Correlation of β-Lactamase Production and Colistin Resistance among Enterobacteriaceae Isolates from a Global Surveillance Program

Antimicrob Agents Chemother. 2015 Dec 14;60(3):1385-92. doi: 10.1128/AAC.01870-15.

Abstract

The increasing use of carbapenems for treating multidrug-resistant (MDR) Gram-negative bacterial infections has contributed to the global dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Serine and metallo-β-lactamases (MBLs) that hydrolyze carbapenems have become prevalent and endemic in some countries, necessitating the use of older classes of agents, such as colistin. A total of 19,719 isolates of Enterobacteriaceae (excluding Proteeae and Serratia spp., which have innate resistance to colistin) were collected from infected patients during 2012 and 2013 in a global surveillance program and tested for antimicrobial susceptibility using CLSI methods. Isolates of CRE were characterized for carbapenemases and extended-spectrum β-lactamases (ESBLs) by PCR and sequencing. Using EUCAST breakpoints, the rate of colistin susceptibility was 98.4% overall, but it was reduced to 88.0% among 482 carbapenemase-positive isolates. Colistin susceptibility was higher among MBL-positive isolates (92.6%) than those positive for a KPC (87.9%) or OXA-48 (84.2%). Of the agents tested, only tigecycline (MIC90, 2 to 4 μg/ml) and aztreonam-avibactam (MIC90, 0.5 to 1 μg/ml) consistently tested with low MIC values against colistin-resistant, ESBL-positive, and carbapenemase-positive isolates. Among the 309 (1.6%) colistin-resistant isolates from 10 species collected in 38 countries, 58 carried a carbapenemase that included KPCs (38 isolates), MBLs (6 isolates), and OXA-48 (12 isolates). These isolates were distributed globally (16 countries), and 95% were Klebsiella pneumoniae. Thirty-nine (67.2%) isolates carried additional ESBL variants of CTX-M, SHV, and VEB. This sample of Enterobacteriaceae demonstrated a low prevalence of colistin resistance overall. However, the wide geographic dispersion of colistin resistance within diverse genus and species groups and the higher incidence observed among carbapenemase-producing MDR pathogens are concerning.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / metabolism
  • Colistin / pharmacology*
  • Drug Resistance, Bacterial / drug effects*
  • Enterobacteriaceae / drug effects*
  • Enterobacteriaceae / isolation & purification
  • Enterobacteriaceae / metabolism
  • Enterobacteriaceae Infections / microbiology
  • Humans
  • Microbial Sensitivity Tests
  • beta-Lactamases / metabolism*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • beta-Lactamases
  • carbapenemase
  • Colistin

Grants and funding

This investigation was funded by AstraZeneca Pharmaceuticals as part of a sponsored global surveillance program. The sponsor approved the overall study design. All investigative sites were recruited and study supplies were provided by IHMA, Inc. Analysis of the final MIC and molecular data was performed by IHMA, Inc., and was independent of sponsor analysis for this study.