Molecular mechanisms underlying bacterial resistance to ceftazidime/avibactam.
Luying XiongXueting WangYuan WangWei YuYanzi ZhouXiaohui ChiTingting XiaoYong-Hong XiaoPublished in: WIREs mechanisms of disease (2022)
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 bla KPC 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.
Keyphrases
- klebsiella pneumoniae
- gram negative
- escherichia coli
- multidrug resistant
- gene expression
- urinary tract infection
- infectious diseases
- drug administration
- amino acid
- poor prognosis
- cell proliferation
- newly diagnosed
- transcription factor
- risk factors
- pseudomonas aeruginosa
- prognostic factors
- chronic kidney disease
- climate change
- cystic fibrosis
- smoking cessation