A global genomic analysis of Salmonella Concord reveals lineages with high antimicrobial resistance in Ethiopia.

Antimicrobial resistant Salmonella enterica serovar Concord (S. Concord) is known to cause severe gastrointestinal and bloodstream infections in patients from Ethiopia and Ethiopian adoptees, and occasional records exist of S. Concord linked to other countries. The evolution and geographical distribution of S. Concord remained unclear. Here, we provide a genomic overview of the population structure and antimicrobial resistance (AMR) of S. Concord by analysing genomes from 284 historical and contemporary isolates obtained between 1944 and 2022 across the globe. We demonstrate that S. Concord is a polyphyletic serovar distributed among three Salmonella super-lineages. Super-lineage A is composed of eight S. Concord lineages, of which four are associated with multiple countries and low levels of AMR. Other lineages are restricted to Ethiopia and horizontally acquired resistance to most antimicrobials used for treating invasive Salmonella infections in low- and middle-income countries. By reconstructing complete genomes for 10 representative strains, we demonstrate the presence of AMR markers integrated in structurally diverse IncHI2 and IncA/C2 plasmids, and/or the chromosome. Molecular surveillance of pathogens such as S. Concord supports the understanding of AMR and the multi-sector response to the global AMR threat. This study provides a comprehensive baseline data set essential for future molecular surveillance.

Diagnostic MALDI-TOF MS can differentiate between high and low toxic Staphylococcus aureus bacteraemia isolates as a predictor of patient outcome.

Staphylococcus aureus bacteraemia (SAB) is a major cause of blood-stream infection (BSI) in both healthcare and community settings. While the underlying comorbidities of a patient significantly contributes to their susceptibility to and outcome following SAB, recent studies show the importance of the level of cytolytic toxin production by the infecting bacterium. In this study we demonstrate that this cytotoxicity can be determined directly from the diagnostic MALDI-TOF mass spectrum generated in a routine diagnostic laboratory. With further development this information could be used to guide the management and improve the outcomes for SAB patients.

Stemming the Rise of Antibiotic Use for Community-Acquired Acute Respiratory Infections during COVID-19 Pandemic.

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.

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.

Therapeutic drug monitoring of meropenem and piperacillin-tazobactam in the Singapore critically ill population - A prospective, multi-center, observational study (BLAST 1).

PURPOSE: To determine percentage of patients with sub-therapeutic beta-lactam exposure in our intensive care units (ICU) and to correlate target attainment with clinical outcomes. MATERIALS AND METHODS: Multi-centre, prospective, observational study was conducted in ICUs from three hospitals in Singapore from July 2016 to May 2018. Adult patients (≥21 years) receiving meropenem or piperacillin-tazobactam were included. Four blood samples were obtained during a dosing interval to measure and determine attainment of therapeutic targets: unbound beta-lactam concentration above (i) minimum inhibitory concentration (MIC) at 40% (meropenem) or 50% (piperacillin) of dosing interval (40-50%fT > MIC) and (ii) 5 × MIC at 100% of dosing interval (100%fT > 5 × MIC). Correlation to clinical outcomes was evaluated using Cox regression. RESULTS: Beta-lactam levels were highly variable among 61 patients, with trough meropenem and piperacillin levels at 21.5 ± 16.8 mg/L and 101.6 ± 81.1 mg/L respectively. Among 85 sets of blood samples, current dosing practices were able to achieve 94% success for 40-50%fT > MIC and 44% for 100%fT > 5 × MIC. Failure to achieve 40-50%fT > MIC within 48 h was significantly associated with all-cause mortality (HR: 9.0, 95% CI: 1.8-45.0), after adjustment for APACHE II score. Achievement of 100%fT > 5 × MIC within 48 h was significantly associated with shorter length of hospital stay. CONCLUSION: Current dosing practices may be suboptimal for ICU patients. Beta-lactam TDM may be useful.

Family-centered care management strategies for term and near-term neonates with brief hospitalization in a level III NICU in Shenzhen, China during the time of COVID-19 pandemic.

