Linezolid-associated adverse events and outcomes in the treatment of multidrug/rifampicin-resistant tuberculosis: A systematic review and meta-analysis of randomized controlled trials

This meta-analysis evaluated the safety and efficacy of linezolid-containing regimens for multidrug/rifampicin-resistant tuberculosis. Seven databases (January 2001-February 2026) were searched for randomized controlled trials comparing linezolid-containing regimens with standard of care (SOC). Pooled risk differences (RDs) and 95% confidence intervals (CIs) were estimated using random-effects models. Across 12 included studies (n = 3019), linezolid-containing regimens did not significantly increase myelosuppression or gastrointestinal, renal, and hepatic disorders. However, peripheral neuropathy (RD 0.043 [95% CI 0.005-0.081]) was higher compared with SOC. Lower doses or shorter linezolid durations were associated with fewer adverse events (AEs) and less AE-related treatment discontinuation. The linezolid group had fewer unfavorable outcomes (RD -0.150 [95% CI -0.211 to -0.089]) and higher sputum culture conversion (RD 0.047 [95% CI 0.003-0.092]). Lower-dose (≤600 mg) or shorter-duration (≤9 months) regimens demonstrated improved efficacy than SOC, with comparable tolerability. These findings support linezolid's key role in WHO-recommended regimens, informing safe and more effective TB care globally.