AbstractBackgroundAntimicrobial Resistance Research Articles

2814. The Impact of Novel Antibiotics on Curbing Antimicrobial Resistance and Infection Spread a Dynamic Modeling Study

Abstract Background Antimicrobial resistance (AMR) is a growing global concern. Novel antibiotics (ABXs) target resistant pathogens causing gram-negative (GN) bacterial infections. This study assesses the broader impact of novel ABX use on the US healthcare system, including preventing the onward spread of infections and reducing the level of high-threat AMR. Methods A stochastic dynamic transmission model was developed to simulate the interaction between infection transmissibility, bacterial resistance development, and multiple lines of ABX. Included infection types were intra-abdominal infections, urinary tract infections and hospital-acquired /ventilator-associated pneumonia. Included AMR types were carbapenem-resistant and ESBL-producing enterobacterales (CRE and ESBLE), and multi-drug resistant pseudomonas aeruginosa (MDRP). The model has compartments for non-infected, colonized, or infected patients, with a sensitive or resistant strain in a US hospital. Infected patients receive antibiotics resulting in infection clearance or use of an alternate ABX class. Sensitive pathogens gain resistance due to drug pressure or conversely could lose resistance. Ordinary differential equations were used to estimate compartment membership. The primary data source was the Premier healthcare database (172 hospitals, 2016-2020). The model examined the potential reduction in AMR levels and avoided hospital infections, by comparing two scenarios: targeted use of novel ABX for specific AMR types and the status quo with limited novel ABX use. Results When even novel ABXs are reserved as the 2nd or 3rd line of treatment, compared to the status quo, it could result in a ∼1.5% reduction in hospital infections and a change in CRE, ESBLE, and MDRP by −2.5%, −3.6%, and −2.1%, respectively, on an annual basis. The cumulative impact of novel ABXs over 5-10 years was much larger but subject to higher prediction uncertainty. The primary driver of results are infection clearance rates, risk of resistance gain on various ABX, and uptake of novel ABX. Conclusion Targeted use of novel ABXs for resistant pathogens could lead to improved, earlier infection clearance with most types of infections and pathogens, thereby reducing infection transmission and rise of high-threat AMR in the long-term. Disclosures Apoorva Ambavane, PhD, Merck & Co., Inc: Grant/Research Support Michal Litkiewicz, MSc, Merck & Co., Inc: Grant/Research Support Aditya Sardesai, MSc, CSL Seqirus: Advisor/Consultant|Merck & Co. Inc: Grant/Research Support|Merck & Co. Inc: Grant/Research Support Diana Teloian, MA, Merck & Co., Inc: Grant/Research Support Engels N. Obi, PhD, Merck & Co Inc: Employee Joe Yang, PhD, Merck & Co., Inc: Employee|Merck & Co., Inc: Stocks/Bonds

717. Antimicrobial Resistance of Gram-Negative Bacteria in Respiratory Isolates from an Intensive Care Unit in Guatemala

Abstract Background Antimicrobial resistance (AMR) among Gram-negative bacteria (GNB) is a growing concern in public health, particularly in ICU settings. Over the past few decades, there has been a significant increase in ESBL and carbapenem resistance in Latin America, which has resulted in higher mortality rates and increased healthcare costs. One way to understand local bacterial resistance profiles is to examine respiratory isolates, which can serve as a proxy for resistance observed in the clinical setting. It is critical for clinicians to be aware of these profiles in order to make informed decisions about treatment options. Methods A retrospective study was conducted on all respiratory isolates from the ICU of a third-level national hospital over a 6-month period. All respiratory isolates were analyzed for to identify microorganisms and their AMR to selected antibiotics, including Ceftriaxone (CRO), Ceftazidime (CAZ), Cefepime (CEF) and carbapenems. Results A total of 500 isolates were obtained during the study period, resulting in the isolation of 988 microorganisms. GNB represented 92.3% (n=912) of these isolates. Pseudomonas spp was the most common GNB identified (28.07%), followed by Acinetobacter (26.97%) and Klebsiella spp (20.94%). Stenotrophomona isolates were excluded from the analysis as resistance profiling for this organism is not routinely performed in the institution, leaving a total of 868 isolates for AMR analysis. A total of 527 GNB isolates (60.78%) were identified as resistant to both 3rd generation cephalosporines and CEF. Strains with this resistance pattern were considered highly suggestive of ESBL production. Moreover, 66.78% (n=579) of GNB’s analyzed evidenced resistance to carbapenems, with 13.61% (n=118) of strains having been identified as carbapenemase-producing bacteria. Some GNB exhibited alarming levels of resistance as evidenced in table 1.Table 1.Resistance of selected GNBPercentage of bacterial strains from respiratory isolates resistant to selected antibiotics. Conclusion The high level or resistance observed in GNB from respiratory isolates in this study is concordant with other data from Latin America. While the prevalence of GNB in respiratory isolates does not necessarily correlates with clinical infection rates, the high level of resistance found may be an indicator of the AMR epidemiology of infections in this ICU. Disclosures All Authors: No reported disclosures

