Antimicrobial Stewardship Research Articles

Trends in Antimicrobial Consumption in Tertiary Care Hospitals in Costa Rica from 2017 to 2021: A Comparative Analysis of Defined Daily Doses per 100 Bed Days and per 100 Discharges.

Background: Antimicrobial consumption (AMC) data in Latin America are scarce and usually spread out across different sources used to make AMC calculations, making it difficult to both standardize and compare regions through similar time frames. The main objective was to analyze AMC trends in Social Security tertiary care hospitals in Costa Rica in the period spanning January 2017 to December 2021, using both the defined daily dose (DDD)/100 bed days and DDD/100 discharges. Methods: This is a retrospective observational study of antimicrobial consumption. Global consumption trends were calculated and expressed as DDD/100 bed days and DDD/100 discharges. Trends in antimicrobial consumption were analyzed using a simple linear regression model to determine potential differences in antimicrobial usage throughout the study's duration. Results: A statistically significant increase in the consumption expressed in DDD/100 discharges was observed in the following groups: carbapenems, 7.6% (trend: 64.68, p < 0.0001), trimethoprim-sulfamethoxazole: 12.6% (trend: 16.45, p < 0.0001), quinolones 9.4% (trend: 36.80, p = 0.02), vancomycin 2.0% (trend: 16.30, p = 0.03), echinocandins: 6.0% (trend: 15.17, p = 0.01) and azole antifungals: 12.10% (trend: 102.05, p < 0.0001). Additionally, a statistically significant increase of 10.30% in the consumption of azole antifungals expressed in DDD/100 bed days was observed (p = 0.0008). In contrast, a statistically significant decrease in consumption, expressed in DDD/100 discharges, was identified for cephalosporins -6.0% (p < 0.0001) and macrolides -16.5% (p < 0.0001). Macrolides also showed a downward trend in consumption, as expressed in DDD/100 bed days (-14.3%, p < 0.0001). According to World Health Organization (WHO) access, watch and reserve (AWaRe) classification trend analysis, only the reserve group showed a statistically significant upward change of 9.2% (p = 0.016). Conclusions: This five-year analysis demonstrated trends over time in overall antimicrobial consumption measured in DDD/100 bed days and DDD/100 discharge rates that correlate. In general, for all antimicrobials, after the implementation of antimicrobial stewardship programs (ASP), a downward trend is reported; in contrast, during the COVID-19 pandemic the AMC shows a general upward trend. The comparison between DDD/100 bed days and DDD/100 discharges allows for complementary comparisons to be made regarding antimicrobial exposure in a clinical setting.

A systematic review and meta-analysis on the prevalence of extended-spectrum beta-Lactamase-Producing Klebsiella Pneumonia in Nigeria

Background: Rapid emergence and proliferation of extended spectrum beta-lactamase producing Klebsiella pneumoniae (ESBL-KP) constitute a serious health problem globally. Objectives: The aim of this study was to evaluate the pooled prevalence of ESBL-KP and ESBL genes in Nigeria. Methods: A quantitative method (Meta-analysis) design was used to summarize pooled results of primary studies. Different databases [Google Scholar, PubMed, and African Journal Online (AJOL)] were searched for relevant studies. Meta-analysis was done using random-effects model. I2 and Egger test was used to ascertain heterogeneity and publication bias evaluation. Results: Eighteen observational studies were selected and the pooled prevalence of ESBL-KP in Nigeria was 47.3% [95% confidence interval (CI) 37 – 58%]. Among the genes encoding ESBL, OXA had the highest pooled prevalence in the selected studies [57% (95% CI 32, 76)], followed by TEM [55% (95% CI 36, 70)], CTX-M [54% (95% CI 38, 70)], and 41% (95% CI 27, 57). Heterogeneity tests (I2) was observed to be between 69.22 and 95.63 % for ESBL-KP and ESBL genes in the studies. Egger tests showed no publication bias (0.09 – 0.99). Conclusions: This meta-analysis demonstrated that the prevalence of ESBL-KP is increasing in Nigeria. Hence, antimicrobial stewardship and infection control measures for the prevention and spread of these strains be implemented. Keywords: Extended spectrum beta-latamase; Klebsiella Pneumonia; meta-analysis; Nigeria.

The Spectrum of Pathogens Associated with Infections in African Children with Severe Acute Malnutrition: A Scoping Review.

