
ized muscle spasm, dysphagia, and laryngospasm can develop; isolation of a strain of S. aurew producing the toxic shock syn-
the disease can progress to involve more muscle groups, causing drome toxin 1 and the absence of circulating antibodies to the
generalized rigidity. Ventilation can be impaired by involve- toxin could help establish the definitive diagnosis.
ment of the diaphragm, chest, and abdominal musculature. Antibiotic-resistant bacteria of special note and the subject
Severe episodes require endotracheal intubation and mechanical of much controversy are the methicillin-resistant strains of
ventilation. The treatment is mainly supportive and involves S. atmUS (MRSA) (see Chapters 15 and 41). Since the 1960s, these
aggressive critical care management of the hemodynamic and strains have been reported and treated as if they were distinct
respiratory systems. pathogens with more virulence than other methicillin-sensitive
When the diagnosis is made, tetanus immune globulin should strains. Undoubtedly, the emergence of antibiotic-resistant
be administered immediately to neutralize any circulating free organisms is of concern, and efforts should be made to limit
their inroads. However, the unique concern about MRSA in management of bum wound infection, surgical debridement
particular has resulted in temporary closure of bum and other should be accomplished expeditiously as outlined previously.
intensive care fucilities and restriction of patients' movements
among levels of care. The benefits of these practices must al-
ways be weighed against their clinical, epidemiologic, and SUMMARY
economic value.
The virulence and pathologic significance of MRSA com- Despite significant improvements in the survival of bum pa-
pared with methicillin-sensitive strains causing infections in tients, infectious complications continue to be the major cause
bum wound patients were evaluated in a 1989 study (27). Colo- of morbidity and mortality. Control of invasive bacterial bum
nization with any strain of Staphylococcus was identified in 658 wound infection by effective topical antimicrobial agents and
bum patients treated during a 6-year period; of this total, 319 prompt excision and split-thickness skin grafting of the burn
(or nearly half) of these patients were colonized with MRSA. wound clearly are possible with modem bum care. In addition,
In this group, a total of 253 staphylococcal infections occurred strict isolation techniques and infection control policies have
in 178 patients: 58% of infections were pulmonary and 38% significantly minimized the occurrence of bum wound infec-
were bacteremias. In 58 out of the 178 patients, infections were tions in general and those caused by gram-negative organisms
caused by MRSA. The outcomes of patients infected with MRSA in particular. In those patients in whom a bum wound infec-
or methicillin-sensitive strains of S. auml.S (MSSA) were com- tion develops, bacterial infection has been largely supplanted
pared using a multiple logistic regression analysis of mortality. by infection caused by nonbacterial opportunists, namely,
In both groups, all patients were treated with vancomycin, and fungi and yeasts. Scheduled wound surveillance and microbio-
no differences in the observed and predicted mortality were logic monitoring with the use of wound biopsies to provide his-
found between groups. We believe these findings suggest that tologic confirmation of bum wound infection permits prompt
both MRSA and MSSA in bum patients can lead to serious ad- diagnosis of microbial invasion at a stage when timely institu-
verse outcomes. The main concern related to frequent use of tion of antibiotic therapy and surgical intervention can save
vancomycin is the possible development of vancomycin and the patient.
methicillin resistance prompted by the recent recognition of
vancomycin-resistant strains of S. aunous and enterococci (see
Chapter 15). Individual centers should adopt strict criteria for
REFERENCES
diagnosing specific infections in bum patients and specific in-
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dications for antibiotic use on the basis of the prevalence of octerittia of burn i'\iury. In: Herndon DN, ed. 'llllrllllum C..... Houaton, TX: .Ellevier;
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comycin and other antimicrobials. 2. Rewun:eo for optional care of patienta with burn i'\iury. In: Rl:srnm:cJ for Oplimal Ctm af
1M lttju<rd Padlm. Chlcago, IL: Committee on Trauma, American Colleg<> of Surgl'ono;
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AER.OMONAS SpP. tig<'n ""Preuion and neutrophil respiratory bunt activity after thermal injury. Bums.
1993;19:5-11.
Human infection with Aeromonas spp. most often is associated 4. Burleoon DC, Vaughn GK. Mason AD Jr, et aL .Flow cytometric meaaurement of rat
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1987;122:216-220.
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by Aenmwnas spp. are rare; <20 episodes have been reported a fundamental immunological deficiency in patienta with major burna. AM Swg.
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6. Molloy llG, Neator M, CollinJ KH. The humoral immune reaponae after !henna! injury: an
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globulin I)'Ilthcllio in mkc.J'Itrnmta. 1993;35:75()...755.
veloped during their hospital stays (28). In six of the eight pa- 8. Sbirani KZ, Vaughn GM, McManuo AT, et aL Replacement thernpywith modified immuno-
tients, the organism was isolated from wound cultures as well. globulin Gin bum patients: preliminary kinetic otudico. AaJMtrl. 1984;76:175-180.
Aquatic exposure was known or suspected in only three of the 9. Cioffi WG, Burleson DG, Pruitt BA Jr. Leukocyte reoponoea to injury. Am Swrg.
1993;128:1260--1267.
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11, Droat AC, Cioffi WG Jr, Carrougher GJ, et al. The relationohip of granulocyte F-a<tin le¥-
within 48 hours of injury. Subcutaneous abscess formation is
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12. Kim SH, Hubbard GB, Wurley BL, et aLA rapid oection ~bnique for burn wound biopoy.
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19. McManw AT, Maoon AD Jr, McManw WF, et aL A decade of reduced gnun negative
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23. Pruitt RA. Jr. Phycomycoti.c infectiono. In: A!eDnder SW, ed. ftOO/mu in GmmJl Sutgor]. 1989;12+.1456-1459.
Philadelphia, PA: Lippincott; 1984. 28. Ba.rillo DJ, McManuo AT, Cioffi we, et al. Aeromonaa bacteraemia in bum patienu. Bunu.
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Nasia Safdar, Dennis G. Maki, and Leonard A. Mermd
Infections due to Infusion Therapy

Reliable intrava!CUlar access for the administration of fluids the fluid {i.e., infulate) administered through the cannula.
and electrolytes, blood producta, drugs, and nutritional sup- Cannulas, which cause moat endemic IVDR-BSis, produce BSI
port, and for hemodynamic monitoring ia now one of the moat far more frequently than contaminated infusate, the source of
essential features of modem medical care (Table !J8.1). Each moat epidemics of infusion-asaociated BSI ( 1).
year in the United States, -150 million intravascular device.t are It is important to understand the different stages and forms
purchased by hospitals and cl.inia. The vast majority are pe- of device-related inflammation or infection, which range from
ripheral venous catheters; howe'Yt!r, >5 million central venous infusion phlebitis-usually Ullrelated to infection-to asymp-
devices of various types are sold in the United States annually. tomatic colonization of the intravascular device-usually by
More than one-half ofall epidemics of healthcare-aasodated akin commemals with little intrinsic virulence-to overwhelm-
bacteremia or candidemia reported in the world literature being septic shock originating from an infected thrombus in a
tween 1965 and 1991 are derived from vascular access in some cannulated great central vein or from infusate heavily contami-
form (1,2). One-third to one-half of episodes of healthcare- nated by gram-negative bacllU.
associated endocarditia have been traced to infected intravas-
cular catheters (~7), and healthc~ciated int.ravalcular INFUSION PHLEBITIS
device-related bloodstream infection (IVDR-BSI) ia associated
with a 12% to 28% attributable mortality (S-11). Yet, infusion Infwion pkllbitis, defined as inflammation of the cannulated
therapy generally has an underappreciated potential for pro- vein-pain, erythema, tenderness, or an inflamed, palpable,
ducing iatrogenic disease. For example, <50% of the intemive thrombosed vein-is a frequent cause of pain and discomfort
care unita (ICUs) in the United Kingdom had a written policy to the millions ofpatients who receive infusion therapy through
concerning the care of central venous catheters (CVCs) after peripheral intravenous (IV) cannulas each year in U.S. hospi-
insertion (12). tals. Moat investigaton have concluded that infusion phlebitia
Infusion-related BSI is too frequently unrecognized, in great is primarily a physicochemical phenomenon, and prospective
measure because of its relative infrequency. The percentage of studies have shown that the cannula material, length, and bore
i.nftuions identified as producing BSI ia rufficiently low--<1% size; operator skill on insertion; the anatomic site of cannula-
on the average-that an average phylician or nurse is unlikely tion; the duration of cannulation; the frequency of dressing
to encounter more than an occasional episode. But even a low changes; the character of the infusate; and host factors such as
incidence of infection applied to the estimated 30 million pa- patient age, Caucasian race, female gender, and the preaence
tients who receive infusion therapy in U.S. hospitals annually of underlying diseases si.gnilicantly influence the risk of infu-
translates into an estimated 50,000 to 100,000 BSis nation- sion phlebitis (Table 38.2).
wide each year (1,2,1~), with 55,000 due to CVCs in U.S.ICUs In a prospective clinical study of 1,054 peripheral IV cath-
(14,15). Because neither the device nor the infuaate is routinely eters, the Kaplan-Meier risk for phlebitia exceeded 50% by
cultured, the source of the BSI in a large proportion of epi- the fourth day after catheterization. IV antibiotics (relative
sodes is never recognized. risk [RR], 2.0), female gender (RR, 1.9), catheterization be-
IVDR-BSI u 1arge1j jJreomtiJhiL This premise fonns the thesis yond 48 hours (RR. 1.8), and catheter material (polyetber
for this review: the primary goal must not be simply to iden- urethane [Vwon]; tetraOuoroethylene-hexafluoropropylene
tify and treat these iatrogenic infections, but rather to prevent [Teflon]; RR, 0.7) were strong predictors of phlebitis in a Cox
them. By critically scrutinizing existing knowledge of the patho- proportional hazards model (each, p < .003) (17). The best-fit
genesis and epidemiology of device-related infection-the re~t model for severe phlebifu identified the same predictors plua
ervoirs ofhealthcare-associated infection (HAl) pathogens and catheter-related infection (RR, 6.2), phlebitis with the previous
modes of transmission to patients' infusion:t-rational and ef- catheter (RR, 1.5), and anatomical site (hand:forearm, RR, 0.7;
fective guidelines for prevention can be formulated (16). wrlst:forearm, RR, 0.6).
Although not all studies have identified an association be-
tween phlebifu and catheter-related infection (18,19), this
SOURCESANDFORM SOF large, prospective study showed a strong statistical auociation,
INFUSION-RELATED INFLAMMATION as have other studies (20-24). Phlebitis can also be produced
AND BLOODSTREAM INFECTION by contaminated infusate. Patients with BSI from intrinsically
contaminated Ouid in a large, nationwide epidemic traced to
There are three major sources of BSI associated with any in- the contaminated producta of one U.S. manufacturer in 1970
travascular device: (a) colonization of the cannula wound, to 19'71 had a much higher incidence of phlebitia than patients
(b) colonization of the cannula hub, or (c) contamination of receiving IV fluids who did not develop BSI (25).
561
TABLE 38.1 Applications of Infusion TABLE 38.2 Risk Factors for Infusion
Therapy Phlebitis in Peripheral
in the 2000s IV Therapy Identified in
Fluid and electrolyte replacement Prospective Studies by
'liamfusion therapy Multivariate Discriminant
Blood products Analysis or in Prospective,
Exchange transfusion
Pl3.!1I1lapheresis and apheresis
llandomized, ControHed
IV drug administration Trial•
hnmediate circulatory acce55 for critically ill patients Catheter material
High blood and tissue levels Polypropylene vs. Teflon
Drugs that cause wsue necrosis Silicone elastomer vs. polyurethane
Drugs that cause thrombolysis Teflon vs. polyether urethane
Hemodialysis Teflon vs. steel needles
Hemodynamic monitoring Catheter size
Central venom catheters Large bore vs. smaller bore
Central venow preuure 8 vs. 2 inches Teflon
Pulmonary artery Swan--Can.z catheters Insertion in emergency room vs. inpatient units
Pulmonary artery pre55ure Disinfection of skin with antiseptic before catheter insertion
Pulmonary artery occlusion (left atrial filling) pre55ure Experience and skill of the person inserting the catheter
Thermodilution cardiac output House officers, nurses vs. hospital IV Team
Arterial catheters House officers, nurses vs. decentralized unit IV nurse educator
Continuom arterial blood pre55ure Increasing the duration of catheter placement in site
Total parenteral nutrition Subsequent catheters beyond the frrst infusate
Hyperalimentation (central venow catheters) Low-pH solutions (e.g., dextrose-containing)
Peripheral parenteral nutrition (peripheral IV catheters) Potassium chloride
Special nutritional support regimens for: Hypertonic glucose, amino acids, lipid for parenteral nutrition
Acute renal failure Antibiotics (especially )-lactams, vancomycin, metronidazole)
Hepatic failure High rate of flow of IV fluid (>90 mL/ hour)
Cardiac cachexia Disinfection of insertion site before catheter insertion
Pancreatiw None vs. chlorhexidine/ alcohol
Acquired immunodeficiency syndrome Frequent IV Dressing Changes
Intra-ru-terial cancer chemotherapy Daily vs. every 48 hours
Catheter-related infection
IV, intravenom. Host fiu:tors
"Poor-quality" peripheral veins
Insertion site
Only a small proportion of patients with IV cannula-associ- Upper arm, wrist vs. hand
Age
ated peripheral vein phlebitis have infusion-related infection, Children; older vs. younger
and <50% of patients with peripheral IVDR-BSI show phlebitis; Adults: younger vs. older
however, the presence of phlebitis connotes a substantially in- Sex
creased risk of infection and indicates the need for immediate Female vs. male
removal of the catheter to reduce the severity of phlebitis, for Race
symptomatic relief, and to prevent catheter colonization from White vs. African American
Underlying medical disease
progressing to BSI. Individual biologic vulnerability
Factors shown not to increase risk in well-controlled, prospective,

CANNULA-RELATED INFECTIONS
randomized trials include catheters made of polyethylene vs. sili-
Between 5% and 25% of intravascular devices are colonized conized elastomer or of Teflon vs. siliconized elastomer; type of
by skin organisms at the time of removal, as reflected by semi- antiseptic solutions used for cutaneous disinfection; use of topical
antimicrobial ointment or spray on catheter insertion sites; type of
quantitative or quantitative cultures showing large numbers
dressing (e.g., gauze vs. transparent polyurethane dressing); dress-
of organisms on the intravascular portion of the removed
ing change every 48 hour vs. not at all; administration of infusate
catheter or its tip. Colonization, which in most instances is by gravity flow vs. pump; administration of IV antibiotics by slow in-
asymptomatic, provides the biologic setting for systemic infec- fusion vs. "IV pwh" over 2 minutes; maintenance of heparin loeb
tion to occur and can be considered synonymous with local- with saline vs. heparinized saline; and frequency of routine change
ized infection. However, colonized cannulas are more likely of IV delivery system.
than noncolonized ones to show phlebitis or local inflamma- onenotes significantly greater risk of phlebitis; factors found to
tion, especially purulence-pus spontaneously draining or ex- be significant predictors of risk in a prospective study of 1,054 pe-
pressible from the insertion site-and are fur more likely to ripheral IV catheters at the University of Wisconsin Hospital and
cause systemic infection (i.e., cannula-related bacteremia or Clinics.
IV, intravenous.
fungemia) (21,26,27).
From Mali DG, Ringer M . Risk factors for infusion-related phle-
One of the most serious forms of intravascular device-related
bitis with small peripheral venous catheters. A randomized con-
infection occurs when intravascular thrombus surrounding the trolled study. Ann Intern Med. 1991;114:845--854, with permission.
cannula becomes infected. This causes septic (suppurative)
Chapter 38 • Inf«tions due to In.fwion Therapy 563
thrombophlebitis when it occurs in association with peripheral

IV cannulas (28,29), or septic thrombosis of a great central
TABLE 38.3 Clinical, Epidemiologic, and
vein when associated with centrally placed catheters (30,31). Microbiologic: Features of
With suppurative phlebitis, the vein becomes an intravascular lntravasc:ular Device-Related
absceM, discharging myriads of microorganisms into the blood- Bloodstream Infec:tion
stream, even after the cannula has been removed. The clinical Suggestive of Device-Related
picture is predictable: overwhelming BSI with high-grade and Nonspecific Etiology
often unremitting bacteremia or fungemia. This syndrome is
Fever Patient unlikely candidate for blood-
most likely to be encountered in burned patients or other ICU
stream infection (e.g., young, no
patients who have heavy cutaneous colonization and develop underlying di&eaaes)
a cannula-related infection that goes unrecognized, permit- Chills, shaking, rigors" Source of bloodstream infection
ting microorganisms to proliferate to high levels within the inapparent
intravascular thrombus. The catheter insertion site is devoid Hypotension, shock." No identifiable local infection
of signs of inflammation >50% of the time, and the clinical Hyperventilation Intravascular device in place, especially
picture may not present until several days after the catheter has central venous catheter
Respiratory failure Inflammation or purulence at
been removed. In any patient with an IV catheter who develops
insertion site
high-grade BSI that persists after an infected cannula has been Gastrointestinal" Abrupt onset, associated with shock"
removed, it is likely the patient has an infected thrombus in the Abdominal pain, Bloodstream infection refractory to
recently cannulated vein, and may even have secondary endo- vomiting antimicrobial therapy, or dramatic
carditis or seeding to other distant sites (32). improvement with removal of can-
The microorganisms most frequently implicated in sup- nula and infusion"
purative phlebitis are predominantly Staphylococcus aurew and Diarrhea Bloodstream infection caused by staphy-
Candida sp. (28-31). Although coagulase-negative staphylo- lococci (especially coagulase-negative
staphylococci), Corynebacterium
cocci commonly cause IVDR-BSI, they rarely cause suppurative
(especially JK-1) or Bacillus spp.,
thrombophlebitis, poMibly because of their lesser tendency to Candida,
bind to host-derived protein components of thrombus com- Confusion Trichophyton, Fusarium, or MaiassD:ia spp.
pared with other pathogens such as S. aunus (33,34). Seizures
Suppurative phlebitis of peripheral IV catheters is now rare,
and the syndrome of IV suppuration is predominantly a com- "Commonly seen in overwhelming gram-negative bloodstream
plication of eves, characteristically catheters that have been infections originating from contaminated infusate, peripheral
suppurative phlebitis, or septic thrombosis of a central vein.
left in place for many days in heavily colonized ICU patients.
BLOODSTREAM INFECTION FROM contaminated products, or the undue susceptibility to infection

