Surgical prophylaxis in pancreatoduodenectomy: Is cephalosporin still the drug of choice in patients with biliary stents in situ?

BACKGROUND: Universal surgical prophylaxis for pancreatoduodenectomy (PD) is practiced, with cephalosporins recommended in most guidelines. Recent studies suggest piperacillin-tazobactam (PTZ) prophylaxis in biliary-stented patients is superior in preventing surgical site infections (SSIs). This study aims to refine surgical prophylaxis recommendations based on the local microbial profile and evaluate the clinical outcomes of biliary-stented compared with non-stented patients. METHODS: This was a retrospective study of all consecutive PD patients at Singapore General Hospital between January 2013 to December 2019. The primary outcome was post-operative SSI rates. Secondary outcomes included rates of ceftriaxone-resistant Klebsiella pneumoniae, Escherichia coli, and Enterococcus species from intraoperative bile cultures and 30-day mortality. RESULTS: There were 130 biliary-stented and 211 non-stented patients included. Majority of biliary-stented patients received ceftriaxone ± metronidazole prophylaxis (83/130, 63.8 %) while 30/130 (23.8 %) received PTZ. Most non-stented patients received ceftriaxone ± metronidazole prophylaxis (163/211, 77.3 %). Between biliary-stented and non-stented patients, post-operative SSIs (40.8 % vs 38.4 %, p = 0.662), and 30-day mortality rates (1.5 % vs 1.4 %, p = 1.000) were comparable. The adjusted odds of post-operative SSIs was significantly lower in biliary-stented patients prescribed PTZ as compared to non-PTZ prophylaxis (0.29, 95 % CI (0.10-0.79), p = 0.015). Ceftriaxone-resistant Klebsiella spp. and/or Escherichia coli (27.6 % vs 3.8 %, p < 0.001) as well as Enterococcus species (46.1 % vs 11.5 %, p < 0.001), were more prevalent in intraoperative bile cultures of biliary-stented patients, while frequencies in non-stented patients were low. CONCLUSION: PTZ prophylaxis effectively reduced SSIs in stented patients post-pancreatoduodenectomy. Based on the local microbial profile, ceftriaxone prophylaxis may be used for prophylaxis in non-stented patients.

Donor-derived dengue infections - A review of screening protocol and outcomes in an endemic country.

BACKGROUND: Donor-derived dengue infections present significant challenges to organ transplantation, particularly in endemic regions like Singapore. Although primarily transmitted by Aedes mosquitoes, dengue can also be transmitted through organ transplantation, occasionally with fatal outcomes. This study aims to evaluate the outcomes and evolution of dengue screening protocols for potential deceased donors in Singapore from 2006 to 2022. METHODS: Initially, screening was done via dengue immunoglobulin M (IgM), targeting donors with specific clinical criteria (thrombocytopenia, drop in platelet count, prolonged prothrombin time/partial thromboplastin time, and discretion of the transplant team), later transitioning to blood dengue reverse transcription-polymerase chain reaction (RT-PCR) in 2007 with similar criteria, and subsequently universal screening in 2016. In 2021, urine dengue RT-PCR was added following a case of donor-derived dengue infection from an aviremic but viruric donor. RESULTS: Out of 431 potential deceased donors, 395 (91.6%) underwent dengue screening, with six (1.5%) testing positive for dengue. In 2006, three positive screens were identified: two through dengue IgM and one via blood dengue RT-PCR; subsequent years saw one positive screen each in 2007, 2008, and 2019 via blood dengue RT-PCR. Potential deceased donors with a positive blood dengue screen were rejected as solid organ and tissue donors. Those with negative blood dengue RT-PCR but positive urine dengue RT-PCR would be rejected as kidney donors, but the use of other organs and tissues was at the discretion of the transplantation team. CONCLUSION: The optimal screening protocol remains uncertain, but our findings suggest that a universal screening strategy utilizing both blood and urine dengue RT-PCR could be considered in dengue-endemic countries.

