bluuebunny/crossref_metadata_2025 huggingface dataset:
P-1747. Cost Avoidance Analysis of Outpatient Parenteral Antimicrobial Therapy (OPAT) Plan Reconciliation on Patients Enrolled in Value-Based Payment Models at an Academic Hospital
Authors: Ross Jennifer , Boeser Kimberly , Hordyk Matt , Manhani Bhupinder , Hirsch Elizabeth B , Evans Michael , Sieling William D , Kline Susan E , Galdys Alison
Published: January 2025

Background

Outpatient parenteral antimicrobial therapy (OPAT) has many potential benefits, including avoidance of hospitalizations, reduced length of stay, and prevention of hospital-associated conditions. However, suboptimal OPAT delivery can result in readmissions and emergency department (ED) visits—outcomes that are unfavorable for patients and disincentivized within value-based care (VBC) models. Structured OPAT programs have been shown to decrease unscheduled healthcare use. Total cost of care (TCOC) analyses for OPAT program justification have not been well described. We therefore analyzed TCOC for a cohort of OPAT recipients enrolled in VBC pre- and post-implementation of OPAT plan reconciliation in June 2020.

Methods

Unique, adult OPAT patients discharged to home or post-acute care facilities from an academic hospital between 6/2019 and 6/2022 were included. Infectious diseases (ID) pharmacist reconciliation of OPAT plans prior to hospital discharge launched on 6/14/2020; all OPAT recipients discharged on or after this date were included in the post-implementation cohort. Average one-year post-intervention TCOC avoidance per patient was calculated using patient charges, a proxy for payor cost. The percentage of patients enrolled in a VBC plan was determined to calculate implied TCOC reduction annually.

Results

Nine hundred sixty-two OPAT patients were included: 198 pre- and 764 post-implementation. Fewer patients were included in the pre-intervention group given unretrievable financial data due to archiving rules. In our cohort, 16.9% of patients were enrolled in a VBC plan. Both pre- and post-intervention cohorts showed an increase in TCOC after index OPAT hospitalization; pre-intervention at 155% and post at 29%. This yielded a post-intervention average one-year cost avoidance of $15,754.55/patient. Based on our institution’s historical OPAT volume of 950 patients cared for annually, these data equate to an implied TCOC reduction of $2,529,409/year.

Conclusion

Implementation of formal ID pharmacist reconciliation of OPAT plans generated significant cost avoidance amongst OPAT patients enrolled in VBC plans. This is evidence that outcomes incentivized by VBC models align with outcomes facilitated by structured OPAT programs.

Disclosures

Jennifer Ross, PharmD, BCIDP, Shionogi Inc.: Advisor/Consultant Elizabeth B. Hirsch, PharmD, FCCP, FIDSA, GSK: Advisor/Consultant|GSK: Honoraria
P-1751. Why do we call in the Blues (and Purples)? Critical Result Reporting of Gram Stains for Gram Positive Cocci in Blood Cultures
Authors: Fischer Julia , Lorenzo Michael , Schimmel Jennifer
Published: January 2025

Background

Gram positive cocci (GPC) in blood cultures (BLCX) can represent pathogens or contaminants. Many laboratories notify care teams of a positive BLCX with the gram stain as a critical results report (CRR). However, PCR results about 90 minutes later and can provide useful information to distinguish a contaminant from a pathogen. The present study describes healthcare utilization surrounding CRR of gram stain result without the PCR result.

Methods

Retrospective observational study of patients with positive BLCX. Patients were excluded if their BLCX had yeast, polymicrobial growth, a gram-negative organism, or were < 18 years of age. Clinical and healthcare utilization information was collected using the electronic medical record. We defined the following as “true pathogens” (TP): MRSA, MSSA, Enterococcus, Streptococcus pyogenes, Streptococcus agalactiae and Streptococcus pneumoniae. We also defined TP as a coagulase-negative staphylococcus or other Strep species with 2/2 positive BLCX with intraarticular or endovascular hardware present and with 4 SIRS criteria. A “likely contaminant” (LC) was defined as coagulase negative staphylococcus or Strep species (not included in the initial TP definition) with 1-2 BLCX positive, with or without intraarticular or endovascular hardware present, and < 4 SIRS criteria.