CONTAMINATED INFUSATE of many patients. If affected patients are to survive, the causal
relationship between an infusion and the BSI must be recog-
It is also important to recognize that the infusate-parenteral nized as early as possible.
fluid, blood products, or IV medications-administered The general clinical features of infusion-related bacteremia
through an intravascular device also can become contaminated or fungemia are nonspecific and indiscernible from BSis arising
and produce infusion-related BSI, which is more likely than from any local site of infection, such as urinary tract infection
cannula-related infection to culminate in frank septic shock. (UTI) or surgical site infection (SSI) (Table 38.3). There also
Contaminated fluid is a rare cause of endemic infection with appears to be a poor correlation between clinical judgment and
short-term peripheral IV devices, but the infusate is more com- microbiologic confirmation ofiVDR-BSI (41). Infusion-related
monly associated with infections of catheters used for hemo- BSI occurring in ICU patients can be particularly insidious:
dynamic monitoring, evCs, and, poMibJy, surgically implanted bacteremia or fungemia is usually identified by positive blood
cuffed Hickman or Broviac catheters (35-38). Most healthcare- cultures, but is attributed to healthcare-associated pneumonia,
associated epidemics of infusion-related BSI, however, have UTI, or SSI, or is simply accepted as "cryptogenic" and treated
been traced to contamination of infusate by gram-negative ba- empirically.
cilli, introduced during its manufacture (intrinsic contamina- Certain clinical, epidemiologic, and microbiologic findings
tion) (25) or during its preparation or administration in the can be extremely helpful to the clinician evaluating a hospital-
healthcare system (extrinsic contamination) (1,2,39,40). ized patient with a picture ofhealthcare-aMociated BSI or cryp-
togenic bacteremia or candidemia, and point toward an IVD as
the source (Table 38.3):
DIAGNOSIS OF INFUSION-RELATED
1. The patient is an unlikely candidate for BSI, being healthy
BWODSTREAM INFECTION and without underlying predisposing diseases (25,42).
2. No local infection to account for a picture ofBSI (25,42).
CLINICAL FEATURES
3. An IVD in place, especially a eve, at the outset of BSI (42).
Although meticulous aseptic technique during cannula inser- 4. Local inflammation (21,26,27,43), especially purulence
tion and good follow-up care greatly reduce the risk of IVDR- at the insertion site (27,43), which while present in only
BSI, sporadic episodes and even epidemics can still be expected a minority of instances, is strongly suggestive of a catheter-
occasionally to occur because of human error, intrinsically related infection.
5. Abrupt onset, associated with fulminant shock-suggestive as much as standard blood cultures. The wide availability of
of massively contaminated infusion (44). radiometric blood culture systems (BACTEC system; Becton
6. Healthcare-associated BSI caused by staphylococci ( 42), es- Dickinson, Sparks, Maryland, USA), in which blood cultures
pecially coagulase-negative staphylococci, Corynebacterium are continuously monitored for microbial growth (approxi-
(especially JK-1), or Bacillus spp., or Candida (42), Fusar- mately every 20 minutes), has led to a clever application of this
ium, Trichophyton, or Malassezia spp., suggests IVDR-BSI. In system for the detection of IVDR-BSI (62). The differential
contrast, bacteremia caused by streptococci, aerobic gram- time to positivity (DTP) of blood cultures drawn through the
negative bacilli-especially Pseudomunas aeruginosa-or an- IVD and concomitantly from a peripheral vein has been evalu-
aerobes is very unlikely to have originated from an infected ated as a surrogate for paired quantitative blood cultures. The
IVD (42). detection of positivity in a blood culture drawn from the IVD
7. BSI refractory to antimicrobial therapy or dramatic im- >2 hours before positivity of the culture drawn from a periph-
provement with removal of the cannula or discontinuation eral site has been shown to be highly predictive of IVDR-BSI in
of the infusion (25,42). several studies of both short- and long-term catheters (62,63).
In a meta-wJ.alysis of 49 studies evaluating eight different meth-
During a large, nationwide outbreak in 1970 to 1971 ods for diagnosis ofiVDR-BSI, DTP had a sensitivity of0.90 and
due to intrinsic contamination of one U.S. manufacturer's specificity of 0.83 (27).
products, patients treated with antibiotics to which the epi- The volume of blood cultured is critical to maximize the
demic organisms were susceptible remained clinically septic, yield of blood cultures for diagnosis of bacteremia or can-
continued to have positive blood cultures after 24 hours or didemia: in adults, obtaining at least 20 mL, ideally 30 mL,
more of appropriate therapy, and did not improve clinically per drawing-each specimen containing 10 or 15 mL, in-
until their infusions were serendipitously or intentionally re- oculated into aerobic and anaerobic media-significantly
moved (25). improves the yield, compared with obtaining only 10 mL at
Focal retinal lesions--cotton-wool spot patches--may be each drawing and culturing a smaller total volume (64,65).
seen in patients with disseminated Candida spp. infection de- It is rarely necessary to obtain >2 15-mL cultures or three
riving from eves, even in those without positive blood cul- 10-mL cultures in a 24-hour period. If at least 30 mL of blood
tures (45). Careful ophthalmologic examination should be is cultured, 99% of detectable bacteremias should be identi-
routinely performed in the evaluation of patients with eves fied (64).
with suspected IVDR-BSI, especially patients receiving total It is common practice in many ICUs to draw blood cul-
parenteral nutrition (TPN). BSI from arterial catheters may tures through central venous or arterial catheters or, in neo-
be heralded by embolic lesions that manifest as tender, ery- nates, through umbilical catheters. Comparative studies of
thematous papules, 5 to 10 mm in diameter, appearing in the standard blood cultures drawn through central venous or arte-
distal distribution of the involved artery, usually in the palm rial catheters in adults usually have shown good concordance
or sole-Osier nodes (46,47). Arterial bleeding from the inser- with cultures drawn by percutaneous peripheral venipuncture
tion site is often the harbinger of BSI caused by an infected (66-68), but rates offalse-positive (contaminated) cultures can
arterial catheter and may denote an infective pseudoaneurysm be considerably higher with catheter-drawn specimens (69-71) .
( 46,48,49). Endocarditis, particularly right-sided, is a rare but The practice of drawing nonqualitative blood cultures through
well-documented complication of flow-directed pulmonary indwelling vascular catheters probably ought not to be encour-
artery catheters (50-52). aged because of the risk of introducing contamination during
the manipulation (72).
If the laboratory has an automated quantitative system avail-
BLOOD CULTURES
able for culturing blood, such as the Isolator® system, catheter-
Blood cultures are essential to the diagnosis of IVDR-BSI (see drawn blood cultures can permit the diagnosis of IVDR-BSI to
Chapter 9), and in any patient suspected of infusion-related be made with reasonable sensitivity and specificity (both in the
infection, two or three separate 10-mL blood cultures should range of 90%), without removing the catheter (73--79). With
be drawn (53-55), ideally from peripheral veins, by separate infected catheters, a quantitative blood culture drawn through
venipunctures. If the patient is receiving antimicrobial therapy, the catheter usually shows a marked step-up-often > 10-fold-
blood cultures obtained immediately before a dose is due to in the concentration of organisms compared with quantitative
be administered-when blood antibiotic levels are likely to be blood cultures drawn at the same time percutaneously through
low-may provide a higher yield. The use of resin-containing a peripheral vein.
media to adsorb and remove any antibiotic present in the Quantitative catheter-drawn blood cultures probably have
blood specimen (56), adsorb serum factors detrimental to their greatest utility in diagnosis of device-related infection with
the growth of Enterobacteriaceae (57), and lyse the cell wall surgically implanted cuffed Hickman or Broviac catheters and
of neutrophils, thereby releasing intracellular pathogens (58), subcutaneous central venous ports (73--76).
may also increase the yield (59). Finding microbes on Gram stain or acridine orange stain of
The use of a biphasic system, such as the Isolator® blood drawn through eves has been shown to be highly sensi-
(E.I. DuPont, Nemours and Co., Wilmington, Delaware, USA), tive and specific for diagnosing IVDR-BSI (80,81). If confirmed
or systems with selective high-blood-volume fungal media by others using the same and other IVDs, these may be the
(BACTEC; Becton Dickinson Diagnostic Instrument Systems, methods of choice for the rapid diagnosis of serious intravascu-
Sparks, Maryland, USA) appear to significantly enhance the lar catheter-related infections. Intracellular bacteria have been
laboratory detection of fungemia (60,61). However, quantita- found on Wright-stained peripheral smears in asymptomatic
tive blood cultures are labor-intensive and cost almost twice patients with occult evC-BSI (82).
Chapter 38 • InfectWn.s dtu to Injwion Therapy 565
MICROBIOLOGY OF INTRAVASCULAR 15% to 40% association with concordant BSI. Cannulas positive
DEVICE-RELATED BLOODSTREAM INFECI'ION on semiquantitative culture also are strongly associated with
local inflammation (21).
The microbiologic profile of BSI {Table ~.3) can strongly
A good correlation between high colony counts and IVDR-
suggest an infusion-related source. Cryptogenic staphylococ- BSI has been demonstrated with cultures of catheter segments
cal BSI, particularly with coagulase-negative staphylococci, BSI
semiquantitatively on solid media (90-92) or quantitatively in
caused by BaciUus or Corynebacterium (especially JK-1) spp. or liquid media-removing organisms from the catheter by vor-
Enterococcus, or fungemia caused by Candida, Jibsarium, 'JlrU:M-
texing or sonication (90,93,94). The latter techniques appear
phyton, or Malasset.ia spp., especially in a patient with a eve, is
to have the greatest sensitivity and specificity for the diagnosis
most likely to reflect a catheter-related infection ( 1,2,42). of vascular catheter-related infection (95,96). However, a nega-
BSis caused by En~acti!T' cloacae or, especially, Pant~a
tive catheter culture may not rule out a catheter-related BSI
(formerly En~acter) agglomerans, Burlcholdtria cepacia, Ste- (CR-BSI) (37,41,95-97). Using >1 catheter culture technique
notroplwmonas maltophilia, or Citrobacter spp., in the setting of
increases the yield (96), as does bedside plating of catheters for
infusion therapy, may signal an epidemic and should prompt semiquantitative culture (98). Direct Gram stains (99) or acri-
studies to rule out contaminated infusate (83). A BSI duster
dine orange stains (100) of intravascular segments of removed
should mandate a full-11cale investigation, which may include catheters also show excellent correlation with quantitative tech-
culturing of large numbers of in-use infusions and informing
niques for culturing catheters and can permit rapid diagnosis
the local, state, and Federal public health authorities. Such
of catheter-related infection.
actions avened a large, nationwide epidemic in 1973, when,
A reliable diagnosis of infection caused by contaminated
prompted by five unexplained BSis in three hospitals, intrinsic
infusate requires a sample of fluid to be aspirated from the
contamination of one U.S. company's products was identified line and cultured quantitatively (8~). A variety of techniques
and a recall put into effect so rapidly that the outbreak was
are now available for culturing or processing parenteral ad-
limited to the five initially recognized patients (84). It must mixtures and fluid medications in the laboratory for microbial
be emphasized, however, that for BSI surveillance to be maxi-
contamination (101,102). Because there is no evidence that an-
mally effective, all blood culture isolates must always be fully aerobic bacteria can grow in parenteral crystalloid admixtures,
identified-that is, identified to the genus and species level.
anaerobic culture techniques are not necessary unless blood or
Failure to do so during the 1970 to 1971 nationwide epidemic
another biologic product is involved.
traced to the contaminated products of one U.S. manufacturer
resulted in preeminent hospitals experiencing large numbers
of infections that were recognized as infusion-related only in DEFINITIONS FOR INFUSION-RELATED
retrospect (25) . INFECTION
Cryptogenic healthcare-associated BSI caused by psychro- Using the results of semiquantitative or quantitative culture
philic (cold-growing) organisms, such as non-aeruginosa pseu-
of the catheter and cultures of the hub of the catheter and
domonads, Ochrobactru.m anthropi (formerly Achromobacti!T'), of infusate aspirated from the line at the time the catheter
Flavobacterium, E~, or Serratia spp. (85,86), or by SalfiW-
is removed, and concomitant blood cultures, it is possible to
mlla (87) or Y.minia spp. (88), with a picture of overwhelming
formulate rigorous definitions for intravascular device-related
BSI, may indicate a contaminated blood product.
infection (103) (Table ~.4).
The term "catheter sepsis" appears frequently in the lit-
CULTURES OF INTRAVASCULAR DEVICES erature, but lacks stringent criteria. Although sepsis has been
defined by a consensus panel (104), the term as applied to
Some laboratories still culture vascular catheters qualitatively, catheter-related infections may be insensitive because many of
amputating the tip aseptically and immersing it in liquid these infections are due to coagulase-negative staphylococci,
media. Unfonunately, a positive culture by this technique is and in some studies, only 55% to 71% of patients with bacte-
diagnostically nonspecific because a single organism picked remia due to this pathogen had leukocytosis (105,106). Also,
up from the skin as the catheter is removed can produce a the maximal body temperature is <38•c in many patients with
positive-false-positive-culture (89). Many IVDR-BSis derive coagulase-negative staphylococcal BSI (106,107). This term
from local infection of the transcutaneous cannula tract (see should likely not be further promulgated in the literature,
discussion later). The culture of the external surface of the especially in those prospective, comparative studies involving
withdrawn cannula should reflect the microbiologic status of IVDs (103).
the wound, and quantitative culture should more accurately In addition, the definitions listed previously may be unnec-
distinguish infection from contamination. A standardized, essarily rigorous for use in clinical HAl surveillance because
semiquantitative method for culturing vascular cannulas in very few clinicians obtain cultures of catheter hubs or infusate,
solid media was developed in 1977 (21). Colony counts on even if the cannula is cultured. Moreover, patients with dissemi-
semiquantitative culture are bimodally distributed, as they are nated candidiasis originating from an infected catheter often
in quantitative urine cultures. The method provides excellent have negative blood cultures. It is also important to realize that
discrimination between colonization and insignificant con- multiple sites are often colonized when cultures are performed
tamination acquired during catheter removal. Fifteen or more at the time of catheter withdrawal and it may be difficult to
colony-forming units (cfu) growing on a semiquantitative plate distinguish with certainty the source of many catheter-related
is regarded as a positive culture, and denotes significant growth BSis. Therefore, for routine surveillance, the use of the Cen-
or colonization (21). On the basis of experience with > 10,000 ters for Disease Control and Prevention (CDC) definitions is
IVDs, positive cultures found using this technique have shown a recommended (108,109,110).
-~ §C :) 6JJ:i. Definitions for Intravascular Device-Related Infection

CATHETER COWNIZATION
Significant growth of a microbial pathogen from the catheter tip, subcutaneous segment of the catheter, or catheter hub
LOCALIZED INTRAVASCULAR CATHETER-RELATED INFECTION

A Microbiologically Proven Exit Site Infection: Purulent exudate within 2 em of the catheter exit site, in the absence of concomitant BSI
B. Clinically Suspected Exit Site Infection: Erythema or induration within 2 em of the catheter exit .site, in the absence of concomitant BSI
and without concomitant purulence
C. Tunnel Infection: Tenderness, erythema, or induration >2 em from the catheter exit site along the subcutaneous ttact of a tunneled
(e.g., Hickman or Broviac) catheter, in the absence of concomitant BSI
D. Pocket Infection: Purulent fluid in the subcutaneous pocket of a totally implanted intravascular catheter that may or may not be associated
with spontaneous rupture and drainage or necrosis of the overlying skin, in the absence of concomitant BSI
SYSTEMIC INFECTION
A IVDR-BSI: Concordant microbial growth between a catheter segment or hub, infusate, or exit site exudate, and percutaneously drawn
blood cultures or concordant microbial growth between catheter-drawn and percutaneously drawn quantitative blood cultures (catheter-
drawn blood cultures: percutaneously drawn blood cultures 2!:4:1)
1. Primary Hub-Related BSI: Concordant growth from the catheter hub and a percutaneously drawn culture, regardless of the catheter tip
results, with negative cultures or growth of a different microbe from the exit site and/or subcutaneous catheter segment culture by the
roll-plate method. A negative culture or discordant growth from the catheter tip by the roll-plate method (21) supports the diagnosis
2. Primary Skin-Related BSI: Concordant growth from the exit .site and/ or subcutaneous catheter segment by the roll-plate method, and
a percutaneously drawn blood culture with negative cultures or growth of a different microbe from the hub and infusate; concordant
growth from the catheter tip by the roll-plate method further supports the diagnosis
ll. Primary Infusate-Related BSI: Concordant growth from the infusate and a percutaneously drawn blood culture with negative cultures or
discordant growth from the hub, exit site, and/ or subcutaneous catheter segment by the roll-plate method
B. Definite Intravascular Catheter-Related Sepsis: CR-BSI infection in the setting of sep.sis-defming symptoms ( 104)
C. Probable Intravascular Catheter Sepsis: Sepsis in the setting of negative blood cultures, resolution of sepsis-defming symptoms shortly after
catheter withdrawal, and a catheter component with significant growth of a microbial pathogen or growth from purulent material at the
exit site or subcutaneous pocket, or erythema and induration extending along the tunnel ttact of a Hickman or Broviac catheter
CANNULA-ASSOCIATED INFECTION eves used for hemodialysis have been associated with the high-
est rates ofBSI, > 10% ( 126-128); however, cuffed hemodialysis
INCIDENCE OF CANNULA-RELATED catheter use appears to be associated with a lower incidence of
BLOODSTREAM INFECTION BSI (129,130). Peripherally inserted central catheters (PICCs)
pose a substantially lower risk of CR-BSI (0.04 to 0.4 per 100
IVDR-BSI is perhaps the least frequently recognized HAl. The catheter-days) when used in the outpatient setting, but have a
true incidence of IVDR-BSI is underestimated in most centers risk similar to percutaneously placed eves when used in the
because a catheter is often not suspected as a source of the pa- inpatient setting, especially the ICUs (131). Swan-Ganz pulmo-
tient's clinical picture of healthcare-associated BSI, and is not nary artery catheters used for hemodynamic monitoring are
cultured. Prospective studies in which every device enrolled is associated with a 1% rate of BSI or 0.3 per 100 catheter-days
cultured at the time of removal clearly indicate that every type (116). The lowest rates of infection with eves have been with
of IVD carries some risk of causing BSI, but the magnitude of surgically implanted Hickman or Broviac catheters that incor-
risk per device varies greatly, depending on its type (2) . porate a Dacron cuff, which have been associated with rates of
Table 38.5 shows the representative rates of infection infection in the range of 0.1 bacteremias or fungemias per 100
for various types of intravascular devices (111). The lowest catheter-days (132,133), and surgically implanted subcutane-
rates are with small peripheral N steel needles and Teflon ous central venous ports, associated with rates of BSI of <0.05
or polyurethane catheters: large, prospective studies have per 100 device-days (132,133). In prospective studies, the in-
shown rates of -0.2 BSis per 100 peripheral N catheters cidence of BSI has been demonstrated to be lower in patients
(17-20,23,109,112-115); two large, comparative trials have who have subcutaneously implanted ports compared with those
shown that if N cannulas are inserted under scrupulous asep- with tunneled catheters with a Dacron cuff (134-139).
tic conditions, plastic catheters probably pose no greater risk It has been estimated that 90% ofiVDR-BSis originate from
of device-related bacteremia or candidemia than steel needles eves of various types (2),leading to -55,000 BSis in U.S. ICUs
(112). Prospective studies of arterial catheters used for he- each year (14,15). Data from the CDC's National Nosocomial
modynamic monitoring have found rates of infusion-related Infections Surveillance (NNIS) study have shown that the in-
bacteremia in the range ofl% (116). cidence of secondary BSis, deriving from identifiable local
The device that poses the greatest risk of iatrogenic BSI is infections such as UTis, SSis, or pneumonias, has remained
the eve in its numerous forms (11,117-119). Many prospec- stable over the past decade; in contrast, the incidence of pri-
tive studies of short-term, noncuffed, single- or multilumen mary healthcare-associated BSis, the largest proportion of
catheters inserted percutaneously into the subclavian or inter- which derive from IVDs, has increased more than 2-fold over
nal jugular vein have found rates of CR-BSI in the range of 2% this same period (2,140), reflecting the great increase in the
to 5% (11,90,120-125). Percutaneously inserted, noncuffed use of infusion therapy and, especially, the use of eves of all
CMfMr J8 • Inftctiqns dtu to Injwion 'I"'wroJ.1J 567
types. It seems dear that the greatest hope for reducing the risk
TABLE38.5 Appi.'O.Ximate Jliska of of IVDR-BSI will come from better underatanding of iufe<:tion
Bloodstream Infection with eve,, which will form the basis for more effective strate-
.Assodab:d. with Various gies for prevention.
Types of De-rica for
Intravucular .Auas• (Ill)
BPIDBMIOLOGY
Type ofDeYic:e
Periphenl IV catheters The first and perhaps most important q~tion that must be
Plastic catheten 0.1 addressed to develop effective strategies for prevention is to de-
Steel needles 2.0 termine the m~or source or sources of microotgani.siWI that
Venous cutdown 5.7 can colonize a percutaneoua IVD (FigUre 38.1) and cauae in-
Midline catheters 0.4 vasive infection leading to bacteremia or candidemia (141).
Arterial catheters for hemodynamic 0.8
An intravascular catheter can easily become colonized extralu-
monitoring
minally by organisms from the patient's cutaneous microflora.
Periphenlly inserted cenbal catheten
Inpatient and outpatient 5.1 Contamination may occur during catheter insertion (142) or
Inpatient 2.4 shortly thereafter (143). Microorganisms can also contaminate
Outpatient 5.5 the catheter hub where the administration set attaches to the
Short-term noncuJI'ed central venous catheter, or they may gain access to the fluid column and be
catheters infused directly into the patient's bloodstream; the device can
Nonmedicated also become infected hematogenously from remote sources of
Nonmnneled u local infection; or the device might even be contaminated from
1\umeled 4.7
Medicated its manufacture-which fortunately is very rare.
Chlorhexidine/silver tulfadiazine 2.6 A large body of clinical and microbiologic data indicates
Minocydine/rifampin 1.0 that most IVDR-BSls caused by short-term, percutaneously in-
Silver-impregnated 5.2 serted, noncuffed cathetera are caused by extraluminal micro-
Silver iontophoretic 4.0
organisms of cutaneous origin that invade the transcutaneous
Benzalkonium chloride u insertion wound at the time the catheter is inserted or in the
Pulmonary artery catheters 1.5
Hemodialysis catheten days after insertion.
Temporary, noncuJI'ed 8.0 Numerous prospective rtudies of intravascular device-related
Long-term, cuJred, and tunneled 2U infection have shown that coagulase-negative s:taphylococci,
CuJfed and mnneled central venous 2%.5 the predominant aerobic species on the human skin, are
catheters now the most common agents of CR-BSI (1,2,11,52,109,112-
Subcutaneous venous pons
115,117,125,13.2,140). The vast majority of vascular CR-BSis are
Central 5.6
Peripheral 4.0 caused by microorganisms that colonize the skin of hospitalized
lntraJoWrtit balloon pump!! 5.0 patients: rtaphylococci, both coagulase-negative and coagulase-
Left ventricular auist devices 26.1 positive (S. mmw); Candida, Coryntlxu:tt:rim, and Bacillus spp.;
and, to a lesser degree, aerobic gram-negative bacilli (Table 38.6).
"Based on data from recently published, prospective studies. Prospective studies have also shown strong concordance
~Rates per 100 devices.
between organisms present on slcin surrounding the catheter
CONTAMINATED
SKIN ORGANISMS INFUSATE
Endogenous Flora CONTAMINATION Fluid
Extrinsic OF Medication
HCW CATHETER HUB
Contam Disinfectant Extrinsic
Extrinsic (HOW) Manufacturer
Invading Wound Endogenous (Skin)
CONTAMINATION OF DEVICE
PRIOR TO INSERTION
Skin
Figure 38.1. SoW"Ces of intravascular
cannula-related infection. The .sources are ..._ .__ ..__ Vein
the skin flora, contamination of the catheter
hub, contamination ofinfusate, and hema-
togenous colonization of the intravascular
device and its fibronectin-fibrin sheath. Fibrin Sheath, HEMATOGENOUS
HCW, healthcare worker. Thrombus From Distant L.ocallnfection
High counts of microorganisms on semiquantitative

TABLE 38.6 Microorganisms Most
culture of the external surface of a removed catheter are
Frequently Encountered strongly associated with bacteremia caused by the catheter
in Various Forms of (21,26,90-92,127,151,157,158).
Intravascular Line-Rdated Microscopic examination of infected eves has shown heavy
Infection colonization of the external surface (99,100), especially with
short-term catheters (159).
Soun:e Pathogens
Prospective studies have shown that the use of a more
Catheter-related effective cutaneous antiseptic (e.g., chlorhexidine) for antisep-
Peripheral IV catheter Coagulase-negative staphylococci"
sis of the insertion site at the time of catheter insertion and
Staphylocoaus aurnu
Qmdidaspp.• in follow-up care of the catheter greatly reduces the risk of
Central venous catheters Coagulase-negative staphylococci infusion-related BSI (36,160-162).
S. aurnu Prospective trials have shown that antiseptics or antimicrobi-
Candida spp. als applied topically to the intravascular catheter insertion site
Corynebacteriumspp. (especiallyJK-1) can reduce the risk ofCR-BSI (128,163).
KfiJbsiella and Enterobacterspp.
Surgically implanted Broviac or Hickman catheters, which
Mycobacwium spp.
niclwphyton beigrlii have a subcutaneous Dacron cuff that becomes ingrown by
Fusarium spp. tissue and poses a mechanical barrier against invasion of the
MalassG:ia Jutfur3 tract by skin organisms, have been associated with considerably
Contaminated IV infusate Tribe Klebsielleae lower rates of CR-BSI (...0.20 episodes per 100 catheter-days)
Enterobacter cloacae (164--166) than short-term, noncuffed eves (0.6 to 1.0 per
Enterobacter agglomemns
100 catheter-days) (26,99,117,120,121,123) (Table 38.5). With
Sermtia ma'IUSCens
KfiJbsiella spp. one exception (167), prospective, randomized, clinical trials
Burlclwlderia cepada of a subcutaneous silver-impregnated cuff that can be attached
Btlrlclwlderia acidivorans, Burlclwlderia to a short-term (<10 to 14 days) eve at the time of insertion
pickettii can also reduce the risk of catheter colonization and CR-BSI
Steootroplwmonas maltophilia (121,122,168). However, with more prolonged catheteriza-
Citrobacter frrundii
tion (>14 days), this device does not appear to be efficacious
Ffawbactmum spp.
Candida tropicalis
(169-171). Studies have shown that novel short-term (-7 days)
Contaminated blood E. cloacae eves with an externally coated antimicrobial (172,173) or an-
products S. ma?UScens tiseptic or heparin (174--178) greatly reduce the incidence of
Och~manthf'IJ/Ii catheter colonization and, in some instances, CR-BSI. Again,
Ffawbacterium spp. the efficacy of these novel devices has not been demonstrated
Burlclwlderia spp. with more prolonged catheterization (179,180). This may re-
Yersinia spp.
flect the greater importance of the catheter hub as a source
Sal1fltmtllla spp.
of invading pathogens, compared with the skin at the inser-
"Also seen with peripherallY catheters in association with the tion site, with more prolonged catheterization (95,159). A
administration of lipid emulsion for parenteral nutritional support. number of studies have shown that the colonized hubs of IVDs
IV, intravenous. are an important source of pathogens causing CR-BSis (38),
particularly with more prolonged duration of catheterization
(37,95,157,159,181-183).
Central venous and arterial catheters can also become colo-
nized hematogenously, from remote, unrelated sites of infec-
insertion site and organisms recovered from eves producing tion, but the evidence suggests that this occurs relatively less
BSI (26,38,52,120-122,142,144,145). There appears to be a frequently than colonization from microbes at the insertion
direct parallel between the level and profile of cutaneous col- site or catheter hub (36,38,52,121,184,185) (Table 38.7), ex-
onization at the insertion sites of short-term central venous, cept in patients with short bowel syndrome (186) .
arterial, or peripheral IV catheters and the risk of CR-BSI Although infusate not infrequently becomes contaminated
(146,147). by small numbers of organisms, mainly skin commensals such
ICU and hemodialysis patients with cutaneous colonization as coagulase-negative staphylococci, with the exception of ar-
by S. aumtS experience 4- to 6-fold higher rates of IVDR-BSI terial catheters used for hemodynamic monitoring (35,36),
(148,149). The use of recombinant interleukin-2, with or with- endemic BSis originating from contaminated infusate also ap-
out lymphokine-activated killer (LAK) cells for cancer immu- pear to be uncommon in the United States, although common
notherapy, which is associated with frequent dermatotoxicity in many facilities with limited resources (36,115,121). In con-
(desquamation) and heavy cutaneous colonization by S. aureus, trast, contaminated infusate is the single most common identi-
has been associated with a prohibitively high incidence of eve- fied cause of epidemic healthcare-associated BSI (1,2), caused
related S. aumtS BSI (150). predictably by microorganisms capable of multiplying in par-
Bum patients, who have huge populations of microorgan- enteral glucose-containing admixtures, members of the tribe
isms on the skin surface, experience very high rates of CR-BSI Klebsielleae (Klebsiella, Enterobacter, and Serratia spp.), B. cepa-
(151,152) (see Chapter 37). cia, BurMolderia pickettii, or Citrobacterspp. (83). Nearly 100 epi-
Numerous outbreaks of IVDR-BSI have been traced to con- demics of infusion-related BSI since 1965 have been traced to
taminated cutaneous antiseptics (153-156). contaminated infusate or IV medications, with microorganisms
CMfMr J8 • Inftctiqns dtu to Injwion 'I'IwraJ.1J 569
TABLE38.7 Potential Soulus of Swan-Gauz Pulmonary Artery (PA) Catheter-Belated Bloodstream

