Nosocomial (Healthcare Associated) Infections Daniel J.

Diekema, MD, FACP

Financial disclosure: Research funding received from Merck, Pfizer, Astellas, Cerexa, PurThread Technologies, bioMerieux, Innovative Biosensors, Inc.
No products manufactured by the above companies will be discussed during this presentation.

Nosocomial (Healthcare Associated) Infections Clinical Questions:

What are the most common hospital or healthcare-associated infections? What prevention measures can be used to prevent these infections? What basic infection control procedures are relevant to the hospital-based physician?
Focus will be on prevention, with most time devoted to infections with the greatest morbidity and mortality.

Nosocomial Infection Definition

hAcquired in a hospital or healthcare facility (healthcare-associated) hNot present or incubating at admission hfor most bacterial infections, onset of symptoms >48 hours after admission hsymptoms may not present until after discharge

Nosocomial Infections: An ongoing epidemic

h5-10% of all inpatients acquire infection during hospitalization: Up to 2 million persons infected annually Responsible for up to 90K deaths/year Increase length of stay, increase costs 24 days, up to $28K per nosocomial ICU
bloodstream infection $30 billion in direct costs to US hospitals
Pittet D, et al. JAMA 1994;271:1598-1601. http://www.cdc.gov/ncidod/dhqp/pdf/Scott_CostPaper.pdf

Nosocomial Infections
Distribution by site of infection
Other: C. difficile

Bloodstream Lung

Urinary Tract

Surgical Site

Nosocomial Bloodstream Infection

hCDC: 31K deaths annually from nosocomial BSI hMost (>85%) are associated with CVCs h15 million CVC days/year in US ICUs hIf rate of BSI is 5.3 per 1000 CVC days: h80,000 catheter-associated BSI (CA-BSI) hIf attributable mortality is 12-25%: h10K-20K deaths per year from CA-BSI
Mermel L. Ann Intern Med 2000;132:391. CDC. MMWR 51;RR-101 Klevens, et al. Pub Health Rep 2007;122:160-6

Sources of Central-Line Associated Bloodstream Infections (CLABSI)

hMigration of organisms from the catheter-skin interface over the external surface of the catheter hMigration of organisms from the catheter hub down the internal surface of the catheter hHematogenous seeding of the catheter tip hContamination on insertion hContaminated infusates

Prevention strategies focus on controlling bacterial flora at the insertion site

CLABSI: Prevention bundles

hInstitute for Healthcare Improvement, VA ICU collaborative, Canadian ICU collaborative, etc. hIncorporate five practices for which the evidence strongly supports reduction in CA-BSI: hDaily review of need for central line hHand hygiene hUse of maximal sterile barriers for insertion hChlorhexidine for skin antisepsis hUse subclavian or IJ as preferred insertion site

CLABSI: Prevention bundles

hKeystone Project, over 100 Michigan ICUs h mean CA-BSI rate from 7.7 to 1.4 per 1000 catheter-days (66% reduction) hReduced median to zero hReduction persisted out to 18 months
Quasi-experimental design, Hawthorne effect, incomplete data collection, little process information But still Pronovost P, et al. NEJM 2006;355:2725-32.

Keystone Project: 36 month follow up

Pronovost, et al. BMJ 2010;340:c309

Preventing CLABSI: Where do we go from here?

hUnanswered questions: hHow to sustain a BSI reduction? hWhat is the role of new technologies and approaches?
Antimicrobial devices/dressings, antimicrobial lock solutions, etc.

hHow should we move the reduction outside of the ICU environment?

Preventing CLABSI: Sustaining a reduction

hShort term, education-based interventions extinguish over time! hA durable change in process and culture is required ( complexity) hChecklists, process measures hEmpower staff to stop insertion hUnit leadership and buy-in hSupport from hospital leadership

CLABSI: New approaches for prevention

hWhere can we put more antimicrobials? hCatheters
Antimicrobial impregnated catheters Antimicrobial lock solutions

hDressings
CHG impregnated dressings

hPatients
CHG bathing (source control)

CHG impregnated dressings: A randomized, controlled trial

hRandomized controlled trial of CHG impregnated sponge dressing vs. standard dressings hOutcomes: catheter colonization, CABSI, clinical sepsis h1653 pts from 7 ICUs randomized h4 groups, stratified by dressing type and 3 vs. 7 day dressing changes
Timsit, et al. JAMA 2009;301:1231-41.

CHG impregnated dressings: A randomized, controlled trial

Incidence/1000 catheter days Outcome Catheter colonization CA-BSI Control 15.8 1.3 CHG 6.3 0.4 ITT analysis HR [95% CI] 0.4 [0.3-0.5] 0.2 [0.1-0.7]

Timsit, et al. JAMA 2009;301:1231-41.