2154. Cross-resistance of Ceftolozane-Tazobactam and Imipenem-Relebactam Against Clinical P. aeruginosa Isolates from Bloodstream and Respiratory Tract Infections– SMART United States 2019-2021

Abstract Background Antimicrobial resistance among Pseudomonas aeruginosa is challenging with limited treatment options. Ceftolozane/tazobactam (C/T) maintains activity against P. aeruginosa resistant to commonly used β-lactams. Imipenem/relebactam (IMI/REL) can restore the activity of IMI against P. aeruginosa. C/T and IMI/REL can be affected by different mechanisms of resistance, and pathogens can be nonsusceptible to one agent but susceptible to the other. We evaluated the activity of C/T and IMI/REL against P. aeruginosa isolates collected from patients with lower respiratory tract (LRTI) and bloodstream (BSI) infections in the United States as part of the global SMART surveillance program. Methods In 2019-2021, 24 US clinical labs collected up to 100 consecutive, aerobic or facultative, gram-negative pathogens from LRTI and up to 50 from BSI. Of 8643 collected isolates, 1986 (23%) were P. aeruginosa. Susceptibility was determined with CLSI broth microdilution and 2023 CLSI breakpoints. Results Among P. aeruginosa BSI and LRTI isolates, 88% were susceptible (S) to both C/T and IMI/REL, 2% were nonsusceptible (NS) to both agents; 8% were S to C/T but not to IMI/REL, and 2% were S to IMI/REL but not to C/T (Table 1). Among MDR and DTR isolates, 45% and 29%, respectively, were S to both C/T and IMI/REL and 11% and 20%, respectively, were NS to both. Among C/T-NS isolates, 57.3% and 44.0% were S to IMI/REL and ceftazidime/avibactam (CZA), respectively (Table 2). Among IMI/REL-NS isolates, 83% were C/T-S, 69% CZA-S, and < 43% were S to all other studied β-lactams and LVX. Among CZA-R isolates, 61% and 47% remained S to C/T and IMI/REL, respectively. Conclusion Resistance to both C/T and IMI/REL was not common among recent clinical isolates of P. aeruginosa from the US, and both agents represent important treatment options. A significant proportion of isolates NS to one agent were S to the other, especially among MDR and DTR isolates. The data suggest that susceptibility to both agents should be tested. Disclosures Sibylle Lob, MD, Merck & Co., Inc.: Honoraria Mark G Wise, PhD, Merck & Co., Inc.: Honoraria|Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation Fakhar Siddiqui, MD, MBA, Merck & Co Inc.: Employee Daniel F. Sahm, PhD, Merck & Co., Inc.: Honoraria|Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation

2231. Point Prevalence Survey on Antimicrobial Appropriateness in a Tertiary Care Hospital in Saudi Arabia

Abstract Background Antimicrobial resistance is a significant global health problem. Optimizing the use of antimicrobial agents is a key strategic objective for any antimicrobial stewardship program (ASP). In the literature, 9-64% of antimicrobials prescriptions were inappropriate the hospital setting. We aim to evaluate antimicrobial utilization practices and subsequently implement informed interventions to optimize antimicrobial use by conducting a point prevalence survey (PPS). Methods This is a single-center PPS at King Fahad Specialist Hospital-Dammam, Saudi Arabia. The hospital is specialized in Transplant, Oncology/hematology, and Neuroscience, with approximately 350 beds. All inpatient wards were conducted over one week period ward by ward. All inpatients on active antimicrobials were included. Data were collected from patients’ electronic medical records based on the WHO methodology for PPS on antibiotic use in hospitals. The outcome (appropriateness of antimicrobial treatment) included five elements: indication, duration, administration route, spectrum, and dosing. Assessments were made according to the local and international guidelines and the ASP team (Infectious diseases consultant and pharmacist). Results A total of 316 patients’ medical records were screened. Of whom 121 were included. Nineteen (16%) patients were pediatrics, and 102 (84%) were adults. Patients’ characteristics are presented in Table 1. A total of 207 systemic antimicrobials were recorded, 117/207 (57%) therapeutic and 90/207 (43%) prophylactic. The antimicrobials were inappropriate in 73 /207 (35%) antimicrobial orders that included 84 elements. Eleven out of the 73 orders have more than one inappropriate element. The main reasons were inappropriate indication 31/84 (37%), followed by the antimicrobial spectrum 21/84 (25%). Figure 1Table 1:Characteristics of patients receiving systemic antimicrobial treatment, n (%)Figure 1:Elements of antimicrobials inappropriateness Conclusion This point prevalence survey showed 35% of the antimicrobial prescription in the inpatient setting was inappropriate. The most common reasons were the indication followed by the spectrum and duration of antimicrobials. These findings provide valuable insight into stewardship's best approach and interventions to improve antimicrobials appropriateness. Disclosures All Authors: No reported disclosures

565. Antimicrobial susceptibility profiles of Acinetobacter species in blood: 10-year experience from a major United States reference laboratory

