A Real-World Pharmacovigilance Study of Ceftazidime/avibactam: Data Mining of the FDA Adverse Event Reporting System (FAERS) Database

Abstract

Abstract Introduction Ceftazidime/avibactam (CAZ/AVI) is a combination of a well-known third-generation, broad-spectrum cephalosporin with a new beta-lactamase inhibitor that has been approved for the treatment of various infectious diseases (especially MDR-GNB infections) by the FDA. Aim The present study extensively assessed real-world CAZ/AVI-related adverse events (AEs) through data mining of the FDA Adverse Event Reporting System (FAERS) database to better understand toxicities. Methods The signals of CAZ/AVI-related AEs were quantified using disproportionality analyses, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN) and the multi-item gamma Poisson shrinker (MGPS) algorithms. System organ classifications (SOCs) and preferred terms (PTs) from the Medical Dictionary for Regulatory Activities (MedDRA) were used in the definition. Results A total of 628 instances of CAZ/AVI-related AEs were identified among 10,114,815 records gathered from the FAERS database. A total of 61 PTs with significant disproportionality that simultaneously met the criteria of all four algorithms were retained. Several unexpected safety signals may also occur, including melaena, hypernatraemia, depressed level of consciousness, brain oedema, petechiae, delirium, and shock haemorrhagic. The median onset time for AEs associated with CAZ/AVI was 4 days, with nearly half cases occurring within 3 days after CAZ/AVI initiation. Conclusions Some of our research findings were consistent with the information described in drug labels and monographs, and we also discovered potential novel and unexpected AE signals associated with CAZ/AVI. Future clinical investigations are needed to validate our findings and establish their relationship. Our findings might serve as important supporting data for future CAZ/AVI safety investigations.