bluuebunny/crossref_metadata_2025 huggingface dataset:
P-1763. Implementation of a Pharmacy-based Automated MRSA PCR Screening Intervention to Guide Discontinuation of Vancomycin for Pneumonia
Authors: Azem Reem , Saade Elie , Veltri Courtney , Newman Nicholas , Kolehmainen Natalie , Dang Khoi , Stempak Lisa M , Wilson Brigid , Hojat Leila S
Published: January 2025

Background

Vancomycin is administered for suspected methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in hospital settings, but is also associated with adverse effects, emergence of resistance, and requires lab and pharmacy monitoring. MRSA nares screening has excellent negative predictive value for MRSA pneumonia and results faster than culture. We sought to decrease vancomycin overuse by identifying patients at low risk for MRSA pneumonia using rapid polymerase chain reaction (PCR) as part of an automated pharmacy-based intervention.

Methods

We performed a retrospective cohort study of inpatients prescribed vancomycin for pneumonia at University Hospitals Cleveland Medical Center from November to May 2022 (pre-intervention) and November 2022 to May 2023 (post-intervention). In June 2022, we implemented a rapid MRSA PCR screen that was automatically added to orders when vancomycin was ordered for pneumonia. We compared median time to vancomycin discontinuation between the two groups. We performed a desirability of outcome ranking and response adjusted for duration of antibiotic risk (DOOR-RADAR) analysis, ranking patients according to duration of therapy within clinical categories to assess the effect of the intervention on patient-centered outcomes.

Results

We identified 127 pre-intervention and 125 post-intervention patients (Table 1). Median vancomycin order to discontinue time was lower in post-intervention patients, though this was meaningfully different only for patients whose PCR test was collected after the automated order was placed (41.75 vs 55 hours respectively, p = 0.035) (Table 2). Most patients in the post-intervention group with vancomycin duration >48 hours had delayed collection or were treated for other infections (Figure 1). The DOOR ranks for median time to discontinuation within clinical outcome categories were not meaningfully different between the two groups (p >0.05) (Table 2 and Figure 2) which may relate to sample size.

Conclusion

Vancomycin treatment duration was shorter in patients after a pharmacy-based automated MRSA PCR screening intervention when implemented efficiently. This research will guide future interventions including pairing automated rapid testing with active stewardship response.

Disclosures

Elie Saade, MD, MPH, FIDSA, Janssen Global Services: Advisor/Consultant|Janssen Global Services: Advisor/Consultant|Janssen Research and Development: Advisor/Consultant|Janssen Research and Development: Advisor/Consultant Lisa M, Stempak, MD, Cytovale Inc.: Advisor/Consultant
P-1765. Are we there yet? The ongoing journey for improving management of asymptomatic bacteriuria
Authors: Kenney Rachel M , Gunaga Satheesh , Cahill Megan M , Leman Lori , Beaulac-Harris Amy , Eriksson Erin , Geyer Abigail , Shallal Anita , Stein Tricia L , Mazzetti Nicole , Kaiser Kiera , Dubay Janeen , Arthur Ashli , Higginbottom Manal , Jayaprakash Namita , Dass Sairia , Haddad Ayyoub , Boxwalla Asgar , Kaatz Scott , Tibbetts Robert , Veve Michael , Suleyman Geehan
Published: January 2025

Background

Treating asymptomatic bacteriuria (ASB) with antibiotics contributes to preventable patient harm. This quality improvement study aimed to evaluate the effectiveness of ongoing diagnostic and antibiotic stewardship interventions in reducing unnecessary testing and treatment of ASB.

Methods

This retrospective, cross-sectional quality improvement study spanned from 1/2017-3/2024 at a five-hospital urban and suburban health system in Michigan. Interventions included i). Implementation of urinalysis with reflex to urine culture in 2/2019, with reflex criteria revised in 7/2022 to ≥ 10 WBCs; ii). Adoption of a urine culture hard stop after hospitalization day 3 (3/2021); iii). Introduction of an ASB progress note smart phrase and educational initiative via a 1-page handout and narrated slides in the first quarter of 2023. The primary endpoint was the proportion of patients with ASB who received antibiotic treatment, as defined by Vaughn et al JAMA Intern Med 2023. Secondary endpoints encompassed the number of provider smart phrase documentations; overall urine culture volume per year; proportion of all positive urine cultures representing ASB; and overall ASB antibiotic use, calculated as the ratio of ASB treated with antibiotics to all positive urine cultures.

Results

The annual volume of urine cultures decreased by approximately 25% (Figure 1), from 87,556 in 2017 to 65,955 in 2023. The percentage of positive cultures representing ASB is depicted in Figure 2. The ASB smart phrase was documented in the medical record of 233 patients over one year: 165 (71%) were women, with a median age of 72 [48, 82] years. Emergency medicine providers utilized the smart phrase most frequently (97/233, 42%), followed by consultants (79/233, 34%). Overall ASB antibiotic use ranged from 9.7-22.7% in Q1 2022 and declined to 4.5-7% in Q1 2024. The primary endpoint, the system-wide average treatment of patients with ASB, declined modestly over time, but improvements were inconsistent among hospitals (Figure 3).

Conclusion

Ongoing interventions targeting diagnostic and antibiotic stewardship through educational efforts were associated with a reduction in testing and treatment of ASB. However, suboptimal treatment of ASB remain a concern.