Results

Of 94 patients with BLCX positive for GPC, 54 were categorized as TP, and 40 as LC. 36 (67%) of patients with a TP on BLCX received vancomycin (VAN) before CRR and 19 (35%) received VAN after CRR. 12 (30%) patients with a LC on BLCX received VAN before CRR and 11 (28%) received VAN after CRR. For those not on VAN before CRR and were placed on VAN after the call, 10 (24%) had TP and (28%) had LC identified. Repeat BLCXs were performed in 93% of patients with TP and 83% of patients with LC. Infectious Disease (ID) consults were placed in 63% of TP and 73% for LC. Echocardiograms were performed in 57% for TP and 60% for LC.

Conclusion

Workup and treatment for GPC identified in BLCX were similar for TP and LC. VAN is being over-utilized for LC which could lead to patient harm. Unnecessary resources are being expended in the workup of LC. Using PCR results instead of the gram stain as the CRR may provide more complete information to providers to inform decision making.

Disclosures

All Authors: No reported disclosures
P-1764. Point Prevalence Study of Antibiotic Appropriateness and Economical Cost in a Tertiary Care Trauma Hospital of Northern India to Tailor Antibiotic Stewardship Interventions
Authors: Garg Rahul , Wankhade Archana B , Banerjee Tuhina
Published: January 2025

Background

Conducting Point prevalence surveys (PPSs) is challenging, especially in developing countries, in the absence of electronic records, lack of dedicated resources and high patient load. This survey was conducted to provide background data for strengthening antimicrobial stewardship(AMS) practices and estimate the economic cost of antimicrobial resistance per antibiotic consumed in a tertiary care trauma hospital in India.

Summary of Quality indicators of antibiotic prescribing (in %)

Methods

The survey included all inpatients admitted in wards and intensive care units of the hospital (300 beds) during World Antibiotic Awareness Week 2023. Standardised modules were adopted from the Global PPS for collecting data on patient demographics, prescribed antimicrobial agents with dosage, indication(s) and duration of treatment, and microbiolgical results. Further, the cost minimization analysis was carried out to assess the treatment cost and variations in costs arising due to generic or branded prescribing.

Results

Among the 254 patients admitted, the patients treated with at least one antimicrobial was 88.6% (N=225). The median (IQR) day of hospitalization was 7 (3.75) days. The highest prevalence of antimicrobial use was in the ICU (100%), followed by Emergency medicine (97.5%). The majority of patients received empiric than targeted antimicrobial therapy. Antimicrobial prescription was mostly for surgical prophylaxis (49.04%). Among patients for >7 days on treatment, microbiological culture were sent in 16.7% (5/30) patients. Antibiotic quality indicators such as reason in notes and documentation of review date were comparatively lower (Figure-1). Treatment costs varied significantly with prescriptions of maximum and minimum-priced brands, ranging from 69.81%-1490%. Branded therapy were three times costlier than generic therapy in 36 (52.9%) regimens.

Conclusion

Poor transition from empiricism to rationalism, continuation of surgical prophylaxis for more than one day and underutilization of microbiological tests were noted. There was large variations in treatment cost of infections depending on regimen chosen. Adherence to local antibiotic policy, optimal dosing and regular audit with positive feedback of antibiotic use to treating physician can be useful approaches to implement the AMS Program in the study centre.

Disclosures

All Authors: No reported disclosures
P-1781. Development of an Inpatient Pharmacist-Driven Penicillin Allergy De-Labeling Protocol
Authors: Anderson Brandon , Herstine Emily , Gens Krista
Published: January 2025

Background

Up to 10% of the US population reports a penicillin allergy. However, when further tested, over 95% of these patients could tolerate a penicillin. Unnecessary avoidance of penicillins results in more broad antibiotic treatment, leading to several worsened patient outcome, including increases in resistance, C. difficile rates, mortality, cost, and more.

