Emergence of carbapenem-resistant Enterobacteriaceae as causes of bloodstream infections in patients with hematologic malignancies

Abstract

Carbapenem-resistant Enterobacteriaceae (CRE) are increasingly prevalent pathogens. However, little is known about their emergence in patients with hematologic malignancies. We identified 18 patients with hematologic malignancies over 3.5 years who developed bloodstream infections (BSIs) caused by CRE. Fourteen BSIs were caused by Klebsiella pneumoniae, three by Enterobacter cloacae, and one was polymicrobial. Initial empirical antimicrobial therapy was active in two patients (11%), and a median of 55 h elapsed between culture collection and receipt of an active agent. Ten patients (56%) died, including nine (69%) of 13 neutropenic patients, with a median of 4 days from culture collection until death. CRE isolates were analyzed for carbapenemase production, β-lactamase genes and outer membrane porin deletions and characterized by multilocus sequence typing and pulsed-field gel electrophoresis (PFGE). Carbapenem resistance mechanisms included Klebsiella pneumoniae carbapenemase production and CTX-M-15 production with an absent outer membrane porin protein. No isolate had ≥95% homology on PFGE, indicating a heterogeneous, non-outbreak population of isolates. CRE BSIs are emerging in patients with hematologic malignancies and are associated with ineffective initial empirical therapy, long delays in administration of active antimicrobials and high mortality rates. New diagnostic, therapeutic and preventive strategies for CRE infections in this vulnerable population are needed.