Favorable outcomes of COVID-19 in vaccinated hematopoietic stem cell transplant recipients: A single-center experience.

INTRODUCTION: A high incidence of mortality and severe COVID-19 infection was reported in hematopoietic stem cell transplant (HSCT) recipients during the early phases of the COVID-19 pandemic; however, outcomes with subsequent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, such as the omicron variant, have yet to be reported. Additionally, rollout of COVID-19 vaccinations in subsequent pandemic waves may modify COVID-19 disease severity and mortality in this immunocompromised population. We describe COVID-19 outcomes among a highly vaccinated population of HSCT recipients at a single center during successive waves of community transmission arising from the SARS-CoV-2 delta and omicron variants. METHODS: We retrospectively reviewed medical records of all HSCT recipients at our institution who tested positive for SARS-CoV-2 from May 2021 to May 2022. Descriptive statistics were reported; the chi-square test was utilized to identify factors associated with 90-day all-cause mortality and severity of COVID-19 infection. RESULTS: Over the 1-year study period, 77 HSCT recipients at our center contracted COVID-19 (43 allogenic; 34 autologous). Twenty-six (33.8%) patients were infected with the SARS-CoV-2 delta variant, while 51 (66.2%) had the SARS-CoV-2 omicron variant. Thirty-nine (50.6%) patients required hospitalization. More than 80% had received prior COVID-19 vaccination (57.1% with two doses, 27.3% with three doses). The majority (90.9%) had mild disease; only one (1.3%) patient required mechanical ventilation. Active hematological disease at time of COVID-19 infection was associated with increased odds of mortality [odds ratio (OR) = 6.90, 95% confidence interval (CI) = 1.20-40]. The 90-day all-cause mortality was 7.8% (six patients). Infection with the omicron variant (vs. delta) was associated with less severe illness (OR = 0.05, 95% CI = 0.01-0.47) and decreased odds of mortality (OR = 0.08, 95% CI = 0.01-0.76). Being on immunosuppression (OR = 5.10, 95% CI = 1.10-23.60) and being unvaccinated at disease onset (OR = 14.76, 95% CI = 2.89-75.4) were associated with greater severity of COVID-19 infection. CONCLUSION: We observed favorable outcomes with COVID-19 infection in a cohort of vaccinated HSCT patients. The SARS-CoV-2 omicron variant was associated with both less severe illness and decreased odds of mortality. As COVID-19 moves toward endemicity, early access to treatment and encouraging vaccination uptake is crucial in mitigating the challenge of COVID-19 management among HSCT recipients. Surveillance and assessment of clinical outcomes with new SARS-CoV-2 variants also remains important in this immunocompromised population.

An outpatient model of care for COVID-19 infected kidney transplant patients - The hospital-at-home.

BACKGROUND: The COVID-19 pandemic is protracted and episodic surges from viral variants continue to place significant strain on healthcare systems. COVID-19 vaccines, antiviral therapy and monoclonal antibodies have significantly reduced COVID-19 associated morbidity and mortality. Concurrently, telemedicine has gained acceptance as a model of care and a tool for remote monitoring. These advances allow us to safely transit our inpatient-based care for COVID-19 infected kidney transplant recipients (KTRs) to a hospital-at-home (HaH) model of care. METHODS: KTRs with PCR-proven COVID-19 infection were triaged by teleconsult and laboratory tests. Suitable patients were enrolled into the HaH. Remote monitoring via teleconsults were conducted daily until patients were de-isolated based on a time-based criterion. Monoclonal antibodies were administered in a dedicated clinic where indicated. RESULTS: Eighty-one KTRs with COVID-19 were enrolled into the HaH between February and June 2022, 70 (86.4%) completed HaH recovery without complications. Eleven (13.6%) patients required inpatient hospitalization for medical issues (n = 8) and weekend monoclonal antibody infusion (n = 3). Patients requiring inpatient hospitalization had longer transplant vintage (15 years vs. 10 years, p = .03), anaemia (haemoglobin 11.6 g/dL vs. 13.1 g/dL, p = .01), lower eGFR (39.8 vs. 62.9 mL/min/1.73 m2 , p < .05) and lower RBD levels (<50 AU/mL vs. 1435 AU/mL, p = .02). HaH saved 753 inpatient patient-days with no deaths observed. Hospital admission rates from the HaH programme was 13.6%. Patients who required inpatient care had direct access admission without utilization of emergency department resources. CONCLUSION: Selected KTRs with COVID-19 infection can be safely managed in a HaH programme; alleviating strain on inpatient and emergency healthcare resources.