Example Inpatient Penicillin Allergy De-Labeling Protocol

Visual representation of an example penicillin allergy de-labeling protocol

Methods

Key penicillin allergy de-labeling protocol development steps included assessment of local penicillin allergy prevalence, identification of key stakeholder groups, effectively communicating why de-labeling is important, and incorporating feedback from each stakeholder group into protocol language. Operational considerations included creation of standardized order sets and documentation tools, as well as defining scope and prioritization of patients by determining who is most likely to benefit from de-labeling. The last step was development of educational materials for pharmacists and nurses to effectively use the protocol, as well as patient education materials.

Flowsheet outlining documentation requirements, including standardized allergy comments, progress note templates, and after visit summaries

Results

The Allina penicillin allergy de-labeling protocol was developed through collaborative efforts of pharmacy, infectious disease, allergy, and nursing. Within the protocol, patients with penicillin allergies listed in their charts are interviewed by a pharmacist, who calculates a PEN-FAST risk score. Patients with reactions that are consistent with intolerance rather than allergy may have their allergy removed without further testing. If reactions are consistent with allergy, but their PEN-FAST risk score is low (0-2), patients are eligible to complete an oral amoxicillin challenge. If PEN-FAST risk score is moderate to high (3-5), patients are eligible for referral to outpatient allergy for further testing.

De-Labeling Protocol Development Process

Example roadmap that can be used to develop a penicillin allergy de-labeling protocol in nearly any healthcare setting

Conclusion

The penicillin allergy de-labeling protocol was approved system-wide through pharmacy and nursing committees and will soon be rolled out to individual sites. This example may serve as a roadmap for development of penicillin de-labeling programs in other health systems and could be adapted as needed to work effectively in many healthcare settings.

Disclosures

All Authors: No reported disclosures
P-1791. Low Utilization of Methicillin-Resistant Staphylococcus aureus Screening in Orthopedic Surgeries
Authors: Huerta-Vera Genesis S , Green Lauren , Parimi Kavya , Chaudhary Nabihah A , Wein Megan , McCormick Pamela J , Pursglove Marci L , Arbulu Ricardo
Published: January 2025

Background

Guidelines recommend screening for methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization to identify patients undergoing orthopedic implants who may benefit from perioperative vancomycin. Culture-based MRSA screening may take days to result, yet it is the only technique available in many centers, including ours. Therefore, we investigated the proportion of cases in which MRSA screening results are available at time of orthopedic implants at our center, and explored the rationale for perioperative choice when this information is absent.

Methods

We conducted a retrospective chart review of all consecutive patients 18 years or older who underwent orthopedic implant procedures for the calendar year 2023 at UPMC Mercy, Pittsburgh, PA. Patients undergoing multiple procedures within 24 hours were counted once. We report a preliminary analysis for 44% of the total population. Data was analyzed by MRSA screening status.

Results

In 251 surgeries performed in 247 patients, MRSA screening within one year prior to surgery was available only in 63 (25.1%). An additional 43 (17.1%) had results older than one year, while 145 (57.8%) had no MRSA screening. Patients that had MRSA available within a year did not defer from those with older or absent results in the proportion of emergent surgeries, types of surgeries, or perioperative prophylactic antibiotics received (Table 1). Only 43 (17.3%) patients had MRSA screen collected during the admission.

Only four patients received perioperative vancomycin, only one had a clear indication for this choice (Table 2). Of six patients with an indication for perioperative vancomycin, none received this antibiotic.

Conclusion

In patients undergoing orthopedic implants, MRSA screening results were available at time of surgery in less than half of cases, screening was infrequently ordered during the admission for surgery, and the results did not seem to affect the antibiotic choice. Non-systematic input from the three orthopedic surgeons with the highest volume at our center suggests this low utilization is due to: a. questioning the value of the screening and vancomycin prophylaxis, b. lack of systematization (of ordering, reviewing), and c. the perception that the results are unlikely to be available at the time of surgery.

Disclosures

All Authors: No reported disclosures
P-1792. Impact of Integrated Interventions of Prescriber Education and De-escalation Strategies on Implementing WHO Access: Watch Targets: Insights from a South Indian Tertiary Care Setting
Authors: Leelarani Martinraj Jasper Victoria , Samuel Bibila , Thomas Feba Mary , Senthil Harini , George Keren Ann
Published: January 2025

Background

The study aims to determine the Access: Watch ratio, as recommended by the WHO AWaRE guide 2022, to regulate antimicrobial prescribing practices, highlighting the importance of educational sessions for successful AMS interventions.Table 1:Quantification of antibiotic use during the study periodBased on Days of therapy (DOT), an AMS metric.