Understanding the interplay between infections and severe acute malnutrition is critical in attaining good clinical outcomes when managing malnourished children. However, review studies describing the profile of the associated pathogens in the malnourished African paediatric population are sparse in the literature. We aimed to identify the spectrum of pathogens from studies reporting infections in severely malnourished African children, as well as the antibiotic resistance pattern and clinical outcomes. A systematic literature review of the PubMed database was conducted following PRISMA guidelines from January 2001 to June 2024. The search algorithm was ((marasmus) OR (kwashiorkor) OR (severe acute malnutrition) OR (protein energy malnutrition)) AND (Africa). For a more comprehensive retrieval, an additional search algorithm was deployed: ((HIV) OR (tuberculosis)) AND (severe acute malnutrition). We included 60 studies conducted between 2001 and 2024. Most of the studies were from East Africa (n = 45, 75%) and Southern Africa (n = 5, 8.3%). A total of 5845 pathogens were identified comprising 2007 viruses, 2275 bacteria, 1444 parasites, and 119 fungal pathogens. The predominant pathogens were HIV, Mycobacterium tuberculosis, and malaria parasites accounting for 33.8%, 30%, and 24.2% of pathogens identified. Antibiotic susceptibility testing was documented in only three studies. Fatality rates were reported in 45 studies and ranged from 2% to 56% regardless of the category of pathogen. This review affirms the deleterious effect of infections in malnourished patients and suggests a gross underdiagnosis as studies were found from only 17 (31.5%) African countries. Moreover, data on fungal infections in severely malnourished African children were nearly absent despite this population being at risk. Thus, there is an urgent need to prioritize research investigating African children with severe acute malnutrition for fungal infections besides other pathogens and improve the availability of diagnostic tools and the optimized usage of antibiotics through the implementation of antimicrobial stewardship programmes.

Implementation of an algorithm for testing, diagnosis, and antibiotic stewardship of asymptomatic bacteriuria in pregnancy

BackgroundAsymptomatic bacteriuria (ASB) affects 2-15% of pregnant women, with 20-40% developing symptoms later. Symptomatic urinary tract infections (UTIs) are more common in pregnancy, with a prevalence of 33%, posing risks like preterm delivery, low birth weight, and maternal pyelonephritis. The gold standard for UTI detection is a urine culture, but point-of-care urinalysis dipsticks are frequently performed as screens during regular obstetric visits. Leukocyte esterase has been used to justify treatment in the asymptomatic, even with low sensitivity and specificity. Confirmatory tests are crucial to avoid false positives and ensure optimal outcomes. Current guidelines for urinalysis dipstick interpretation and the decision to treat ASB in pregnancy are limited. It remains unclear if an evidence-based algorithm can improve test utilization, diagnosis, and treatment decisions for ASB in pregnancy. ObjectivesThe primary objective of our study is to develop, implement, and evaluate an evidence-based algorithm to guide urinalysis interpretation, culturing, diagnosis, and antibiotic stewardship of asymptomatic bacteriuria in pregnant patients during routine obstetric visits. Study DesignThe project involves both retrospective and quasi-experimental prospective chart reviews of pregnant patients aged 18 and older, beyond 20 weeks gestation, from routine obstetric visits with urinalysis dipstick tests. A doctorate in clinical laboratory sciences student developed an educational algorithm to guide urinalysis dipstick interpretation, culturing necessity, and treatment decisions based on evidence-based practice. Our study considered patient records from February 1 – 28, 2022 as retrospective (pre-algorithm implementation) data and January 24 - February 22, 2023, as prospective (post-algorithm implementation) data. Data collected from the electronic medical record included de-identified patient information, urinalysis results, culture dates and outcomes, antibiotic prescriptions, UTI or ASB diagnoses, provider details, adverse pregnancy outcomes, and demographics. Data analysis using SPSS version 29 involved chi-square tests, likelihood ratios, and effect size calculations, with P-values <0.05 considered statistically significant. ResultsIn our study, we examined a total of 1,176 patient records. Pre-implementation data included 440 records, with 224 abnormal and 216 normal urinalyses. Post-implementation data encompassed 736 records, of which 255 were abnormal and 481 were normal. The patient demographics predominantly featured White (87%), with a median maternal age of 27 years and a gestational age of 32 weeks. Our pre-implementation analyses revealed significant associations between algorithm deviations with both culture utilization (P <.001) and antibiotic stewardship (P <.001). However, no significant associations were observed between algorithm deviations and adverse patient outcomes. Culture underutilization decreased significantly from 43.0% (189/440) pre-implementation to 29.5% (217/736) post-implementation (P < .001). The overall reduction in ASB prevalence from 16.3% (8/49) to 6.7% (10/67) suggests a decrease of nearly 60%. Additionally, antibiotic overprescription decreased significantly from 1.6% (4/258) pre-implementation to 0.8% (4/522) post-implementation (P = .003), with a reduction from 7.1% (3/42) to 2.4% (1/41) among abnormal urinalyses. ConclusionOur findings show a strong alignment between the use of the algorithm and subsequent clinical decisions, underscoring its potential to enhance patient care and management in obstetric settings. Notably, adherence to the algorithm was higher among providers displaying prudent antibiotic use.