In£cctioo, Bual on a Prospccti"R Study of 442 Swan-Ganz Pulmonary Artery Catheters
Ccnmmtiomd ltighly Permeable
PolyauedlaDe Polyaretlullle
Gaue (!days) (5 clays) (5 days) o...n
Total no. of cathe~reJated bloodstream iDfectioas 2 1 2 5
Microbiologic
Concordance with aource
IntravucuJar •egment of introducer or PA catheter 2 1 2 5
Skin 1 1 2
Hub 1 1 1 5
lnfwate 1 1 1 5
Exiiavaacular portion of PA catheter, beneath 1 1
external protective alene
Hematopoua &om remote aoun:e 1 1
From Maki DG, Stolz SS, WheelerS, et al. A proapective, randomized trial of gauze and two polyurethane drellinp for lite care of pulmonary
artery catheten: implications for catheter managemenL Crit o-M& 1994;22:17~1757, with pennilaion.
most frequendy introduced during preparation or administra· be promoted by surface exoglycocalyx (206,207). Whereas sub-
tion in the hospital (extrinsic contamination) or during its therapeutic levels of antibiotics reduce microbial adherence
manufacture (intriwsic contamination). (194,208), once microorganisms such u coagulase-negative
Analysis of risk factors predispming to intravascular staphylococci colonize a prosthetic surface, boat defewses be-
catheter-related infection by stepwise logistic regression of data come secondarily impaired and are unable to spontaneously
from large, prospective studies of peripheral IV catheters (115), eradicate the infection (209,210). Moreover, once associated
arterial catheters med for hemodynamic monitoring (35), with a foreign surface, microorganisms exhibit increued resis-
multilumen CVCs med in ICU patients (S6), or Swan-Ganz tance to antimicrobials (211-216). Itshould be no surprise that
pulmonary artery catheters (184) shows that heavy cutaneous infections of prosthetic implants are difficult to cure with anti-
colonization of the insertion site is one of the most powerful microbial therapy alone, even with prolonged administration
predictors of catheter-related infection with all types of short· of high doses of bactericidal drugs.
term, percutaneously imerted catheters (Table 38.8) (187).
PATHOGENESIS BWODSTREAM INFECTION

FROM CONTAM1NATED INFUSATB
Examination of an infected IVD by scanning electron mi·
croscopy characteristically shows the surface covered by an It took > 10 years after the introduction of intravascular plastic
amorphous film (159,185,188), presumably representing host catheters before they were ultimately recognized as an impor-
proteiws, with microcolonies of the infecting organism en- tant source of serious iatrogenic infection; however, it required
cued in a thick matrix of glycocaly.x (slime), all comprising a
"biofilm" (189) (Figure 38.2). Studies of the pathobiology of
prosthetic device-related infection have shown considerable
differences in the capacity of microorganisms to adhere to
various prosthetic materialll. In vitro, catheters made of Tef-
lon or polyurethane are more resistant to bacterial adherence,
especially by staphylococci, than catheters made of polyethyl-
ene, polyvinylchloride, or, especially, silicone (190,191). These
differences are maintained if the experiments are done with
previously implanted catheters or catheters precoated with spe-
cific pluma procatheters or catheters precoated with specific
plasma proteins (192-195).
Initial attachment of Staphylococcus epultrrmidis directly to
a catheter is mediated, in part, by the hydrophobicity of the
strain (196) and by specific adhesins (197-201). Initial attach·
ment of S. atmW to catheters appears to be more dependent
on the presence of preadllorbed plasma or tissue proteiws such
u fibronectin, thrombospondin, fibrin, vitronectin, and Jam.
inin (33,M,195,202). Because many of these proteins are an
integral part of thrombm formation, the presence of throm·
bus on the catheter surface also appears to promote adherence Figure 38.2-. Sc:mning electron micrograph of an infected central
and catheter-associated infection (96,20~205). Persistence of venous catheter (X6,000). The amorphous matrix encaaing the
bacteria and fungi attached to the catheter surface appears to microcolonies of Staph,~oc:occu.s epidermidis is glycocalyx (slime).
TABLE 38.8 Risk Factors for Intravascular Catheter-Related Infection Based on Multivariate Analysis
of Data from Large, Prospective Studies
No. of Catheters
Type of Catheter (Ref.) Studied Risk Factom Relative Risk
Peripheral IV (115) 2,050 Cutaneous colonization of site > 1o2 cfu ll.9
Contamination of catheter hub 3.8
Moisture on site, under dressing 2.5
Placement >ll days 1.8
Systemic antimicrobial therapy 0.5
Peripheral IV (162) (pediatric 826 Heavy colonization of insertion site ll.6
patients) Catheterization for 2:72 hours 2.0
Gestational age :Sll2 weeks 1.8
Ampicillin infusion 0.4
Cutaneous antisepsis with chlorhexidine 0.2
Arterial (ll5) 491 Cutaneous colonization of site >102 cfu 10.0
Second catheter in site, placed over guidewire
Umbilical artery (ll99) (pediatric 189 Very low birth weight
patients) Prolonged antibiotic therapy
Antibiotic therapy at the time of catheter removal
Umbilical vein (399) 144 High birth weight
(pediatric patients) Hyperalimentation in high-birth-weight patients
Central venous (400) ll45 Exposure of catheter to unrelated bacteremia 9.4
Cutaneous colonization of site > 1(12 cfu 9.2
Placement >4 days
Central venous (192) 188 Catheter-related thrombosis
Central venous ( 401) 1,258 Respiratory tract colonization or infection
Hypoalbuminemia
Central venous (llll) 76 Heavy insertion site colonization 13.2
Difficult catheter insertion 5.4
Female gender 0.2
Underlying secondary diagnosis 0.2
Central venous ( 402) 1,212 Internal jugular vein insertion ll.ll
Patient transfer within the hospital 3.0
Disease of the gastrointestinal tract 2.4
Prolonged hospital length of stay before catheter insertion 1.0
Concomitant antibiotic use O.ll
Polyurethane catheter 0.2
Central venous (26) 140 Insertion site colonized with organisms other than 14.9
coagulase-negative staphylococci
Insertion site erythema 4.4
Insertion site colonized with >50 cfu of coagulase-negative 6.4
staphylococci or > 1 cfu of any other microbe
Pulmonary artery (184) 297 Cutaneous colonization of site > 1o5 cfu 5.5
Internal jugular vein cannulation 4.ll
Duration >3 days 3.1
Placement in operating room under less stringent barrier precautions 2.1
Pulmonary artery (40ll) 86 Catheterization >5 days 14.4
Antibiotic use 0.2
Hemodialysu (126) 5ll Chronic renal failure 7.2
Peripheral, central venous, arterial, 1,649 Age <1 year
and pulmonary artery (pediatric Dwell time = 3 days
patients) ( 404) Inotropic support
Peripheral, central venous, ll5ll Dutant focus of infection 8.7
arterial (27ll) Inappropriate catheter care 5.3
Prolonged hospitalization > 14 days ll.5
Peripheral, central venous, arterial 101 Insertion site colonization at catheter removal 6.2
(bum patients) (152)
Peripheral, central venous, 62ll Duration of catheterization 7 to 14 days ll.9
pulmonary artery, arterial (18ll) Duration of catheterization > 14 days 5.1
Coronary care unit 6.7
Surgery service 4.4
Second catheterization 7.6
Insertion site colonization 56.6
Hub colonization 17.9
Hickman (405) 690 Double-lumen catheter 2.1
Obesity 1.7
Granulocytopenia 1.6
Implantable port (ll50) 1,550 Increased number ofline breaks per day
Cfu, colony-forming units.

Reduced nurse:patient ratio in ICU (406-408)
570
>40 years and the occurrence of epidemic gram-negative BSis reported due to extrinsic contamination of a lipid-based anes-
in hospitals across the United States in 1970 and 1971 (25) to thetic, propofol (Diprivan; Stuart Pharmaceuticals, Wilming-
bring about awareness that fluid given in intravascular infu- ton, Delaware, USA) (40) . This anesthetic agent, which initially
sions--infusate-also was vulnerable to contamination. It has did not contain a bacteriostatic agent, supported the exuber-
become clear that although the majority of IVDR-BSis derive ant growth of several gram-negative, gram-positive bacteria and
from infection of the percutaneous infection wound or con- Candida alhicans (226).
tamination of the catheter hub, contamination of infusate is The growth properties of most microorganisms in com-
the most common cause of epidemic IVDR-BSI (1). From 1965 mercial parenteral admixtures and the vast aggregate experi-
to 1978, 28/30 (85%) reported epidemics of infusion-related ence with epidemic or endemic BSis traced to contaminated
BSis were traced to contaminated infusate, with the organisms infusate have shown that the identity of an organism causing
introduced during its manufacture (intrinsic contamination, healthcare-associated BSI can point strongly toward contami-
which accounted for 7/20 epidemics) or during its preparation nated fluid as the plausible source: P. agglomerans, E. cloacae, Ser-
and administration in the hospital (extrinsic contamination, ratia marcescens, B. cepacia, or Citrobacter spp. cultured from the
which accounted for the remaining 21 outbreaks) (1,2). blood of a patient receiving infusion therapy should prompt
strong suspicion of contaminated infusate-parenteral fluid
or anN drug (Table 38.6). Conversely, recovery of organisms,
GROWfH PROPERTIES OF MICROORGANISMS
such as E. coli, Proteus spp., Acinetobacter spp., or staphylococci,
IN PARENTERAL FLUIDS
all of which grow poorly, if at all, in parenteral admixtures, sug-
The pathogens implicated in nearly all reported BSis linked gests strongly that the BSI is unlikely to be due to contaminated
to contaminated infusate have been aerobic gram-negative ba- infusate.
cilli capable of rapid growth at room temperature (25 •q in the
solution involved (83): for example, certain members of the MECHANISMS OF FLUID CONTAMINATION
family Enterobacteriaceae in 5% dextrose-in-water, and pseu-
domonads or Serratia spp. in distilled water. It must be empha- As noted, the vast majority of published healthcare-associated
sized that microbial growth in most parenteral solutions-the BSis traced to contaminated infusate occurred in an epidemic
exception being lipid emulsion-actually is quite limited. setting (1,2). Parenteral fluids do, however, commonly become
In 1970, we evaluated the ability of 105 clinical isolates from contaminated during administration in the hospital. Culture
human HAis, representing 9 genera and 13 species, to grow at sunreys of in-use N fluids in the hospital have shown contam-
room temperature (25°C) in 5% dextrose-in-water, the most fre- ination rates in the range of 1% to 2% (227-229). However,
quently used commercial parenteral solution (217). Of 51 strains most of the organisms recovered from positive in-use cultures
of the tribe K.lebsielleae-.KlebsieUa, Enterobacter, and Serratia are common skin commensals that are generally considered
spp.--50 attained concentrations of ~100,000 cfu/mL within of low virulence and grow poorly, if at all, in the parenteral
24 hours, beginning with washed organisms at an initial con- admixture; the level of contamination (<10 cfu/mL) usually
centration of 1 cfu/mL. In contrast, only 1/54 strains of other is far too low to produce clinical illness, even in the most com-
bacteria, including staphylococci, Escherichia coli, P. aeruginosa, promised host. When contamination occurs with gram-negative
Acinetobacter spp., or Candida spp., showed any growth in 5% bacilli capable of proliferation in the product to concentrations
dextrose-in-water. With most microorganisms, even with a level > 102 to 1011 cfu/mL, however, the risk of BSI and even septic
of contamination exceeding 106 cfu/mL of fluid, evidence of shock becomes substantial.
microbial growth was not visible to the unaided eye. The likelihood of fluid becoming contaminated during use
A review of studies of the growth properties of microorgan- is directly related to the duration of unintermpted infusion
isms in various commercial parenteral products has shown (83) through the same administration set and the frequency with
that rapid multiplication in 5% dextrose-in-water appears lim- which the set is manipulated. Microorganisms gain access from
ited mainly to the tribe Klebsielleae and B. cepacia; in distilled air entering bottles as they evacuate, from entry points into the
water, P. aeruginosa, B. cepacia, Acinetobacterspp., or Serratiaspp.; administration set-during injections into the line or aspira-
and in lactated Ringer's solution, P. aeruginosa, Enterobacter, or tion of blood specimens from the ND through the line-or at
Serratia spp. Normal (0.9%) sodium chloride solution allows the junction between the administration set and the catheter
the growth of most bacteria while supporting the growth of hub. Microorganisms capable of growth in fluid, once intro-
Candida spp. rather poorly. Candida spp. can grow in the syn- duced into a running infusion, may persist in an administra-
thetic amino acid-25% glucose solutions used for TPN, but tion set for many days despite multiple replacements of the
only very slowly; most bacteria are greatly inhibited (218). bottle or bag and high rates of flow (25); it appears more likely,
Most microorganisms grow rapidly in commercial 10% lipid however, that the majority of introduced contaminants are rap-
emulsion for infusion (Intralipid®) (219,220); in a study of 57 idly cleared from the running infusion by the continuous flow
strains, we found that 12/13 bacterial species tested and Can- (227-230), especially if the organisms grow poorly in the fluid.
dida spp. multiplied in Intralipid almost as rapidly as in bacte- A healthcare worker may rarely encounter a filmy cloud in
riologic media (219). Infections with Ma/a.sse;r;iajurfuralso have a glass N bottle. Microscopic examination of the material re-
been associated with the administration of lipids (221-223). veals it is a filamentous fungus, such as Penicillium or Aspergilr
This is not surprising because this dimorphic, lipophilic yeast lus spp. Molds usually gain access to glass N bottles through
cannot synthesize medium- and long-chain fatty acids and uses microscopic cracks long before the bottle is hung for use, and
exogenous lipids, such as those found in supplemented TPN, over the course of weeks or months grow to produce visible
for growth (220). Use ofTPN supplemented with lipids has also cloudiness or filmy precipitates. Fortunately, "fungus balls" in
been shown to significantly increase the BSI risk by coagulase- N bottles have rarely resulted in systemic infection in patients
negative staphylococci (224,225). Epidemics have also been receiving a mold-contaminated infusion (231) .
The incidence of endemic healthcare-associated BSI caused Enterobacter spp. that are able to multiply rapidly in the 0.9%
by extrinsically contaminated IV fluid is not precisely known, saline commonly used in these infusions.
but on the basis of studies of the pathogenesis of device-related Endemic BSis resulting from the transfusion of contami-
infection, is 5- to 10-fold lower than the incidence of endemic nated blood products have been rare, presumably because
cannula-related BSI. Moreover, prospective studies of the op- most blood products are routinely refrigerated, because con-
timal interval for periodic replacement of administration sets tamination is low level, and because of universal awareness
(227-233) (Table 38.9), which have involved cultures of in- that blood products must be used promptly after removal from
fusate from large numbers of in-use infusions in an institution, refrigeration (86,239). BSI from contaminated whole blood is
have shown low rates of contamination and a very low risk of associated with adverse reactions in 50% of episodes, includ-
related BSI: a meta-analysis of five studies in which >9,000 infu- ing fever (80%), rigors (53%), hypotension (37%), and nausea
sions in five hospitals were prospectively cultured, with no asso- or vomiting (26%) , with an associated mortality of 35% (86).
ciated episodes of bacteremia or candidemia identified, yields Overwhelming shock is usually due to contamination with
an incidence of endemic BSI due to contaminated infusate of massive numbers of psychrophilic (cold-growing) organisms
<1 episode per 2,000 IV infusions. It must be emphasized, how- such as Serratia spp., B. cepacia, S. maltophilia, Y~inia spp., or
ever, that IV infusate can be identified as the source of BSI only other uncommon, nonfermentative gram-negative bacilli (e.g.,
if it is cultured. Because this rarely occurs in most hospitals, Flavobacterium sp.) in the contaminated unit {86-88,240}. Bac-
unless there is a cluster of BSis-an epidemic-that occurs, it teria often have been visible on a direct Gram-stained smear
is likely that most sporadic (endemic) BSis caused by contami- of the product. Blood products should be infused immediately
nated fluid go unrecognized or are attributed to the IVD. after they are removed from refrigeration. On completion of
Approximately 50% of the BSis caused by arterial infusions the transfusion, the entire delivery system should be replaced.
used for hemodynamic monitoring stem from the contamina- If BSI is suspected of being related to a contaminated blood
tion of fluid in the infusion (35), perhaps because these infu- product, the entire infusion should be removed. Aliquots of
sions consist of a stagnant column offluid subjected to frequent the remaining product should be cultured aerobically and
manipulations, including frequent drawing of blood specimens. anaerobically on solid media at both 35° to 37°C and 16° to
However, more recent studies have demonstrated that infusate 20°C {83}. Platelet units may be stored at room temperature
contamination of hemodynamic pressure-monitoring equip- for 5 days before use and may be more prone to contamina-
mentis rare (234). Over the past 20 years, there have been 28 tion with large numbers of microbial pathogens. As many as
epidemics of healthcare-associated BSI traced to contaminated 10% of platelet pools used for transfusion are contaminated
fluid in arterial infusions used for hemodynamic monitoring with bacteria (239) . Although most contaminants are skin flora
(235-238). Nearly all of these epidemics have involved gram- (241), contamination with gram-negative bacilli has been re-
negative bacilli, particularly S. man:esam, pseudomonads, or ported (86,87).
TABLE 38.9 Studies of &placing Intravenous Administration Sets at Periodic Intervals

as an Infection Control Measure
Prevalence of Contamination in
Sets Changed at Interwls
Location No. of Sets
Reference of Patients Types of Infusion Cultured 241umrr 481umrr 721umrr bullfinite
(229) Ward Mainly peripheral" 2,537 0.4 0.6
(232) Ward, ICU Peripheral 694 0.5 1.0 0.7
Central, access"'b plm TPN 119 0 0 0
(233) ICU Peripheral (62%) plm central, 676 2.0 4.0
access (38%)•
(230) Ward Peripheral 219 0.8 0.8
(227) ICU Peripheral, plus central, access" 1,194 5.0 4.4
(228) Ward,ICU Peripheral 878 0.2 1.0
Central, access 331 1.9 1.2
Central, TPN 165 2.7 4.4
Ward All types 1,168 0.5 1.4
ICU All types 204 :i.2 1.8
"'nfiWons for TPN excluded; contamination rates with different types of infusions not given.
bAccess refers to a central venom infusion used for admin~tering fluids, blood products, delivery of drugs, or hemodynamic monitoring,
but not TPN.
ICU, intensive care unit; TPN, total parenteral nutrition.
From Maki DG, Botticelli JI, LeRoy ML, et al. Prospective study of replacing administration sets for intravenom therapy at 48- vs. 72-hour
intervals: 72 hours~ safe and cost-effective.JtlM. 1987;258:1777-1781, with permission.
The most important measures to prevent rare sporadic BSis

from contaminated in-use infusate are stringent asepsis during
TABLE 38.10 kportcd Sources of
the preparation and compounding of admixtures in the hos- Epidemics of Intravascular
pital central pharmacy or on individual patient-care units, and Device-Related Bloodstream
good aseptic technique when infusions are handled during use Infection
(e.g., during injections of medications or changing bags or bot- Extrinsic contamination
tles of fluids) . It also appears that replacing the administration Antiseptics or disinfectants
set at periodic intervals can prevent the buildup of dangerous Arterial pressure-monitoring infwate
introduced contaminants and further reduce the risk of related Disinfectants
'fransducers
BSI; during the large, nationwide U.S. epidemic in 1971 due to
Heparin
the contaminated products of one manufacturer, the empiric Ice for chilling blood gas syringes
recommendations that the entire delivery system be routinely Aneroid pressure calibration device
changed every 24 hours and that at every change of the can- Hand carriage by medical personnel
nula all equipment be totally replaced resulted in a substan- Hemodialys~related
tial reduction in epidemic BSis (25). Since that time, routinely Inadequate decontamination of reused dialyzer coils
Contaminated dialysate water
replacing the delivery system at periodic intervals has been
Contaminated disinfectants
practiced in most North American hospitals as an important Parenteral crystalloid solution s
measure for reducing the hazard of contaminated infusate. Lipid emulsion
However, in some instances, routine replacement at more pro- Hyperalimentation solutions in central pharmacy
longed intervals may be associated with epidemics, particularly IV medications, multidose vials
in vulnerable patient populations and when the fluids infused Theft offentanyl and replacement by (contaminated)
promote microbial growth (242). distilled water
Blood products
Whole blood
Platelet packs
EPIDEMIC INFUSION-RELATED Blood donor with silent transient bacteremia
Intravenous radiologic contrast media
BLOODSTREAM INFECTIONS Sclerosing solution for injecting esophageal varices
Central venous catheter hubll
OUTBREAKS DUE TO INTRINSIC Leaking catheter hub administration set connections
CONTAMINATION Adhesive tape used in IV site dressings
Warming bath for blood products
Since 1970, there have been >12 reported epidemics of Green soap
infusion-related BSI caused by intrinsically contaminated Hand carriage by medical personnel
infusate-blood products, IV drugs, or vacutainer tubes Heart-lung machines
(Table 38.10)-illustrating the potential iatrogenic hazards of Intra-aortic ballo on pumps
Inordinately prolonged intravascular catheterization in
infusion therapy. The frequency and size of these outbreaks
ICU patients
have declined since the late 1980s (2), reflecting the apprecia- Intrinsic (manufacturer-related) contamination
tion of the importance of stringent quality control during the Commercial IV crystalloid solutions, container closures
manufacturing process. Blood products
The first and largest epidemic-and the outbreak that more Platelet packs
than any other factor brought about wide-scale appreciation of HUIDail albumin
the iatrogenic hazards of infusion therapy-had its onset several Plasma protein fraction (PPF)
IV drugs
years ago when one U.S. manufacturer of large-volume paren-
Vacutainer tubes
terals began to distribute bottles of fluid with a new elastomer-
lined screw-cap closure (25). By early 1970, the first episodes of IV, intravenous; ICU, intensive care uniL
infusion-related BSI caused by biologically characteristic strains
of E. cloacae and P. agglmnerans (designated Erwinia at the time)
were reported to the CDC, although a retrospective review sub-
sequently showed that numerous hospitals had been experienc- distribution of the company's product with the new closures,
ing epidemic BSis for a number of months. Although it was and the epidemic was terminated only by a nationwide product
established very early, virtually at the outset of the investigation, recall in early Aprill971.
that epidemic BSis resulted from contaminated IV fluids, the Since 1975, numerous additional outbreaks have been re-
ultimate source of contamination-intrinsic contamination ported from hospitals in a number of countries, all involving
of the new closures-was not conclusively established until gram-negative bacilli and parenteral products shown to have
March, 1971. Between july 1970 and April1971, 25 U.S. hospi- been contaminated during manufacture (83,84,243-255) . Most
tals reported nearly -400 episodes of infusion-related BSI to the have been of national scope. A large outbreak in Greece in 1981
CDC (Figure 38.3). It is likely that there were> 10,000 episodes (244) reaffirmed the findings of the large 1970 to 1971 U.S.
nationwide. More than 20 microbial species, including P. ap outbreak (25) that screw-cap closures are not microbiologically
merans, were isolated from the closures of previously unopened safe for fluids used in medical care that must remain sterile.
bottles. Organisms were readily dislodged from the cap liner Outbreaks of pyrogenic reactions (247) and epidemic Pseudo-
and introduced into the IV fluid when bottles were handled un- monas spp. BSI (248) have been traced to intrinsically contam-
der conditions duplicating normal in-hospital use. The appear- inated normal serum albumin, and an epidemic of BSI with
ance of epidemic BSis in individual hospitals paralleled the 0. antkropi has been traced to organisms from contaminated
30
25 HOSPITALS REPORTING 41 2 CASES:
COC - FOA ALERT
0 E. CLOACAE (114) E. SPECIES (89)
MARCH 13, 1971
25
81 MIXEO INFECTION WITH EPIDEMIC
+ RECALL
STRAINS (9)
MARCH 22. 1971
• E. AGGLOMERANS (182)
"'
~
20
15
•• ~
<
u
10
•t
5 ,.. ::-
..
nR n ~ MR
~=~
0 R !:ill
JAN FEB MAR APR MAY JUNE

