Sappasithiprasong Hospital

Thailand

Sappasithiprasong Hospital

Thailand

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Chetchotisakd P.,Khon Kaen University | Chierakul W.,Mahidol University | Chaowagul W.,Sappasithiprasong Hospital | Anunnatsiri S.,Khon Kaen University | And 17 more authors.
The Lancet | Year: 2014

Background Melioidosis, an infectious disease caused by the Gram-negative bacillus Burkholderia pseudomallei, is difficult to cure. Antimicrobial treatment comprises intravenous drugs for at least 10 days, followed by oral drugs for at least 12 weeks. The standard oral regimen based on trial evidence is trimethoprim-sulfamethoxaxole (TMP-SMX) plus doxycycline. This regimen is used in Thailand but is associated with side-effects and poor adherence by patients, and TMP-SMX alone is recommended in Australia. We compared the efficacy and side-effects of TMP-SMX with TMP-SMX plus doxycycline for the oral phase of melioidosis treatment. Methods For this multi-centre, double-blind, non-inferiority, randomised placebo-controlled trial, we enrolled patients (aged ≥15 years) from five centres in northeast Thailand with culture-confirmed melioidosis who had received a course of parenteral antimicrobial drugs. Using a computer-generated sequence, we randomly assigned patients to receive TMP-SMX plus placebo or TMP-SMX plus doxycycline for 20 weeks (1:1; block size of ten, stratified by study site). We followed patients up every 4 months for 1 year and annually thereafter to the end of the study. The primary endpoint was culture-confirmed recurrent melioidosis, and the non-inferiority margin was a hazard ratio (HR) of 1.7. This study is registered with www.controlled-trials. com, number ISRCTN86140460. Findings We enrolled and randomly assigned 626 patients: 311 to TMP-SMX plus placebo and 315 to TMP-SMX plus doxycycline. 16 patients (5%) in the TMP-SMX plus placebo group and 21 patients (7%) in the TMP-SMX plus doxycycline group developed culture-confirmed recurrent melioidosis (HR 0.81; 95% CI 0.42-1.55). The criterion for non-inferiority was met (p=0.01). Adverse drug reactions were less common in the TMP-SMX plus placebo group than in the TMP-SMX plus doxycycline group (122 [39%] vs 167 [53%]). Interpretation Our findings suggest that TMP-SMX is not inferior to TMP-SMX plus doxycycline for the oral phase of melioidosis treatment, and is preferable on the basis of safety and tolerance by patients.


Limmathurotsakul D.,Mahidol University | Kanoksil M.,Sappasithiprasong Hospital | Wuthiekanun V.,Mahidol University | Kitphati R.,Ministry of Public Health | And 5 more authors.
PLoS Neglected Tropical Diseases | Year: 2013

Background: Melioidosis is a serious infectious disease caused by the Category B select agent and environmental saprophyte, Burkholderia pseudomallei. Most cases of naturally acquired infection are assumed to result from skin inoculation after exposure to soil or water. The aim of this study was to provide evidence for inoculation, inhalation and ingestion as routes of infection, and develop preventive guidelines based on this evidence. Methods/Principal Findings: A prospective hospital-based 1:2 matched case-control study was conducted in Northeast Thailand. Cases were patients with culture-confirmed melioidosis, and controls were patients admitted with non-infectious conditions during the same period, matched for gender, age, and diabetes mellitus. Activities of daily living were recorded for the 30-day period before onset of symptoms, and home visits were performed to obtain drinking water and culture this for B. pseudomallei. Multivariable conditional logistic regression analysis based on 286 cases and 512 controls showed that activities associated with a risk of melioidosis included working in a rice field (conditional odds ratio [cOR] = 2.1; 95% confidence interval [CI] 1.4-3.3), other activities associated with exposure to soil or water (cOR = 1.4; 95%CI 0.8-2.6), an open wound (cOR = 2.0; 95%CI 1.2-3.3), eating food contaminated with soil or dust (cOR = 1.5; 95%CI 1.0-2.2), drinking untreated water (cOR = 1.7; 95%CI 1.1-2.6), outdoor exposure to rain (cOR = 2.1; 95%CI 1.4-3.2), water inhalation (cOR = 2.4; 95%CI 1.5-3.9), current smoking (cOR = 1.5; 95%CI 1.0-2.3) and steroid intake (cOR = 3.1; 95%CI 1.4-6.9). B. pseudomallei was detected in water source(s) consumed by 7% of cases and 3% of controls (cOR = 2.2; 95%CI 0.8-5.8). Conclusions/Significance: We used these findings to develop the first evidence-based guidelines for the prevention of melioidosis. These are suitable for people in melioidosis-endemic areas, travelers and military personnel. Public health campaigns based on our recommendations are under development in Thailand. © 2013 Limmathurotsakul et al.