Enhancing antimicrobial management: A 5–year retrospective analysis of urinary pathogen susceptibility at a tertiary care centre from January 2018 to December 2022

Objective: The study aims to collect data on prevalence and antibiotic susceptibility patterns of uropathogens in a hospital in India, and to analyze any changes that have occurred over the past 5 years. Methods: This retrospective study was conducted over 5 years at Lady Hardinge Medical College &amp; Associated Hospitals, New Delhi. Urine samples from patients who attended outpatient department or were admitted with diagnosis of urinary tract infection (UTI) were included in this study. Samples were cultured and tested to identify bacteria and determine antibiotic susceptibility using the Kirby-Bauer disc diffusion method. Results: A total of number of 151395 urine specimens were collected from January 2018 to December 2022. The prevalence of UTI was 7.5% (11372/151395) with the majority of patients being aged above 40 years (19.3%). The prevalence was higher in females (12.7%) as compared to males (3.2%). Escherichia (E.) coli was the predominant pathogen, accounting for 59.8% of cases, followed by Klebsiella spp. at 18.9%, and Enterococcus spp. at 8.3%. Gram-negative bacteria accounted for 89.5% of the isolates and exhibited good susceptibility to aminoglycosides and piperacillin-tazobactam, but showed resistance to fluoroquinolones. Methicillin-resistant Staphylococcus aureus (MRSA) was present in 35% of Staphylococcus (S.) aureus isolates with high susceptibility to glycopeptides and nitrofurantoin. Conclusions: The data suggest the need for careful selection of empirical therapy due to increasing resistance patterns. The stringent use of antimicrobial agents is pivotal to the control of antimicrobial resistance. Antibiotic susceptibility data contributes to tailoring the antibiotic stewardship programs to local needs.

Impact of age on antimicrobial prescriptions in hospitalized children at three academic centres in South Africa: a point prevalence survey.

Antimicrobial resistance is a global threat in children, and the emergence of multi-drug-resistant organisms is of concern. This secondary analysis of an antimicrobial point prevalence survey (PPS) in children evaluates the impact of age on antimicrobial use. The mean antimicrobial prescriptions were assessed in neonates, infants, young children (1-5 years), school-going children (6-12 years), and adolescents (13-15 years) from a cross-sectional PPS at three academic hospitals between September 2021 and January 2022. Primary and secondary diagnoses, antibiotic type (World Health Organization AWaRe and Anatomical Therapeutic Chemical classifications), and the incidence of healthcare-associated infections (HAI) were evaluated per age category. Multiple regression models were used to analyse age-related risk factors for HAI. The number of antimicrobials per child (1.7-1.9 per patient) was higher in neonates and infants compared to children 6-12 years old (1.4 per patient). Watch antibiotics, especially carbapenems, were commonly prescribed in neonates (32.5%) and infants (42.2%). Reserve antimicrobial use was notable in neonates (4.7%) and infants (4.1%). The incidence risk ratio (IRR) of HAI was higher in neonates and infants (IRR 2.13; 95% CI 1.23-3.70, IRR 2.20; 95% CI 1.40-3.45, respectively) compared to 6- to 12-year-olds. On multivariate analysis of participants according to age, being HIV infected, length of stay >6 days, high McCabe severity score, having surgery and receipt of blood transfusion were associated with an increased risk of HAI (P < .001 for all) while on univariate analysis only, being premature and/or underweight was associated with an increased risk of HAI in infants (P < .001 for both). Infants with risk factors for HAI significantly influenced antimicrobial prescribing, underscoring the necessity for tailored antimicrobial stewardship and enhanced surveillance. The increased use of Watch antibiotics, particularly carbapenems, in infants warrants closer scrutiny. Further research is required to identify inappropriate antimicrobial use in high-risk hospitalized young children.

Trends in antimicrobial resistance amongst Salmonella Typhi in Bangladesh: A 24-year retrospective observational study (1999-2022).

Rising antimicrobial resistance (AMR) in Salmonella Typhi restricts typhoid treatment options, heightening concerns for pan-oral drug-resistant outbreaks. However, lack of long-term temporal surveillance data on AMR in countries with high burden like Bangladesh is scarce. Our study explores the AMR trends of Salmonella Typhi isolates from Bangladesh, drawing comparisons with antibiotic consumption to optimize antibiotic stewardship strategies for the country. The typhoid fever surveillance from 1999 to 2022 included two pediatric hospitals and three private clinics in Dhaka, Bangladesh. Blood cultures were performed at treating physicians' discretion; cases were confirmed by microbiological, serological, and biochemical tests. Antibiotic susceptibility was determined following CLSI guidelines. National antibiotic consumption data for cotrimoxazole, ciprofloxacin, and azithromycin was obtained from IQVIA-MIDAS database for comparison. Over the 24 years of surveillance, we recorded 12,435 culture-confirmed typhoid cases and observed declining resistance to first-line drugs (amoxicillin, chloramphenicol, and cotrimoxazole); multidrug resistance (MDR) decreased from 38% in 1999 to 17% in 2022. Cotrimoxazole consumption dropped from 0.8 to 0.1 Daily defined doses (DDD)/1000/day (1999-2020). Ciprofloxacin non-susceptibility persisted at >90% with unchanged consumption (1.1-1.3 DDD/1000/day, 2002-2020). Low ceftriaxone resistance (<1%) was observed, with slightly rising MIC (0.03 to 0.12 mg/L, 1999-2019). Azithromycin consumption increased (0.1 to 3.8 DDD/1000/day, 1999-2020), but resistance remained ≤4%. Our study highlights declining MDR amongst Salmonella Typhi in Bangladesh; first-line antimicrobials could be reintroduced as empirical treatment options for typhoid fever if MDR rates further drops below 5%. The analysis also provides baseline data for monitoring the impact of future interventions like typhoid conjugate vaccines on typhoid burden and associated AMR.

