含贝达喹啉方案治疗耐多药肺结核疗效与安全性的Meta分析

目的 系统评价含贝达喹啉方案治疗耐多药肺结核(multidrug-resistant pulmonary tuberculosis,MDR-PTB)的疗效与安全性。方法 检索中文数据库,包括中国知网、万方、维普、中国生物医学文献数据库,以及英文数据库,包括The Cochrane Library、PubMed、Embase,搜集含贝达喹啉方案治疗MDR-PTB的随机对照试验,检索时限从建库至2021年12月,由2位研究人员独立筛选文献、提取数据、评价文献质量后,采用RevMan 5.4软件对纳入的数据进行异质性检验分析,对文章进行发表偏倚分析。结果 研究纳入10篇文献,共802例患者。Meta分析结果显示,与常规抗结核治疗方案相比,含贝达喹啉方案治疗MDR-PTB可提高12周末痰菌阴转率(OR=3.17,95%CI:1.85~5.43,P<0.01)、治疗24周末痰菌阴转率(OR=4.09,95%CI:2.74~6.12,P<0.01)、空洞闭合率(OR=3.11,95%CI:1.68~5.74,P<0.01)、病灶吸收率(OR=4.44,95%CI:2.40~8.22,P<0.01)和临床治愈率(OR=4.15, 95%CI:2.27~7.58,P<0.01),降低病亡率(OR=5.22,95%CI:1.16~16.96,P<0.01);与常规抗结核治疗方案相比,含贝达喹啉方案治疗MDR-TB的8周末痰菌阴转率(OR=1.79,95%CI:0.98~3.26,P=0.06)、药物不良反应发生率(OR=2.72,95%CI:0.61~12.19,P=0.19)差异无统计学意义。结论 与常规抗结核治疗方案相比,含贝达喹啉的化疗方案治疗MDR-PTB有助于加速痰菌阴转,提高患者临床疗效,不会增加不良反应,但仍需严密监测心电图,警惕贝达喹啉的心脏毒性。

Meta analysis of efficacy and safety of the treatment containing bedaquiline for multidrug-resistant pulmonary tuberculosis

Objective: To systematically evaluate the efficacy and safety of the treatment containing bedaquiline for multidrug-resistant pulmonary tuberculosis (MDR-PTB). Methods: Randomized controlled trials (RCTs) of bedaquiline-containing regimens for the treatment of MDR-PTB were searched and collected from Chinese databases (China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP and China Biomedical Literature Database (CBM)) and English databases (The Cochrane Library, PubMed, Embase). The retrieval time was from the establishment of the database to December 2021. Two researchers independently screened the literature, extracted data, and evaluated the quality of the literature. RevMan 5.4 software was used to analyze the heterogeneity of the included data, and the publication bias. Results: A total of 802 patients were included in 10 articles. Meta-analysis results showed that compared with conventional anti-tuberculosis regimens, bedaquiline-containing regimens in the treatment of MDR-PTB could increase the negative conversion rate of sputum at the end of 12 weeks after treatment (OR=3.17, 95%CI: 1.85-5.43, P<0.01), improve the negative rate of sputum bacteria at the end of 24 weeks after treatment (OR=4.09, 95%CI: 2.74-6.12, P<0.01), the cavity closure rate (OR=3.11, 95%CI: 1.68-5.74, P<0.01), the absorption rate of lesions (OR=4.44, 95%CI: 2.40-8.22, P<0.01) and clinical cure rate (OR=4.15, 95%CI: 2.27-7.58, P<0.01), and reduce the level of mortality (OR=5.22, 95%CI: 1.16-16.96, P<0.01). However, there was no significant difference in sputum negative conversion rate at the end of 8 weeks after treatment (OR=1.79, 95%CI: 0.98-3.26, P=0.06) and incidence of adverse drug reactions (OR=2.72, 95%CI: 0.61-12.19, P=0.19) at the end of 8 weeks after treatment with bedaquiline-containing regimens for MDR-PTB. Conclusion: Compared with conventional anti-tuberculosis treatment, the chemotherapy regimens containing bedaquiline for MDR-PTB help to accelerate the negative conversion of sputum bacteria and improve the clinical efficacy, with no increase in adverse reactions; however, ECG should be closely monitored to be alert to the cardiotoxicity of bedaquiline.