Publication: A Comparison Between 12 Versus 20 Weeks of Trimethoprim-sulfamethoxazole as Oral Eradication Treatment for Melioidosis: An Open-label, Pragmatic, Multicenter, Non-inferiority, Randomized Controlled Trial
Issued Date
2021-12-06
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ISSN
15376591
Other identifier(s)
2-s2.0-85111784703
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Mahidol University
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SCOPUS
Bibliographic Citation
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. Vol.73, No.11 (2021), e3627-e3633
Suggested Citation
Siriluck Anunnatsiri, Wipada Chaowagul, Prapit Teparrukkul, Ploenchan Chetchotisakd, Kittisak Tanwisaid, Supphachoke Khemla, Surapong Narenpitak, Moragot Pattarapongsin, Wirod Kongsawasd, Pornrith Pisuttimarn, Wilawan Thipmontree, Piroon Mootsikapun, Seksan Chaisuksant, Wirongrong Chierakul, Nicholas P.J. Day, Direk Limmathurotsakul A Comparison Between 12 Versus 20 Weeks of Trimethoprim-sulfamethoxazole as Oral Eradication Treatment for Melioidosis: An Open-label, Pragmatic, Multicenter, Non-inferiority, Randomized Controlled Trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. Vol.73, No.11 (2021), e3627-e3633. doi:10.1093/cid/ciaa1084 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/77410
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Title
A Comparison Between 12 Versus 20 Weeks of Trimethoprim-sulfamethoxazole as Oral Eradication Treatment for Melioidosis: An Open-label, Pragmatic, Multicenter, Non-inferiority, Randomized Controlled Trial
Author(s)
Siriluck Anunnatsiri
Wipada Chaowagul
Prapit Teparrukkul
Ploenchan Chetchotisakd
Kittisak Tanwisaid
Supphachoke Khemla
Surapong Narenpitak
Moragot Pattarapongsin
Wirod Kongsawasd
Pornrith Pisuttimarn
Wilawan Thipmontree
Piroon Mootsikapun
Seksan Chaisuksant
Wirongrong Chierakul
Nicholas P.J. Day
Direk Limmathurotsakul
Wipada Chaowagul
Prapit Teparrukkul
Ploenchan Chetchotisakd
Kittisak Tanwisaid
Supphachoke Khemla
Surapong Narenpitak
Moragot Pattarapongsin
Wirod Kongsawasd
Pornrith Pisuttimarn
Wilawan Thipmontree
Piroon Mootsikapun
Seksan Chaisuksant
Wirongrong Chierakul
Nicholas P.J. Day
Direk Limmathurotsakul
Other Contributor(s)
Faculty of Tropical Medicine, Mahidol University
Chaiyapoom Hospital
Udon Thani Center Hospital
Faculty of Medicine, Khon Kaen University
Khon Kaen University
Maharaj Nakhon Ratchasima Hospital
Khon Kaen Regional Hospital
Nuffield Department of Medicine
Sunpasitthiprasong Hospital
Nakhon Phanom Hospital
Srisaket Hospital
Chaiyapoom Hospital
Udon Thani Center Hospital
Faculty of Medicine, Khon Kaen University
Khon Kaen University
Maharaj Nakhon Ratchasima Hospital
Khon Kaen Regional Hospital
Nuffield Department of Medicine
Sunpasitthiprasong Hospital
Nakhon Phanom Hospital
Srisaket Hospital
Abstract
BACKGROUND: Treatment of melioidosis comprises intravenous drugs for at least 10 days, followed by oral trimethoprim-sulfamethoxazole (TMP-SMX) for 12 to 20 weeks. Oral TMP-SMX is recommended for 12 weeks in Australia and 20 weeks in Thailand. METHODS: For this open-label, pragmatic, multicenter, noninferiority, randomized controlled trial, we enrolled patients with culture-confirmed melioidosis who had received oral eradication treatment for 12 weeks and had no clinical evidence of active melioidosis. We randomly assigned patients to stop treatment (12-week regimen) or continue treatment for another 8 weeks (20-week regimen). The primary end point was culture-confirmed recurrent melioidosis within 1 year after enrollment. The noninferiority margin was a hazard ratio (HR) of 2.0. The secondary composite end point, combining overall recurrent melioidosis and mortality, was assessed post hoc. RESULTS: We enrolled 658 patients: 322 to the 12-week regimen and 336 to the 20-week regimen. There were 5 patients (2%) in the 12-week regimen and 2 patients (1%) in the 20-week regimen who developed culture-confirmed recurrent melioidosis (HR, 2.66; 95% confidence interval [CI], .52-13.69). The criterion for noninferiority of the primary event was not met (1-sided P = .37). However, all-cause mortality was significantly lower in the 12-week regimen group than in the 20-week regimen group (1 [.3%] vs 11 [3%], respectively; HR, 0.10; 95% CI, .01-.74). The criterion for noninferiority of the secondary composite end point, combining overall recurrent melioidosis and mortality, was met (1-sided P = .022). CONCLUSIONS: Based on the lower total mortality and noninferiority of the secondary composite end point observed, we recommend the 12-week regimen of TMP-SMX for oral eradication treatment of melioidosis. CLINICAL TRIALS REGISTRATION: NCT01420341.