BACKGROUND: Adopting the family-centered care (FCC) approach in the neonatal care has been shown to improve breastfeeding rate and parental satisfaction. To minimize the transmission of COVID-19, family visit in neonatal intensive care unit (NICU) was suspended in China. In order to maintain the benefits of FCC, the Hong Kong University-Shenzhen Hospital NICU modified FCC strategies. We evaluated the effects of new strategies and aimed to share our results and experience with other NICUs during the COVID-19 pandemic. METHODS: Using prospectively collected hospital databases, we retrospectively compared the demographic and clinical data of neonates, rates of breastfeeding at discharge, nosocomial infection and parental satisfaction one month before (open group) and after (closed group) the implementation of alternative FCC management strategies when family visit was suspended during COVID-19 pandemic. RESULTS: During the COVID-19 pandemic, we organized a multidisciplinary task force and adopted strategies of triage and screening, management of suspected infants, and breastfeeding promotion with effective communication. The nosocomial infection rate and parental satisfaction for open and closed groups (144 and 108 term and near-term neonates with brief hospitalization, respectively) were not different (1% vs. 0%, p = 1.00; 98.6 vs. 98.8, p = .80; respectively). Breastfeeding rate at discharge decreased but the difference was not significant (74% vs. 80%, p = .29). CONCLUSIONS: In our experience, in term and near-term neonates with brief hospitalization, the alternative FCC strategies maintained high parental satisfaction without increased nosocomial infection rate, but strong support for breastfeeding was needed. Through multidisciplinary collaboration, the continuation of "modified" FCC in a level III NICU is feasible in the context of COVID-19 pandemic with reduced family visitation and participation in the care.

Estimating the economic cost of carbapenem resistant Enterobacterales healthcare associated infections in Singapore acute-care hospitals.

Quantifying the costs of hospital associated infections (HAIs) caused by carbapenem-resistant Enterobacterales (CRE) can aid hospital decision makers in infection prevention and control decisions. We estimate the costs of a CRE HAI by infection type and the annual costs of CRE HAIs to acute-care hospitals in Singapore. We used tree diagrams to estimate the costs (in Singapore dollar) of different CRE HAI types from the health service perspective and compared them to the costs of carbapenem-susceptible HAIs. We used two approaches to estimate costs-direct costs of consumables for infection prevention and treatment; and costs associated with lost bed days. Cost of a HAI were extrapolated to annual CRE HAI incidence in Singapore acute-care hospitals to estimate the annual cost to the hospitals. We found that the cost of a CRE HAI based on direct cost and lost bed days are SGD$9,913 (95% CI, SGD$9,431-10,395) and SGD$10,044 (95% CI, SGD$9,789-10,300) respectively. CRE HAIs are markedly higher than the carbapenem-susceptible HAIs for all infection types. In both approaches, CRE pneumonia was the costliest infection. Based on a CRE HAI incidence of 233 per 100,000 inpatient admissions, CRE HAIs costed SGD$12.16M (95% CI, SGD$11.84-12.48M) annually based on direct costs, and SGD$12.33M (95% CI, SGD$12.01-12.64M) annually based on lost bed days. In conclusion, we described the cost of CRE HAIs in Singapore hospitals and identified infections with the highest costs. The findings may be useful in informing future economic evaluations of competing CRE HAI prevention and treatment programmes.

The Dolaflexin-based Antibody-Drug Conjugate XMT-1536 Targets the Solid Tumor Lineage Antigen SLC34A2/NaPi2b.

