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Carbapenem-Resistant Enterobacteriaceae and the Impact on Gastroenterology

Mary Beth Graham, MD, FIDSA, FACPDivision of Infectious DiseaseMedical College of Wisconsin

DisclosuresNone

I would like to thank my colleague and mentor, Charles E. Edmiston Jr., PhD, CIC, Professor Emeritus, Department of Surgery MCW for the gracious use of some of his slides

Acknowledgements

Outline• Discuss the emergence of Carbapenem

Resistant Enterobacteriaceae (CRE) as a pathogen in the USp g

• Discuss the role of invasive GI procedures in the potential spread of CRE

• Discuss the ways to prevent spread of CRE

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Antibiotic Resistance• Each year in the US, at least 2 million people

acquire serious infections with bacteria that are resistant to one or more antibiotics designed to t t thtreat them.

• At least 23,000 people die each year as a result of an antibiotic resistant infection.

• The use of antibiotics is the single most important factor leading to antibiotic resistance in the world.

CDC – Antibiotic Resistance Threats in the United States, 2013

From www.cdc.gov

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What is an MDRO?• MDRO – Multi-Drug Resistant Organism• No consensus definition• Various definitions used in the literature:• Various definitions used in the literature:

• Resistance to 1 or more antibiotics• Resistance to 1 or more classes of antibiotics• Resistance to all but one antibiotic or class• Resistance to all antibiotics or classes

Clinical Importance of MDROs• Options for treatment are limited• MDROs have been associated with

– Increased lengths of stay– Increased cost– Increased morbidity and mortality

• Worse outcomes for resistant organisms have been shown for: VRE, Pseudomonas, Acinetobacter, Enterobacter, E. Coli, K. pneumoniae (CRE)

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MDR Gram Negative Infections• Multidrug-resistant gram-negative bacilli (GNB)• Per CDC – these organisms are particularly

worrisome as they are becoming resistant to nearly all drugs that would be considered fornearly all drugs that would be considered for treatment.

• The most serious gram negative infections are health care associated and most common pathogens are:– Enterobacteriaceae– Pseudomonas aeruginosa– Acinetobacter

MDR GNB• Grouped according to resistance

– Extended-spectrum β-Lactamase (ESBL) producing enterobacteriaceaep g

– Carbapenem-resistant Enterobacteriaceae (CRE)

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CRE• Carbapenem Resistant

Enterobacteriaceae• Uncommon in US prior to 1992p• Carbapenemase producing

Enterobacteriaceae most commonly producing Klebsiella pneumoniae carbapenemase (KPC) are widely disseminated in US (first reported in 2001)

Epidemiology of CRE• CRE have been associated with high mortality rates (up

to 40 to 50% in some studies).• In addition to β-lactam/carbapenem resistance, CRE

often carry genes that confer high levels of resistance tooften carry genes that confer high levels of resistance to many other antimicrobials, often leaving very limited therapeutic options.– “Pan-resistant” KPC-producing strains have been reported.

• CRE have spread throughout many parts of the United States and have the potential to spread more widely.

KPC• KPC is a class A –lactamase

– Confers resistance to all β–lactams including extended-spectrum cephalosporins and p p pcarbapenems

• Occurs in Enterobacteriaceae– Most commonly in Klebsiella pneumoniae– Common cause of both healthcare and

community acquired infections

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KPC• Felt by many to be more virulent than

Acinetobacter or Pseudomonas

• KPCs are plasmid based and often flanked by transposon sequences:– Resistance can be transferred– Plasmids often contain other resistance genes

http://www.cdc.gov/hai/organisms/cre/TrackingCRE.html

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NDM• Several different metallo-β-lactamase-producing CRE

strains have been identified in the United States since 2009.

• New Delhi metallo-β-lactamase (NDM)• New Delhi metallo-β-lactamase (NDM)• Verona integron encoded metallo-β-lactamase (VIM)• Imipenemase (IMP) metallo-β-lactamase. • In the United States these have generally been found

among patients who received medical care in countries where these organisms are known to be present.

