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

G B Migliori; G Sotgiu; N R Gandhi; D Falzon; K DeRiemer; R Centis; M G Hollm-Delgado; D Palmero; C Pérez-Guzmán; M H Vargas; L D'Ambrosio; A Spanevello; M Bauer; E D Chan; H S Schaaf; S Keshavjee; T H Holtz; D Menzies; “The Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB”

doi:10.1183/09031936.00136312

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

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

Authors

G B Migliori^#¹, G Sotgiu^#², N R Gandhi³, D Falzon⁴, K DeRiemer⁵, R Centis¹, M G Hollm-Delgado⁶, D Palmero⁷, C Pérez-Guzmán⁸, M H Vargas⁹, L D'Ambrosio¹, A Spanevello¹⁰, M Bauer⁶, E D Chan¹¹, H S Schaaf¹², S Keshavjee¹³, T H Holtz¹⁴, D Menzies⁶; “The Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB”

Collaborators

“The Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB”:
S Ahuja, D Ashkin, M Avendano, R Banerjee, J N Bayona, M C Becerra, A Benedetti, M Burgos, C-Y Chiang, H Cox, N H Dung, D Enarson, K Flanagan, J Flood, L Garcia-Garcia, R M Granich, M D Iseman, L G Jarlsberg, H R Kim, W J Koh, J Lancaster, C Lange, W C M de Lange, C C Leung, J Li, S P Mishustin, C D Mitnick, M Narita, P O'Riordan, M Pai, S K Park, G Pasvol, J Pena, A Ponce-de-Leon, M I D Quelapio, V Riekstina, J Robert, S Royce, K J Seung, L Shah, T S Shim, S S Shin, Y Shiraishi, J Sifuentes-Osornio, M J Strand, P Tabarsi, T E Tupasi, R van Altena, M Van der Walt, T S Van der Werf, P Viiklepp, J Westenhouse, W W Yew, J J Yim

Affiliations

¹ World Health Organization Collaborating Centre for Tuberculosis and Lung Diseases, Fondazione S. Maugeri, Care and Research Institute, Tradate, Italy.
² Epidemiology and Medical Statistics Unit, Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
³ Department of Medicine and Department of Epidemiology and Population Health, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York, USA.
⁴ STOP TB Department, World Health Organization, Geneva, Switzerland.
⁵ School of Medicine, University of California Davis, Davis, California, USA.
⁶ Montreal Chest Institute, McGill University, Montreal, Canada.
⁷ Pulmonology Division, Hospital F. J. Muñiz, Buenos Aires, Argentina.
⁸ Instituto de Servicios de Salud del Estado de Aguascalientes, and Unidad de Medicina Ambulatoria Aguascalientes, Instituto Mexicano del Seguro Social, Aguascalientes, Mexico.
⁹ Instituto Nacional de Enfermedades Respiratorias, and Medical Research Unit in Respiratory Diseases, Instituto Mexicano del Seguro Social, Mexico DF, Mexico.
¹⁰ Università degli Studi dell'Insubria, Varese, and Fondazione S. Maugeri, Care and Research Institute, Tradate, Italy.
¹¹ Pulmonary Department, Denver Veterans Affair Medical Center and National Jewish Health, Denver, Colorado, USA.
¹² Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa.
¹³ Department of Global Health & Social Medicine Harvard Medical School, Boston, Massachusetts, USA.
¹⁴ Centers for Disease Control and Prevention, Atlanta, GA, USA.

^# Contributed equally.

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.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adult
Antitubercular Agents / pharmacology
Cohort Studies
Drug Resistance, Bacterial*
Drug Therapy, Combination / methods
Extensively Drug-Resistant Tuberculosis / drug therapy*
Female
Humans
Male
Microbial Sensitivity Tests
Multivariate Analysis
Mycobacterium tuberculosis / drug effects
Reproducibility of Results
Treatment Outcome

Substances

Antitubercular Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding