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Clinical Microbiology and Infection Prevention

Article  in  Journal of Clinical Microbiology · September 2011

DOI: 10.1128/JCM.00690-11

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JOURNAL OF CLINICAL MICROBIOLOGY, Sept. 2011, p. S57–S60
0095-1137/11/$12.00 doi:10.1128/JCM.00690-11
Copyright © 2011, American Society for Microbiology. All Rights Reserved.
Clinical Microbiology and Infection Prevention
Daniel J. Diekema1,2* and Michael A. Saubolle3,4
Division of Infectious Diseases, University of Iowa College of Medicine,1 and Infection Prevention Program, University of
Iowa Hospitals and Clinics,2 Iowa City, Iowa; Division of Infectious Diseases, Laboratory Sciences of
Arizona/Sonora Quest Laboratories, Phoenix, Arizona3; and Department of
Medicine, University of Arizona College of Medicine, Tucson, Arizona4
Health care-associated infections (HAIs) represent one of
the most common complications of care, affecting 5 to 10% of
patients admitted to acute-care hospitals worldwide. These
HAIs are associated with enormous morbidity and mortality,
resulting in more than 90,000 deaths each year in the United
States (8). Every health care facility must therefore have a
program charged with monitoring and preventing infections in
the health care environment. Preventing infections requires
the ability to detect them when they occur, which is why the
clinical microbiology laboratory (CML) plays a key role in HAI
prevention.
Some of the major roles played by the CML in infection
prevention include contributions to (i) surveillance, (ii) out-
break detection and management, (iii) antimicrobial steward-
ship, (iv) deliberations of the infection control committee, and
(v) education. In each of these areas, the CML faces new
challenges as it seeks to contribute fully to the urgent task of
preventing HAIs.
Surveillance. Review of CML data remains the most com-
mon method for case finding in HAI surveillance; therefore,
the most important role of the CML is to promptly and accu-
rately detect nosocomial pathogens and their antimicrobial
resistance patterns (1, 5). The CML must also work with the
infection prevention program (IPP) and the information tech-
nology (IT) department to determine how microbiology data
are delivered and linked to other surveillance data to stream-
line this process.
Major surveillance challenges facing the CML include the
continued emergence of novel infectious agents (e.g., the 2009
H1N1 influenza A virus), novel antimicrobial-resistant patho-
gens (e.g., vancomycin-intermediate/resistant Staphylococcus
aureus [VISA/VRSA], carbapenem-resistant Enterobacteria-
ceae [CRE]), and new governmental and public health man-
dates (e.g., mandated active surveillance culturing in some
states and in the VA health care system and public reporting of
HAI rates). Finally, the CML is under increasing pressure to
provide rapid test results. As hospital lengths of stay decrease
(12), the window of clinical relevance becomes smaller and
smaller.
Outbreak detection and management. The CML has impor-
tant roles to play in any potential outbreak situation, including
early recognition of possible clusters and outbreaks, rapid no-
tification of and collaboration with the IPP, additional case
finding, and provision of molecular typing for determination of
* Corresponding author. Mailing address: Division of Infectious
Diseases, University of Iowa College of Medicine, 200 Hawkins Drive,
Iowa City, IA 52246. Phone: (319) 356-8615. Fax: (319) 356-4916.
E-mail: daniel-diekema@uiowa.edu.
S57
VOL. 49, NO. 9 SUPPL.
relatedness, which requires maintenance of an organism bank
(Table 1). The laboratory should also act in a consultative
capacity with the IPP to help determine whether an outbreak
is “real” or a potential pseudo-outbreak due to contamination
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of specimens outside or within the laboratory. In addition, the
laboratory can help generate hypotheses as to the potential
source of an outbreak, its reservoir, and its mode of spread,
through molecular typing of the suspected organisms and through
testing the environment and/or personnel as necessary.
Outbreaks are often detected retrospectively, either after
they have resolved or when they are already beginning to wane.
Therefore, a major challenge to the CML is in detecting out-
breaks early enough to allow effective intervention and impact
morbidity and mortality. Effective and regular communication
between CML personnel and infection preventionists is essen-
tial to this effort, as many outbreaks are first noted at the CML
benches when technologists notice unusual clusters of organ-
isms or antimicrobial resistance patterns. The future of early
detection will likely be found in real-time data-mining software
that can raise flags based upon subtle changes in rates of test
ordering or positive test results.
