Unnecessary Antimicrobial Use Research Articles

Risk individualisation and moral injury in the treatment of infection as impediments to the tackling of antimicrobial resistance

Antimicrobial resistance (AMR) is subject to extensive risk reduction approaches. A central strategy is reducing the unnecessary use of antimicrobials across agriculture and human and animal health care without jeopardising health outcomes for all species concerned. A prominent framework is antimicrobial stewardship which seeks to balance access to effective infection treatments with ensuring that effective antimicrobials are available for future generations. Balancing these goals has proven challenging and the consumption of antimicrobials and AMR both continue to grow. To shed light on this situation, we examined the risk reasoning that underpins AMR reduction in interviews with 51 practitioners, scientists and policy-makers working on AMR in Australia and the UK. Important themes in our analysis were that action to reduce infection risks clashed with AMR reduction rationalities. Participants were often not able to explain how treating an infection for an individual patient could harmonise with the longer-term goal of AMR reduction. Due to the potential for patient harm, making decisions to use antimicrobials was narrated as individualised and moralised. We argue that more effective AMR reduction depends on addressing this fundamental tension in AMR risk, and its individualising and moralising effects, as the starting point – not the outcome – of policy and practice for AMR reduction.

Etiology and epizootology of bovine mastitis (analytical review)

Mastitis is one of the most common global diseases of dairy cattle, it is detected in 5–36% animals in a herd undergoing a single examination, and the incidence reaches 68% within a year, given that some cows get reinfected more than once. The disease causes significant economic losses to dairy industry both in the Russian Federation and globally. Mastitis is an inflammation of the mammary gland that develops in response to the effects of various factors of the external and internal environment, which are classified as mechanical, physical, biological, etc. Based on the clinical symptoms, the disease has two forms: clinical and subclinical. Both the animal and its milk shall be subjected to a thorough examination for the diagnosis establishment. The final stage of the mastitis diagnosis in cows is laboratory testing. In this case, the most informative is the bacteriological method, which helps to isolate a pathogen’s pure culture, identify it and determine sensitivity to antimicrobial drugs. The latter plays a specific role in indicating the direction of further therapeutic measures, since the obtained data facilitate selection of effective antibiotics against certain pathogens. Incorrect treatment, incompliances with the prescribed therapy, as well as unnecessary use of antimicrobials can lead to the generation of multi-resistant bacteria. Due to the widespread spread of antibiotic-resistant microorganism strains, despite the large number of drugs currently used, their effectiveness is constantly decreasing. The prospects for the further use of antibiotics as therapeutics are questioned by many researchers and international organizations due to antibiotic resistance rapidly developing in many agents. Vaccination plays a significant role in infectious disease control. The use of vaccines not only reduces mastitis occurrence in cows, but also significantly improves the quality of dairy products.

Understanding barriers to reducing antimicrobials on Australian dairy farms: A qualitative analysis

IntroductionReducing antibiotic use in production animal systems is one strategy which may help to limit the development of antimicrobial resistance. To reduce antimicrobial use in food‐producing animals, it is important to first understand how antibiotics are used on farm and what barriers exist to decreasing their use. In dairy production systems, mastitis is one of the most common reasons for administering antimicrobials. Therefore, it is important to understand the motivations and behaviours of dairy farmers in relation to the diagnosis, treatment and prevention of mastitis.Materials and methodsIn this study, we interviewed a sample of dairy farmers and dairy industry professionals from the major dairying regions of eastern Australia regarding their current practices used to diagnose, treat, and control subclinical and clinical mastitis. Inductive thematic analysis was used to code interview transcripts and identify the recurrent themes.ResultsFour overarching themes were identified: (1) the challenges associated with the detection and diagnosis of clinical mastitis, including with laboratory culture, (2) the motivations behind treatment decisions for different cases, (3) decisions around dry cow therapy and the role of herd recording, and (4) concerns regarding the development of antimicrobial resistance.DiscussionThis study identifies several challenges which may limit the ability of Australian dairy farmers to reduce antimicrobial use on farm, such as the need for rapid and reliable diagnostic tests capable of identifying the pathogenic causes of mastitis and the difficulties associated with conducting herd recording for the implementation of selective dry cow therapy. Industry professionals were concerned that farmers were not using individual cow records to aid in treatment decisions, which could result in unnecessary antimicrobial use. The results of this study can act as the basis for future research aimed at assessing these issues across the broader Australian dairy industry.