Abstract Background Antimicrobial resistance (AMR) is a threat to healthcare, and infections with antimicrobial resistant organisms carry significant morbidity and mortality. Owing to high rates of AMR, the Centers for Disease Control and Prevention listed Acinetobacter baumannii as a top priority pathogen for research and development of new antimicrobial agents. Antimicrobial susceptibility testing is challenging for this organism, and susceptibility profiles are variable, leading to need of a potential guidance document with assistance in selecting effective empiric therapeutic regimens. Methods We retrospectively reviewed the microbiology and antimicrobial susceptibility testing (AST) results for Acinetobacter spp. from blood culture isolates submitted to Mayo Clinic Laboratories from December 2012 to 2022. AST was performed using agar dilution and interpretations following Clinical & Laboratory Standards Institute (CLSI) guidelines. Isolates were identified by MALDI mass spectrometry and/or 16S sequencing, as available (Figure 1).Figure 1:Isolate identification Isolate identification description. Isolates were analyzed based on this classification used in out laboratory. Results 804 blood culture isolates were included. A. baumannii/calcoaceticus complex (27%) was most frequently isolated, followed by A. lwoffii (22%), and showed the highest resistance across all antimicrobials (73% susceptible or below) (Figure 2). A. baumannii/calcoaceticus complex showed rising resistance rates over time from 2012 to 2022 for meropenem, minocycline and ampicillin-sulbactam (Figure 3). Cefiderocol non-susceptible rate was 35% for A. baumannii/calcoaceticus complex.Figure 2:Antimicrobial susceptibility profiles for Acinetobacter spp. Description of susceptibility profiles for Acinetobacter spp. isolates, based on the classification used by our laboratory. Antimicrobials are presented at the top and isolates on the left. Number of isolates analyzed are presented in the table with the percentage of the isolates susceptible to each antibiotic class in parenthesis.Figure 3:Acinetobacter baumannii/calcoaceticus complex isolates and resistance, trend Trend of isolates per year and resistance percentage to meropenem, colistin, minocycline and amp-sulb. Number of isolates per year at the base of each bar; percentage of resistance for antimicrobials expressed on lines. Amp-sulb = ampicillin-sulbactam. Conclusion A. baumannii/calcoaceticus complex showed high levels of resistance ( >75%) across multiple antimicrobials and increasing rates of resistance over time from 2012 to 2022. A high number of cefiderocol non-susceptible organisms is also concerning (Figure 2). Disclosures Audrey N. Schuetz, MD, Merck: Advisor/Consultant

1245. Knowledge, Attitudes, and Practices of Healthcare Workers towards Antimicrobial Stewardship in Dr. Paulino J. Garcia Memorial Research and Medical Center: A Cross Sectional Study

Abstract Background Antimicrobial resistance, a challenge faced by the public health sector, occurs when pathogens are no longer susceptible to common medicines used to treat them. Several studies have shown that reduction in antibiotic prescription could be done successfully through behavioral intervention. It is important to ensure that antimicrobials are prudently used to preserve its efficacy and enable maximum therapeutic effect. This study assessed the knowledge, attitudes, and practices of healthcare workers towards antimicrobial stewardship at Dr. Paulino J. Garcia Memorial Research and Medical Center in Nueva Ecija, Philippines. Methods Cross-sectional design was used in this study. Stratified random sampling and proportional allocation to each stratum was used. Healthcare workers including physicians who routinely prescribed antibiotics; nurses assigned at the wards, and pharmacists were included. Questionnaires were self-administered. Kruskal-Wallis H Test and Dwass-Steel-Critchlow-Fligner pairwise comparisons were used in data analysis. Results There were a total of 142 participants. Significant differences were noted on actual knowledge between physicians and nurses, on hand hygiene between physicians and nurses and nurses and pharmacists, on perceived knowledge between surgical area and family medicine and medical area and family medicine. There was also a significant difference between physicians and nurses on attitudes towards antimicrobial stewardship. There were no significant differences noted in the practices of healthcare workers. Conclusion Healthcare workers are essential in the fight against antimicrobial resistance. Physicians, nurses, and pharmacists had overall good knowledge, attitudes, and practices towards antimicrobial stewardship but despite this, attention must be given to subsets of the study garnering a poor or moderate level of knowledge. This must be addressed by reinforcing previous known concepts and conducting regular trainings and seminars. Factors affecting the knowledge and practice of antimicrobial stewardship program must also be explored. Disclosures All Authors: No reported disclosures

Antimicrobial Resistance in the Upper Respiratory Tract of Children Compared with Adults

