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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 FROM AUTHOR]

Background: Scrub typhus (ST) is a disease caused by an obligate intracellular bacterium, Orientia tsutsugamushi, an organism that requires a BSL3 laboratory for propagation. The disease is hallmarked by an eschar at the site of the chigger bite, followed by the development of fever, malaise, myalgia, anorexia, and papulomacular rash. Indirect immunofluorescent assay (IFA) is the gold standard for scrub typhus diagnosis, however, the subjectivity of the assay, the need for a specialized laboratory and instruments has limited the wide use of the test in resource limited areas.Methods: A recombinant-protein based enzyme linked immunosorbent assay (ELISA) using the most abundant and immunodominant protein for the detection of Orientia specific antibodies in serum has been developed. The performance of the assay was evaluated using prospectively collected acute sera from 248 randomly selected patients in Thailand. The ELISA assay was evaluated using two different cutoff values.Results: The receiver operating characteristic (ROC) curve generated cutoff values gave slightly better consistency with diagnosis of ST than those cutoff values established by averaging ELISA optical density of known negatives at 99% confidence interval. Both cutoff values provided similar statistical parameters when compared with the diagnosis of ST, indicating the validity of both calculations to derive cutoff values. These results suggest that both IgG and IgM ELISA performed well to accurately diagnose scrub typhus cases in endemic areas using only acute serum samples.Conclusions: We have successfully developed an ELISA assay for the detection of Orientia-specific antibodies in serum that could provide effective screening of acute sera under clinical setup and it is also a useful assay to estimate seroprevalence in various endemic areas. [ABSTRACT FROM AUTHOR]

Objective: We aimed at comparing clinical/immunological outcomes in human immunodeficiency virus (HIV)-infected patients who were treated with CYP2B6-guided and conventional efavirenz (EFV) therapy., Methods: This study was a 24-week prospective randomized controlled trial. Eligible patients were HIV-infected adults yet to start antiretroviral therapy. Twenty-four HIV-infected patients were recruited and randomly assigned to genotype CYP2B6 polymorphism before ART initial dose. Patients with CYP2B6 *6/*6 received 400 mg EFV-based regimen and those with other genotypes received 600 mg EFV-based therapy., Results: For CYP2B6 polymorphism, 12 patients were extensive metabolizers, ten patients were intermediate metabolizers, and only two patients were poor metabolizers (*6/*6). The overall mean EFV plasma concentrations were similar in both groups. The mean drug concentrations (standard deviation) were 1.675 (0.963), 1.445 (0.778), and 1.899 (0.808) µg/mL at week 4, 12, and 24, respectively. The CYP2B6 *6/*6 patient who received low dose of EFV had lower mean EFV level than those who received a normal dose, 1.916 versus 3.915 µg/mL (P<0.001), respectively. Seventy percent of the patients had neuropsychiatric adverse events, especially dizziness., Discussion: There was a trend toward association of the CYP2B6 polymorphism and plasma EFV concentrations in this study. Reduced EFV dose should be considered in CYPB6 *6/*6 carrier to keep the drug concentration in therapeutic range.

Background: Clostridium difficile-associated disease (CDAD) is an important cause of hospital-acquired diarrhea., Objective: To determine the prevalence, risk factors, diagnosis, treatments and outcomes of the patients with CDAD in hospitalized patients at Siriraj Hospital., Material and Method: The medical records of hospitalized patients aged older than 14 years who developed hospital-acquired diarrhea and their stool samples were sent for detection of C. difficile toxins from March to June 2008 were reviewed. Risk factors of CDAD were identified by reviewing medical records of CDAD patients (case group) and patients who had hospital-acquired diarrhea without C. difficile toxins (control group). The patients in the control group were matched with the case group in terms of gender and age., Results: Three hundred and twenty three stool samples obtained from 255 adult hospitalized patients were sent to microbiology laboratory for detection of C. difficile toxins. The prevalence of CDAD in suspected C. difficile-associated hospital-acquired diarrhea was 12.3% (95% CI 8.5% to 17.6%). Univariate analysis showed that antibiotic use (> or =2 agents), proton pump inhibitor (PPI) use, hematologic malignancy, receiving chemotherapy or immunosuppressive agents were associated with CDAD. Multivariate analysis revealed that only antibiotic use (> or =2 agents), PPI use and hematologic malignancy were independent risk factors associated with CDAD. Nasogastric intubation was observed to be associated with CDAD as a protective factor from both univariate and multivariate analyses. Diagnosis of CDAD in most of the patients was made by a presence of C. difficile toxin in their stool samples. Response rate to metronidazole was 74.5%. The recurrence rate of CDAD was 3.2%. The mortality rate due to CDAD was 3.2%., Conclusion: CDAD is not uncommon in the patients with hospital-acquired diarrhea especially in those who have hematologic malignancy, receive multiple antibiotics or receive PPI. Metronidazole is an acceptable treatment for CDAD. The recurrence rate of CDAD and mortality rate due to CDAD are low.