Disclosures

Rachel M. Kenney, PharmD, BCIDP, Medtronic Inc: Spouse is an employee, stockholder Erin Eriksson, PharmD, BCPS, BCIDP, Stryker Corp: Stocks/Bonds (Public Company)
P-1768. Evaluation of Pharmacist-Driven Automatic 5-day Stop Dates for Ceftriaxone in Respiratory Tract Infections
Authors: Adams David T , Kaur Satwinder S
Published: January 2025

Background

Despite 2019 ATS/IDSA CAP guideline support for a 5-day treatment duration, compliance with these recommendations remains suboptimal. Patients that receive extended courses of antibiotics are at increased risk for adverse outcomes, longer hospitalization stays, and development of antimicrobial resistance. The objective of this study was to compare hospital length of stay (LOS) and length of therapy (LOT) before and after a pharmacist-driven automatic stop date protocol for ceftriaxone for CAP and COPD exacerbations.

Methods

A retrospective cohort study conducted at Texas Health Harris Methodist Hospital Fort Worth evaluated patients before June 2023, and after November 2023. Patients were excluded if treatment indications were for non-respiratory indications, received ≤2 ceftriaxone doses, admitted into the ICU, LOS ≥10 days, or if placed on hospice within 72 hours of admission. Pharmacists then adjusted ceftriaxone orders to 5 total days for CAP and COPD exacerbations. The primary outcome was hospital LOS and LOT. Secondary outcomes included 30-day all-cause in-hospital mortality and 30-day hospital readmission due to infections.

Results

295 patients were included in the final analysis with 145 patients in the pre- and 150 patients in the post-group. After implementation of the protocol, a statistically significant reduction in hospital LOS was observed in the post-group (4 days vs 5 days, p < 0.0001). There was also a statistically significant reduction in median LOT for CAP and COPD (5 days vs 7 days, p < 0.0001). No increase in 30-day all-cause mortality (0% vs 4%, p =0.012) or 30-day hospital re-admission rates due to infections (3% vs 8%, p =0.033) were observed in the post- compared to the pre-group.

Conclusion

Based on the results of this study, implementation of a pharmacist-driven automatic 5-day stop date protocol for ceftriaxone is an effective antimicrobial stewardship initiative that can help increase compliance to guideline recommendations for CAP and COPD while also decreasing hospital LOS. Additionally, this initiative was not associated with increased rates of mortality or hospital re-admissions compared to longer durations and influenced discharge antibiotic prescription habits.

Disclosures

All Authors: No reported disclosures
P-1772. Reduction in Vancomycin-Associated Acute Kidney Injury with Montelukast
Authors: Teran Nicholas , Phe Kady , Tam Vincent
Published: January 2025

Background

Vancomycin is the most common antimicrobial used for the treatment of serious infections implicated by β-lactam resistant Gram-positive bacteria but has been associated with acute kidney injury (AKI) in up to 43% of cases. Reduction in renal injury associated with nephrotoxins has been reported in an animal model with adjuvant montelukast. However, it is unclear if this protective effect could be translated to improve patient outcomes. The objective of this study was to ascertain if montelukast is correlated with reduced vancomycin-associated AKI.

Methods

We conducted a retrospective study of adults (≥ 18 years) who received intravenous vancomycin at our institution between 01/2020-01/2024. Patients were included if they met these criteria: vancomycin therapy ≥ 3 days and baseline serum creatinine (SCr) < 1.5 mg/dL. Patients who received concomitant montelukast (intervention) were compared to those without (control). The primary outcome was the prevalence of AKI (rise in SCr ≥ 1.5x baseline) as defined by Risk, Injury, Failure, Loss, or End-stage kidney disease (RIFLE) criteria. The primary outcome was compared using the Fisher’s exact test while the duration of vancomycin therapy was compared by the Student’s t test. Independent risk factors associated with AKI were identified by multivariate logistic regression.

Results

Of 1739 patients screened, 110 patients were included in the intervention arm and 330 in the control. Patients received vancomycin for similar durations (mean ± SD, 5.1 ± 4.1 vs 5.9 ± 3.3 days, respectively; P = 0.06) and serum trough concentrations were comparable (P = 0.39). The intervention cohort experienced 2.7% AKI compared with 10.6% in the control (P = 0.01). The multivariate logistic regression analysis revealed that weight (OR, 1.02; 95% CI, 1.004 to 1.03; P = 0.011) and intensive care unit admission (OR, 6.9; 95% CI, 2.8 to 17.1; P < 0.001) were independently associated with acute kidney injury, while montelukast was protective (OR, 0.29; 95% CI, 0.09 to 0.98; P = 0.046).

Conclusion

This study suggests that montelukast may be protective against vancomycin-associated nephrotoxicity, which may reduce patient harm and healthcare costs. Additional studies to investigate the nephroprotective mechanism will be conducted to corroborate these findings.

Disclosures

All Authors: No reported disclosures
629. Evaluation of Neurocysticercosis Healthcare Provider Diagnostic Practices in Houston, Texas
Authors: Sepulveda Theresa , Centeno Fernando H , Serpa Jose , Weatherhead Jill E , Clark Eva
Published: January 2025

Background

Neurocysticercosis (NCC) is a neglected tropical disease caused by infection with the pork tapeworm Taenia solium that affects 2-8 million people globally and is responsible for ∼30% of epilepsy cases in endemic countries. Based on case series data, > 4,000 new NCC cases are estimated to occur annually in the US. The gold standard for NCC diagnosis as outlined in the Infectious Disease Society of America (IDSA) guidelines is neuroimaging with computed tomography (CT: to detect calcifications) and magnetic resonance imaging (MRI: to detect viable disease), followed by confirmatory serologic testing with the enzyme-linked immunoelectrotransfer blot (EITB) or other reliable assay. Our study aims to describe healthcare provider diagnostic practices at a public healthcare system serving at-risk patients in Texas.