Abstract Background Antimicrobial resistance (AMR) is a growing global public health threat. In 2019, resistant bacterial infections and respiratory tract infections were a leading cause of death in children worldwide. While the gut is a known reservoir of AMR genes, there is little data on the AMR burden in the respiratory tract. We used metagenomic RNA next-generation sequencing (mNGS) to describe bacterial AMR genes detected in the upper respiratory tract of children and compare with adults. Methods We leveraged two established cohort studies of children and adults diagnosed with acute respiratory illnesses in the inpatient and outpatient setting in California and Colorado. Nasopharyngeal (NP) swabs were collected between March to September 2020. Specimens underwent RNA extraction and paired-end Illumina sequencing. AMR genes were detected using the ARG-ANNOT database and the CZID pipeline. Children ≤18 years of age and adults≥ 40 years of age were eligible for inclusion in the analysis. We described and compared AMR genes and AMR gene classes detected in children and adults. P-values were calculated using the Wilcoxon rank-sum test. A multiple logistic regression model was fitted to evaluate the association of age cohort (children vs adults) with presence of AMR genes, while accounting for possible confounding from sex and encounter setting. 95% confidence intervals (CI) were calculated using the Wald CI. Results NP swab mNGS data from 236 patients (82 children, 154 adults) were analyzed. Children were a median age of 4 years (range: 0-17 years), and adults were a median age of 62 years (range: 40-89 years). Both cohorts were 50% male. AMR genes were detected in 44 (54%) children and 109 (71%) adults. Genes conferring resistance to beta-lactams (n=112, 47%), macrolides (n=89, 38%), and tetracyclines (n=72, 31%) were the most frequently detected. Among children, children ages 0 to 2 years had a higher number of AMR genes than children of other age groups, particularly when compared with children ages 3 to 10 years (p-value: 0.031) (Figure 1A). When comparing children with adults, children had fewer AMR genes (p-value: 0.014) as well as fewer AMR gene classes (p-value: 0.031) (Figure 1B). In the multiple logistic regression model, children still had lower odds of any AMR genes detected compared with adults (odds ratio: 0.39, 95% CI: 0.21-0.71). Figure 1. Box plots of (A) the number of antimicrobial resistance (AMR) genes detected in children stratified by age, and (B) the number of AMR genes and AMR gene classes detected in children (n=82) and adults (n=154). The size of the individual data points within the box plots correlates with the number of patients at each data point. Conclusion Children had fewer AMR genes and gene classes than adults in their upper respiratory tract microbiome. Despite this, over half of the children had detectable resistance genes, and children 2 years and younger had more AMR genes than other children. Almost half of the children had resistance genes to beta-lactams, the most frequently prescribed antibiotics to children. These findings suggest that presence of AMR organisms in the airway is common even in children, and that continued efforts to reduce AMR burden in this population are essential.

Antimicrobial stewardship: knowledge, attitudes and practices regarding antimicrobial use and resistance among non-healthcare students at the University of Zambia.

Antimicrobial resistance (AMR) poses a significant threat to the world and could become humanity's next major challenge. This study assessed non-healthcare students' knowledge, attitude and practices (KAP) towards antimicrobial use (AMU) and AMR at the University of Zambia. This cross-sectional study was conducted among 443 non-healthcare students from August to October 2022 using a structured questionnaire. Data analysis was done using IBM SPSS version 24.0. Of the 433 participants, 55.2%, 63.5% and 45% had moderate KAP scores regarding AMU and AMR. The prevalence of self-medication with antibiotics was 76.7%. Male participants were less likely to have good knowledge (OR = 0.524, 95% CI: 0.347-0.792) and positive attitudes (OR = 0.585, 95% CI: 0.364-0.940) towards AMU and AMR compared with females. Students who were studying Engineering and Mining were more likely to have good knowledge of AMR (OR = 1.891, 95% CI: 1.197-2.987) compared with those in Social Sciences. Those who were in their fourth and fifth years were more likely to have positive attitudes towards AMU and AMR (OR = 1.851, 95% CI: 1.147-2.986) compared with those who were in the first, second and third years. Finally, students who practised self-medication were less likely to have good self-reported practice towards AMR (OR = 0.442, 95% CI: 0.278-0.702) compared with those who did not. This study demonstrated that non-healthcare students had moderate KAP regarding AMU and AMR. All university students should be provided with education about AMU and AMR through free short courses, seminars, workshops, and AMR and antimicrobial stewardship awareness campaigns.

Gamification as an educational tool to address antimicrobial resistance: a systematic review

Abstract Background Antimicrobial resistance (AMR) poses a serious threat to global healthcare, and inadequate education has been identified as a major challenge by the WHO. The human , animal and agricultural sectors contribute to the emergence of AMR. Gamification has emerged as an innovative tool to improve knowledge and change behaviours. Our study provides an overview of the literature on existing games in prescribers’ education across the One Health sectors, with a particular focus on the impact of gamification on learning. Methods Using the PRISMA guidelines, we searched Cochrane, PubMed, Scopus and Google Scholar for articles related to gamification for future prescribers of antimicrobials from inception until 28 March 2023. Retrieval and screening of articles was done using a structured search protocol with strict inclusion/exclusion criteria. Results A total of 120 articles were retrieved, of which 6 articles met the inclusion criteria for final analysis. High-income countries had the most studies, with one global study incorporating low- to middle-income countries. All games were evaluated in the human sector. Board and card games, featuring scoring and point systems, were the most prevalent game types. Most games focused on improving knowledge and prescribing behaviours of medical students, with bacteria or antibiotics as the only content. All studies highlighted the significant potential of gamification in mitigating AMR, promoting antimicrobial stewardship, and improving retention of information compared with conventional lectures. Conclusions Our review found an absence of studies in the animal and environmental sectors, disproportionately focused on medical students with questionable sample size, inadequate assessment of game content and effectiveness, and opportunities for game developers.