Target selection for antibody-drug conjugates (ADC) frequently focuses on identifying antigens with differential expression in tumor and normal tissue, to mitigate the risk of on-target toxicity. However, this strategy restricts the possible target space. SLC34A2/NaPi2b is a sodium phosphate transporter expressed in a variety of human tumors including lung and ovarian carcinoma, as well as the normal tissues from which these tumors arise. Previous clinical trials with a NaPi2b targeting MMAE-ADCs have shown objective durable responses. However, the protein-based biomarker assay developed for use in that study was unable to discern a statistically significant relationship between NaPi2b protein expression and the probability of response. XMT-1536 is a NaPi2b targeting ADC comprised of a unique humanized antibody conjugated with 10-15 auristatin F- hydroxypropylamide (AF-HPA) payload molecules via the Dolaflexin platform. AF-HPA is a cell-permeable, antimitotic compound that is slowly metabolized intratumorally to an active, very low-permeable metabolite, auristatin F (AF), resulting in controlled bystander killing. We describe the preclinical in vitro and in vivo antitumor effects of XMT-1536 in models of ovarian and lung adenocarcinoma. Pharmacokinetic analysis showed approximately proportional increases in exposure in rat and monkey. Systemic free AF-HPA and AF concentrations were observed to be low in all animal species. Finally, we describe a unique IHC reagent, generated from a chimeric construct of the therapeutic antibody, that was used to derive a target expression and efficacy relationship in a series of ovarian primary xenograft cancer models.

Treatment and Outcomes of Infections Caused by Diverse Carbapenemase-Producing Carbapenem-Resistant Enterobacterales.

Background: Diverse sequence types (ST) and various carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) infections, which complicate treatment strategies, have emerged in Singapore. We aim to describe these CP-CRE infections and clinical outcomes according to their carbapenemase types and determine the hierarchy of predictors for mortality that are translatable to clinical practice. Methods: Clinically significant CP-CRE infections were identified in Singapore General Hospital between 2013 and 2016. Retrospectively, all clinically relevant data were retrieved from electronic medical records from the hospital. Univariate analysis was performed. To further explore the relationship between the variables and mortality in different subsets of patients with CP-CRE, we conducted recursive partitioning analysis on all study variables using the "rpart" package in R. Results: One hundred and fifty five patients were included in the study. Among them, 169 unique CP-CRE were isolated. Thirty-day all-cause in-hospital mortality was 35.5% (n = 55). There was no difference in the severity of illness, or any clinical outcomes exhibited by patients between the various carbapenemases. Root node began with patients with Acute Physical and Chronic Health Evaluation (APACHEII) score ≥ 15 (n = 98; mortality risk = 52.0%) and <15 (n = 57; mortality risk = 9.0%). Patients with APACHEII score ≥ 15 are further classified based on presence (n = 27; mortality risk = 23.0%) and absence (n = 71, mortality risk = 62.0%) of bacterial eradication. Without bacterial eradication, absence (n = 54) and presence (n = 17) of active source control yielded 70.0 and 35.0% mortality risk, respectively. Without active source control, the mortality risk was higher for the patients with non-receipt of definite combination therapy (n = 36, mortality risk = 83.0%) when compared to those who received (n = 18, mortality risk = 47.0%). Overall, the classification tree has an area under receiver operating characteristic curve of 0.92, with a sensitivity of 0.87 and specificity of 0.91. Conclusion: Different mortality risks were observed with different treatment strategies. Effective source control and microbial eradication were associated with a lower mortality rate but not active empiric therapy for CP-CRE infection. When source control was impossible, definitive antibiotic combination appeared to be associated with a reduction in mortality.

Elimination of Extracellular Adenosine Triphosphate for the Rapid Prediction of Quantitative Plate Counts in 24 h Time-Kill Studies against Carbapenem-Resistant Gram-Negative Bacteria.

