Global Dissemination of blaKPC into Bacterial Species beyond Klebsiella pneumoniae and In Vitro Susceptibility to Ceftazidime-Avibactam and Aztreonam-Avibactam

Antimicrob Agents Chemother. 2016 Jul 22;60(8):4490-500. doi: 10.1128/AAC.00107-16. Print 2016 Aug.

Abstract

The Klebsiella pneumoniae carbapenemase (KPC), first described in the United States in 1996, is now a widespread global problem in several Gram-negative species. A worldwide surveillance study collected Gram-negative pathogens from 202 global sites in 40 countries during 2012 to 2014 and determined susceptibility to β-lactams and other class agents by broth microdilution testing. Molecular mechanisms of β-lactam resistance among carbapenem-nonsusceptible Enterobacteriaceae and Pseudomonas aeruginosa were determined using PCR and sequencing. Genes encoding KPC enzymes were found in 586 isolates from 22 countries (76 medical centers), including countries in the Asia-Pacific region (32 isolates), Europe (264 isolates), Latin America (210 isolates), and the Middle East (19 isolates, Israel only) and the United States (61 isolates). The majority of isolates were K. pneumoniae (83.4%); however, KPC was detected in 13 additional species. KPC-2 (69.6%) was more common than KPC-3 (29.5%), with regional variation observed. A novel KPC variant, KPC-18 (KPC-3[V8I]), was identified during the study. Few antimicrobial agents tested remained effective in vitro against KPC-producing isolates, with ceftazidime-avibactam (MIC90, 4 μg/ml), aztreonam-avibactam (MIC90, 0.5 μg/ml), and tigecycline (MIC90, 2 μg/ml) retaining the greatest activity against Enterobacteriaceae cocarrying KPC and other β-lactamases, whereas colistin (MIC90, 2 μg/ml) demonstrated the greatest in vitro activity against KPC-positive P. aeruginosa This analysis of surveillance data demonstrated that KPC is widely disseminated. KPC was found in multiple species of Enterobacteriaceae and P. aeruginosa and has now become a global problem.

MeSH terms

  • Azabicyclo Compounds / pharmacology*
  • Aztreonam / pharmacology*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Ceftazidime / pharmacology*
  • Drug Combinations
  • Enterobacteriaceae / drug effects
  • Enterobacteriaceae / enzymology
  • Enterobacteriaceae / genetics
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / enzymology
  • Klebsiella pneumoniae / genetics
  • Microbial Sensitivity Tests
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / enzymology
  • Pseudomonas aeruginosa / genetics
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism

Substances

  • Azabicyclo Compounds
  • Bacterial Proteins
  • Drug Combinations
  • avibactam, ceftazidime drug combination
  • avibactam
  • Ceftazidime
  • beta-Lactamases
  • carbapenemase
  • Aztreonam

Grants and funding

This investigation was funded by AstraZeneca Pharmaceuticals as part of a 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.