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. 2017 Mar 24;61(4):e02349-16.
doi: 10.1128/AAC.02349-16. Print 2017 Apr.

Multicenter Clinical and Molecular Epidemiological Analysis of Bacteremia Due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE Epicenter of the United States

Michael J Satlin  1 , Liang Chen  2 , Gopi Patel  3 , Angela Gomez-Simmonds  4 , Gregory Weston  5 , Angela C Kim  6 , Susan K Seo  7 , Marnie E Rosenthal  8   9 , Steven J Sperber  10 , Stephen G Jenkins  11 , Camille L Hamula  12 , Anne-Catrin Uhlemann  4 , Michael H Levi  13 , Bettina C Fries  5   14 , Yi-Wei Tang  15 , Stefan Juretschko  16 , Albert D Rojtman  17 , Tao Hong  18 , Barun Mathema  19 , Michael R Jacobs  20 , Thomas J Walsh  21   22 , Robert A Bonomo  23   24 , Barry N Kreiswirth  2
Affiliations

Multicenter Clinical and Molecular Epidemiological Analysis of Bacteremia Due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE Epicenter of the United States

Michael J Satlin et al. Antimicrob Agents Chemother. .

Abstract

Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among Enterobacteriaceae bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (cps), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation. The prevalences of carbapenem resistance among Klebsiella pneumoniae, Enterobacter spp., and Escherichia coli bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were K. pneumoniae and 92% produced K. pneumoniae carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing K. pneumoniae (KPC-Kp). The wzi154 allele, corresponding to cps-2, was present in 93% of KPC-3-Kp, whereas KPC-2-Kp had greater cps diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-Kp had an CAZ-AVI MIC of ≥4/4 μg/ml. There was a median of 47 h from bacteremia onset until active antimicrobial therapy, 38% of patients had septic shock, and 49% died within 30 days. KPC-3-Kp bacteremia (adjusted odds ratio [aOR], 2.58; P = 0.045), cancer (aOR, 3.61, P = 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79; P = 0.03) were independently associated with mortality. Active empirical therapy and combination therapy were not associated with survival. Despite a decade of experience with CRE, patients with CRE bacteremia have protracted delays in appropriate therapies and high mortality rates, highlighting the need for rapid diagnostics and evaluation of new therapeutics.

Keywords: carbapenem-resistant Enterobacteriaceae; clinical outcomes; molecular epidemiology; resistance mechanisms.

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Figures

FIG 1
FIG 1
Multilocus sequence types (MLST) (a) and wzi gene alleles, stratified by MLST and KPC type (b), among carbapenem-resistant Klebsiella pneumoniae.
See this image and copyright information in PMC

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