Antimicrobial stewardship. Every hospital must now have
an antimicrobial stewardship program, guidelines for which
have been published by the Infectious Diseases Society of
America and the Society for Healthcare Epidemiology of
America (4). Antimicrobial stewardship efforts are directly de-
pendent on reports from the CML, so good communication
between the laboratory, pharmacy, IPP, and a stewardship
team is essential. For guiding empirical antimicrobial therapy,
unit-specific and tailored antibiograms should be updated on a
regular basis and provided to clinicians at the bedside. Such
antibiogram data can also be used for evaluation of trends in
important antimicrobial resistance rates and for education of
clinicians regarding optimal antimicrobial use. For guiding di-
rected antimicrobial therapy, patient-specific culture and sus-
ceptibility data are needed. This allows for a prospective audit
of antimicrobial use with feedback to the prescriber.
A major challenge to effective stewardship is an inability to
obtain antimicrobial susceptibility data from the CML in a
timely and efficient manner. Reducing the analytic turnaround
time is only the starting point, however. The data then have to
be incorporated quickly into antimicrobial management, which
often cannot be done if laborious chart reviews are required
for each patient on antimicrobial therapy. Computer decision
support systems can solve this problem by automatically iden-
tifying potential opportunities to optimize therapy, using real-
time analysis of data from several sources (e.g., pharmacy,
electronic medical record, and laboratory) (11).
S58 CAMP CLIN MICRO J. CLIN. MICROBIOL.

TABLE 1. Steps in nosocomial outbreak investigation and the role of the laboratory at each stepa
Investigative step Role of the clinical microbiology laboratory

Recognize problem.............................................................Surveillance and early warning system, ideally part of the laboratory information system;
notify infection control personnel of infection clusters, unusual resistance patterns,
possible patient-to-patient transmission
Establish case definition ....................................................Assist and advise regarding inclusion of laboratory diagnosis in case definition
Confirm cases......................................................................Perform laboratory confirmation of diagnosis
Complete case finding........................................................Characterize isolates with accuracy, store all sterile-site isolates and epidemiologically
important isolates, search laboratory database for new cases
Establish background rate of
disease and compare to attack rate
during suspected outbreak ............................................Provide data for use in ongoing surveillance, which provide baseline rates for selected
units and infection sites; search laboratory database for all prior cases of the entity if
baseline rate is not prospectively monitored
Characterize outbreak (descriptive
epidemiology)..................................................................Perform typing of involved strains, compare to previously isolated endemic strains to
determine if the outbreak involves a single strain (this can be done only if selected

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pathogens are routinely stored 关see above兴)
Generate hypotheses about causation:
reservoir, mode of spread, vector.................................Perform supplementary studies or cultures as needed, but only if justified by
epidemiologic link to transmission: personnel, patients. environment
Case-control study or cohort study
Institute control measures.................................................Adjust laboratory procedures as necessary
Ongoing surveillance to document
efficacy of control measures ..........................................Maintain surveillance and early-warning function of the laboratory
a
Adapted from reference 5.

Infection control committee participation. It is paramount
that the clinical microbiologist participates on the infection
prevention/control committee and acts as a consultant to in-
fection preventionists. He or she is the best person to provide
expertise in the interpretation of culture results, advice about
the utility of microbiological approaches to an infection control
problem, and input regarding the CML resources needed to
accomplish the goals of the committee. He or she should de-
scribe how changes in the methods used for detection, identi-
fication, and susceptibility testing of nosocomial pathogens will
impact the IPP.
The benefits of close collaboration and interaction between
the CML and the IPP are difficult to measure but are real. One
large survey of CML directors found that those hospitals with
CML directors on the infection prevention/control committee
were more likely to have CML involvement in formulary de-
cisions, to produce an annual antibiogram, and to provide
molecular typing support (6).
Several ongoing trends challenge these valuable personal
interactions between CML and IPP personnel. Consolidation
of CML services, off-site moves of CML laboratories, and total
reliance on the electronic medical record to the exclusion of
first-hand observation (e.g., review of plates or Gram stains)
too often keep clinicians and infection preventionists out of the
CML and keep CML personnel confined to the laboratory.
