Drug resistance beyond extensively drugresistant tuberculosis: Individual patient data meta-analysis

Giovanni Battista Migliori, Giovanni Sotgiu, Neel R. Gandhi, Dennis Falzon, Kathryn DeRiemer, Rosella Centis, Maria Graciela Hollm-Delgado, Domingo Palmero, Carlos Pérez-Guzmán, Mario H. Vargas, Lia D'Ambrosio, Antonio Spanevello, Melissa Bauer, Edward D. Chan, H. Simon Schaaf, Salmaan Keshavjee, Timothy H. Holtz, Dick Menzies

Research output: Contribution to journalArticle

189 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)169-179
Number of pages11
JournalEuropean Respiratory Journal
Volume42
Issue number1
DOIs
StatePublished - Jul 1 2013

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Migliori, G. B., Sotgiu, G., Gandhi, N. R., Falzon, D., DeRiemer, K., Centis, R., Hollm-Delgado, M. G., Palmero, D., Pérez-Guzmán, C., Vargas, M. H., D'Ambrosio, L., Spanevello, A., Bauer, M., Chan, E. D., Schaaf, H. S., Keshavjee, S., Holtz, T. H., & Menzies, D. (2013). Drug resistance beyond extensively drugresistant tuberculosis: Individual patient data meta-analysis. European Respiratory Journal, 42(1), 169-179. https://doi.org/10.1183/09031936.00136312