1970
JULy AUG SEPT OCT NOV OEC I
WEEK ENOING 10 17 24 31 714 2128 714 2128 4 1118 25 2 9 162330 6 13 20 27 4 1118 25 1 8 15 22 28 5 1219 28 31017 24 31 714 2128 5 1219 28 2 916 2330 613 2027 613 20 27 31017 24 1
JAN FEB
1971
MAR APR MAY
Fipre 38.3. Nationwide outbreak of heal.thcare-associated bacteremias due to intrinsic conWDinati.on of one U.S. manufacturer's large-
volume parenteral products. Three hundred and ninety-tnen episodes of lV-associated bloodstream infection in 25 tabulated U.S. hospitals,
occurring between july 1, 1970 and ApriJ27, 1971, ful61led the criteria for epidemic caliCI. The epidemic wall cuzUiled immediately in individual
hospitals and nationally by a nationwide recall of the manufacturer's products. (From Mali DG, Rhame FS, Mackel D, et al. Nationwide epidemic
of bloodstream infection caused by contaminated intrav=ous product.. Am] Med... 1976;60:471-485, with permission.)
rabbit antithymocyte globulin (249). Most notably, outbreib its common occurrence in patients without a predilection to
of~ spp. infection have been traced to intriruic con- systemic infection, and the dramatic clinical response to dill-
tamination of10% povidone-iodine (250), an agent widely used continuing the infusion (Th.ble 38.3)-do not differentiate
worldwide for cutaneous antisepsis for the preparation of the between intrinsic and extrinsic sources of contamination. The
CVC insertion site (251). Dilute chlorhexidine solution, which distinction must be made epidemiologically.
is increasingly being used for skin antisepsis, (36,160-162), may If intrinsic contamination of a couunercially distributed
support the growth of bacteria. leading to epidemic BSI (156). product is identified, or even strongly suspected, especially if
All of these outbreaks illustrate how subtle and insidious the clinical infections have occurred aa a consequence, the local,
factors that influence sterility can be. In many instances, there state, and Federal (CDC and the Food and Drug Administra·
was no documented failure of the sterilization process. Instead, tion [FDA]) public health authorities must be immediately
seemingly minor alterations in the manufacturing process re- contacted. Unopened samples of the suspect lot or lots should
sulted in cont.aurination of individual units in the manufactur- be quarantined and saved for analysis.
ing plant after the sterilization stage (252).
Although intrinsic contamination is, fortunately, exceed-
OUT.BREAKS DUE TO EXTRINSIC
ingly rare, its potential for producing hann is great because of
CONTAMINATION
the large numbers of patients in multiple hospitals who may be
affected. .Aho, direct contamination ofinfusate at the manufac- Even when commercially manufactured products are sterile on
turing level give, contaminants an opportunity to proliferate to arrival in the hospital, circwnstances of hospital use can com-
dangerously high concentrations. promise that initial sterility. .& previously noted, most sporadic
It seems likely that intrinsic contamination is a continuous infections resulting from infusion therapy, whether due to the
source of infusion-related BSI, but of such low magnitude that cannula or contaminated infusate, are of extrinsic origin. Simi·
the resulting BSis are never identified aa related to intriruic larly, most reported epidemics have originated from exposure
contamination. Only when infusion-as.sociated BSLJ occur in of multiple patients' infusions to a common source of contami-
epidemic numbers is intrinsic contamination likely to be sus- nation in the hospital (2,40,235,253-257).
pected and proven. A substantial increase in the incidence of Numerous outbreaks of infusion-related BSI have been
cryptogenic infusion-associated BSI, particularly with Enterobac- caused by the use of unreliable chemical antiseptics, or antisep-
m- spp., pseudomonad$, .Built1uJideria spp., or c~ spp., tics such aa aqueous benzalkonium and aqueous chlomexidine
should prompt immediate, in-depth studies to exclude intrinsic used for cutaneous antisepsis (153-156) or, in more recent
contamination. There are no clinical clues to reliably differen- years, for decont.aurinating transducer components used in he-
tiate intrinsic from extrinsic contamination. BSI from contami- modynamic monitoring (235) (Th.ble 38.10).
nated fluid baa the same manifestations and signs as CR-BSI Despite the numerous reports of epidemic gram-negative
and other healthcare-associated BSis. The few clues to infu- BSis deriving from contaminated disinfectants used for decon·
sion-related BSI-absence of an obvious source of infection, tamin.ating reusable transducer components in hemodynamic
monitoring during the 1970s, one-third of all healthcare-associ- 48 hours before use. The necessity for stringent attention to a
ated BSI outbreaks investigated by the CDC between 1977 and BSI in central admixture programs cannot be overemphasized.
1987 were traced to contamination of infusions used for arte- Fluid admixtures should be used within 6 hours or immediately
rial pressure monitoring (255). Since 1980, there have been refrigerated.
28 healthcare-associated BSI outbreaks associated with arterial Investigations of >100 epidemics (1,2) have documented
pressure monitoring reported in the literature, nearly all caused contamination of in-use infusate or contamination of cannula
by gram-negative bacilli, most frequently by S. marcescens or Bur- insertion sites, deriving from a myriad of extrinsic sources in
kholdma spp. (235-238). Two-thirds of these epidemics were the hospital (Table 38.10). In many outbreaks, the hospital res-
linked to failed decontamination of reusable transducer com- ervoir of the epidemic pathogen and even the mode of trans-
ponents. Epidemic organisms were most commonly found on mission eluded detection, but the microorganism was found
metal transducer heads, in the interface between transducers in large numbers on the hands of healthcare providers caring
and disposable chamber domes. Eight epidemics were traced for patients receiving infusion therapy and handling their in-
to introduction of organisms into dosed monitoring systems fusions. Manipulations of the delivery system, especially the
from external sources of contamination in the hospital, such as administration set, appear to provide a highly effective means
contaminated ice used to chill syringes for drawing arterialized for access of microorganisms to in-use infusate, as illustrated
blood for blood gas measurements, heparinized saline from by HAl outbreaks across the United States traced to in-use con-
multidose vials, and contaminated external devices to calibrate tamination of the IV anesthetic, propofol (Diprivan®). The
pressure-monitoring systems. The epidemic organisms were solution, when initially marketed did not contain a bacterio-
found on the hands ofhealthcare providers in at least nine out- static agent. The anesthetic provided a rich medium for rapid
breaks; however, most of the reports do not provide sufficient microbial proliferation (226), and outbreaks of primary BSI
data to establish the precise mechanism of fluid contamination. or SSI with a variety of gram-positive and gram-negative organ-
With all forms of infusion therapy, the connection between isms and yeasts were traced to in-use contamination ofpropofol
the administration set and the catheter must be secure. This administered in the operating room, because of poor aseptic
is especially important with eves, where accidental discon- technique, storage of opened vials at room temperature, and
nections can result in exsanguination or life-threatening air use of single vials for multiple patients (40,263,264). Similarly,
embolus or blood loss. In TPN, a faulty connection also may a veritable explosion of hospital outbreaks of healthcare-asso-
increase the risk of iatrogenic infection: one reported outbreak ciated candidemia in the past two to three decades (264-266),
of 23 CR-BSis caused by different strains of coagulase-negative primarily in ICUs, has been linked to carriage of the epidemic
staphylococci was linked to a manufacturing defect that re- strain on the hands of healthcare providers handling vulner-
sulted in hyperalimentation solution leaking from administra- able patients' IVDs and infusions.
tion set/ catheter connections and seeping under dressings,
where it resulted in heavy bacterial overgrowth (258). Another
APPROACH TO AN EPIDEMIC
outbreak of coagulase-negative staphylococcal BSis has been
associated with excessive manipulation of a catheter delivery If an epidemic is suspected, the epidemiologic approach must
system because of air appearing in the IV pump tubing. This be methodical and thorough, yet expeditious. It is directed to-
resolved when the IV pump was placed at or below the heart ward establishing the bona fide nature of the putative epidemic
level of the patients, and air entry into the tubing ceased (259). infections (267) and existence of an epidemic, defining the res-
During the 1970s, numerous outbreaks of gram-negative ervoirs and modes of transmission of the epidemic pathogens,
BSI, particularly with pseudomonads other than P. aeruginosa, and, most importantly controlling the epidemic quickly and
were traced to contamination of dialysate in patients' hemo- completely. Control measures obviously are predicated on ac-
dialysis machines (260) (see Chapter 24); however, improved curate delineation of the epidemiology of the causative patho-
quality control, the decontamination of reused dialyzer coils, gen (see Chapter 6).
and the widespread use of disposable dialyzers have resulted in The essential steps in dealing with a suspected outbreak of
a marked decline in the incidence of HAl outbreaks traced to healthcare-associated BSI can be found in Table 38.11. To illus-
contaminated dialysate (2). trate the approach to an epidemic of infusion-related BSI, the
Compounding of admixtures is another important means epidemiologic investigation of an extraordinary outbreak that
by which contamination can be introduced (261). The greatest occurred in the University of Wisconsin Hospital and Clinics is
concern about this mode of contamination, especially if it oc- recounted (39).
curs in the central pharmacy, is that a large number of patients During a 2-week period in late March 1985, three patients in
may be exposed. Moreover, the delay between compounding our university hospital acquired primary healthcare-associated
and use provides opportunity for proliferation of introduced BSI with a similar nonfermentative gram-negative bacillus. All
microorganisms to levels that can cause overwhehning septic three patients had had open heart surgery between March 11
shock when administered. Two large outbreaks of candidemia and March 25 and became bacteremic 48 to 148 hours after
have been traced to contaminated solutions used for IV hyper- operation.
alimentation (262,263); in each outbreak, a vacuum system in The BSI pathogen in each patient was B. pickettii biovariant
the hospital's pharmacy used to evacuate fluid from bottles be- 1. The organism was also cultured from the IV fluid of two of
fore introducing other admixture components was shown to the patients at the time because, serendipitously, during the
be heavily contaminated by the epidemic strain of Candida spp. outbreak most adult patients in the hospital receiving IV fluids
Presumably, organisms refluxed into the bottles during com- were participating in a study of IV catheter dressings (115); as
pounding of the admixtures. In outbreaks traced to contami- part of the study protocol, specimens were routinely obtained
nants introduced during compounding, after compounding, from patients' IV fluid when the catheter was removed. Are-
bottles were permitted to stand at room temperature for up to view of nearly 1,000 cultures of IV fluid from the infusions
of participants in the study since its outset 3 months earlier identified in blood cultures from our institution, indicating
showed that three additional surgical patients operated on in that the cluster of three episodes and six instances of contami-
March had had IV fluid cultures positive for B. pickettii biovari- nated infusate without BSI represented a true epidemic, and
ant 1, even though none had shown clinical signs ofBSI. Molec- with the results of the subtyping, a common-source epidemic.
ular subtyping by restriction enzyme digestion and pulsed-field The CDC and the manufacturer were contacted: none of
electrophoresis showed all six isolates to be identical. Three more than 70 NNIS hospitals had reported B. pickettii BSis
more patients who had been operated on in January had had in the past year, and the manufacturer had never identified
IV fluid cultured positive for a similar nonfermentative gram- contamination with B. pickettii in its quality-control microbio-
negative bacillus; although the three isolates were no longer logic sampling of fentanyl before distribution, or received any
available, the results of screening by AP-20E biochemical panel complaints from users about suspected contamination of their
(API Analytab, Inc., Plainville, New York, USA) at the time were fentanyl. Moreover, a survey of surrounding hospitals that also
identical to those of the six patients with B. pickettii contamina- used the manufacturer's fentanyl revealed none experiencing
tion of IV fluid, with or without associated BSI. healthcare-associated BSis with B. ~ttii.
All of the patients had had multiple positive blood cultures A case-control study comparing the nine infected patients,
and were in septic shock. B. pickettii had not been isolated from all of whom had had recent surgery, and 19 operated patients
any local site of infection, such as the urinary tract, lower respi- who had had negative IV fluid cultures in the IV dressing study
ratory tract, or surgical site, in any of the patients. showed that all nine cases but only 9/19 operated controls
A review of healthcare-associated BSis over the preced- had received fentanyl intravenously in the operating room
ing 7 years showed that B. pickettii had not previously been (p = .05); the mean total dose given to the nine case-patients
was far greater than that given to control-patients who received
the drug (3,080 vs. 840 pg, p < .001).
At the time, fentanyl was used at the University of Wisconsin
TABLE 38.ll Evaluation of a Suspected Hospital only in the operating rooms (ORs) as part of balanced
Epidemic of Healthc:are- anesthesia. The drug was received in 20-mL ampules from the
Aasodated. Bloodstream manufacturer, and each week one of three pharmacy techni-
Infections cians, by rotation, predrew into sterile syringes all fentanyl
Administrative preparedness
likely to be needed the following week in the ORs. Each day,
Immediately retrieve putative epidemic blood isolates for one of the technicians delivered enough predrawn syringes
confirmation of identity through spaces and subtyping by to the ORs to meet the needs of the patients being operated
one or more methods; on that day. Cultures of predrawn fentanyl in syringes in the
Biotyping central pharmacy, prompted by the findings of the case-control
Antimicrobial susceptibility pattern (antibiogram) study, showed that 20/50 (40%) 30-mL syringes sampled were
Serotyping contaminated by B. pickettii in a concentration >104 cfu/mL;
Phage typing
Bacteriocin typing none of the 35 5- or 2-mL syringes showed contamination
SDS-PAGE protein electrophoresis (p < .001).
Polymerase chain reaction Extensive culturing in the central pharmacy was negative for
Pulsed-field gel electrophoresis evidence of environmental contamination by B. pickettii, with
Immunoblot pattern one exception: B. pickettiibiovariant 1, with an identical antimi-
Multifocus enzyme electrophoresis crobial susceptibility pattem and restriction enzyme fragment
Restriction enzyme digestion and restriction fragment
pattem to the epidemic strain recovered from blood cultures
polymorphism patterns
DNA probes or patients' IV infusions, was cultured in a concentration of 28
Preliminary evaluations and control measures to 80 cfu/mL from five specimens of distilled water drawn from
IdentifY and characterize individual cases in time, place, a tap in the central pharmacy. The epidemic strain was shown
and risk factors to multiply well in the fentanyl solution, attaining concentra-
Strive to identify the source of bloodstream infections tions > 104 cfu/mL within 48 hours.
Ascertain if cases represent true bloodstream infections, A second case-control study strongly suggested that the epi-
rather than "pseudo-bacteremias•
Ascertain if cases represent a true epidemic, rather than a
demic was caused by theft of fentanyl from 30-mL syringes by
"pseudo-epidemic" a pharmacy staff member and replacement with distilled wa-
Provisional control measures ter that the individual thought was sterile, but that, unfortu-
IntensifY surveillance, to detect every new case nately, was contaminated by B. pickettii. The pharmacy member
Review general infection control policies and procedures resigned early in the investigation. On April 29, the hospital's
Determine the need for assistance, especially extramural system for providing fentanyl and other narcotics to the ORs
(local, state, Centers for Disease Control and Prevention) was changed; narcotics were no longer predrawn into syringes
Epidemiologic investigations
Clinicoepidemiologic studies, especially case-control studies
in the central pharmacy, but were delivered to the ORs in un-
Microbiologic studies opened vials or ampules; anesthesiologists' orders for narcot-
Definitive control measures ics are filled by a staff pharmacist assigned to the OR. There
Confirm control of epidemic by intensified follow-up have been no further B. pickettiiBSis since March 25, 1985, and
surveillance cultures of >6,000 samples of hospitalized patients' IV fluid in
Report the findings research studies since that time have shown no further contam-
ination by B. pickettii.
SDS-PAGE; sodium dodecyl sulfute-polyacrylamide gel
electrophoresis.
This outbreak illustrates the power of epidemiology (e.g.,
case-control analyses) to identify the probable cause of an
epidemic. It further illustrates the potential for contamination for insertion and maintenance and more intensive education
of parenteral drugs or admixtures and the extraordinary range and training of nurses and physicians (284). The importance
of epidemiologic mechanisms of healthcare-associated BSI de- of adequate staffing of nurses to care for patients with eves
riving from such contamination. has recently been demonstrated (285). After controlling for
other risk factors associated with catheter-related infection in a
logistic regression model, as the patient-to-nurse ratio doubled
STRATEGIES FOR PREVENTION owing to nurse understaffing in an ICU, the risk of evCBSI in-
creased dramatically (odds ratio [OR], 62). This seminal obser-
Extensive guidelines for the prevention of catheter-related in- vation suggests that in this era of fiscal restraint in healthcare,
fection have been published (268). Specific interventions are cost-cutting measures that lead to understaffing of personnel
discussed in the following sections. aimed at caring for IVDs will ultimately increase cost and in-
crease the risk of HAis in today's hospitalized patients.
ASEPTIC TECHNIQUE
CUTANEOUS ANTISEPSIS (286)
To accord it due respect, any device for vascular access must be
thought of in fundamental terms as a direct conduit between Given the evidence for the important role of cutaneous micro-
the external world, with its myriad of microorganisms, and the organisms in the genesis of many IVDR infections, measures
bloodstream of the patient Vigorous hand hygiene, ideally to reduce cutaneous colonization of the insertion site would
with an antiseptic-containing preparation, and gloving always seem of the highest priority, particularly the use of chemi-
must precede the insertion of a peripheral IV cannula and also cal antiseptics of the site. Several studies, including a meta-
should precede later handling of the device or the administra- analysis, have shown that the use of 2% chlorhexidine with
tion set (269). Furthermore, sterile gloves should be routinely alcohol, rather than 10% povidone-iodine or 70% alcohol,
used during the insertion of peripheral IV cannulas in high- for cutaneous antisepsis before insertion of an IVD and in
risk patients, such as those with severe bums. Sterile gloves are postinsertion site care can substantially reduce the incidence
strongly recommended for the placement of all other types of of IVD-related infection (36,160-162,287). In one prospec-
IVDs-arterial and all evc,-that are associated with a higher tive investigation, 668 patients' central venous and arterial
risk of associated BSI (16). catheters in a surgical ICU were randomized to 10% povi-
The efficacy of maximal barrier precautions in the preven- done-iodine, 70% alcohol, or 2% aqueous chlorhexidine with
tion of nontunneled evCrelated infection has been demon- alcohol for antisepsis of the site before insertion and site care
strated (270,271). In this study, the incidence of CR-BSI was every other day thereafter (36). Chlorhexidine was associated
6.3 times higher in those patients who were prospectively ran- with the lowest incidence of infection; of the 14 infusion-re-
domized to have their catheters inserted with only sterile gloves lated BSis, one was in the chlorhexidine group and 13 were
and small sterile drapes, compared with those patients whose in the other two groups (OR, 0.16; p = .04) (Table 38.13).
catheters were inserted with maximal barrier precautions (i.e., Other investigators have also found that the use of aqueous
mask, cap, sterile gloves, gown, and large, sterile drape) (271). chlorhexidine to prepare the catheter insertion site is asso-
In another study, the use of maximal barrier precautions with ciated with a lower incidence of catheter-related infection
eve insertion, in addition to a mandatory 5-minute scrub of compared with povidone-iodine.
the insertion site, reduced the incidence catheter colonization In a historical analysis of the impact on the incidence of CR-
from 36% to 17% (272). Considering that of all IVDs, eves BSI of using different antiseptics for site care and disinfection of
are most likely to produce healthcare-associated BSI, maximal tubing connections in a home TPN program, 0.58 episodes per
barrier precautions during the insertion of such devices, par- catheter-year were observed during the use of 10% povidone-
ticularly the use of a long-sleeved surgical gown, large, sterile iodine as contrasted with 0.26 to 0.28 episodes per catheter-
sheet drape and sterile gloves, to minimize touch contamina- year during the use of a 0.5% to 2% tincture of iodine or 0.5%
tion should be routinely used (16,271). tincture of chlorhexidine (288). In prospective, randomized
Inappropriate catheter care is an independent risk fac- studies comparing the blood culture contamination rate using
tor for catheter-related infections (273). Not surprisingly, the povidone-iodine vs. iodine tincture to prepare the puncture
use of special IV therapy teams, consisting of trained nurses site, the use of iodine tincture was associated with a contamina-
or technicians to ensure a high level of aseptic technique dur- tion rate one-half that of the povidone-iodine group (289).
ing catheter insertion and in follow-up care of the catheter,
has been associated with substantially lower rates of catheter-
INSERTION SITE
related infection (114,272,274-282) (Table 38.12). Such teams
are highly cost effective, reducing the costs of complications of According to the CDC's Healthcare Infection Control Practices
infusion therapy nearly 10-fold (281,282). Advisory Committee (HICPAC) guidelines, the preferred site
In the absence of a dedicated IV team, some investigators for the insertion of nontunneled eves in adult patients is the
have carried out intensive educational programs in catheter subclavian vein (rating 1A) (268). The femoral site is associated
care. In one study, this led to improved care overall and a con- with higher rates of catheter colonization as well as increased
comitant reduction of colonization of the catheter insertion risk for deep vein thrombosis compared with the other sites
site; however, the incidence of catheter hub colonization was in adults (184,268,290-292) . In a randomized controlled trial
unchanged (283). In some U.S. hospitals, all eves, particularly (RCT) comparing the femoral and subclavian sites, the use of
those dedicated to TPN, are cared for by such teams. Other the femoral site was associated with a higher overall rate of in-
investigators have also shown that institutions can greatly re- fectious complications (19.8% vs. 4.5%; p < .001) (292). The
duce their CR-BSI rate by scrutiny of catheter care protocols internal jugular site has been associated with higher rates of
TABLE 38.12 Impact of a Dedicated IV Team on the Rate of Catheter-Related Bloodstream Infection
Incidence of IV-related
Type of Study Type of Bloodstream Infection
(Ref.) Catheter Care Given By No. of Cathetem (per 100 Cathetem) pvalue
CONC~BUTNOTBANDO~
(274) PIV House officers 4,270 0.40
IV team 470 0.04 <.001
(275) CVC.TPN Ward nurses 33 21.2
IV nurses 78 2.3 <.001
(276) CVC-TPN Ward nurses 391 26.2
IV team 284 1.3 <.001
(277) CVC.TPN Ward nurses 179 24.0
IV team 377 3.5 <.001
(278) CVC-TPN House officers 45 28.8
IV nurses 30 3.3 <.001
HISTORICAL CONTROLS
IV team 172 4.7 <.001
IV nurses 48 4.0 <.001
(281)" PIVandCVC House officers .001
IV team
RANDOMIZED, CONCURRENT CONTROLS

