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Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients

Ahuja, Shama D. and Ashkin, David and Avendano, Monika and Banerjee, Rita and Bauer, Melissa and Bayona, Jamie N. and Becerra, Mercedes C. and Benedetti, Andrea and Burgos, Marcos and Centis, Rosella and Chan, Edward D. and Chiang, Chen-Yuan and Cox, Helen S. and D'Ambrosio, Lia and DeRiemer, Kathy and Dung, Nguyen Huy and Enarson, Donald and Falzon, Dennis and Flanagan, Katherine and Flood, Jennifer and García García, María L. and Gandhi, Neel and Granich, Reuben M. and Hollm-Delgado, María G. and Holtz, Timothy H. and Iseman, Michael D. and Jarlsberg, Leah G. and Keshavjee, Salmaan and Kim, Hye-Ryoun and Koh, Won-Jung and Lancaster, Joey and Lange, Christoph and de Lange, Wiel C. M. and Leimane, Vaira and Leung, Chi Chiu and Li, Jiehui and Menzies, Dick and Migliori, Giovanni Battista and Mishustin, Sergey P. and Mitnick, Carole D. and Narita, Masa and O'Riordan, Philly and Pai, Madhukar and Palmero, Domingo and Park, Seung-kyu and Pasvol, Geoffrey and Peña, Jose and Pérez-Guzmán, Carlos and Quelapio, Maria I. D. and Ponce-de-Leon, Alfredo and Riekstina, Vija and Robert, Jerome and Royce, Sarah and Schaaf, H. Simon and Seung, Kwonjune J. and Shah, Lena and Shim, Tae Sun and Shin, Sonya S. and Shiraishi, Yuji and Sifuentes-Osornio, José and Sotgiu, Giovanni and Strand, Matthew J. and Tabarsi, Payam and Tupasi, Thelma E. and van Altena, Robert and Van der Walt, Martie and Van der Werf, Tjip S. and Vargas, Mario H. and Viiklepp, Pirett and Westenhouse, Janice and Yew, Wing Wai and Yim, Jae-Joon (2012) Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients. Plos Medicine, Vol. 9 (8), e1001300. ISSN 1549-1277. Article.

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DOI: 10.1371/journal.pmed.1001300

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Abstract

Backgroung 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.

Item Type:Article
ID Code:7978
Status:Published
Refereed:Yes
Uncontrolled Keywords:Multidrug resistant tuberculosis (MDR-TB), treatment outcomes, fluoroquinolones, ethionamide, prothionamide
Subjects:Area 06 - Scienze mediche > MED/01 Statistica medica
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Biomediche
Publisher:Public Library of Science
ISSN:1549-1277
Copyright Holders:© 2012 Ahuja et al.
Deposited On:21 Sep 2012 11:51

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