Traditional in vitro time-kill studies (TKSs) require viable plating, which is tedious and time-consuming. We used ATP bioluminescence, with the removal of extracellular ATP (EC-ATP), as a surrogate for viable plating in TKSs against carbapenem-resistant Gram-negative bacteria (CR-GNB). Twenty-four-hour TKSs were conducted using eight clinical CR-GNB (two Escherichia coli, two Klebsiella spp., two Acinetobacter baumannii, two Pseudomonas aeruginosa) with multiple single and two-antibiotic combinations. ATP bioluminescence and viable counts were determined at each timepoint (0, 2, 4, 8, 24 h), with and without apyrase treatment. Correlation between ATP bioluminescence and viable counts was determined for apyrase-treated and non-apyrase-treated samples. Receiver operator characteristic curves were plotted to determine the optimal luminescence threshold to discriminate between inhibitory/non-inhibitory and bactericidal/non-bactericidal combinations, compared to viable counts. After treatment of bacteria with 2 U/mL apyrase for 15 min at 37 °C, correlation to viable counts was significantly higher compared to untreated samples (p < 0.01). Predictive accuracies of ATP bioluminescence were also significantly higher for apyrase-treated samples in distinguishing inhibitory (p < 0.01) and bactericidal (p = 0.03) combinations against CR-GNB compared to untreated samples, when all species were collectively analyzed. We found that ATP bioluminescence can potentially replace viable plating in TKS. Our assay also has applications in in vitro and in vivo infection models.

Molecular Epidemiology of Escherichia coli Producing CTX-M and pAmpC ß-Lactamases from Dairy Farms Identifies a Dominant Plasmid Encoding CTX-M-32 but No Evidence for Transmission to Humans in the Same Geographical Region.

Third-generation cephalosporin resistance (3GC-R) in Escherichia coli is a rising problem in human and farmed-animal populations. We conducted whole-genome sequencing analysis of 138 representative 3GC-R isolates previously collected from dairy farms in southwest England and confirmed by PCR to carry acquired 3GC-R genes. This analysis identified blaCTX-M (131 isolates encoding CTX-M-1, -14, -15, -and 32 and the novel variant CTX-M-214), blaCMY-2 (6 isolates), and blaDHA-1 (1 isolate). A highly conserved plasmid was identified in 73 isolates, representing 27 E. coli sequence types. This novel ∼220-kb IncHI2 plasmid carrying blaCTX-M-32 was sequenced to closure and designated pMOO-32. It was found experimentally to be stable in cattle and human transconjugant E. coli even in the absence of selective pressure and was found by multiplex PCR to be present on 26 study farms representing a remarkable range of transmission over 1,500 square kilometers. However, the plasmid was not found among human urinary E. coli isolates we recently characterized from people living in the same geographical location, collected in parallel with farm sampling. There were close relatives of two blaCTX-M plasmids circulating among eight human and two cattle isolates, and a closely related blaCMY-2 plasmid was found in one cattle and one human isolate. However, phylogenetic evidence of recent sharing of 3GC-R strains between farms and humans in the same region was not found.IMPORTANCE Third-generation cephalosporins (3GCs) are critically important antibacterials, and 3GC resistance (3GC-R) threatens human health, particularly in the context of opportunistic pathogens such as Escherichia coli There is some evidence for zoonotic transmission of 3GC-R E. coli through food, but little work has been done examining possible transmission via interaction of people with the local near-farm environment. We characterized acquired 3GC-R E. coli found on dairy farms in a geographically restricted region of the United Kingdom and compared these with E. coli from people living in the same region, collected in parallel. While there is strong evidence for recent farm-to-farm transmission of 3GC-R strains and plasmids-including one epidemic plasmid that has a remarkable capacity to be transmitted-there was no evidence that 3GC-R E. coli found on study farms had a significant impact on circulating 3GC-R E. coli strains or plasmids in the local human population.

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.

Clinical Experience with High-Dose Polymyxin B against Carbapenem-Resistant Gram-Negative Bacterial Infections-A Cohort Study.

