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 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 Ն4/4 g/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 ϭ 0.045), cancer (aOR, 3.61, P ϭ 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79; P ϭ 0.03) were independently associated with mortality. Active empirical ther-

Ceftazidime-Avibactam Is Superior to Other Treatment Regimens against Carbapenem-Resistant Klebsiella pneumoniae Bacteremia

“…At these centers, mortality rates for CRE bacteremia in 2013 (before availability of C-A) were unchanged from those a decade earlier (11). Notably, time to receipt of active treatment in our study was not an independent predictor of clinical success or survival.…”

<b><i>Pseudomonas aeruginosa</i></b> and <b><i>Klebsiella</i></b> <b><i>pneumoniae</i></b> Adaptation to Innate Immune Clearance Mechanisms in the Lung

“…Carbapenem-resistant (CRKP) and even colistin-resistant strains have become more endemic, colonizing healthy humans [61]. As an opportunist, these MDR organisms can cause severe disease that is often difficult to treat, associated with persistent bacteremia and high mortality, and disproportionately affecting patients with comorbidities and critical illness (> 50%) [62]. …”

Two for the price of one: emerging carbapenemases in a returning traveller to New York City

“…The most common CRE types isolated in the USA are class A, K. pneumoniae carbapenemases 7. NDM-1 is a metallo-β-lactamase (MBL) endemic to South Asia, which is infrequently encountered in the USA.…”