Making sense of ‘implementation gaps’ as a governance problem of antimicrobial resistance

Abstract Background Antimicrobial resistance (AMR) is a pressing global health issue. National Action Plans on AMR (NAP-AMR) are key to mitigate AMR, however, effective translation of action plans has been a governance challenge worldwide. This study explores the implementation gap in Austria by examining experiences of experts involved in domestic AMR policy. Methods This study was guided by grounded theory. Data were collected through qualitative interviews, a focus group, and participation in AMR symposia. Overall, 13 participants were identified through theoretical sampling. Data collection and analysis took place until theoretical saturation was achieved. Results Experts identified the following central themes affecting AMR mitigation: absence of a binding legal framework, paucity of AMR data, low risk perception among decision makers, lack of funding, and insufficient incentive systems for people dedicated to AMR stewardship. Conclusions The interpretation of these findings suggests policy fragmentation, scattered responsibilities, agenda conformity and a lack of recognition as core features which impede a sustainable and effective AMR-related governance. The results should alert policymakers to sustainable public health interventions in the following areas: a) Institutional responsibilities need to be restructured to prioritize AMR stewardship as a guiding principle. b) Investments are necessary for nationwide implementation of AMR stewardship and surveillance systems. c) Financial and symbolic incentives for people dedicated to AMR mitigation are imperative. Key messages • There is a tension between local efforts to make adjustments to mitigate AMR and the current approach of ‘superimposing’ reforms on existing structures. • Effective measures to address AMR require that priority be given to mitigating AMR.

Evaluating Gamification of Antimicrobial Resistance as an Educational Tool: A Systematic Review

Abstract Background Antimicrobial resistance (AMR) poses a serious threat to global healthcare, and inadequate education has been identified as a major challenge by the World Health Organization. Gamification has emerged as an innovative tool to improve knowledge and change behaviours at the grassroots level. This scoping review provides an overview of existing games in prescribers’ education across the One Health sectors, with a particular focus on the impact of gamification in learning. Methods Using the PRISMA guidelines, we searched Cochrane, PubMed, Scopus, and Google Scholar for articles related to gamification for future prescribers’ of AMR until March 28, 2023. Retrieval and screening of articles was done using a structured search protocol with strict inclusion/exclusion criteria. Results A total of 120 articles were retrieved, of which 6 articles met the inclusion criteria for final analysis. Brazil, UK and France were the sites of almost all the gamification trials, with an additional global study incorporating low-middle income countries. All studies were tested in the human healthcare sector only. Board and card games were the most common types of games, with scoring and point systems as the most common game elements. All games focused on improving knowledge and prescribing behaviours of undergraduate students, with bacteria or antibiotics being the only content. Many studies highlight the significant role gamification can play in mitigating AMR, promoting antimicrobial stewardship (AMS), and improving retention of information compared to conventional lectures. Conclusions Our review highlights a lack of standardised content and gameplay across games addressing AMR for future prescribers of antibiotics, and a gap in assessing gamification of AMR as a tool to promote AMS across all three sectors. Our findings will guide the development of a game in the next phase of the project, as a longitudinal study across Norway and Zambia, focused on the One Health approach. Key messages • Tackling AMR requires improved education and awareness of healthcare workers, veterinarians, and agriculture workers around AMR stewardship issues. • The One Health approach is necessary to mitigate AMR, and the foundation of future prescribers’ is vital. Innovative learning tools like gamification can play a pivotal role in this fight.

Improving healthcare professionals’ interactions with patients to tackle antimicrobial resistance

Abstract Background Antimicrobial resistance (AMR) is one of the most important public health threats. It is important for healthcare professionals (HCPs) who prescribe, dispense, administer and/or monitor antimicrobials to mitigate inappropriate antimicrobial use. This review identified existing interventions which aim to improve HCPs’ interaction with patients and examined factors that enables or hinders appropriate behaviours. Methods We searched MEDLINE, EMBASE, Science Citation Index, Social Sciences Citation Index, Google Scholar, internet and conducted forward and backward citation searching from eligible studies. We included studies of any design, published in English language from year 2010 to 2023. We applied narrative synthesis and used the COM-B (Capability, Opportunity, Motivation - Behaviour) as a theoretical framework for barriers and facilitators at HCP and patient levels. Results We included 59 studies of diverse designs examining a range of interventions from 16 countries. Many interventions involved multiple components beyond HCPs’ interaction with patients, e.g., Treat Antibiotics Responsibly, Guidance, Education and Tools (TARGET). Patient interaction components mostly involved use of posters, leaflets, videos, interactive decision support tools and C reactive protein point-of-care testing. The interventions were often found to be useful. Barriers and facilitators identified related to capability (e.g., knowledge/understanding about AMR, diagnostic uncertainties, awareness of interventions, forgetfulness); opportunity (e.g., time constraint, intervention accessibility) and motivation (e.g., patient's desire for antibiotics, fear of litigation). Conclusions There are many useful interventions to improve HCPs and patients’ interactions for appropriate behaviours in antibiotic use. The barriers and facilitators identified in this review should be considered by intervention designers/adopters and policy makers to improve implementation and effectiveness. Key messages • Factors hindering appropriate antimicrobial use are complex. • This review can inform the development and implementation of strategies to improve healthcare professional’ interaction with the users.

