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= 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= 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.