Epidemiology of ventilator-associated tracheobronchitis and ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria at a tertiary care hospital in Thailand.

Objectives: To investigate the epidemiology of MDR Gram-negative bacilli ventilator-associated tracheobronchitis (MDR GNB-VAT) and MDR GNB ventilator-associated pneumonia (MDR GNB-VAP) among mechanically ventilated patients. Methods: We conducted a retrospective observational study among hospitalized patients who underwent continuous mechanical ventilation for ≥48 h at Siriraj Hospital, Thailand. Results: During the 18 month study period, 1824 unique patients underwent continuous mechanical ventilation (12 216 ventilator-days). The cumulative incidences of MDR GNB-VAT and -VAP were 8.4% and 8.3%, respectively. The incidence rates of MDR GNB-VAT and -VAP were 12.52 and 12.44 episodes/1000 ventilator-days, respectively. Among those with VAT, the cumulative incidence and incidence rate of subsequent VAP development within 7 days were 11.76% and 2.81 episodes/1000 ventilator-days, respectively. The median durations of mechanical ventilation before having VAP and VAT were 9 and 12 days, respectively. Multivariate analysis identified three independently associated factors for patients having VAP compared with having VAT: underlying cerebrovascular disease [adjusted OR (aOR): 0.46; 95% CI: 0.27-0.78; P = 0.04], previous surgery (aOR: 0.68; 95% CI: 0.57-0.8; P < 0.001) and acute renal failure (aOR: 1.75; 95% CI: 1.27-2.40; P = 0.001). Conclusions: The study revealed high incidences of MDR GNB-VAT and -VAP among mechanically ventilated patients. The independent risk factors for having VAP can help identify patients at risk for developing VAP and who need early weaning from mechanical ventilation.

Influence of occupational exposure to pigs or chickens on human gut microbiota composition in Thailand.

Pig farming's influence on human gut microbiota has been observed previously, but its pervasiveness is unclear. We therefore aimed at studying whether pig farming influenced human gut microbiota composition in Thailand and whether poultry farming did too. We collected human stool samples (71 pig farmers, 131 chicken farmers, 55 non-farmers) for 16S rRNA sequencing and performed subsequent DADA2 analyses of amplicon sequence variants. We found that Alpha diversity values were highest among chicken farmers. Relative abundances of Prevotellaceae were significantly higher among pig farmers than among chicken farmers and non-farmers (p < 0.001). Beta diversity plots revealed different clustering according to occupation. The presence or absence of antimicrobial-resistant Escherichia coli was not associated with changes in gut microbiota composition. In conclusion, occupation was the strongest factor influencing gut microbiota composition in Thailand. We hypothesize that Prevotellaceae amplicon sequence variants are transmitted from pigs to pig farmers.

A One Health approach to assessing occupational exposure to antimicrobial resistance in Thailand: The FarmResist project.

This Southeast Asia-Europe research project will use a One Health approach to identify the major parameters responsible for the presence of animal-associated antimicrobial resistant bacteria in animal production facilities in Thailand and the risk of their transmission from animals to humans. We will focus on traditional, small, extensive pig and poultry farms where information on antibiotic use is scarce and animals live in close contact with humans. This cross-sectional study will be based on the epidemiological analysis of the antimicrobial resistance (AMR) present in fecal samples from animals and humans. Extended spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) and Enterobacteriaceae resistant to colistin will be actively searched in the feces of farm animals (pigs and poultry), small wild rodents and farmers. Phenotypic (selective plating) and genotypic (multilocus seuquence typing and sequencing) methods will be used for the detection of AMR, the identification of antibiotic resistance genes (ARGs) and the characterization of strains carrying resistance genes. Questionnaires will be administered to investigate the effects of antibiotic use, farm characteristics and biosecurity measures on the occurrence of AMR in animals. Subsequently, the fecal carriage of AMR and ARGs in farmers will be compared to a control population with no occupational contacts with animals, thus enabling an estimation of the risk of transmission of AMR/ARGs from animals to farmers.

Accuracy of ICD-10 Coding System for Identifying Comorbidities and Infectious Conditions Using Data from a Thai University Hospital Administrative Database.