Antibiotic stewardship program (ASP) in palliative care: antibiotics, to give or not to give.

Antimicrobial therapy in terminally ill patients remains controversial as goals of care tend to be focused on optimizing comfort. International guidelines recommend for antibiotic stewardship program (ASP) involvement in antibiotic decisions in palliative patients. The primary objective was to evaluate the clinical impact of ASP interventions made to stop broad-spectrum intravenous antibiotics in terminally ill patients. This was a retrospective chart review of 459 terminally ill patients in Singapore General Hospital audited by ASP between December 2010 and December 2018. Antibiotic duration, time-to-terminal discharge for end-of-life care, time-to-mortality, and mortality rates of patients with antibiotics ceased or continued upon ASP recommendations were compared. A total of 283 and 176 antibiotic courses were ceased and continued post-intervention, respectively. The intervention acceptance rate was 61.7%. The 7-day mortality rate (47.3% vs 61.9%, p = 0.003) was lower in the ceased group, while 30-day mortality rate (76.0% vs 81.2%, p = 0.203) and time-to-mortality post-intervention (3 [0-24] vs 2 [0-27] days, p = 0.066) did not differ between the ceased and continued groups. After excluding the 57 patients who had antibiotics continued until death within 48 h of intervention, only time-to-mortality post-intervention was statistically significantly shorter in the ceased group (3 [0-24] vs 4 [0-27], p < 0.001). Of the 131 terminally discharged patients, antibiotic duration (4 [0-17] vs 6.5 [1-14] days, p = 0.001) and time-to-terminal discharge post-intervention (6 [0-74] vs 10.5 [3-63] days, p = 0.001) were shorter in the ceased group. Antibiotic cessation in terminally ill patients was safe, and was associated with a significantly shorter time-to-terminal discharge.

Current state of antimicrobial stewardship in organ transplantation in Singapore.

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.

A retrospective study of intravenous pentamidine for Pneumocystis jirovecii pneumonia prophylaxis in adult patients with hematologic malignancies-its utility during respiratory virus pandemics.

OBJECTIVES: In hematology, prophylaxis for Pneumocystis jirovecii pneumonia (PCP) is recommended for patients undergoing hematopoietic stem cell transplantation and in selected categories of intensive chemotherapy for hematologic malignancies. Trimethoprim-sulfamethoxazole (TMP-SMX) is the recommended first-line agent; however, its use is not straightforward. Inhaled pentamidine is the recommended second-line agent; however, aerosolized medications were discouraged during respiratory virus outbreaks, especially during the COVID-19 pandemic, in view of potential contamination risks. Intravenous (IV) pentamidine is a potential alternative agent. We evaluated the effectiveness and tolerability of IV pentamidine use for PCP prophylaxis in adult allogeneic hematopoietic stem cell transplantation recipients and patients with hematologic malignancies during COVID-19. RESULTS: A total of 202 unique patients who received 239 courses of IV pentamidine, with a median of three doses received (1-29). The largest group of the patients (49.5%) who received IV pentamidine were undergoing or had received a hematopoietic stem cell transplant. The most common reason for not using TMP-SMX prophylaxis was cytopenia (34.7%). We have no patients who had breakthrough PCP infection while on IV pentamidine. None of the patients developed an infusion reaction or experienced adverse effects from IV pentamidine. CONCLUSIONS: Pentamidine administered IV monthly is safe and effective.

