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.
Subject(s)
Melioidosis , Trimethoprim, Sulfamethoxazole Drug Combination , Administration, Oral , Australia , Humans , Melioidosis/drug therapy , Thailand , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic useABSTRACT
Background: Helicobacter pylori (H. pylori) infection is related to peptic ulcer diseases and gastric cancer and eradication of H. pylori should be expected to decrease the risk of their development. Factors affecting H. pylori eradication are antibiotic resistance, CYP2C19 genotypes, drug regimen and patient compliance. Increment of omeprazole and amoxicillin dosage in clarithromycin-containing triple therapy regimen may overcome these problems and may be a better choice than the conventional clarithromycin-containing triple therapy regimen. Objective: To compare the eradication rates with modified triple therapy (MTT) and standard triple therapy (STT) as first-line treatment. Materials and Methods: The study was an open label, multicenter, randomized controlled trial. A total of 170 patients infected with H. pylori diagnosed by rapid urease test were randomly assigned into 2 groups. The first was treated with a 14-day MTT (20 mg omeprazole t.i.d., 500 mg amoxicillin t.i.d., and 500 mg clarithromycin b.i.d.) and the second with a 14-day STT (20 mg omeprazole b.i.d., 1000 mg amoxicillin b.i.d., and 500 mg clarithromycin b.i.d.). H. pylori eradication was evaluated by 14C-urea breath test. CYP2C19 genotypes, clarithromycin resistance, side effects and patient compliance were also recorded. Results: There were 85 patients in each group. The H. pylori eradication rate in the MTT group was 84.7% by ITT analysis and 91.1% by PP analysis, compared to the STT group values of 76.5% and 87.8% (p = 0.18 and 0.51), respectively. CYP2C19 genotypes and patient compliance were similar in both groups. Prevalence of clarithromycin resistance was 7.0%. Side effects were all mild with no significant differences between the twogroups. Conclusions: MTT is not superior to STT. From this study, MTT may not be recommended as the first-line treatment for H. pylori infection in Thailand because eradication rates proved to be less than 90% by ITT analysis.