OBJECTIVE: To determine the accuracy of International Statistical Classification of Disease and Related Health Problems, 10th Revision (ICD-10) coding system in identifying comorbidities and infectious conditions using data from a Thai university hospital administrative database. MATERIAL AND METHOD: A retrospective cross-sectional study was conducted among patients hospitalized in six general medicine wards at Siriraj Hospital. ICD-10 code data was identified and retrieved directly from the hospital administrative database. Patient comorbidities were captured using the ICD-10 coding algorithm for the Charlson comorbidity index. Infectious conditions were captured using the groups of ICD-10 diagnostic codes that were carefully prepared by two independent infectious disease specialists. Accuracy of ICD-10 codes combined with microbiological dataf or diagnosis of urinary tract infection (UTI) and bloodstream infection (BSI) was evaluated. Clinical data gathered from chart review was considered the gold standard in this study. RESULTS: Between February 1 and May 31, 2013, a chart review of 546 hospitalization records was conducted. The mean age of hospitalized patients was 62.8 ± 17.8 years and 65.9% of patients were female. Median length of stay [range] was 10.0 [1.0-353.0] days and hospital mortality was 21.8%. Conditions with ICD-10 codes that had good sensitivity (90% or higher) were diabetes mellitus and HIV infection. Conditions with ICD-10 codes that had good specificity (90% or higher) were cerebrovascular disease, chronic lung disease, diabetes mellitus, cancer HIV infection, and all infectious conditions. By combining ICD-10 codes with microbiological results, sensitivity increased from 49.5 to 66%for UTI and from 78.3 to 92.8%for BS. CONCLUSION: The ICD-10 coding algorithm is reliable only in some selected conditions, including underlying diabetes mellitus and HIV infection. Combining microbiological results with ICD-10 codes increased sensitivity of ICD-10 codes for identifying BSI. Future research is needed to improve the accuracy of hospital administrative coding system in Thailand.

Preliminary clinical study of the effect of ascorbic acid on colistin-associated nephrotoxicity.

Nephrotoxicity is a dose-limiting factor of colistin, a last-line therapy for multidrug-resistant Gram-negative bacterial infections. An earlier animal study revealed a protective effect of ascorbic acid against colistin-induced nephrotoxicity. The present randomized controlled study was conducted in 28 patients and aimed to investigate the potential nephroprotective effect of intravenous ascorbic acid (2 g every 12 h) against colistin-associated nephrotoxicity in patients requiring intravenous colistin. Thirteen patients received colistin plus ascorbic acid, whereas 15 received colistin alone. Nephrotoxicity was defined by the RIFLE classification system. Additionally, urinary neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl-beta-d-glucosaminidase (NAG) were measured as markers of renal damage, and plasma colistin concentrations were quantified. The baseline characteristics, clinical features, and concomitant treatments of the patients in the two groups were comparable. The incidences of nephrotoxicity were 53.8% (7/13) and 60.0% (9/15) in the colistin-ascorbic acid group and the colistin group, respectively (P = 0.956; relative risk [RR], 0.9; 95% confidence interval, 0.47 to 1.72). In both groups, the urinary excretion rates of NGAL and NAG on day 3 or 5 of colistin treatment and at the end of colistin treatment were significantly higher than those at the respective baselines (P < 0.05). However, the urinary excretion rates of these biomarkers at the various times during colistin treatment did not differ significantly between the groups (P > 0.05). The plasma colistin concentrations in the two groups were not significantly different (P > 0.28). The clinical and microbiological outcomes and mortality of the patients in the two groups were not significantly different. This preliminary study suggests that ascorbic acid does not offer a nephroprotective effect for patients receiving intravenous colistin. (This study has been registered at ClinicalTrials.gov under registration no. NCT01501968.).

Prevalence of antibiotic resistance in fecal flora of patients undergoing transrectal ultrasound-guided prostate biopsy in Thailand.

OBJECTIVE: The objective of this study was to determine the prevalence of antibiotic resistance in fecal flora of patients undergoing transrectal ultrasound-guided needle biopsy of the prostate (TRUSB) and the factors associated with such antibiotic resistance. METHODS: A prospective study of patients undergoing TRUSB was conducted. Rectal swabs were performed and sent for cultures and antibiotic susceptibility testing before TRUSB. Clinical characteristics were determined. RESULTS: 287 Gram-negative isolates from 144 patients were identified, 80.1% were Escherichia coli and 13.9% were Klebsiella pneumoniae. 27 patients who received antibiotics within 3 months exhibited higher prevalence of organisms with extended-spectrum beta-lactamases (ESBL) production (40.7 vs. 22.2%) and ceftriaxone-resistance (48.1 vs. 28.2%). 134 patients received a short-course antibiotic prophylaxis in which fluoroquinolone (FQ) contributed to 89.6% of cases. Patients who received antibiotic prophylaxis showed a higher prevalence of organisms resistant to ceftriaxone (34.3 vs. 0%), ciprofloxacin (90.3 vs. 30%) and FQ (95.5 vs. 50%) and a trend of more ESBL production (27.6 vs. 0%). CONCLUSIONS: Previous antimicrobial use and prophylaxis with FQ are correlated with a higher prevalence of FQ and ceftriaxone resistance and ESBL production. A single dose of ceftriaxone without short-course FQ use is recommended as antibiotic prophylaxis in TRUSB.