New approaches for prevention: CHG bathing (Source Control)

hMulticenter study (5 centers, 6 ICUs)

Monitored CHG bathing Unmonitored CHG bathing

Montecalvo et al. Am J Med 2012;125:505-511.

CLABSI: Applying prevention methods

Pressures will increase to address this fraction: Are all infections preventable?

CA-BSI Hand hygiene Daily CVC review rate Optimal insertion site MSB for insertion 2% CHG for skin prep CHG bathing

CHG dressings AM impreg CVC AM lock prophylaxis

Time

CLABSI: Moving prevention out of the ICU

hOne day prevalence survey of central venous catheter use at 6 large academic healthcare centers h29% of 2459 patients had CVCs h43-80% of ICU patients h7-39% of non-ICU patients h70% of CVCs were in non-ICU patients
Climo M, et al. Infect Cont Hosp Epidemiol 2003;24:942-5.

Preventing CLABSI: Summary

hStart with a bundle of 5 proven practices hCulture of safety, unit leadership
Empower nursing staff

h complexity, redundancy
Line placement kits/carts, checklists

hApply newer approaches as needed hCHG dressings, bathing hMove prevention out of the ICU hLine placement and care teams

Ventilator Associated Pneumonia

hMost common nosocomial infection in the ICU h25% of all NI reported from Med-Surg ICUs hAffects between 9-27% of intubated patients hIncreased morbidity, mortality and LOS hIncreases LOS by 7-9 days hIncreases hospital costs by $11- 40K hAttributable mortality from 10-25%
Hidron AI, et al. Infect Cont Hosp Epidemiol 2008;29:996. Safdar N, et al. Crit Care Med 2005;33:2184-93. Rello J, et al. Chest 2002;122:2115-2121. Rello J, et al. Chest 1991;100:439-444.

Limitations of VAP Definitions

The wards and the post-mortem room show a very striking contrast in their pneumonia statistics Sir William Osler, 1907

hOne third with VAP have no autopsy evidence hOne fourth without VAP have autopsy evidence hAspects of definition are subjective hConditions with similar clinical findings:
hatelectasis, pulmonary edema, thromboembolic dz, ARDS, alveolar hemorrhage, hypersensitivity pneumonitis, pulmonary contusion, combinations of disorders (e.g. BSI + pulmonary edema)
Klompas M. JAMA 2007;297:1583.

hLower VAP rates could mean:

hExcellent care, fewer actual infections hChange in application of definition or diagnostic practices

Subjectivity and inaccuracy in the VAP definition allow hospitals to undertake practices that will markedly decrease their VAP rates and yet do little or nothing to improve patient outcomes.
Klompas M, Platt R. Ann Intern Med 2007;147:803-805. Klompas M. Thorax 2009;64:463-65

Pathogenesis of VAP
hEntry of pathogens into lower respiratory tract colonization infection hLeakage/aspiration around ET tube Biofilm adherent to ET tube hInhalation of contaminated aerosols hDirect inoculation hHematogenous spread hInfection often multifocal hSampling issues?
Niederman, Craven, et al. Am J Resp Crit Care Med 2005;171:388-416.

Preventing VAP: use of mechanical ventilation

hFacilitate/accelerate weaning hProtocols require adequate staffing hReintubation also increases VAP risk hUse non-invasive ventilation when possible hPositive pressure ventilation/facemask hCOPD exacerbations, acute hypoxemic respiratory failure, immunocompromise with inflitrates and respiratory failure
Niederman, Craven, et al. Am J Resp Crit Care Med 2005;171:388-416.

Multifactorial Interventions: The ventilator bundle

hImplementation of those interventions with the supporting evidence/feasibility hHand Hygiene hElevation of HOB hSedation vacation each day hAssessment of readiness to wean hPUD and DVT prophylaxis hChlorhexidine oral care (new)
www.ihi.org

Spontaneous awakening trial + spontaneous breathing trial

hIntervention arm had fewer: hVent days hICU days hHospital days hDeaths hNo difference in reintubation rates
Girard et al. Lancet 2008;371:126-34.

Reducing aspiration risk: Continuous subglottic suctioning

hMeta-analysis, 13 studies, 2442 pts hVAP RR = 0.55; 95% CI 0.46-0.66 hDecreased ICU LOS by ~1.5 days, MV by ~1 day
Muscedere et al. Crit Care Med 2011;39:1985-91.

VAP rates appear to be declining across the country.

