Florida Health Care Association District 2 January 13, 2015 A.C. Burke, MA, CIC 11/20/2014 1
To describe carbapenem-resistant Enterobacteriaceae. To identify laboratory detection standards for carbapenem-resistant Enterobacteriaceae (CRE). To identify five core and two supplemental prevention strategies to prevent the spread of CRE in long-term care. 11/20/2014 2
Top Threats Clostridium difficile CRE Multi-drug resistant Neisseria gonorrhoeae 11/20/2014 3
Lack of treatment options Typically resistant to all beta-lactams, and often to aminoglycosides and quinolones High mortality (>40%) Incidence and prevalence unknown in Florida At least 8 outbreaks in Florida from 2008-2013 Laboratory detection challenging 11/20/2014 4
Patel, Rasheed, Kitchel. 2009. Clin Micro News. CDC, unpublished data 11/20/2014 5
DC AK HI PR Patel, Rasheed, Kitchel. 2009. Clin Micro News. CDC, unpublished data 11/20/2014 6
DC KPC KPC, NDM KPC, NDM, OXA KPC, NDM, VIM KPC, NDM, VIM, IMP AK HI PR Patel, Rasheed, Kitchel. 2009. Clin Micro News. MMWR MMWR Morb Mortal Wkly Rep. 2010 Jun 25;59(24):750. MMWR Morb Mortal Wkly Rep. 2010 Sep 24;59(37):1212. CDC, unpublished data 11/20/2014 7
Aerobic gram-negative bacteria (GNB) Enterobacteriaceae Klebsiella spp. Escherichia coli Citrobacter freundii Enterobacter spp. Serratia spp. Salmonella spp. Photo source: CDC 11/20/2014 9
Normal gut flora for humans, poultry, and livestock Urinary tract infections, wound infections, pneumonia, septicemia, meningitis Easily spread by touch, food, and water Important cause of health care and communityassociated infections 11/20/2014 10
A sub-class of beta-lactam antibiotics Other beta-lactam antibiotics penicillins, cephalosporins Broadest spectrum of antibacterial activity Agents of last resort Includes doripenem, imipenem, meropenem Ertapenem reduced GNB and enterococcal activity 11/20/2014 11
ESBL+ GNB = Extended spectrum beta-lactamase producing GNB ESBL inactivates penicillins and cephalosporins Not carbapenems ESBL+ GNB may be resistant to quinolones and aminoglycosides Increasing prevalence of ESBL+ GNB in health care has driven increasing use of carbapenems 11/20/2014 12
11/20/2014 Photos Source: CDC 13
ESBL Treat with carbapenems Carbapenemases 11/20/2014 14
BETA-LACTAMASES Antibiotic-inactivating enzymes Beta-lactam antibiotics CARBAPENEMASES Antibiotic-inactivating enzymes Klebsiella pneumoniae carbapenemase (KPC) New Delhi Metallobetalactamase 1 (NDM1) Verona Integron coded Metallo-betalactamase (VIM) Carbapenems 11/20/2014 15
Not an organism It is an enzyme More specifically, set of 13 enzymes First detected in Klebsiella pneumoniae KPC first identified in North Carolina in 1996 Organism may be KPC producing May spread between bacteria Most common mechanism of resistance in Klebsiella spp. 11/20/2014 16
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Antibiotic resistant = bacterium will grow in presence of antibiotic Minimum Inhibitory Concentration (MIC) = lowest concentration of an antibiotic that prevents bacterial growth 11/20/2014 18
Establish standards Define resistant ( R ), intermediate ( I ), and susceptible ( S ) for every antibiotic and bacterial species by MIC Breakpoints MIC vary by antibiotic and by organism Not all laboratories follow most current CLSI standards 11/20/2014 19
CLSI 2009 Standard M100-S19 CLSI 2010 Standard M100-S20 CLSI 2012 Standard M100-S22 Lowered susceptibility breakpoints for testing Enterobacteriaceae to carbapenems in 2010 Simplified detection, follow-up laboratory tests such as Modified Hodge Test (MHT) no longer needed Intermediate or resistant result is sufficient to signal a treatment and an infection control alert 11/20/2014 20
Food and Drug Administration (FDA) has not yet cleared commercial susceptibility testing systems using updated CLSI standards. Manufacturers cannot update software or systems with standards not yet promulgated by the FDA. 11/20/2014 21
MIC (mcg/ml) S I R Doripenem Imipenem Meropenem 1 2-4 8 16 Perform laboratory test to detect carbapenemase activity-mht, CarbaNP, PCR Non-susceptible = MHT+ or I or R = not S 11/20/2014 22