Identifying quantitative evidence-based parameters to monitor emerging resistance to new antibiotics

Abstract Background Antimicrobial resistance (AMR) has a major public health burden, and newly-approved molecules have shown fast emerging of resistance. This study aims at assessing and developing an innovative framework to monitor and benchmark emerging resistance to new antibiotics in Europe. Methods Within the European ECRAID-Base project and the EPI-Net platform, data were extracted at two levels: reporting of emerging resistance to the 12 new antibiotics approved by EMA since 2012 and related outbreaks, and active resistance monitoring in national surveillance systems in 32 European countries. The burden of emerging resistance was measured through the following indicators: time lag between approval and first resistance report, average number of outbreaks, trend in the number of yearly publications standardised by the logarithm of the total number and weighted by the pooled resistance rate, and inclusion of new antibiotics in national surveillances. Results Overall, 956 articles reported resistance to new antibiotics since 2012. Resistance to ceftolozane-tazobactam (CLZ-TAZ) was the most reported, followed by ceftazidime-avibactam (CAZ-AVI); resistance to eravacycline and delafloxacin was less reported. For 6 antibiotics, resistance occurred within one year of approval. Out of 35 surveillance systems reviewed, only 13 (in 12 countries) included at least one new antibiotic; CLZ-TAZ and CAZ-AVI, monitored in 11 and 12 countries respectively, were the most surveyed. Resistance trends showed greater increase for imipenem-relebactam, CAZ-AVI, and meropenem-vaborbactam. Nine outbreaks were detected, including 136 patients: CAZ-AVI was responsible for the highest number of outbreaks (five). Conclusions Resistance was detected to new antibiotics, yet very few countries have active monitoring systems to detect it. Appropriate monitoring and benchmarking of emerging resistance to new antibiotics is pivotal to support careful antibiotic policies at country and global level. Key messages • Emerging resistance to new antibiotics was assessed through quantitative parameters: some drug combinations would deserve further attention, given the increased resistance reports and surveillance gap. • Analysis of these parameters might suggest that combinations of existing agents are prone to developing resistance, and hence support focusing research on the development of novel-class drugs.

B-236 Portable 2 Hour Sample-to-Answer Multi-pathogen Phenotypic Antibiotic Susceptibility Test (AST)

Abstract Background Antimicrobial Resistance is a rapidly growing issue worldwide, arising from the overuse and misuse of antibiotics. The strongest tool the medical community has available to combat AMR is rapid, correct application of antibiotics to identified bacterial infections. Clinics and physician offices seek on-site rapid solutions to speed the pathway to timely and appropriate antibiotic therapies. GeneCapture is prototyping a rapid, sample-to-answer product to provide antibiotic susceptibility results directly from infected urine or wound samples. The test provides a susceptible vs non-susceptible call in under two hours and can be applied to samples with single or mixed pathogens. With support from the Defense Health Agency, a portable table-top instrument and disposable cartridge are being engineered to run this test at the point of care, allowing same-day prescriptions. The process is currently operational on the lab bench. Methods Fluorescent labeling of bacterial species, followed by optical counting, determines population growth with/without a suite of antibiotics. An on-board algorithm instantly converts raw cell numbers into a differential call of Susceptible or Non-susceptible for each bug/drug pair. A disposable cartridge with on-board antibiotics has been designed and is being finalized for fabrication. The optical counting is operating in a desktop device. Results Testing to date includes 124 strains from 7 of the most common Urinary Tract Infection and wound pathogens against a panel of six antibiotics. A total of 541 antibiotic/bacterial strain pairs in single or multiple pathogen antibiotic susceptibility testing (AST), are producing an initial 88.7% agreement to gold standard culture results. These results are all generated in two hours or less of assay time and represent a strong preliminary data set. Conclusion This 2-hour portable, novel, phenotypic AST profiling will produce informed and effective treatment options for medics, clinics and physician offices long before existing AST methods could return results.

47 Clinical Approach to Febrile Urinary Tract Infections in Young Children Presenting to the Paediatric Emergency Department: A Retrospective Study of National Guideline Compliance