Antibiotic prescription pattern in pediatric intensive care unit in a tertiary care hospital: A cross-sectional study

Background: Incidence of infections in patients admitted to the Pediatric intensive care unit (PICU) is high which results in the use of antimicrobials for a prolonged duration and numbers. The rising incidence of antibiotic resistance has made it obligatory for antibiotics to be prescribed reasonably in pediatric patients. Aims and Objectives: The objective of this study was to analyze the antibiotic prescription pattern for patients admitted in pediatric intensive care unit in a tertiary care hospital. Materials and Methods: This cross-sectional study was conducted in PICU. Two hundred and seventy-five pediatric patients were incorporated in this study. The patients’ data were collected from the case sheets, recorded, and analyzed. Results: The majority (80%) of patients admitted in PICU received antibiotic(s). About 68.18% of patients were prescribed only one antibiotic. Patients in the age group of 1 m–<1 year (58.18%) received more antibiotics. Pneumonia emerged to be the foremost reason for antibiotic use (45%), followed by Meningitis (14.54%). Ceftriaxone (28.27%) was the antibiotic prescribed most often. About 80.34% of antibiotics were prescribed by their generic names and 5.86% of antibiotics were prescribed as fixed-dose combinations. Conclusion: Antimicrobial resistance has become a global issue that should be tackled with extreme prudence and vigilance. This study provides insight on antibiotic prescription pattern in PICU and can prevent unnecessary use of antimicrobials.

Reaching high-hanging fruit in antimicrobial stewardship: a hospital-based intervention to withdraw inappropriately prescribed antimicrobials.

Antimicrobial stewardship programs (ASPs) are responsible for addressing unnecessary antimicrobial use. We describe our experience with a unique intervention to withdraw unnecessary antimicrobials. Design, Setting, Participants: descriptive case series of adult inpatients at a single academic medical center, December 2021 to December 2022; Intervention: hospital-wide policy allowing ASP to discontinue inappropriate antimicrobials in select cases not resolved by prospective audit and feedback; Measures: count, date, and generic names of antimicrobials prescribed; reason for antimicrobial withdrawal (prolonged duration, no evidence of infection, or other); withdrawals by inpatient service (surgical or medical); time from antimicrobial start date to withdrawal intervention; days of therapy (DOT) saved; "nudge effect" defined as the prescribing team self-discontinuing withdrawn antimicrobial within 24 hours of withdrawal notice; appeals to withdrawals; ordering of alternative antimicrobials following withdrawal; incident infections, readmission, in-hospital mortality within 30 days of withdrawal intervention. There were 54 antimicrobials withdrawn among 36 unique patients during the study period; piperacillin-tazobactam followed by vancomycin were the most frequently withdrawn agents; prolonged duration of therapy or prophylaxis followed by no evidence of infection were the most common reasons for withdrawal; withdrawals occurred most often on surgical services; an estimated 236 DOT (27.2 DOT per 100 patient-days) were saved; 32% of withdrawals were appealed; alternative antimicrobials were ordered following 20% of withdrawals; no incident infections, readmissions or in-hospital deaths were definitively attributed to withdrawal intervention. Our antimicrobial withdrawal intervention was a safe and effective addition to ASP activities to reduce inappropriate antimicrobial use and improve prescriber accountability.

559. Results of the implementation of a molecular pneumonia panel at a hospital in the Dominican Republic: expanding the scope of detection and management

Abstract Background Lower respiratory tract infections (LRTIs) have been associated to significant morbidity and mortality. Conventional microbiology methods often fail to identify the etiological agent due to lack of sensitivity or viral or fastidious pathogens. Pneumonia molecular diagnostics is able to expand the scope of pathogens detected, therefore, we describe our experience in the incorporation of this method, the difference in etiological identification and clinical decision making. Methods We performed a retrospective cohort study of 75 patients with Filmarray pneumonia panel from November 2020 to September 2022. We described demographics, co-morbid conditions, outcomes and correlation with standard cultures in patients who were admitted with LRTI at the Hospital General de la Plaza de la Salud, a 289-bed tertiary teaching hospital in the Dominican Republic. Results Amongst the 75 patients, 56.6% were male and the average age was 51 years old. The most common comorbidities were diabetes mellitus (81.6%), hypertension (40.8%) and nephropathy (10.5%). The panels had a positivity rate of 74.6% (56/75) versus a 35% (14/40) seen in cultures. The most frequent microbial targets detected were S. aureus (18%), P. aeruginosa (14,3%) and K. pneumoniae group (10%) and at least one antimicrobial resistance gene was detected in 50% (28/56), distributed as MecA/C and MREJ (35%), CTX-M (38%), KPC (10%), NDM (10%), VIM (8%), IMP (8%) and OXA-48 like (3%). A positive culture was most likely to occur when the number of copies/mL in the panel was ≥ 10˄5 (p-value < 0.001). A viral target was detected in 21 patients (28%) alone or coinfecting with a bacterial agent. Conclusion Not only did the pneumonia panels allow an earlier detection of the etiological agent, but they also identified more pathogens compared to cultures. This enabled targeted management by reducing the unnecessary use of antimicrobials as well as activating infection control measures when necessary (i.e Influenza). The results seen in this study, along with the expanded scope of pathogens detected, will definitely serve as an update into our current LRTI hospital guidelines. Disclosures All Authors: No reported disclosures

