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

185 Citations (Scopus)

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

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Drug Resistance
Meta-Analysis
Tuberculosis
Prothionamide
Capreomycin
Extensively Drug-Resistant Tuberculosis
Ethionamide
Aminosalicylic Acid
Cycloserine
Pyrazinamide
Ethambutol
Injections
Kanamycin
Amikacin
Pharmaceutical Preparations
Multivariate Analysis

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Migliori, G. B., Sotgiu, G., Gandhi, N. R., Falzon, D., DeRiemer, K., Centis, R., ... 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

Drug resistance beyond extensively drugresistant tuberculosis : Individual patient data meta-analysis. / Migliori, Giovanni Battista; Sotgiu, Giovanni; Gandhi, Neel R.; Falzon, Dennis; DeRiemer, Kathryn; Centis, Rosella; Hollm-Delgado, Maria Graciela; Palmero, Domingo; Pérez-Guzmán, Carlos; Vargas, Mario H.; D'Ambrosio, Lia; Spanevello, Antonio; Bauer, Melissa; Chan, Edward D.; Schaaf, H. Simon; Keshavjee, Salmaan; Holtz, Timothy H.; Menzies, Dick.

In: European Respiratory Journal, Vol. 42, No. 1, 01.07.2013, p. 169-179.

Research output: Contribution to journalArticle

Migliori, GB, Sotgiu, G, Gandhi, NR, Falzon, D, DeRiemer, K, Centis, R, Hollm-Delgado, MG, Palmero, D, Pérez-Guzmán, C, Vargas, MH, D'Ambrosio, L, Spanevello, A, Bauer, M, Chan, ED, Schaaf, HS, Keshavjee, S, Holtz, TH & Menzies, D 2013, 'Drug resistance beyond extensively drugresistant tuberculosis: Individual patient data meta-analysis', European Respiratory Journal, vol. 42, no. 1, pp. 169-179. https://doi.org/10.1183/09031936.00136312
Migliori, Giovanni Battista ; Sotgiu, Giovanni ; Gandhi, Neel R. ; Falzon, Dennis ; DeRiemer, Kathryn ; Centis, Rosella ; Hollm-Delgado, Maria Graciela ; Palmero, Domingo ; Pérez-Guzmán, Carlos ; Vargas, Mario H. ; D'Ambrosio, Lia ; Spanevello, Antonio ; Bauer, Melissa ; Chan, Edward D. ; Schaaf, H. Simon ; Keshavjee, Salmaan ; Holtz, Timothy H. ; Menzies, Dick. / Drug resistance beyond extensively drugresistant tuberculosis : Individual patient data meta-analysis. In: European Respiratory Journal. 2013 ; Vol. 42, No. 1. pp. 169-179.
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