(114) PIV House officers 427 2.1
IV team 433 0.2 <.05
(282) PIV House officers 453 1.5
IV team 412 0.0 <.02
"Catheter-related bacteremia with house officers (4.5/1,000 patient discharges) vs. with IV team (1.7/ 1,000 patient discharges).
IV, intravenous; PIV, peripheral IV catheter; CVC, central venous catheter; TPN, total parenteral nutrition.
between the two sites (2.3 vs. 1.5; p = .42) (290). A prospective,
TABLE 38.13 Results of a Prospective,
observational study comparing the subclavian, intemaljugular,
Randomized Trial of Three and femoral insertion sites found that colonization was lowest
Cntaneous Antiseptics for at the subclavian site, but no difference in the rates of infec-
Prevention of Intravascular tion between the sites (293,294). Although no RCT to date has
Device-Rdated Bloodstream compared the three insertion sites, on the basis of the available
Infection data, we recommend the subclavian site as the preferred site
for eve insertion with the use of real-time ultrasound to mini-
10%
Povidon~ 70% 2% mize mechanical complications.
Source of Blood- iodine Alcohol Chlorhexidine Using real-time ultrasound guidance for catheter
stream Infection (n = 227) (n = 227) (n = 214) insertion decreases associated mechanical complications and
Catheter-related 6 3 1
infection (268,294,295). In a randomized study comparing
From contaminated: real-time ultrasound guidance with the landmark technique
Infusate 3 for catheter placement in the intemal jugular vein, the use
Hub 1 of ultrasound resulted in significantly fewer complications,
All sources (%) 7 (3.1) 6 (2.6) 1 (0.5) 4 including fewer CR-BSis (p < .001) (295). A meta-analy-
sis revealed that the use of ultrasound for insertion at the
"Compared with the other two groups combined
internal jugular and subclavian vein sites decreased failure
(OR, 0.16; p=.04).
From Mali DG, Alvarado CJ, Ringer M. A prospective, (RR, 0.32; 95% confidence interval [CI], 0.18 to 0.55), com-
randomized trial of povidone-iodine, alcohol and plications during catheter placement (RR, 0.22; 95% CI,
chlorhexidine for prevention of infection with central 0.10 to 0.45), and the need for multiple placement attempts
venous and arterial catheters. Lancet. 1991;338:339-343, (RR, 0.60; 95% CI, 0.45 to 0.79) in comparison with the land-
with permission. mark technique (296).
SIMULATION-BASED TRAINING
CR-BSis than the femoral and subclavian sites in several stud-
ies (123,184,268). However, a RCT comparing the jugular A recent observational study, completed in an urban teach-
and femoral sites found no difference in the risk for infection ing hospital, evaluated the impact of a simulation-based
educational intervention on the rates of CR-BSis in a medical vascular catheters, transparent dressings permit continuous in-
ICU (297). Ninety-two second- and third-year internal medi- spection of the site, secure the device reliably, and are generally
cine and emergency medicine residents completed the educa- more comfortable than gauze and tape. Moreover, transparent
tion program, which included a pretest, an informational video dressings permit patients to bathe and shower without saturat-
demonstrating proper eve insertion technique, training with ing the dressing. Clinical trials of these dressings have been
ultrasound, hands-on practice using the simulator device, and prompted by the knowledge that cutaneous occlusion with tape
a posttest with a required minimum score. There were 3.2 in- or impervious plastic films results in an explosive increase in
fections per 1,000 catheter-days in the 16 months before the cutaneous microflora, with overgrowth of gram-negative bacilli
intervention in this medical ICU. There were 4.86 infections and yeasts (303) . Although polyurethane dressings are semi-
per 1,000 catheter-days in a comparator unit in the same hospi- permeable-impervious to extrinsic microbial contaminants
tal, the surgical ICU, during this preintervention period. The and liquid-phase moisture, and variably permeable to oxygen,
rate ofCR-BSis in the medical ICU during the 16-month inter- carbon dioxide, and water vapor-and studies in healthy volun-
vention period, when all second- and third-year residents had teers have shown little effect of these dressings on the cutane-
completed the training, decreased to 0.5 per 1,000 catheter- ous flora (304), a meta-analysis has raised concern that these
days. The rate in the surgical ICU, where no rotating residents dressings could increase cutaneous colonization and the risk of
completed the simulation training, remained stable at 5.26 catheter-related infection {305) .
per 1,000 catheter-days during the same 16-month time period Transparent polyurethane dressings are more expensive
(297). The cost savings attributable to this simulation training than gauze and tape, and to obviate the issue of greater cost
were evaluated using data from the year before and the year and to increase convenience, many users leave transparent
following the training (298). The annual net savings resulting dressings on for prolonged periods, for up to 7 days or even
from the simulation-based training, after accounting for the longer. It has been questioned whether transparent dress-
cost of the training program, was >$700,000 (2,008 dollars), ings left on for prolonged periods might increase the risk of
which translated into a 7 to 1 rate of return on the investment catheter-related infection. There have been a number of tri-
in the training program (based on the cost of training being als comparing polyurethane dressings with gauze and tape on
$112,000). The use of simulation-based training exemplifies peripheral venous catheters (18,19,113,115,306-310). Three
cutting-edge methods for the successful education of health- trials (306-308) have found significantly higher rates of cath-
care personnel regarding proper eve insertion, fulfilling an eter colonization with transparent dressings left on indefi-
important recommendation in the CDC guidelines for the pre- nitely. Other investigators also found a higher rate in catheters
vention of CR-BSis (268). dressed with a transparent dressing, but only during the sum-
mer months (113). In additional studies, however, significant
differences were found (18,19,115,309,310). The rates of cath-
TOPICAL ANTIMICROBIAL OINTMENTS (299)
eter colonization in all of these trials have been low with all
In theory, application of topical antimicrobial agents to the dressings, in the range of 1.6% to 8.5%. Only three CR-BSis
catheter insertion site should confer some protection against were identified among the nearly 4,000 catheters studied in all
microbial invasion. Clinical trials of topical polyantibiotic oint- of the reported trials.
ments (i.e., polymyxin, neomycin, or bacitracin) on periph- In a prospective, randomized trial of various dressings used
eral venous catheters have shown only moderate or no benefit with 2,088 Teflon peripheral IV catheters (115), the transpar-
(163,300), and the use of polyantibiotic ointments has been ent polyurethane dressing studied, left on for the lifetime of
associated with an increased frequency of Candida spp. infec- the catheter, was not associated with increased cutaneous colo-
tions (122,163). In prospective, randomized trials, application nization under the dressing or an increased rate of catheter
of the topical antibacterial, mupirocin, which is active primarily colonization, compared with the control gauze and tape dress-
against gram-positive organisms, to catheter insertion sites has ing; however, there were no CR-BSis. Cutaneous colonization
been associated with a significant reduction in eve coloniza- was not heavier under transparent dressings during the spring
tion, but not arterial or peripheral catheter colonization. With- and summer months, as previously described (113), perhaps
out colonization by Candida spp., the impact on CR-BSI could because the hospital was air-conditioned. Multivariate analysis
not be assessed (301). However, widespread use of mupirocin showed cutaneous colonization of the insertion site (RR, 3.9)
at catheter insertion sites may lead to resistance (302), and for and moisture under the dressing (RR, 2.5) to be significant
this reason it is not recommended for routine application to risk factors for catheter-related infection (Table 38.8). These
the eve insertion site. data indicate that it is probably not cost-effective to redress pe-
There have been two prospective studies of topical ripheral IV catheters at periodic intervals, and that for most
povidone-iodine ointment applied to eve sites; one large, patients either sterile gauze or a transparent dressing can be
randomized trial in a surgical ICU showed no benefit (303), used and left on until the catheter is removed (16).
but a more recent comparative trial with subclavian hemodi- Studies of transparent dressings on short-term, noncuffed
alysis catheters showed a 4-fold reduction in the incidence of central venous and/or pulmonary artery catheters have yielded
hemodialysis CR-BSI (128). conflicting results (38,310-319), in part reflecting differences
in study protocols (e.g., the use of topical antimicrobial oint-
ments under the dressing in the control gauze group, but not
DRESSINGS
in the transparent dressing group) and different dressings stud-
The importance of the cutaneous microflora in the pathogen- ied. One group of investigators (313) reported a 3-fold increase
esis of IVDR infection might suggest that the dressing applied in infectious complications associated with subclavian catheters
to the catheter insertion site could have considerable influence using transparent dressings for s7 days compared with gauze
on the incidence of catheter-related infection. When used on replaced three times weekly, but the difference did not achieve
580 Section m • Endemic and Epidemic Hospitm Injtction.s
statistical significance. Others (311) have found a much higher CHANGIN G CATHETE RS OVER A GUIDEW IRE
rate of eR-BSI using transparen t dressings compared with gauze
The Seldinger technique, in which the vessel is identified and
and tape (16% vs. 0% ). In a similar trial performed in an ICU,
there were no significant differences in catheter-related infec- entered percutaneo usly with a fine-gauge needle and can-
nulated with a guidewire passed through the needle, after
tion with transparen t dressings compared with gauze dressings
which the cannula is guided into the vessel over the guidewire,
when the transparen t dressing was changed every 2 days (316);
however, in these high-risk IeU patients, we observed a signifi- has been a major advance, permitting vessels to be cannu-
cant buildup of skin flora, associated with a 50% increase in lated with large catheters with much less risk of vascular in-
jury and, in the case of subclavian or internal jugular eves,
catheter-related infection, when transparen t dressings were left
pneumotho rax, and with less manipulati on and potential for
on for up to 7 days between changes, suggesting that if used
on eves in ICU patients, the dressing studied may need to contamina tion. To avoid iatrogenic pneumotho rax and other
be replaced more frequently. Other prospective trials, which mechanica l complications associated with percutaneo us in-
in aggregate studied hundreds of eves in high-risk patients, sertion of a new cannula, particularly a eve, new catheters
many of whom were receiving TPN through the catheter, did are commonly placed over a guidewire in the site of an old
not find an increased risk of catheter-re lated infection associ- catheter (124). Prospective, RCTs have shown that routinely
replacing eves over guidewires is unnecessary (124,167,321).
ated with transparen t dressing left on for a prolonged duration,
In the largest of these studies (124), the incidence of eR-BSI
as compared with gauze and tape replaced more frequently
(38,310,312,314,315,317-319). In a large, prospective, ReT, per 1,000 catheter-days was nearly 2-fold higher in patients
we fuund no difference in the incidence of catheter coloniza- randomize d to the guidewire groups, and 75% of CR-BSis and
tion or CR-BSI in patients whose catheters were covered with fungemias occurred within 72 hours of guidewire exchange or
catheter insertion. In a study performed in a pediatric IeU,
gauze and tape dressing changed every 2 days, convention al
polyuretha ne dressing, or a polyuretha ne dressing with a high eves were left in place without routine guidewire exchange
moisture vapor transmission rate, both replaced every 5 days (322). Despite prolonged catheteriza tion, the incidence den-
(38). However, at the time of catheter withdrawal, insertion sity of catheter-re lated infection did not increase with the du-
site colonization was greater under both polyuretha ne dress- ration of time the catheters were left in situ. Similar results
ings compared with the gauze and tape dressing group. There were found in a study of adult oncology patients whose non-
cuffed, nontunnel ed eves were left in place for a mean of
was no significant difference in colonizatio n between the poly-
136 days (323). These data suggest that routine guidewire
urethane dressing groups. Similarly, the incidence of evCBSI
exchange of eves is unnecessar y in patients who are without
was no different for patients whose catheters were dressed with
unexplaine d fever and without induration or drainage from
gauze and tape every 2 days compared with transparen t dress-
ing every 5 days in a multicente r trial; however, colonization the catheter insertion site. In two prospective studies of central
was significantly more common in the polyuretha ne dressing venous and Swan-Ganz pulmonary artery catheters, the inci-
group (319) . dence of catheter-re lated infection was not significantly differ-
ent among patients whose catheters were routinely changed
Two randomize d studies of the use of transparen t dressings
on surgically implanted, cuffed Hickman or Broviac catheters over guidewires or left in place (124,321). However, the data
derived from all prospective clinical trials of Swan-Ganz
~ave been reported in which microbiolo gic data were pro-
VIded (316,320); in both trials, one in renal transplant patients pulmonary artery catheters demonstra te that the incidence
(316) and the other in bone marrow transplant recipients of BSI rises sharply on the fifth day of catheteriza tion (52).
Because of these conflicting results, firm recommen dations
(320), the transparen t dressing studied provided satisfactory
cover, and even when left on for prolonged periods, for up to regarding the safe duration of Swan-Ganz pulmonary artery
catheters cannot be made at this time.
5 to 7 days, was not associated with a significantly increased
One prospective study of arterial catheten found that
risk of exit site or tunnel infection, or of eR-BSI. These stud-
ies of central venous, pulmonary artery, or long-term tunneled there was a greater incidence of CR-BSis when catheters were
cathe.ters suggest that either transparen t or gauze and tape routinely exchanged over guidewires compared with cath-
dressmgs can be safely used to cover the insertion site of these eters removed after 7 days and inserted into a new site (35).
devices. Other studies have shown that the incidence density of arte-
rial catheter-related infection did not increase with the dura-
There have been few reported studies of transparen t poly-
urethane dressings with arterial catheters (19,316). In one tion of time the catheters were left in place (324,325), and in
three prospective studies in which the catheters, transducers,
prospective study of dressings for arterial catheters used for
hemodynam ic monitoring in a surgical ICU, the use of the and plasticware were not routinely changed (326-328), the in-
transparen t dressing, even when replaced every other day, was cidences of catheter colonization (2.9%) and CR-BSI (0.2%)
wer~ quite low and comparabl e with those in other prospective
associated with a 5-fold increased incidence of eR-BSI, com-
studies. Therefore, these data suggest that arterial catheten
pared with gauze and tape (316). The greatly increased risk of
similar to eves, may not need to be replaced at routine inter:
infection associated with transparen t dressings used on arterial
va1s as long as signs of localized infection are absent and the
catheters found in this study may reflect the presence of mac-
patient is without unexplaine d fever. It is important to remem-
ros~op~c blood in the puncture wound, under arterial pressure,
ber that all invasive devices, including intravascular catheters of
which 18 common under transparen t dressings on arterial cath-
eters; if the blood cannot be cleared, it may provide a rich me- any type, increase the risk of infection, and their need should
dium for microbial proliferation, which can result in infection be assessed on a daily basis. In one study, nearly 20% of patients
on medical wards had idle catheters for 2::2 consecutive days,
of th~ cathete~. In a recent large, randomize d trial, a highly
adhesive dressmg reduced detachmen t but increased catheter and 20% of all patient-days of N catheter use were idle and
colonization. unnecessarily increasing the risk of catheter infection in these
patients (329). In a follow-up study, intensive educational ef- Also, no blood was drawn through the catheters in this study,
forts reduced the incidence ofidle catheters (330). which is common practice in the United States. This may have
If it is considered desirable to replace a central venous or led to a lower incidence of hub-related BSI, further magnifying
arterial catheter because it has been in place for a prolonged the difference in tunneled and nontunneled catheter groups
period and there is suspicion of infection (e.g., unexplained fe- with regard to BSI. In another study (323), nontunneled eves
ver), it is not unreasonable to replace the catheter in the same in immunocompromised patients inserted for prolonged peri-
site over a guidewire if the patient has limited sites for new ac- ods of time also had a very low incidence of BSI when the cath-
cess or would be at high risk for the percutaneous puncture eters were cared for by specialized IV nurses. Therefore, eves
required for the placement of a new catheter in a new site (e.g., cared for by specialized IV nurses may not need to be tunneled
has coagulopathy or is morbidly obese). However, it is impera- in an attempt to reduce the incidence of catheter-related infec-
tive that the same meticulous aseptic technique that should be tion. The utility of tunneled subclavian eves in situations with-
mandatory during insertion of any new catheter must be em- out specialized IV nursing teams requires further study.
ployed, including the routine use of sterile gloves and a sterile
drape, and for eves, a sterile gown as well. After vigorously
ANTIMICROBIAL LOCK SOLUTIONS
cleansing the site and the old catheter with the antiseptic solu-
tion, inserting the guidewire, removing the old catheter, and The major mechanism for CR-BSis in patients with long-term
cleansing the guidewire and site once more with the antiseptic devices is intraluminal colonization. For this reason, antimicro-
solution, the operator should reglove and redrape the site be- bial lock solutions have been tried as a logical step to prevent
cause the original gloves and drapes are likely to be contami- colonization of the intraluminal surfaces of long-term devices
nated from manipulation of the old catheter. Mter regloving and thereby reduce the rate of CR-BSis. A small amount of the
and repreparing the site, the new catheter can be inserted over antimicrobial solution is instilled into the lumen of the cath-
the guidewire. eter and allowed to remain for a specific amount of time, af-
It is also important to routinely culture the old catheter after which it is either flushed or removed. A meta-analysis of
ter guidewire exchange and, if the patient is febrile or shows seven randomized trials, involving mostly cancer patients, in
other signs of BSI, to obtain blood cultures. If these cultures which vancomycin-containing lock solutions were used demon-
demonstrate that the old catheter was colonized, the new cath- strated a significantly reduced risk for CR-BSis (RR, 0.49; 95%
eter just placed in the old site should be immediately removed CI, 0.26 to 0.95) (332). A recent systematic review and meta-
to prevent progression to CR-BSI (or perpetuation of ongoing analysis of patients undergoing hemodialysis included studies
CR-BSI) because the new catheter has been inserted into an of several lock solutions: various antibiotic combinations, mi-
infected tract. The need for continued access would mandate nocycline with EDTA, and nonantibiotic antiseptic solutions
placement of a new catheter in a new site. If, on the other including citrate and citrate with taurolidine. All lock solu-
hand, the culture of the old catheter is negative, it has been tions tested showed benefit regarding prevention of CR-BSis
possible to preserve access and to examine the initial catheter (333). Ethanol has also been shown to be safe and effective as
microbiologically and exclude it as the cause of fever or BSI, an antimicrobial lock solution (334-336). A recently published
without subjecting the patient to the hazards associated with prospective, double-blind, randomized trial comparing ethanol
percutaneous insertion of a new catheter. with heparinized saline in immunosuppressed hematology pa-
If the old insertion site is inflamed at the outset, especially tients showed a 4-fold decrease in the number ofCR-BSis in the
if it is purulent, or the patient shows signs of sepsis that might ethanol group compared with the controls (OR, 0.18; 95% CI,
be originating from the catheter, or the catheter recently has 0.05 to 0.65) (336). Although a number of new antibiotics show
been shown to be infected by quantitative blood cultures drawn promise as lock solutions in in vitro studies, further research
through the catheter, it is strongly recommended that a new of their efficacy in a clinical trial is necessary (337). In general,
catheter not be inserted over a guidewire into an old, poten- antiseptic lock solutions are preferable to antibiotic lock solu-
tially infected site. tions because of their greater spectrum of activity and smaller
risk for promoting antibiotic resistance.
The current CDC HICPAC guidelines for the prevention
THE EFFECT OF SUBCUTANEOUS TUNNEL
of CR-BSis include a recommendation for the use of antimi-
INSERTION OF CENTRAL VENOUS CATHETERS
crobial/antiseptic lock solutions in patients with long-term
Subcutaneous tunnel insertion of eves has traditionally been catheters who have had multiple CR-BSis despite good aseptic
carried out in an effort to reduce the risk of catheter-related technique (Rating II) (268). The use of antimicrobial lock so-
infection. In a prospective, randomized study in immunocom- lutions for the prevention of CR-BSis in long-term devices in
promised patients, the incidence of CR-BSI was the same in patients with episodes of CR-BSI at high risk for recurrence,
those patients whose catheters were tunneled, compared to such as those on hemodialysis, is recommended.
those whose catheters were not (330). In a randomized trial of
catheters used for administering TPN (279), the incidence of
DAILY CHLORHEXIDINE BATHING
catheter sepsis was reduced with tunneling of catheters before,
but not after, a trained IV nurse assumed complete responsibil- Chlorhexidine bathing has been proposed and evaluated as a
ity for catheter care. In a more recent, prospective, randomized strategy for reducing the rates of CR-BSis ( 338-341). Bleasdale
study, tunneling eves inserted into the internal jugular vein et al. compared daily chlorhexidine bathing (n = 391; 2,210
dramatically reduced the incidence ofCR-BSI (RR, 0.19) (331). patient-days) with soap and water bathing (n = 445; 2,119
However, this may be difficult to extrapolate to the U.S. experi- patient-days) among patients in two medical reus in a 2-arm
ence, since most tunneled catheters in the United States are crossover trial (338). There was a significant reduction in
inserted in the subclavian, rather than the internal jugular vein. the risk for CR-BSis associated with the use of chlorhexidine
bathing compared with the control group (4.1 vs. 10.4 infec- the duration of use allows considerable cost savings to hospi-
tions per 1,000 patient-days; incidence difference, 6.3; 95% tals (228). Other prospective studies have demonstrated that
CI, 1.2 to 11.0). A recent meta-analysis of RCTs and quasi- replacement of the IV delivery system every 96 to 120 hours
experimental studies evaluating chlorhexidine bathing vs. did not increase the incidence of catheter-related infection
a control bathing method (soap and water) demonstrated (324,347). It is important to remember that replacement of the
a significant reduction in risk for CR-BSI associated with IV delivery system at more prolonged intervals may predispose
chlorhexidine bathing (pooled RR, 0.32; 95% CI, 0.22 to 0.46; to epidemic BSI, particularly when the fluids infused promote
p < .0001; J2 = 17%) ( 342). However, a retrospective analy- microbial growth (242).
sis, not included in the meta-analysis, evaluating the effect of Three clinical settings might be regarded as exceptions
switching from soap and water bathing to daily chlorhexidine to using 72 to 96 hours as an interval for routine set change:
cleansing in a surgical ICU found no difference in the rates (a) during administration of blood products or (b) lipid
of CR-BSis when the different periods were compared (343). emulsions, (c) infusion of propofol, or (d) if an epidemic of
The IDCPAC/CDC guidelines for the prevention of CR-BSis infusion-related BSI is suspected. In these circumstances, it is
recommend daily chlorhexidine bathing as a strategy for reduc- most prudent that administration sets be changed routinely at
ing the rate of CR-BSis (rating II); however, most of the studies 24-hour intervals or even more frequently. Minute amounts of
have been limited to ICUs, and the impact seems to be greatest blood buffers acidic solutions and provides organic nutrients
for the prevention of VRE-BSis; thus, the conflicting results of that greatly enhance the ability of most microorganisms to grow
recent studies warrant further research in this area (268). in parenteral fluids (217). Moreover, most hospital pathogens,
including coagulase-negative staphylococci, some gram-negative
bacilli, Candida spp., or M. furfur, grow rapidly in commercial
CATHETER SECUREMENT
lipid emulsion (219,220,225,242), and BSI outbreaks have been
Sutureless securement devices avoid disruption around the associated with administration of lipid emulsion (242,245,348).
catheter entry site and may decrease the degree of bacterial Studies suggest that the infusion system, including the ad-
colonization (344). Catheter stabilization also helps decrease ministration set and other delivery components, for hemo-
the risk for phlebitis, catheter migration and dislodgment, and dynamic monitoring may not need routine replacement as
also mitigates the risk of sharps injury to the healthcare prolong as the catheter insertion site is without induration or dis-
vider from inadvertent needlestick injury (268). charge and the patient is without an unresolved source of fever
The choices for device securement include sutures, tape, (234,326--328).
and catheter securement devices such as StatLock® (Venetec The type of infusion pump and delivery system used may af-
Intemational, a subsidiary of CR Bard). Sutures may be uncom- fect the incidence of catheter-related infection. Line breaks as-
fortable for the patient, pose a risk of needlestick injury to the sociated with some infusion pumps and delivery systems appear
provider, and foster inflammation at the catheter insertion site, to be susceptible to air entry into the tubing, leading to greater
increasing the risk of infection. StatLock®, a sutureless catheter manipulation, and at one institution this was associated with an
securement device, reduces catheter-related complications in- outbreak of coagulase-negative staphylococcal BSI (259). Some
cluding possibly CR-BSis (344-346). A randomized trial com- systems require significantly fewer line breaks than others
paring sutures to StatLock® for PICC securement revealed a (349), and this may lessen the risk of catheter-related infection
significant decrease in the number of CR-BSis in the StatLock® because an excessive number of line breaks per day has been
group (2 vs. 10; p = .032) (344). The use of a securement de- demonstrated to be an independent risk factor for catheter-
vice for peripheral IV and extended-dwell catheters, such as related infection (350).
PICCs, and their use with PICCs is recommended in the recent Needleless IV systems have come into widespread use in an
CDC guidelines (rating II) (268). The impact of securement effort to reduce the risk of exposure to blood-home pathogens.
devices on non-PICC central lines needs further study. However, the risk of CR-BSI associated with the use of these
systems has not been systematically addressed in prospective,
randomized trials. A number of studies have found that these
MEASURES AIMED AT systems may actually increase the risk of catheter-related infec-
THE DELIVERY SYSTEM tion (257,351-355). A unifYing problem is the inability to clean
the inner components of these systems; once they become
Numerous studies have shown that most CR-BSis are not caused contaminated, bacteria and fungi can proliferate to large num-
by contaminated infusate (1,2); however, infusate can occasion- bers, leading to intraluminal seeding of the blood (351,352).
ally become contaminated and cause endemic bacteremia or Another issue increasing the risk of CR-BSI may be lack of
fungemia (36--38,121,184). If an infusion runs continuously education or proper training of end users to ensure that the
for an extended period, the cumulative risk of contamination hub is adequately decontaminated before each access. At our
increases, and further, there is increased risk that the contami- institution, we have recently transitioned to a positive pressure
nants can grow to dangerously high concentrations that will needleless connector and noted a sharp increase in CR-BSis.
result in BSI in the recipient of the fluid. For nearly 20 years, Direct observations of HCW behavior showed that the hub was
most U.S. hospitals routinely replaced the entire delivery sys- not being disinfected before each use. Intensive in-services
tem of patients' IV infusions at 24- or 48-hour intervals (1,2), training and feedback resulted in the reduction of CR-BSis to
to reduce the BSI risk from extrinsically contaminated fluid. baseline levels while continuing the use of the needleless con-
Prospective studies (Table 38.9), however, now indicate that IV nector. Prospective studies are needed to determine the safety
delivery systems do not need to be replaced more frequently of needleless systems with regard to needlestick injury, catheter
than every 72 to 96 hours, including infusions used for TPN hub colonization, and BSI, particularly with regard to socioad-
or any infusions in ICU patients (227,228,230); extending aptive factors that may impact risk. The use of antiseptic caps
on needleless connectors may decrease the risk of such exter- Given the multiplicity of potential sources for infection of
nal colonization; further studies are needed to assess their im- an IVD and the importance of adherence of microorganisms
pact on BSI risk. to the catheter surface in the pathogenesis of infection, it
Terminal in-use membrane filters continue to be advo- would seem logical that the best strategy for prevention might
cated as a means of reducing the hazard of contaminated in- be to develop a catheter material implicitly resistant to colo-
fusate. However, filters must be changed at periodic intervals nization. It has been demonstrated that hydrophilic catheters
and can become blocked, leading to added manipulations of are less likely to become colonized by bacteria in in vitro as-
the system and, paradoxically, greater potential for contami- says (370,371). Binding a nontoxic antiseptic or antimicrobial
nation (356,357). Some commercial in-line filters may also to the catheter surface or incorporating such a substance into
permit the passage of endotoxin (357,358). The increased the catheter material itself might prove to be the most effective
risk for phlebitis associated with the administration of IV an- technologic innovation for preventing device-related infection.
tibiotics may be reduced by removing the microparticulates In a prospective, RCT of central venous or arterial catheters in
that are associated with compounding these drugs with 0.22- a surgical ICU, catheters coated with cefazolin bonded to the
or 0.44-p.m in-line fllters {359); however, not all randomized surface with a cationic surfactant were associated with a 7-fold
trials have shown a substantial reduction in phlebitis with reduction in colonization of the catheter; however, there were
the use of in-line filters {360). Moreover, filters are expen- no CR-BSis identified in the study population (172). More re-
sive, and their use adds substantially to the costs of phlebitis cently, catheters coated with minocycline and rifampin have
from microparticulates. Few controlled, prospective clinical been shown to significantly reduce the incidence of catheter
trials have been done to assess the effect of in-line filters on colonization and CR-BSis (173). The widespread use of these
the incidence of serious catheter-related infections. In these devices is also tempered by the risk of the development of re-
studies, small numbers of patients were enrolled and the out- sistance to these valuable antibiotics (372). We have studied a
comes were variable (361,362); however, studies carried out novel eve in which the catheter material itself, polyurethane,
in animals suggest that with heavily contaminated infusate, is impregnated with minute quantities of silver sulfadiazine
in-line filters reduce mortality (362). Large, prospective, and chlorhexidine (Arrowgard; Arrow International, Read-
double-blind clinical studies establishing their efficacy and ing, Pennsylvania, USA); in a randomized, comparative trial in
cost-effectiveness are needed before their routine use can be 402 patients in a surgical ICU, antiseptic catheters were 2-fold
advocated, especially as a control measure for the prevention less likely to be colonized and 4-fold less likely to produce BSI
of rare sporadic BSis resulting from extrinsic contamination (177). Adverse effects from the test catheter were not seen. In
ofinfusate (16). a prospective, randomized study, other investigators also have
found that this device reduced the incidence of catheter-related
infection (178); however, with more prolonged catheterization,
INNOVATIVE TECHNOLOGY efficacy appears to wane (179,180) (Table 38.14). Silver-coated
catheters also have been shown to reduce the incidence of
The development and application of novel technology holds catheter-related infection (174), as have catheters bound with
the greatest promise for a quantum reduction in the risk of benzalkonium or heparin (175,176). The strategies that hold
infusion-related BSI, especially infection due to the percuta- the greatest promise are those that will change the IVD itself in
neous device used for intravascular access: innovations in the a novel way that is unlikely to promote resistance to antibiotics
design or construction of the infusion apparatus that implicitly or antiseptics. One innovative approach is to apply an electric
deny access of microorganisms to the system or that prevent or- current to the catheter (373,374). In vitro studies with these
ganisms that might gain access from proliferating to high con- catheters demonstrate that they inhibit the growth of bacteria
centrations or colonizing the implanted cannula can obviate and fungi (373) and are resistant to colonization, and that appli-
poor aseptic technique or undue patient vulnerability. cation of an electric current sterilizes colonized catheters (373).
In a bum model, silver-coated dressings reduced the tissue
penetration of P. aeruginosa in animals and may reduce the risk
of catheter-related infections (363). Previous studies of incor- TABLE 38.14 Efficacy of The
porating an antiseptic, namely povidone-iodine, into a trans- Chlorhexidine/SBve:r
parent catheter dressing to suppress cutaneous colonization Sulfadiazine Catheter
under the dressing have been disappointing (115). However, in (CHSS) (Arrowgard™)
view of the superiority of chlorhexidine over povidone-iodine in Preventing Catheter
for cutaneous antisepsis of vascular catheter sites (36,160-162), Colonization and Catheter-
incorporation of chlorhexidine into a dressing's adhesive has
Related Bloodstream
been proven to be more effective. A chlorhexidine-impregnated
Infection (CR-BSI)
urethane sponge composite {BioPatch; Johnson & Johnson,
Arlington, Texas, USA) has been shown to significantly reduce Catheter
epidural catheter colonization, from 29% to 4% (364). In sev- Colonization (%) CR-BSI (%) Duration
eral RCTs, use of the BioPatch has reduced catheter coloniza- CHSS Corrlrol CHSS Omlrol (Day-) ~
tion and CR-BSis (365-369). In a large, recent, randomized
trial, the benefit of the BioPatch has also been extended to ar- 13.5 24.1" 1.0 7.6• 6 168
18.1 30.8" 0 2.6 -8 169
terial catheters and internal jugular lines (365). This study also 10--11
6.3 7.5 171
documented in an RCT that such transparent dressings could 10.9 12.1 8.7 8.1 12-13 170
be replaced every 7 days; this recommendation has been in-
cluded in the CDC HICPAC IV guideline. •p< .05.
In an animal model of S. aureus catheter-related infection, these the use of EDTA with minocycline reduced eR-BSis (384).
catheters were more effective in preventing infection than the These solutions have significantly reduced the risk of eR-BSI in
silver sulfadiazine-chlorhexidine-impregnated catheters (374). high-risk pediatric oncology or neonatal IeU patients.
Strategies aimed at reducing hub-related BSI have been d~ In the past several years, studies have demonstrated that
vised, and in a clinical trial, a novel hub incorporating an iodine we should have zero tolerance for catheter-related infections.
tincture reservoir reduced the incidence of BSI 4-fold (375). Interventions using a ubundle approach" for insertion and for
Recently, in an in vitro study in which we contaminated the sur- maintenance, which has included many of the interventions
face of mechanical valve needleless connectors and then disin- discussed previously, have been able to reduce catheter-related
fected them with alcohol or used a chlorhexidine-impregnated infection (including evCBSI) rates in ICUs to very low levels
cap, we found that the cap, we was significantly more likely to (sometimes zero for many months) (Table 38.15) (385-387).
eliminate contaminants than was alcohol when used for 10 sec- The current practice in many healthcare facilities falls short of
onds (376). Although no clinical trials have been performed on those used in successful prevention programs (ll1). As more
the best antiseptic to use for IVD disinfection, it is clear that suf- and more facilities throughout the world implement the bun-
ficient contact time (at least 15 to 30 seconds of alcohol) is nec- dle approach for catheter-related infection prevention using
essary to ensure that the contaminants are removed. the most effective measures (131,187,388-391), many lives will
The addition of a nontoxic, biodegradable or easily metabo- be saved (385).
lized antiseptic to N fluid or N admixtures (377-381) might
eliminate the hazard of fluid contamination altogether and, fur-
ther, reduce the risk of hub contamination, obviating the need MULTIFACETED APPROACH
for periodic replacement of the delivery system. The use of USING A CHECKLIST
vancomycin-containing flushes or catheter/valve dwells has been
shown to reduce the risk of CR-BSI and to potentially salvage A multifaceted approach must be used to effectively reduce the
some contaminated eves (382,383). In hemodialysis patients, risk for eR-BSis. The Institute for Healthcare Improvement
(IHI) developed the concept of "bundles" to aid in risk reduc-
tion. A bundle, according to the IHI, is a structured way of im-
TABLE 38.15 Central Venous Catheter proving the processes of care and patient outcomes using a set
of generally three to five practices in the form of a checklist
Bloodstream Infection
that, when performed collectively and reliably, have been shown
(CVC-BSI) Prevention to improve patient outcomes (392). The !HI-recommended
lnaertion and Maintenance evidenc~based bundle for eve care includes the following:
Bundles (a) hand hygiene; (b) maximal barrier precautions upon inser-
INSERTION BUNDLE: tion; (c) chlornexidine with alcohol for skin antisepsis; (d) opti-
Hand hygiene by catheter inserters mal catheter site selection, with subclavian vein as the preferred
Maximum barrier precautiom (gowns, gloves, mask, cap) site for nontunneled catheters and avoidance of femoral lines;
Chlorhexidine (with alcohol) skin antisepsis of catheter and (d) daily review of line necessity with prompt removal ofun-
insertion site necessary lines (392). In a large, multicenter study, by Pronovost
Trained catheter inserters et al. in which evidence-based interventions nearly identical to
Proper selection of type of catheter and insertion site
those of the IHI CVC insertion bundle were used for 18 months,
(avoid femoral)
Insert catheters only when medically necessary a significant reduction in eR-BSis from baseline was observed in
Have all materials needed for catheter insertion at the bedside 103 IeUs throughout the state of Michigan, with incidence rate
before starting imertion (cart or kit) ratios at 0 to 3 months of 0.62 (95% ei, 0.47 to 0.81) and at 16
Time-out called if proper procedures are not followed to 18 months of 0.34 (95% ei, 0.23 to 0.5) (393). These num-
(then start again) bers represented up to a 66% reduction in the rates of eR-BSis.
Use of aseptic technique during catheter manipulation These low rates were sustained in the 18 months following the
(including hub disinfection)
intervention period as the interventions were integrated into
Remove catheters when no longer medically necessary
Executive leadership support for bundle implementation standard practice at the individual centers (394).
Frequent feedback of bundle compliance and outcomes Bhutta et al. undertook a prospective quasi-experimental
(catheter-related infection rates) study in a pediatric IeU at a children's hospital, which in-
cluded the stepwise introduction of interventions over a 5-year
MAINTENANCE BUNDLE: period (395). The interventions included maximal barrier
Select the safest needleless connector precautions, a transition to antibiotic-impregnated eves, an-
Scrub the hub of the needleless connector (chlorhexidine nual handwashing campaigns, the chlorhexidine-impregnated
or alcohol for 15 seconds) during manipulation dressing (BioPatch), and the use of chlorhexidine in lieu of
Use the chlorhexidin~impregnated (BioPatch) dressing
Use antiseptic- or antimicrobial-impregnated catheters povidone-iodine for skin antisepsis. Significant decreases in the
Use antiseptic or antimicrobial locks rates of infection occurred over the intervention period. These
Chlorhexidine bathing ofiCU patients were sustained over the 3-year follow-up. The annual rates d~
Replace dressing when wet, soiled, or damaged; routinely creased from 9. 7 per 1,000 catheter-days with a eve in 1997 to
replace dressings at 7 (transparent) or 2 (gauze) days. 3.0 per 1,000 days in 2005 (RR, 0.75; 95% CI, 0.35 to 1.26). The
Use of aseptic technique during catheter manipulation investigators agreed that multifaceted interventions of this na-
(including hub disinfection)
ture reduce eR-BSis but require a multidisciplinary team and
Remove catheters when no longer medically necessary
institutional support.
The recent implementation of a multifaceted approach in 12. Inglio 'IJ, Sproat LJ, Hawkey PM, et aL Infeetion control in intenoive care unito: U.K. na-
tionalouney. Br]A......U..l992;68(2):2lf>-220.
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maintenance bundles, chlorhexidine-impregnated dressings blood stream iofectiono-United Statel, 2001, 2008, and 2009. MMWR Mm6 Morl4l ~
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noncuffed ohort~ central venouo catheter>. Int...Jiw C.... Mill. 2004;50(1):62-07. 405. Rello J, Coll P, Net A, et. al. Infection of pulmonary artery catheter>. Epidemiologic char-
!190. Crnich Cj, Maki DG. The promile of novel technology for the prevention ofinll'aValeular actcriotics and multivariate analylio of riot factor>. CAm. 1995;103(1):1S2-ll!6.
device-related blood.otream infection. I. Pathogeneoio and ohort~ dericeo. Clin Infta 404. Damcn J, Van der 'I'Wcel I. Pooitive tip cultureo and related rilk. facton uoociated with
DU. 2002;54(9):1%'2-124!. intravaacular catheterization in pediatric cardiac patienta. Grit Cant Mill. 1988;16(5):
591. Crnich qJ, Maki DG. The pronrloe of novel technology fur the prevention of intra- 221-228.
vascular device-related blood.otream infection. II. Lon~ devicco. Clin Infocl DU. 405. Newman KA, Reed WP, SchimpJr SC, et al. Hickman catheter> in aooociation with inten-
2002;54(10): 1362-1568. oive cancer chemotherapy. Sv{1port Cant r::.m.:..-. 1998;1 (2):92-97.
592. Haraden C. "Wbat io a bundle? blip://www.ilri.org/IHI/Topico/Critica!Care/Intcnoioe 406. Fridtin SK, Pear SM, WiiliamJon Til, et al. The role of under>tafling in central ..,ouo
Carc/ImprovcmentStories/Whatballundle.htm. Acceued ~0 July, 2010. cathet.er.......ctated blood.otream infections. hifrct CmurolH..p~ 1996;17 (!) : 1~158.
593. Pronaroot P, Needham D, Berenholtz S, et al. An intervention to decreue cathetel" 407. Cimintti JP, Haao J, Saiman L, et al. Impact of otaJ!ing on bloodatream infection• in the
related bloodatream infection• in the ICU. N E"'f)J Ml!d. 2006;~55 (26) :2725--27~2. neonatal intcnoioe care unit. Arm .l'ediatrAd6/m; Mill. 2006;160(8) :852--&16.
594. Pronaro1t PJ, Goeochel CA, Colantuoni E, et al. Suotaining reduction• in catheter re- 408. Alomo-Ecbanove J, Edwardo .)R, Richard.o MJ, et al. Efl'ect of nune otafling and
lated blood.otream infectiono in Michigan intenoin: care unito: ob:ocrvational otudy. BMJ. antimicromal-imprego.ated central venouo catheters on the risk fur blood.otream infec-
2010;ll40:c509. tiono in intenoive care unita. Infocl CotllroiHos[>Ep~ 200S;24:916-925.
39 Raymond Y. Chinn
Infections of Intplantable Cardiac

