First report of KPC variants conferring ceftazidime-avibactam resistance in Colombia: introducing KPC-197

Microbiol Spectr. 2024 Jun 4;12(6):e0410523. doi: 10.1128/spectrum.04105-23. Epub 2024 May 3.

Abstract

Resistance to ceftazidime-avibactam (CZA) due to Klebsiella pneumoniae carbapenemase (KPC) variants is increasing worldwide. We characterized two CZA-resistant clinical Klebsiella pneumoniae strains by antimicrobial susceptibility test, conjugation assays, and WGS. Isolates belonged to ST258 and ST45, and produced a KPC-31 and a novel variant KPC-197, respectively. The novel KPC variant presents a deletion of two amino acids on the Ω-loop (del_168-169_EL) and an insertion of two amino acids in position 274 (Ins_274_DS). Continued surveillance of KPC variants conferring CZA resistance in Colombia is warranted.

Importance: Latin America and the Caribbean is an endemic region for carbapenemases. Increasingly high rates of Klebsiella pneumoniae carbapenemase (KPC) have established ceftazidime-avibactam (CZA) as an essential antimicrobial for the treatment of infections due to MDR Gram-negative pathogens. Although other countries in the region have reported the emergence of CZA-resistant KPC variants, this is the first description of such enzymes in Colombia. This finding warrants active surveillance, as dissemination of these variants could have devastating public health consequences.

Keywords: KPC variants; Klebsiella pneumoniae; ceftazidime/avibactam; whole genome sequencing.

MeSH terms

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

Substances

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