Evaluation of Ertapenem use with impact assessment on extended-spectrum beta-lactamases (ESBL) production and gram-negative resistance in Singapore General Hospital (SGH).

BACKGROUND: Ertapenem (preferred choice for ESBL-producing organisms) use exhibited an increasing trend from 2006 to 2008. As extensive use of ertapenem might induce the mutation of resistant bacteria strains to ertapenem, we aimed to assess the appropriateness and impact of ertapenem-use, on ESBL production, the trends of gram-negative bacterial resistance and on the utilization of other antibiotics in our institution. METHODS: Inpatients who received a dose of ertapenem during 1 January 2006 to 31 December 2008, were reviewed. Pertinent patient clinical data was extracted from the pharmacy databases and assessed for appropriateness based on dose and indication. Relevant data from Network for Antimicrobial Resistance Surveillance (Singapore) (NARSS) was extracted, to cross-correlate with ertapenem via time series to assess its impact on hospital epidemiology, trends of gram-negative resistance and consumption of other antibiotics from 2006 to mid-2010. RESULTS: 906 cases were reviewed. Ertapenem therapy was appropriate in 72.4% (93.7% success rate). CNS adverse events were noted in 3.2%. Readmission rate (30-day) due to re-infection (same pathogen) was 5.5%. Fifty cases had cultures growing Pseudomonas aeruginosa within 30 days of ertapenem initiation, with 25 cases growing carbapenem-resistant Pseudomonas aeruginosa.Ertapenem use increased from 0.45 DDD/100 patient days in 2006 to 1.2 DDD/100 patient days in mid-2010. Overall, the increasing trend of ertapenem consumption correlated with 1) increasing incidence-densities of ciprofloxacin-resistant/cephalosporin-resistant E. coli at zero time lag; 2) increasing incidence-densities of ertapenem-resistant Escherichia. coli and Klebsiella spp. at zero time lag; 3) increasing incidence-density of carbapenem-resistant Pseudomonas aeruginosa, at zero time lag.Increasing ertapenem consumption was significantly correlated with decreasing consumption of cefepime (R2 = 0.37344) 3 months later. It was significantly correlated with a decrease in imipenem consumption (R2 = 0.31081), with no time lag but was correlated with subsequent increasing consumption of meropenem (R2 = 0.4092) 6 months later. CONCLUSION: Ertapenem use was appropriate. Increasing Ertapenem consumption did not result in a decreasing trend of ESBL producing enterobacteriaceae and could result in the selection for multi-drug resistant bacteria.

National surgical antibiotic prophylaxis guideline in Singapore.

INTRODUCTION: Institutional surgical antibiotic prophylaxis (SAP) guidelines are in place at all public hospitals in Singapore, but variations exist and adherence to guidelines is not tracked consistently. A national point prevalence survey carried out in 2020 showed that about 60% of surgical prophylactic antibiotics were administered for more than 24 hours. This guideline aims to align best practices nationally and provides a framework for audit and surveillance. METHOD: This guideline was developed by the National Antimicrobial Stewardship Expert Panel's National Surgical Antibiotic Prophylaxis Guideline Development Workgroup Panel, which comprises infectious diseases physicians, pharmacists, surgeons and anaesthesiologists. The Workgroup adopted the ADAPTE methodology framework with modifications for the development of the guideline. The recommended duration of antibiotic prophylaxis was graded according to the strength of consolidated evidence based on the scoring system of the Singapore Ministry of Health Clinical Practice Guidelines. RESULTS: This National SAP Guideline provides evidence-based recommendations for the rational use of antibiotic prophylaxis. These include recommended agents, dose, timing and duration for patients undergoing common surgeries based on surgical disciplines. The Workgroup also provides antibiotic recommendations for special patient population groups (such as patients with ß-lactam allergy and patients colonised with methicillin-resistant Staphylococcus aureus), as well as for monitoring and surveillance of SAP. CONCLUSION: This evidence-based National SAP Guideline for hospitals in Singapore aims to align practices and optimise the use of antibiotics for surgical prophylaxis for the prevention of surgical site infections while reducing adverse events from prolonged durations of SAP.

Importance of control groups when delineating antibiotic use as a risk factor for carbapenem resistance, extreme-drug resistance, and pan-drug resistance in Acinetobacter baumannii and Pseudomonas aeruginosa: A systematic review and meta-analysis.