Methods

The study analyzed antimicrobial usage data from 360 patients from March to July 2023. It quantified DOT by comparing Access and Watch group antibiotics. The first three months focused on auditing antimicrobial prescribing practices, followed by a session on rational prescribing and an educational survey. The second two months focused on feedback on the impact of educational interventions.Figure 1:Trend of Access:Watch ratio of antibiotics during the study period

Results

The use of Cefoperazone + Sulbactam, a broad-spectrum watch class antibiotic, was high in April and May (48.7 and 50.7, respectively) but decreased to 19.3 and 18.1 in the subsequent months following educational interventions. Optimization of de-escalation practices through audit and feedback strategies, emphasized in the continuing medical education sessions, contributed to this reduction. The Access: Watch Ratio increased from 0.45 to 0.52 over the study period, indicating a reduction in Watch antibiotic use. Pre-survey results showed 88.9% of prescribers considered de-escalation safer, increasing to 100% post-intervention. Various case-scenarios presented to prescribers showed improved understanding and adoption of rational antibiotic prescribing and de-escalation strategies after the educational session.

Conclusion

Integrated interventions, including prescriber education and de-escalation strategies, were effective in achieving the WHO Access: Watch target in our South Indian tertiary care setting. The reduction in Watch antibiotic use and the increase in the Access: Watch ratio demonstrate the impact of these interventions on antimicrobial prescribing practices. Ongoing education and support for rational antibiotic use are critical in addressing antimicrobial resistance.

Disclosures

All Authors: No reported disclosures
P-1793. Revitalizing Antibiotic Selection Through De-labeling of Outdated Antibiotic Allergies: Insights to Improving Antimicrobial Stewardship from South India
Authors: Leelarani Martinraj Jasper Victoria , Dorairajan Sureshkumar , Amargeeth Surendhar , Pooja P , Shanmugam J
Published: January 2025

Background

Self-reported drug allergies need to be revised or re-assessed, often. Therefore, this study aims to assess self-reported drug allergies among patients and identify potential candidates for de-labeling outdated or inappropriate antibiotic allergies, as part of antimicrobial stewardship interventions promoting rational antibiotic prescribing, as they facilitate the use of overly-broad spectrum antibiotics contributing to increased risk of antimicrobial resistance and adverse effects.Table 1:Antibiotic allergies and Potential candidates for de-labeling in the study

Methods

This observational study was conducted in three tertiary care hospitals in South India from October to November 2023. Patients with drug allergy labels underwent thorough interviews utilizing the PEN-FAST clinical decision rule, adopted for risk stratification of all antibiotic allergies. The rule employed a score < 3 to identify low-risk penicillin allergies, potentially eligible for allergy de-labeling. Self-reported drug allergies were documented in an Excel sheet, with descriptive statistics were applied for analysis.

Results

Among 857 patients analyzed, 58 (74.3%) patients reported antibiotic allergies. Penicillin and Sulfa allergy labels were the most prevalent allergy labels. Notably, 62.5% patients with low-risk Penicillin allergy and a vast majority of patients with Sulfa and Quinolone allergy are potential candidates for de-labeling, after employing the validated tool assessing the timeframe, severity and characterization of allergic reactions.

Conclusion

In summary, The results of the study underscores the importance of adopting validated tools to revitalize antibiotic selection, de-labeling of > 60% inappropriate or outdated allergies and hence, enabling the use of first-line antibiotics in approximately 50-100% of the patients labeled with antibiotic allergies.

