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


ABSTRACT:

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.

SUBMITTER: Ahuja SD 

PROVIDER: S-EPMC3429397 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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

Ahuja Shama D SD   Ashkin David D   Avendano Monika M   Banerjee Rita R   Bauer Melissa M   Bayona Jamie N JN   Becerra Mercedes C MC   Benedetti Andrea A   Burgos Marcos M   Centis Rosella R   Chan Eward D ED   Chiang Chen-Yuan CY   Cox Helen H   D'Ambrosio Lia L   DeRiemer Kathy K   Dung Nguyen Huy NH   Enarson Donald D   Falzon Dennis D   Flanagan Katherine K   Flood Jennifer J   Garcia-Garcia Maria L ML   Gandhi Neel N   Granich Reuben M RM   Hollm-Delgado Maria G MG   Holtz Timothy H TH   Iseman Michael D MD   Jarlsberg Leah G LG   Keshavjee Salmaan S   Kim Hye-Ryoun HR   Koh Won-Jung WJ   Lancaster Joey J   Lange Christophe C   de Lange Wiel C M WC   Leimane Vaira V   Leung Chi Chiu CC   Li Jiehui J   Menzies Dick D   Migliori Giovanni B GB   Mishustin Sergey P SP   Mitnick Carole D CD   Narita Masa M   O'Riordan Philly P   Pai Madhukar M   Palmero Domingo D   Park Seung-kyu SK   Pasvol Geoffrey G   Peña Jose J   Pérez-Guzmán Carlos C   Quelapio Maria I D MI   Ponce-de-Leon Alfredo A   Riekstina Vija V   Robert Jerome J   Royce Sarah S   Schaaf H Simon HS   Seung Kwonjune J KJ   Shah Lena L   Shim Tae Sun TS   Shin Sonya S SS   Shiraishi Yuji Y   Sifuentes-Osornio José J   Sotgiu Giovanni G   Strand Matthew J MJ   Tabarsi Payam P   Tupasi Thelma E TE   van Altena Robert R   Van der Walt Martie M   Van der Werf Tjip S TS   Vargas Mario H MH   Viiklepp Pirett P   Westenhouse Janice J   Yew Wing Wai WW   Yim Jae-Joon JJ  

PLoS medicine 20120828 8


<h4>Background</h4>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.<h4>Methods and findings</h4>Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual pa  ...[more]

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