KPC-39-Mediated Resistance to Ceftazidime-Avibactam in a Klebsiella pneumoniae ST307 Clinical Isolate

Antimicrob Agents Chemother. 2021 Nov 17;65(12):e0116021. doi: 10.1128/AAC.01160-21. Epub 2021 Oct 4.

Abstract

Resistance to the ceftazidime (CAZ)-avibactam (AVI) combination is increasingly being reported. Here, we report a CAZ-AVI-resistant Klebsiella pneumoniae strain belonging to the high-risk sequence type 307 (ST307) clone and producing Klebsiella pneumoniae carbapenemase 39 (KPC-39), a single-amino-acid variant of KPC-3 (A172T). Cloning experiments, steady-state kinetic parameters, and molecular dynamics simulations revealed a loss of carbapenemase activity and increased affinity for CAZ. KPC-39 was identified in a patient without prior exposure to CAZ-AVI, suggesting silent dissemination in European health care settings.

Keywords: KPC; avibactam resistance; carbapenemase.

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
  • 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
  • carbapenemase