309 Carbapenemase-producing Enterobacteriaceae: Identification, Epidemiology and Risk Factors at the Johns Hopkins Hospital

Friday, March 19, 2010
Grand Hall (Hyatt Regency Atlanta)
Tal E. Berkowitz, MPH , Johns Hopkins University, Baltimore, MD
Andrew Lee, MHS , Johns Hopkins University, Baltimore, MD
Elaine Fadden , Johns Hopkins Hospital, Baltimore, MD
Warren C. Lee , Johns Hopkins University, Baltimore, MD
Paul D. Stamper, MPH , Johns Hopkins Hospital, Baltimore, MD
Tsigereda Tekle, MT , Johns Hopkins Hospital, Baltimore, MD
Karen C. Carroll, MD , Johns Hopkins Hospital, Baltimore, MD
Lisa L. Maragakis, MD, MPH , Johns Hopkins University, Baltimore, MD
Background: Carbapenemase-producing Enterobacteriaceae (CPE) are emerging MDR pathogens in the healthcare setting.   The CDC recently published guidelines for hospitals to control CPE through infection control practices and surveillance.

Objective: To identify CPE and define the epidemiology of and risk factors for these organisms in a tertiary care hospital in Baltimore.

Methods: Starting in October 2007, all Enterobacteriaceae except Proteus sp., Morganella morganii, and Providencia sp. were screened for carbapenemase production.    Initial identification and susceptibility testing was performed using Phoenix (BD Diagnostics, Sparks, MD).  Isolates identified as resistant to at least one carbapenem agent and to one or more agents in cephalosporin subclass III were referred for carbapenemase testing by modified Hodge test (MHT) according to CLSI guidelines.  MHT positive isolates by were tested for KPC2 by a published real-time PCR method.  Susceptibility testing for tigecycline and colistin was performed using E-test and/or a tube dilution method.  A case- control study was performed.  Data were collected from the medical records of 44 patients whose clinical cultures grew CPE between October 1, 2007 and September 30, 2009.  Controls patients were randomly selected from patients admitted to the hospital during the study period for at least as long as the exposure time of case patients.  Cases and controls were matched on exposure time in a 1:1 ratio.

Results: Over an 18 month period, 245 unique isolates contributed by 114 patients met our criteria for testing by MHT. Ninety-eight (40%) were MHT positive: Enterobacter sp. 66/149(44.3%), Klebsiella sp. 24/58(41.4%), Citrobacter sp. 5/17(29.4%), Serratia sp. 1/4 (25%), and E. coli 2/17 (11.8%).  97 MHT positive isolates were tested by PCR and 87(89.7%) were confirmed as KPC2. Among KPC2-PCR positive isolates, 74% were tigecycline susceptible and 93% had colistin MICs of <= 1ug/ml.  The average age of case patients in the study was 57.4 years and 45% were female.  19 (43%) case patients grew CPE from cultures of sputum, 12 (27%) grew it in urine, and 4 patients had bacteremia.  52% of the case patients died during the hospitalization compared with 11% of the controls (p<.001).  Severity of illness assessed with a modified APACHE III score (OR=1.06, CI 1.01-1.09)) and solid organ transplantation (OR=5.34, CI 1.3-22) were independent risk factors for CPE acquisition after controlling for receipt of broad spectrum antimicrobial agents.

Conclusions: CPE occur in our hospital among a variety of different species, primarily Enterobacter  sp. in contrast to other locales reporting Klebsiella as the primary isolates.   Case patients had a high crude mortality.  Solid organ transplantation was a significant, independent risk factor for CPE acquisition.  Screening for CPE with MHT is important to identify organisms that would otherwise not be recognized.