Effectiveness of caregiver educational materials for paediatric community-acquired pneumonia in the emergency department: a qualitative study.

The objective of this study was to better understand caregiver perspectives on educational materials relating to paediatric community-acquired pneumonia and antibiotic stewardship in the emergency department setting. This was a phenomenologically informed qualitative study. Caregivers of young children in Hamilton, Ontario were presented with four educational materials (animated video, physician led lecture-style video, caregiver led testimony-style video, and a printed brochure) providing information relating to treatment strategies for community-acquired pneumonia. Caregivers were then asked open-ended questions about how they felt about the effectiveness of the media used. The principles of conventional content analysis guided the coding and synthesis of the transcribed interviews. Eleven caregivers were interviewed. Most caregivers preferred the animated video and brochure to the lecture-style physician video and caregiver testimonial video. Common themes for effective educational materials included visually attention-grabbing graphics, accessible language, and formats they could reference following their visit (e.g. brochure). The busy nature of the emergency department setting can impede effective communication between clinicians and parents. Employing educational materials may allow for more informed parent-provider communication on care decision making. Caregivers in our study prioritized the simplest information formats for education around community-acquired pneumonia and antimicrobial stewardship which could be referenced following discharge. This was best accomplished by short, animated videos and brochures. Results from this study can inform development of future educational materials used in paediatric emergency department settings to optimize caregiver education and corresponding care plan adherence.

Therapeutic Indices of Topical Antiseptics in Wound Care: A Systematic Review.

Chronic wounds place a heavy burden on healthcare systems and markedly reduce the ability of patients to engage in activities of daily living. One major factor contributing to impaired wound healing is bacterial bioburden. With the rise in antibiotic resistance and the slowdown in antibiotic development pipelines, alternative antimicrobial strategies are important. The objective of this systematic review is to determine the topical antiseptic therapeutic index values for bacterial species commonly isolated from chronic wounds. The therapeutic index is a ratio of the lowest concentration that causes mammalian cell cytotoxicity over the minimum bactericidal concentration. Higher values indicate greater safety and potential clinical benefit. A systematic literature search was performed in Medline and Embase, resulting in the inclusion of 37 articles that reported on the minimum bactericidal concentration in bacterial species commonly isolated from chronic wounds and their cytotoxicity concentrations in mammalian cells. The therapeutic indices for the topical antiseptics included in this study were generally low, with most ranging between 0.5-3.0. The highest therapeutic index values for Escherichia coli (5.49), Staphylococcus aureus (6.31) and Pseudomonas aeruginosa (8.81) were achieved by hypochlorous acid, whereas the highest therapeutic index values for methicillin resistant S aureus (12.1) was achieved by polyhexamethylenebiguanide. Antibiotic stewardship principles may need to be applied to topical antiseptics due to some isolated evidence of topical antiseptic resistance and cross-resistance to antibiotics. The choice of antiseptic should not be made solely based on therapeutic index values, but individualized to the patient, with consideration for the wound healing condition that may include covert infection.

Implementing the Infectious Diseases Society of America Antimicrobial Stewardship Core Curriculum: Survey Results and Real-World Strategies to Guide Fellowship Programs.

The Infectious Diseases Society of America (IDSA) developed the Core Antimicrobial Stewardship (AS) Curriculum to meet the increasing demand for infectious diseases (ID) providers with AS expertise. Notable diversity in implementation approaches has been observed among ID fellowship programs using the curriculum. We sought to describe individual approaches and develop a curriculum implementation roadmap. We surveyed ID fellowship programs that had previously implemented the IDSA Core AS curriculum. The survey included questions regarding program characteristics, curriculum participants and presentation format, resources and barriers, and implementation strategies. Commonly reported program features were summarized in the context of the self-reported implementation strategies. Implementation guides were developed based on the most common characteristics observed. Of 159 programs that had purchased the curriculum, 37 responded, and 34 (21%) were included in the analysis. The curriculum was primarily taught by AS physicians (85%) and AS pharmacists (47%). The most common conference structure was a longitudinal conference series (32%), and eLearning was the most common presentation format. Limited AS faculty time (76%) and limited first-year fellow availability (62%) were frequently reported as barriers, and dedicated AS curricular time was a resource available to most programs (67%); implementation guides were created for these 3 program features. Programs reported a variety of implementation barriers and resources, with several common themes emerging, allowing for the development of tailored curriculum planners for 3 commonly observed program characteristics. This work will equip fellowship programs with curriculum implementation strategies and guide future enhancements of the IDSA Core and Advanced AS curricula.

Sustainment of perioperative antimicrobial prophylaxis guidelines in children following discontinuation of an educational intervention to support stewardship.

Adherence to perioperative antimicrobial guidelines among Greek children was markedly decreased years after the discontinuation of an antimicrobial stewardship (AS) intervention. An educational intervention is effective to improve the perioperative antimicrobial use, but the continuous implementation of AS is important for its long-term sustainability.

