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Meta-Analysis
. 2013 Jul;42(1):169-179.
doi: 10.1183/09031936.00136312. Epub 2012 Oct 11.

Drug resistance beyond extensively drug-resistant tuberculosis: individual patient data meta-analysis

G B Migliori #  1 , G Sotgiu #  2 , N R Gandhi  3 , D Falzon  4 , K DeRiemer  5 , R Centis  1 , M G Hollm-Delgado  6 , D Palmero  7 , C Pérez-Guzmán  8 , M H Vargas  9 , L D'Ambrosio  1 , A Spanevello  10 , M Bauer  6 , E D Chan  11 , H S Schaaf  12 , S Keshavjee  13 , T H Holtz  14 , D Menzies  6 ; “The Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB”
Collaborators, Affiliations
Meta-Analysis

Drug resistance beyond extensively drug-resistant tuberculosis: individual patient data meta-analysis

G B Migliori et al. Eur Respir J. 2013 Jul.

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.

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