PubMed | Mahidol University, University of Oxford, Sappasithiprasong Hospital and London School of Hygiene and Tropical Medicine
Type: Clinical Study | Journal: PLoS neglected tropical diseases | Year: 2015

Melioidosis is an increasingly recognised cause of sepsis and death across South East Asia and Northern Australia, caused by the bacterium Burkholderia pseudomallei. Risk factors include diabetes, alcoholism and renal disease, and a vaccine targeting at-risk populations is urgently required. A better understanding of the protective immune response in naturally infected patients is essential for vaccine design.We conducted a longitudinal clinical and immunological study of 200 patients with melioidosis on admission, 12 weeks (n = 113) and 52 weeks (n = 65) later. Responses to whole killed B. pseudomallei were measured in peripheral blood mononuclear cells (PBMC) by interferon-gamma (IFN-) ELIspot assay and flow cytometry and compared to those of control subjects in the region with diabetes (n = 45) and without diabetes (n = 43).We demonstrated strong CD4+ and CD8+ responses to B. pseudomallei during acute disease, 12 weeks and 52 weeks later. 28-day mortality was 26% for melioidosis patients, and B. pseudomallei-specific cellular responses in fatal cases (mean 98 IFN- cells per million PBMC) were significantly lower than those in the survivors (mean 142 IFN- cells per million PBMC) in a multivariable logistic regression model (P = 0.01). A J-shaped curve association between circulating neutrophil count and mortality was seen with an optimal count of 4000 to 8000 neutrophils/l. Melioidosis patients with known diabetes had poor diabetic control (median glycated haemoglobin HbA1c 10.2%, interquartile range 9.2-13.1) and showed a stunted B. pseudomallei-specific cellular response during acute illness compared to those without diabetes.The results demonstrate the role of both CD4+ and CD8+ T-cells in protection against melioidosis, and an interaction between diabetes and cellular responses. This supports development of vaccine strategies that induce strong T-cell responses for the control of intracellular pathogens such as B. pseudomallei.


Limmathurotsakul D.,Mahidol University | Wongratanacheewin S.,Khon Kaen University | Teerawattanasook N.,Sappasithiprasong Hospital | Wongsuvan G.,Mahidol University | And 5 more authors.
American Journal of Tropical Medicine and Hygiene | Year: 2010

Melioidosis is a serious community-acquired infectious disease caused by the Gram-negative environmental bacterium Burkholderia pseudomallei. A prospective cohort study identified 2,243 patients admitted to Sappasithiprasong Hospital in northeast Thailand with culture-confirmed melioidosis between 1997 and 2006. These data were used to calculate an average incidence rate for the province of 12.7 cases of melioidosis per 100,000 people per year. Incidence increased incrementally from 8.0 (95% confidence interval [CI] = 7.2-10.0) in 2000 to 21.3 (95% CI = 19.2-23.6) in 2006 (P < 0.001; χ2 test for trend). Male sex, age ≥ 45 years, and either known or undiagnosed diabetes were independent risk factors for melioidosis. The average mortality rate from melioidosis over the study period was 42.6%. The minimum estimated population mortality rate from melioidosis in 2006 was 8.63 per 100,000 people (95% CI = 7.33-10.11), the third most common cause of death from infectious diseases in northeast Thailand after human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and tuberculosis. Copyright © 2010 by The American Society of Tropical Medicine and Hygiene.


Kanoksil M.,Sappasithiprasong Hospital | Jatapai A.,Mahidol University | Peacock S.J.,Mahidol University | Peacock S.J.,University of Cambridge | Limmathurotsakul D.,Mahidol University
PLoS ONE | Year: 2013

Background: National statistics in developing countries are likely to underestimate deaths due to bacterial infections. Here, we calculated mortality associated with community-acquired bacteremia (CAB) in a developing country using routinely available databases. Methods/Principal Findings: Information was obtained from the microbiology and hospital database of 10 provincial hospitals in northeast Thailand, and compared with the national death registry from the Ministry of Interior, Thailand for the period between 2004 and 2010. CAB was defined in patients who had pathogenic organisms isolated from blood taken within 2 days of hospital admission without a prior inpatient episode in the preceding 30 days. A total of 15,251 CAB patients identified, of which 5,722 (37.5%) died within 30 days of admission. The incidence rate of CAB between 2004 and 2010 increased from 16.7 to 38.1 per 100,000 people per year, and the mortality rate associated with CAB increased from 6.9 to 13.7 per 100,000 people per year. In 2010, the mortality rate associated with CAB was lower than that from respiratory tract infection, but higher than HIV disease or tuberculosis. The most common causes of CAB were Escherichia coli (23.1%), Burkholderia pseudomallei (19.3%), and Staphylococcus aureus (8.2%). There was an increase in the proportion of Extended-Spectrum Beta-Lactamases (ESBL) producing E. coli and Klebsiella pneumoniae over time. Conclusions: This study has demonstrated that national statistics on causes of death in developing countries could be improved by integrating information from readily available databases. CAB is neglected as an important cause of death, and specific prevention and intervention is urgently required to reduce its incidence and mortality. © 2013 Kanoksil et al.


