High dose of rifampicin in the treatment of tuberculous meningitis: a systematic review and meta-analysis of randomized controlled trials

Introduction The efficacy and safety of high-dose rifampicin in patients with tuberculous meningitis (TBM) remain uncertain. Method A comprehensive search of PubMed, Embase, Web of Science, and the Cochrane Database was conducted to identify randomized controlled trials (RCTs) evaluating the efficacy and safety of high-dose rifampicin treatment in patients with TBM, up to October 8, 2024. The primary outcome was all-cause mortality at the longest follow-up period reported by individual trials, while the secondary outcome was the incidence of serious adverse events. We applied a random-effects model and calculated risk ratios (RR) with 95% confidence intervals (CIs) of pooled outcomes. Result Seven RCTs involving 1,296 TBM patients were included. High-dose rifampicin did not reduce all-cause mortality (RR = 0.88, 95% CI: 0.55-1.43,P= 0.61). Similarly, it was not associated with a reduction in serious adverse events (RR = 0.96, 95% CI: 0.62-1.50,P= 0.87). Conclusion This meta-analysis of seven RCTs involving 1,296 patients with TBM found that high-dose rifampicin treatment neither significantly reduced all-cause mortality nor decreased serious adverse events.