and Vascular Devices
INTRODUCTION DAis related to central lines or vascular access for dialysis; these
topics are reviewed elsewhere.
The Centers for Disease Control and Prevention (CDC) re-
port that heart diaease is the leading cause of death for both
men and women in the United States. In a population of PATHOGENESIS
312.8 million, an estimated 600,000 people die of heart dis-
ease every year and more than half (385,000) ru.ccumb to Following the implantation of a medical device, successful in·
coronary heart disease, the most common type of heart dis- tegration occurs when host cells adhere to the surface of the
ease (1). Therefore, strategies to prevent and manage cardio- device, multiply, and form granulation tiasue that envelops the
vascular disease have become national healthcare priorities. device and renders it resistant to invasion by microorganisms.
Significant technologic advances have made it possible to cir- However, in a permiuive host, this normal event is replaced
cumvent the natural history of cardiovascular disease by pro- by adhesion of microbes onto the device. The majority of im·
viding implantable devices that replace or bypass the failing planted DAis are caused by the staphylococci; Staphylococcus
components of the cardiovascular system. In doing so, these aumu produces a number of adherence molecules collec-
devices can salvage a limb or sustain life by maintaining hemo- tively known as the microbial surface components recognizing
dynamic and electrical stability. Prosthetic valves, permanent
pacemakers, implantable cardioverter-defibrillators (ICDs),
left ventricular assist devices (LVAD), total artificial hearts, vas- TABLE 39.1 Inddenc:e of Implantable
cular stents, vascular patches, and vascular grafts are included Cardiac and Vucular-
in this group of devices. .A.oclatcd Infectioos
The incidence of device-associated infection (DAis) varies
and depends on the type of implanted device (Table S9.1). Jm:idence of IDfectiaa
In most instances, DAis are rare, with the notable exception Type of Prosthesis ("; lllmp, Median)
of LVADs, where the infection rates range between 25% and Jntnu:ardiac
'75% (2,~). Regardless of their frequency, infectious complica- Prosthetic valves• 5.1%-6.4%
tions associated with DAis are associated with significant mor-
Permanent pacemaker <6%
bidity and mortality.
Most patients who develop implantable cardiac or vascular Implantable defibrillator <4%
DAis are in older age groups; have required frequent hospital- Left venbicular uaist device• 25%-70% (40%)
izations; have significant comorbid conditions, ruch as diabetes Coronary atenta Rare
and renal failure; and are often subjected to intense antimicro- Pledgets, conduits, patches, plugs Rare
bial pressure that result in colonization with multidrug-resistant
organiams (MDRO.J), thereby increasing the risk of develop- Arterial
ing healthc~ciated infection (HAl) with these organ· Vucular grafts' 1%-6% (4%)
isms. The implanted devices are made of inert materials with Peripheral vucular atenll Rare
inherent properties to overcome immunologic barriers. How- Carolid Dacron patches Rare
ever, exposure of the foreign body to microbes results in the
Closure devices S1.9%
elaboration of a biofilm that contributes to the persistence of
DAis. Additionally, mechanical failure, thromboembolic events, dW!tbin the fint year, 5 to 7 yean, 15 yean.
hemolysis, and anticoagulation-associated bleeding disorders 'ca1cubted for various time periocL. (occuning SS months of
also compromise the longevity and functional capabilities of implant).
these devices. Such complications increase with the duration "Includes arteriovenous, Cemoropopliteal, aortic grafts (ovenll rate).
of device use. Adapted from Baddour LM, Dettmann MA. Bolger AF, et al.
This chapter examines the pathogenesis common to all im- Nonva1vular cardi.cmucular device-related infections. Cirtullllicm.
plantable cardiac and vascular DAis in healthcare settings, re- 2005;108:201>2051; Darouiche RO. Current concepts: treat-
ment of infections associated with mrgical implant. N EJtfl]M.d.
views specific DAis, discusses the strategies to prevent HAis, and
2004;550:1422-1429, with permission.
identifies further research needs. The chapter does not discuss
592
Chapter 39• Infectrons ofImplantable Cardiac and Vascular JHvices 593
adhesive matrix molecules (MSCRAMM). These molecules Comorbid conditions, such as diabetes mellitus, malnutrition,
bind the microorganisms onto the surface of medical devices or age have deleterious effects on chemotaxis, phagocytosis, and
after interacting with host plasma proteins, such as fibronec- adherence of granulocytes, components in the initial line of de-
tin and fibrinogen, a process similar to the implicated patho- fense against invading microbes (23,24). Hyperglycemia, espe-
genesis for infective endocarditis (2,4,5). The exposure of cially in the immediate postoperative period, is a risk factor for
host plasma proteins results from increased turbulence due to SSis as described in the cardiac bypass literature (25-28).
an alteration of the normal cardiovascular flow and from the Microbial exposure can occur with intraoperative contami-
physiologic shear rates caused by the implanted device. An in nation, as a result of hematogenous seeding from a secondary
vitro model suggests that the shear stress induces apoptosis of bloodstream infection (BSI) or from an extension of a local
neutrophils, thereby preventing the host's first line of immu- infection as occurs with pacemaker or lCD infections. Whether
nologic response from fully activating (6-8). In this setting, microbial exposure results in infection depends on microbial
elaboration of microbial virulence factors overcomes the host's virulence factors and the host's response to the implanted
immunologic barrier and initiates a cascade of events that cul- device. Once the protective biofilm forms, eradication of the
minates in the formation of an intricate extracellular matrix, pathogen and its infection requires not only appropriate anti-
the biofilm. Within the confines of the biofilm, the microbes microbial therapy but, more importantly, explantation of the
reside and create an environment that is relatively impervious cardiac or vascular device.
to antimicrobials and resistant to the innate host defenses. The
presence of an avascular foreign body increases the risk of sur-
gical site infection (SSI), by reducing the infecting dose of mi- PROSTHETIC VALVE ENDOCARDITIS
croorganisms that cause SSI.
Microorganisms attach to medical devices in the free- EPIDEMIOLOGY
floating (planktonic) form, divide, interact, become embed-
ded in a biofilm, and then transform into the surface-associated More than 90,000 patients per year undergo heart valve re-
form. An adhesive matrix then creates a protective complex placement in the United States (29). Prosthetic valves are
that becomes heterogenous with multiple channels transport- either mechanical that are constructed of carbon alloys, a ball-
ing nutrients and oxygen to the microorganisms within the and-cage, single tilting disk, or more common, hi-leaflet tilting
biofilm. The surface cells divide, and as the thickness of the disk configuration or bioprosthetic valves that include porcine
biofilm increases, the host's normal immune response to mi- heterografts, bovine pericardium constructed into three cusps
crobiologic challenge is blunted, and the capacity of the host mounted on a stent, and the rarely used homografts, which are
neutrophil's ability to phagocytize, affect intracellular killing, preserved human aortic valves or pulmonary autografts (30).
and proliferate is diminished. Microorganisms embedded Traditionally, prosthetic valve endocarditis (PVE) is classi-
in biofilms are much more resistant than planktonic cells to fied as early (occurring <60 days of implantation), intermediate
antimicrobials and can survive despite concentrations 10 to (2-12 months), or late (>12 months). CONS is the pathogen
1,000 times what is necessary to eradicate planktonic forms. commonly isolated in early PVE and attributed to intraopera-
In a suspended state of activity, these forms become resistant tive contamination or hematogenous seeding from a second-
to the cell wall, growth-phase-dependent antimicrobials, such ary source, such as a central venous catheter. However, patients
as penicillin, cephalosporins, and vancomycin. In the deeper infected with CONS, a fairly indolent organism, may not have
layers of the biofilm, microorganisms require less nutritional clinical manifestations until the intermediate period. There-
support and are better able to tolerate environments of lower fore, for surveillance purposes, the CDC's National Healthcare
oxygen tension, a characteristic that renders the microorgan- Safety Network (NHSN; formerly the National Nosocomial In-
ism resistant to the aminoglycosides, agents maximally effec- fections Surveillance, or NNIS, system) defines a healthcare-
tive in aerobic conditions (9,10). Clinically, the persistence associated postoperative SSI as any SSI that occurs within 1 year
of DAis caused by S. aurew and Staphylococcus lugdunensis has of device implantation (31); however, there is ongoing discus-
been attributed to small colony-variant phenotypes that can sion at CDC that may redefine the length of the surveillance
exchange genetic material codes for an antimicrobial-resistant period for device-associated SSis.
phenotype that ensures their survival (11,12). Biofilms The incidence of PVE varies according to the duration of
have been most studied in S. aureus; however, emerging evi- the follow-up period and is estimated to be around 3.1% (data
dence suggests their role in the pathogenesis of DAis due to from 1980s) during the first 12 months. The risk of infection
coagulase-negative staphylococci (CONS), Pseudomonas aerugi-- is highest within the first 3 months and declines to a fairly
nosa, and other gram-negative rods, enterococci, and Candida constant rate of 0.3% to 0.6% annually thereafter (32-34).
albicans (13-20). A recent study on early PVE (i.e., occurring <12 months after
In conditions that may be environmentally hostile to mi- valve surgery) of 77 patients reported decreasing rates compar-
crobial growth and replication, microorganisms imbedded in ing two periods, 1.5% in 1992 to 1994 versus 0.7% in 1995 to
a biofilm enter into a dormant or latent state. Although these 1997 (35). A long-term study of the Veterans Affairs population
microorganisms are viable, they are not culturable. It has been in the 1990s reported the incidence of PVE to increase from
shown that members of these biofilm communities periodically 3% to 5.7% at 5 years to 13% at 15 years (36).
awaken from this latent state to ~test" the environment. If
favorable conditions are detected, these ~scout" microorgan-
RISK FACTORS
isms signal the remaining members of the biofilm community
to revert from a dormant state to an active state (21,22). The risk factors associated with PVE include implantation of mul-
These observations explain the resilience of biofilm-associated tiple prostheses (32), longer cardiopulmonary bypass time (36),
microorganisms. valve replacement in the setting of infective endocarditis,
594 Section m • Endemic and Epidemic Hospital InfectWns
New York Heart Association (NYHA) functional class III or IV; to tom gloves used by the surgical team (55). Refinements in
alcohol consumption, fever in the intensive care unit, gastro- molecular typing techniques have enabled investigators to link
intestinal bleeding, and healthcare-associated BSI (HA-BSI) outbreaks to a common source.
(34,39--42). Three studies reviewed the risk of PVE in patients In early studies, PVE was associated with mortality rates of
who developed HA-BSI and reported rates between 11% and 10% to 70%. A recent multicenter study reported a 23% PVE
50%. Investigators in one study of 51 patients reported that ap- mortality rate, possibly a reflection of earlier detection, more
proximately half of the patients with a prosthetic valve (PV) or optimal use of combination antimicrobial therapy, and prompt
a ring who developed S. aureus BSI (SA-BSI) had definite evi- surgical intervention (48). The risk factors for higher mortality
dence of PVE at the time of the BSI (using the modified Duke rates resulting from PVE include early PVE (~1 year of onset),
criteria (43,44)) and that the risk was independent of the type, infection with Staphylococcus spp., presentation or development
location, or age of the PV or ring. The most common source of ofheartfailure, infections involving the aortic valve, and medical
early (<12 months of valve placement) SA-BSI was SSis (59%), management alone. Management of S. aureus PVE with surgical
whereas patients with late SA-BSI (>1 year after valve place- intervention was associated with a 28% mortality rate in contrast
ment) had an unidentified source of BSI in 48% of patients. to 48% in the medical group in one study (56). American So-
The hallmark features of definite PVE in this study were per- ciety of Anesthesiology (ASA) class IV and bioprosthetic valves
sistent fever and sustained BSI ( 45) . In the second study of were independent predictors of mortality when subjected to
171 patients with PVs (excluding 33% of patients who had a multivariable analysis. A subset of medically treated patients
diagnosis of PVE at the time of the BSI), 15% of patients devel- characterized by age <50 years, ASA score III, and the absence of
oped PVE with a mean of 45 days after documentation of the cardiac, central nervous system, and systemic complications was
BSI despite having received antimicrobial therapy. Thirty-three cured without surgical intervention. Comparing surgical treat-
percent were attributed to BSI due to intravascular devices, and ment of native to PVs, the 30-day outcomes were better for the
skin infections accounted for another 30%; the mitral valve site former; however, long-term outcomes of the two groups were
and Staphylococcus spp. BSI were significantly associated with the similar. S. aureus infections were associated with a significantly
development of PVE ( 46). The third study describes 37 patients higher mortality when compared with other pathogens (57).
with PV who had no evidence of PVE during the initial 4-week
follow-up period after documentation of postoperative candi-
MICROBIOLOGY
demia; 11% of patients who had sustained fungemia developed
fungal PVE ( 4 7). The studies highlight the importance of pre- Within the first 12 months of implantation, the predomi-
venting BSI and skin infections following PV implantation. nant organisms, in decreasing order of frequency, are CONS,
To better assess the risk of PVE in healthcare settings, a pro- S. aureus, fungi/yeast, gram-negative bacilli, and enterococci
spective cohort study conducted by the International Collabo- (Table 39.2). Further stratification of the time period to the
ration on Endocarditis of 556 patients, HAl, acquired in both first 60 days of implant identified S. aureus (36%), followed
inpatient and outpatient settings, the latter defined as identifi- by CONS as the predominant organisms (48). Of the 16% of
cation of PVE within 48 hours of admission, but with extensive 537 patients with CONS-PVE in non-drug-injecting patients,
healthcare contact, had a relative frequency of 37%, with 70% 48% were diagnosed after 60 days of valve implantation (58). In
occurring as inpatients and the remaining 30% acquired as out- late PVE (> 12 months), non-enterococcal streptococcus was the
patients. Most of the healthcare-acquired PVE were diagnosed most common pathogen, a finding similar to native valve endo-
within the first 60 days of implantation, with 70% occurring carditis (excluding the intravenous drug-using population).
within the first year. S. aureus was the most common organism
in 34% of patients (48).
CLINICAL MANIFESTATIONS, DIAGNOSIS, AND
Early studies comparing mechanical with bioprosthetic
THERAPY OF PROSTIIETIC VALVE ENDOCARDms
valve and aortic versus mitral valve on the incidence of PVE
were inconclusive; however, a recent study reported that the Fever is a common manifestation of PVE, and the presence of
incidence of early PVE (occurring <12 months of implanta- sustained fever in a patient with a PY, regardless of the timing of
tion) was similar in mechanical and bioprosthetic valves. Mter implantation, should prompt a clinical investigation to confirm
a longer observation period, the incidence of PVE was higher or exclude the diagnosis. Often it is tempting in clinical practice
with bioprosthetic valves owing to the platelet-fibrin thrombus to attribute fever in the postoperative patient to a urinary tract
deposition on aging leaflets that can become a nidus for in- infection or early pneumonia and initiate empiric antibiotic
fection (33). In early PVE, infection develops along the suture therapy on the basis of clinical suspicion. However, in patients
lines of the prosthesis-annulus interface and perivalvular tis- with PVs, it is a good practice to obtain blood cultures before
sue with resultant dehiscence of sutures. Late infection is simi- initiating empiric antimicrobials to avoid missing a diagnosis
lar to native valve endocarditis and begins with platelet-fibrin of PVE. The salient clinical features of PVE show similarities
thrombi deposition on the prosthesis followed by adherence with native valve endocarditis and are determined by the time
of microorganisms. Early PVE was significantly lower for pros- of onset, the virulence of the pathogen, and host responses.
thetic mitral valve than for aortic valve replacement (37,38). Patients with PVE due to a pathogen such asS. aureus can pres-
Although outbreaks of healthcare-associated PVE are un- ent with fulminant sepsis in association with central nervous
common, they have been described for Mycobacterium chelonae system emboli and hemorrhagic events with intracardiac mani-
because of contamination of the bioprosthetic valve (49); Staph- festations (e.g., acute valvular failure, conduction abnormali-
ylococcus epidermidis in association with surgical staff carriage ties, or progression ofperivalvular infection) resulting in rapid
(50-53); Legiomlla pneumophila and Legiunella dumojftifrom ex- cardiac decompensation and with septic peripheral emboli. In
posure of wounds and chest/mediastinal tubes to tap water in a contrast, infections caused by the more indolent organisms,
healthcare facility (54); and Candida parapsilosis possibly related such as CONS, are associated with a subacute presentation
Chapter 39• Infectrons ofImplantable Cardiac and Vascular JHvices 595
TABLE 39.2 Etiology of Prosthetic Valve The attributable financial impact of the treatment of heart
failure is estimated at >39 million dollars. While the incidence
Endocarditis
and prevalence of heart failure continue to increase, the donor
Number of Cases (%) pool has remained static over time. The 2,000 heart transplants
performed each year contrast with the 3,000 patients awaiting
Tbneof~tofPVE
transplant at any given time (60,61).
<1 z fiiOPfiJu >12 riiOfltlu The introduction of the LVAD catapulted the management
of severe end-stage cardiomyopathy refractory to inotropic
~ N=Z69 N=194
therapy, intra-aortic balloon counterpulsation, or both, into a
Streptococcll.!l (excludes 12 (4%) 61 (!11 %)
new era. LVADs were originally approved in 1994 by the Food
enterococcus)
and Drug Administration (FDA) as a bridge to transplantation.
Enterococcus 2!1 (8%) 22 (11%)
Subsequent studies demonstrated that the use of the LVAD
S~a~Jhylococcus auR!W 48 (18%) !14 (18%) was associated with improvement in hemodynamic and end-
Coagula..e-negative 102 (!18%) 22 (11%) organ function and conferred a meaningful survival benefit in
staphylococci implanted patients as compared with controls managed with
Diphtheroids 10 (4%) 5 (3%) medical therapy alone. An impressive 70% of patients survived
until heart transplantation (62,63). Furthermore, following
Gram-negative bacilli 24 (9%) 11 (6%)
transplantation, the survival at 3 years was 95% ± 4% for the
HACEK• 0 11 (6%) LVAD group and 65% ± 10% years for the control inotropes-
Fungi/yeast 26 (10%) !I (1%) alone group (64). Even in the presence of LVAD-associated in-
Polymicrobial/other 6 (2%) 9 (5%) fections, heart transplantation recipients had similar outcomes,
Culture negative 9 (!1%) 16 (8%) including long-term survival, when compared with patients
without LVAD infections (65-67), although there was a dou-
aHACEK, Haemophilw aphrophilu.s, Actinobacillw acti~i bling ofLVAD-support days that delayed transplantation with a
tai'IS, Cardiobacterium lwminis, EiJumella sp., and Kingella sp. (fastidi- trend toward longer hospital stays posttransplant and increased
ous gram-negative rods). early mortality resulting from a newly acquired infection in the
Adapted from Karchmer AW, Longworth D. Infections of intracar-
cohort with LVAD-related infection (68,69). These important
diac devices. Canliol Clin. 200!1;21 :253--271 and Gordon SM, Serkey
observations quieted the unease of su~ecting LVAD-associated
JM, Longworth DL, et al. Early onset prosthetic valve endocardi-
tis: the Cleveland Clinic experience 1992-1997. Ann 1'1wrcu: Suf1:.
infected patients to intense immunosuppression following
2000;69:1388-1392, with permission. their transplants for fear of aggravating their infections (68).
When it became apparent that patients managed with the
LVAD had better outcomes compared to their medically treated
characterized by peripheral stigmata of endocarditis (autoim- counterparts, the indications for LVAD implantation broad-
mune arthralgias/arthritis, Osler nodes,Janeway lesions). ened to include those ineligible for transplantation (destination
In the absence of antimicrobial exposure, it is estimated that therapy). The Randomized Evaluation of Mechanical Assistance
blood cultures would be positive in ~90% of patients with PVE for the Treatment of Congestive Heart Failure (REMATCH)
(33). Isolation of organisms such asS. aureus and Candida spp. trial investigated the use ofLVADs for destination therapy (63).
without evidence of a secondary source of infection is likely due In LVAD recipients, sepsis from any cause accounted for 41%
to PVE. However, ascertaining the significance of the isolation of deaths, whereas the mortality was 17% in patients without
of skin organisms, such as CONS or diphtheroids, can be diffi- sepsis. Within 3 months after implantation, the probability of
cult unless there is demonstration of persistent BSI with sugges- an HAl related to the LVAD was 28%. The Kaplan-Meier sur-
tive clinical and echocardiographic features. With refinements vival analysis did show a 48% reduction in the risk of death from
of molecular typing techniques, confirmation of the presence any cause in those patients randomized to LVAD implantation
of clonality is possible and helpful when it is important to dis- during the first year. However, the aggregate adverse event rate
was twice as likely to occur in LVAD patients. By the second year
tinguish pathogens from contaminants; however, the possibility
of polymicrobial infections also should be considered (59). of study, the survival rate of 23% between the two groups was
AB with native valve endocarditis, the modified Duke criteria not statistically significant The LVAD recipients who did not
are used to establish a diagnosis of PVE (43,44). Echocardio- develop sepsis had superior survival rates of 60% at 1 year and
graphic findings, therapy (i.e., need for bactericidal antimi- 38% at 2 years compared to 39% and 8%, respectively, in LVAD
crobial agents, issues with combination therapy, treatment of patients who developed sepsis. Localized infections, such as
MDROs, and optimal use of pharmacodynamic strategies), and percutaneous site or pocket infection, did not have an adverse
indications for surgical intervention are beyond the scope of impact on survival (71). An additional2 years of observation in
this chapter and discussed elsewhere (33). the REMATCH trial revealed that patients randomized to LVAD
implantation in the period after 2000 had a statistically signifi-
cantly higher survival rate of 59% at 1 year and 38% at 2 years
LEFT VENTRICULAR ASSIST DEVICES when compared to the 44% and 21% rates, respectively, for the
medically treated group. The improved survival rate in patients
EPIDEMIOLOGY implanted during the second study period was attributed to the
experience gained in areas of patient care and device modifica-
Heart failure compromises the health of >5. 7 million tions (72). The current survival rates with the continuous-flow
Americans. About 670,000 new episodes are diagnosed each LVADs for the bridg~to-transplant population is at least 80% at
year, and 282,000 persons die because of heart failure annually. 1 year and 70% at 2 years (72).
596 Section m • Endemic and Epidemic Hospital InfectWns
The LVAD infection attack rate is estimated to be around and 55% at 2 years were reported. Infections following im-
30% (range, 16% to 37%) and likely reflects the population plantation developed in 16% of patients with an overall rate
and device studied (73-75). A review of 46 patients with LVAD- of 17.46 infections per 100 patient-months during the first
associated infections (the most common being the driveline 12 months after implant. Beyond the first 30 days after im-
site) noted that infections developed at an average of 65 days plantation, infection was second to heart fuilure as the most
postimplantation with a mortality rate of 17% (eight patients) common cause of death in this cohort of patients, with rates
with (five of eight) infected patients dying from sepsis before of 12.9%, 17.4%, and 15.4% of deaths {N = 122) occurring
transplantation (76). Postoperative LVAD-associated infections from infections in the bridge-to-transplantation, bridge-to-
were identified in 46% of 35 patients in whom 36 LVADs were candidacy, and destination patients, respectively. There was a
implanted for a mean of 73 days. Deep SSis were associated significant decrease (p < .0001) in infectious complications,
with the requirement for postoperative hemodialysis (77). comparing the first-generation pulsatile LVAD (28.9 infectious
Zierer reviewed the first-generation LVAD late-onset driveline complications/100 months of device use, 406 patients) and the
infections between 1995 and 2005. Late driveline infections second-generation continuous-flow LVAD (11.8/100 months
developed in 17 or 23% of patients that occurred at a median of device use, 548 patients) (82). Other investigators also have
of 158 days after implantation. Although the number and du- concluded that there was a reduction in LVAD-associated and
ration of readmissions to the hospital greatly increased, there nondevice-associated infections in patients ineligible for trans-
was a nonstatistical decrease in survival, 41% versus 70% at plantation (80,83,84).
5 years (78). A report on healthcare-associated LVAD-associated BSis
Refinement in the design and technology of LVADs led to in 214 patients revealed an incidence of 38%; the BSI was
the introduction of the second-generation, continuous-flow statistically significantly associated with death {the over-
devices that include the HeartMate II (Thoractec), MicroMed all incidence of BSI in recipients of LVADs from any cause
DeBakey (MicroMed), Jarvik 2000 Heart Uarvik Heart), and was 49%). Fungemia had the highest hazard ratio (10.9)
VentrAssist (Ventracor). With an improved design that includes followed by gram-negative (with Pseudomonas aeruginosa pre-
a more compact device that is simpler with fewer moving parts, dominating) and gram-positive bacteremia. The duration
a smaller percutaneous driveline, and that has eliminated the of LVAD support before the onset of any BSI was 19.5 days
use of polyurethane membranes or PVs that would increase the for gram-negative bacilli, 28 days for yeast, and 242 days for
risk of infections, along with the experience gained with time, gram-positive cocci (69). Forty-six LVAD-associated infections
the recipients of the continuous-flow LVADs had significantly were described in 50% (38/76) of patients who underwent
better survival rates and lower incidence of infectious complica- LVAD implantation as a bridge to transplantation. Twenty-
tions compared to those who had received the first-generation nine LVAD-associated BSis included five episodes of LVAD
pulsatile devices. endocarditis and 17 localized LVAD infection {i.e., exit site,
Despite improvement in survival advantage and durability of LVAD pocket infections) (68). In a study of 109 consecutive
the second-generation continuous-flow LVADs, infection and patients supported by LVADs as a bridge to transplant, 65
sepsis continue to be a major complication that occur in pa- patients (60%) during 584 ± 389 device-days developed a BSI
tients undergoing implantation as a bridge to transplantation that resulted in a significant adverse impact on survival after
and for destination therapy. LVAD implantation. The risk factors associated with death
In the HeartMate II bridge-to-transplantation trial, a sig- included postoperative right heart failure and BSis caused
nificant proportion of patients had local non-LVAD infec- by pathogens other than gram-positive cocci. The investiga-
tions (28%), sepsis (20%), or LVAD driveline infections within tors concluded that urgent cardiac transplantation should be
1 year (14%) after LVAD implantation (79). More recently, the considered in these patients. None of the 22 patients who
HeartMate II destination therapy trial has demonstrated even were transplanted had a recurrence of their BSI and all were
higher rates of infection, including local non-LVAD infections alive at 3 years posttransplant (85).
(49%), sepsis (36%), and LVAD-related infections (35%) in the
HeartMate II therapy arm (80). Even so, this study also con-
MICROBIOLOGY
cluded that the HeartMate II had better survival rates, lower
incidences ofLVAD-related infections, local non-LVAD-related The microbiology of LVAD-associated infections is fairly con-
infections, and sepsis compared to its earlier counterpart. sistent with gram-positive organisms predominating and likely
Topkara reported his experience with 81 patients who under- resulting from the disruption of the cutaneous barrier with the
went implantation of the second-generation (continuous-flow) subsequent biofilm formation, followed by P. aerugi1WSa and en-
LVADs. Forty-two (51.9%) patients developed at least one type teric gram-negative rods. CONS was the most frequent patho-
of infection. Additionally, the patients who developed sepsis gen isolated in BSis in LVAD-implanted patients from any cause,
had increased mortality (61.9% septic vs. 18% nonseptic pa- followed by S. aumus (of which 36% were methicillin-resistant
tients) at 2 years, whereas patients who developed driveline or [MRSA]), Candida sp., and P. aeruginosa. Although the entero-
pocket infections had no effect on survival, although all infec- cocci accounted for only about 8% of BSis, 50% of the isolates
tions resulted in a significantly prolonged hospital stay and a were vancomycin-resistant (69). A more recent review reported
trend toward increased mortality (81). that of 221 BSis that occurred in 65 patients, the majority was
The national database, the Interagency Registry for caused by gram-positive cocci (159 or 72%), with 101 caused
Mechanical Circulatory Support (INTERMACS), reported by S. aurms (MRSA, 65 or 29%; methicillin-susceptible [MSSA],
data on 1,158 LVADs that were implanted between june 2006 36 or 16%) and 50 or 23% caused by CONS followed by gram-
and March 2009. There were 1,092 primary implants and 66 negative rods (17%) and fungi (6%) {85). Of the 300 patients
nonprimary implants, of which 564 were second-generation who received a VAD, 108 (36%) developed VAD infection, in-
devices. The survival rates of 83% at 6 months, 74% at 1 year, cluding 85 bacterial and 23 fungal infections. The most common
Chapter J9 • lnfeaiuns oflmpkmtabk Canliac and Vascular Dtvias 597
bacterial causes of infection were S. aunow, CONS enterococci,

