TY - JOUR
T1 - Multidrug Resistant Pulmonary Tuberculosis Treatment Regimens and Patient Outcomes
T2 - An Individual Patient Data Meta-analysis of 9,153 Patients
AU - Ahuja, Shama D.
AU - Ashkin, David
AU - Avendano, Monika
AU - Banerjee, Rita
AU - Bauer, Melissa
AU - Bayona, Jamie N.
AU - Becerra, Mercedes C.
AU - Benedetti, Andrea
AU - Burgos, Marcos
AU - Centis, Rosella
AU - Chan, Eward D.
AU - Chiang, Chen Yuan
AU - Cox, Helen
AU - D'Ambrosio, Lia
AU - DeRiemer, Kathy
AU - Dung, Nguyen Huy
AU - Enarson, Donald
AU - Falzon, Dennis
AU - Flanagan, Katherine
AU - Flood, Jennifer
AU - Garcia-Garcia, Maria L.
AU - Gandhi, Neel
AU - Granich, Reuben M.
AU - Hollm-Delgado, Maria G.
AU - Holtz, Timothy H.
AU - Iseman, Michael D.
AU - Jarlsberg, Leah G.
AU - Keshavjee, Salmaan
AU - Kim, Hye Ryoun
AU - Koh, Won Jung
AU - Lancaster, Joey
AU - Lange, Christophe
AU - de Lange, Wiel C.M.
AU - Leimane, Vaira
AU - Leung, Chi Chiu
AU - Li, Jiehui
AU - Menzies, Dick
AU - Migliori, Giovanni B.
AU - Mishustin, Sergey P.
AU - Mitnick, Carole D.
AU - Narita, Masa
AU - O'Riordan, Philly
AU - Pai, Madhukar
AU - Palmero, Domingo
AU - Park, Seung kyu
AU - Pasvol, Geoffrey
AU - Peña, Jose
AU - Pérez-Guzmán, Carlos
AU - Quelapio, Maria I.D.
AU - Ponce-de-Leon, Alfredo
AU - Riekstina, Vija
AU - Robert, Jerome
AU - Royce, Sarah
AU - Schaaf, H. Simon
AU - Seung, Kwonjune J.
AU - Shah, Lena
AU - Shim, Tae Sun
AU - Shin, Sonya S.
AU - Shiraishi, Yuji
AU - Sifuentes-Osornio, José
AU - Sotgiu, Giovanni
AU - Strand, Matthew J.
AU - Tabarsi, Payam
AU - Tupasi, Thelma E.
AU - van Altena, Robert
AU - van der Walt, Martie
AU - van der Werf, Tjip S.
AU - Vargas, Mario H.
AU - Viiklepp, Pirett
AU - Westenhouse, Janice
AU - Yew, Wing Wai
AU - Yim, Jae Joon
N1 - Funding Information:
JR is a Consultant for bioMérieux. WWY has been indirectly sponsored to participate in International Conferences by GlaxoSmithKline and Pfizer in the last 3 years. CDM is on the Scientific Advisory Board for Otsuka pharmaceuticals development of OPC67683 (Delaminid), a new anti-TB compound. SK received salary support from the Eli Lilly Foundation as part of funding for the activities of Partners In Health by the Foundation's MDR-TB Partnership. This funder was not involved in the study design; collection, analysis and interpretation of data; writing of the paper; and/or decision to submit for publication. The Partners In Health project in Tomsk received funding from Mr. Tom White, the Open Society Institute, the Bill and Melinda Gates Foundation, and the Global Fund to fight AIDS, Tuberculosis and Malaria. None of these funders were involved in the study design; collection, analysis and interpretation of data; writing of the paper; and/or decision to submit for publication. KD is an unpaid, volunteer member of the New Diagnostics Working Group (NDWG), formed of members of the Stop TB Partnership. The Secretariat of the NDWG is hosted by FIND (Foundation for New Innovative Diagnostics). JB was working as consultant for Otsuka Pharmaceutical for the implementation of clinical trial in Peru. JB was co PI of a NIH grant in Peru, Epidemiology of Tuberculosis. MP and GP are members of the Editorial Board of PLOS Medicine. All other authors have declared that no competing interests exist.
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pmed.1001300
DO - 10.1371/journal.pmed.1001300
M3 - Article
C2 - 22952439
AN - SCOPUS:84865541246
SN - 1549-1277
VL - 9
JO - PLoS Medicine
JF - PLoS Medicine
IS - 8
M1 - e1001300
ER -
