Center for Innovative Drug Development and Therapeutic Trials for Africa (CDT-Africa), College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, Addis Ababa University, Addis Ababa, Ethiopia.
Int J Mycobacteriol. 2021 Jul-Sep;10(3):312-319. doi: 10.4103/ijmy.ijmy_135_21.
Mycobacterium tuberculosis (TB) practically affects any part of the body, but when the brain is involved, the consequences are devastating. Tuberculous meningitis (TBM) is the most severe form of drug-susceptible TB, with an estimation of more than 100,000 new cases occurring every year and a high mortality rate globally. The treatment strategy is based on pulmonary TB (PTB) management regimens which consider rifampicin as the backbone. Optimal treatment regimens for PTB may not be the most effective option for TBM due to difference in TB drug penetration across the blood-cerebrospinal fluid barrier, hence the need for other treatment options. This study aims to review the efficacy and safety of higher doses of rifampicin (>10 mg/kg) compared to 10 mg/kg rifampicin as part of standard therapy for the treatment of TBM.
A systematic review and meta-analysis was conducted to assess the efficacy and safety of high-dose rifampicin for TBM. A search was done on PubMed, Google Scholar, and Cochrane library databases without publication date limit to identify studies providing data on the use of high-dose rifampicin for the treatment of TBM. Titles and abstracts were screened for relevance by three reviewers. Two reviewers used a predefined checklist on the inclusion criteria to assess full text for their eligibility in the review. A heterogeneity test was conducted to assess the variations among study outcomes. The risk ratio (RR) with a 95% confidence interval (CI) was calculated as a measure of intervention effect. The study is registered on PROSPERO and the registration number is CRD42020212737.
Five Phase 2 trials with a total of 1028 participants were included in this meta-analysis. All the five trials were used to analyze safety data, which found that there was no significant increase in the risk of Grade 3-5 adverse events in high-dose rifampicin (RR = 1.05; 95% CI = 0.95-1.18). Only four of them were included for the analysis of efficacy. The findings indicated that exposure to high-dose rifampicin is not associated with a reduced risk of mortality (RR = 0.95; 95% CI = 0.78-1.16).
It can be concluded from this meta-analysis that there is no significant relation of high-dose rifampicin with adverse events and the reduction of mortality in TBM patients. Whether in future optimized TBM treatment regimen will include high-dose rifampicin or not should be determined by a large-scale clinical trial.
结核分枝杆菌（TB）实际上可影响身体的任何部位，但当其涉及大脑时，后果是毁灭性的。结核性脑膜炎（TBM）是最严重的药物敏感型 TB 形式，每年估计有超过 10 万例新发病例，全球死亡率很高。治疗策略基于肺结核（PTB）管理方案，其中将利福平视为骨干。由于 TB 药物在血脑脊液屏障中的穿透性不同，PTB 的最佳治疗方案可能不是 TBM 的最有效选择，因此需要其他治疗选择。本研究旨在综述较高剂量利福平（>10mg/kg）与标准治疗方案中 10mg/kg 利福平相比治疗 TBM 的疗效和安全性。
进行了系统评价和荟萃分析，以评估 TBM 中高剂量利福平的疗效和安全性。在没有出版日期限制的情况下，在 PubMed、Google Scholar 和 Cochrane 图书馆数据库中进行了搜索，以确定提供高剂量利福平治疗 TBM 数据的研究。由三名评审员筛选标题和摘要以确定相关性。两名评审员使用预定的清单根据纳入标准评估全文是否符合审查要求。进行了异质性检验以评估研究结果之间的差异。风险比（RR）及其 95%置信区间（CI）被计算为干预效果的度量。该研究已在 PROSPERO 上注册，注册号为 CRD42020212737。
纳入了这项荟萃分析的 5 项 2 期试验，共有 1028 名参与者。所有 5 项试验均用于分析安全性数据，发现高剂量利福平并未增加 3-5 级不良事件的风险（RR=1.05；95%CI=0.95-1.18）。只有其中 4 项试验被纳入疗效分析。结果表明，接触高剂量利福平与降低 TBM 患者的死亡率风险无关（RR=0.95；95%CI=0.78-1.16）。
从这项荟萃分析中可以得出结论，高剂量利福平与 TBM 患者的不良事件和死亡率降低之间没有显著关系。在未来的 TBM 治疗方案中是否包括高剂量利福平，应通过大规模临床试验来确定。
