基于FAERS数据库对儿童用大环内酯类抗生素的不良事件信号挖掘  

Data Mining for Adverse Events of Macrolide Antibiotics in Children Based on the FAERS Database

作　　者：王文雪 唐丽 刘兰 WANG Wenxue;TANG Li;LIU Lan(Department of Pharmacy,Wuhan Children’s Hospital(Wuhan Maternal and Child Healthcare Hospital),Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430015,China;Hemodialysis Division,Jingshan People's Hospital,Hubei Province,Jingshan 431800,China;Department of Pharmacy,the First People’s Hospital of Xiantao City,Xiantao 433000,China)

机构地区：[1]华中科技大学同济医学院附属武汉儿童医院(武汉市妇幼保健院)药剂科,武汉430015 [2]湖北省京山市人民医院血液透析室,京山431800 [3]湖北省仙桃市第一人民医院药剂科,仙桃433000

出　　处：《医药导报》2025年第4期576-583,共8页Herald of Medicine

摘　　要：目的检测儿童使用大环内酯类抗生素的不良事件(AEs)信号,为儿童用药安全提供参考。方法收集美国食品药品管理局不良事件报告系统(FAERS)中2004年1月—2024年3月大环内酯类相关不良反应报告,采用报告比值比法(ROR)和贝叶斯置信传播神经网络法(BCPNN)对儿童用大环内酯类抗生素进行信号挖掘。结果FAERS数据库共检索18岁以下儿童报告2133648份,去重后提取阿奇霉素相关报告7589份,克拉霉素3673份,红霉素820份。累及的阳性系统器官广泛(16个),包括皮肤及皮下组织类疾病、耳及迷路类疾病、胃肠系统疾病、神经/系统、免疫系统等。对阿奇霉素和克拉霉素进行比例失衡分析得出相关阳性信号,阿奇霉素232个,克拉霉素194个。报告频数最多的AEs包括皮疹、呕吐、腹泻、超敏反应等,而阿奇霉素信号最强依次是史蒂文斯-约翰逊综合征(SJS)、超敏反应、药物性肝损伤等,克拉霉素信号最强依次是味觉倒错、唇部肿胀、中毒性表皮坏死松解症(TEN)、梦魇、精神障碍等。新发现的可疑信号包括阿奇霉素17例,克拉霉素21例。对相同的AEs进行卡方检验发现两者在呼吸困难、超敏反应、皮疹、SJS、呕吐等具有差异。结论儿童使用大环内酯抗生素应注意皮肤、胃肠、耳等毒性及超敏反应,特别警惕严重皮肤反应,新发可疑不良事件及精神毒性,保证儿童的治疗安全。Objective To analyze signals of adverse events(AEs)related to macrolide antibiotic in children from the US FDA Adverse Event Reporting System(FAERS),and provide a reference for clinical safe medication in children.Methods The AEs reports of children(less than 18 years old)were extracted from FAERS during January 2004 to March 2024,and the reports of odds ratio(ROR)and information component of Bayesian confidence propagation neural network(IC)were used to analyze the signals of macrolide antibiotics in children.Results There were 2133648 reports of children from FAERS,including azithromycin(7589 cases),clarithromycin(3673 cases),and erythromycin(820 cases).The significant signals of system organ class(SOC)were 16 in total,such as skin disorders,ear and labyrinth disorders,gastrointestinal disorders,nervous system,immune system disorders,etc.A proportional imbalance analysis was performed on macrolide antibiotics(azithromycin and clarithromycin),and obtained relevant positive signals,including azithromycin(232)and clarithromycin(194).The most frequently reported AEs included rash,vomiting,diarrhea,hypersensitivity and so on.The strongest signals of azithromycin were Stevens-Johnson syndrome(SJS),hypersensitivity reactions,drug-induced liver injury,etc.,while the strongest signals of clarithromycin were dysgeusia,lip swelling,toxic epidermal necrolysis(TEN),nightmare,psychotic disorder,etc.17 unlisted signals of azithromycin and 21 of clarithromycin were found.The same PT of azithromycin and clarithromycin had significant difference,such as dyspnea,hypersensitivity,rash,SJS,vomiting,and more.Conclusions To ensure the safety of children's treatment,children using macrolide should pay attention to skin,gastrointestinal,ear and other toxicity and hypersensitivity reactions,especially serious skin reactions,unlisted suspicious AEs and psychiatric disorders.

关 键 词：大环内酯类抗生素 儿童 真实世界 美国食品药品管理局不良事件报告系统 信号挖掘 

分 类 号：R969[医药卫生—药理学] R978.1[医药卫生—药学]