Adjunct linezolid in patients with tuberculous meningitis for mortality or neurological disability prevention: a meta-analysis of randomized controlled trials

Background This systematic review aimed to evaluate the effectiveness of linezolid as an adjunct to the current tuberculous meningitis standard of care in preventing death and neurological disability. Methods The MEDLINE, Embase, and CENTRAL databases were searched until 5 January 2024. We included randomized controlled trials in individuals with clinically diagnosed tuberculous meningitis comparing adjunct linezolid to standard treatment alone. We synthesized results using an inverse-variance random-effects meta-analysis, reporting the probability of treatment benefit with a Bayesian hierarchical normal-normal model. Results Three trials were included. There was a risk reduction in mortality (RR 0.45, 95% CI 0.21 to 0.97; 3 RCTs, n = 87 patients; moderate certainty evidence). The probability of a clinically relevant benefit (RR < 0.9) was 93.95%, and 74.86% for a large prevention in mortality (RR < 0.5). The probability of harm is less than 2.5% (RR > 1.1). However, the effect on neurological disability was uncertain (RR 0.76, 95% CI 0.45 to 1.28; 2 RCTs, n = 64 patients; very low certainty evidence). Conclusions Linezolid shows considerable promise in reducing mortality in patients with tuberculous meningitis, one of the most severe and challenging central nervous system infections. Larger-scale trials should elucidate its effect on neurological disability and optimize dosing strategies.