Klebsiella pneumoniae carbapenemase variants: the new threat to global public health

Clin Microbiol Rev. 2023 Dec 20;36(4):e0000823. doi: 10.1128/cmr.00008-23. Epub 2023 Nov 8.

Abstract

Klebsiella pneumoniae carbapenemase (KPC) variants, which refer to the substitution, insertion, or deletion of amino acid sequence compared to wild blaKPC type, have reduced utility of ceftazidime-avibactam (CZA), a pioneer antimicrobial agent in treating carbapenem-resistant Enterobacterales infections. So far, more than 150 blaKPC variants have been reported worldwide, and most of the new variants were discovered in the past 3 years, which calls for public alarm. The KPC variant protein enhances the affinity to ceftazidime and weakens the affinity to avibactam by changing the KPC structure, thereby mediating bacterial resistance to CZA. At present, there are still no guidelines or expert consensus to make recommendations for the diagnosis and treatment of infections caused by KPC variants. In addition, meropenem-vaborbactam, imipenem-relebactam, and other new β-lactam-β-lactamase inhibitor combinations have little discussion on KPC variants. This review aims to discuss the clinical characteristics, risk factors, epidemiological characteristics, antimicrobial susceptibility profiles, methods for detecting blaKPC variants, treatment options, and future perspectives of blaKPC variants worldwide to alert this new great public health threat.

Keywords: Klebsiella pneumoniae; blaKPC variants; ceftazidime-avibactam.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Drug Combinations
  • Klebsiella pneumoniae* / genetics
  • Microbial Sensitivity Tests
  • Public Health*
  • beta-Lactamase Inhibitors / pharmacology
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism

Substances

  • carbapenemase
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • beta-Lactamases
  • beta-Lactamase Inhibitors
  • Drug Combinations