Drug resistance beyond extensively drug-resistant tuberculosis: individual patient data meta-analysis.
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.
World Health Organization Collaborating Centre for Tuberculosis and Lung Diseases, Fondazione S. Maugeri, Care and Research Institute, Tradate, Italy.
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Migliori
Epidemiology and Medical Statistics Unit, Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
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Sotgiu
Department of Medicine and Department of Epidemiology and Population Health, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York, USA.
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Gandhi
STOP TB Department, World Health Organization, Geneva, Switzerland.
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Falzon
School of Medicine, University of California Davis, Davis, California, USA.
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DeRiemer
World Health Organization Collaborating Centre for Tuberculosis and Lung Diseases, Fondazione S. Maugeri, Care and Research Institute, Tradate, Italy.
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Centis
Montreal Chest Institute, McGill University, Montreal, Canada.
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Hollm-Delgado
Pulmonology Division, Hospital F. J. Muñiz, Buenos Aires, Argentina.
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Palmero
Instituto de Servicios de Salud del Estado de Aguascalientes, and Unidad de Medicina Ambulatoria Aguascalientes, Instituto Mexicano del Seguro Social, Aguascalientes, Mexico.
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Pérez-Guzmán
Instituto Nacional de Enfermedades Respiratorias, and Medical Research Unit in Respiratory Diseases, Instituto Mexicano del Seguro Social, Mexico DF, Mexico.
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Vargas
World Health Organization Collaborating Centre for Tuberculosis and Lung Diseases, Fondazione S. Maugeri, Care and Research Institute, Tradate, Italy.
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D'Ambrosio
Università degli Studi dell'Insubria, Varese, and Fondazione S. Maugeri, Care and Research Institute, Tradate, Italy.
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Spanevello
Montreal Chest Institute, McGill University, Montreal, Canada.
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Bauer
Pulmonary Department, Denver Veterans Affair Medical Center and National Jewish Health, Denver, Colorado, USA.
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Chan
Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa.
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Schaaf
Department of Global Health & Social Medicine Harvard Medical School, Boston, Massachusetts, USA.
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Keshavjee
Centers for Disease Control and Prevention, Atlanta, GA, USA.
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Holtz
Montreal Chest Institute, McGill University, Montreal, Canada.
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Menzies
D000328:Adult; D000995:Antitubercular Agents / Q000494:pharmacology; D015331:Cohort Studies; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination / Q000379:methods; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D015999:Multivariate Analysis; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D015203:Reproducibility of Results; D016896:Treatment Outcome
D000995:Antitubercular Agents