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Background: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

At the start of the COVID-19 pandemic, there was an increase in the use of antibiotics for the treatment of community-acquired respiratory tract infection (CA-ARI) in patients admitted for suspected or confirmed COVID-19, raising concerns for misuse. These antibiotics are not under the usual purview of the antimicrobial stewardship unit (ASU). Serum procalcitonin, a biomarker to distinguish viral from bacterial infections, can be used to guide antibiotic recommendations in suspected lower respiratory tract infection. We modified our stewardship approach, and used a procalcitonin-guided strategy to identify "high yield" interventions for audits in patients admitted with CA-ARI. With this approach, there was an increase in the proportion of patients with antibiotics discontinued within 4 days (16.5% vs. 34.9%, p < 0.001), and the overall duration of antibiotic therapy was significantly shorter [7 (6–8) vs. 6 (3–8) days, p < 0.001]. There was a significant decrease in patients with intravenous-to-oral switch of antibiotics to "complete the course" (45.3% vs. 34.4%, p < 0.05). Of the patients who had antibiotics discontinued, none were restarted on antibiotics within 48 h, and there was no-30-day readmission or 30-day mortality attributed to respiratory infection. This study illustrates the importance of the antimicrobial stewardship during the pandemic and the need for ASU to remain attuned to prescriber's practices, and adapt accordingly to address antibiotic misuse to curb antimicrobial resistance. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding febrile neutropenia (FN) incidence reduction by fluoroquinolone (FQ) prophylaxis in the January 2011 issue.

• 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. [ABSTRACT FROM AUTHOR]

Background Voriconazole (VOR) and posaconazole (POS) exhibit wide pharmacokinetic variability. Various factors including race and genetic polymorphisms are at play and this may affect treatment response. We aim to evaluate the utility of VOR/POS TDM among Southeast Asians that are predominantly intermediate/poor VOR metabolizers. Methods All adults with VOR/POS TDM performed at our institution from 2015 to 2018 were included. We determined proportion of patients and doses required to achieve TDM targets [(2 – 5.5 mg/L (VOR) or ≥ 0.7 and ≥ 1.0 mg/L (POS prophylaxis and treatment respectively)], and correlate levels with treatment efficacy and safety. Results VOR/POS TDM was performed mostly among patients with hematological malignancy or solid-organ transplant (146/174, 83.9%). Less than half (32/70, 45.7%) of patients on VOR achieved target—18 (25.7%) were < 2 mg/L while 20 (28.5%) had levels > 5.5 mg/L. Doses required to achieve TDM target ranged from 1.9–11.4 mg/kg/day. Drug interactions, critically ill state and change in drug formulation were major causes of intra-patient variability. One-fifth (n = 14) experienced transaminitis; corresponding VOR trough levels were 0.5–> 7.5 mg/L. Neurotoxicity was also seen in 3 (4.3%) patients—all 3 had VOR trough ≥ 6.7 mg/L and saw symptom resolution upon dose reduction. There appears to be no association between the achievement of TDM targets and response rates. Majority (81/104, 77.9%) of patients on POS achieved TDM targets. Patients prescribed POS tablet were significantly more likely to attain targets compared with suspension 600 mg/day [19/26 (73.0%) vs. 27/62 (43.5%), P < 0.05] and 800 mg/day [17/26 (65.3%) vs. 4/16 (25.0%), P < 0.05)]. Of 23 with sub-therapeutic levels, 19 (82.6%) responded to dose increase and/or change in acid-reducing agents. Breakthrough infection occurred despite troughs ≥ 0.7 mg/L [5/42 (11.9%) vs. 2/40 (5.0%) when < 0.7 mg/L (P = 0.3)]. Treatment failure was observed in 2 patients (troughs > 1.0 mg/L). Conclusion VOR/POS TDM should be implemented in Southeast Asians due to significant unpredictability in dose exposure and potential to avoid need for switch to alternative anti-fungals due to intolerability. Higher POS trough cutoff may be required for effective anti-fungal prophylaxis. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.