Multidrug Resistant Pulmonary Tuberculosis Treatment Regimens and Patient Outcomes: An Individual Patient Data Meta-analysis of 9,153 Patients

Shama D. Ahuja, David Ashkin, Monika Avendano, Rita Banerjee, Melissa Bauer, Jamie N. Bayona, Mercedes C. Becerra, Andrea Benedetti, Marcos Burgos, Rosella Centis, Eward D. Chan, Chen Yuan Chiang, Helen Cox, Lia D'Ambrosio, Kathy DeRiemer, Nguyen Huy Dung, Donald Enarson, Dennis Falzon, Katherine Flanagan, Jennifer FloodMaria L. Garcia-Garcia, Neel Gandhi, Reuben M. Granich, Maria G. Hollm-Delgado, Timothy H. Holtz, Michael D. Iseman, Leah G. Jarlsberg, Salmaan Keshavjee, Hye Ryoun Kim, Won Jung Koh, Joey Lancaster, Christophe Lange, Wiel C M de Lange, Vaira Leimane, Chi Chiu Leung, Jiehui Li, Dick Menzies, Giovanni B. Migliori, Sergey P. Mishustin, Carole D. Mitnick, Masa Narita, Philly O'Riordan, Madhukar Pai, Domingo Palmero, Seung kyu Park, Geoffrey Pasvol, Jose Peña, Carlos Pérez-Guzmán, Maria I D Quelapio, Alfredo Ponce-de-Leon, Vija Riekstina, Jerome Robert, Sarah Royce, H. Simon Schaaf, Kwonjune J. Seung, Lena Shah, Tae Sun Shim, Sonya S. Shin, Yuji Shiraishi, José Sifuentes-Osornio, Giovanni Sotgiu, Matthew J. Strand, Payam Tabarsi, Thelma E. Tupasi, Robert van Altena, Martie van der Walt, Tjip S. van der Werf, Mario H. Vargas, Pirett Viiklepp, Janice Westenhouse, Wing Wai Yew, Jae Joon Yim

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Abstract

Background: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB. Methods and Findings: Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1-6.0]), ofloxacin (aOR: 2.5 [1.6-3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3-2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7-4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7-4.3]), ofloxacin (aOR: 2.3 [1.3-3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4-2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 4.5 [3.4-6.0]).Conclusions:In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment.Please see later in the article for the Editors' Summary.

Original languageEnglish (US)
Article numbere1001300
JournalPLoS Medicine
Volume9
Issue number8
DOIs
StatePublished - Aug 2012

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ASJC Scopus subject areas

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Ahuja, S. D., Ashkin, D., Avendano, M., Banerjee, R., Bauer, M., Bayona, J. N., Becerra, M. C., Benedetti, A., Burgos, M., Centis, R., Chan, E. D., Chiang, C. Y., Cox, H., D'Ambrosio, L., DeRiemer, K., Dung, N. H., Enarson, D., Falzon, D., Flanagan, K., ... Yim, J. J. (2012). Multidrug Resistant Pulmonary Tuberculosis Treatment Regimens and Patient Outcomes: An Individual Patient Data Meta-analysis of 9,153 Patients. PLoS Medicine, 9(8), [e1001300]. https://doi.org/10.1371/journal.pmed.1001300