Population pharmacokinetic studies have suggested that high polymyxin B (PMB) doses (≥30,000 IU/kg/day) can improve bacterial kill in carbapenem-resistant Gram-negative bacteria (CR-GNB). We aim to describe the efficacy and nephrotoxicity of patients with CR-GNB infections prescribed high-dose PMB. A single-centre cohort study was conducted from 2013 to 2016 on septic patients with CR-GNB infection and prescribed high-dose PMB (~30,000 IU/kg/day) for ≥72 h. Study outcomes included 30-day mortality and acute kidney injury (AKI) development. Factors associated with AKI were identified using multivariable regression. Forty-three patients with 58 CR-GNB received high-dose PMB; 57/58 (98.3%) CR-GNB were susceptible to PMB. The median daily dose and duration of high-dose PMB were 32,051 IU/kg/day (IQR, 29,340-34,884 IU/kg/day) and 14 days (IQR, 7-28 days), respectively. Thirty-day mortality was observed in 7 (16.3%) patients. AKI was observed in 25 (58.1%) patients with a median onset of 8 days (IQR, 6-13 days). Higher daily PMB dose (aOR,1.01; 95% CI, 1.00-1.02) and higher number of concurrent nephrotoxins (aOR, 2.14; 95% CI; 1.03-4.45) were independently associated with AKI. We observed that a sizable proportion developed AKI in CR-GNB patients described high-dose PMB; hence, the potential benefits must be weighed against increased AKI risk. Concurrent nephrotoxins should be avoided to reduce nephrotoxicity.

In Vitro Pharmacodynamics of Fosfomycin against Carbapenem-Resistant Enterobacter cloacae and Klebsiella aerogenes.

The increase of carbapenem-resistant Enterobacterales (CRE) and lack of therapeutic options due to the scarcity of new antibiotics has sparked interest toward the use of intravenous fosfomycin against systemic CRE infections. We aimed to investigate the in vitro pharmacodynamics of fosfomycin against carbapenem-resistant Enterobacter cloacae and Klebsiella aerogenes Time-kill studies and population analysis profiles were performed with eight clinical CRE isolates, which were exposed to fosfomycin concentrations ranging from 0.25 to 2,048 mg/liter. The 24-h mean killing effect was characterized by an inhibitory sigmoid maximum effect (Emax) model. Whole-genome sequencing was performed to elucidate known fosfomycin resistance mechanisms. Fosfomycin MICs ranged from 0.5 to 64 mg/liter. The isolates harbored a variety of carbapenemase genes including blaIMP, blaKPC, and blaNDM Five out of eight isolates harbored the fosA gene, while none harbored the recently discovered fosL-like gene. Heteroresistant subpopulations were detected in all isolates, with two out of eight isolates harboring heteroresistant subpopulations at up to 2,048 mg/liter. In time-kill studies, fosfomycin exhibited bactericidal activity at 2 to 4 h at several fosfomycin concentrations (one isolate at ≥16 mg/liter, two at ≥32 mg/liter, two at ≥64 mg/liter, two at ≥128 mg/liter, and one at ≥512 mg/liter). At 24 h, bactericidal activity was only observed in two isolates (MICs, 0.5 and 4 mg/liter) at 2,048 mg/liter. From the Emax model, no significant bacterial killing was observed beyond 500 mg/liter. Our findings suggest that the use of fosfomycin monotherapy may be limited against CRE due to heteroresistance and rapid bacterial regrowth. Further optimization of intravenous fosfomycin dosing regimens is required to increase efficacy against such infections.

Determining the Development of Persisters in Extensively Drug-Resistant Acinetobacter baumannii upon Exposure to Polymyxin B-Based Antibiotic Combinations Using Flow Cytometry.