Hospitalised patients as stewards of their own antibiotic therapy: a qualitative analysis informing the strategic design of interventions to encourage shared decision-making in tertiary hospital settings in Singapore.

Background: Shared decision-making (SDM) on antibiotic therapy may improve antibiotic use in tertiary hospitals, but hospitalised patients are apprehensive about being involved in it. Understanding the facilitators and barriers to SDM can inform the design and implementation of interventions to empower these patients to engage in SDM on their antibiotic therapies. Methods: We conducted qualitative interviews with 23 adult patients purposively sampled with maximum variation from the three largest tertiary-care hospitals in Singapore (April 2019─October 2020). Thematic analysis was conducted using the Theoretical Domains Framework and Capability, Opportunity, Motivation, Behaviour (COM-B) model to identify areas for intervention. Results: Hospitalised patients lacked comprehensive knowledge of their antibiotic therapies and the majority did not have the skills to actively query their doctors about them. There was a lack of opportunities to meet and interact with doctors, and patients were less motivated to engage in SDM if they had a self-perceived paternalistic relationship with doctors, trusted their doctors to provide the best treatment, and had self-perceived poor knowledge to engage in SDM. To empower these patients, they should first be educated with antibiotic knowledge. Highlighting potential side effects of antibiotics could motivate them to ask questions about their antibiotic therapies. Environment restructuring, as facilitated by nurses and visual cues to nudge conversations, could create opportunities for interactions and motivating patients into SDM on their antibiotic therapies. Conclusion: Education and environmental restructuring should be explored to empower hospitalised patients to engage in SDM on their antibiotic therapies.

The Safety of Aztreonam Versus Ceftazidime in Patients Labeled With Penicillin Allergy: A Cohort Study.

PURPOSE: Penicillin allergy is the most common drug allergy among hospitalized patients. Traditionally, aztreonam is recommended for patients labeled with penicillin allergy (PLWPA) in our institutional empirical antibiotic guidelines. Due to a global aztreonam shortage in December 2022, the antimicrobial stewardship unit recommended ceftazidime as a substitute. There is a paucity of real-world data on the safety profile of ceftazidime in PLWPA. Hence, we evaluated tolerability outcomes of ceftazidime use in PLWPA. METHODS: This retrospective cohort study compared PLWPA in Singapore General Hospital who received aztreonam (October 2022-December 2022) or ceftazidime (December 2022-February 2023). Patients were stratified according to their risk of allergic reaction (AR) based on history of penicillin allergy. The severity of AR was based on the Delphi study grading system. The primary outcome was development of AR after initiation of aztreonam or ceftazidime. The secondary tolerability outcomes include hepatotoxicity and neurotoxicity. FINDINGS: There were 168 patients in the study; 69 were men (41.1%) and the median age was 69 years (interquartile range: 59-76 years). Incidence of AR was statistically similar in both arms: 1 of 102 patients (0.98%) in the aztreonam arm vs 2 of 66 patients (3.03%) in the ceftazidime arm (P = 0.33). The patient in the aztreonam arm was deemed at medium risk of having an AR and developed localized rashes (grade 1). Both patients in the ceftazidime arm were deemed at high risk of AR and developed localized skin reaction (grade 1). Hepatotoxicity was observed in 1 patient prescribed aztreonam. No patients in the ceftazidime arm developed adverse events. IMPLICATIONS: Ceftazidime appears to be better tolerated and cheaper compared with aztreonam in PLWPA, and serves as an antimicrobial stewardship strategy to conserve broader-spectrum antibiotics use.

Immune monitoring of prevalent kidney transplant recipients using Torque Teno Virus: Protocol for a single-centre prospective cohort study.

