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

作者：Giovanni Sotgiu, Rosella Centis, Lia D’Ambrosio, J. W. C. Alffenaar, Holly A. Anger, José Antonio Caminero, Paolo Castiglia, Saverio De Lorenzo, Giovanni Ferrara, Won‐Jung Koh, Giesela F. Schecter, Tae Sun Shim, Rupak Singla, Alena M. Skrahina, Antonio Spanevello, Zarir Udwadia, M.P. Gil Villar, Elisabetta Zampogna, Jean-Pierre Zellweger, Alimuddin I. Zumla, Giovanni Battista Migliori · 发表于：European Respiratory Journal · 年份：2012 · DOI：10.1183/09031936.00022912 · 被引用次数：420 · 研究领域：Tuberculosis Research and Epidemiology、Mycobacterium research and diagnosis、Diagnosis and treatment of tuberculosis

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. 12 studies (11 countries from three continents) reporting complete information on safety, tolerability, efficacy of linezolid-containing regimes in treating MDR-TB cases were identified based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analysis was performed using the individual data of 121 patients with a definite treatment outcome (cure, completion, death or failure). Most MDR-TB cases achieved sputum smear (86 (92.5%) out of 93) and culture (100 (93.5%) out of 107) conversion after treatment with individualised regimens containing linezolid (median (inter-quartile range) times for smear and culture conversions were 43.5 (21-90) and 61 (29-119) days, respectively) and 99 (81.8%) out of 121 patients were successfully treated. No significant differences were detected in the subgroup efficacy analysis (daily linezolid dosage ≤ 600 mg versus >600 mg). Adverse events were observed in 63 (58.9%) out of 107 patients, of which 54 (68.4%) out of 79 were major adverse events that included anaemia (38.1%), peripheral neuropathy (47.1%), gastro-intestinal disorders (16.7%), optic neuritis (13.2%) and thrombocytopenia (11.8%). The proportion of adverse events was significantly hig...