Association between seasonal influenza vaccination and antimicrobial use in Japan from the 2015-16 to 2020-21 seasons: from the VENUS study.

Seasonal influenza vaccination might be considered an antimicrobial resistance (AMR) countermeasure because it can reduce unnecessary antimicrobial use for acute respiratory infection by mitigating the burden of such diseases. To examine the association between seasonal influenza vaccination and antimicrobial use (AMU) in Japan at the community level and to examine the impact of influenza vaccination on the frequency of unnecessary antimicrobial prescription for upper respiratory infection. For patients who visited any healthcare facility in one of the 23 wards of Tokyo, Japan, due to upper respiratory infection and who were aged 65 years or older, we extracted data from the Vaccine Effectiveness, Networking, and Universal Safety (VENUS) study database, which includes all claims data and vaccination records from the 2015-16 to 2020-21 seasons. We used the average treatment effect (ATE) with 1:1 propensity score matching to examine the association of vaccination status with frequency of antibiotic prescription, frequency of healthcare facility consultation, risk of admission and risk of death in the follow-up period of the same season (from 1 January to 31 March). In total, 244 642 people were enrolled. Matched data included 101 734 people in each of the unvaccinated and vaccinated groups. The ATE of vaccination was -0.004 (95% CI -0.006 to -0.002) for the frequency of antibiotic prescription, -0.005 (-0.007 to -0.004) for the frequency of healthcare facility consultation, -0.001 (-0.002 to -0.001) for the risk of admission and 0.00 (0.00 to 0.00) for the risk of death. Our results suggest that seasonal influenza vaccination is associated with lower frequencies of unnecessary antibiotic prescription and of healthcare facility consultation.

Rapid detection of gastrointestinal pathogens using a multiplex polymerase chain reaction gastrointestinal panel and its role in antimicrobial stewardship

ObjectivesThe FilmArray gastrointestinal panel (FAGIP) is widely used to detect infectious diarrhoea due to its outstanding sensitivity compared to conventional methods, but there is geographic variation, such as in the distribution of pathogens, among populations. MethodsThis was a retrospective study that analysed patients with acute diarrhoea who underwent FAGIP tests from all age groups during 2022. We compared positive rates of FAGIP between paediatric (n = 245) and adult patients (n = 242) of different origins. The targeted therapy rate and antimicrobial agent use rate were also analysed. ResultsAmong the 487 stool samples evaluated, the overall, community-origin (CO), and nosocomial (NC) positivity rates of paediatric patients were significantly higher than those of adults (73.9 % vs. 43.0 %, p = 0.000; 76.2 % vs. 51.7 %, p = 0.000; 50.0 % vs. 19.7 %, p = 0.000). Salmonella was the most frequently detected pathogen (35.9 %) in children, while the predominant pathogen in adult patients was toxin A/B-genic Clostridioides difficile (13.2 %). There was a significantly lower antimicrobial agent use rate after FAGIP results were available (79.1 % vs. 64.5 %, p = 0.000) and a higher rate of targeted therapy towards C. difficile infection in adults than in children (84.4 % vs. 69.0 %, p = 0.011). ConclusionPaediatric diarrhoea patients showed higher positivity rates than adult patients. Application of FAGIP for acute diarrhoea might lower unnecessary antimicrobial use.

