Safety and tolerability of linezolid to treat tuberculosis: a systematic review and meta-analysis.

OBJECTIVE: In a previous review, we summarized the safety of linezolid-containing regimens to treat rifampin-resistant/multidrug-resistant tuberculosis (RR/MDR-TB), underscoring the persistent need for shorter and safer regimens. The objective of the present study was to explore the safety and tolerability directly attributable to linezolid in regimens designed to treat RR/MDR-TB in studies published between 2009 and 2025. METHODS: We searched PubMed/MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for studies reporting on the safety and tolerability of linezolid since it was introduced as a repurposed drug in the treatment of tuberculosis. RESULTS: A total of 22 studies (including 26 arms) were identified, with a total of 3,014 patients. There was significant variation in geographic distribution, sample size (range, 8-655), linezolid dose (range, 300-1,200 mg), duration, and other core variables. The pooled rate of favorable outcomes among cohort studies (cure or treatment completion) was = 80.1%. Hematologic disorders (including anemia, thrombocytopenia, and leukopenia, in 33.1%) and peripheral neuropathy (in 33.9%) were the most common adverse events (AEs), followed by psychiatric and neurological disorders (in 12.3%), myalgia (in 7.0%), optic neuropathy (in 7.8%), gastrointestinal events (in 1.9%), ototoxicity (in 2.9%), and rash (in 1.0%). Serious AEs were rarely reported. CONCLUSIONS: Although the recommended linezolid-containing regimens are considered safe, linezolid still causes frequent and severe AEs. A new drug with similar characteristics but lower toxicity will significantly improve the safety of antituberculosis regimens, with improved adherence and treatment outcomes.