Polymyxin B-based combinations are increasingly prescribed as a last-line option against extensively drug-resistant (XDR) Acinetobacter baumannii It is unknown if such combinations can result in the development of nondividing persister cells in XDR A. baumannii We investigated persister development upon exposure of XDR A. baumannii to polymyxin B-based antibiotic combinations using flow cytometry. Time-kill studies (TKSs) were conducted in three nonclonal XDR A. baumannii strains with 5 log10 CFU/ml bacteria against polymyxin B alone and polymyxin B-based two-drug combinations over 24 h. At different time points, samples were obtained and enumerated by viable plating and flow cytometry. Propidium iodide and carboxyfluorescein succinimidyl ester dyes were used to differentiate between live and dead cells and between dividing and nondividing cells, respectively, at the single-cell level, and nondividing live cells were resuscitated and characterized phenotypically. Our results from viable plating showed that polymyxin B plus meropenem and polymyxin B plus rifampin were each bactericidal (>99.9% kill compared to the initial inoculum) against 2/3 XDR A. baumannii strains at 24 h. By flow cytometry, however, none of the combinations were bactericidal against XDR A. baumannii at 24 h. Further analysis using cellular dyes in flow cytometry revealed that upon exposure to polymyxin B-based combinations, XDR A. baumannii entered a viable but nondividing persister state. These bacterial cells reinitiated division upon the removal of antibiotic pressure and did not have a growth deficit compared to the parent strain. We conclude that persister cells develop in XDR A. baumannii upon exposure to polymyxin B-based combinations and that nonplating methods appear to complement viable-plating methods in describing the killing activity of polymyxin B-based combinations against XDR A. baumannii.

In vitro Pharmacodynamics and PK/PD in Animals.

In the last decade, considerable advancements have been made to identify the pharmacokinetic/pharmacodynamic (PK/PD) index that defines the antimicrobial activity of polymyxins. Dose-fractionation studies performed in hollow-fiber models found that altering the dosing schedule had little impact on the killing or suppression of resistance emergence, alluding to AUC/MIC as the pharmacodynamic index that best describes polymyxin's activity. For in vivo efficacy, the PK/PD index that was the most predictive of the antibacterial effect of colistin against P. aeruginosa and A. baumannii was ƒAUC/MIC.

Real-Time PCR Assay for Differentiation of Typhoidal and Nontyphoidal Salmonella.

Rapid and accurate differentiation of Salmonella spp. causing enteric fever from nontyphoidal Salmonella is essential for clinical management of cases, laboratory risk management, and implementation of public health measures. Current methods used for confirmation of identification, including biochemistry and serotyping as well as whole-genome sequencing analyses, take several days. Here we report the development and evaluation of a real-time PCR assay that can be performed directly on crude DNA extracts from bacterial colonies for the rapid identification of typhoidal and nontyphoidal Salmonella.

Discontinuation of antibiotic therapy within 24 hours of treatment initiation for patients with no clinical evidence of bacterial infection: a 5-year safety and outcome study from Singapore General Hospital Antimicrobial Stewardship Program.

BACKGROUND: Overprescribing antibiotics for patients with no bacterial infection is of growing global concern. It is important for timely Antimicrobial Stewardship Program (ASP) intervention to discontinue antibiotics for patients whose symptoms can be explained by non-infective causes, and without availability of bacterial cultures and susceptibilities reports. This study aimed to evaluate clinical outcomes and safety of early ASP review in these patients. METHODS: A retrospective review of the ASP database (January 2010 to December 2014) was conducted to identify patients for whom ASP recommended discontinuation of empiric antibiotics within 24 hours of prescribing. Demographics were collected. Clinical outcomes - duration of therapy, length of hospital stay (LOS), infection-related readmissions, and all-cause mortality - were compared between interventions accepted and rejected groups. Continuous data were analysed via unpaired Student's t-test. Categorical data were analysed using χ2 test or Fisher's exact test, as appropriate. RESULTS: The ASP team recommended 794 interventions (overall acceptance rate of 72.9%, 579 of 794). There were no significant between-group differences in underlying demographics, and Charlson comorbidity index score. However, the interventions acceptance group had significantly shorter duration of therapy by 2.61 days (2.72 ± 3.04 vs. 5.33 ± 2.54 days; P < 0.01) and LOS by 7.41 days (7.98 ± 13.14 vs. 15.39 ± 22.62 days; P < 0.01), with estimated cost savings of SGD10 817 per patient. There were no significant between-group differences in 14-day mortality and readmission rates. CONCLUSION: Prompt ASP interventions at Singapore General Hospital were associated with significant reductions in duration of therapy and LOS, with cost savings. It was demonstrated that it is safe to discontinue antibiotics within 24 hours of prescribing for patients with no evidence of bacterial infections.