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

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