基于FAERS的头孢他啶/阿维巴坦致神经系统异常的不良反应信号挖掘与分析

Signal mining and analysis of adverse drug reactions associated with nervous system disorders induced by ceftazidime/avibactam based on FAERS database

目的:通过对头孢他啶/阿维巴坦(ceftazidime/avibactam,CAZ/AVI)导致神经系统异常相关药物不良反应(adverse drug reactions,ADRs)信号的挖掘分析,为临床安全合理用药提供依据。方法:基于2015年1月至2021年6月美国食品药品监督管理局的不良事件报告系统(FAERS),采用报告比值比法(reporting odds ratio,ROR)和贝叶斯法判别可信区间产比神经网络法(bayesian confidence propagation neural network,BCPNN)进行数据挖掘,筛选CAZ/AVI给药后导致神经系统异常的相关ADRs,并将其与美罗培南、亚胺培南/西司他丁和头孢他啶进行比较。结果:该研究共收集到CAZ/AVI相关ADRs共694例,其中88例与神经系统异常相关。女性患者比例稍高于男性(54.55%vs.34.09%),65岁以上患者所占比例较高(15.91%),用药后中位发病时间为6.5 d。CAZ/AVI与美罗培南和头孢他啶相比,致神经系统异常的风险增加[ROR=1.66(95%CI:1.28~2.13),IC025=0.46;ROR=1.36(95%CI:1.02~1.81),IC025=0.21]。CAZ/AVI与美罗培南、亚胺培南/西司他丁和头孢他啶相比,CAZ/AVI发生脑病[ROR=2.73(95%CI:1.85~4.04),IC025=0.81;ROR=2.26(95%CI:1.46~3.51),IC025=0.52;ROR=1.81(95%CI:1.15~2.84),IC025=0.34]、肌阵挛[ROR=4.74(95%CI:2.56~8.81),IC025=0.97;ROR=4.31(95%CI:2.04~9.10),IC025=0.63]、昏迷[ROR=2.77(95%CI:1.26~6.08),IC025=0.57;ROR=2.69(95%CI:1.08~6.71),IC025=0.39]和癫痫[ROR=1.67(95%CI:1.05~2.67),IC025=0.30]的风险增加。结论:该研究表明CAZ/AVI具有增加神经系统异常风险的倾向,这些不良反应应引起临床注意,特别是用于有中枢神经系统病史的患者,从而为临床安全用药提供参考,或避免用于高风险人群。

OBJECTIVE To provide reference for rational and safe clinical practice through signal mining and analysis of the adverse drug reactions(ADRs)associated with nervous system disorders incuded by ceftazidime/avibactam(CAZ/AVI).METHODS Reporting odds ratio(ROR)and Bayesian confidence propagation neural network(BCPNN)analysis were used for data mining to screen the ADRs associated with nervous system disorders after the administration of CAZ/AVI based on Food and Drug Administration's Adverse Event Reporting System(FAERS)from January 2015 to June 2021,and compared CAZ/AVI with meropenem,cilastatin sodium/imipenem and ceftazidime.RESULTS A total of 694 adverse reaction reports of CAZ/AVI were collected,and among them,88 ones were related to nervous system disorders.The proportion of female patients was slightly higher than that of male patients(54.55%vs.34.09%),and the proportion of patients over 65 years old was higher(15.91%).The ADRs median occurrence time was 6.5 days after CAZ/AVI treatment.CAZ/AVI showed increased risks of nervous system disorders compared with meropenem and ceftazidime[ROR=1.61(95%CI:1.27-2.05),IC025=0.43;ROR=1.46(95%CI:1.01-1.91),IC025=0.25].Compared with meropenem,cilastatin sodium/imipenem and ceftazidime,CAZ/AVI showed increased risks of encephalopathy[ROR=2.73(95%CI:1.85-4.04),IC025=0.81;ROR=2.26(95%CI:1.46-3.51),IC025=0.52;ROR=1.81(95%CI:1.15-2.84),IC025=0.34],myoclonus[ROR=4.74(95%CI:2.56-8.81),IC025=0.97;ROR=4.31(95%CI:2.04-9.10),IC025=0.63],coma[ROR=2.77(95%CI:1.26-6.08),IC025=0.57;ROR=2.69(95%CI:1.08-6.71),IC025=0.39]and seizure[ROR=1.67(95%CI:1.05-2.67),IC025=0.30].CONCLUSION This study shows CAZ/AVI tends to increase risks of nervous system disorders.The poor clinical outcomes of the events should attract clinical attention,especially for patients with a history of nervous system disorders,which provide reference for clinical safe medication,or it should be avoided to be applied to high risk population.