INTRODUCTION: Kidney transplant recipients (KTRs) suffer from immunosuppression-related adverse events (iRAEs), such as infections and malignancy from chronic immunosuppression, but are also at risk of graft loss from rejection with underimmunosuppression. Biomarkers that predict both iRAEs and rejection while allowing individualisation of immunosuppression exposure are lacking. Although plasma viral DNA levels of torque teno virus (TTV), a widely prevalent, non-pathogenic virus, have been shown to predict both iRAE and rejection in newly transplanted KTRs within the first year after transplant, its role for prevalent KTRs on stable immunosuppression is less clear.This study aims to determine the prognostic value of TTV levels for severe infections (defined as infections requiring hospitalisation) in prevalent KTRs on stable immunosuppression for at least 3 months and compare it against that of other commonly available biomarkers. The study also aims to explore the relationship between TTV levels and factors affecting the 'net state of immunosuppression' as well as other clinical outcomes. METHODS AND ANALYSIS: This is a single-centre, prospective, observational cohort study of 172 KTRs on stable immunosuppression for more than 3 months. TTV levels will be measured using the TTV R-GENE kit upon recruitment when study subjects are admitted and when kidney allograft biopsies are performed. Subjects will be monitored for iRAEs and rejection for at least 12 months. The relationship between TTV load and clinical outcomes such as severe infections will be analysed and compared against that from other common biomarkers and previously published predictive scores. ETHICS AND DISSEMINATION: The study was approved by the SingHealth Centralised Institutional Review Board (2023/2170). The results will be presented at conferences and submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05836636.

Comparative Activities of Novel Therapeutic Agents against Molecularly Characterized Clinical Carbapenem-Resistant Enterobacterales Isolates.

Limited treatment options exist for the treatment of carbapenem-resistant Enterobacterales (CRE) bacteria. Fortunately, there are several recently approved antibiotics indicated for CRE infections. Here, we examine the in vitro activity of various novel agents (eravacycline, plazomicin, ceftazidime-avibactam, imipenem-relebactam, and meropenem-vaborbactam) and comparators (tigecycline, amikacin, levofloxacin, fosfomycin, polymyxin B) against 365 well-characterized CRE clinical isolates with various genotypes. Nonduplicate isolates collected from the largest public health hospital in Singapore between 2007 and 2020 were subjected to antimicrobial susceptibility testing (broth microdilution or antibiotic gradient test strips). Susceptibilities were defined using Clinical and Laboratory Standards Institute (CLSI) or Food and Drug Administration (FDA) interpretative criteria. Sequence types and resistance mechanisms were characterized using short-read whole-genome sequencing. Overall, tigecycline and plazomicin exhibited the highest susceptibility rates (89.6% and 80.8%, respectively). However, the tigecycline susceptibility breakpoint utilized here may be outdated in view of prevailing pharmacokinetic-pharmacodynamic (PK/PD) data. Susceptibility varied by carbapenemase genotype; the ß-lactam/ß-lactamase inhibitor combinations were equally active (92.3 to 99.2% susceptible) against KPC producers, but only ceftazidime-avibactam retained high susceptibility (98.7%) against OXA-48-like producers. Against metallo-ß-lactamase producers, only plazomicin exhibited moderate activity (77.0% susceptible). Aminoglycoside activity was also influenced by carbapenemase genotypes. This work provides an insight into the comparative activity and presumptive utility of novel agents in this geographic region. IMPORTANCE This study determined the susceptibilities of carbapenem-resistant Enterobacterales isolates to various novel antimicrobial agents (ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam, eravacycline, and plazomicin). Whole-genome sequencing was performed for all strains. Our study findings provide insights into the comparative activities of novel agents in this geographic region. Plazomicin and ceftazidime-avibactam exhibited the lowest nonsusceptibility rates and may be considered promising agents in the management of carbapenem-resistant Enterobacterales infections. We note also that antibiotic activity is influenced by genotypes and that understanding the geographic region's molecular epidemiology could aid in the definition of the presumptive utility of novel agents and contribute to antibiotic decision-making.

inPhocus: Current State and Challenges of Phage Research in Singapore.

