Abstract
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, cycloserine/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.
Footnotes
For editorial comments see page 5.
Support statement: Funding for this study was provided, in part, by the Stop TB Department of the World Health Organization, through a grant from USAID. Funding for data gathering at participating centres was provided in: the State of California from the Centers for Disease Control Cooperative Agreement Funds; Mexico (Veracruz) from the Mexican Secretariat of Health, the National Institutes of Health of the United States (A135969 and K01TW000001), the Wellcome Trust (176W009), the Howard Hughes Medical Institute (55000632), and the Mexican Council of Science and Technology (SEP 2004-C01-47499, FOSSIS 2005–2 (14475), (87332)) South Africa from the South African Medical Research Council funding. M. Bauer and D. Menzies were supported by salary awards from the Fonds de Recherche en Santé de Québec; G.B. Migliori and R. Centis receive support from the European Community's Seventh Framework Programme (FP7/2007–2013) under grant agreement FP7-223681; L. Shah was supported by the Canadian Institutes of Health Research (Canada Graduate Scholarship) and N. Gandhi received a Doris Duke Charitable Foundation Clinical Scientist Development Award.
Conflict of interest: None declared.
- Received August 29, 2012.
- Accepted September 20, 2012.
- ©ERS 2013