Characterization of KPC-82, a KPC-2 Variant Conferring Resistance to Ceftazidime-Avibactam in a Carbapenem-Nonsusceptible Clinical Isolate of Citrobacter koseri

Antimicrob Agents Chemother. 2021 Jun 17;65(7):e0015021. doi: 10.1128/AAC.00150-21. Epub 2021 Jun 17.

Abstract

KPC-82 is a KPC-2 variant identified in a carbapenem-nonsusceptible Citrobacter koseri that confers high-level resistance to ceftazidime-avibactam. Genomic analysis revealed that blaKPC-82 is carried by a chromosomally integrated Tn4401 transposon (disrupting porin gene phoE) and evolved by a 6-nucleotide tandem repeat duplication causing a two-amino-acid insertion (Ser-Asp) within the Ala267-Ser275 loop. Similar to related KPC variants, KPC-82 showed decreased carbapenemase activity when expressed in a heterologous background and remained susceptible to carbapenem/β-lactamase inhibitor combinations.

Keywords: CRE; Citrobacter koseri; KPC; carbapenems; ceftazidime-avibactam.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Azabicyclo Compounds / pharmacology
  • Bacterial Proteins / genetics
  • Carbapenems* / pharmacology
  • Ceftazidime / pharmacology
  • Citrobacter koseri*
  • Drug Combinations
  • Klebsiella pneumoniae
  • Microbial Sensitivity Tests
  • beta-Lactamases / genetics

Substances

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