Lin Hao, Zhu Chen, Liu Shuang, Bi Yingmin, Hu Jindong, Ju Mohan
Department of Oncology, Huashan Hospital, Fudan University, Shanghai, China.
Department of Hematology, Huashan Hospital, Fudan University, Shanghai, China.
BMC Pharmacol Toxicol. 2025 Mar 11;26(1):58. doi: 10.1186/s40360-025-00894-3.
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.
头孢地尔是一类新型药物，已被批准用于治疗革兰氏阴性菌感染。其获批上市为临床医生治疗耐抗菌药物革兰氏阴性菌感染提供了更多选择。我们研究的目的是通过挖掘美国食品药品监督管理局不良事件报告系统（FAERS）的数据，评估头孢地尔在现实世界中的安全性。
我们纳入了2019年第4季度（2019Q4）至2024年第3季度（2024Q3）提交给FAERS的有关头孢地尔的不良事件（AE）报告。进行了不成比例分析，包括报告比值比（ROR）、比例报告比（PRR）、贝叶斯置信传播神经网络（BCPNN）和多项目伽马泊松收缩器（MGPS）技术，以识别接受头孢地尔治疗的患者中不良事件报告不成比例的信号。如果ROR的95%置信区间（CI）下限>1、PRR≥2（而PRR的卡方≥4）、信息成分（IC025）的95%CI下限>0、经验贝叶斯几何均值（EBGM05）的95%CI下限>2且报告了至少3例不良事件，则检测到报告不成比例的信号。
从FAERS数据库收集的592份与头孢地尔相关的不良事件（AE）报告中，共确定了29个显著的首选术语（PTs）。头孢地尔引起的不良事件涉及24个系统器官类别（SOC）。还呈现了29个报告不成比例的阳性信号，如病原体耐药（n = 16，ROR 189.35，PRR 184.26，IC 7.52，EBGM 183.89）、全身性念珠菌感染（n = 3，ROR 138.79，PRR 138.19，IC7.11，EBGM 137.88）、耐药性（n = 30，ROR 131.96，PRR 125.33，IC6.97，EBGM 125.16）和药物效果低于预期（n = 6，ROR 68.42，PRR 67.74，IC6.08，EBGM 67.69）。最常观察到的是死亡、耐药性和治疗失败。
我们的研究结果为头孢地尔在现实世界中的安全性提供了重要证据。这些信息可能有助于临床医生和药剂师提高警惕，并在临床实践中提高头孢地尔的整体安全性。