Bacteriophages and phage-derived proteins are a promising class of antibacterial agents that experience a growing worldwide interest. To map ongoing phage research in Singapore and neighboring countries, Lee Kong Chian School of Medicine, Nanyang Technological University Singapore (NTU) and Yong Loo Lin School of Medicine, National University of Singapore (NUS) recently co-organized a virtual symposium on Bacteriophage and Bacteriophage-Derived Technologies, which was attended by more than 80 participants. Topics were discussed relating to phage life cycles, diversity, the roles of phages in biofilms and the human gut microbiome, engineered phage lysins to combat polymicrobial infections in wounds, and the challenges and prospects of clinical phage therapy. This perspective summarizes major points discussed during the symposium and new perceptions that emerged after the panel discussion.

Aortic endograft infection secondary to Burkholderia pseudomallei: A case report and review of the literature.

Aortic graft infection is a rare complication after endovascular aneurysm repair that is usually caused by gram-positive organisms such as Staphylococcus spp or gram-negative organisms such as Enterobacteriaceae or Salmonella spp. We have presented a unique case of a patient with acute graft infection secondary to Burkholderia pseudomallei. Because treatment of B. pseudomallei infections is challenging owing to its inherent resistance to multiple antibiotics, we have proposed an approach for managing similar cases in the future. Lifestyle advice on avoiding soil exposure in the postoperative period after endovascular aneurysm repair might be an important preventative measure in endemic regions.

Dengue virus infection among renal transplant recipients in Singapore: a 15-year single-centre retrospective review.

INTRODUCTION: Dengue is a mosquito-borne viral infection endemic in Singapore. Its impact in renal transplantation is limited to small case series. We aimed to characterise the clinical presentation and outcomes of dengue infection among renal transplant recipients in Singapore. METHODS: We conducted a 15-year retrospective review of dengue in renal transplant patients treated at Singapore General Hospital between January 2005 and October 2019. The diagnosis of dengue was made if there were a compatible clinical syndrome and a positive dengue diagnostic assay (Dengue NS1 antigen, IgM or RT-PCR). RESULTS: 31 patients were diagnosed with dengue, 18 (58.1%) were deceased donor recipients. The median age was 52 (IQR 40-61) years; 16 (51.6%) were females. The median time to diagnosis was 99 (IQR 18-169) months from transplant. The most common clinical symptoms were fever (87.1%), myalgia (41.9%), gastrointestinal symptoms (38.7%) and headache (25.8%). 19 (61.3%) patients had dengue without warning signs, 9 (29.0%) had dengue with warning signs, 3 (9.7%) had severe dengue and 30 (96.8%) were hospitalized. 17 (54.8%) patients had graft dysfunction, 16 (94.1%) of whom had recovery of graft function. 1 (3.2%) patient required dialysis and subsequently died. There were two cases of donor-derived infections (DDIs) with favourable outcomes. CONCLUSION: Our experience with dengue in renal transplant recipients is concordant with published data. Although graft dysfunction is common, it is often transient with favourable outcomes. Outpatient management may be considered for mild infections. Although dengue DDIs are uncommon, more stringent donor screening may be considered in endemic regions.

Hospital Pharmacists and Antimicrobial Stewardship: A Qualitative Analysis.

Antimicrobial stewardship programmes (ASPs) in hospitals are predominantly led by specific ASP physicians and pharmacists. Limited studies have been conducted to appreciate non-ASP-trained hospital pharmacists' perspectives on their roles in antimicrobial stewardship. Focus group discussions (FGDs) were conducted with 74 pharmacists, purposively sampled from the 3 largest acute-care public hospitals in Singapore, to explore facilitators and barriers faced by them in antimicrobial stewardship. Applied thematic analysis was conducted and codes were categorised using the social-ecological model (SEM). At the intrapersonal level, pharmacists identified themselves as reviewers for drug safety before dispensing, confining to a restricted advisory role due to lack of clinical knowledge, experience, and empowerment to contribute actively to physicians' prescribing decisions. At the interpersonal level, pharmacists expressed difficulties conveying their opinions and recommendations on antibiotic therapy to physicians despite frequent communications, but they assumed critical roles as educators for patients and their caregivers on proper antibiotic use. At the organisational level, in-house antibiotic guidelines supported pharmacists' antibiotic interventions and recommendations. At the community level, pharmacists were motivated to improve low public awareness and knowledge on antibiotic use and antimicrobial resistance. These findings provide important insights into the gaps to be addressed in order to harness the untapped potential of hospital pharmacists and fully engage them in antimicrobial stewardship.

