European Respiratory Society

Efficacy, safety and tolerability of linezolid containing regimens in treating MDR-TB and XDR-TB: systematic review and meta-analysis

G Sotgiu, R Centis, L D'Ambrosio, JWC Alffenaar, HA Anger, JA Caminero, P Castiglia, S De Lorenzo, G Ferrara, WJ Koh, GF Schecter, TS Shim, R Singla, A Skrahina, A Spanevello, ZF Udwadia, M Villar, E Zampogna, JP Zellweger, A Zumla, G.B. Migliori


Linezolid is used off-label to treat multidrug-resistant tuberculosis (MDR-TB) in absence of systematic evidence. We performed a systematic review and meta-analysis on efficacy, safety and tolerability of linezolid-containing regimes based on individual data analysis.

Twelve studies (11 countries; three continents) reporting complete information on safety, tolerability, efficacy of linezolid-containing regimes in treating MDR-TB cases were identified based on PRISMA guidelines. Meta-analysis was performed using individual data of 121 patients with a definite treatment outcome (cure, completion, death, failure).

Most MDR-TB cases achieved sputum smear (86/93, 92.5%) and culture (100/107, 93.5%) conversion after treatment with individualized linezolid-containing regimens (median (IQR) time to smear and culture conversion being 43.5 (21–90) and 61 (29–119) days, respectively) and 99/121 (81.8%) were successfully treated. No significant differences were detected in the subgroup efficacy analysis (daily linezolid dosage ≤ 600 mg vs. > 600 mg). Adverse events (AEs) were observed in 58.9% (63/107) of which 68.4% (54/79) were major AEs, including anaemia (38.1%), peripheral neuropathy (47.1%), gastro-intestinal disorders (16.7%), optic neuritis (13.2%) and thrombocytopenia (11.8%). The proportion of AEs was significantly higher when the linezolid daily dosage exceeded 600 mg.

The study results suggest an excellent efficacy but also the necessity of caution in the prescription of linezolid.