Disclosures

All Authors: No reported disclosures
P-1813. Improving Adherence to an Antibiotic Pre-Authorization Protocol at a Community Academic Medical Center
Authors: Sutton Spencer , Yan Xuping , Tandon Richa , Colgrove Robert
Published: January 2025

Background

Preauthorization is integral to antimicrobial stewardship and is associated with decreased utilization of restricted antimicrobials, lower cost, and reduced development of antimicrobial resistance. Implementation of such a program is resource-intensive and dependent on the skill of the approving provider. The aim of this quality improvement project was to update the preauthorization program at a community hospital and increase protocol adherence from 23.8% to 85% by September 1st, 2023.Figure 1:Adherence to the Preauthorization Process presented as a P-chart, representing the rate of the desired outcome with variable sample size over time. Statistical significance identified through mean-line shift, based on 8 consecutive data points above or below a previous mean line.

Methods

A community academic medical center developed a workgroup of infectious diseases (ID) pharmacists and physicians to optimize the existing antibiotic preauthorization policy. Baseline data were collected over a one month period, based on policy requirements for approval prior to implementation of improvement initiatives. Updates implemented an ID pharmacist into the approval process, streamlined request communication, and standardized documentation of approval. Requests were considered adherent to protocol if the process metrics of appropriate use were met. This included following the off-hours pathway appropriately and completion of standardized documentation prior to order verification. Balancing metrics included duration of restricted antimicrobial utilization. Data were extracted through a query of electronic medical records with manual chart review of patients who received at least one dose of a restricted antimicrobial. Data were analyzed through descriptive statistics pursuant to the Institute of Healthcare Improvement’s Model for Improvement or Wilcoxon Rank-Sum, where appropriate.

Results

Between September 2022 and September 2023, 701 restricted therapies were ordered. Of these, 410 were not associated with an infectious diseases consult. Mean protocol adherence increased from 23.8% (5/18) to 86.2% (307/356) [Fig. 1]. Median duration of restricted antimicrobial therapy decreased from 4.0 days to 3.0 days (p=0.0025).

Conclusion

The implemented updates to the preauthorization program markedly increased protocol adherence and decreased duration of restricted antimicrobial therapy. This work demonstrates the feasibility and quality impact of implementing antimicrobial stewardship initiatives in a community hospital setting.

Disclosures

All Authors: No reported disclosures
P-1815. Estimation of the cases with suspected community-acquired pneumonia where antibiotic intervention could occur after 48 hours: Application of an electronic algorithm for real-time screening
Authors: Kim Bongyoung , Klein Eili , Fabre Valeria , Cosgrove Sara E
Published: January 2025

Background

Timely identification of unnecessary antibiotics (abx) started for suspected community-acquired pneumonia (CAP) is vital for antibiotic stewardship programs (ASPs). We estimated potential opportunities for ASP intervention among patients flagged as potentially having CAP by an electronic algorithm using electronic health record data that allows for real-time case detection.

Methods

We screened all adult patients admitted to Johns Hopkins Hospital (1,150 beds) between 12/2023-2/2024 using the algorithm which is based on the following variables: i) abx targeting CAP ≥48h, ii) respiration rate ≥24/min, iii) white blood cell (WBC) >12,000/mm3, and iv) natural language processing (NLP)-derived radiology results compatible with pneumonia. Patients admitted to oncology or with sickle cell disease were excluded. Manual chart review was performed to adjudicate true CAP, defined as the presence of signs/symptoms of pneumonia with corresponding radiographic findings, while excluding alternative diagnoses, based on the clinical course observed within 48 h. We characterized factors associated with patients without CAP, particularly radiological interpretation, and the proportion eligible for ASP intervention at 48 h of admission.

Results

122 of the 152 cases (80.3%) identified by the electronic algorithm were adjudicated as non-CAP based on clinical criteria. Compared to CAP cases, non-CAP cases were less likely to have fever (40.0% vs. 9.8%, P < 0.001) and cough/sputum (76.7% vs. 42.6%, P = 0.001). Common diagnoses for non-CAP cases were volume overload (19.7%), other pulmonary disorders (18.9%), chronic lung disease exacerbation (14.8%), and viral pneumonia (12.3%).

Most unnecessary abx were initiated in the emergency room (85.2%, 104/122); 60.6% (63/104) were continued for >24 hours after admission, and 48.4% (59/122) could have been intervened upon at 48 hours of admission.

63.1% of non-CAP cases had radiographic interpretations suggesting CAP, with poor correlation between radiological interpretation and clinical diagnosis of true CAP (kappa 0.221).