Methods

We retrospectively identified patients ≥ 18 years old tested for NCC in the Harris Health System [HHS] between 2017-2021, systematically extracted variables from the patients’ electronic medical records, and recorded this data via a REDCap instrument. We classified NCC patients by NCC type and performed descriptive statistics.

Results

We identified 113 patients with NCC (Table 1). Family medicine (n=44, 39%) or internal medicine (n=29, 26%) providers evaluated most patients in their first diagnostic encounter. Presenting signs/symptoms included seizure (n=75, 66%) and chronic headaches (n=77, 68%). 77% of patients with calcified disease and 88% with viable disease were diagnosed within 5 years after symptom onset. Only 63% of patients had both CT and MRI completed. Zero initial providers ordered EITB confirmatory serologic testing; n=4, 3% ordered other types of serologic testing. Only five patients ultimately had EITB sent; of those, two tested positive. While 47% of initial providers referred patients to neurology and 18% referred to neurosurgery, only 35% referred to tropical medicine or infectious diseases specialties.

Conclusion

Improved education of frontline healthcare providers on NCC presentation and diagnosis may reduce time to NCC diagnosis. Future work should target the need for structured education and standardization of diagnostic practices especially amongst frontline healthcare providers serving at-risk communities in the US.

Disclosures

All Authors: No reported disclosures
P-1777. Low adherence to institutional antibiotic clinical practice guideline in patients diagnosed with Clostridioides difficile infection
Authors: Marcus Joseph , Scheps Kayla R , Matthews Zachary K
Published: January 2025

Background

Previous antimicrobial therapy is a common risk factor for Clostridioides difficile infections (CDIs). Clinical practice guidelines (CPGs) assist clinicians in prescribing the correct antibiotics for various clinical syndromes to avoid unnecessary or overly broad-spectrum antibiotic use. Retrospective analysis of CDIs may serve as a guide for the high-risk antimicrobials included in CPG development.

Methods

Patients who tested positive for C. difficile at Brooke Army Medical Center from November 2022 to October 2023 were reviewed. Demographics, C. difficile treatment, antibiotic allergies, antibiotics received in the preceding 90 days prior to a positive test, and indication for antibiotic therapy were recorded. If a treatment indication appeared on the institutional CPG, adherence to the antibiotic recommendation was recorded. Patients who received no antibiotics or only antibiotics as guided by the correct CPG were considered unpreventable.

Results

During the study period, 128 positive cases were identified. The median patient age was 56.5 years [IQR: 25-75.3] (Table 1). 80% of cases were ultimately treated for infection, with fidaxomicin representing the treatment of choice in 81% of treated patients. In the preceding 3 months prior to a positive test, 67% of patients had at least one day of antibiotic exposure. The median number [IQR] of total antibiotic days within 30, 60, and 90 days of a positive test was 1 [0-7], 3.5 [0-8.75], and 5 [0-9.75] respectively. For 47 (55%) cases, all antibiotic indications within the previous 90 days appeared on the CPG. However, prescribers did not adhere to the CPG (Table 2) in 22 (47%) of these cases. The most common inpatient and outpatient indications not on the CPG were perioperative antibiotics and otitis media, respectively. Overall, only 58 cases (45%) were considered unpreventable.

Conclusion

In this single center study, retrospective analysis of individual C. difficile cases provided direction for the antimicrobial stewardship team by identifying CPG recommendations that were not followed as well as identifying conditions not on previous CPGs. Tying patient harm from CDIs with inappropriate antimicrobial use builds the local evidence base to prevent future CDIs.

Disclosures

All Authors: No reported disclosures
P-1784. Reduction of bacterial resistance in isolates from nosocomial infections through a program of antibiotic stewardship based on a local mobile application in a hospital in Mexico City; 10 years of success
Authors: Castañeda-Méndez Paulo , Castillo-Álvarez José Luis , Aguilar Esperanza Aleman , Medina-Montaño Griselda , Soto-Ramirez L U I S E , Aguilar-Zapata Daniel , Mar Javier Reyes
Published: January 2025

Background

Hospital-acquired infections caused by multidrug-resistant microorganisms (MDR-HAI) are associated with high healthcare costs, prolonged hospital stays, and concerning morbidity and mortality. The prevalence of MDR-HAI has increased worldwide as a result of the COVID-19 pandemic. In this context, antimicrobial stewardship programs (ASP) have become more relevant.

Methods

A mobile application was implemented for hospital staff to guide optimal antibiotic use. This application is based on local resistance patterns for major nosocomial microorganisms, to provide treatment recommendations (initial regimen based on suspicion, adjustment according to microbiological results, antibiotic discontinuation, etc.). Descriptive statistics were performed.