Courtesy of Shelley Magill, MD, PhD (CDC/NHSN)

VAP Prevention: Summary

hVAP is common, and increases LOS, hospital costs, and mortality hBetter diagnostics for VAP are needed to reduce misclassification hVAP prevention literature is murky, but:
hIHI bundle + oral care with chlorhexidine hContinuous subglottic suctioning hOther approaches (silver coated ET tubes, selective DD, etc.) if rate remains high

Clostridium difficile
hAnaerobic, sporeforming bacillus hGram-positive hPresent in soil and environment hHospitals are major reservoirs

C. difficile associated disease (CDAD)

Asymptomatic colonization Diarrhea (mild to severe) Colitis +/- pseudomembranes Toxic megacolon Colonic perforation/peritonitis Sepsis & acute abdomen without diarrhea
High severity Low severity

Main Risk Factors for CDAD

hAntimicrobial use hAdvanced age
hUse of PPIs or H2 blockers hInfected roommate hProlonged hospital stay hMultiple, severe underlying conditions hImmunosuppressive therapy

Main Host Defenses against CDAD hIntact microbiota of colon hHumoral immune response Events leading to CDAD: hAntimicrobial use hC. difficile exposure/carriage h? Defect in humoral immunity

CDAD risk lasts for at least 3 months after receipt of antibiotics

Hensgens, et al. J Antimicrob Chemother 2012;67:742-48.

Importance of serum antibody response to Toxin A

hBaseline serum antibodies do not predict who will develop CDAD hIncrease in toxin A IgG (anamnestic response) predicts asymptomatic carriage (P <.001) hA low (or absent) Ab response in pts with CDAD hNew data suggest efficacy of monoclonal antibodies to prevent CDAD recurrence (7% vs 25%)
Kyne et al. NEJM 2000;342:390 Lowy et al. NEJM 2010;362:197

Changing Epidemiology of CDAD

hIncreasing rates world-wide hMore severe disease hMore treatment failures hMore colectomies hMore CDAD-related deaths hCommunity-acquired cases

Incidence of C. difficile-related Hospitalization in U.S.

Zilberberg MD, et al. Emerg Infect Dis. 2008;14:929-31.

More CDAD, more deaths

BI/NAP 1 Strain Epidemic Strain

hGreat geographic variability in rates of BI/NAP1 hAccounts for 61% of CDAD isolates from recent multicenter sample of acute care CDAD in Chicago
Black SR et al. Infect Control Hosp Epidemiol 2011;32(9):897-902

Transmission
hTransmitted via fecal-oral route hSpread via healthcare workers hands and contaminated environments hHand Hygiene hAlcohol-based hand cleaners do not eliminate spores. hMust wash hands with soap and water

Risk Factors - Environment

hSpores can persist in rooms up to 40 days after infected patient is discharged hSpores have been recovered from: hHospital toilets hMetal bedpans hCommodes hThermometers hFloors hResistant to many commonly used cleaning agents. hDetergents may not eliminate C. difficile spores

C. difficile Transmission & Relationship to Prior Room Occupants

110% Increased risk

Shaugnessey et al. Infect Control Hosp Epidemiol 2011;32:201.

Prevention and Control Strategies

hPreventing patient to patient spread hHand hygiene (handwashing) hGowns, gloves, isolating, cohorting hDedicating items to patient hRoom cleaning and disinfection
Dilute bleach on units with higher rates

hDecreasing antimicrobial use

www.cdc.gov

CDAD Primary Treatment

hD/C antibiotics alone relieves symptoms in 10-20% of mild cases hOral metronidazole or vancomycin relieves symptoms in > 95% of cases hProblem: Up to 20-30% of patients have recurrences

Adjuvant Therapies Described for Severe or Relapsing CDAD

hProlonged po vanco taper hRifaximin chaser hProbiotics hIntestinal microbiota transplant* hImmunotherapy hIVIG hMonoclonal antibodies
*Gough et al. Clin Infect Dis 2011;53:994-1002

Reducing C. difficile: Summary

hOur greatest HAI challenge at this time hRequires increased, intensive attention to: hAntimicrobial stewardship
Every hosptial must have an active program Tackles the key risk factor for C. difficile disease

hEarly accurate detection + isolation/HH hEnvironmental cleaning and disinfection

C. difficile forms spores that are difficult to eradicate Monitoring of cleaning process necessary Bleach based cleaning may be required New technologies also in the works
E.g. Hydrogen peroxide vapor, other touchless methods

