Efficacy and Safety of High-Dose Rifampicin in the Management of Tuberculosis Meningitis: A Systematic Review and Meta-Analysis.

Tuberculosis meningitis (TBM) represents the most severe type of tuberculosis (TB), and it is characterized by high mortality and neurological complications. Rifampicin is a major part of the standard treatment of TB; however, conventional doses often achieve subtherapeutic levels in the central nervous system. High-dose rifampicin has been suggested to enhance drug exposure and, possibly, improve the clinical outcomes. This study is a systematic review and meta-analysis evaluating the effectiveness and safety of high-dose rifampicin compared with standard-dose rifampicin in the treatment of TBM. PubMed, the Cochrane Library, and ScienceDirect were searched to identify randomized controlled trials (RCTs) published between 2010 and 2026. The included studies involved adult patients with TBM receiving either high-dose or standard-dose rifampicin. Pharmacokinetic results and risk ratios (RR) were estimated using a random-effects model with data pooling to estimate mean differences (MD) and confidence intervals (CI). Eight RCTs were included. The maximum plasma concentration (Cmax) (MD 23.89 µg/mL; 95% CI (8.56, 39.21)) and total drug exposure (AUC(0-24)) (MD 148.66 µg·h/mL; 95% CI (19.38, 277.94)) were both found to be significantly higher with high-dose rifampicin compared to standard-dose rifampicin. No significant difference, however, was found in six-month mortality (RR 1.00; 95% CI (0.80, 1.26)). The risk of neurological adverse events was higher with high-dose rifampicin (RR 1.34), with other adverse events such as hepatotoxicity and hypersensitivity reactions being comparable between groups. In general, high-dose rifampicin enhances pharmacokinetic exposure in TBM, but with no significant reduction in mortality and a higher risk of neurological adverse events. More large-scale randomized trials are required to identify optimal dosing practices and improve clinical outcomes.