KPC-53, a KPC-3 Variant of Clinical Origin Associated with Reduced Susceptibility to Ceftazidime-Avibactam

Antimicrob Agents Chemother. 2020 Dec 16;65(1):e01429-20. doi: 10.1128/AAC.01429-20. Print 2020 Dec 16.

Abstract

This study reports on the characterization of a Klebsiella pneumoniae clinical isolate showing high-level resistance to ceftazidime-avibactam associated with the production of KPC-53, a KPC-3 variant exhibiting a Leu167Glu168 duplication in the Ω-loop and a loss of carbapenemase activity. Whole-genome sequencing (WGS) revealed the presence of two copies of blaKPC-53, located on a pKpQIL-like plasmid and on a plasmid prophage of the Siphoviridae family, respectively. The present findings provide new insights into the mechanisms of resistance to ceftazidime-avibactam.

Keywords: CZA resistance; carbapenem-resistant Enterobacterales; mutant KPC carbapenemase; phagemid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Azabicyclo Compounds / pharmacology
  • Bacterial Proteins / genetics
  • Ceftazidime / pharmacology
  • Drug Combinations
  • Drug Resistance, Multiple, Bacterial / genetics
  • Humans
  • Klebsiella Infections* / drug therapy
  • Klebsiella pneumoniae / genetics
  • Microbial Sensitivity Tests
  • beta-Lactamases / genetics

Substances

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