Yi Xin Liew

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

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.MethodologyRandomized 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.ResultsEleven 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.ConclusionAntibiotic prophylaxis does not significantly reduce the incidence of infected pancreatic necrosis but may affect all-cause mortality in acute necrotizing pancreatitis.

Prospective audit and feedback in antimicrobial stewardship: is there value in early reviewing within 48 h of antibiotic prescription?

Antimicrobial stewardship programme (ASP) methodologies are not well defined, with most preferring to wait ≥72-96 h following antibiotic prescription before reviewing patients. However, we hypothesise that early ASP reviews and interventions are beneficial and do not adversely impact patient safety. This study aimed to evaluate the impact of early ASP interventions within 48 h of antibiotic prescription on patient outcomes and safety. A prospective review of ASP interventions made within 48 h of antibiotic prescription in Singapore General Hospital (SGH) from January to December 2012 was conducted. Patient demographics and outcomes were extracted from the database maintained by the ASP team. For culture-directed treatment, there was a shorter mean duration of therapy (DOT) in the accepted group compared with the rejected group (2.26 days vs. 5.56 days; P<0.001). ASP interventions did not alter the length of hospital stay (LOS), 30-day mortality, 14-day Clostridium difficile infection (CDI), 30-day re-admissions and 14-day re-infection (all P>0.05). For empirical treatment, a shorter DOT (3.61 days vs. 6.25 days; P<0.001) and decreased 30-day all-cause mortality (P=0.003) and infection-related mortality (P=0.002) were observed among patients in the accepted group compared with the rejected group. There was no significant difference in LOS, 14-day CDI and 30-day re-admission (all P>0.05). In conclusion, acceptance of early interventions recommended by ASP in SGH was associated with a reduction in DOT without compromising patient safety. This is evident even during empirical therapy when not all clinical information was available.

Prevalence of Healthcare-Associated Infections and Antimicrobial Use Among Adult Inpatients in Singapore Acute-Care Hospitals: Results From the First National Point Prevalence Survey.

Background We conducted a national point prevalence survey (PPS) to determine the prevalence of healthcare-associated infections (HAIs) and antimicrobial use (AMU) in Singapore acute-care hospitals. Methods Trained personnel collected HAI, AMU, and baseline hospital- and patient-level data of adult inpatients from 13 private and public acute-care hospitals between July 2015 and February 2016, using the PPS methodology developed by the European Centre for Disease Prevention and Control. Factors independently associated with HAIs were determined using multivariable regression. Results Of the 5415 patients surveyed, there were 646 patients (11.9%; 95% confidence interval [CI], 11.1%-12.8%) with 727 distinct HAIs, of which 331 (45.5%) were culture positive. The most common HAIs were unspecified clinical sepsis (25.5%) and pneumonia (24.8%). Staphylococcus aureus (12.9%) and Pseudomonas aeruginosa (11.5%) were the most common pathogens implicated in HAIs. Carbapenem nonsusceptibility rates were highest in Acinetobacter species (71.9%) and P. aeruginosa (23.6%). Male sex, increasing age, surgery during current hospitalization, and presence of central venous or urinary catheters were independently associated with HAIs. A total of 2762 (51.0%; 95% CI, 49.7%-52.3%) patients were on 3611 systemic antimicrobial agents; 462 (12.8%) were prescribed for surgical prophylaxis and 2997 (83.0%) were prescribed for treatment. Amoxicillin/clavulanate was the most frequently prescribed (24.6%) antimicrobial agent. Conclusions This survey suggested a high prevalence of HAIs and AMU in Singapores acute-care hospitals. While further research is necessary to understand the causes and costs of HAIs and AMU in Singapore, repeated PPSs over the next decade will be useful to gauge progress at controlling HAIs and AMU.

Clinical Efficacy of Polymyxin Monotherapy versus Nonvalidated Polymyxin Combination Therapy versus Validated Polymyxin Combination Therapy in Extensively Drug-Resistant Gram-Negative Bacillus Infections.

