Adjunctive linezolid in patients with tuberculous meningitis for the prevention of mortality or neurologic disability: 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 neurologic disability. Methods The MEDLINE, Embase, and CENTRAL databases were searched until 5 January 2024. We included randomized controlled trials evaluating the effectiveness of linezolid in individuals with clinically diagnosed tuberculous meningitis. For the statistical analysis, we used a Bayesian random-effects model with a weakly informative prior. Results Three trials were included in this review. Linezolid has a 92% probability of preventing one death per 100 treated patients (RR 0.55, 95% CrI 0.23 to 1.31; I 2 = 13%; n = 104 patients; low-certainty evidence), with a mean number needed to treat (NNT) of 6 patients. Further, there is an 87% probability that one poor neurologic outcome is prevented per 100 patients (RR 0.72, 95% CrI 0.40 to 1.30; I 2 = 22%; n = 104 patients; low-certainty evidence), with a mean NNT of 7. The risk of grade 3 or 4 adverse events was not increased with linezolid, although this is uncertain. Conclusions Linezolid may reduce mortality and neurologic disability in adult, HIV-positive individuals with tuberculous meningitis. Further trials should investigate ideal dosing and applicability to other populations. Clinical trial number Not applicable.