Bastos ML, Hussain H, Weyer K, Garcia-Garcia L, Leimane V, Leung CC, Narita M, Penã JM, Ponce-de-Leon A, Seung KJ, Shean K, Sifuentes-Osornio J, Van der Walt M, Van der Werf TS, Yew WW, Menzies D; on behalf of The Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB; on behalf of The Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB.; Clin Infect Dis. 2014 Aug 5. pii: ciu619. [Epub ahead of print]

BACKGROUND: Individualized treatment for multi-drug resistant tuberculosis (MDR-TB) and extensively drug-resistant (XDR) TB depends upon reliable and valid drug susceptibility tests (DST) for pyrazinamide, ethambutol and second-line TB 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-TB and XDR-TB.

METHODS: We conducted an analysis of individual patient data assembled from 31 previously published cohort studies of patients with MDR, and XDR-TB. 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 8,955 analyzed patients, in-vitro susceptibility to individual drugs was consistently and significantly associated with higher odds of treatment success (compared to 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, while for second line injectables and fluoro-quinolones, odds ranged from 2.4 to 4.6.

CONCLUSION: Drug Susceptibility Tests for ethambutol, pyrazinamide, and second-line TB drugs appear to provide clinically useful information to guide selection of treatment regimens for MDR- and XDR-TB.

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