ABSTRACT Polymyxins have emerged as a last-resort treatment of extensively drug-resistant (XDR) Gram-negative Bacillus (GNB) infections, which present a growing threat. Individualized polymyxin-based antibiotic combinations selected on the basis of the results of in vitro combination testing may be required to optimize therapy. A retrospective cohort study of hospitalized patients receiving polymyxins for XDR GNB infections from 2009 to 2014 was conducted to compare the treatment outcomes between patients receiving polymyxin monotherapy (MT), nonvalidated polymyxin combination therapy (NVCT), and in vitro combination testing-validated polymyxin combination therapy (VCT). The primary and secondary outcomes were infection-related mortality and microbiological eradication, respectively. Adverse drug reactions (ADRs) between treatment groups were assessed. A total of 291 patients (patients receiving MT, n = 58; patients receiving NVCT, n = 203; patients receiving VCT, n = 30) were included. The overall infection-related mortality rate was 23.0% (67 patients). In the multivariable analysis, treatment of XDR GNB infections with MT (adjusted odds ratio [aOR], 8.49; 95% confidence interval [CI], 1.56 to 46.05) and NVCT (aOR, 5.75; 95% CI, 1.25 to 25.73) was associated with an increased risk of infection-related mortality compared to that with treatment with VCT. A higher Acute Physiological and Chronic Health Evaluation II (APACHE II) score (aOR, 1.14; 95% CI 1.07 to 1.21) and a higher Charlson comorbidity index (aOR, 1.28; 95% CI, 1.11 to 1.47) were also independently associated with an increased risk of infection-related mortality. No increase in the incidence of ADRs was observed in the VCT group. The use of an individualized antibiotic combination which was selected on the basis of the results of in vitro combination testing was associated with significantly lower rates of infection-related mortality in patients with XDR GNB infections. Future prospective randomized studies will be required to validate these findings.

A procalcitonin-based guideline promotes shorter duration of antibiotic use safely in acute pancreatitis

We read with interest the article by Hoeboer et al. Like critically ill patients in the intensive care unit (ICU), patients with acute pancreatitis (AP) develops systemic inflammatory response syndrome, which is difficult to distinguish from sepsis. Hence, physicians often prescribe broad-spectrum prophylactic antibiotics for fear of undertreatment. This is exacerbated by the fact that early studies have reported findings in favor of prophylactic antibiotics in AP. However, these positive findings have been attributed to poor study designs, and recent randomized trials have shown that routine antibiotic prophylaxis did not confer benefits, but resulted in increased hospitalization costs and antimicrobial resistance. In light of the current situation, the Singapore General Hospital (SGH) Antimicrobial Stewardship Team (ASP) developed a procalcitonin-based guideline for AP in collaboration with the General Surgery Department, to guide prudent antibiotic prescribing (Fig. 1). Procalcitonin was employed as it can predict bacterial infections in critically ill patients and allowed early diagnosis of infected necrosis in AP. While the guideline was widely implemented in SGH, adherence was not enforced and eventual adherence was autonomously decided by the primary physician. Hence, we aim to evaluate the adherence to and impact of the guideline on antibiotic utilization and patient outcomes. A retrospective study was performed for all patients admitted from JanuaryeDecember 2011 with a primary diagnosis of AP (ICD-9 code 577.0). Patients were excluded if they were severely immunosuppressed; for patients with recurrent AP, only the first episode was included. Included patients were segregated into two groups: adherence (Group I) and non-adherence to protocol (Group II). The allocation of patients to either group was decided independently by the two study members; if a lack of consensus was observed, the opinion of a third member was sought. The study was approved by the institutional ethics committee. The primary outcome was difference in intravenous antibiotic use (days of therapy); in addition, an adjusted outcome was estimated using multi-variable regression, to correct for differences in baseline. Secondary outcomes included differences in 30-day crude mortality, days to enteral feeding, days to resolution of fever and white blood cell (WBC) count. Sample size requirements were estimated based on the PRORATA trial; assuming a mean of 10.8 days therapy in the non-adherence group, approximately 95 patients per group provided power of 80% (two-sided

