Abstract
Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB. Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1-6.0]), ofloxacin (aOR: 2.5 [1.6-3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3-2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7-4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7-4.3]), ofloxacin (aOR: 2.3 [1.3-3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4-2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 4.5 [3.4-6.0]). In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment. Please see later in the article for the Editors' Summary.
Highlights
The increasing incidence of multidrug resistant tuberculosis (MDR-TB), defined as resistance to at least isoniazid and rifampin, is a major concern for TB control programs worldwide
In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs
We addressed several questions formulated by an expert committee of the World Health Organization (WHO) responsible for revision of guidelines for treatment of MDR-TB [7]
Summary
The increasing incidence of multidrug resistant tuberculosis (MDR-TB), defined as resistance to at least isoniazid and rifampin, is a major concern for TB control programs worldwide. Three systematic reviews have recently examined determinants of treatment outcomes in MDR-TB [3,4,5] These three reviews identified no randomized trials, and the majority of the observational studies identified reported results with individualized treatment. There were considerable differences between studies in the diagnostic methods used, treatment regimens given, and clinical characteristics of the patient populations. As a result, these metaanalyses could only analyze pooled odds of treatment success associated with proportions of patients with specific clinical characteristics or receiving specific treatments. These metaanalyses could only analyze pooled odds of treatment success associated with proportions of patients with specific clinical characteristics or receiving specific treatments This approach has considerable limitations for a clinical problem of this complexity. Global efforts to control tuberculosis are being thwarted by the emergence of M. tuberculosis strains that are resistant to several antibiotics, including isoniazid and rifampicin, the two most powerful, first-line (standard) anti-tuberculosis drugs
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