上海交通大学医学院附属瑞金医院北院2013-2017年使用替加环素致肝功能异常不良反应回顾性分析

Retrospective analysis of the adverse drug reaction of hepatic dysfunction induced by tigecycline in Ruijin Hospital North Branch Affiliated to School of Medicine,Shanghai Jiao Tong University from 2013 to 2017

目的:分析替加环素相关肝功能异常发生情况,以指导替加环素的临床合理应用,减少药品不良反应(ADRs)发生。方法:利用医院信息系统采集上海交通大学医学院附属瑞金医院北院2013-2017年接受替加环素治疗且疗程>2 d病例的病史信息,提取其中出现肝功能异常者(共115例),归纳并分析患者使用替加环素后的症状、体征、实验室检查指标变化。结果:115例接受替加环素治疗后出现肝功能异常的患者感染性诊断主要为肺部感染[45例(39.13%)]、血流感染[15例(13.04%)]、感染性休克[15例(13.04%)]和不明部位感染[11例(9.57%)],病原学培养结果以肺炎克雷伯菌(25.78%)和鲍曼不动杆菌(19.53%)为主,联合用药以头孢哌酮钠舒巴坦钠、美罗培南和亚胺培南西司他丁钠居多。患者出现的肝功能异常程度不同,主要表现为肝酶和胆红素水平升高,用药5~31 d出现指标异常,ADRs发生的平均时间为用药(12.16±6.94)d。患者出现肝功能异常后均接受不同方案的降酶、保肝等对症处理,仅48例患者的转归数据可以随访,所监测指标恢复正常的时间为2~37 d,平均好转时间为(13.31±9.27)d。结论:临床使用替加环素时应高度警惕肝功能损伤类ADRs的发生,加强用药监测,密切随访肝酶等生化指标,以提高临床用药安全性。

Objective:To analyze the occurrence of hepatic dysfunction induced by tigecycline,so as to provide reference for rational use of tigecycline and reduce related adverse drug reactions(ADRs).Methods:Medical history data of 115 patients with hepatic dysfunction after treatment with tigecycline for over 2 days in Ruijin Hospital North Branch Affiliated to School of Medicine,Shanghai Jiao Tong University from 2013 to 2017 were collected by using the hospital information system.One hundred and fifteen patients with hepatic dysfunction were enrolled for study.Changes in symptoms,vital signs and laboratory indexes after taking tigecycline were summarized and analyzed.Results:Of the 115 patients with hepatic dysfunction after treatment with tigecycline,45(39.13%)were diagnosed as lung infection,15(13.04%)were diagnosed as blood stream infection,15(13.04%)were diagnosed as septic shock and 11(9.57%)were diagnosed as unknown site infection.The results of bacterial culture showed that Klebsiella pneumoniae(25.78%)and Acinetobacter baumannii(19.53%)were primary pathogens.Cefoperazone sodium and sulbactam sodium,meropenem,imipenem and cilastatin sodium were primary drugs used in combined medication.The seriousness of hepatic dysfunction in the patients varied quite considerably,with the main manifestations of the elevation of hepatic enzyme and bilirubin levels.Abnormal indexes appeared in patients during 5-31 days of medication.The time for the occurrence of ADRs was on the average(12.16±6.94)days of medication.Those patients with hepatic dysfunction all received symptomatic treatment with different regimens of enzyme reduction and liver protection.Only 48 patients were advised to have medical follow-ups in view of good outcome data.After treatment,the time for recovery of liver function was 2-37 days,and the time for obvious symptom improvement was(13.31±9.27)days on the average.Conclusion:Great attention should be paid to ADRs associated with hepatic damage when using tigecycline.At the same time,efforts should be made to intensify drug monitoring,and such biochemical indexes as liver enzyme should be closely followed up,so as to ensure the safety of clinical medication.