Healthcare-Acquired Outbreaks via GI Endoscopes

Infections Associated with Accessories

• Infections associated with biopsy forceps• Contaminated biopsy forceps. (Dwyer DM. Gastroint

Endosc 1987;33:84)• Contaminated biopsy forceps (no cleaning between• Contaminated biopsy forceps (no cleaning between

cases). Graham DY. Am J Gastroenterol 1988;83:974)

• Biopsy forceps not sterilized (glut exposed,? time) Bronowicki JP. NEJM 1997;334:237)

• Reusable endoscopic accessories that break the mucosal barrier should be mechanically cleaned and sterilized between patients

Transmission of Infection During GI Endoscopy

Viruses - Attributable• 8 cases of HCV (possible contamination of multi-dose vials)• 5 cases of HBV – suboptimal reprocessing practices

B t iBacteria• 48 cases of Salmonella (1974 - 1988) – colonization to death• 216 cases of Pseudomonas aeruginosa – water, elevator

channel, failure to dry all channels (70% alc.)• 12 cases of H. pylori • Miscellaneous Gram-negatives (<20 cases) - ERCP• M. tuberculosis, atypical Mycobacteria - bronchoscopy

Nelson DB, Muscarella LF. World J Gastroenterology 2007;12:3953Nelson DB, Muscarella LF. World J Gastroenterology 2007;12:3953--39643964

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Healthcare-Associated Infections via GI Endoscopes

• Observations• Number of reported infections is small,

suggesting a very low incidencesuggesting a very low incidence• Endemic transmission may go

unrecognized (e.g. inadequate surveillance, low frequency, asymptomatic infections)

Spach DH. Ann Int Med 1993 Weber DJ, Rutala, WA. Gastroint Dis 2002

Healthcare-Associated Infections via GI Endoscopes

Infections traced to:• Inadequate cleaning (clean all channels)• Inappropriate/ineffective disinfection (time

exposure, perfuse channels, test concentration, ineffective disinfectant, inappropriate disinfectant)

• Failure to follow recommended disinfection practices (tap water rinse)

• Flaws is design of endoscopes or AERs

CRE• Klebsiella pneumoniae or Escherichia coli

• ERCP• Scope – elevator – risk factorp

• Failure to remove bioburden• Epidemiologically linked• Careful attention to manual

cleaning

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FDA reports• Olympus ERCP Endoscope

– Reported 12/2012– 16 patients developed Klebsiella pneumoniae

infections after ERCPinfections after ERCP.– Problem related to difficulty in reliably

cleaning and disinfecting the “elevator”• Response

– Reprocessing changed from automated high-level disinfection to gas sterilization

Early identification and control of carbapenemase-producing Klebsiella pneumoniae, originating from contaminated

endoscopic equipment.AJIC 2013;41:562-4

• Florida – 2 hospitals• 7 cases of carbapenem resistant K. pneumoniae identified

between June 2008 and Jan 2009.• All 7 patients had ERCP at the same endoscopy center• 46 additional patients who were seen at the same

endoscopy center were screened• 3 additional patients were found to be colonized with

CRE• Institution blamed episode on inadequate cleaning of the

complex terminal part of the ERCP scope that contains the scope elevator

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• 39 case patients were identified from January 2013

JAMA 2014;312(14):1447-1455

39 case patients were identified from January 2013 through December 2013, 35 with duodenoscope exposure in an Illinois hospital.

• No lapses in duodenoscope reprocessing were identified; however, NDM-producing Escherichia coli was recovered from a reprocessed duodenoscope and shared more than 92% similarity to all case patient isolates by PFGE.

NDM-Producing CRE Associated With Duodenoscope Exposure - Infection Prevention

• During October 2013, the hospital changed its duodenoscope reprocessing procedure from automated high-level disinfection to gas au o a ed g e e d s ec o o gassterilization with ethylene oxide.

• The hospital completed 3 rounds of post-reprocessing cultures on all duodenoscopes in service.– All cultures were negative for Enterobacteriaceae

Surveillance of CRE• Inpatient facilities should have an awareness of

whether or not CRE (at least E. coli and Klebsiella spp.) have ever been cultured from

ti t d itt d t th i f ilit d ifpatients admitted to their facility and, if so, whether these positive cultures were collected within 48 hours of admission.

