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

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. ; Ghandi, Neel ; Granich, Reuben M. ; Hollm-Delgado, Maria G. ; Holtz, Timothy H. ; Iseman, Michael D. ; Jarlsberg, Leah G. ; Keshavjee, Salmaan ; 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 D. ; Narita, Masa ; O'Riordan, Philly ; Pai, Madhukar ; Palmero, Domingo ; Park, Seung-kyu ; Pasvol, Geoffrey ; Pena, Jose ; Perez-Guzman, Carlos ; Quelapio, Maria I. D. ; Ponce-De-Leon, Alfredo ; Riekstina, Vija ; Robert, Jerome ; Royce, Sarah ; Schaaf, H. Simon ; Seung, Kwonjune J. ; Shah, Lena ; Shim, Tae Sun ; Shin, Sonya S. ; Shiraishi, Yuji ; Sifuentes-Osornio, Jose ; 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 (2012-08-28)

CITATION: Ahuja, S. D., et al. 2012. Mutlidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes : an individual patient data meta-analysis of 9,153 patients. PLoS Medicine, 9(8): 1-16, doi: 10.1371/journal.pmed.1001300.

The original publication is available at http://journals.plos.org/plosmedicine

Article

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 refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/79325
This item appears in the following collections: