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, S. Ahuja, D. AshkinM. 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, V. Leimane, 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

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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
Pages (from-to)169-179
Number of pages11
JournalEuropean Respiratory Journal
Volume42
Issue number1
DOIs
Publication statusPublished - Jul 1 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

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., Ahuja, S., ... Yim, J. J. (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