Surgical Site Infections

h2nd most common nosocomial infection hOver half present after discharge hOrganism distribution--percent
hStaphylococcus aureus hCoagulase negative staph hEnterococcus spp. hEscherichia coli hPseudomonas aeruginosa 20 14 12 8 8

Surgical Site Infections

Risk Factors: Only some can be modified
hInfection at another site treat infections pre-operatively hDuration of procedure surgical technique and asepsis hDiabetes, hyperglycemia careful glucose control hShaving operative site preoperatively clip, dont shave! hHypothermia intraoperatively normothermia (warm pt) hS. aureus carrier state S. aureus decolonization hLow oxygen tension? high flow oxygen? (conflicting data) hAdvanced age hObesity hLength of postoperative stay hSurgical wound classification

Surgical Site Infections

Other Methods of Prevention
hPerioperative antibiotic prophylaxis hPublished guidelines exist hTiming of administration is critical Initiate within 1 hour prior to incision hDecolonize patients who carry S. aureus? hFor S. aureus carriers, some studies show benefit to decolonization hConsider first for major cardiothoracic or orthopedic procedures (e.g. Prosthetic jts)
Bode et al. N Engl J Med 2010;362:9-17

Surgical Site Infections

S. aureus screening hS. aureus decolonization

Bode et al. N Engl J Med 2010;362:9-17

Catheter-associated urinary tract infection (CA-UTI)

hUrinary tract is most common HAI site hAssociated with urinary tract catheters hThough less morbid than other HAIs, sheer number contributes substantially to LOS, cost, morbidity/mortality, abx use h17% of hospital BSI of urinary source hMajority of CA-UTI may be preventable
http://www.cdc.gov/hicpac/pdf/CAUTI/CAUTIguideline2009final.pdf

http://www.cdc.gov/hicpac/pdf/CAUTI/CAUTIguideline2009final.pdf http://www.cdc.gov/ncidod/dhqp/HAI_shea_idsa.html

Catheter-associated urinary tract infection (CA-UTI)

hPrinciples of prevention, divided into 3 modules for implementation: hAppropriate catheter use (I)
Proper indications, remove ASAP

hAseptic placement (II)

Appropriately trained personnel only

hProper maintenance (III)

Closed drainage system Unobstructed urine flow

Nosocomial Infections Summary

hNIs affect 5-10% of hospitalized pts and cause significant morbidity and mortality hEvidence-based interventions can greatly infection rates, save lives hChallenges: moving prevention outside of the ICU environment, sustaining gains, pushing rates to irreducible minimum.and hand hygiene!

Additional data slides for Q&A

CLABSI: Prevention Strategies

hAnatomic site of catheter insertion
hDensity of skin flora at insertion site is a risk factor
Complication category Contamination Clinical sepsis Bloodstream infxn Femoral (n, 134) 26 (19%) 4 2 Subclavian (n, 136) 6 (4%) 1 1 p-value <0.001 0.07

hData suggest infection rates differ by site: FEMORAL > IJ > SUBCLAVIAN
Merrer, et al. JAMA 2001;286: 700-707. Mermel, et al. Am J Med 1991;91:197-205.

CLABSI: Prevention Strategies

hHand hygiene
hHospital-wide hand hygiene campaign with alcohol product led to in over nosocomial infection and in MRSA BSI

Pittet D, et al. Lancet 2000;356:1307.

CLABSI: Prevention Strategies

hMaximal Sterile Barrier Precautions
Prospective randomized trial of MSB during catheter insertion CA-BSI rate 6-fold higher in control group
Raad II, et al. ICHE 1994;15:231-238.

Educational program for catheter insertion Increase maximal barrier use 44% 65% Decrease CA-BSI 4.5 2.9 per 1000 pt days
Sherertz R, et al. Ann Intern Med 2000;132:641

CLABSI: Prevention Strategies

hSkin antisepsis
hChlorhexidine (2%) is now preferred 2.3 (chlorhex) vs. 7.1 (EtOH) vs. 9.3 (P-I) bloodstream infections per 100 catheters
Maki DG, et al. Lancet 1991;338:339-43.

Metanalysis: 7 studies of CHG versus P-I Pooled RR 0.5 (0.3-0.9), favored CHG
Ann Int Med 2002;136:792-801.

New approaches for prevention:

Antimicrobial impregnated catheters
hChlorhexidine/silver sulfadiazine: hMeta-analysis: OR 0.56 (0.37-0.84, p=0.005) vs. placebo
Veenstra DL, et al. JAMA 1999;281:261-7

hMinocycline/rifampin: hSeveral randomized trials demonstrate reduction in CA-BSI compared with placebo
Raad I, et al. Ann Int Med 1997;128:267-74 Darouiche R, et al. NEJM 1999;340:1-8 Chatzinikolaou I, et al. Am J Med 2003;115:352-57. Hanna H, et al. J Clin Onc 2004;22:3163-71 Darouiche R, et al. Ann Surg 2005;242:192-200.

