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

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

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Title: Multidrug Resistant Pulmonary Tuberculosis Treatment Regimens and Patient Outcomes: An Individual Patient Data Meta-analysis of 9,153 Patients
Author: Ahuja, Shama D.; Ashkin, David; Avendano, Monika; Banerjee, Rita; Bauer, Melissa; Bayona, Jamie N.; Becerra, Mercedes C.; Benedetti, Andrea; Burgos, Marcos; Centis, Rosella; Chan, Eward D.; Chiang, Chen-Yuan; Cox, Helen; D'Ambrosio, Lia; DeRiemer, Kathy; Dung, Nguyen Huy; Enarson, Donald; Falzon, Dennis; Flanagan, Katherine; Flood, Jennifer; Garcia-Garcia, Maria L.; Gandhi, Neel; Granich, Reuben M.; Hollm-Delgado, Maria G.; Holtz, Timothy H.; Iseman, Michael D.; Jarlsberg, Leah G.; Keshavjee, Salmaan A.; Kim, Hye-Ryoun; Koh, Won-Jung; Lancaster, Joey; Lange, Christophe; de Lange, Wiel C. M.; Leimane, Vaira; Leung, Chi Chiu; Li, Jiehui; Menzies, Dick; Migliori, Giovanni B.; Mishustin, Sergey P.; Mitnick, Carole Diane; Narita, Masa; O'Riordan, Philly; Pai, Madhukar; Palmero, Domingo; Park, Seung-kyu; Pasvol, Geoffrey; Peña, Jose; Pérez-Guzmán, Carlos; Quelapio, Maria I. D.; Ponce-de-Leon, Alfredo; Riekstina, Vija; Robert, Jerome; Royce, Sarah; Schaaf, H. Simon; Seung, Kwonjune Justin; Shah, Lena; Shim, Tae Sun; Shin, Sonya Sunhi; Shiraishi, Yuji; Sifuentes-Osornio, José; Sotgiu, Giovanni; Strand, Matthew J.; Tabarsi, Payam; Tupasi, Thelma E.; van Altena, Robert; Van der Walt, Martie; Van der Werf, Tjip S.; Vargas, Mario H.; Viiklepp, Pirett; Westenhouse, Janice; Yew, Wing Wai; Yim, Jae-Joon

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Citation: Ahuja, Shama D., David Ashkin, Monika Avendano, Rita Banerjee, Melissa Bauer, Jamie N. Bayona, Mercedes C. Becerra, et al. 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.
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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.
Published Version: doi:10.1371/journal.pmed.1001300
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3429397/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10589800
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