Results

In 2013, before the implementation of the application, the compliance rate was 25% for hospital-acquired infections and 42.2% adherence to guidelines. After the introduction of the application, compliance in 2014 was 56.7%, with a reported 20% MDR-HAI rate. In 2015, the usage was 60.7% and MDR-HAI rate was 18%. In 2016, compliance was 68.7% and MDR-HAI rate was 16%. In 2017, compliance was 73.7% and MDR-HAI rate was 14%. In 2018, the prevalence of MDR-HAI was 15%, while the usage of local guidelines was 78.7%. In 2019, compliance was 81.1% and MDR-HAI rate was 16.9%. Considering the COVID-19 pandemic (starting in 2020) as a period in which there was a significant increase in the presence of MDR-HAI worldwide, thanks to the implementation of the application, the percentage of MDR-HAI decreased from 27.8% to 11.1% in 2023 (Image 1). The number of different types of infections (VAP, HAP, UTI, ICS, BSI) also decreased by following the guidelines recommendations.

Conclusion

These programs are necessary as part of the healthcare program to control the morbidity and complications of MDR-HAI. Simple and user-friendly electronic applications, such as the one implemented in our hospital, have led to increased compliance and a decrease in bacterial resistance of infections acquired in our institution.

Disclosures

All Authors: No reported disclosures
P-1790. Multifaceted Stewardship for Oral Antimicrobial Agents in the Outpatient Setting of a Japanese Tertiary Care Center
Authors: Horiuchi Hiroshi , Tagashira Yasuaki , Takizawa Asami , Gu Yoshiaki
Published: January 2025

Background

Oral antimicrobials accounted for approximately 90% of all antimicrobial prescriptions. The 2023-2027 Japanese National Action Plan on Antimicrobial Resistance encourages reducing prescriptions for oral broad-spectrum antimicrobials, especially third-generation cephalosporins (3GC), fluoroquinolone (FQ), and macrolide (MC). However, only a few studies have examined antimicrobial stewardship programs (ASP) in the outpatient setting in Japan.

In this study we aim to evaluate the effectiveness of multifaceted ASP for oral antimicrobials in the outpatient setting of a Japanese tertiary care center.

Methods

The present, before-after trial was conducted in the outpatient setting of a Japanese tertiary care center. The pre-intervention period was from October 2021 to September 2023, and the implementation period was from October 2023 to March 2024. The intervention consisted of 1) an infectious disease (ID) physician’s focused, educational lectures for prescribers; 2) local treatment guidelines for common infectious diseases; 3) monthly reports to all physicians on changes in days of therapy (DOT) with 3GC, FQ, and MC per 100 visits; and 4) post-prescription review and feedback from a designated ID physician. Interrupted time-series analysis (ITSA) was used to assess changes in the monthly DOT per 100 visits.

Results

In total, 344,330 and 89,898 patients visited, and 15,324 (4.45%) and 3,845 (4.28%) prescriptions were issued during the pre-intervention and intervention periods, respectively. ITSA revealed an immediate decrease in DOT per 100 visits for 3GC (-1.03; 95% confidence interval [CI]: -1.31 to -0.74; P< 0.001 for intercept) and a decreasing trend in FQ and MC during the intervention period (-0.71 and -0.41; 95% CI: -0.54 to -0.27 and -1.18 to -0.25; P< 0.001 and 0.004, respectively). ITSA also found a decreasing trend in the DOT per 100 visits for all oral antimicrobials (-2.04; 95% CI: -2.88 to -1.20; P< 0.001).

Conclusion

Multifaced ASP was able to reduce the prescription rate of three antimicrobials targeted by the Japanese National Action Plan on Antimicrobial Resistance in the outpatient setting of a community hospital.

Disclosures

Yoshiaki Gu, MD, PhD, MPH, MSD K.K.: Grant/Research Support
631. Cost-effective diagnostic algorithms for Ugandan patients with solid tumors who develop chemotherapy-associated febrile illness
Authors: Gulleen Elizabeth , Mbrusha Immaculate , Mubiru Dennis , Pedun Bernadette , Omoding Abrahams , Moore Christopher , Phipps Warren , Rajasingham Radha
Published: January 2025

Background

Microbiology diagnostic tests are often prohibitively expensive in resource-limited settings. Cost-effective diagnostic algorithms could potentially guide diagnostic evaluation for chemotherapy-associated febrile illness in resource-limited settings where comprehensive testing is not possible. This is particularly true in sub-Saharan Africa, where the high prevalence of HIV and tuberculosis (TB) place patients at increased risk of developing opportunistic infections that do not frequently occur among patients receiving chemotherapy in the United States or Europe.

Methods

We created a decision analytic model to evaluate the costs, diagnostic yield, and cost-effectiveness of diagnostic algorithms for adult inpatients with solid tumors who developed fever within 30 days of receiving chemotherapy in Uganda. Since Uganda has a high prevalence of HIV and TB, diagnostics included serum cryptococcal antigen (CrAg) lateral flow assay, Alere TB urinary lipoarabinomannan (LAM), malaria rapid testing, and aerobic blood cultures. We considered the following testing algorithms: 1) a comprehensive approach where all tests were performed, and 2) various stepwise algorithms where tests were performed in series and stopped testing with the first positive result. We obtained prevalence data from a cohort of 100 patients with solid tumors who were admitted to the Uganda Cancer Institute (Kampala, Uganda) with fever. Test performance was taken from the published literature.

Results

A comprehensive diagnostic testing strategy yielded 64% of correct diagnoses at a cost of $97.85 per correct diagnosis. Of the stepwise strategies, testing CrAg first yielded the cheapest strategy, at a cost of $85.49 per correct diagnosis, and the highest number of appropriate diagnoses (59%). The incremental cost-effectiveness ratio was $234 per additional correct diagnosis for the comprehensive over this sequential strategy.

