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

Abstract

Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant <i>Enterobacteriaceae</i> (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 <i>Enterobacteriaceae</i> bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (<i>cps</i>), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation. The prevalences of carbapenem resistance among <i>Klebsiella pneumoniae</i>, <i>Enterobacter</i> spp., and <i>Escherichia coli</i> bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were <i>K. pneumoniae</i> and 92% produced <i>K. pneumoniae</i> carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing <i>K. pneumoniae</i> (KPC-<i>Kp</i>). The <i>wzi154</i> allele, corresponding to <i>cps-2</i>, was present in 93% of KPC-3-<i>Kp</i>, whereas KPC-2-<i>Kp</i> had greater <i>cps</i> diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-<i>Kp</i> 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-<i>Kp</i> bacteremia (adjusted odds ratio [aOR], 2.58; <i>P</i> = 0.045), cancer (aOR, 3.61, <i>P</i> = 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79; <i>P</i> = 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.