Abstract Background Antimicrobial resistance is one of the greatest threats to global health. Antibiotic overuse drives antimicrobial resistance. Suspected urinary tract infection (UTI) is a key area of over-prescribing in many clinical settings but has not been investigated in the paediatric emergency department (ED). Objectives Here, we explore compliance with national UTI management guidelines in a paediatric emergency department setting and characterize patient and provider factors associated with guideline non-compliance. Design/Methods We performed retrospective chart review of patients ages 60 days to 36 months, discharged with a diagnosis of UTI from a single, urban, tertiary care paediatric emergency department (PED) with a diagnosis of UTI. Random visits were chosen using a computer algorithm. Primary outcomes were: 1) proportion of patients receiving guideline-compliant investigation and treatment, and 2) the proportion of children whose antibiotic prescriptions were appropriately adjusted upon return of urine culture and antibiotic susceptibilities (C&S). The guideline was the Canadian Paediatric Society statement on management of UTI, as well as the BC Children’s Hospital institutional UTI management guideline. Descriptive statistics and odds ratios between associations were calculated. Results We reviewed 402 charts. The proportion of infants receiving guideline-compliant testing and treatment was 25.9% (95% CI: 21.8-30.4%). Of those who were prescribed antibiotics, 79.6% (95% CI: 74.7-83.8%) received a first-line recommended agent and 58.9% (95% CI: 53.8-63.8%) received fully compliant therapy with respect to agent, dose, duration, and frequency. 19.4% (15.4-24.2%) of patients who were prescribed empiric cephalexin received an inappropriately high total daily dose. The proportion of patients receiving age-appropriate testing method was 52.2% (95% CI: 47.4-57.1). Febrile children were more likely to receive age-appropriate urine sample collection by catheterized sample (OR: 2.77 95% CI: 1.81-4.25) compared with afebrile children. Ultimately, 50.7% (95% CI: 40.4-49.6%) of patients discharged with a diagnosis of UTI and prescription for antibiotic met diagnostic criteria for UTI based on urinalysis and culture results. Of patients whose C&S mandated a change in therapy, 60.8% (95% CI: 55.8-65.7%) had their agent changed or discontinued. Conclusion Paediatric emergency medicine physicians frequently order inappropriate investigation and empiric treatment of UTI in young children. Discontinuation of empiric antibiotics in culture-negative children may be an impactful stewardship intervention in the PED.

61 Antibiotic Resistant Patterns of Bacterial Pathogens Causing Invasive Neonatal Infections in Northern Alberta

Abstract Background Antimicrobial resistance is one of the most serious global health threats facing the world today. The neonatal intensive care unit (NICU) is a clinical environment that houses newborn infants who are highly susceptible to overwhelming infection. Early and decisive treatment with powerful anti-microbials tends to be the preferred clinical choice for treating sick infants empirically. Prolonged exposure to antimicrobials can result in multi-drug resistant organisms (MDROs), which can be associated with mortality due to an increase in virulence, delay in appropriate treatment, and a lack of treatment options. An updated antibiogram is important for determining the optimal empirical antimicrobial choice for sepsis evaluations. There is currently a lack of antimicrobial susceptibility data for bacterial pathogens in the Northern Alberta region. Objectives The objective of this study is to understand the antibiotic resistance patterns among isolates responsible for bacteremia and meningitis in the NICUs in Northern Alberta through the standard antibiograms produced by microbiology laboratories. Design/Methods We conducted a retrospective study to analyze antimicrobial resistance patterns found in NICUs during 2013-2021 in Northern Alberta. Bacteria isolated from blood and cerebrospinal fluid according to commonly used antibiotics in NICUs were collated to create a provincial antibiogram. Results A total of 5562 isolates were included in this antibiogram. The most frequently isolated organisms were Escherichia coli (1521), Staphylococcus aureus (1157), members of coagulase-negative staphylococcus (534), Enterococcus faecalis (326), and Klebsiella pneumoniae (357) in neonatal populations. Among the 1157 S. aureus isolates, 24% were resistant to oxacillin (i.e., “methicillin-resistant S. aureus” or MRSA) and 1% were resistant to vancomycin (i.e., “vancomycin-resistant S. aureus” or VRSA). Of the 326 strains of Enterococcus spp., there were no vancomycin-resistant enterococci (VRE) identified. Among gram-negative isolates, 251 out of the 2690 (9.6%) were producing extended-spectrum beta-lactamase (ESBL), in which 52% and 94% were susceptible to gentamicin and amikacin respectively. Among the non-ESBL-producing isolates, E. coli (1521) and K. pneumoniae (357), 7% of the E. coli strains and 1% of the K. pneumoniae strains were resistant to gentamicin. Conclusion The provincial antibiogram is a useful clinical tool that can best inform clinicians on the appropriate choice of empirical antimicrobial agent based on commonly identified invasive pathogens in neonatal infections within Northern Alberta. Our findings on these resistant patterns can aid next steps for developing an antimicrobial stewardship program.

High Burden of Intestinal Colonization With Antimicrobial-Resistant Bacteria in Chile: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic. From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive. A total of 775 hospitalized adults and 357 community dwellers were enrolled. Among hospitalized subjects, the prevalence of colonization with FQR, ESCR, CR, or MDR-GNB was 46.4% (95% confidence interval [CI], 42.9-50.0), 41.2% (95% CI, 37.7-44.6), 14.5% (95% CI, 12.0-16.9), and 26.3% (95% CI, 23.2-29.4). In the community, the prevalence of FQR, ESCR, CR, and MDR-GNB colonization was 39.5% (95% CI, 34.4-44.6), 28.9% (95% CI, 24.2-33.6), 5.6% (95% CI, 3.2-8.0), and 4.8% (95% CI, 2.6-7.0), respectively. A high burden of antimicrobial-resistant GNB colonization was observed in this sample of hospitalized and community-dwelling adults, suggesting that the community is a relevant source of antibiotic resistance. Efforts are needed to understand the relatedness between resistant strains circulating in the community and hospitals.

