Global trends of ceftazidime-avibactam resistance in gram-negative bacteria: systematic review and meta-analysis

The emergence of antimicrobial resistance in Gram-negative bacteria (GNB) is a major global concern. Ceftazidime-avibactam (CAZ-AVI) has been identified as a potential treatment option for complicated infections.

This meta-analysis aimed to evaluate the global resistance proportions of GNB to CAZ-AVI comprehensively.

Studies were searched in Scopus, PubMed, and EMBASE (until September 2024), and statistical analyses were conducted using STATA software (version 20.0).

CAZ-AVI resistance proportions were determined in 136 studies, with 25.8% (95% CI 22.2-29.7) for non-fermentative gram-negative bacilli and 6.1% (95% CI 4.9-7.4) for Enterobacterales. The CAZ-AVI resistance proportion significantly increased from 5.6% (95% CI 4.1-7.6) of 221,278 GNB isolates in 2015-2020 to 13.2% (95% CI 11.4-15.2) of 285,978 GNB isolates in 2021-2024. Regionally, CAZ-AVI resistance was highest in Asia 19.3% (95% CI 15.7-24.23.4), followed by Africa 13.6% (95% CI 5.6-29.2), Europe 11% (95% CI 7.8-15.2), South America 6.1% (95% CI 3.2-11.5) and North America 5.3% (95% CI 4.2-6.7). Among GNB resistance profiles, colistin-resistant isolates and XDR isolates exhibited the highest resistance proportions (37.1%, 95% CI 14-68 and 32.1%, 95% CI 18.5-49.6), respectively), followed by carbapenem-resistant isolates and MDR isolates [(25.8%, 95% CI 22.6-29.3) and (13%, 95% CI 9.6, 17.3)].

A high proportion of GNB isolates from urinary tract infections remained susceptible to CAZ-AVI, indicating its potential as a suitable treatment option. However, the increasing resistance trends among GNB are concerning and warrant continuous monitoring to maintain CAZ-AVI's effectiveness against GNB infections.