Journal
CLINICAL INFECTIOUS DISEASES
Volume 59, Issue 10, Pages 1364-1374Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cid/ciu619
Keywords
tuberculosis; drug susceptibility test; treatment outcomes; multidrug resistant; meta-analysis
Categories
Funding
- Stop Tuberculosis Department of World Health Organization, through a grant from the US Agency for International Development
- Centers for Disease Control and Prevention, state of California
- European Community in Italy [FP7-223681]
- Mexican Secretariat of Health in Mexico (Veracruz)
- US National Institutes of Health in Mexico (Veracruz) [A135969, K01TW000001]
- Wellcome Trust in Mexico (Veracruz) [176W009]
- Howard Hughes Medical Institute in Mexico (Veracruz) [55000632]
- Mexican Council of Science and Technology: SEP in Mexico (Veracruz) [2004-C01-47499, FOSSIS 2005-2 [14475, 87332]]
- South African Medical Research Council in South Africa
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico, Science Without Borders program [200097/2012-1]
- Fonds de Recherche en Sante de Quebec
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Background. Individualized treatment for multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis depends upon reliable and valid drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line tuberculosis drugs. However, the reliability of these tests is uncertain, due to unresolved methodological issues. We estimated the association of DST results for pyrazinamide, ethambutol, and second-line drugs with treatment outcomes in patients with MDR tuberculosis and XDR tuberculosis. Methods. We conducted an analysis of individual patient data assembled from 31 previously published cohort studies of patients with MDR and XDR tuberculosis. We used data on patients' clinical characteristics including DST results, treatment received, outcomes, and laboratory methods in each center. Results. DST methods and treatment regimens used in different centers varied considerably. Among 8955 analyzed patients, in vitro susceptibility to individual drugs was consistently and significantly associated with higher odds of treatment success (compared with resistance to the drug), if that drug was used in the treatment regimen. Various adjusted and sensitivity analyses suggest that this was not explained by confounding. The adjusted odds of treatment success for ethambutol, pyrazinamide, and the group 4 drugs ranged from 1.7 to 2.3, whereas for second-line injectables and fluoroquinolones, odds ranged from 2.4 to 4.6. Conclusions. DST for ethambutol, pyrazinamide, and second-line tuberculosis drugs appears to provide clinically useful information to guide selection of treatment regimens for MDR and XDR tuberculosis.
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