Molecular mechanisms underlying bacterial resistance to ceftazidime/avibactam

WIREs Mech Dis. 2022 Nov;14(6):e1571. doi: 10.1002/wsbm.1571. Epub 2022 Jul 26.

Abstract

Ceftazidime/avibactam (CAZ/AVI), a combination of ceftazidime and a novel β-lactamase inhibitor (avibactam) that has been approved by the U.S. Food and Drug Administration, the European Union, and the National Regulatory Administration in China. CAZ/AVI is used mainly to treat complicated urinary tract infections and complicated intra-abdominal infections in adults, as well as to treat patients infected with Carbapenem-resistant Enterobacteriaceae (CRE) susceptible to CAZ/AVI. However, increased clinical application of CAZ/AVI has resulted in the development of resistant strains. Mechanisms of resistance in most of these strains have been attributed to blaKPC mutations, which lead to amino acid substitutions in β-lactamase and changes in gene expression. Resistance to CAZ/AVI is also associated with reduced expression and loss of outer membrane proteins or overexpression of efflux pumps. In this review, the prevalence of CAZ/AVI-resistance bacteria, resistance mechanisms, and selection of detection methods of CAZ/AVI are demonstrated, aiming to provide scientific evidence for the clinical prevention and treatment of CAZ/AVI resistant strains, and provide guidance for the development of new drugs. This article is categorized under: Infectious Diseases > Molecular and Cellular Physiology.

Keywords: ceftazidime/avibactam; efflux pump; outer membrane protein; resistance mechanism; β-lactamase.

Publication types

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

MeSH terms

  • Adult
  • Anti-Bacterial Agents* / pharmacology
  • Ceftazidime* / pharmacology
  • Humans
  • Microbial Sensitivity Tests
  • beta-Lactamases / genetics

Substances

  • Ceftazidime
  • avibactam
  • Anti-Bacterial Agents
  • beta-Lactamases