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Antibiotic stewardship programs (ASPs) are well established in the public hospitals in Singapore, but they are not mandatory for transplant programs. Given the positive impact of ASPs in non-organ transplant patients (improved use of broad-spectrum antibiotics, reduced length of stay, and lower healthcare costs), stewardship principles are likely to benefit transplant recipients.We reviewed the progress made in ASPs in the Asia Pacific region as well as the progress of our ASP over the last decade since it was established. We also described how stewardship strategies have evolved for the purposes of our transplant program.Currently, pressing stewardship issues for our transplant program include high antibiotic consumption, as well as the burden, morbidity, and mortality associated with drug-resistant bacterial infections. Transplanting the model of stewardship onto a transplant program ignores the intricacies of transplant patients; the bespoke form of stewardship, "handshake stewardship", is more appropriate.To advance the cause of ASP in the transplant unit in Singapore, stakeholder buy-in is key; empowering transplant physicians to be stewardship-focused would be more sustainable in the long run. In addition, expanding our diagnostic armamentarium, optimizing existing therapeutics and multi-disciplinary team involvement (including stakeholders from microbiology, and infection prevention teams) are vital.

Highlights • During the COVID-19 outbreak, antibiotic use has increased, especially respiratory antibiotics. • Healthcare resources are diverted to containment and management of COVID-19 cases, but the efforts of antibiotic stewardship programmes (ASPs) must run in parallel to mitigate antibiotic misuse and antimicrobial resistance. • ASPs must be operationally adaptable, and possess robust surveillance systems that detect subtle changes in prescribing and resistance trends. • This is an opportunity to execute a syndromic approach to guide antibiotic prescribing. • Continued engagement and education of prescribers to ensure appropriate prescription of antibiotics is important., Healthcare resources are being diverted for the containment and control of coronavirus disease 2019 (COVID-19). During this outbreak, it is cautioned that antibiotic misuse may be increased, especially for respiratory tract infections. With stewardship interventions, the duration of antibiotic therapy and length of stay of hospitalized patients can be reduced significantly. Antibiotic stewardship programmes should continually engage and educate prescribers to mitigate antibiotic misuse during the COVID-19 pandemic.

Background Rising rates of antimicrobial resistance worldwide has dire consequences on patient care, as infections with resistant organisms impair patients’ recovery, resulting in protracted illness and hence prolonged hospital stay. Antimicrobial Stewardship Programs (ASPs) have shown to effectively reduce antibiotic resistance. Locally, we observed that patients with neurological conditions were often initiated on antibiotics for change in mental state or isolated fevers. Little is known whether these patients truly require antibiotics and hence, we aim to study the impact of ASP in these patients. Methods Retrospective review of ASP database between January 2014 and December 2017 was conducted, among all patients admitted to the neurology department in SGH and in whom the ASP team recommended discontinuation of empiric use of antibiotics. Demographics were collected. Clinical outcomes, duration of antibiotics therapy, length of hospital stay (LOS), infection-related readmissions and mortality, were compared between interventions accepted and rejected groups. Results The ASP team recommended 184 interventions [overall acceptance rate of 82.6% (152/184)]. There was no significant difference in underlying demographics, and Charlson Co-morbidity score between the 2 groups. However, the interventions-acceptance group had shorter duration of therapy by 1.67 days (4.99 ± 2.50 days vs. 6.66 ± 2.34 days; P < 0.01) and LOS by 2 days (22.5 ± 51.4 days vs. 24.5 ± 3.04 days; P = 0.83). There were no significant differences in 14-day mortality and readmission rates between the 2 groups. Conclusion In patients with neurological conditions, ASP interventions were safe, and associated with a significant reduction in the duration of therapy and LOS. Disclosures All authors: No reported disclosures.