Epidemiology of suspected Clostridium difficile-associated hospital-acquired diarrhea in hospitalized patients at Siriraj Hospital.

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.

Comparison of the efficacy and safety between generic intravenous omeprazole (Zefxon) and original omeprazole (Losec) in the adjunct treatment of non-variceal upper gastrointestinal bleeding in Siriraj Hospital.

BACKGROUND: Clinical efficacy and safety of generic omeprazole have not been well studied in Thailand. OBJECTIVE: Determine whether generic omeprazole (Zefxon) is inferior to original omeprazole (Losec) in the treatment of non-variceal upper gastrointestinal bleeding (UGIB) in Siriraj Hospital. MATERIAL AND METHOD: Medical records of adult patients with the diagnosis of non-variceal UGIB receiving intravenous omeprazole (either Zefxon or Losec) in Siriraj Hospital between January 2006 and September 2010 were reviewed Noninferiority study was used to investigate whether the generic omeprazole was no more than 10% less effective than the original omeprazole. The primary endpoints were recurrent bleeding and mortality within seven and 30 days. Surgery, endoscopic retreatment, blood transfusions, length of hospital stay and safety were also analyzed RESULTS: Of 200 randomly selected patients in each group, there was no difference in age, gender co-morbidities, severity of UGIB, endoscopic findings and endoscopic intervention between patients receiving generic omeprazole and original omeprazole. Overall rate of recurrent bleeding, mortality, and surgical intervention within 30 days were 12.3%, 5.5% and 2.0%, respectively. The rates of recurrent bleeding, overall mortality, and non-variceal UGIB related mortality within seven and 30 days were not significantly different between the two groups. Neither were the rates of endoscopic retreatment and surgery. The incidence of adverse side effects was 3.5% in each group. Cox regression analysis showed no significant association between type of omeprazole and recurrent bleeding or mortality. Compared to the original omeprazole, the hazard ratio of recurrent bleeding, overall mortality, and non-variceal UGIB related mortality in patients receiving generic omeprazole was 1.44 (95% CI 0.82-2.53; p = 0.21), 2.12 (95% CI 0.90-5.43; p = 0.08) and 1.82 (95% CI 0.53-6.21; p = 0.34), respectively. CONCLUSION: Although the original omeprazole Losec tended to have more favorable outcomes in the treatment of non-variceal UGIB in the present study, non-inferiority test showed that the efficacy and safety of the generic omeprazole Zefxon was not inferior to those of the original omeprazole.

Clinical impact of methicillin resistance on outcome of patients with Staphylococcus aureus infection: a stratified analysis according to underlying diseases and sites of infection in a large prospective cohort.

OBJECTIVE: This study was conducted to identify the predictors of mortality and to evaluate the impact of methicillin resistance on outcome in patients with Staphylococcus aureus infection according to underlying conditions and type of infection. METHODS: An observational cohort study including 4949 patients with S. aureus infection was conducted. We compared data from patients with MRSA infection with those with MSSA infection. RESULTS: The 30-day mortality rate of MRSA group was significantly higher than that of MSSA group (15.6% vs. 6.2%, P < 0.001). However, MRSA infection was not found to be independent risk factor for mortality after adjusting for other variables (OR = 1.03, 95% CI = 0.80-1.32). When we analyzed patients with S. aureus bacteremia (n = 709), MRSA infection was found to be significantly associated with mortality in multivariate analysis (Adjusted OR = 1.69, 95% CI = 1.15-2.49). When the 30-day mortality rates were compared according to underlying diseases, the 30-day mortality rate of MRSA group was significantly higher than that of MSSA group in patients with malignancy or renal diseases. MRSA infection was also found to be one of the independent risk factors for mortality in patients with malignancy (adjusted OR = 1.69, 95% CI = 1.06-2.70) and in those with renal disease (adjusted OR = 1.70, 95% CI = 1.0-2.89), after adjustment for host variables. CONCLUSIONS: Methicillin resistance adversely affected the outcome of patients with S. aureus infection, in patients with cancer or renal disease and in those with S. aureus bacteremia, although MRSA infection was not found to be significantly associated with higher mortality in overall patient population.

