Treatment outcomes among patients with extensively drug-resistant tuberculosis: systematic review and meta-analysis

Clin Infect Dis. 2010 Jul 1;51(1):6-14. doi: 10.1086/653115.

Abstract

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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Review
  • Systematic Review

MeSH terms

  • Antitubercular Agents / therapeutic use*
  • Drug Therapy, Combination
  • Empirical Research
  • Extensively Drug-Resistant Tuberculosis / drug therapy*
  • Fluoroquinolones / therapeutic use*
  • Humans
  • Mycobacterium tuberculosis / drug effects
  • Treatment Outcome

Substances

  • Antitubercular Agents
  • Fluoroquinolones