Conclusion

Comprehensive diagnostic testing is optimal for patients who experience post-chemotherapy febrile illness in resource-limited settings. If this strategy is not available, stepwise testing with CrAg then TB LAM is the optimal strategy to maximize correct diagnosis and minimize costs.

Disclosures

All Authors: No reported disclosures
P-1806. ABLE to De-Label: Liberating Patients from Penicillin Chart Allergies
Authors: Martinez-Palmer Meaghan , Olabode Adenike , Xu Teena , Khan Parisa F
Published: January 2025

Background

The Veterans Affairs Clinical Pharmacy Practice Office Allergy to Beta Lactam Evaluation (ABLE) initiative was launched at the at the Michael E DeBakey VA Medical Center in October 2023. The primary implementation tool was a standardized note template, streamlining the documentation and assessment of penicillin allergy information. Patients who had tolerated penicillins since reaction or had side effects were eligible for immediate de-labeling. Those with unknown reactions, IgE-mediated allergies >10 years ago, or non-severe IgE-mediated allergies >5 years ago were considered candidates for penicillin allergy testing. All other reactions were considered ineligible for further evaluation.

Results of ABLE intervention

Results of ABLE intervention from October 2023-February 2024

Methods

Patients labeled as penicillin allergic who were previously seen in ID clinic were contacted via unscheduled telephone calls to clarify allergy histories, identify opportunities for de-labeling, and provide recommendations for alternative beta-lactam use. The primary outcome was the proportion of “penicillin-allergic” patients successfully de-labeled.

ABLE Intervention Flowchart

Results

Of 88 patients identified, 16 (18%) were deceased and 13 (15%) were de-labeled prior to ABLE implementation in October 2023. 56 of the 59 remaining patients received at least one attempt at telephone contact. 24 patients received the ABLE intervention. Of these, 8 patients (33%) were immediately de-labeled, and 1 declined to have the allergy removed despite being eligible. Another 13 patients (54%) were eligible for further allergy testing, of which 5 (21%) accepted a referral to Allergy clinic. Two patients (8%) were not eligible for further testing. One patient who was successfully de-labeled regained the penicillin allergy label.

Conclusion

The ABLE initiative improves antimicrobial stewardship and patient care by accurately assessing and managing penicillin allergies. These findings suggest those who are eligible for immediate de-labeling based on chart review should be prioritized for intervention. However, based on the acceptance rate of this telephonic intervention, alternative modalities of implementation should be explored.

Disclosures

All Authors: No reported disclosures
P-1807. Using The Modified Delphi Method to Create Expert Consensus for Candidate Variables for Risk-Adjusted Benchmarking Metrics of Hospital Antimicrobial Consumption
Authors: Goto Michihiko , Barlam Tamar F , Cosgrove Sara E , Davila Heather , Drekonja Dimitri M , Echevarria Kelly , Goedken Cassie Cunningham , Goetz Matthew B , Hsueh Kevin , Mergenhagen Kari A , Taylor Lindsay , Hernandez David , Livorsi Daniel J
Published: January 2025

Background

Studies have shown that both patient- and hospital-level factors can influence the evaluation of antimicrobial consumption, and appropriate risk adjustments are necessary for reliable benchmarking. The curation of candidate variables through experts can be helpful in gaining the trust of users. We conducted a modified two-stage Delphi method to build consensus on candidate variables that should be considered in developing a risk-adjustment model for benchmarking metrics of hospital antimicrobial consumption.

Summary of Expert Consensus for Candidate Variables for Risk-Adjusted Benchmarking Metrics

Methods

In preparation, we listed potential variables for consideration from past literature (8 facility characteristics, 6 patient demographics, 4 care processes, 56 comorbidities, 42 procedure categories). We distributed a survey to a 9-member expert panel to rate variables independently to “can be considered” or “should not be included” with comments. Consensus was defined as agreement by 7 or more out of 9 members, and the results with comments were presented to the panel at a conference call for further discussions. The second survey was distributed, focusing on items that did not reach consensus or the panel suggested reconsideration.

Results

At the first survey, 8 facility characteristics, 3 patient demographics, 4 care processes, 27 comorbidities, and 19 procedure categories reached a consensus. The panel discussed the remaining 29 comorbidities and 23 procedure categories and whether any item that reached consensus required reconsideration on a follow-up conference call. In the second survey, 3 facility characteristics, 2 patient demographics, 27 comorbidity categories, and 4 procedure categories were included in the second survey based on the discussion. At the end of the process, 7 facility characteristics, 6 patient demographics, 4 care processes, 49 comorbidities, and 41 procedure categories reached a consensus (Figure).

Conclusion

In this modified two-stage Delphi process, we successfully classified the majority of variables as either to be considered or not to be included in statistical model development. These variables, curated by subject matter experts, can serve as a foundation for further model development for objective evaluation and benchmarking of hospital antimicrobial consumption.

