基于FAERS数据库对儿童用喹诺酮类抗菌药物的不良反应信号挖掘

Data mining for adverse reaction signals of fluoroquinolones in children based on the FAERS database

目的:挖掘儿童使用喹诺酮类代表性药物(环丙沙星、左氧氟沙星与莫西沙星)的不良反应(adverse drug reaction, ADR)信号,为临床安全用药提供参考。方法:利用OpenVigil2.1工具从美国FAERS数据库中提取2004年第1季度至2022年第2季度18岁以下儿童数据,采用报告优势比(reporting odds ratio, ROR)与比例报告比(proportional reporting ratio, PRR)对三种喹诺酮类药进行ADR信号挖掘,重点分析肌肉骨骼系统ADR。结果:FAERS数据库共检索到18岁以下儿童的报告323 032份,其中环丙沙星相关报告1 163份、左氧氟沙星相关报告617份、莫西沙星相关报告256份。经ROR法和PRR法共挖掘得到ADR信号387个,其中环丙沙星222个,左氧氟沙星117个,莫西沙星48个;ADR信号累及的系统器官广泛(24个),主要包括胃肠系统、肌肉骨骼系统与神经系统等。对于肌肉骨骼系统,环丙沙星检出信号26个,左氧氟沙星14个,莫西沙星并未检出信号;关节痛报告频数最多,而信号强度最高的是肌腱类疾病,包括肌腱疼痛、肌腱炎、肌腱病变等均出现了显著信号。结论:儿童使用喹诺酮类抗菌药物需严格监测ADR,特别警惕于肌肉骨骼系统损伤,保障患者的治疗安全。

OBJECTIVE To analyze the adverse drug reaction(ADR)signals in children treated with fluoroquinolones,including ciprofloxacin,levofloxacin and moxifloxacin,so as to provide reference for clinical medication safety.METHODS Using a pharmacovigilance tool(OpenVigil2.1),we extracted the ADR data of children under 18 years old from the US Food and Drug Administration Adverse Event Reporting System(FAERS)during the first quarter of 2004 and the second quarter of 2022.Reporting odds ratio(ROR)and proportional reporting ratio(PRR)mining algorithms were used to evaluate ADR signals for ciprofloxacin,levofloxacin and moxifloxacin.The high-risk ADR signals of musculoskeletal system were analyzed.RESULTS A total of 323032 reports on children under the age of 18 were reported in the FAERS database,of which 1163 were for ciprofloxacin-related reports,617 were for levofloxacin-related reports and 256 were for moxifloxacin-related reports.After the detection by ROR and PRR,387 ADR signals were obtained,including 222 for ciprofloxacin,117 for levofloxacin and 48 for moxifloxacin.ADR signals involved extensive system organs(n=24),mainly including gastrointestinal system,musculoskeletal system and nervous system.For the musculoskeletal ADRs,26 signals were detected for ciprofloxacin,and 14 for levofloxacin,and no signal was detected for moxifloxacin.The most frequently reported ADR was arthralgia,while tendon diseases were detected with the highest signal intensity,including tendon pain,tendinitis and tendon disorder.CONCLUSION Since children in China belong to the off-label population of fluoroquinolones,ADR should be strictly monitored during the medication,especially for musculoskeletal diseases,to ensure the treatment safety of patients.