Real-world study of adverse events associated with ceftazidime/avibactam based on the U.S. Food and Drug...

Ceftazidime/avibactam (CZA), a combination of the third-generation cephalosporin ceftazidime and the novel, non-β-lactam β-lactamase inhibitor avibactam, was widely used in the treatment of multidrug-resistant (MDR) Gram-negative bacterial pathogens. In light of the growing prevalence of MDR Gram-negative bacterial infection, it is imperative to gain a deeper understanding of the true extent of adverse events (AEs) associated with CZA.

AE reports primarily associated with CZA were retrieved from the Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2015 to the first quarter of 2025, and all AEs were extracted. AE signal detection was conducted using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) methods. Additionally, a multivariable logistic regression analysis was performed to evaluate the safety of CZA combined with meropenem, explicitly adjusting for confounders such as age, sex, and concomitant nephrotoxins.

A total of 2,444 AE reports with CZA as the preferred suspected drug were obtained, identifying 89 preferred terms (PTs) involving 24 system organ classes (SOCs). The ratio of males to females was approximately two times higher in all cases, with the highest number of reports originating from China. Some significant AE signals have been revealed by four methods, including renal and urinary disorders (n = 112, ROR 2.49, PRR 2.43, EBGM 2.43, IC 1.28) and hepatobiliary disorders (n = 98, ROR 5.04, PRR 4.88, EBGM 4.88, IC 2.29). Regarding combination therapy with meropenem, multivariable analysis revealed a specific safety signal: the risk of respiratory failure remained significantly elevated [adjusted OR (aOR) 3.26, P = 0.038] independent of baseline severity. Conversely, acute kidney injury showed no significant association (aOR 1.07, P = 0.868), suggesting that the respiratory risk is pharmacodynamically driven rather than a result of generalized clinical deterioration.

The present study identified significant and novel AEs signals for CZA. Notably, the specific association between the CZA-meropenem combination and respiratory failure warrants vigilant clinical monitoring, distinct from general disease progression risks.