Journal
EUROPEAN RESPIRATORY JOURNAL
Volume 42, Issue 1, Pages 169-179Publisher
EUROPEAN RESPIRATORY SOC JOURNALS LTD
DOI: 10.1183/09031936.00136312
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Funding
- Stop TB Department of the World Health Organization through USAID
- State of California from the Centers for Disease Control Cooperative Agreement Funds
- Mexico (Veracruz) from the 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 2004-001-47499, FOSSIS 2005-2 (14475), 87332]
- South Africa from the South African Medical Research Council
- Fonds de Recherche en Sante de Quebec
- European Community [FP7-223681]
- Canadian Institutes of Health Research
- Doris Duke Charitable Foundation
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The broadest pattern of tuberculosis (TB) drug resistance for which a consensus definition exists is extensively drug-resistant (XDR)-TB. It is not known if additional drug resistance portends worsened patient outcomes. This study compares treatment outcomes of XDR-TB patients with and without additional resistance in order to explore the need for a new definition. Individual patient data on XDR-TB outcomes were included in a meta-analysis comparing outcomes between XDR alone and three nonmutually exclusive XDR-TB patient groups: XDR plus resistance to all the second-line injectables (sli) and capreomycin and kanamycin/amikacin (XDR+2sli) XDR plus resistance to second-line injectables and to more than one group 4 drug, i.e. ethionamide/protionamide, cydoserine/terizidone or para-aminosalicylic acid (XDR+sliG4) and XDR+sliG4 plus resistance to ethambutol and/or pyrazinamide (XDR+sliG4EZ). Of 405 XDR-TB cases, 301 were XDR alone, 68 XDR+2sli, 48 XDR+sliG4 and 42 XDR+sliG4EZ. In multivariate analysis, the odds of cure were significantly lower in XDR+2sli (adjusted OR 0.4, 95% CI 0.2-0.8) compared to XDR alone, while odds of failure and death were higher in all XDR patients with additional resistance (adjusted OR 2.6-2.8). Patients with additional resistance beyond XDR-TB showed poorer outcomes. Limitations in availability, accuracy and reproducibility of current drug susceptibility testing methods preclude the adoption of a useful definition beyond the one currently used for XDR-TB.
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