Immune responses of selected phagotopes from monoclonal antibodies of Burkholderia pseudomallei.

Random peptide libraries displayed by bacteriophage T7 and M13 were employed to identify mimotopes from 4 monoclonal antibodies (MAbs) specific to Burkholderia pseudomallei. Insert DNA sequences of bound phages selected from four rounds of panning with each MAb revealed peptide sequences corresponding to B. pseudomallei K96243 hypothetical protein BPSL2046, hypothetical protein BpseP_02000035, B. pseudomallei K96243 hypothetical protein BPSS0784, B. pseudomallei 1710b hypothetical protein BURPS1710b_1104, and B. cenocepacia H12424 TonB-dependent siderophore receptor, all located at the outer membrane. The immune responses from all selected phagotopes were significantly higher than that of lipopolysaccharide. The study demonstrates the feasibility of identifying mimotopes through screening of phage-displayed random peptide libraries with B. pseudomallei MAbs.

Vancomycin overuse in Siriraj Hospital.

OBJECTIVE: An emergence of vancomycin resistant organisms particularly vancomycin-resistant enterococci (VRE) has become a serious public health concern. To prevent and control the spread of vancomycin resistant organisms, the prudent use of vancomycin is strongly recommended by the Hospital Infection Control Practices Advisory Committee (HICPAC). MATERIAL AND METHOD: A 6-week prospective observational study of vancomycin use was conducted in hospitalized patients at Siriraj Hospital from February to March 2005. Indications of initiating and continuing vancomycin were categorized according to HICPAC recommendations. Factors related to the appropriateness of vancomycin use were also evaluated. RESULTS: At initiation, vancomycin was inappropriately and empirically prescribed 19/222 times (8.6%) and 166/222 times (74.8%), respectively. After microbiological results were obtained, the rate of inappropriate prescription continued 132/222 times (59.5%). Furthermore, inappropriate use was significantly correlated with the type of department. There was a higher rate in the Department of Pediatrics, Surgery and Ophthalmology when compared with that of the Department of Medicine (p = 0.001). The inappropriate use also correlated with topical use (p < 0.001), intravenous administration (p = 0.012) and no consultation with an infectious disease specialist (p = 0.001). The overuse did not improve the clinical outcome. CONCLUSION: A substantial rate of inappropriate use of vancomycin was found in Siriraj Hospital. Intervention to improve appropriateness of vancomycin use should be urgently implemented to prevent and control the emergence of vancomycin resistant organisms.

Risk index for predicting complications and prognosis in Thai patients with neutropenia and fever.

BACKGROUND: New strategies in the treatment of febrile neutropenic patients have been proposed during the past decade. It is more and more widely accepted that febrile neutropenic patients are a heterogeneous population and they have varying risks for complications and death. However, most of the data have been collected from patients in Western countries. The purpose of the study was to identify types of infection and etiologic organisms in febrile neutropenic patients at Siriraj Hospital, Thailand, and also to develop a prediction model in order to identify patients who are expected to have a favorable outcome or a low-risk subset. METHOD: The medical records of chemotherapy-induced neutropenic patients with fever hospitalized at Siriraj Hospital, Thailand, from January 1999 to December 2000 were analyzed. Data included patient characteristics, epidemiological data and the potential factors at the onset of fever for predicting patient outcome. A scoring system for predicting patients with favorable outcome was developed. The scoring system developed from this study was compared with a previously used scoring system. RESULTS: Of 220 patients with 267 febrile neutropenic episodes, 71.8 per cent had hematologic malignancies and 28.2 per cent had solid tumors. Bacteremia was found in 61 episodes (22.8%) and gram negative bacilli were the most common causative organism in bacteremia (88.6%). Overall mortality was 17.7 per cent. Multivariate analysis revealed that the factors predicting outcome were burden of illness, control of cancer, duration of neutropenia and dehydration. The scoring system developed from this set of data revealed that a score > or = 16 identified patients with a favorable outcome with a specificity of 90.2 per cent, sensitivity of 76.6 per cent and positive predictive value of 85.4 per cent. CONCLUSION: The causative organisms of bacterial infections in febrile neutropenic patients in Thailand are still gram negative bacteria. The locally developed risk index has a fair accuracy to identify patients with favorable outcome and may be used to identify patients suitable for less aggressive treatment strategies.

Risk factors for falls in the Thai elderly in an urban community.