Disclosures

Michihiko Goto, MD MSCI, Merck: Grant/Research Support Daniel J. Livorsi, MD, Merck: Grant/Research Support
P-1809. Strategies to Optimize Antibiotic Stewardship for Patients with COVID-19 Using a Systems Engineering Framework
Authors: Pulia Michael , Griffin Meggie , Schwei Rebecca , Scalzo Sarah , Ikenberry Helena , Kaur Ashleen , Pop-Vicas Aurora E , Schulz Lucas , Werner Nicole
Published: January 2025

Background

The COVID-19 pandemic stressed antimicrobial stewardship (AMS) programs with increased workloads and lack of guidance on the treatment of COVID-19. Throughout the pandemic, COVID-19 patients have received antibiotics for this viral illness despite reported low rates of confirmed bacterial co-infections. The purpose of this study was to identify challenges to and strategies for successful antibiotic stewardship for COVID-19 inpatients.

Part 1 of Table 1

Methods

We utilized the Premier Healthcare Database to identify hospitals with appropriate antibiotic prescribing before and maintained during the pandemic while facing significant COVID-19 patient burden. We conducted semi-structured interviews with pharmacists, physicians, and quality leaders involved in AMS during the pandemic. Interview guides were developed according to participants’ roles using the Systems Engineering Initiative for Patient Safety (SEIPS) framework. Interviews were recorded, transcribed, and analyzed iteratively using directed content analysis guided by the SEIPS model.

Part 2 of Table 1

Results

We conducted 30 interviews from 19 different high-performing health care systems across the country. We interviewed 17 pharmacists, 12 physicians and 1 nurse. The main challenges participants identified included lack of knowledge and formal guidance on how to treat COVID-19, feelings of helplessness, and diagnostic uncertainty. Strong, clear leadership from hospital leaders or infectious disease groups, organizational and national guidelines and clinical experience caring for COVID-19 helped providers overcome lack of knowledge, and guidelines on how to treat COVID-19 assuaged feelings of helplessness. Diagnostic tools including host response biomarkers (e.g. procalcitonin) and chest imaging were utilized and incorporated into workflows to help overcome diagnostic uncertainty and guide antibiotic prescribing.

Part 3 of Table 1

Conclusion

Successful strategies for COVID-19 antibiotic stewardship included overcoming knowledge gaps with clear leadership from infectious disease teams and implementation of structured COVID-19 diagnostic and treatment guidelines.

Disclosures

All Authors: No reported disclosures
P-1831. Clostridioides difficile infection alters the prefrontal cortex transcriptomics in a preclinical model
Authors: Costa Deiziane , Yang Suemin E , Brett Moreau G , Shin Jae Hyun , Warren Cirle A
Published: January 2025

Background

Dementia is associated with poor outcomes of Clostridioides difficile infection (CDI) in older adults. Changes in brain metabolites profile was detected in preclinical model of CDI. Recently, we discovered that CDI-promoted brain neuroinflammation occurs after peak of the infection. Here, we investigated how CDI changes the transcriptomics of prefrontal cortex of C. difficile-infected mice.

Methods

6-month-old mice were infected with C. difficile and euthanized on day 7 post-infection (pi) and bulk RNA-sequencing was performed on prefrontal cortex. Changes in the main upregulated or downregulated genes were confirmed by protein assays. Spearman correlation analyses were also performed.

Results

Infected mice developed diarrhea and weight loss, resulting in maximum weight loss and diarrhea on day 3 pi, which were resolved by day 7 pi. Differential gene expression analysis pointed 136 differentially expressed genes: 75 upregulated (Lcn2, Plin4, Fkbp5, Slc38a5, Lrg1, Ucp2, Slc2a1, Spint1, and Trpv4) and 61 downregulated (Pprc1, Zfp169, Bnip5, Chrm4, Grm3, Hmgcr, Zfp804b, Gpm6b, and Ncam) on day 7. Gene set enrichment (KEGG) analysis showed upregulation of genes associated with oxidative phosphorylation, Parkinson’s disease and Alzheimer’s disease, as well as downregulation of genes associated with axon guidance and neuroactive ligand-receptor interaction and T cell receptor signaling pathway in infected mice. Using protein assays, prefrontal cortex levels of GFAP, a marker of astrocytes, were increased in the infected mice, pointing to reactive astrocytes response. Increased levels of Lcn2, which can be secreted by astrocytes, followed by increased MPO and calprotectin in prefrontal cortex, cecum and serum of infected mice were detected. Levels of systemic MPO, a marker of inflammation, and fecal Lcn2, a marker of epithelial barrier disruption, correlates positively with the levels of Lnc2 in prefrontal cortex.

Conclusion

Our findings demonstrate that CDI induces transcriptomic changes in the prefrontal cortex, including genes associated with oxidative phosphorylation and dementia secondary to Parkinson’s and Alzheimer’s disease, among others. Astrocytes-derived Lnc2 in the prefrontal cortex may contribute to the neuroinflammatory effect associated with CDI.

Disclosures

Jae Hyun Shin, MD, Ferring: Grant/Research Support
P-1839. Elucidating Key Interactions Between Macrophages and the Fungal Pathogen Coccidioides
Authors: Symington Jane , Voorhies Mark , English Bevin , Sil Anita
Published: January 2025

Background

In the environment, the fungal pathogen Coccidioides grows as hyphae, yet when its spores (arthroconidia) are inhaled by a host, they develop instead into a parasitic form called the spherule. Spherules can be elicited in vitro in the presence of specific media, elevated temperatures, and high CO2, yet what triggers this transition in vivo and the role of host immune cells in this transition remains largely unknown.