BACKGROUND: Carbapenem-resistant (CR), extremely drug-resistant (XDR), and pan-drug-resistant (PDR) Acinetobacter baumannii and Pseudomonas aeruginosa pose a huge clinical threat. This study reviews the impact of control groups on the association of antecedent antibiotic use and the acquisition of CR/XDR/PDR A. baumannii and P. aeruginosa. METHODS: Studies investigating the role of antibiotics as a risk factor for CR/XDR/PDR A. baumannii and P. aeruginosa acquisition in adult hospitalized patients from 1950 to 2016 were identified in the databases. These were divided into two groups: antibiotic-resistant versus antibiotic-sensitive pathogens (group I); antibiotic-resistant versus no infection (group II). A random-effects model was performed. RESULTS: Eighty-five studies (46 A. baumannii, 38 P. aeruginosa, and one of both) involving 22 396 patients were included. CR was investigated in 60 studies, XDR in 20 studies, and PDR in two studies. Prior antibiotic exposure was associated with significant acquisition of CR/XDR/PDR A. baumannii and P. aeruginosa in both groups I and II (p<0.05). Antibiotic classes implicated in both groups included aminoglycosides, carbapenems, glycopeptides, and penicillins. Cephalosporin use was not associated with resistance in either group. Fluoroquinolone exposure was only associated with resistance in group I but not group II. CONCLUSIONS: Control groups play an important role in determining the magnitudes of risk estimates for risk factor studies, hence careful selection is necessary. Antibiotic exposure increases the acquisition of highly resistant A. baumannii and P. aeruginosa, thus appropriate antibiotic use is imperative.

Role of antibiotic prophylaxis in necrotizing pancreatitis: a meta-analysis.

UNLABELLED: Several studies have yielded conflicting results on the role of antibiotic prophylaxis in improving outcomes in acute necrotizing pancreatitis. A meta-analysis was carried out to investigate the impact of antibiotic prophylaxis in the incidence of infected pancreatic necrosis and mortality. METHODOLOGY: Randomized controlled trials and cohort studies investigating impact of prophylactic systemic antibiotic used in acute necrotizing pancreatitis were retrieved from online databases. An overall analysis was done with all studies (Group 1), followed by subgroup analyses with randomized controlled trials (Group 2) and cohort studies (Group 3). Risk ratios (RR) were calculated for the impact of antibiotic prophylaxis in the incidence of infected pancreatic necrosis and mortality in each group using random effects model. RESULTS: Eleven studies involving 864 patients were included. No significant differences in the incidence of infected pancreatic necrosis were observed with prophylactic antibiotic use in all groups. Prophylactic antibiotic use was not associated with significant differences in all-cause mortality in Group 2 (RR = 0.75; p = 0.24) but was associated with a reduction in Groups 1 (RR = 0.66, p = 0.02) and 3 (RR = 0.55, p = 0.04). There was no statistical difference in the incidence of fungal infections and surgical interventions. CONCLUSION: Antibiotic prophylaxis does not significantly reduce the incidence of infected pancreatic necrosis but may affect all-cause mortality in acute necrotizing pancreatitis.

Impact of an antimicrobial stewardship programme on patient safety in Singapore General Hospital.

Whilst studies have shown that antimicrobial stewardship programmes (ASPs) can effectively reduce antibiotic utilisation, cost of care and even antimicrobial resistance rates, ASPs should avoid the perception that the goal is primarily to reduce antibiotic purchases and costs, instead of focusing on improving the quality of care. In addition, to address the concern of primary physicians who deemed that ASPs' choices of antibiotics were often inadequate, the impact of ASPs on patient safety should be monitored and evaluated. The aim of this study was to analyse the impact of ASP interventions on patient safety in Singapore General Hospital (SGH), a 1559-bed, large, acute, tertiary-care hospital in Singapore. A retrospective database review of data on ASP interventions issued between October 2008 and September 2010 was performed. The database maintained by the ASP team detailed patients' demographic data as well as outcomes of issued interventions. The ASP recommended 1256 interventions in a total of 1249 admissions in six departments. Shorter average length of stay (mean ± standard deviation 19.4 ± 19.9 days vs. 24.2 ± 24.2 days) was observed among patients of physicians who accepted ASP suggestions compared with patients of physicians who rejected ASP interventions (P<0.01). ASP interventions did not alter all-cause mortality (P=0.191). In addition, the number of infection-related re-admissions (P<0.001) and the 14-day re-infection rate (P=0.009) were higher among patients whose physicians rejected ASP interventions. In conclusion, interventions recommended by the ASP in SGH were safe and were associated with a reduction in the duration of hospital stay, 14-day re-infection rate and infection-related re-admissions.