• If CRE have been present, facilities should also determine:– If there is evidence of intra-facility transmission– Which wards/units are most affected

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Infection Prevention Considerations For Endoscopy Personnel

• To ensure that the facility has appropriate infection prevention policies and procedures in place and supplies to allow healthcare personnel to provide safe care.

• To systematically assess personnel adherence to correct infection prevention practices. Assessment of adherence should be conducted by direct observation of healthcare personnel during the performance of theirdirect observation of healthcare personnel during the performance of their duties. a. Facility Policies 7. Injection Safetyb. General IC Education and Training 8. Respiratory Hygienec. Occupational Health 9. Environmental Cleaningd. Surveillance and Disease Reporting 10. Reprocessing P & Pe. Hand Hygiene 11. Sterilization (Reusables)f. Personal Protective Equipment 12. High-Level Disinfection (Reusables)

http://www.cdc.gov/HAI/pdfs/guidelines/ambulatory-care-checklist-07-2011.pdf

Manufacturer’s Recommendations

Endoscope Reprocessing

• Worldwide endoscopy reprocessing varies greatly• India, of 133 endoscopy centers, only 1/3 performed

e en a minim m disinfection (1% gl t for 2 min)even a minimum disinfection (1% glut for 2 min)• Brazil, “a high standard …occur only exceptionally”• Western Europe, >30% did not adequately disinfect• Japan, found “exceedingly poor” disinfection protocols• US, 25% of endoscopes revealed >100,000 bacteria

Schembre DB. Gastroint Endoscopy 2000;10:215

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• While the FDA has cleared an endoscope cleaner and reprocessor (ECR) device which eliminates the need for manual cleaning – in 2007 the ASGE and SGNA expressed the following concern: “Members are cautioned about dispensing with manual washing and brushing steps before the capabilities of the new machine are confirmed in independent studies and clinical practice.”

• This was reiterated in 2009 by SGNA: “It is necessary to follow all steps for the manual cleaning of the endoscope prior to using an automated reprocessor. No independent confirmatory data are currently available to show that automated reprocessors are able to provide cleaning of endoscopes that is comparable to that of manual washing and brushing.”

Endoscope ReprocessingImpact of Human Factors

• Employee perception of the importance of endoscope reprocessing

• Least popular task – Leak Testing• Occupational health issue attributed to reprocessing• Occupational health issue attributed to reprocessing

endoscopes• Reprocessing efficiency – truncating selective steps to

move the process along• Significant difference in number of reprocessing steps

skips in manual vs automated reprocessing (p=0.001)• Alcohol flush and forced-air drying commonly skipped.

Ofstead CL, et al. Gastroenterol Nurs 2010;33;304-311

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ETO Sterilization Pros and Cons

• UPMC Presbyterian Hospital in Pittsburgh– researchers tracked an increase in antibiotic-resistant infections

among ERCP patients before determining that standard disinfection failed to entirely eliminate bacteria from the flexibledisinfection failed to entirely eliminate bacteria from the flexible scopes' channels. Sterilization with ethylene oxide likewise halted the infectious spread.

• "We are confident that the change from disinfection to sterilization of GI scopes is necessary in preventing serious infections and we are glad to share our findings with hospitals nationwide“ Carlene Muto, MD, MS, UPMC Presbyterian's director of infection prevention.

ETO Sterilization Pros and Cons• Sterilization’s long processing and aeration time,

the toxicity of some sterilizing agents to staff and patients, and its incompatibility with some d i k id d d ti lik ldevices make widespread adoption unlikely

• The FDA hasn’t cleared this technique for sterilizing endoscopes, many hospitals no longer carry ethylene oxide, and the 12- to 15-hour processing time is unwieldy.

ENDOSCOPE SAFETYQuality Control Issues

• Ensure protocols equivalent to guidelines from professional organizations (APIC, SGNA, ASGE)

• Are the staff who reprocess the endoscope ifi ll t i d i th t j b?specifically trained in that job?

• Are the staff competency tested at least annually?• Conduct IC rounds to ensure compliance with

policy• Consider microbiologic sampling of the

endoscope

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Final Considerations• Endoscopes represent a potential healthcare-

associated infection hazard• Proper cleaning and disinfection will prevent

transmission healthcare-acquired pathogens• Current guidelines should be strictly followed• Compliance must be monitored• Safety and efficacy of new technologies must be

validated

Questions?