New approaches for prevention:

Antimicrobial lock solutions
hInstillation of antimicrobials into lumen hMeta-analysis of 7 trials of vancomycin lock solution, mostly cancer pts with long term CVCs hCA-BSI RR = 0.49 [0.26-0.95], p=0.03
Safdar N, Maki D. Clin Infect Dis 2006;43:474-84.

hPractices vary widely h<20% of EIN members have used

Recurrent BSI and limited access options <1% use routinely Vancomycin (68%), EtOH (9%) most common
Polgreen et al. Infect Cont Hosp Epidemiol 2010;31:554-57.

Reducing aspiration risk: Semi-recumbent positioning

One of three RCTs demonstrated significant in VAP Overall trend favors semirecumbent position Patients should not be completely supine. Alexiou, et al. J Crit Care 2009;24:515-522

Preventing VAP: The sedation vacation

hDaily interruption of sedation: h128 patients on mechanical ventilation randomized to daily interruption of sedation until awake hDuration of ventilation 4.9 vs. 7.3 days (p=0.004)

Kress JP et al. N Engl J Med 2000;342:1471-77.

Preventing VAP: Chlorhexidine oral care

hRecent meta-analyses of oral antisepsis
12 CHG RCTs RR 0.7 [95% CI, 0.5-0.9]1
Effect most pronounced for 2% (vs. 0.12%)

(1) Labeau, et al. Lancet ID 2011;11:845 (2) Kola et al. J Hosp Inf 2007;66:207.

S-DD for VAP Prevention

hPro: hAccumulated trials data support efficacy in reducing VAP and mortality hCons: hImpact of systemic + oral antimicrobials on resistance emergence hCan oral decontamination with chlorhexidine provide similar benefit?

Preventing VAP:
Antmicrobial (silver) coated ET tubes
h2003 pts randomized hAmong those intubated > 24 hrs: h4.8 vs. 7.5% microconfirmed VAP, p=0.03 hNo diff in vent days, LOS, mortality, MD suspicion of VAP hReducing VAP, or reducing colonizers?

Kollef et al. JAMA 2008;300:805.

Ventilator Associated Pneumonia: Risk Factors (partial list) hMechanical ventilation hRecumbent position hIncreased gastric pH aspiration hEnteral feeding h level of consciousness hAdvanced age hMale sex hPre-existing pulmonary disease
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5303a1.htm Niederman et al. Am J Resp Crit Care Med 2005;171:388-416.

hOnly four studies met inclusion criteria hAll had methodologic problems

The IHI Ventilator Bundle: Meta-analysis

All were before-after study designs Little information re diagnostic approach before and after Selection/publication bias, confounding? Resar et al. Jt Comm J Qual Pt Saf 2005;31:243. Berriel-Cass et al. Jt Comm J Qual Pt Saf 2006;32:612. Youngquist et al. Jt Comm J Qual Pt Saf 2007;33:219. Unahalekhaka et al. Jt Comm J Qual Pt Saf 2007;33:387.

h38-60% reduction in VAP post-intervention

hIs the bundle cost-effective? Which aspects are most important? Should new elements be added?

Zilberberg et al. Crit Care Med 2009;37:305.

hRCT in 12 Italian ICUs, N = 600 adults hEarly trach (6-8 d) vs. late (13-15 d) hVAP: 14% early vs. 21% late (p=0.07) h risk for VAP (HR, 0.66 [0.42-1.04], remaining on vent (HR, 0.7 [0.56-0.87]), remaining in ICU (HR, 0.7 [0.55-0.97]), h Mortality risk, but NS (HR, 0.8)
Terragni, et al. JAMA 2010;303:1483

Major issues with CLABSI definition

hDesigned to be sensitive, not specific hDoes pos blood cx + CVC = CLABSI? hMany infections that meet CLABSI criteria may be from gut translocation hEnterococcus, Candida, Gram negs hCDC has working group assembled to consider changes to CLABSI definition

hInterpret clinical signs as strictly as possible hInterpret CXRs as strictly as possible hRequire consensus between 2 or more IPs hSeek intensivist endorsement before accepting case hRequire BAL for diagnosis hSet quantitative growth thresholds for diagnosis hTransfer patients who require prolonged ventilation hExpand surveillance to include uncomplicated postop patients
Am J Infect Cont 2011, Sept 22 (Epub ahead of print)