Methods

We performed live imaging of Coccidioides posadasii Silveira arthroconidia in the presence or absence of murine bone marrow derived macrophages isolated from wildtype (C57BL/6) mice. Images were taken hourly over a 3-day time course. We recorded the time at which hyphae first appeared, the number of spherules at the final time point, and average size of spherules at the final time point. We utilize fluorescent dyes to determine if arthroconidia are phagocytosed and to assess host cell death. RNAseq was performed on RNA isolated from arthroconidia cultured with macrophages over 48hrs. Experiments were conducted at 37C and 5% CO2.

Results

We observed that the presence of macrophages strongly promotes the ability of Coccidioides arthroconidia to transition to spherules at conditions that would otherwise promote formation of hyphae. In wells with macrophages, arthroconidia produced more spherules, and these spherules were generally larger in size than those produced in vitro in the absence of host cells. The presence of macrophages also delayed the time that hyphae first appeared. Using a transwell system, we found that physical contact with macrophages was necessary to promote spherule development and reduce hyphae formation. We discovered that Coccidioides arthroconidia are phagocytosed by macrophages and spherules can develop within macrophages. RNAseq of Coccidioides arthroconidia cultured with macrophages show enrichment of transcripts associated with spherule growth in vitro as well as those previously identified from Coccidioides-infected murine or human lungs.

Conclusion

Macrophages strongly promote the ability of Coccidioides arthroconidia to transition to the parasitic form of Coccidioides in a contact-dependent manner. This work creates a foundation for better understanding initial critical interactions between macrophages and Coccidioides.

Disclosures

All Authors: No reported disclosures
P-1848. Reduction of microbial burden on environmental floor samples through advanced photohydrolysis technology and its impact on Candida auris, fungi, and aerobic bacteria
Authors: Trosch Kimberly , Carenza Amy , Birx Deborah , Huslage Kirk , Obiekwe Uzoamaka D
Published: January 2025

Background

The continued rise of antimicrobial resistance (AMR) and reduction of pharmacological options has created an urgent need for new treatments or countermeasures to combat the spread of multi-drug resistant organisms (MDROs). Focus on MDROs has become paramount with the rise of Candida auris (C. auris) infections that are associated with high mortality and AMR. Attention must be given to pathogen reservoirs such as the surfaces of floors, which have an underappreciated potential to transfer pathogens to hands from objects in contact with the floor.

Mean CFUs of Aerobic Bacteria from Baseline to Post-Activation #4.

Methods

An experimental study to explore the impact of advanced photohydrolysis (AP) technology inside a high acuity hospital unit with active C. auris infections was performed from September 2023 to January 2024 and investigated the effect of the AP system on floor colony forming units (CFUs) of aerobic bacteria, fungi, and C. auris. Baseline pre-activation samples were compared to post-activation samples, which occurred every four weeks on Tuesday mornings prior to shift change and daily environmental services (EVS) cleaning.

Mean CFUs of Fungi from Baseline to Post-Activation #4.

Results

Pairwise comparisons with a Bonferroni correction found median floor fungal CFUs achieved a statistically significant reduction of 99% (p=.011) from Baseline to Post-Activation #4. Aerobic bacteria decreased 98%; C. auris by 66% but did not achieve statistical significance.

The mean CFUs on high-touch surfaces were reduced for aerobic bacteria by 82% and fungi by 99%. C. auris was reduced by 100% from Baseline to Post-Activation #3 (41 CFUs to 0 CFUs) but increased in Post-Activation #4 due to two positive sample locations in a patient room with an active C. auris infection. Although the locations were positive for C. auris, they both tested under 500 CFU/cm2, which is associated with a reduced level of infection risk from environmental bioburden.

Mean CFUs of Candida Auris from Baseline to Post-Activation #4.

Conclusion

This study clearly demonstrates that despite intensive efforts by EVS, serious microbes remain on floors; however, application of the AP technology provided a continual and persistent decline in floor microbial burden all without the need for additional skilled labor or increases in cleaning and disinfection practices. A forthcoming study will analyze how these demonstrated environmental changes affected patient outcomes.

Disclosures

Kimberly Trosch, RN, BSN, ActivePure Technologies: Full time employee Amy Carenza, BBA, ActivePure Technologies: Full time employee Deborah Birx, MD, ActivePure Technologies: Advisor/Consultant
P-1851. Influence of the COVID-19 Pandemic on Antimicrobial Resistance Patterns in Pediatric Group A Streptococcus Infections in Houston, TX
Authors: Segura Maria Gabriela , Aboulhosn Aya , Sanson Misu A , Vega Luis , Chinwala Sakina , Sommer Lauren M , McNeil Jonathon C , Flores Anthony R
Published: January 2025

Background

Group A Streptococcus (GAS) causes a large spectrum of disease, including invasive, pharyngeal and skin / soft tissue (SSTI)1. Penicillin remains the mainstay therapy but recently, resistance to second-line therapies has steadily increased, especially after COVID19, with macrolide-resistant GAS as an emerging threat2. Given recent surges of GAS associated with later stages of the pandemic,4 we sought to compare pre-pandemic (2013-2019) and pandemic (2020-2023) GAS epidemiology and antimicrobial resistance patterns.Figure 1Total number of isolates and distribution of disease types per year.