and P. a6Umginosa. The most common fungal etiologic agent
was C. albicans. Only the use of total parenteral nutrition was
associated with the development of a fungal VAD infection in
multivariate analyses (odds ratio, 6.95; 95% confidence inte'l'-
val, I. 71 to 28.16; p =.007). Patients who experienced a fungal
VAD infection were le.ss likely to be cured (17.4% vs. 56.3%;
p = .001) and had greater mortality (91% w. 61%; P= .006),
compared with those who experienced a bacterial VAD infec-
tion (75).
Of 47 isolates from 76 LVAD patients who developed
LVAD-a.ssociated infections, 78% and 19% of LVAD-asso-
ciated infections were due to gram-positive organisms and
gram-negative rods, respectively, with only one infection due
to yeast. Diabetes mellitu.s was identified as a risk factor for
the ~0 BSis in this cohort. There was a striking incidence of
poattransplantati.on-invuive vancomydn-reaistant E~
faecium (VREF) infections in six patients with an associated
mortality of 67%. 11Us i5 in marked contrast to LVA!Hupport
patients who did not develop LVAD-associated infections, and
there were no postoperation-invasive VREF infections (68).
ResiJJtant Stllphykxoccm and P. ~nosa were the most com-
mon pathogens leading to device- and nondevice-related local
infections (81).
RISK FACI'ORS
Patients who require implantation of an LVAD to treat terminal
heart failure have inherent risk. factors that predispose them Figure 39.1. HeartMateTM left ventricular assillt device (LVAD).
to infectious complications as with other postoperative SSia.
These include cardiac cachexia, age (84), renal disease (77),
diabetes (68), obesity (73,86), and malnutrition. Prolonged flow. Implantation of the LVAD requires an extended median
hospitalization (65), repeat operative procedures (65), dura- sternotomy. A driveline connects the blood pump to an exte'l'-
tion of device use (i.e., central venous catheters, mechanical nal power source that ellits through the abdominal wall, usu·
ventilation), trauma to the driveline site (78), parenteral nutri- ally contralateral to the side of the pump. Figure 39.1 depicts
tion (75), and duration ofLVAD support (78,84). the second-generation, continuous-flow LVAD, and Figure 39.2
LVAD implantation is associated with progressive defects of
cellular immunity by inducing an aberrant activation ofT cells,
resulting in programmed CD4 cell death (87-90). Ankersnitt
et al. concluded that the defects in cellular immunity predis-
pose patients to infections cauaed by Candida sp., and the risk
of developing disseminated candidiasis in that study was 28% in
LVAD recipients compared to 3% of controls (87). This finding
coupled with the fact that advanced age (patients on destina·
tion therapy) also is associated with decreased cellular inunu-
nity (14) introduces zrugor challenges ahead for mechanical
circulatoxysupport (91).
The design of the LVAD may also contribute to infectious
complications after LVAD implantation. Devices with reduced
surface area, smaller drivelines, and less turbulence of flow have
been associated with a reduction in infection risk (80,82-84).
TYPES OF LEFI' VENTlUCULAR.ASSIST

