Resistance to ceftazidime-avibactam and underlying mechanisms

J Glob Antimicrob Resist. 2020 Sep:22:18-27. doi: 10.1016/j.jgar.2019.12.009. Epub 2019 Dec 19.

Abstract

Objective: Ceftazidime-avibactam (CAZ-AVI) is a novel synthetic β-lactamase inhibitor combination. Although the combination has been available clinically for only a few years, cases of resistance to CAZ-AVI have already been reported.

Methods: In the present review, we summarize the distribution of CAZ-AVI-resistant strains and the possible resistance mechanisms.

Results: There are no significant differences in CAZ-AVI resistance rates across different regions. CAZ-AVI maintains good activity against Gram-negative bacteria, especially Enterobacteriaceae. Pseudomonas aeruginosa is less susceptible to CAZ-AVI compared with Enterobacteriaceae, with a resistance rate ranging from 2.9 to 18%. The resistance to CAZ-AVI exceeds 50% in Acinetobacter baumannii. A higher resistance rate to CAZ-AVI is associated with carbapenem resistance. Moreover, β-lactamase-related amino acid substitutions are the main mechanisms that lead to CAZ-AVI resistance. Membrane protein amino acid substitutions and efflux pumps also play important roles in CAZ-AVI resistance.

Conclusions: To maintain its efficacy, CAZ-AVI should not be used for pathogens that are naturally resistant to it. For CAZ-AVI-resistant strains, other effective antibacterial agents or CAZ-AVI in combination with other antibacterial agents should be considered.

Keywords: Antimicrobial strategies; Ceftazidime–avibactam; Resistance mechanisms; Resistance rate; β-Lactamases.

Publication types

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

MeSH terms

  • Azabicyclo Compounds* / pharmacology
  • Ceftazidime* / pharmacology
  • Drug Combinations
  • Microbial Sensitivity Tests

Substances

  • Azabicyclo Compounds
  • Drug Combinations
  • avibactam, ceftazidime drug combination
  • Ceftazidime