Education. CMLs also play an essential role in the education
of future hospital epidemiologists and infection preventionists.
Most hospital epidemiologists are trained in infectious diseases
(though some are also laboratorians and CML directors). The
ACGME requirements for training in infectious diseases re-
quire structured clinical microbiology training, and infection
preventionists also require microbiology training. The trends
referred to above (CML consolidation and off-site moves)
complicate this educational role, as does the difficult financial
situation of many hospitals. Who pays for the time and effort
required to deliver this educational content?
DISCUSSION
As a starting point, the discussants agreed that CMLs should
no longer be viewed as merely playing supportive roles for
infection prevention but rather should be seen as an essential
element of the IPP at every health care facility. Viewing the
CML as part and parcel of the IPP may help health care
administrators understand the importance of adequate funding
for the CML, particularly as CML activities increase to meet
infection prevention priorities. Effective prevention saves not
only lives but money, and these savings are rarely credited to
the CML.
Additional discussion focused upon specific aspects of the
CML activities outlined above, including (i) increasing calls for
active surveillance cultures (ASCs) to detect multidrug-resis-
tant organism (MDRO) carriers, (ii) a more standardized ap-
proach to immediate or urgent notification of IPP personnel,
(iii) a uniform definition for multiply drug-resistant Gram-
negative rods (MDR-GNRs) of infection control significance,
and (iv) limitations inherent in current approaches to antibi-
ogram generation.
Active surveillance. The role of broadly applied active sur-
veillance cultures (ASCs) in detection of MDRO carriers re-
mains unclear. Nonetheless, many hospitals have adopted this
approach for control of methicillin-resistant Staphylococcus
aureus (MRSA), often in response to legislative mandates. The
issue of MRSA active surveillance is addressed in another
paper in this series. Therefore, our discussion was focused on
surveillance for MDR-GNRs, which continue to emerge as a
major threat in the health care environment (14).
Can our experience thus far with MRSA inform our future
VOL. 49, NO. 9 SUPPL., 2011
TABLE 2. Can the MRSA experience inform screening for MDR
Gram-negative rods?
Parameter MRSA MDR-GNR
Transmissibility of key resistance Low High
determinant(s)
Complexity of resistance Low High
mechanism(s)
Lab methods for detection of Yes In development
carrier state
Established/effective Yes No
decolonization protocols
Literature base assessing Abundant Scant
screening approaches
approach to MDR-GNR active surveillance? As outlined in
Table 2, there are several important differences between
MRSA and the MDR-GNRs that suggest the answer may be
“no.” Whereas a single gene (mecA) provides a straightforward
gold standard for MRSA detection, resistance mechanisms for
MDR-GNR are multiple and highly complex. In contrast to
MRSA, many of the most important MDR-GNR resistances
are carried on mobile genetic elements (e.g., ESBLs and car-
bapenemases), laboratory methods for routine detection of the
carrier state are still being evaluated, decolonization protocols
are not currently available or feasible, and the literature
base to support screening is scant. Harris et al. recently
outlined the additional data required to inform decisions
about MDR-GNR screening, including (i) the performance
of available screening methods for organisms of interest (e.g.,
sensitivity, specificity, and frequency of screening), (ii) the pro-
portion of MDR-GNR infections that are due to in-hospital
transmission, (iii) the “undetected ratio” of colonized patients
(the proportion of colonized patients not detected by clinical
cultures), and finally (iv) the effectiveness of contact precau-
tions in preventing MDR-GNR transmission (7). Although
some studies have begun to address these questions (15), most
discussants agreed with the two experienced health care epidemi-
ologists who recently stated that “more data are needed… before
we launch headlong into implementing large-scale active sur-
veillance programs that threaten to divert resources from other
important infection prevention initiatives” (10).
In the meantime, participants felt that the use of MDR-
GNR active surveillance cultures should be limited to new
introductions of problematic MDR-GNRs (e.g., carbapenem-
resistant Enterobacteriaceae) or outbreak settings. At all other
times, the emphasis should remain fixed on so-called “horizon-
tal” approaches to infection prevention, those tried-and-true
practices that are applied to all at-risk patient populations and
are designed to prevent infections due to all pathogens (e.g.,
hand hygiene and bundled practices for prevention of device-
associated infections).
