High-dose rifampicin for the treatment of tuberculous meningitis: a meta-analysis of randomized controlled trials.

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: Tuberculous meningitis (TBM) is one of the most serious types of extrapulmonary tuberculosis and has caused distress to human. Effective treatment is particularly important. The aim of this meta-analysis is to compare the efficacy of high-dose and standard-dose rifampicin. METHODS: Databases including PubMed, Web of Science, Embase, Scopus and the Cochrane Library databases were electronically searched to identify randomized controlled trials that reported high-dose rifampicin in treatment of patients with TBM. The retrieval time is limited from inception to June 2021. Two reviewers independently screened literature, extracted data and assessed risk bias of included studies. Meta-analysis was performed by using STATA 12.0 software. RESULTS AND DISCUSSION: A total of 12 studies involving 1596 patients were included. The meta-analysis results showed no significant differences in 6-month mortality, 9-month mortality, Grade I-II AE, Grade III-V AE, hepatotoxicity, hepatotoxicity Grade I-II and cardiologic events between high-dose rifampicin (or high-dose rifampicin plus moxifloxacin or levofloxacin) and standard-dose groups. The log(Cmax ) (WMD 0.69, 95%CI 0.59-0.79, p 0.001) and log(AUC0-24h ) (WMD 0.79, 95%CI 0.71-0.88, p 0.001) were higher with high-dose rifampicin. Subgroup analysis revealed the rise of log(Cmax ) in high-dose rifampicin orally was consistent with intravenous administration compared with the control (WMD 0.69, 95%CI 0.66-0.73, p 0.001). WHAT IS NEW AND CONCLUSION: High-dose rifampicin was not a protective factor for 6-month mortality, despite increased plasma Cmax and AUC0-24h . However, the above conclusions are still required to be verified through more RCTs due to the limited quantity of included studies.