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

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. Twelve weeks of oral TMP-SMX is recommended in Australia, and 20 weeks in Thailand. Methods For this open-label, pragmatic, multicenter, non-inferiority, 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 (12-week regimen) or continue treatment for another eight weeks (20-week regimen). The primary endpoint was culture-confirmed recurrent melioidosis within one year after enrollment. The non-inferiority margin was a hazard ratio (HR) of 2.0. The secondary composite endpoint combining overall recurrent melioidosis and mortality was assessed post-hoc. Results 658 patients were enrolled: 322 to the 12-week regimen and 336 to the 20-week regimen. Five patients (2%) in the 12-week regimen and 2 patients (1%) in the 20-week regimen developed culture-confirmed recurrent melioidosis (HR 2.66; 95% confidence interval [CI] 0.52-13.69). The criterion for non-inferiority of primary event was not met (one-sided P=.37). However, all-cause mortality was significantly lower in the 12-week regimen group than in the 20-week regimen group (1 [0.3%] vs. 11 [3%]; HR 0.10; 95% CI 0.01-0.74). The criterion for non-inferiority of the secondary composite endpoint combining overall recurrent melioidosis and mortality was met (one-sided P=.022). Conclusions Based on the lower total mortality and non-inferiority of the secondary composite endpoint observed, we recommend the 12-week regimen of TMP-SMX for oral eradication treatment of melioidosis.

EBUS-TBNA diagnosis of mediastinal melioidosis in patient presented with lymphadenopathy and SVC thrombosis: A rare manifestation in non-diabetic patient

“…Previous studies have demonstrated favorable responses to ceftazidime in cases of mediastinal melioidosis [ 15 , 21 ]. Following ceftazidime, a 12-week course of trimethoprim-sulfamethoxazole was administered during the eradication phase, which is strongly supported by research [ 7 ]. Additionally, anticoagulant treatment was initiated in the initial phase to address SVC thrombosis and continued for 3 months.…”

“…In northeastern Thailand, melioidosis ranks as the third leading infectious cause of death, following HIV and tuberculosis [ 6 ]. Poorly controlled diabetes, chronic alcohol use, and chronic renal disease are known risk factors predisposing individuals to melioidosis, as they affect the function of innate immunity, particularly neutrophil function [ 1 , [5] , [6] , [7] , [8] ]. Prolonged corticosteroid uses and immunosuppressive agents also increase the risk of melioidosis [ 4 ].…”

A clinical study on clinical features,manifestations and drug resistance of melioidosis

“…Treatment outcomes and prognosis 8 : 1) treatment outcomes: a. cure: the patient tested negative for Burkholderia pseudomallei , the imaging results were unremarkable, and the clinical symptoms disappeared completely after systematic treatment; b. improvement: the patient tested negative for Burkholderia pseudomallei despite the presence of residual lesions displayed by imaging equipment or clinical symptoms; c. stable condition: the patient was still positive for Burkholderia pseudomallei but his/her clinical symptoms were moderately alleviated or remained stable; d. death: the patient died of Burkholderia pseudomallei infection during the course of treatment. 2) Prognosis: a. free of recurrence/exacerbation: the patient was cured and remained negative for Burkholderia pseudomallei during the follow-up period without recurrence of any symptoms, or the patient showed an improvement or remained stable, i.e., negative for Burkholderia pseudomallei without exacerbation of symptoms; b. post-discharge mortality: the patient died of Burkholderia pseudomallei infection due to recurrence or aggravation of the condition.…”

DNase I and chitosan enhance efficacy of ceftazidime to eradicate Burkholderia pseudomallei biofilm cells

“…Therapeutic management of melioidosis comprises initial intravenous administration of ceftazidime (CAZ) for at least 10 days, followed by oral trimethoprim-sulfamethoxazole (TMP-SMX) for 12 to 20 weeks [13][14][15] . Antimicrobial resistance of clinical B. pseudomallei is infrequent 16 but β-lactam resistance can be associated with the alteration of a gene encoding a penicillin-binding protein 3 during prolonged ceftazidime therapy 17 .…”