Machine learning pipeline for blood culture outcome prediction using Sysmex XN-2000 blood sample results in Western Australia

BackgroundBloodstream infections (BSIs) are a significant burden on the global population and represent a key area of focus in the hospital environment. Blood culture (BC) testing is the standard diagnostic test utilised to confirm the presence of a BSI. However, current BC testing practices result in low positive yields and overuse of the diagnostic test. Diagnostic stewardship research regarding BC testing is increasing, and becoming more important to reduce unnecessary resource expenditure and antimicrobial use, especially as antimicrobial resistance continues to rise. This study aims to establish a machine learning (ML) pipeline for BC outcome prediction using data obtained from routinely analysed blood samples, including complete blood count (CBC), white blood cell differential (DIFF), and cell population data (CPD) produced by Sysmex XN-2000 analysers.MethodsML models were trained using retrospective data produced between 2018 and 2019, from patients at Sir Charles Gairdner hospital, Nedlands, Western Australia, and processed at Pathwest Laboratory Medicine, Nedlands. Trained ML models were evaluated using stratified 10-fold cross validation.ResultsTwo ML models, an XGBoost model using CBC/DIFF/CPD features with boruta feature selection (BFS) , and a random forest model trained using CBC/DIFF features with BFS were selected for further validation after obtaining AUC scores of 0.76 pm 0.04 and 0.75 pm 0.04 respectively using stratified 10-fold cross validation. The XGBoost model obtained an AUC score of 0.76 on a internal validation set. The random forest model obtained AUC scores of 0.82 and 0.76 on internal and external validation datasets respectively.ConclusionsWe have demonstrated the utility of using an ML pipeline combined with CBC/DIFF, and CBC/DIFF/CPD feature spaces for BC outcome prediction. This builds on the growing body of research in the area of BC outcome prediction, and provides opportunity for further research.

P06 Stewardship potential—the hidden burden of antibiotic prophylaxis in primary care

Abstract Background This study aimed to decrease unnecessary long-term antimicrobial use in primary care by identifying and highlighting patients with long-term or repeated exposure to antibiotics to GP teams for review. The broad spectrum antimicrobial co-amoxiclav was targeted following data showing rising DDD per prescription in our Health Board. Methods Community antibiotic prescribing from the national Prescribing Information System (PIS) was searched for NHS Lothian (126 GP practices) using DDD to identify patients. Long courses of co-amoxiclav were defined as ≥63 DDD. Ninety-eight patients were identified with high antimicrobial usage and a data collection form was sent to the Primary Care Pharmacy teams to voluntarily collate data for each patient. Results The data collection form had a 97% response rate. Of the 94 patients with full data 62 (66%) patients had co-amoxiclav initiated due to secondary care specialist advice and 26 (28%) had been initiated by primary care. Forty-four patients (47%) were aged 65 or over, putting them at high risk of Clostridioides difficile. Forty-one patients had multiple courses of co-amoxiclav and 39 patients were prescribed co-amoxiclav as prophylaxis; of these 59% were for urinary tract infection (UTI). Thirty-four of 94 patients (36%) had been on prophylaxis for over 5 years with 9 patients on co-amoxiclav for over 20 years. Of note in 39 of 94 patients no microbiology samples were available and where samples were available (n=55), narrower spectrum options were available in 38 patients (69%) and 17 patients (31%) had samples showing resistance to co-amoxiclav. Following this intervention to highlight use, the number of patients on long-term courses or prophylaxis with co-amoxiclav reduced by 70% in the following year. Conclusions Patients on long-term antibiotics are priorities for antimicrobial stewardship interventions. This work demonstrated that ongoing appropriateness and efficacy of long-term antibiotic courses were not routinely reviewed. Using pharmacy data proved an effective method to highlight patients and ultimately reduce patient antibiotic exposure. UTI prophylaxis was the majority patient group in this study and interventions to review and decrease long-term UTI prophylaxis in our Board using this method are underway.

Group A ß-hemolytic streptococcal pharyngitis: An updated review.