Standardized approaches to urgent notification of IPP per-
sonnel. The detection of certain epidemiologically important
pathogens requires immediate notification of the IPP so that
transmission prevention measures can be initiated immediately
(including, if applicable, notification of public health au-
thorities). Examples of organisms for which urgent notifica-
tion should occur include Mycobacterium tuberculosis, Neisseria
meningitidis, certain MDROs, and agents of bioterrorism (e.g.,
CONVENTIONAL VERSUS MOLECULAR METHODS S59
Bacillus anthracis, Yersinia pestis, and orthopox viruses). How-
ever, the discussants pointed out that the list of organisms for
immediate IP notification differs from one institution to an-
other and that it would be appropriate to establish more uni-
formity. We recognize that some institutions may wish to in-
clude organisms or results that others do not (for example, an
MDRO may have become endemic in one hospital, to the
point that the IP program no longer requires immediate noti-
fication, while another hospital has not yet had introduction of
the MDRO and needs such notification). Nonetheless, com-
piling a standard list of “critical” infection prevention results
should be a fairly straightforward matter and would start with
a simple survey of laboratories to determine what current prac-
tice is at a wide range of facilities.
Standardizing the MDR-GNR definitions. In addition to
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optimizing communication with the IPP, the discussants agreed
that a widely accepted definition of what constitutes “MDR” for
Gram-negative rods would be helpful. Given the diversity of
inherent and acquired resistance among the Gram-negative
bacteria, institutions vary substantially in their approach to
this. Recent efforts have provided a good start (13), but the
utility of these definitions must be tested in diverse health care
settings. A further complicating feature is the ability of labo-
ratories to detect MDR-GNRs or to differentiate those that
require additional infection prevention interventions (e.g., con-
tact precautions or transmission investigations) from those that
do not. For example, the CLSI recently changed breakpoints
for Enterobacteriaceae and cephalosporins and carbapenems,
obviating the need for ESBL confirmatory testing or modified
Hodge testing for clinical use. Unfortunately, many IPPs had
become accustomed to using the ESBL/Hodge test results to
guide institution of contact (barrier) precautions. In one insti-
tution, this change resulted in a 35% increase in the number of
MDR-GNR isolates identified and a concomitant increase in
the hospital’s use of contact precautions (3).
The effectiveness of contact precautions in reducing MDR-
GNR transmission in health care settings is not known, so of
course neither is the relative effectiveness of this intervention
against different types of MDR-GNR (e.g., those with trans-
missible or plasmid-borne resistance determinants versus those
with chromosomally mediated determinants). Future studies to
address these questions will require a standard approach to
defining those MDR-GNRs that ought to trigger specific in-
fection prevention measures. This assumes that the CML has
the tools to differentiate among these MDR-GNRs, which
remains a challenge. Both ESBL and Hodge confirmatory test-
ing are poor substitutes for molecular methods for detection of
ESBLs and carbapenemases, but in their absence most labo-
ratories must rely solely on an organism’s resistance phenotype
to determine the likelihood that it carries a resistance de-
terminant of epidemiologic significance. As more carbapen-
emases emerge (9), there will be an increasing need for
rapid, cost-effective methods for their identification.
Limitations of the current approach to antibiogram prepa-
ration. There was also a short discussion regarding the extent
to which the current CLSI guideline for antibiogram prepara-
tion (2) may underestimate the problem of emerging resistance
by including only the first isolate of a single species from an
individual patient. Given that antimicrobial resistance often
emerges during hospitalization, later isolates (second, third,
S60 CAMP CLIN MICRO
or tenth!) may provide a very different susceptibility profile.
Again, a multilaboratory collaborative study to produce anti-
biograms using alternative approaches may help determine
whether this problem is clinically important.
SUMMARY
The CML is an essential element of the IPP in every health
care facility, playing critical roles in surveillance, outbreak de-
tection and management, antimicrobial stewardship, risk as-
sessment and planning (through participation on the infection
control committee), and education. Close collaboration be-
tween CML and IPP personnel is required to ensure optimal
HAI prevention, which saves money and lives.
