Linezolid for the treatment of complicated drug-resistant tuberculosis: a systematic review and meta-analysis

BACKGROUND: Current treatment for drug-resistant tuberculosis (DR-TB) is inadequate, and outcomes are significantly poorer than for drug-susceptible TB, particularly for patients previously treated with second-line drugs, treatment failures or extensively drug-resistant (XDR-) TB patients (complicated DR-TB). Linezolid is not recommended for routine DR-TB treatment due to the lack of efficacy data, but is suggested for patients where adequate second-line regimens are difficult to design. OBJECTIVE: To conduct a systematic review and meta-analysis to assess existing evidence of efficacy and safety of linezolid for DR-TB treatment. METHODS: We searched PubMed, Embase and abstracts from World Conferences of The Union for studies published through February 2011. We included all studies in which linezolid was given systematically to DR-TB patients and where treatment outcomes were reported. RESULTS: A total of 11 studies were included in our review, representing 148 patients. The pooled proportion for treatment success was 67.99% (95%CI 58.00-78.99, tau(2) 129.42). There were no significant differences in success comparing daily linezolid dose (<= 600 vs. >600 mg) and mean linezolid duration (<= vs. >7 months). The pooled estimate for the frequency of any adverse events was 61.48% (95%CI 40.15-82.80), with 36.23% (95%CI 20.67-51.79) discontinuing linezolid due to adverse events. CONCLUSION: Treatment success with linezolid was equal to or better than that commonly achieved for uncomplicated DR-TB, and better than previous reports for previously treated patients and those with XDR-TB. While data are limited, linezolid appears be a useful drug, albeit associated with significant adverse events, and should be considered in the treatment of complicated DR-TB.