Group A ß-hemolytic streptococcus (GABHS) is the leading bacterial cause of acute pharyngitis in children and adolescents worldwide. This article aims to familiarize clinicians with the clinical manifestations, evaluation, diagnosis, and management of GABHS pharyngitis. A search was conducted in December 2022 in PubMed Clinical Queries using the key term "group A β-hemolytic streptococcal pharyngitis". This review covers mainly literature published in the previous ten years. Children with GABHS pharyngitis typically present with an abrupt onset of fever, intense pain in the throat, pain on swallowing, an inflamed pharynx, enlarged and erythematous tonsils, a red and swollen uvula, enlarged tender anterior cervical lymph nodes. As clinical manifestations may not be specific, even experienced clinicians may have difficulties diagnosing GABHS pharyngitis solely based on epidemiologic or clinical grounds alone. Patients suspected of having GABHS pharyngitis should be confirmed by microbiologic testing (e.g., culture, rapid antigen detection test, molecular point-of-care test) of a throat swab specimen prior to the initiation of antimicrobial therapy. Microbiologic testing is generally unnecessary in patients with pharyngitis whose clinical and epidemiologic findings do not suggest GABHS. Clinical score systems such as the Centor score and McIssac score have been developed to help clinicians decide which patients should undergo diagnostic testing and reduce the unnecessary use of antimicrobials. Antimicrobial therapy should be initiated without delay once the diagnosis is confirmed. Oral penicillin V and amoxicillin remain the drugs of choice. For patients who have a non-anaphylactic allergy to penicillin, oral cephalosporin is an acceptable alternative. For patients with a history of immediate, anaphylactic-type hypersensitivity to penicillin, oral clindamycin, clarithromycin, and azithromycin are acceptable alternatives. Early diagnosis and antimicrobial treatment are recommended to prevent suppurative complications (e.g., cervical lymphadenitis, peritonsillar abscess) and non-suppurative complications (particularly rheumatic fever) as well as to reduce the severity of symptoms, to shorten the duration of the illness and to reduce disease transmission.

The dawn of repurposing vitamins as potential novel antimicrobial agents: A call for global emergency response amidst AMR crisis.

Amidst, the global pandemic of antimicrobial resistance (AMR), the rate at which AMR increases overwhelms the increased efforts to discover new effective antimicrobials. There is a persistent need for alternative treatment modalities so as to keep up with the pace. AMR is the leading cause of death in the world and its health and economic consequences suggest the urgent need for sustainable interventions. Vitamins have consistently proven to have antimicrobial activity as well as slowing down the AMR rate by influencing the AMR genes even towards extensive multidrug resistant strains. Evidences suggest that the use of some vitamins on their own or in combination with existing antimicrobial agents could be a breakthrough towards combating AMR. This will widen the antimicrobial agents' options in the treatment arena, preserve the antimicrobial agents susceptible to develop resistant so that they can be used in severe infections only, reduce the tension and burden of the AMR crisis significantly and give enough room for development of new antimicrobial agents. Moreover, almost all viral, fungal, parasitic and bacterial resistant strains of concern as listed by World Health Organization have been found to be sensitive to several vitamins either synergistically with other antimicrobials or independently. Considering their widened spectrum of immunomodulatory and antimicrobial effect, some vitamins can further be repositioned as prophylactic antimicrobial agents in clinical situations like in presurgeries prophylaxis so as to avoid unnecessary use of antimicrobials especially antibiotics. Various relevant AMR stakeholders should invest in clinical trials and systematic reviews with available data to enable quick repositioning of some potential vitamins as antimicrobial agents as an emergency rapid response towards AMR Crisis. This includes the preparation of guidelines containing specificity of which vitamin to be used for treatment of which type of infection.

Diagnostic and Therapeutic Management of Urinary Tract Infections in Catalonia, Spain: Protocol for an Observational Cohort Study.