An unusual case of Scedosporium apiospermum fungaemia in an immunocompetent patient with a left ventricular assist device and an implantable cardiac device.

Left ventricular assist device (LVAD)-related infections are a leading cause of morbidity and mortality, with fungal infections being particularly difficult to manage. We report a case of an immunocompetent 39-year-old male with an LVAD and an implantable cardiac device (ICD) who developed fatal Scedosporium apiospermum fungaemia. To the best of our knowledge, this is the first reported case of LVAD-related S. apiospermum fungaemia.

Who listens and who doesn't? Factors associated with adherence to antibiotic stewardship intervention in a Singaporean tertiary hospital.

INTRODUCTION: Antibiotic stewardship programmes (ASPs) can improve patient outcomes by prospective audit and feedback with interventions. However, adherence to ASP interventions is not mandatory. Identifying factors associated with improved adherence may help to enhance ASP recommendations and activities. METHODS: A retrospective cohort study was conducted, comprising all ASP interventions performed as part of the prospective audit and feedback strategy in our institution (an acute tertiary-care hospital in Singapore) from January 2016 to July 2018. Adherence to ASP intervention was ascertained based on documented compliance with the recommended interventions within 48h. Factors associated with adherence to ASP interventions, such as patient demographics, clinical condition, type of infection, and characteristics of ASP interventions were identified using the χ2 test for categorical variables. On multivariate analysis, factors independently associated with adherence to ASP intervention were identified using logistic regression. RESULTS: Adherence to ASP intervention was 81.9% (5758/7028). On univariate and multivariate analysis, interventions coupled with direct communication via phone call (adjusted odds ratio [aOR] 1.61, 95% CI 1.23-2.08) were associated with higher odds of adherence, whereas admission to a surgical unit, intervention involving carbapenem use, and recommendation to de-escalate or discontinue antibiotics were associated with lower odds of adherence to ASP interventions. CONCLUSION: Although adherence rates to ASP interventions were relatively high, interventions made to the surgical unit and recommendations related to carbapenem use were not so well received. Interventions communicated verbally via phone call were well received, highlighting the need for a close working relationship between ASP teams and hospital physicians.

Antimicrobial stewardship programme: a vital resource for hospitals during the global outbreak of coronavirus disease 2019 (COVID-19).

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.

Performance of Population Pharmacokinetic Models in Predicting Polymyxin B Exposures.

Polymyxin B is the last line of defense in treating multidrug-resistant gram-negative bacterial infections. Dosing of polymyxin B is currently based on total body weight, and a substantial intersubject variability has been reported. We evaluated the performance of different population pharmacokinetic models to predict polymyxin B exposures observed in individual patients. In a prospective observational study, standard dosing (mean 2.5 mg/kg daily) was administered in 13 adult patients. Serial blood samples were obtained at steady state, and plasma polymyxin B concentrations were determined by a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The best-fit estimates of clearance and daily doses were used to derive the observed area under the curve (AUC) in concentration-time profiles. For comparison, 5 different population pharmacokinetic models of polymyxin B were conditioned using patient-specific dosing and demographic (if applicable) variables to predict polymyxin B AUC of the same patient. The predictive performance of the models was assessed by the coefficient of correlation, bias, and precision. The correlations between observed and predicted AUC in all 5 models examined were poor (r2 < 0.2). Nonetheless, the models were reasonable in capturing AUC variability in the patient population. Therapeutic drug monitoring currently remains the only viable approach to individualized dosing.