DEVICE-ASSOCIATED INF.BCTIONS,
DIAGNOSIS, AND .MANAGEMENT
The components of the LVAD (e.g., HeartMate) consist of an
intracorporeal blood pump encased in titanium (placed in the
abdominal cavity or preperitoneal pocket), an inflow cannula
(inserted into the apex of the left ventricle), an outflow cannula
(inserted into the ascending aorta), and porcine valves within
the inflow and outflow cannulas to maintain unidirectional Figure 39.2-. Comparison of HeartMate XVE and HeartMate n.
598 St!Ction III • ~ andEpukmic Hospilllllnftctitms
infection, it can be difficult to differentiate irritation due to

an inadequately immobilized driveline from infection becau.se
pain and erythema are common features to both situations.
Pump pocket infections can result from secondary infection
of a localized hematoma or seroma from the operative proce-
dure or inadvertent trauma. The clinical presentation depends
on the pathogenicity of the microorganism. The characteristic
features of infection can be absent, and infection should be
ruspected on the basis of unexplained leukocytosis, general-
ized malaise, and low-grade fevers. In some instances, palpation
over the incision can lead to the discovery of an abscess {92).
LVAD-asaociated endocarditis is characterized by the in-
volvement of the surface components of the mechanical device
that is in contact with blood-the blood pump and the inflow
or outflow tracts. It shares many of the clinical features diagnos-
tic of infective endocarditis (i.e., persistent BSI, systemic signs
and symptoiWI [e.g., fever, toxicity. emboli, immune complex
di.sease, valvular incompetence]).
Radiographic studies (e.g., ultrasonography, computed to-
mography [CT], and nuclear imaging for abscess localization)
Figure 39.3. Driveline exit site infection. are of limited value in the presence of hardware and the absence
of standards for interpretation, but can be helpful in identifying
a fluid collection(s) that can lead to a diagnostic aspiration. Oc-
compares the first-generation, pulsatile (now retired) with the casionally, small fluid collections may not be visible by cr imag-
second-generation LVAD. ing rtudies, but are identified by ultrasound (Figures 39.5 and
Although the driveline is tunneled before exiting the abdo- 39.6). Consequently, both types of studies should be performed
men, its size and the bulk of the battery pack increase the risk to identify a fluid collection for diagnostic aspiration that would
of skin trauma, resulting in the loss of the protective skin ba:flo be u.sed to guide antimicrobial therapy. The combination of
rier and permits invasion by microorganisms. integrated molecular and anatomic hybrid imaging using leu-
The spectrum of LVAD-associated infectioWI is categorized kocyte scintigraphy and single-photon emission computed to-
according to the anatomical site and are not mutually exclu- mography (SPECI')/Cf suggest that this approach might be
sive: (a) driveline exit site (Figure 39.3), (b) pump pocket more sensitive in detecting LVAD infections {Figure 39.7) (93).
(Figure 39.4), and the least frequent, (c) endocarditis (2,68,69). Distinguishing LVAD-related BSI from a non-LVA.I).related
Pathogens causing LVAD infections can result from intraopera- BSI can be difficult; however, identical mkroorgani.siWI recov-
tive inoculation, from entty through the percutaneous driveline ered from the device (e.g., valves, intemal pump surface, and
exit .site, or from hematogenous seeding from central venou.s pump pocket) and the bloodstream would suggest an LVAD-
catheter-as.sociated BSh, catheter-associated uriD.ary tract infec- associated BSI. Single positive blood cultures for cutaneous
tion, or ventilator-associated pneumonia. In driveline exit site organisms (e.g., CONS, diphtheroids) should be interpreted
infections, there is often evidence of localized inflammation at with caution because these organisms are common cau.ses of
the exit site accompanied by poor tissue healing; seropurulent/ pseudobacteremia; therefore, multiple cultures are necessary
purulent drainage can be present with variable systemic mani- to interpret the results correctly.
festations of infection. In the early phases of driveline exit .site
MANAGRMB.NT
The therapy of LVAD-associated infections depends on the in-
fected site. Driveline exit site and pocket infections are man-
aged by (a) aggressive wound care, (b) immobilization of the
driveline to avoid further tisru.e trauma, (c) gentle debride-
ment of devitalized tissue and cleansing of exit site, and (d)
exploration of the pump pocket as indicated. Use of poly-
methylmethacrylate {PMMA) beads containing vancomycin
and tobramycin (and potentially other antimicrobial agents)
that coat the external surface of the LVAD is an experimen-
tal approach to managing pocket infection {92,94), but more
research is warranted to determine the optimum bead mate-
rial, size, shape, and positioning. Placement of a KCI vacuum-
assi.sted closure (VAC) device (WoundVac....) is reported to be
beneficial after appropriate drainage and debridement of large
wounds (95).
LVA.Do.wociated endocarditis usually requires device re-
moval, urgent transplantation, and bactericidal antibiotics
Fipre 39.4, Pump pocket infection. (66,96,97). A report by Nurozler et at. on fungal endocarditis
Chapter J9 • lnfeaiuns oflmpkmtabk Canliac and Vascular Dtvias 599
Figure 39.5. CT .scan showing absence of

fluid along the driveline.
revealed that early diagne»is, prompt institution of antimicrobi- component for destination therapy patients with recalcitrant
als, and device removal and replacement followed by transplan- infections in whom device exchange ill associated with pro-
tation were a.uociated with an 80% favorable outcome in five hibitive risb. However, with increasing duration of device use,
patients (98). pathogens tend to be multidrug-resistant, and therapy relies on
Culture remits dictate the choice of systemic bactericidal parenteral and potentially nephrotoxic agents.
antimicrobials. Continuous antimicrobial treatment before, To minimize the sequelae of intraoperative contamination
during, and after transplantation was associated with fewer during device implantation, surgical infection prophylaxis
relapse& when compared to limited courses of antimicrobials (SIP) ill standard; however. there is much variation in the
(p < .001). Discontinuing antimicrobiah after a 2- to &week choice of antimicrobial agents among institutions. Currently,
coune was associated with relapse or a secondary infection; there is no consensus on the ideal SIP regimen for LVAD im-
however, the survival rates for the two groups at 1 year were sim- plantation. Some centers use a combination of five different
ilar (68). Ireatm.ent strategies include the use of a suppre.ssive perioperative antibiotics including vancomycin, a quinolone,
Fipre 39.6. Ultrasound from

the patient showing fluid along the
driveline.
600 Sldion III • ~and Epid4mic Hosp;Ml Infodimu
F.ip.re 39.7. SPECT/Cf showing perforation of the drivel.ine into bowel.
rifampin, fluconazaole, and a ,Slactam or a monobactam (77); TOTAL AR.TJFICIAL HBAR.TS

other i.mtitutioru recommend a quinolone or P.Iactam plna
vancomycin (68). An electronic survey w.u conducted to The total artifi.ciaJ. heart (TAH) was designed to provide the
characterize the SIP used in institutions performing LVADs necessary mechanical support for patients with severe biventric-
(99). Of the usable data from 21 out of 85 U.S. centers, ular failure that i& refractory to inotropic therapy and replaces
42.9% used a four~rog regimen (three antibiotics and fluco- both native cardiac ventricles and all cardiac valves. Indications
nazole), 2ll.8% used a thre~g regimen (three antibiotics for use include aortic i.mufticiency, severe ventricular arrhyth-
or two antibiotic:& and fluconazole), 23.8% used a two-drug mias, left ventricular thrombus, and calcified left ventricular
regimen, and 9.5% used vancomycin alone. Vancomycin is aneurysm. It also is considered for those patients who are not
the one antibiotic that is consistendy represented in all regi- transplant candidates by virtue of their underlying di&eaae,
mens, more for the coverage against CONS than for MRSA. auch as amyloidosis or cardiotox:icity from chemotherapy, dif-
Some i.mtitutions elect to add antipseudomonal coverage th.a t fuse cardiac tumors, failure, and heart transplants from graft
b.u included piperacillin/tazobactam, ceftazidime/cefcpime, failure and rejection, the latter group being candidates for dea-
or a quinolone; however, recent auaceptibility data suggest tination therapy (1 02).
that P. anugirwsa is becoming increasingly resistant to the Two TAHs, the CardioWeat Total Artificial Heart and Ahio-
quinolones (1 00). Rifampin is well-represented to enhance Cor, are CUITently under investigation. The CardioWest Total
gram-positive coverage. Although yeaat are not common Artificial Heart uses pneumatic drives and shares the same
pathogens in IAVD infections, institutions using ~~ agents characteristics with the LVAD in terms of infection ruk (i.e., the
for SIP include fluconazole, and thi& b.u led one institution presence of an external driveline). A bridge-to-transplantation
to suggest that infrequent i&olation of yeast as a pathogen study of 81 patients reported a 79% survival rate in the study
in LVAD infections is due to fluconazole prophylaxis (101). group compared with 46% in the control, medically treated
Bagdasarians reported his institution's experience with LVAD- group. The 1-year survival for TAH recipients was '10%. This co-
associated fungemia from October 1996 to April 2009. Out bon included 1'1 d.riveline infections, seven BSis (six associated
of 292 patients, seven patients developed LVAD-associated with an infusion catheter), and five mediastinal infections. In
fungemia with an attack. rate of 0.1 infectiom/1,000 device- 68 patients, there were no delays to tnnsplantation or deaths
days. Of the seven infections, two were due to Aspergillw spp., due to infection. Transplantation w.u delayed in five patienta
two were caused by fluconazole-resi&tant isolates (Candida kfll.. owing to any infection; when further stratified, three infections
sei, Candida glalmJta), and three were caused by fluconazole- were related to the TAH-two drivelines and one mediastinum.
susceptible strai.m (C. albicans (2), C. parapsilosi.s), occurring Seven deaths were attributed to infection from any cause; one
2 days, 14 days, and 10 months, re&pectively, following LVAD w.u from mediastinitis (103).
implant. All Candida spp. infections, except for fungemia The AbioCor TAH, targeted for destination patients, uses
caused by C. pampsilo.sis, were diagnosed by a positive catheter an electrohydraulic actuator system. The 30-day survival for the
tip and an appropriate clinical presentation, and all received first seven patients was 71% compared to the 13% predicted
SIP that included fluconazole. survival for patients medically treated; at 60 days, the survival
Preoperative colonization (e.g., tracheal aspirates from ven- was 43%. When reviewed in 2004, two patients were still alive at
tilated patients or wouncb) and infection should be comidered 234 and 181 days. No DAis were reported in this small cohort,
when choosing preoperative prophylactic agents. The impact and it is believed that the absence of a percutaneona external
of broad-spectrum SIP on the emergence of MDROs and the access decreases the mk of infection significantly in eliminat-
development of Clostridium dijjiciU infection has not been ing a portal of entry for microorganisms. The large size of this
formally evaluated, but is a perceived risk. TAH, however, lnCTea.Be$ the ruk for thrombosis (104).
Chapter 39 • lnfectrons ofImplantable Cardiac and Vascular JHvices 60 l
CARDIAC IMPLANTABLE ELECTRONIC inexperience also contribute to the infection risk after CIED
DEVICE INFECTIONS implantation (110-112).
Secondary BSI can seed the implanted device, and localized
EPIDEMIOLOGY trauma resulting in hematomas can cause tension along the su-
ture line, disrupt the skin barrier, and expose the implant.
Cardiac implantable electronic devices (CIEDs) include per-
manent pacemakers and ICDs that provide electrical stability to
patients with ischemic cardiomyopathy or other conditions that
MICROBIOLOGY
place them at risk for fatal ventricular arrhythmias. Implanta- The predominant pathogen causing CIED-associated infections
tion of CIEDs involves subcutaneously inserting a generator is Staphylococcus spp. ( 108); other skin pathogens that have been
or defibrillator into the chest (most common) or abdominal implicated in pocket infections include Curynebactnium sp., ~
wall; lead wires are threaded into the soft tissues, enter at the pionibactnium acnes, and Micrococcus, which result when the
subclavian vein, and gain access to the right side of the heart; device erodes through the skin. In one series of 87 pacemaker-
the electrodes are implanted in the right atrium and/or right associated and 36 ICD-associated infections, the most com-
ventricular endocardium. mon pathogens were CONS (68%), S. aun"US (23%), or enteric
It is estimated that 3.25 million pacemakers are implanted gram-negative bacilli (13%) (105). Sixty-five percent to 75% of
worldwide and 300,000 CIEDs, of which 180,000 are generator pocket infections and up to 89% of device-related
cardioverter-defibrillators, are implanted in the United States endocarditis are caused by S. aun"US or CONS, predominantly
annually. Infection rates from earlier reports vary between 1 % S. epidermidis (113). Episodes arising within 2 weeks of implan-
and 7% (2,3,105). However, as the indications for CIEDs in- tation are more likely to be due to S. aun"US (114). Among
crease, so has the number of device implantations and infec- staphylococci causing device infection, methicillin resistance
tious complications. The National Hospital Discharge Survey should be assumed until antimicrobial-susceptibility tests dem-
(NHDS) database reports that between 2004 and 2006, the onstrate methicillin susceptibility. Instances of Candida sp. or
number of CIED implantation rose by 12%, while the num- fungi such as AspergiUus spp. are rare (115-117). Fungal infec-
ber of hospitalizations for infectious complications increased tions occurred at the rate of 0.1% (3,648 procedures); the as-
by 57%, in part attributed to a higher representation of pa- sociated risk factors include abdominal placement, local versus
tients with risk factors, such as end-organ failure and diabetes systemic infection, and longer duration from original impla

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ta

President, Jason andJarvis Associates, I.LC

Hilton Head Island, South Carolina;

San Francisoo, Califumia

• Wolters Kluwer j Lippincott Williams & Wilkins

© 2014 by UPPINCOIT WILLIAMS & WILKINS, a WOLTERS KLUWER business

Two Commerce Square

[DNLM: 1. Cross Infection-prevention & control. 2. Cross Infection-etiology. WX 167]

professional responsibility of the practitioner.

Axel Gamulin, MD William R. Jarvis, MD Janice I.o, MD

Contributors vi 10 Use of Computerized Systems

SECTION 1: General 11 The Role of the Laboratory

12 The Practice of Epidemiology

9 Epidemiologic Methods for 18 Epidemiology and Control

SECTION II: Functional Areas SECTION III: Endemic and

28 Ambulatory Care Settings ....... 428 41 The Importance of Infection Control

43 Preventing Transmission of 46 Miscellaneous Procedure-Related

Epidetniolo gy of Healthcare -Associated

Epidemic CUrve- Conllnuou• Common Source

~.1' $~ ; / ~.!' ~" / , / .;-~" / /

Incidence Number of new events Cases/time, rate

Examples/Comments Specific for

Steps in Constructing an Epidemic Curve (C.nrinwetl)

is related. This error is related to the concept of power. Power

underestimate of the true association between exposure and QUASI-EXPERIMENTAL STUDIES

airborne, common vehicle, or a vector as the means of trans- Droplet Trsnsmission

TABLE 1.3 Epidemiological RcK>urccs (with an Emphasis on Hcalthcarc-Assodatcd Infections/

EPIDEMIOLOGICAL PRINCIPALS SPECIFIC TO HEALmCARE EPIDEMIOLOGY TOPICS

The Healthcare Epidetniologist

responsible for providing formal infection prevention training

a senior administrator (e.g., vice president of medical affairs)

to recall that in addition to tramfer of pathogens from the

dine, and iodophors (38,48-57). Other enveloped viruses

HR, handrubbing; HW, handwashing

an increase in alcohol-based hand rub consumption correlated

Occupational Health Services

IMMUNIZATION PROGRAMS MANAGEMENT OF JOB-RELATED ILLNESSES

The modes of transmission of MRSA do not appear to GROUP A STREPTOCOCCUS INFECTIONS

The Developntent of Infection

CliniMI CIJre Arem

0.65 0. 7 0. 75 0.8 0.85

The Use of Prevalence Surveys

ECDC prevalence survey of healthcare-assoclated Infections and antimicrobial use

Hospital code I I ,.0 iii" 5'

Ward name (abbrevia1Bd)/Unit ID I I

Patients - - - - Patient stay - Patient Infected

i- ------ ------- ~------- ----f)--------------1------+------+----+-----h I

Introduce yourself to ward manager.

Collect ONE set of patient notes (medical, nursing,

If notes are If notes are unclear,

Complete data collection for all patients.

Pass on data forms to

1!. Humphrey~ H, Smyth ETM. Pn:nlence IIU'Ve)'l of healthcan>-auociated infectiono: what

Su""'Y.] H..p lnfoa. 2008;69:62~. 2007;!5(10):631-$7.

Investigating Endemic and Epidemic

TABLE 8.2A Distribution of Device-Associated Healthcare-Assoclated Infections (HAIS) Reported to

BumiCU 18 690 (!1.0) 271 (2.7) 206 (2.4) 213 (4.7)

TABLE 8.2A Distribution of Device-Associated Hcalthcarc-Assoclated Infections (HAIS) hportcd to

PICU4 65 958(4.1) 621 (6.2) 197 (2.3) 140 (3.1)

tJRate per 1,000 device days.

should be taken (discussed later). In general, it is recom- CONDUCTING AN EPIDEMIOLOGIC

air (27,28). Acinetobacter or Serratia spp. emerge in situations

Parenteral Duration Fever after Date of Culture