Antibiotic resistance is an individual and public health problem; multidrug-resistant infections could cause an estimated 10 million deaths worldwide by 2050. Unnecessary use of antimicrobials is the most important cause of resistance generation in the community, and an estimated 80% of antimicrobials are prescribed in primary health care, frequently for urinary tract infections (UTIs). This paper presents the protocol for the first phase of the Urinary Tract Infections in Catalonia (Infeccions del tracte urinari a Catalunya) project. We aim to examine the epidemiology of the different types of UTIs in Catalonia (an autonomous community in Spain) and their diagnostic and therapeutic management by health professionals. Furthermore, we aim to evaluate the correlation between types and total consumption of antibiotics for recurrent UTIs in 2 cohorts of women with the presence and severity of infectious complications of urological origin, especially pyelonephritis and sepsis, and 2 potentially serious infections: pneumonia and COVID-19. The study is a population-based observational cohort study including adults with a diagnosis of UTI registered in the Information System for the Development of Research in Primary Care (in Catalan: Sistema d'informació per al desenvolupament de la investigació en atenció primària), the Minimum Basic Data Sets of Hospital Discharges and Emergency Departments (in Catalan: Conjunt mínim bàsic de dades a l'hospitalització d'aguts i d'atenció urgent), and data from the Hospital Dispensing Medicines Register (in Catalan: Medicació hospitalària de dispensació ambulatòria) of Catalonia from the period between 2012 and 2021. We will evaluate the variables obtained from the databases to analyze the proportion of different types of UTIs, the percentage of adequate antibiotic treatments prescribed or received for recurrent UTIs according to the national guidelines, and the proportion of UTIs with complications. We expect to describe the epidemiology of UTIs in Catalonia from 2012 to 2021, as well as describe the diagnostic and therapeutic management of UTIs by health professionals. We expect to find a high percentage of UTI cases with inadequate management according to the national guidelines, considering that on many occasions UTIs are treated with second- or third-line antibiotic therapies with a preference for the longest regimens. Furthermore, the use of antibiotic suppressive therapies, or prophylaxis, in recurrent UTIs will likely be highly variable. Moreover, we aim to determine whether women with recurrent UTIs treated with antibiotic suppressive therapies have a higher incidence and severity of potentially serious future infections, with special attention to acute pyelonephritis, urosepsis, COVID-19, and pneumonia, compared to women who receive antibiotic treatment after they present with a UTI. This is an observational study of data from administrative databases that will not allow causality analysis. The limitations of the study will be handled according to the appropriate statistical methods. European Union Electronic Register of Post-Authorisation Studies EUPAS49724; https://www.encepp.eu/encepp/viewResource.htm?id=49725. DERR1-10.2196/44244.

Improving diagnostic antimicrobial stewardship in respiratory tract infections: a protocol for a scoping review investigating point-of-care testing programmes in community pharmacy

IntroductionDiagnostic uncertainty regarding the cause of respiratory tract infections (RTIs) multiplies the problem of unnecessary use of antibiotics and antimicrobial resistance in primary care. Point-of-care testing (POCT) programmes have been...

Challenges and opportunities in the implementation of an antimicrobial stewardship program in Nepal

Abstract Antimicrobial resistance (AMR) continues to be a serious global public issue. Unnecessary and inappropriate use of antimicrobials has been identified as a major contributing factor for AMR. Implementation of antimicrobial stewardship programs (ASPs) is valued as a key strategy to combat AMR. Although ASP is a key intervention to improve appropriate use of antibiotics, there is limited experience and research to describe its implementation in low-income countries such as Nepal. Grande International Hospital (GIH) is the first health organization in Nepal to implement and sustain a multidisciplinary ASP and infection control program. Challenges faced in implementing ASP include lack of acceptance from physicians, lack of knowledge regarding antibiotic prescribing, lack of staff for ASP activities, limitations in diagnostic testing to inform ASP, and limitations in antibiotic choice due to antibiotic unavailability. Our ASP includes the following components: an ASP committee, an antibiotic prescribing reference guide with dosage recommendations, inpatient formulary restriction system, educational outreach and programming for physicians and other stakeholders, and periodic review and revision of the program and reference guide. The ASP provided opportunities to address several knowledge gaps across our healthcare institution including improved knowledge and competency regarding rational use of antibiotics, access to quality medicines and better care to patients. It is our hope that, by describing the challenges and opportunities we experienced while implementing our ASP, we can support and encourage other institutions to adapt and implement ASPs in Nepal and other resource-limited settings.

Identification of outcomes reported for hospital antimicrobial stewardship interventions using a systematic review of reviews.

Randomized trials of hospital antimicrobial stewardship (AMS) interventions aimed to optimize antimicrobial use contribute less to the evidence base due to heterogeneity in outcome selection and reporting. Developing a core outcome set (COS) for these interventions can be a way to address this problem. The first step in developing a COS is to identify and map all outcomes. To identify outcomes reported in systematic reviews of hospital AMS interventions. Cochrane Database of Systematic Reviews, MEDLINE and Embase were searched for systematic reviews published up until August 2019 of interventions relevant to reducing unnecessary antimicrobial use for inpatient populations in secondary care hospitals. The methodological quality of included reviews was assessed using AMSTAR-2, A (revised) MeaSurement Tool to Assess systematic Reviews. Extracted outcomes were analysed using deductive and inductive thematic analysis. A list of overarching (unique) outcomes reflects the outcomes identified within the systematic reviews. Forty-one systematic reviews were included. Thirty-three (81%) systematic reviews were of critically low or low quality. A long list of 1739 verbatim outcomes was identified and categorized under five core areas of COMET (Core Outcome Measures in Effectiveness Trials) taxonomy: 'resources use' (45%), 'physiological/clinical' (27%), 'life impact' (16%), 'death' (8%) and 'adverse events' (4%). A total of 421 conceptually different outcomes were identified and grouped into 196 overarching outcomes. There is significant heterogeneity in outcomes reported for hospital AMS interventions. Reported outcomes do not cover all domains of the COMET framework and may miss outcomes relevant to patients (e.g. emotional, social functioning, etc.). The included systematic reviews lacked methodological rigour, which warrants further improvements.