BACKGROUND: Instability or falls in the elderly are a health condition meeting all criteria for prevention i.e. high frequency, evidence of preventability and a high burden of morbidity. The consequences of a fall affect not only the elderly per se such as fractures and various kinds of physical and mental impairment, but also the family and the society as a whole in terms of the financial expenditure involved. The need for a comprehensive study to identify the risk factors for falls among the Thai elderly is, therefore, crucial for further management. OBJECTIVE: To identify the significant risk factors for falls among the Thai elderly for further prevention and management. METHOD: A cross-sectional study in the urban community around Siriraj Hospital, Bangkok. 1,043 community-dwelling people aged > or = 60 years were recruited. A structured questionnaire, including mental test and physical examinations as well as various laboratory tests, were used to identify the risk factors for falls between faller and control groups. RESULTS: The overall prevalence of falls among elderly Thais in an urban area was 19.8 per cent during a period of 6 months. However, the prevalence was 24.1 per cent in women but only 12.1 per cent in men. Older people who were likely to fall also had a lower bone mass which predisposed them to future fractures. The independent risk factors for falls after multiple logistic regression analysis were: female gender, hypertension, deafness, poor memory, poor self-perceived health status, poor performance in the instrumental activities of daily living, kyphoscoliosis, use of spectacles, rapid pulse rate after a 5 minute rest, higher serum transferrin and poor nutrition in terms of low lean body mass and reduced serum albumin level. CONCLUSIONS: Special sense, activity of daily living, nutritional status, kyphoscoliosis, hypertension and cognitive ability were six important factors determining the likelihood of fall among the elderly in an urban area.

Risk factors for Pseudomonas aeruginosa bacteremia in Thai patients.

A case control study to determine the risk factors for P. aeruginosa bacteremia was conducted in patients admitted to Siriraj Hospital in 1998. The case group consisted of 65 patients with P. aeruginosa bacteremia. There were 3 control groups. 65 patients with E. coli bacteremia, 64 patients with S. aureus bacteremia and 65 patients without bacteremia. Demographic information and potential risk factors i.e. type of infection, associated diseases/conditions, procedures/surgery, previous/current use of antibiotics and previous/current use of immunosuppressive/cytotoxic agents were extracted from the patients' medical records and compared. Univariate analysis revealed that the factors associated with P. aeruginosa bacteremia were infections acquired while hospitalized, hematologic malignancy, neutropenia, COPD, antibiotic receivers, cytotoxic agents receivers. However, multivariate analysis revealed that only hematologic malignancy, infections acquired while hospitalized and previous use of parenteral antibiotics were risk factors for P. aeruginosa bacteremia.

Efficiency of the glutaraldehyde test strip for monitoring the concentration of glutaraldehyde in reused solutions for disinfecting endoscopes.

BACKGROUND: Glutaraldehyde has been widely used for low-temperature disinfection of endoscopes. The current practice at Siriraj Hospital is to change the glutaraldehyde solution every 21 days or when the solution appears turbid. The disadvantages of this practice include inadequate disinfection of endoscopes if the concentration of glutaraldehyde in a reused solution is insufficient or wasted if the discarded solution is still active. OBJECTIVE: To determine the efficiency of a glutaraldehyde test strip (GTS) in monitoring the amount of glutaraldehyde in a reused solution for disinfecting endoscopes. METHOD: Reused glutaraldehyde solutions for disinfecting bronchoscopes, gastroscopes and colonoscopes were tested for the concentration of glutaraldehyde with a GTS thrice weekly for the first week and then every working day up to 56 days. If the GTS indicated a concentration of glutaraldehyde > or = 1.8 per cent after 21 days, 5 ml of the solution was taken to the laboratory to determine its mycobactericidal activity. RESULTS: All samples of the reused glutaraldehyde solution up to 56 days with a concentration of > or = 1.8 per cent glutaraldehyde on GTS from testings showed mycobactericidal activity. If the glutaraldehyde solution was reused for up to 28, 42 or 56 days, it could save 9,603; 22,813 and 29,415 baht per year respectively for the gastroscopy and colonoscopy units. The corresponding figures were -949; 2,726 and 4,564 baht per year for the bronchoscopy unit. It is estimated that up to 400,000 baht per year could be saved by adopting the strategy of GTS monitoring in all endoscopy units at Siriraj Hospital. CONCLUSION: The current strategy of discarding reused glutaraldehyde solution in the gastroscopy, colonoscopy and bronchoscopy units at Siriraj Hospital may be inappropriate since the reused solution is still mycobactericidal for up to 56 days.