Treatment Outcomes among Patients with Extensively Drug-Resistant Tuberculosis: Systematic Review and Meta-Analysis

Background. The treatment of extensively drug-resistant tuberculosis (XDR TB) presents a major challenge. Second-line antimycobacterial drugs are less effective, more toxic, and more costly than first-line agents, and XDR TB strains are, by definition, resistant to the most potent second-line options: the injectable agents and fluoroquinolones. We conducted a meta-analysis to assess XDR TB treatment outcomes and to identify therapeutic approaches associated with favorable responses. Methods. We searched PubMed and EMBASE databases to identify studies conducted through May 2009 that report XDR TB treatment outcomes. Results. The search yielded 13 observational studies covering 560 patients, of whom 43.7% (95% confidence interval, 32.8%-54.5%) experienced favorable outcomes, defined as either cure or treatment completion, and 20.8% (95% confidence interval, 14.2%-27.3%) died. Random effects meta-analysis and meta-regression showed that studies in which a higher proportion of patients received a later-generation fluoroquinolone reported a higher proportion of favorable treatment outcomes (P=.012). Conclusions. This meta-analysis provides the first empirical evidence that the use of later-generation fluoroquinolones for the treatment of XDR TB significantly improves treatment outcomes, even though drug-susceptibility testing demonstrates resistance to a representative fluoroquinolone. These results suggest that the addition of later-generation fluoroquinolones to XDR TB regimens may improve treatment outcomes and should be systematically evaluated in well-designed clinical studies.