295. SARS-CoV-2 Associated Multisystem Inflammatory Syndrome in Adults (MIS-A): a Multicenter Case Series.

Abstract Background MIS-A frequently presents with symptoms including fevers, cardiovascular, gastrointestinal mucocutaneous, and neurologic involvement in both children and adults. Predominantly occurs in previously healthy children and young adults, disproportionately affecting individuals of African,Latino and Asian descent. Represents one of the most significant and yet under-recognized clinical consequences of SARS-CoV-2 infection. Methods A retrospective review was performed of the identified MIS-A cases admitted to two institutions between January 2020-December 2021. Included cases required evidence of present or previous SARS-CoV-2 infection by either PCR or antigen testing; and meeting the CDC definition for MIS-A. After case identification, we collected clinical and laboratory data to analyze demographics, clinical symptoms, laboratory result, imaging, length of hospitalization and therapeutic interventions. Results Ten cases were identified in the established period of time. The average interval to hospital admission was 31days. Clinical symptoms included fever, malaise, gastrointestinal complaints, dyspnea, diffuse rash. Males outnumbered females in a ratio of 7:3,with African American and Latino patients comprising 80% of the cases. All patients had elevated inflammatory markers and the most commonly manifesting organ dysfunction was cardiovascular system. Conclusion This case series helps reinforce the characterization of an as yet incompletely understood and challenging clinical syndrome, providing insight to guide diagnosis and treatment of MIS-A. A greater understanding of MIS-A may facilitate earlier syndromic recognition in order to improve outcomes, reduce unnecessary antimicrobial use, and reduce costs. Disclosures Ryan C. Maves, MD, AiCuris: Grant/Research Support|Sound Pharmaceuticals: Grant/Research Support|Trauma Insights, LLC: Advisor/Consultant.

1807. Tracking antibiotic de-escalation using a novel metric, days of antibiotic spectrum coverage (DASC)

Abstract Background In the United States, days of therapy (DOT) is the currently preferred method for measuring antibiotic consumption. A major disadvantage of DOT is that it does not account for the antimicrobial’s spectrum. Antibiotic de-escalation is therefore not well-captured by DOT. To overcome the limitation of DOT, we recently proposed a new metric, days of antibiotic spectrum coverage (DASC). DASC is calculated by multiplying DOT and the antibiotic spectrum coverage (ASC) score, which was assigned based on the activities of each antibiotic agent for 11 wild type bacteria and 5 acquired resistance patterns. Here we evaluate the performance of DASC using antibiotic consumption data where the main antimicrobial stewardship program (ASP) activity is daily prospective audit-and-feedback of all inpatients on antibiotics. Methods We analyzed the retrospective cohort of inpatient antibiotic use at Iowa City VA Health Care System from 2017 to 2021. Total monthly DOT was the aggregation of monthly DOT for each antibiotic. DASC for each antibiotic was calculated by multiplying ASC for each antibiotic to DOT. DASC for each antibiotic was aggregated to total monthly DASC. Days-present was used as a denominator for both metrics. Trends of total monthly DOT and DASC were analyzed by simple linear regression. Results There was no significant trend in monthly DOT (Figure A: beta= 0.30, 95%CI: -0.67 to 1.27, p=0.55), but there was a significant downward trend in monthly DASC (Figure B: beta= -6.89, 95%CI: -12.7 to -0.98, p=0.03). Conclusion While a significant downward trend was seen using monthly DASC, no trend was observed using monthly DOT. In contrast to DOT, which captures antibiotic consumption without considering the spectrum, DASC captures both antibiotic consumption and spectrum, suggesting DASC can add another dimension in tracking inpatient antibiotic use. DASC is easily calculated if DOT for each antibiotic is available. Metrics that don’t capture antimicrobial spectrum may not be able detect improvements in avoiding unnecessary use of broad-spectrum antimicrobials, an important target of ASPs. Disclosures Daniel J. Livorsi, MD, Merck & Co.: Grant/Research Support Michihiko Goto, MD MSCI, Merck & Co.: Grant/Research Support.

