目的:抗生素使用是艰难梭菌感染(CDI)的最强可改变的决定因素。然而,以前的研究依赖于聚集的抗生素类别,让处方者没有关于个别抗生素的详细比较风险信息。我们的目标是全面评估特定抗生素的CDI风险。
方法:我们整合了2种方法来获取和排序与单个抗生素或类别相关的CDI风险。最初,我们通过分析来自随机对照试验(RCT)的数据进行了网络比较.随后,使用食品和药物不良事件报告系统(FAERS)数据库进行的真实世界不成比例分析补充并丰富了RCT的发现。
结果:网络比较,包括61个RCT和25,931名患者,结果显示,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(OR3.86,95CI1.61-9.29,P=0.003)的CDI发生率更高.碳青霉烯类之间没有统计学上的显著差异,尽管趋势表明亚胺培南/西司他丁相对于美罗培南CDI发病率升高(OR3.89,95CI0.94-16.09).在FAERS不成比例分析中,几乎所有的抗生素都显示与CDI相关,和CDI风险信号通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相关性(报告比值比112.17,95CI51.68-243.43).此外,口服第三代头孢菌素往往比其他头孢菌素表现出更高的CDI风险信号.
结论:我们的发现揭示了CDI风险的巨大差异,在抗生素类内部和之间,为临床医生在抗生素处方决策和旨在抗生素管理的举措提供有价值的指导。
OBJECTIVE: 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. Our objective was to comprehensively estimate CDI risks across specific antibiotics.
METHODS: We integrated 2 methodologies to access and rank the CDI risk associated with individual antibiotics or classes. Initially, we conducted a network comparison by analyzing 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.
RESULTS: 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 to piperacillin/tazobactam. No statistically significant distinctions emerged among carbapenems, albeit a trend indicating a heightened CDI incidence with imipenem/cilastatin relative to 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 cluster within the majority of antibiotic classes. Among these, lincomycin demonstrated the strongest association (reporting odds ratios 112.17, 95%CI 51.68-243.43). Additionally, oral third-generation cephalosporins tend to exhibit higher CDI risk signals than others.
CONCLUSIONS: Our findings unveiled substantial diversity in CDI risk, both within and among antibiotic classes, providing valuable guidance for clinicians in antibiotic prescription decisions and for initiatives aimed at antibiotic stewardship.