A-241 Verification and Validation Study for a Host Response Assay Based on TRAIL, IP-10, and CRP: Application to Pediatric Emergency Department

Abstract Background Acute febrile illnesses (AFIs) represent a significant disease burden globally; however, the lack of reliable, rapid point-of-care testing makes diagnosis difficult. A simple tool for distinguishing bacterial versus non-bacterial infections would radically improve patient management and reduce indiscriminate antibiotic use. MeMed BV® (MMBV) is a blood test to reliably differentiate between viral and bacterial infections. Three host proteins (TRAIL, IP-10, and CRP) are measured quantitatively and a combinational score (0-100) is computed that indicates the likelihood of bacterial infection (or co-infection) versus viral infection (BV Score). MMBV time to result is 15 min on the MeMed Key® analyzer that conducts chemiluminescence-based immunoassays to measure protein concentrations and calculates the test score, using 100 µL of serum. Methods The verification study design was a comparison of known results to on-site testing for contrived samples. The validation study design was a prospective, single-center, observational, blinded diagnostic accuracy study conducted between 8/3/22 to 5/30/23. The population was pediatric patients with suspected serious infections presenting to Geisinger’s quaternary care Pediatric Emergency Dept. in Danville, PA. The comparator was a clinical chart review and adjudication of over 60 clinical and laboratory variables related to systemic infections. The data review team consisted of one pediatric emergency department physician, one pediatric infectious disease physician, and one microbiology laboratory director. If clinical decisions differed among the three, the team adjudicated with a full chart review including knowledge of the eventual outcome, which served as the final reference standard result. The study aims were to assess the analytical and clinical accuracy of MMBV testing and to assess the test’s potential impact to further inform the provider’s decision to admit or discharge the patient. Results Of 60 contrived samples there was three failed tests (5% failure rate) and 2 discordant results. Analytical accuracy was 55/57 (96.5%) for 28 bacterial, 26 viral, and 1 equivocal control. Of 50 pediatric patients recruited, 8 were excluded because they were trauma patients. Among 42 patients tested, 22/42 (52.4%) were interpreted as bacterial or co-infection, 16/42 (38.1%) as viral or non-infectious, and 4/42 (9.5%) as equivocal. For 37/38 (97.3%) of patients with bacterial/viral MMBV results, the result was concordant with expert adjudication. Of the 42 patients for which potential utility was assessed, all results were in alignment with the clinical decisions made for admission or discharge. Conclusions MMBV performed accurately in pediatric ED patients with symptoms of severe infection, both clinically and analytically. A larger sample size will be tested to assess the utility in ED admission and discharge decisions and antimicrobial stewardship. The prevalence of viral and bacterial or coinfection cases within the sample population is representative of the pediatric population samples.

B-047 A Rapid Host-Response Test Supports Antimicrobial Stewardship at a Micro-Hospital Emergency Department

Abstract Background The management of patients with suspected infections requires identification of the infectious etiology to determine appropriate use of antibiotics. However, differentiating viral from bacterial infection (and co-infection) is often challenging as clinical presentations can be similar and existing diagnostics sometimes fail to identify a clinically relevant pathogen. A host-response test (MeMed BV®, MMBV) that relies on computational integration of three proteins (TRAIL, IP-10 and CRP) measured from blood or serum has demonstrated high diagnostic performance for differentiating bacterial from viral infections, with a negative predictive value &amp;gt;95% across multiple studies. This report evaluates real-world use of MMBV at a micro-hospital Emergency Department (ED) and associated antibiotic prescribing. Methods The study is a retrospective analysis of real-world data collected between January and June 2023. MMBV was ordered by providers at a micro-hospital ED in Tucson, AZ at provider discretion as part of routine care. Prescription among cases with MMBV score &amp;lt;35 was analyzed. This cutoff is indicated by the manufacturer to indicate a viral or other non-bacterial etiology. If an antibiotic was prescribed, the authors conducted a chart review to adjudicate whether the prescription was warranted. Results Data was evaluated between January and June 2023; 116 MMBV tests were ordered by six providers. Most tests (81.9% (95%CI: ±7.0%)) had an MMBV score &amp;lt;35 (mean score 11.3 with standard deviation 10.8). Among these, 92.6% (95%CI: ±5.3%) of cases with viral results were not prescribed antibiotics. MMBV use increased throughout the study period from 12 tests in the first month to 25 in the last month (r = 0.88; p&amp;lt;0.001). There were seven cases where providers chose to prescribe despite a viral MMBV result. Upon chart review, 2/7 were unwarranted prescriptions. Conclusions In the emergency settings, integrating MMBV can effectively guide clinical decision-making, potentially reducing unnecessary antibiotic use. Further research in diverse healthcare settings is needed to validate these findings.

