PLoS Medicine (Jan 2012)

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 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,
  • Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB

DOI
https://doi.org/10.1371/journal.pmed.1001300
Journal volume & issue
Vol. 9, no. 8
p. e1001300

Abstract

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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.