Methods

GAS isolates were collected from Texas Children’s Hospital laboratory from January 2013-December 2023 and grouped into pre-pandemic and pandemic periods. Disease type [invasive (INV), skin and soft tissue infection (SSTI), or pharyngeal (PHG)] was determined from the medical record. Isolates were grown, stocked and emm typed5. Resistance to tetracycline, erythromycin, and clindamycin was determined by disk diffusion. Intermediate and resistant strains were collectively considered non-susceptible (NS).Figure 2Frequency of antibiotic non-susceptibility by year

Results

We analyzed 2,717 isolates (pre-pandemic n=1640; pandemic n=1077) and observed a similar distribution of disease types between the two periods (Figure 1). Distribution of emm types differed with emm12 (1.7-fold) and emm3 (1.6-fold) increasing significantly and emm89 (0.6-fold), emm4 (0.6-fold), emm87 (0.4-fold) and emm6 (0.3-fold) decreasing significantly. Overall NS to any antibiotic increased from 19% to 39% between the two periods (P< 0.0001). NS in the pandemic period was primarily driven by NS to clindamycin, increasing by >3-fold (6% vs 20%) (Figure 2). Among emm types showing NS to clindamycin pre vs pandemic, emm28 increased 10-fold (3% vs 31%, P< 0.0001), emm1 increased 5-fold (5% vs 24%, P =< 0.001), and emm12 increased 2.6-fold (6% vs 16%, P< 0.001) (Figure 3). NS to any antibiotic increased independent of disease type between the two periods.

Figure 3 Frequency of clindamycin non-susceptibility by emm type

Conclusion

NS increased significantly in pandemic period, mostly driven by NS to clindamycin. A small subset of emm types disproportionately contributed to clindamycin NS in pandemic period, although the mechanism remains unknown. Clinicians should be aware of the possible reduced effectiveness of clindamycin in pediatric GAS infections.

Disclosures

Jonathon C. McNeil, MD, Nabriva: site investigator on clinical trial Anthony R. Flores, MD, MPH, PhD, GlycosBio, Inc: Grant/Research Support
P-1855. Dissecting the contribution of Herpesviruses in the emergence of depressive symptoms in Alzheimer's Disease through multi-omics data
Authors: Onisiforou Anna , Zanos Panos
Published: January 2025

Background

The association between members of the Herpesviridae family and the development of Alzheimer's Disease (AD) and Depression is well-documented. However, the specific pathogenic mechanisms through which herpesviruses contribute to the co-occurrence of AD and major depression remain poorly elucidated.

Methods

To explore this hypothesis, we employed an integrated multi-omics bioinformatics approach combining virus-host protein-protein interactions (PPIs) and transcriptomic data. This method was utilized to dissect the complex interplay between herpesvirus infections and the host biological pathways that might be jointly involved in AD and major depression.

Results

Our findings indicate significant overlaps in the herpesvirus-modulated pathways in AD and those implicated in major depression. Notably, specific herpesviruses were found to influence pathways related to neuroinflammation, synaptic function, and mood regulation, which are critical in both AD and depression. Additionally, co-infection with multiple Herpesviridae members was associated with increased susceptibility to developing comorbid AD and major depression.

Conclusion

This study supports the hypothesis that herpesviruses contribute to the pathogenesis of both AD and major depression through shared biological pathways. These insights highlight the potential of targeting these pathways in therapeutic strategies for patients suffering from both conditions. Furthermore, our results underscore the importance of considering viral infections in the clinical management of AD and comorbid depressive symptoms.

Disclosures

All Authors: No reported disclosures
P-1868. Incidence of Rhabdomyolysis in Patients Receiving Daptomycin in a Community Hospital OPAT Program
Authors: Cid Allison N , Gibson Heather D , Arnoczy Gretchen S , Jawanda Jaspaul S , Biritwum Madonna A , Di-Majo Amanda , LeViere Anna
Published: January 2025

Background

Daptomycin is a favorable medication for outpatient parenteral antimicrobial therapy (OPAT) due to its low rate of serious adverse events, however one potential therapy complication is the development of rhabdomyolysis. The aim of this study was to determine the incidence of rhabdomyolysis within a community hospital’s OPAT program.

Methods

A retrospective chart review was performed of patients enrolled in the OPAT program and who received daptomycin therapy from December 2022 to August 2023. The primary outcome of the study was the percentage of patients who developed rhabdomyolysis while on daptomycin therapy. Secondary outcomes included the determination of any patient- or drug-specific risk factors that may have increased the risk of rhabdomyolysis. Patients were included if they were discharged on daptomycin and followed by the formal OPAT program during the study period. Patients who were less than 18 years of age or pregnant were excluded.

Results

There were 83 patients who received daptomycin during the study period and 5/83 (6%) developed rhabdomyolysis. There were 8 (9.6%) patients who had an elevated creatinine kinase (CK) but did not have further progression to rhabdomyolysis. The median daptomycin dose given to patients was 8 mg/kg. Four out of the five patients with rhabdomyolysis were female (80%). The mean BMI of those who developed rhabdomyolysis was 37.9. The mean onset of rhabdomyolysis was 10.8 days. No patients with rhabdomyolysis were on a concomitant statin. None of the five patients experienced death or permanent organ failure.

Conclusion

The development of rhabdomyolysis in our study was higher than anticipated based on previous phase 3 studies. This difference may be due to higher dosing used between studies. Potential factors to consider for increased risk of rhabdomyolysis based on this study include female gender and BMI greater than 35. Statin use did not appear to be associated with an increased risk of rhabdomyolysis. Daptomycin is still a safe and effective antibiotic in the OPAT setting, however CK should be closely monitored.

Disclosures

All Authors: No reported disclosures