A-307 Clinical utility of serum calprotectin in febrile infants presenting to the Emergency Department

Abstract Background Antimicrobial stewardship involves a delicate balance between the risk of undertreating individuals and the potential societal burden of overprescribing antimicrobials. However, early and accurate diagnosis of bacterial infections in critically ill patients is challenging, as the clinical manifestation is non-specific. Furthermore, the results from microbial cultures may be delayed, resulting in delayed antibiotic treatment, which is associated with increased mortality. Neutrophil activation is a major response to bacterial infection and calprotectin is the most abundant protein in the cytosolic fraction of neutrophils, shown as an early marker for neutrophil activation. The objective of this study was to evaluate the clinical performance of serum calprotectin in identifying bacterial infection in febrile infants presenting to an Emergency Department (ED) relative to other common biomarkers of infection. Methods 141 infants aged 28-90 days with suspected infectious disease presenting to the ED at The Hospital for Sick Children in Toronto, were included in this non-interventional investigation. All biomarkers except calprotectin were used in the routine clinical adjudication of the final diagnosis. Residual serum specimens collected as part of the standard care pathway were stored at -80°C prior to analysis of serum calprotectin using GCAL® assay (Gentian AS, Norway). Chart review was completed for key variables including, age (days), sex, chief complaint and temperature at ED presentation, and available laboratory test results (i.e., C-reactive protein and procalcitonin (Architect, Abbott Diagnostics), WBC count and neutrophil count (XN3000, Sysmex Europe GmbH), urinary leukocytes and nitrates, blood and/or urine bacterial culture). Final diagnosis, admission status, and antibiotic prescription at ED discharge were also extracted. Results Final discharge diagnosis in patient population included bacterial infection (n=23), viral infection (n=22), fever of unknown source (n=54) and other/unknown diagnosis (n=42). Antibiotics were prescribed in 36 cases, although bacterial infection could only be confirmed in 23 cases when final diagnosis was made. Statistically significant differences were observed in serum calprotectin (p&amp;lt;0.001), procalcitonin (p&amp;lt;0.001), and CRP (p&amp;lt;0.001) in patients with bacterial infections compared to patients with other discharge diagnoses. ROC curve analysis was performed for the identification of bacterial infections in the entire clinical cohort (n=141) and in only patients with laboratory confirmed bacterial or viral infection (n=41). Calprotectin and procalcitonin showed higher specificity than CRP and WBC count for differentiation between bacterial and viral infection in both cohorts. Performance of calprotectin in detection of bacterial infections was comparable to the performance of CRP, slightly better than performance of procalcitonin and superior to WBC count. Conclusions In this cohort, one third of the children that were prescribed antibiotics did not have confirmed bacterial infection. Hence, there is a need for adequate diagnostic tools to help discriminate between various kinds of infections. This study confirms serum calprotectin as a valuable biomarker for differentiation between types of infection and estimation of disease severity in febrile infants. Access to fast and accurate analysis of circulating calprotectin, combined with good clinical performance has the potential to make this biomarker a valuable complement to the current diagnostics of patients with bacterial infections and sepsis.

A-278 Prevalence of Clostridium Difficile in Long-Term Care Facilities Using BD Max Cdiff Molecular Assay

Abstract Background Clostridium difficile (C.Diff) is a gram positive anaerobe producing Enterotoxin and Cytotoxin (toxin A and B respectively); more than half of million infection is diagnosed yearly with more than 10% of the cases are in patients over 65 years old. Residents in Long-Term Care Facilities (LTCF) are more prone to have C. Diff infection (CDI) because of their age, the frequent use of antibiotics, fragilities, co-morbidity, and living environment. Diagnosing CDI is based on clinical signs and symptoms as well as laboratory tests; however, the enzyme immunoassays are reliable, the tissue culture cytotoxicity is labor intensive. The nucleic acid amplification tests are becoming more the standard as first step in the diagnosis. The BD MAX™ System is a PCR walkaway instrument that provides the sensitivity, specificity and faster turnaround for the C. diff. Methods The BD MAX™ System is an automated in-vitro diagnostic test for the direct qualitative detection of the C. difficile toxin B gene (tcdB) in human liquid or soft stool specimens from patients suspected of having Clostridium difficile Infection (CDI). Premier Toxins A &amp; B is an enzyme immunoassay for the direct detection of Clostridium difficile toxin A and toxin B in stool samples. We collected data from 5,267 samples were collected from resident in LTCF and were run using the EIA assay, 275 samples were ran using the BD Max molecular assay. We had 31 samples that were run using both assays. Statistical analyses were done using Analyse-it. Results Female accounted for 60% of the patients tested; the positivity rate was 13.2% for female and 17.2 for male using the EIA. The positivity rate was 19.2% for female and 30.6% for male when using the molecular assay. The agreement between the EIA and the PCR was 87% based on 31 samples that were run for both assays. Conclusions The BD Max gave the benefit of a fully automated with high sensitivity and specificity for the presence of toxin B producing C. Diff. The difference between the methods could be due to the lack of the sensitivity in the EIA and the fact that the molecular assay might be picking up colonized specimen or the beginning or end of infection. However, the ability to diagnose CDI early and prevent spreading of the disease to other patients is a huge benefit to the facilities. We have to keep in mind also that C.diff infection can be prevented with appropriate use of antibiotics and implementing antibiotic stewardship and infection control plan to prevent and stop spreading of the infection.

