BackgroungTreatment 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 FindingsThree 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]).ConclusionsIn 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.

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients / Sotgiu, Giovanni; Ashkin, David; Avendano, Monika; Banerjee, Rita; Bayona, Jamie N.; Benedetti, Andrea; Burgos, Marcos; Centis, Rosella; Chiang, Chen-Yuan; Cox, Helen S.; D'Ambrosio, Lia; Dung, Nguyen Huy; Enarson, Donald; Flanagan, Katherine; Flood, Jennifer; Gandhi, Neel; Granich, Reuben M.; Holtz, Timothy H.; Iseman, Michael D.; Jarlsberg, Leah G.; Kim, Hye-Ryoun; Koh, Won-Jung; Lancaster, Joey; de Lange, Wiel C. M.; Li, Jiehui; Menzies, Dick; Mishustin, Sergey P.; Mitnick, Carole D.; Narita, Masa; Pai, Madhukar; Palmero, Domingo; Park, Seung-kyu; Peña, Jose; Pérez-Guzmán, Carlos; Ponce-de-Leon, Alfredo; Riekstina, Vija; Royce, Sarah; Schaaf, H. Simon; Shah, Lena; Shim, Tae Sun; Shin, Sonya S.; Sifuentes-Osornio, José; Strand, Matthew J.; Tupasi, Thelma E.; van Altena, Robert; Van der Werf, Tjip S.; Vargas, Mario H.; Yew, Wing Wai; Ahuja, Shama D.; Bauer, Melissa; Becerra, Mercedes C.; Chan, Edward D.; Deriemer, Kathy; Falzon, Dennis; García García, María L.; Hollm-Delgado, María G.; Keshavjee, Salmaan; Lange, Christoph; Leung, Chi Chiu; Migliori, Giovanni Battista; O'Riordan, Philly; Pasvol, Geoffrey; Quelapio, Maria I. D.; Robert, Jerome; Seung, Kwonjune J.; Shiraishi, Yuji; Tabarsi, Payam; Van der Walt, Martie; Viiklepp, Pirett; Yim, Jae-Joon; Leimane, Vaira; Westenhouse, Janice. - In: PLOS MEDICINE. - ISSN 1549-1277. - 9:8(2012). [10.1371/journal.pmed.1001300]

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

Sotgiu, Giovanni;Benedetti, Andrea;
2012

Abstract

BackgroungTreatment 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 FindingsThree 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]).ConclusionsIn 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.
Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients / Sotgiu, Giovanni; Ashkin, David; Avendano, Monika; Banerjee, Rita; Bayona, Jamie N.; Benedetti, Andrea; Burgos, Marcos; Centis, Rosella; Chiang, Chen-Yuan; Cox, Helen S.; D'Ambrosio, Lia; Dung, Nguyen Huy; Enarson, Donald; Flanagan, Katherine; Flood, Jennifer; Gandhi, Neel; Granich, Reuben M.; Holtz, Timothy H.; Iseman, Michael D.; Jarlsberg, Leah G.; Kim, Hye-Ryoun; Koh, Won-Jung; Lancaster, Joey; de Lange, Wiel C. M.; Li, Jiehui; Menzies, Dick; Mishustin, Sergey P.; Mitnick, Carole D.; Narita, Masa; Pai, Madhukar; Palmero, Domingo; Park, Seung-kyu; Peña, Jose; Pérez-Guzmán, Carlos; Ponce-de-Leon, Alfredo; Riekstina, Vija; Royce, Sarah; Schaaf, H. Simon; Shah, Lena; Shim, Tae Sun; Shin, Sonya S.; Sifuentes-Osornio, José; Strand, Matthew J.; Tupasi, Thelma E.; van Altena, Robert; Van der Werf, Tjip S.; Vargas, Mario H.; Yew, Wing Wai; Ahuja, Shama D.; Bauer, Melissa; Becerra, Mercedes C.; Chan, Edward D.; Deriemer, Kathy; Falzon, Dennis; García García, María L.; Hollm-Delgado, María G.; Keshavjee, Salmaan; Lange, Christoph; Leung, Chi Chiu; Migliori, Giovanni Battista; O'Riordan, Philly; Pasvol, Geoffrey; Quelapio, Maria I. D.; Robert, Jerome; Seung, Kwonjune J.; Shiraishi, Yuji; Tabarsi, Payam; Van der Walt, Martie; Viiklepp, Pirett; Yim, Jae-Joon; Leimane, Vaira; Westenhouse, Janice. - In: PLOS MEDICINE. - ISSN 1549-1277. - 9:8(2012). [10.1371/journal.pmed.1001300]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/264242
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