Wuthiekanun V.,Mahidol University | Amornchai P.,Mahidol University | Saiprom N.,Mahidol University | Chantratita N.,Mahidol University | And 9 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2011

A 21-year survey conducted in northeast Thailand of antimicrobial resistance to parenteral antimicrobial drugs used to treat melioidosis identified 24/4,021 (0.6%) patients with one or more isolates resistant to ceftazidime (n ∇ 8), amoxicillin-clavulanic acid (n ∇ 4), or both drugs (n ∇ 12). Two cases were identified at admission, and the remainder were detected a median of 15 days after starting antimicrobial therapy. Resistance to carbapenem drugs was not detected. These findings support the current prescribing recommendations for melioidosis. Copyright © 2011 American Society for Microbiology. All Rights Reserved.


Limmathurotsakul D.,Mahidol University | Wongsuvan G.,Mahidol University | Aanensen D.,Imperial College London | Ngamwilai S.,Mahidol University | And 9 more authors.
Emerging Infectious Diseases | Year: 2014

We identified 10 patients in Thailand with cultureconfirmed melioidosis who had Burkholderia pseudomallei isolated from their drinking water. The multilocus sequence type of B. pseudomallei from clinical specimens and water samples were identical for 2 patients. This finding suggests that drinking water is a preventable source of B. pseudomallei infection.


Chantratita N.,Mahidol University | Tandhavanant S.,Mahidol University | Wongsuvan G.,Mahidol University | Wuthiekanun V.,Mahidol University | And 6 more authors.
American Journal of Tropical Medicine and Hygiene | Year: 2013

Melioidosis is a severe bacterial infection caused by Burkholderia pseudomallei. Rapid antimicrobial therapy is necessary to improve patient outcome, which is aided by direct detection of B. pseudomallei in clinical samples. A drawback for all antigen assays is that the number of B. pseudomallei in blood usually falls below the achievable level of detection. We performed a prospective cohort study of 461 patients with 541 blood cultures to evaluate the utility of a pre-incubation step prior to detection of B. pseudomallei using a monoclonal antibody-based immunofluorescent assay (Mab-IFA). TheMab-IFA was positive in 74 of 76 patients with melioidosis (sensitivity = 97.4%), and negative in 385 patients who did not have blood cultures containing B. pseudomallei (specificity = 100%). The Mab-IFA could be a valuable supplementary tool for rapid detection. We recommend the use of the Mab-IFA to test blood cultures that flag positive in regions where melioidosis is endemic. Copyright © 2013 by The American Society of Tropical Medicine and Hygiene.


Teerawattanasook N.,Sappasithiprasong Hospital | Limmathurotsakul D.,Sappasithiprasong Hospital | Day N.P.J.,Sappasithiprasong Hospital | Wuthiekanun V.,Sappasithiprasong Hospital
American Journal of Tropical Medicine and Hygiene | Year: 2014

We compared the organisms isolated from 30,210 pairs of blood culture bottles by using BacT/Alert system and the conventional system. Overall, 2,575 (8.5%) specimens were culture positive for pathogenic organisms. The sensitivity for detection of pathogenic organisms with the BACT/Alert system (85.6%, 2,203 of 2,575) was significantly higher than that with the conventional method (74.1%, 1,908 of 2,575; P < 0.0001). However, Burkholderia pseudomallei was isolated less often with the BacT/ALERT system (73.5%, 328 of 446) than with the conventional system (90.3%, 403 of 446; P < 0.0001). This finding suggests that use of the conventional culture method in conjunction with the BacT/Alert system may improve the isolation rate for B. pseudomallei in melioidosis-endemic areas. Copyright © 2014 by The American Society of Tropical Medicine and Hygiene.


Sangchan A.,Khon Kaen University | Kongkasame W.,Sappasithiprasong Hospital | Pugkhem A.,Khon Kaen University | Jenwitheesuk K.,Khon Kaen University | Mairiang P.,Khon Kaen University
Gastrointestinal Endoscopy | Year: 2012

Background: Endoscopic biliary stent drainage is effective in the palliative treatment of patients with hilar cholangiocarcinoma (HCA). However, no randomized controlled trial comparing the efficacy of the self-expandable metal stent (SEMS) and the plastic stent (PS) in patients with unresectable complex HCA is available. Objective: To compare the successful drainage rates of endoscopic SEMSs and PSs. Design: A single-center, open-label randomized controlled trial. Setting: University hospital in KhonKaen, Thailand. Patients: One hundred eight patients with unresectable complex, Bismuth type II-IV HCA. Interventions: Endoscopic retrograde cholangiography with unilateral SEMS or PS insertion. Main Outcome Measurements: Successful drainage rate. Limitations: Diagnosis of HCA was made by clinical presentations, imaging studies, and clinical outcome during follow-up. Results: One hundred eight patients were randomly allocated to the SEMS and PS groups. Intention-to-treat analysis revealed that the successful drainage rate in the SEMS group was higher than in the PS group (70.4% vs 46.3%, P = .011). The median survival times were 126 and 49 days, respectively, in the SEMS and PS groups. The overall survival rates of the patients in both groups were statistically different by log-rank test (P = .002). Conclusions: Endoscopic biliary drainage with the SEMS provides better adequacy of drainage and longer survival compared with the PS in patients with unresectable complex HCA. (Clinical trial registration number: NCT00721175.) © 2012 American Society for Gastrointestinal Endoscopy.

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