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, τ2 129.42). There were no significant differences in success comparing daily linezolid dose (≤600 vs. >600 mg) and mean linezolid duration (≤7 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.


CONCLUSIONS
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.
Médecins Sans Frontières, Khayelitsha, Cape Town, South Africa. hcox@burnet.edu.au
H
H
Cox
N
N
Ford
D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy; D006801:Humans; D000069349:Linezolid; D023303:Oxazolidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
D000081:Acetamides; D000995:Antitubercular Agents; D023303:Oxazolidinones; D000069349:Linezolid