Post-market safety profile of cefiderocol: a real-world pharmacovigilance exploratory analysis based on U.S. FDA...

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).

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.

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.

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.