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

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. Three recent systematic review...

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Vydáno v:PLoS medicine Ročník 9; číslo 8; s. e1001300
Hlavní autoři: 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, 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, Peña, Jose, Pérez-Guzmán, 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, 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
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Public Library of Science 01.08.2012
Public Library of Science (PLoS)
Témata:
Adult
Antitubercular Agents - therapeutic use
Clinical trials
Confidence Intervals
Drug resistance
Drug therapy
Female
Health aspects
Humans
Male
Medicine
Meta-analysis
Odds Ratio
Patient outcomes
Physiological aspects
Pulmonary tuberculosis
Recurrence
Studies
Treatment Failure
Tuberculosis
Tuberculosis, Multidrug-Resistant - drug therapy
United States
South Korea
Philippines
Recurrence
Confidence Intervals
Tuberculosis, Multidrug-Resistant
Antitubercular Agents
Humans
Treatment Failure
Adult
Female
Male
Odds Ratio
ISSN:1549-1676, 1549-1277, 1549-1676
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Shrnutí: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. 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]). 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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All members of the Collaborative Group for Meta-Analysis of Individual Patient Data in MDR-TB are the authors and are listed in the manuscript byline.
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.
Performed the experiments. Analyzed the data: SDA DA MA RB MBa JB MCB AB MBu RC EDC CYC HC LD KD NHD DE DF KF JF MLGG NRG RG MGHD THH MDI LGJ SK HRK WJK JLL CL WCMD VL CCL JL DM GBM SM CDM MN PO MP DP SKP GP JMP CPG MIDQ AP VR JR SR HSS KJS LS TSS SSS YS JSO GS MS PT TEP RVA MLV TSV MHV PV JW WWY JJY. Contributed reagents/materials/analysis tools: SDA DA MA RB MBa JB MCB AB MBu RC EDC CYC HC LD KD NHD DE DF KF JF MLGG NRG RG MGHD THH MDI LGJ SK HRK WJK JLL CL WCMD VL CCL JL DM GBM SM CDM MN PO MP DP SKP GP JMP CPG MIDQ AP VR JR SR HSS KJS LS TSS SSS YS JSO GS MS PT TEP RVA MLV TSV MHV PV JW WWY JJY. Wrote the first draft of the manuscript: DM. Contributed to the writing of the manuscript: SDA DA MA RB MBa JB MCB AB MBu RC EDC CYC HC LD KD NHD DE DF KF JF MLGG NRG RG MGHD THH MDI LGJ SK HRK WJK JLL CL WCMD VL CCL JL DM GBM SM CDM MN PO MP DP SKP GP JMP CPG MIDQ AP VR JR SR HSS KJS LS TSS SSS YS JSO GS MS PT TEP RVA MLV TSV MHV PV JW WWY JJY. ICMJE criteria for authorship read and met: SDA DA MA RB MBa JB MCB AB MBu RC EDC CYC HC LD KD NHD DE DF KF JF MLGG NRG RG MGHD THH MDI LGJ SK HRK WJK JLL CL WCMD VL CCL JL DM GBM SM CDM MN PO MP DP SKP GP JMP CPG MIDQ AP VR JR SR HSS KJS LS TSS SSS YS JSO GS MS PT TEP RVA MLV TSV MHV PV JW WWY JJY. Agree with manuscript results and conclusions: SDA DA MA RB MBa JB MCB AB MBu RC EDC CYC HC LD KD NHD DE DF KF JF MLGG NRG RG MGHD THH MDI LGJ SK HRK WJK JLL CL WCMD VL CCL JL DM GBM SM CDM MN PO MP DP SKP GP JMP CPG MIDQ AP VR JR SR HSS KJS LS TSS SSS YS JSO GS MS PT TEP RVA MLV TSV MHV PV JW WWY JJY.
ISSN:1549-1676
1549-1277
1549-1676
DOI:10.1371/journal.pmed.1001300