A multidisciplinary antimicrobial stewardship programme safely decreases the duration of broad-spectrum antibiotic prescription in Singaporean adult renal patients

Patients with chronic kidney disease have increased risk of infections. Thus, physicians may favour prolonged broad-spectrum antibiotic use. Studies focused on antimicrobial stewardship programmes (ASPs) in renal patients are currently lacking. Here we describe the role of a multidisciplinary ASP and the impact of ASP interventions in renal patients. A multidisciplinary ASP was initiated at a tertiary hospital in Singapore. Patients prescribed broad-spectrum parenteral antibiotics were identified daily and were subjected to prospective review with immediate concurrent feedback. ASP data from January 2010 to December 2011 were analysed for all renal patients. Outcome measures included the duration and appropriateness of antibiotics, intervention acceptance rates, cost savings and safety outcomes. A total of 2084 antibiotic courses were reviewed, of which 24% were inappropriate, with meropenem most commonly prescribed inappropriately (31.0%). The commonest reasons for inappropriate use were wrong choice (51.0%) and wrong duration (21.4%). In total, 634 recommendations were made, with high acceptance rates (73.3%). Recommendations to discontinue antibiotics (33.4%) and to optimise doses (17.2%) comprised the bulk of ASP work. A mean reduction of -1.28 days of antibiotic use was observed among patients with interventions accepted versus those rejected (P<0.001), with direct cost savings of SGD

An interactive, point-of-care, computerised antibiotic prescription decision support system and quality of antibiotic prescription in the management of complicated urinary tract infection ☆

90,045. No difference in 30-day mortality (P=0.91) was observed between the accepted and rejected intervention groups. In conclusion, a multidisciplinary ASP resulted in a shorter duration of antibiotic use without compromising safety in renal patients. Continued effort is needed to produce a long-term impact on antibiotic prescription and resistance.

Cost effectiveness of an antimicrobial stewardship programme.

Antimicrobial resistance is a major public health problem. Antimicrobial stewardship programmes (ASPs) have been shown to contain or reduce resistance without adversely impacting the quality of care [1]. Computerised antibiotic prescription systems have been used and can circumvent the limitations of lack of manpower [2]. At Tan Tock Seng Hospital, a 1400-bed university teaching hospital in Singapore, there was an average of 200 new antibiotic orders a day, and 37.8% of carbapenem prescriptions were inappropriate and represented an opportunity for antimicrobial stewardship [3]. In this study, the safety and efficacy of an in-house computerised decision support system in the treatment of complicated urinary tract infections (cUTI) was evaluated. A computer program based on the hospital’s guidelines was designed, which is integrated into a doctor’s antibiotic ordering and interfaced with laboratory and pharmacy information system called ARUS-C (Antibiotic Resistance Utilization and Surveillance–Control). ARUS-C is accessed through the electronic inpatient medication record. It provides recommendations for empirical, definitive and prophylactic antibiotic use. When positive microbiology results are unavailable, ARUS-C provides antibiotic recommendations depending on available clinical laboratory information and other data manually entered by the doctor. Specific infectious diseases and use of active empirical antibiotics are considered when determining the duration of antibiotics. All antibiotic recommendations are adjusted for renal function, and drug allergies are accounted for. ARUS-C also provides alerts and clues that will help decide on diagnosis and management. The doctor preserves autonomy and the whole process takes 20 s. ARUS-C can be a passive guidance tool that is initiated by the doctor or can provide active guidance by mandating compulsory guidance when ‘restricted antibiotics’ are ordered. Any override of ARUS-C recommendations can be routed to the ASP team to allow timely audit and feedback. Prior to implementation, briefing and orientation were conducted and a user manual was made available. A retrospective study was performed from 31 August 2009 to 3 January 2010 to evaluate the effect of passive guidance of

