期刊
PLOS MEDICINE
卷 9, 期 8, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pmed.1001300
关键词
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资金
- USAID
- US Centers for Disease Control Cooperative Agreement Funds
- European Community's Seventh Framework Programme [FP7-223681]
- Mexican Secretariat of Health
- National Institutes of Health of the United States [A135969, K01TW000001]
- Wellcome Trust [176W009]
- Howard Hughes Medical Institute [55000632]
- Mexican Council of Science and Technology [SEP 2004-C01-47499, FOSSIS 2005-2, FOSSIS 14475, FOSSIS 87332]
- South African Medical Research Council
- Fonds de Recherche en Sante de Quebec
- CIHR (Canada Graduate Scholarship)
- Doris Duke Charitable Foundation Clinical Scientist Development Award
- GlaxoSmithKline
- Pfizer
- Eli Lilly Foundation
- Open Society Institute
- Bill and Melinda Gates Foundation
- NIH
- Global Fund to fight AIDS, Tuberculosis and Malaria
Background: 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. Methods and Findings: 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]). Conclusions: 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.
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