Pseudomonas aeruginosa bacteremia is associated with high hospital mortality. Empirical combination therapy is commonly used to increase the likelihood of appropriate therapy, but the benefits of employing >1 active agent have yet to be established. The purpose of this study was to compare outcomes of patients receiving appropriate empirical combination versus monotherapy for P. aeruginosa bacteremia. This was a retrospective, multicenter, cohort study of hospitalized adult patients with P. aeruginosa bacteremia from 2002 to 2011. The primary endpoint (30-day mortality) was assessed using multivariate logistic regression, adjusting for underlying confounding variables. Secondary endpoints of hospital mortality and time to mortality were assessed by Fisher's exact test and the Cox proportional hazards model, respectively. A total of 384 patients were analyzed. Thirty-day mortality was higher for patients receiving inappropriate therapy than for those receiving appropriate empirical therapy (43.8% versus 21.5%; P = 0.03). However, there were no statistical differences in 30-day mortality following appropriate empirical combination versus monotherapy after adjusting for baseline APACHE II scores and lengths of hospital stay prior to the onset of bacteremia ( P = 0.55). Observed hospital mortality was 36.6% for patients administered combination therapy, compared with 28.7% for monotherapy patients ( P = 0.17). After adjusting for baseline APACHE II scores, the relationship between time to mortality and combination therapy was not statistically significant ( P = 0.59). Overall, no significant differences were observed for 30-day mortality, hospital mortality, and time to mortality between combination and monotherapy for P. aeruginosa bacteremia. Empirical combination therapy did not appear to offer an additional benefit, as long as the isolate was susceptible to at least one antimicrobial agent.

Objective.To compare early empiric antifungal treatment with culture-directed treatment in critically ill patients with intra-abdominal sepsis.Methods.A prospective observational cohort study was conducted between August 2010 and July 2011, on SICU patients admitted after surgery for gastrointestinal perforation, bowel obstruction or ischemia, malignancy and anastomotic leakages. Patients who received antifungal treatment within two days of sepsis onset were compared to patients who received culture-directed antifungal treatment in terms of mortality rate and clinical improvement. Patients’ demographics, comorbidities, severity-of-illness scores, and laboratory results were systematically collected and analysed.Results.Thirty-three patients received early empiric and 19 received culture-directed therapy. Of these, 30 from the early empiric group and 18 from culture-directed group were evaluable and analysed. Both groups had similar baseline characteristics and illness severity. Patients on empiric antifungal use had significantly lower 30-day mortality (P=0.03) as well as shorter median time to clinical improvement (P=0.025). Early empiric antifungal therapy was independently associated with survival beyond 30 days (OR 0.131, 95% CI: 0.018 to 0.966;P=0.046).Conclusion.Early empiric antifungal therapy in surgical patients with intra-abdominal sepsis was associated with reduced mortality and warrants further evaluation in randomised controlled trials.

The clinical advantages of prolonged (extended/continuous) infusion remain controversial. Previous studies and reviews have failed to show consistent clinical benefits of extending the infusion time. This meta-analysis sought to determine whether prolonged β-lactam infusions were associated with a reduction in mortality and improvement in clinical success. A search of PubMed, EMBASE and The Cochrane Library for randomised controlled trials (RCTs) and observational studies comparing prolonged infusion with intermittent bolus administration of the same antibiotic in hospitalised adult patients was conducted. Primary outcomes evaluated were mortality and clinical success. A total of 29 studies with 2206 patients (18 RCTs and 11 observational studies) were included in the meta-analysis. Compared with intermittent boluses, use of prolonged infusion appeared to be associated with a significant reduction in mortality [pooled relative risk (RR) = 0.66, 95% confidence interval (CI) 0.53-0.83] and improvement in clinical success (RR = 1.12, 95% CI 1.03-1.21). Statistically significant benefit was supported by non-randomised studies (mortality, RR = 0.57, 95% CI 0.43-0.76; clinical success, RR = 1.34, 95% CI 1.02-1.76) but not by RCTs (mortality, RR = 0.83, 95% CI 0.57-1.21; clinical success, RR = 1.05, 95% CI 0.99-1.12). The positive results from observational studies, especially in the face of increasing antibiotic resistance, serve to justify the imperative need to conduct a large-scale, well-designed, multicentre RCT involving critically ill patients infected with high minimum inhibitory concentration pathogens to clearly substantiate this benefit.

Results from randomized controlled studies and meta-analyses indicate that fluoroquinolone (FQ) prophylaxis reduces the incidence of febrile neutropenia (FN) and infection-related mortality in pati...

Febrile neutropenia remains a major cause of morbidity and mortality in patients receiving chemotherapy. Major prophylactic strategies include granulocyte colony-stimulating factor and antibiotics, the most widely used of which are fluoroquinolones. While fluoroquinolone prophylaxis has been shown to be effective in areas where fluoroquinolone resistance is low, this same efficacy has not been proven in areas where resistance is high, such as in Asia. Given the increase in antimicrobial resistance with the use of prophylaxis, the risks and benefits of this strategy need to be carefully considered. This review presents the evidence for and against fluoroquinolone prophylaxis in areas of high fluoroquinolone resistance.