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. (29th July 2020)

• Record Type: Journal Article
• Authors: Anunnatsiri, Siriluck; Chaowagul, Wipada; Teparrukkul, Prapit; Chetchotisakd, Ploenchan; Tanwisaid, Kittisak; Khemla, Supphachoke; Narenpitak, Surapong; Pattarapongsin, Moragot; Kongsawasd, Wirod; Pisuttimarn, Pornrith; Thipmontree, Wilawan; Mootsikapun, Piroon; Chaisuksant, Seksan; Chierakul, Wirongrong; Day, Nicholas P J; Limmathurotsakul, Direk
• Is Part Of: Clinical infectious diseases. Volume 73:Number 11(2021)
• Page Start: e3627
• Page End: e3633
• Publication Date: 2020-07-29
• Subjects: melioidosis -- eradication -- treatment -- duration; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciaa1084
• Languages: English
• ISSNs: 1058-4838

Abstract

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. Abstract : A comparison study between 12- and 20-week regimens of trimethoprim-sulfamethoxazole (TMP-SMX) as oral eradication treatment for melioidosis shows that 12 weeks of TMP-SMX is adequate for patients who have no clinical evidence of active melioidosis after 12 weeks of treatment.