A-301 Evaluation of Second-Generation Visby Medical Sexual Health Point-of-Care Test: Clinical Concordance, Analytical Error Rates, and Result Turnaround Time

Abstract Background Rapid testing for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis may be useful for antibiotic stewardship initiatives. Our institution recently implemented the second-generation Visby Medical Sexual Health Test (Visby Gen2) for rapid diagnosis of STIs in our emergency department. Here we (1) compared result concordance of the (Visby Gen2) to the first-generation Visby Medical Sexual Health Click Test (Visby Gen1), (2) compared assay failure rates of the Visby Gen1 to Gen2 tests, and (3) compared result turnaround time (TAT) for clinically ordered rapid STI tests to central laboratory STI results. Methods Accuracy was assessed using residual clinical samples in Aptima buffer submitted for routine molecular STI testing (C. trachomatis, N. gonorrhoeae, and T. vaginalis) in the central laboratory on the Panther platform (Hologic). Aptima samples were diluted 1:33 in Visby collection buffer prior to testing on the Visby cartridge. Clinically reported results were used as reference results. Diluted samples with discordant results were re-tested on the reference method and the result from the dilution was used in calculations. Assay failure rates were calculated as the number of failed assays compared to the total assays performed. TAT for rapid and central lab testing was calculated as time of sample received in laboratory to time verified in laboratory information system. Results For Visby Gen1 we observed negative concordance of 100% (41/41) for C. trachomatis, 97.5% (39/40) for N. gonorrhoeae, and 97.1% (34/35) for T. vaginalis. Positive concordance was 91.7% (11/12) for C. trachomatis, 100% (11/11) for N. gonorrhoeae, and 100% (17/17) for T. vaginalis. For Visby Gen1 we observed a 10.5% (12/114) cartridge failure rate. For Visby Gen2, we observed negative concordance of 100% (59/59) for C. trachomatis, 100% (63/63) for N. gonorrhoeae, and 100% (55/55) for T. vaginalis while positive concordance was 100% (10/10) for C. trachomatis, 100% (6/6) for N. gonorrhoeae, and 90.9% (10/11) for T. vaginalis. The Visby Gen2 assay displayed a 4.9% (4/81) cartridge failure rate. Six weeks after implementing the Visby Gen2 assay in our ED, rapid STI panel TAT was 0.48 hours on average (n=20). In the central laboratory the average TAT was 22.31 hours (n=7892). Conclusions Assay concordance to reference method was similar for Visby Gen1 and Gen2 assays. The cartridge failure rate improved by 46.7% with the Gen2 assay which should decrease the need to repeat testing due to assay failure. Result TAT decreased by 97.8% when comparing rapid Visby results to central laboratory. Therefore, Visby STI testing using the Gen2 assay can provide accuracy and rapid results likely to facilitate more rapid patient management.

Application of the Hub-and-Spoke Model in Antimicrobial Stewardship Programmes: A Scoping Review

Background: The hub-and-spoke model (HSM) offers a framework for efficient healthcare service delivery. This scoping review seeks to explore the implementation and effectiveness of the HSM in antimicrobial stewardship (AMS) programmes. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) reporting guideline was followed. A systematic search was conducted in four electronic databases (PubMed, Medline, Cochrane Library, and Google Scholar) from inception until January 2024. Studies where the HSM was used for delivering any AMS activity, intervention, or action, were included. No study-specific filters were applied and all populations, study designs, and health settings were included. Data screening and selection were achieved using Rayyan. Three authors independently screened studies, with conflicts resolved by a fourth author. Data were narratively synthesised. Standard appraisal tools were impractical; however, critical evaluation of data collection and outcome reporting was ensured. Results: Out of 1438 articles, three were included in the scoping review. The primary interventions utilising the HSM in AMS involved reducing antibiotic misuse, training healthcare professionals, case-based learning, establishing AMS programmes, developing antibiograms, and formulating policies or guidelines pertinent to AMS. The studies demonstrated significant clinical improvements in AMS. Clinical outcomes from the studies include a significant reduction in antimicrobial usage and improved antibiotic management, with a notable decrease in days on antimicrobial therapy and increased antibiotic de-escalation. Key facilitators for AMS programme success were tailored education, collaborative learning, strong leadership, strategic practices, and data-driven decisions. Key barriers were leadership challenges, change resistance, knowledge gaps, inadequate data systems, resource limitations, and technological constraints. Conclusions: The review identified a literature gap in HSM use in AMS programmes. Further studies are needed to assess HSM’s effectiveness, feasibility, and cost-effectiveness in AMS contexts.