Optimisation of antimicrobial dosing based on pharmacokinetic and pharmacodynamic principles

We read with interest the recent article by Coulter et al. [1]. n their review, the authors concluded that there is an urgent need or full economic evaluations that compare relative changes both in linical and cost outcomes to enable identification of the most costffective antimicrobial stewardship strategies in hospitals. Indeed, e concurred with this view and reported our cost analysis study ased on patients in whom the antimicrobial stewardship proramme (ASP) intervened. The increasing prevalence of antimicrobial-resistant microrganisms and the rising costs of medical care have led to the andatory implementation of ASPs in all major public hospitals y the Ministry of Health in Singapore [2]. Given the upfront peronnel expenses required to initiate such programmes, return on nvestment remains a concern. We previously reported that interentions recommended by the ASP in Singapore General Hospital SGH) were safe and were associated with a reduction in the duraion of hospital stay, 14-day re-infection rate and infection-related e-admissions, which may potentially translate to cost savings [3]. ence, we conducted a cost analysis study in the same study groups f patients to evaluate whether there was any cost savings to the ospital bill. SGH is a 1559-bed, urban, tertiary-care hospital in Singapore. A etrospective review of the ASP database was conducted focusing n selected safety outcomes [length of hospital stay (LOS), redmissions, 14-day re-infection and mortality] among all patients n whom the institution’s ASP team had prospectively intervened n the broad-spectrum antibiotics prescribed between October 008 and September 2010. Patients were classified into two groups: i) those whose physicians accepted ASP interventions (accepted roup); and (ii) those whose physicians rejected ASP intervenions (rejected group). Hospital bills for these patients were then etrieved from the Department of Finance and were compared etween the accepted and rejected groups. During the study period, atients in involved departments occupied 250 588 bed-days from 2 425 admissions. The SingHealth Centralised Institutional Review oard approved this study. Informed consent was not obtained rom individual patients as the operations of the ASP constiuted routine clinical practice and only anonymised data were nalysed. The demographics and clinical characteristics of patients in hom the ASP interventions were accepted or rejected are escribed in Table 1. The ASP team recommended 1256 interentions in a total of 1249 admissions between October 2008 nd September 2010, of which 743 potentially could have an mpact on patient safety. Overall acceptance of these intervenions was 77.8% (578/743), whilst the remaining 165 interventions 22.2%) were rejected by the primary healthcare team. LOS between

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

While suboptimal dosing of antimicrobials has been attributed to poorer clinical outcomes, clinical cure and mortality advantages have been demonstrated when target pharmacokinetic (PK) and pharmacodynamic (PD) indices for various classes of antimicrobials were achieved to maximise antibiotic activity. Dosing optimisation requires a good knowledge of PK/PD principles. This review serves to provide a foundation in PK/PD principles for the commonly prescribed antibiotics (β-lactams, vancomycin, fluoroquinolones and aminoglycosides), as well as dosing considerations in special populations (critically ill and obese patients). PK principles determine whether an appropriate dose of antimicrobial reaches the intended pathogen(s). It involves the fundamental processes of absorption, distribution, metabolism and elimination, and is affected by the antimicrobials physicochemical properties. Antimicrobial pharmacodynamics define the relationship between the drug concentration and its observed effect on the pathogen. The major indicator of the effect of the antibiotics is the minimum inhibitory concentration. The quantitative relationship between a PK and microbiological parameter is known as a PK/PD index, which describes the relationship between dose administered and the rate and extent of bacterial killing. Improvements in clinical outcomes have been observed when antimicrobial agents are dosed optimally to achieve their respective PK/PD targets. With the rising rates of antimicrobial resistance and a limited drug development pipeline, PK/PD concepts can foster more rational and individualised dosing regimens, improving outcomes while simultaneously limiting the toxicity of antimicrobials.