大剂量利福平治疗结核性脑膜炎的Meta分析  

Meta-Analysis on High-Dose Rifampicin in the Treatment of Tuberculous Meningitis

作　　者：李娜 陈洁 刘幸 朱翔 彭江丽 罗季 李生浩 LI Na;CHEN Jie;LIU Xing;ZHU Xiang;PENG Jiangli;LUO Ji;LI Shenghao(Dept.of Pharmacy,the Third People’s Hospital of Kunming,Kunming 650041,China;Dept.of Liver Disease,the Third People’s Hospital of Kunming,Kunming 650041,China)

机构地区：[1]昆明市第三人民医院药剂科,昆明650041 [2]昆明市第三人民医院肝病科,昆明650041

出　　处：《中国医院用药评价与分析》2024年第10期1230-1234,共5页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：国家自然科学基金资助项目(No.82260408)。

摘　　要：目的:比较大剂量与标准剂量利福平治疗结核性脑膜炎(TBM)的临床疗效和安全性,为临床合理用药提供参考依据。方法:检索数据库(包括PubMed、Embase、Web of Science、the Cochrane Library、中国知网等电子数据库)中截至2023年7月1日发表的使用大剂量利福平治疗TBM患者的随机对照试验。研究组抗结核方案为利福平>10 mg/(kg·d),并联合其他抗结核病药;对照组抗结核方案为利福平10 mg/(kg·d)标准剂量,并联合其他抗结核病药。由2名研究者筛选文献并采用Cochrane 5.1偏倚风险评估工具评价纳入研究的方法学质量,采用RevMan 5.3软件对结局指标进行Meta分析。结果:共纳入7项随机对照试验,涉及1457例患者,Meta分析结果表明,研究组患者的血浆利福平浓度(MD=18.62,95%CI=13.05~24.18,P<0.00001)、脑脊液利福平浓度(SMD=1.37,95%CI=1.02~1.72,P<0.00001)明显高于对照组,0~24 h血药浓度-时间曲线下面积明显高于对照组(MD=157.39,95%CI=100.39~214.39,P<0.00001),差异均有统计学意义。两组患者6个月内死亡率(OR=1.14,95%CI=0.77~1.69,P=0.51)、不良事件发生率(OR=0.93,95%CI=0.68~1.28,P=0.66)、肝损伤发生率(RR=1.03,95%CI=0.77~1.38,P=0.83)比较,差异均无统计学意义。结论:该项研究结果表明,大剂量利福平治疗TBM患者,可显著提高血浆和脑脊液中利福平的浓度,但不增加不良反应发生风险。OBJECTIVE:To compare the clinical efficacy and safety between high-dose and standard-dose rifampicin in the treatment tuberculous meningitis(TBM),so as to provide reference for clinical rational drug application.METHODS:Randomized controlled trials on high-dose rifampicin in the treatment of TBM published up to Jul.1st,2023 were retrieved from databases(including PubMed,Embase,Web of Science,the Cochrane Library,CNKI and other electronic databases).The anti-tuberculosis regimen in the research group was rifampicin>10 mg/(kg·d)in combination with other anti-tuberculosis drugs,and the anti-tuberculosis regimen in the control group was rifampicin at the standard dose of 10 mg/(kg·d)in combination with other anti-tuberculosis drugs.Literature was screened by 2 investigators and the methodological quality of the enrolled studies was evaluated by using the Cochrane 5.1 risk of bias assessment tool,and Meta-analysis on the outcome indicators was performed by using RevMan 5.3 software.RESULTS:A total of 7 randomized controlled trials including 1457 patients were enrolled,Meta-analysis showed that the plasma rifampicin concentration(MD=18.62,95%CI=13.05-24.18,P<0.00001)and cerebrospinal fluid rifampicin concentration(SMD=1.37,95%CI=1.02-1.72,P<0.00001)of the research group were significantly higher than those of the control group,and the area under the blood concentration-time curve from 0 to 24 h was significantly higher in the research group than that in the control group(MD=157.39,95%CI=100.39-214.39,P<0.00001),with statistically significant differences.Compared with the mortality rate within 6 months(OR=1.14,95%CI=0.77-1.69,P=0.51),the differences of the incidence of adverse events(OR=0.93,95%CI=0.68-1.28,P=0.66)and the incidence of hepatic injury(RR=1.03,95%CI=0.77-1.38,P=0.83)between two groups were not statistically significant.CONCLUSIONS:Results of the study suggest that high-dose rifampicin in the treatment of TBM can significantly increase the rifampicin concentration in plasma and cerebrospinal fluid,without

关 键 词：结核性脑膜炎 利福平 大剂量 血浆药物浓度 脑脊液药物浓度 META分析 

分 类 号：R978.3[医药卫生—药品]