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 Flood, Maria 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, and Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB
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.