Post-market safety profile of cefiderocol: a real-world pharmacovigilance exploratory analysis based on U.S. FDA adverse event reporting system (FAERS).

Abstract

Background: Cefiderocol is a new drug class, which is approved to treat Gram-negative bacteria infection. Its approval for marketing has provided clinicians with additional options for treating antimicrobial resistant gram-negative infections. The aim of our study was to assess the safety profiles of cefiderocol in real-world through data mining of the United States Food and Drug Administration Adverse Event Reporting System (FAERS).

Methods: We included adverse event (AE) reports regarding cefiderocol submitted to the FAERS from 2019 quarter 4 (2019Q4) to 2024 quarter 3 (2024Q3). Disproportionality analyses, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN) and Multi-item Gamma Poisson Shrinker (MGPS) techniques were performed to identify the signals of disproportionate reporting of AEs in patients receiving cefiderocol. A signal of disproportionate reporting was detected if the lower limit of the 95% confidence interval (CI) of ROR > 1, the PRR was ≥ 2(while the Chi-Square of PRR was ≥ 4), the lower limit of 95% CI of the information component (IC025) was > 0, the lower limit of 95% CI of the Empirical Bayes Geometric Mean (EBGM05) was > 2 and at least 3 AEs were reported.

Results: A total of 29 significant preferred terms (PTs) were identified among the 592 cefiderocol-associated adverse events (AEs) reports collected from the FAERS database. Cefiderocol-induced adverse events involved 24 System Organ Class (SOC). 29 positive signals of disproportionate reporting are also presented, such as Pathogen resistance (n = 16, ROR 189.35, PRR 184.26, IC 7.52, EBGM 183.89), Systemic candida (n = 3, ROR 138.79, PRR 138.19, IC7.11, EBGM 137.88), Drug resistance (n = 30, ROR 131.96, PRR 125.33, IC6.97, EBGM 125.16), and Drug effect less than expected (n = 6, ROR 68.42, PRR 67.74, IC6.08, EBGM 67.69). The most frequently observed were Death, Drug resistance and Treatment failure.

Conclusions: Our findings offer significant evidence regarding the safety profile of cefiderocol in real-world settings. This information may assist clinicians and pharmacists in enhancing their vigilance and improving the overall safety of cefiderocol in clinical practice.