Session discussants: Eileen Burd, David W. Craft, Gary V. Doern,
W. Michael Dunne, Jr., Gina L. Ewald, Betty Forbes, George Goede-
sky, Larry Hambleton, Sue Kehl, Marjus Kostrzewa, Nathan A. Lede-
boer, Susan Novak-Weekley, Carol H. Smith, Melvin P. Weinstein, and
Alice S. Weissfeld.
REFERENCES
1. Barenfanger, J., J. Bente, and G. Havener. 2009. Optimal performance for
clinical microbiologists and their interaction with infection control staff. Clin.
Microbiol. Newsl. 31:9–15.
2. Clinical and Laboratory Standards Institute. 2009. Analysis and presenta-
tion of cumulative antimicrobial susceptibility test data. Approved guideline,
3rd ed. CLSI document M39-A3. Clinical and Laboratory Standards Insti-
tute, Wayne, PA.
3. Covington, L. E., et al. 2011. New CLSI recommendations: practical impli-
cations of eliminating ESBL testing and implementing new MIC breakpoints
for Enterobacteriaceae at a major teaching hospital, abstr. 632. Abstr. Soc.
View publication stats
J. CLIN. MICROBIOL.
Healthcare Epidemiol. Am. 2011 Annu. Sci. Meet. 1 to 4 April 2011, Dallas,
TX. http://shea.confex.com/shea/2011/webprogram/Paper4335.html.
4. Dellit, T. H., et al. 2007. IDSA and SHEA guidelines for developing an
institutional program to enhance antimicrobial stewardship. Clin. Infect. Dis.
44:159–177.
5. Diekema, D. J., and M. A. Pfaller. 2007. Infection control epidemiology and
clinical microbiology, p. 118–128. In P. R. Murray, E. J. Baron, J. H. Jor-
gensen, and M. A. Pfaller (ed.), Manual of clinical microbiology, 9th ed.
ASM Press, Washington, DC.
6. Diekema, D. J., et al. 2001. Clinical microbiology laboratory support for
infection control and antimicrobial resistance control, abstr. K-1213. Abstr.
41st Intersci. Conf. Antimicrob. Agents Chemother., Chicago, IL, 22 to 25
September 2001.
7. Harris, D. P., J. C. McGregor, and J. P. Furuno. 2006. What infection
control interventions should be undertaken to control multidrug-resistant
Gram-negative bacteria. Clin. Infect. Dis. 43(Suppl. 2):S57–S61.
8. Klevens, R. M., et al. 2007. Estimating healthcare associated infections and
deaths in U.S. hospitals, 2002. Public Health Rep. 122:160–166.
9. Leverstein-Van Hall, M. A., et al. 2010. Global spread of New Delhi metallo-
Downloaded from http://jcm.asm.org/ on January 22, 2016 by guest
beta-lactamase 1. Lancet Infect. Dis. 10:830–831.
10. Maragakis, L. L., and T. M. Perl. 2010. How can we stem the rising tide of
multidrug-resistant Gram-negative bacilli? Infect. Control Hosp. Epidemiol.
31:338–340.
11. McGregor, J. C., et al. 2006. Impact of a computerized clinical decision
support system on reducing inappropriate antimicrobial use: a randomized
controlled trial. J. Am. Med. Inform. Assoc. 13:378–384.
12. Meltzer, D. O., and J. W. Chung. 2010. U.S. trends in hospitalization and
general physician workforce and the emergence of hospitalists. J. Gen. In-
tern. Med. 25:453–459.
13. Paterson, D. L., and Y. Doi. 2007. A step closer to extreme drug resistant in
gram negative bacilli. Clin. Infect. Dis. 45:1179–1181.
14. Peleg, A. Y., and D. C. Hooper. 2010. Current concepts: hospital-acquired
infections due to Gram-negative bacteria. N. Engl. J. Med. 369:1804–1813.
15. Weintrob, A. C., et al. 2010. Natural history of colonization with Gram-
negative multidrug-resistant organisms among hositalized patients. Infect.
Control Hosp. Epidemiol. 31:330–337.