Department of Pharmacy, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China; Department of Pharmacy, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
Int J Antimicrob Agents. 2024 Oct;64(4):107288. doi: 10.1016/j.ijantimicag.2024.107288. Epub 2024 Jul 31.
Antibiotic utilization stands as the strongest modifiable determinant for Clostridioides difficile infection (CDI). However, previous studies have relied on aggregated antibiotic categories, leaving prescribers without detailed comparative risk information for individual antibiotics. The objective of this study was to estimate the risk of CDI comprehensively across specific antibiotics.
Two methodologies were integrated to access and rank the risk of CDI associated with individual antibiotics or classes. Initially, a network comparison was conducted by analysing data from randomized controlled trials (RCTs). Subsequently, a real-world disproportionality analysis using the Food and Drug Adverse Event Reporting System (FAERS) database complemented and enriched the findings from RCTs.
The network comparison, encompassing 61 RCTs with 25,931 patients, revealed that exposure to cefepime [odds ratio (OR) 2.56, 95% confidence interval (CI) 1.20-5.44; P=0.02] and imipenem/cilastatin (OR 3.86, 95% CI 1.61-9.29; P=0.003) exhibited higher frequencies of CDI compared with piperacillin/tazobactam. No significant differences were observed between the carbapenems, albeit a trend indicating higher incidence of CDI with imipenem/cilastatin compared with meropenem (OR 3.89, 95% CI 0.94-16.09). In the FAERS disproportionality analysis, nearly all antibiotics displayed associations with CDI, and CDI risk signals often clustered within the majority of antibiotic classes. Among these, lincomycin demonstrated the strongest association (OR 112.17, 95% CI 51.68-243.43). Additionally, oral third-generation cephalosporins tended to exhibit higher CDI risk signals than other antibiotics.
The findings unveiled substantial diversity in the risk of CDI, both within and between antibiotic classes, providing valuable guidance for clinicians in antibiotic prescription decisions and for initiatives aimed at antibiotic stewardship.
抗生素的使用是艰难梭菌感染（CDI）最强的可改变决定因素。然而，之前的研究依赖于聚合的抗生素类别，使医生无法获得有关个别抗生素的详细比较风险信息。本研究的目的是全面评估特定抗生素与 CDI 相关的风险。
采用两种方法综合评估和评估与个体抗生素或抗生素类别相关的 CDI 风险。首先，通过分析随机对照试验（RCT）的数据进行网络比较。随后，使用食品和药物不良事件报告系统（FAERS）数据库进行真实世界的不成比例分析，补充和丰富 RCT 的结果。
网络比较包括 61 项 RCT 和 25931 名患者，结果表明与哌拉西林/他唑巴坦相比，头孢吡肟（比值比 [OR] 2.56，95%置信区间 [CI] 1.20-5.44；P=0.02）和亚胺培南/西司他丁（OR 3.86，95%CI 1.61-9.29；P=0.003）的暴露与 CDI 的发生频率更高。碳青霉烯类药物之间没有观察到显著差异，尽管有趋势表明亚胺培南/西司他丁与美罗培南相比 CDI 的发生率更高（OR 3.89，95%CI 0.94-16.09）。在 FAERS 不成比例分析中，几乎所有抗生素都与 CDI 相关，并且 CDI 风险信号经常聚集在大多数抗生素类别中。其中，林可霉素表现出最强的关联（OR 112.17，95%CI 51.68-243.43）。此外，口服第三代头孢菌素类药物与其他抗生素相比，往往表现出更高的 CDI 风险信号。
研究结果揭示了抗生素类别内和类别之间 CDI 风险的显著差异，为临床医生在抗生素处方决策和抗生素管理计划方面提供了有价值的指导。