548. Target Enriched NGS Reveals Wide Breadth of Viruses Causing Acute Undifferentiated Fever in Thailand

Abstract Background Despite extensive laboratory testing, infectious agents were not detected in approximately 50% of patients hospitalized for acute undifferentiated febrile illnesses (AUFI) at Siriraj Hospital, Bangkok, Thailand. Unbiased Metagenomic Next Generation Sequencing (mNGS) enables detection of any microbe present in patient samples. Target enrichment for viruses represents a highly sensitive and cost-effective approach for overcoming host background in clinical specimens. Plasma collected from 800 patients with undiagnosed AUFI between 2013-2020 were analyzed by mNGS coupled to target enrichment to identify known and novel viruses. Methods Plasma was pre-treated with benzonase before extraction on an Abbott m2000 instrument. mNGS libraries were prepared from double-stranded cDNA with Illumina Nextera XT reagents on an epMotion then combined in pools of 24 and hybridized to Comprehensive Viral Research Panel (CVRP; Twist Biosciences) probes covering >15,000 strains of vertebrate viruses. Captured viral sequences were amplified, quantified, and sequenced together on a MiSeq. Reads were taxonomically classified by the SURPI pipeline and aligned in CLC Bio Genomics Workbench software. Results CVRP method optimization enabled sequencing of 24-48 libraries per MiSeq run, for which >50% genome coverage was obtained with model viruses spiked into clinical specimens at 1000 cp/ml. This approach revealed an array of >24 different viruses found in 26% of samples. Dengue was the most prevalent at 7.4%, with all four genotypes detected. Other common causes of AUFI such as Chikungunya, HIV-1, HAV, HBV, HCV, and CMV were present in 1.5-2.5% of cases. Less prevalent (< 1%) infections included HEV, HSV-2, EBV, HHV-6, Enterovirus B&D and Parvovirus B19. We also encountered sporadic cases of Measles, Cardiovirus, West Nile, Rotavirus, Picobirnavirus, Polyomavirus 4&5, Kubovirus, and Rabies lyssavirus. Conclusion Target capture successfully demonstrated that viruses were important etiologies for unresolved cases of AUFI in Thailand. This data has led to a better understanding of the epidemiology of this clinical syndrome and has implications for proper management of AUFI, including lower rates of unnecessary testing and antimicrobial use. Disclosures Julie Yamaguchi, BS, Abbott Labs: Employee Michael G. Berg, PhD, Abbott Labs: Employee Pakpoom Phoompoung, MD, Abbott Labs: Grant/Research Support|Abbott Labs: Employee Jenna Malinauskas, MS, Abbott Labs: Employee Gavin Cloherty, PhD, Abbott: Employee|Abbott: Stocks/Bonds|Abbott Labs: Employee Yupin Suputtamongkol, MD, Abbott Labs: Grant/Research Support.

Is diagnostic stewardship possible in solid organ transplantation?

Diagnostic stewardship in solid organ transplant (SOT) recipients has the potential to help these vulnerable patients at risk for over-testing and overtreatment. Herein, we review potential targets for diagnostic stewardship in SOT, such as Clostridioides difficile testing, urine cultures, molecular diagnostics, as well as novel areas of diagnostic stewardship. Bundled interventions focused on appropriate C. difficile testing can result in a significant decrease in testing and clinical diagnosis of C. difficile infection without any harms related to delay in diagnosis. In otherwise stable renal transplant recipients after the first month of transplant, screening urine cultures have not been shown to improve outcomes. Novel targets that require additional study in the SOT population include noninvasive fungal diagnostics and cytomegalovirus testing strategies CONCLUSIONS: Diagnostic stewardship is an innovative approach to improve diagnosis and limit unnecessary antimicrobial use. While there has been little direct exploration of diagnostic stewardship in the SOT population, there is great potential for benefit given frequent testing with diagnostics that have imperfect sensitivity and specificity, and sometimes great cost. Diagnostic stewardship in the SOT population is indeed possible but will require a multidisciplinary effort to ensure that appropriates tests and benefits are realized.