O04 Understanding the key role of accessory genes in AMR phenotype through interpretable machine learning techniques

Abstract Background Antimicrobial resistance (AMR) genes are found to be ubiquitous within the microbiome, even when antimicrobial usage is absent. To identify the AMR phenotype, the most common method is to use a laboratory-based assay. Yet, when dealing with samples from the microbiome, many species are difficult to culture within the laboratory. The vast quantity of strains would be time-consuming to culture. To avoid this, a computational approach may be a more favourable choice. AMR gene finder tools are efficient at determining the AMR genotype. Despite this, how a genotype relates to the AMR phenotype is still an open question. Methods To evaluate the relationship between the AMR phenotype and the AMR genotype, 16 950 genomes from BV-BRC which had corresponding MIC values were analysed. Using Weka’s J48 decision tree model, the relationship between the AMR phenotype and the AMR genotype was analysed. The role of accessory genes in relation to the AMR phenotype was analysed in the same way. Results The J48 models could predict the AMR phenotype accurately using AMR genes and accessory genes; the average accuracy was 91.7% and 92.2%, respectively. The results found that gene co-occurrence, presence and absence of genes are key factors to analyse when identifying the AMR phenotype from genomic data. These factors are not evaluated by commonly used AMR gene finder tools, which could miss vital information to determine the correct phenotype. Conclusions Our results highlight why we should continue to research the relationship between the AMR phenotype and genomic data.

P06 Improving antibiotic prescribing practice in a tertiary burns and plastic surgery department

Abstract Background Antimicrobial resistance is an ever-emerging global public health issue. In the healthcare setting, it is essential to use antimicrobials appropriately and manage infections effectively to help tackle antimicrobial resistance. Objectives To review local antibiotic resistance data, update the plastic surgery infection guidelines based on this data, implement interventions to facilitate compliance with the guidelines and re-audit to assess if these interventions have been effective. Methods A review was undertaken of the previous 3 months of antibiotic susceptibility results for significant staphylococci and streptococci species isolated from blood cultures and wound swabs, and the microbiology results of all local cases of necrotizing fasciitis over a 5-year period. The plastic surgery infection guidelines were updated to reflect the changes in local antibiotic resistance rates. Following implementation of the new guideline, various interventions were undertaken including provision of departmental teaching sessions, ensuring availability of appropriate antibiotics in the burns and plastics theatres and redesigning the guideline to include all plastic surgery and infection guidelines within the one document (previously multiple specific guidelines). Between each intervention, compliance with the guideline was measured to establish if the intervention had made a difference. Results Changes to the guideline included using clindamycin rather than doxycycline for the treatment of cellulitis in penicillin allergic patients, as 44% of Group A Streptococcus isolates identified in wound swabs were resistant to doxycycline. Other changes included the introduction of linezolid if the patient had received a recent or failed course of clindamycin, and the use of cefazolin rather than clindamycin for patients with severe cellulitis with a penicillin allergy, due to the increase in rates of clindamycin resistance. After the three intervention cycles, prescriber compliance with the guideline increased from 50% to 71% demonstrating the need for ongoing intervention and re-evaluation. Conclusions Co-amoxiclav and clindamycin were the most commonly prescribed antibiotics in those patients whose antibiotic prescriptions did not comply with the guidelines. The main reason for this is historical usage of these antibiotics within the specialty; this project demonstrates the challenges in changing established practices in individual clinicians. Interventions to ‘make it easy’ for prescribers to follow antibiotic guidelines (for example, the right antibiotic being easily available at the site of prescription), along with targeted education, can be effective but long-standing prescribing habits within specialist areas may be difficult to change.

Antimicrobial resistance profiles of Escherichia coli isolated from laying hens in Zambia: implications and significance on one health.

Antimicrobial resistance (AMR) has been deepening in the layer poultry sector in Zambia partly due to the inappropriate use of antimicrobials. Escherichia coli (E. coli), a commensal and zoonotic bacterium, can potentially be a source of AMR. This study assessed the phenotypic AMR profiles of E. coli isolated from the apparent health-laying hens in Lusaka and Copperbelt provinces of Zambia. A cross-sectional study was conducted between September 2020 and April 2021 in which 365 cloacal swabs were collected from 77-layer farms based in Lusaka and Copperbelt provinces of Zambia. E. coli isolation and identification were done using cultural and biochemical properties and confirmed using the 16S rRNA gene sequencing. Antimicrobial susceptibility testing (AST) was done using the Kirby-Bauer disc-diffusion method. Data analysis was done using WHONET 2020 and Stata v.16.1. Of the 365 samples, E. coli was isolated from 92.9% (n = 339). The AMR was detected in 96.5% (n = 327) of the isolates, of which 64.6% (n = 219) were multidrug-resistant (MDR). E. coli was highly resistant to tetracycline (54.6%) and ampicillin (54%) but showed low resistance to meropenem (0.9%), ceftazidime (6.2%) and chloramphenicol (8.8%). This study found a high prevalence of E. coli resistant to some commonly used antibiotics in poultry, which is a public health concern because of the potential contamination of eggs and layers of chicken meat that enter the food chain. Urgent attention is needed, including strengthening antimicrobial stewardship and surveillance programmes in layer poultry production in Zambia.