A nationwide mixed-methods study of gaps and barriers to implementation of antimicrobial stewardship programmes in hospitals in Indonesia

There is an urgent need to understand the implementation barriers of antimicrobial stewardship programs (ASP) in low- and middle-income countries. We conducted a mixed-methods study in public and private hospitals across all provinces in Indonesia (March-December 2023). We used a self-assessment questionnaire with a scoring system, and multilevel ordinal regression to assess associations with hospital and district-level characteristics. Focus group discussions (FGD) with hospital stakeholders examined barriers and enablers. We applied a patient safety framework to integrate results. 575 (19%) of 3026 hospitals completed the self-assessment, of whom 516 (89.7%) had a formal ASP (median 4 [IQR1-5] years), and 14 participated in FGD. The median overall ASP development score was 48.4% (35.9-62.5%), classifying 41 (8.0%) hospitals as inadequate (0-25%), 237 (45.9%) as basic (26-50%), 179 (34.7%) as intermediate (51-75%) and 59 (11.4%) as advanced (76-100%). Scores were highest for hospital leadership support (83.4% [66.7-100%]), followed by ASP team and infectious disease training (66.7% [55.6-77.8%]); education (50% [0.0-75.0%]); ASP interventions (43.8% [18.7-68.7%]); hospital infrastructure (42.9% [14.3-71.4%]); and monitoring, reporting and feedback (40.9% [27.3-54.5%]). A higher ASP development score was associated with higher hospital tiered level, longer ASP duration, and higher district-level public health development index and per capita domestic expenditure, but not with hospital ownership or geographic region. FGDs highlighted barriers related to hospital leadership support, staff technical and behavioral skills, cross-disciplinary collaboration, fear of loss of prescriber autonomy, microbiology and IT support, and hospital accreditation. Identified implementation barriers can inform actions for context-specific, sustainable improvement of ASPs.

Adopting prospective antimicrobial stewardship (AMS) practice in high-risk immunosuppressed groups: an urgent call to action in the era of antimicrobial resistance (AMR).

Life-saving immunosuppressive treatments including intensive chemotherapy and bone marrow transplantation expose patients to a considerable risk of death from infection globally. With evolving AMR and transmission, this could spell disaster for patients across the world and society at large. Antimicrobial stewardship (AMS) and prompt appropriate management of potentially fatal, emergent infections are essential. It is now apparent that antibacterial prophylaxis in patients with haematological cancer may not provide survival benefit while simultaneously increasing risks for AMR carriage. With evolving AMR and increasing immunosuppressed populations across the world, we must institute robust AMS practices. Significant resources are used to combat the impact of AMR on immunosuppressed patients. For lower-middle income countries (LMICs) these resources may not be available and as such the impact caused by AMR is greater. By considering the patient journey holistically we consider risk of infection presented to patients temporally and geographically. A short-term and easy to implement approach of multi-disciplinary team (MDT)-style advance care planning for infection is advocated. Antimicrobials, when used appropriately, enable healthcare procedures to occur and exist. Indeed, the very future of clinical medicine will rely on this yet to be realized value of enablement. Proactive effort and change must occur across all sectors with holism; hence our impetus for convening a joint industry and clinical working group. With at-risk immunosuppressed groups being a sentinel for change, awareness and implementation of patient-centric actions for infection are essential and our recommendations serve as an urgent call to action.

Desiccation tolerance and reduced antibiotic resistance: Key drivers in ST239-III to ST22-IV MRSA clonal replacement at a Malaysian teaching hospital

Molecular surveillance of methicillin-resistant Staphylococcus aureus (MRSA) isolated from Hospital Canselor Tuanku Muhriz (HCTM), a Malaysian teaching hospital revealed clonal replacement events of SCCmec type III-SCCmercury to SCCmec type IV strains before the year 2017; however, the reasons behind this phenomenon are still unclear. This study aimed to identify factors associated with the clonal replacement using genomic sequencing and phenotypic investigations (antibiogram profiling, growth rate and desiccation tolerance determination, survival in vancomycin sub-minimum inhibitory concentration (MIC) determination) of representative HCTM MRSA strains isolated in four-year intervals from 2005 – 2017 (n = 16). HCTM Antimicrobial Stewardship (AMS) and Infection Prevention and Control (IPC) policies were also reviewed. Phylogenetic analyses revealed the presence of 3 major MRSA lineages: ST239-III, ST22-IV and ST6-IV; MRSAs with the same STs shared similar core and accessory genomes. Majority of the ST239-III strains isolated in earlier years of the surveillance (2005, 2009 and 2013) were resistant to many antibiotics and harboured multiple AMR and virulence genes compared to ST22-IV and ST6-IV strains (isolated in 2013 and 2017). Interestingly, ST22-IV and ST6-IV MRSAs grew significantly faster and were more resistant to desiccation than ST239-III (p < 0.05), even though the later clone survived better post-vancomycin exposure. Intriguingly, ST22-IV was outcompeted by ST239-III in broth co-cultures; though it survived better when desiccated together with ST239-III. Higher desiccation tolerance and fewer carriage of AMR genes by ST22-IV, together with reduction of antibiotic selection pressure in HCTM (due to AMS and IPC policies) during 2005 – 2017 may have provided the clone a competitive edge in replacing the previously dominant ST239-III in HCTM. This study highlights the importance of MRSA surveillance for a clearer picture of circulating clones and clonal changes. To our knowledge, this is the first genomic epidemiology study of MRSA in Malaysia, which will serve as baseline genomic data for future surveillance.