MHT and Carba NP-cannot distinguish between KPC, NDM1, or VIM MHT detects carbapenemase activity in Klebsiella and E. coli Does not detect in Enterobacter spp. PCR available assays detect some, most, or all known carbapenemases Test for gene Most accurate to detect carbapenemase activity 11/20/2014 23
Antimicrobial Agent Previous breakpoints (M100-S19) MIC (µg/ml) Predating 2010 Update Resistant (R) 2012 breakpoints (M100- S22) MIC (µg/ml) (Revised Jun 2010 and Jan 2012) Susceptible (S) Intermediate (I) Susceptible (S) Intermediate (I) Doripenem - - - 1 2 4 Imipenem 4 8 16 1 2 4 Meropenem 4 8 16 1 2 4 If using M100-S20 or M100-S22 standard, then confirmatory laboratory test not needed. Lower breakpoints are more sensitive. An S result is now an I under new standard. Resistant (R) 11/20/2014 24
National Healthcare Safety Network CRE = non-susceptible, I or R to doripenem, imipenem, or meropenem CLSI CRE = resistance, R to doripenem, imipenem, and meropenem Centers for Disease Control and Prevention CRE toolkit CRE = non-susceptible, I or R to doripenem, imipenem, meropenem, and ceftriaxone, cefotaxime, or ceftazidime More sensitive= higher false positives, fewer false negatives, higher prevalence More specific= higher false negatives, fewer false positives, lower prevalence 11/20/2014 25
Doripenem Imipenem Meropenem MIC (mcg/ml) S I R 1 2 4 Non-susceptible = I or R = not S 11/20/2014 26
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Core measures Recognition and reporting Hand hygiene Contact precautions Resident and staff cohorting Minimize use of invasive devices Promote antimicrobial stewardship CRE screening 29 29
How does your laboratory notify you if CRE is identified? What CLSI standards is your laboratory using? What definition of CRE does your laboratory use? Could resistance to carbapenems be missed (i.e. not reported) if bacteria are susceptible to other antibiotics such as quinolones or trimethoprim-sulfamethoxazole? Which carbapenems are used to test Enterobacteriaceae susceptibility? Note: Ignore results of ertapenem testing 11/20/2014 30
Review lab records for past 12 months to identify previously unrecognized cases Point prevalence survey if unrecognized cases found High risk units Where unrecognized cases were located Stool, rectal, or perirectal swabs for active surveillance/screening testing 11/20/2014 31
Monitor for adherence May use alcoholbased hand gel 11/20/2014 32
CRE infections and colonization Monitor adherence and provide feedback to staff Discontinuing precautions-case by case basis Capability to perform hand hygiene Containment of body fluids (i.e. wounds, continence) Completion of treatment Middle ground for residents with lower risk for transmission contact precautions when providing care in resident room but allow resident in common areas 11/20/2014 33
Single room Cohort with other residents with CRE Cohort staff caring for residents with CRE Staff who care for residents with CRE do not care for any other residents 11/20/2014 34
Devices create another portal of entry for infection Process to assess need of indwelling catheters on regular basis Upon admission or re-admission Indications for use upon insertion Minimum three times weekly to assess ongoing need 11/20/2014 35
Colonization vs. Infection Stop and re-assess therapy when culture results are available More narrow spectrum? Shorter duration? 11/20/2014 36
Epidemiological links to previous cases Point prevalence surveys when case is identified 11/20/2014 37
1. Conduct Active Surveillance Testing Screen high-risk patients at admission Screen patients from facilities known to have CRE 2. Chlorhexidine Bathing Bathe patients with 2% chlorhexidine 3838
CDC. 2012 Toolkit. Guidance for Control of Carbapenem- Resistant Enterobacteriaceae (CRE). Munoz-Price, SL. et al. Clinical Epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis 2013;13: 785 96. CDC. Vital Signs. http://www.cdc.gov/vitalsigns/hai/cre/ CDC. K Allen. February 14, 2013. Epidemiology and Prevention of Carbapenem-Resistant Enterobacteriaceae. Oregon Health Authority. 2013 Toolkit. Guidance for Control of Carbapenem-Resistant Enterobacteriaceae (CRE). 39 39
A.C. Burke, MA, CIC Healthcare-Associated Infection Prevention Program Manager Bureau of Epidemiology Florida Department of Health Email: AC.Burke@flhealth.gov Phone: 850-766-7547 11/20/2014 40