TY - JOUR
T1 - Drug resistance beyond extensively drugresistant tuberculosis
T2 - Individual patient data meta-analysis
AU - Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB
AU - Migliori, Giovanni Battista
AU - Sotgiu, Giovanni
AU - Gandhi, Neel R.
AU - Falzon, Dennis
AU - DeRiemer, Kathryn
AU - Centis, Rosella
AU - Hollm-Delgado, Maria Graciela
AU - Palmero, Domingo
AU - Pérez-Guzmán, Carlos
AU - Vargas, Mario H.
AU - D'Ambrosio, Lia
AU - Spanevello, Antonio
AU - Bauer, Melissa
AU - Chan, Edward D.
AU - Schaaf, H. Simon
AU - Keshavjee, Salmaan
AU - Holtz, Timothy H.
AU - Menzies, Dick
AU - Ahuja, S.
AU - Ashkin, D.
AU - Avendano, M.
AU - Banerjee, R.
AU - Bayona, J. N.
AU - Becerra, M. C.
AU - Benedetti, A.
AU - Burgos, M.
AU - Chiang, C. Y.
AU - Cox, H.
AU - Dung, N. H.
AU - Enarson, D.
AU - Flanagan, K.
AU - Flood, J.
AU - Garcia-Garcia, L.
AU - Granich, R. M.
AU - Iseman, M. D.
AU - Jarlsberg, L. G.
AU - Kim, H. R.
AU - Koh, W. J.
AU - Lancaster, J.
AU - Lange, C.
AU - De Lange, W. C.M.
AU - Leimane, V.
AU - Leung, C. C.
AU - Li, J.
AU - Mishustin, S. P.
AU - Mitnick, C. D.
AU - Narita, M.
AU - O'Riordan, P.
AU - Pai, M.
AU - Park, S. K.
PY - 2013/7/1
Y1 - 2013/7/1
N2 - 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.
AB - 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.
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U2 - 10.1183/09031936.00136312
DO - 10.1183/09031936.00136312
M3 - Article
C2 - 23060633
AN - SCOPUS:84880158505
SN - 0903-1936
VL - 42
SP - 169
EP - 179
JO - European Respiratory Journal
JF - European Respiratory Journal
IS - 1
ER -
