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Meta-Analysis
. 2010 Jul 1;51(1):6-14.
doi: 10.1086/653115.

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

Karen R Jacobson  1 , Dylan B Tierney, Christie Y Jeon, Carole D Mitnick, Megan B Murray
Affiliations
Meta-Analysis

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

Karen R Jacobson et al. Clin Infect Dis. .

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.

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Conflict of interest statement

Potential conflicts of interest. All authors: no conflicts.

Figures

Figure 1
Figure 1
Flowchart depicting methods for article inclusion.
Figure 2
Figure 2
Weighted proportion of favorable outcomes for the selected studies. CI, confidence interval.
Figure 3
Figure 3
Weighted proportion of deaths for the selected studies. CI, confidence interval.
Figure 4
Figure 4
Weighted proportion of favorable outcomes for those studies in which at least 50% of patients received a later-generation fluoroquinolone, compared with those studies in which <50% of patients received a later-generation fluoroquinolone. CI, confidence interval.
See this image and copyright information in PMC

References

    1. Centers for Disease Control and Prevention (CDC) Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs—worldwide, 2000–2004. MMWR Morb Mortal Wkly Rep. 2006;55:301–5. - PubMed
    1. World Health Organization. Countries that had reported at least one XDR-TB case by end. Mar, 2009. [Accessed 17 November 2009]. http://www.who.int/tb/challenges/xdr/xdr_map_mar09.pdf.
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    1. Shah NS, Wright A, Bai GH, et al. Worldwide emergence of extensively drug-resistant tuberculosis. Emerg Infect Dis. 2007;13:380–7. - PMC - PubMed
    1. Kim HR, Hwang SS, Kim HJ, et al. Impact of extensive drug resistance on treatment outcomes in non–HIV-infected patients with multidrug-resistant tuberculosis. Clin Infect Dis. 2007;45:1290–5. - PubMed

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