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&apos;Ambrosio, Lia; Spanevello, Antonio; Bauer, Melissa; Chan, Edward D.; Schaaf, H. Simon; Keshavjee, Salmaan; Holtz, Timothy H.; The Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB; Menzies, Dick; Ahuja, S.; Ashkin, D.; Avendano, M.; Banerjee, R.; Bayona, J.N.; Becerra, M.C.; Benedetti, A.; Burgos, M.; Chiang, C.-Y.; Cox, H.; Dung, N.H.; Enarson, D.; Flanagan, K.; Flood, J.; Garcia-Garcia, L.; Granich, R.M.; Iseman, M.D.; Jarlsberg, L.G.; Kim, H.R.; Koh, W.J.; Lancaster, J.; Lange, C.; De, Lange W.C.M.; Leimane, V.; Leung, C.C.; Li, J.; Mishustin, S.P.; Mitnick, C.D.; Narita, M.; O&apos;Riordan, P.; Pai, M.; Park, S.K.; Pasvol, G.; Pena, J.; Ponce-De-Leon, A.; Quelapio, M.I.D.; Riekstina, V.; Robert, J.; Royce, S.; Seung, K.J.; Shah, L.; Shim, T.S.; Shin, S.S.; Shiraishi, Y.; Sifuentes-Osornio, J.; Strand, M.J.; Tabarsi, P.; Tupasi, T.E.; Van, Altena R.; Van, Der Walt M.; Van, Der Werf T.S.; Viiklepp, P.; Westenhouse, J.; Yew, W.W.; Yim, J.J.

doi:10.1183/09031936.00136312

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Drug resistance beyond extensively drugresistant tuberculosis: Individual patient data meta-analysis

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

Issue Date: 2013-07

Publisher: European Respiratory Society

Citation: European Respiratory Journal, Vol.42 No.1, pp.169-179

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. Copyright © ERS 2013.