Conclusion

ASP interventions to stop abx within 48 h of admission were indicated in ∼50% of non-CAP cases identified by the electronic algorithm.

Disclosures

All Authors: No reported disclosures
P-1818. Pilot Testing of a Stakeholder-driven, Patient Education Intervention in Primary Care to Reduce Use of Antibiotics without a Prescription
Authors: Brehm Tyler , Grigoryan Larissa , Olmeda Kiara , Mancera Azalia , Zoorob Roger , Sidani Mohamad , Laytner Lindsey , Adams Mace , Trautner Barbara
Published: January 2025

Background

Antibiotic use without a prescription (non-prescription use) is a highly prevalent issue that poses significant individual and population level risk. We designed a patient-focused educational brochure to reduce non-prescription antibiotic use and report patient survey results about the brochure’s acceptability, appropriateness, and usability.Figure 1.Brochure Usability, Appropriateness, and Acceptability

For the three criteria of usability, appropriateness, and acceptability, responses of "completely agree" and "agree" were categorized as positive while "neither agree or disagree," "disagree," or "completely disagree" were categorized as negative responses. n = 100 respondents.

Methods

The brochure was developed with input from six racially/ethnically diverse community advisory board members plus 2 experts in health literacy and cultural competency in Hispanic communities. Brochure content included information on safe means of obtaining antibiotics, antibiotic side effects, non-antibiotic treatment of common symptoms, and how to access care at the public clinics. From October 2023 to February 2024, brochures (in English or Spanish) were distributed to 100 patients at two local clinics (50 each). Patients completed a survey about the brochure acceptability, appropriateness, and usability, followed by an open-ended question about suggestions for improvement.

Results

Survey participants were on average 53 years old, 72% female, 72% college educated, and primarily Black (35%), Hispanic or Latino (30%), or Caucasian (28%). 81% had adequate health literacy. Respondents largely found the brochure acceptable (98%), appropriate (98%), and usable (100%). 96% of respondents said the brochure was useful, referencing learning about antibiotic indications (23%), over the counter alternatives for symptom relief (23%), and antibiotic side effects (14%). The most common reason respondents did not find the brochure useful was they already “knew everything in [the] brochure” (n = 4). 15 respondents (15%) had suggestions for improvement such as having an alternative media form (e.g., an audio version) and having the brochure available at the pharmacy (27% each).

Conclusion

We designed a brochure about antibiotic safety that was considered acceptable, appropriate, and usable by our diverse clinic patients. Key learning points reported by patients included antibiotic indications, side effects, and over the counter alternatives. Next the brochure will be the focus of an intervention to reduce non-prescription antibiotic use among our socially vulnerable patient population.

Disclosures

Barbara Trautner, MD, PhD, Abbott Laboratories: Stocks/Bonds (Public Company)|AbbVie: Stocks/Bonds (Public Company)|Bristol Myers Squibb: Stocks/Bonds (Public Company)|Pfizer: Stocks/Bonds (Public Company)|Phiogen Pharma: Advisor/Consultant
P-1857. S100B and other Fecal Biomarkers as Predictors of Clostridioides difficile Infection Severity and Recurrence are Influenced by Age
Authors: Doppalapudi Laasya , Behm Matthew , Costa Deiziane , Rodrigues-Jesus Mônica , Shin Jae Hyun , Warren Cirle A
Published: January 2025

Background

Clostridioides difficile infection (CDI) is an urgent threat in the US. Because disease severity is strongly correlated with intestinal inflammation, the aim of this study was to identify fecal biomarkers associated with poor outcomes and investigate how these biomarkers are influenced by clinical variables.

Methods

Fecal samples from patients diagnosed with CDI were collected from April 2021 to February 2022. Levels of biomarkers for intestinal inflammation (myeloperoxidase-MPO, lipocalin-2-Lcn2, calprotectin, S100 calcium-binding protein B-S100B, IL-6 and brain-derived neurotrophic factor-BDNF) were measured by ELISA. C. difficile isolates were tested for binary toxins gene, cdtA/cdtB, by qPCR.

Results

The majority of patients were females (54%, 88/149), infected by binary positive strain (59%, 88/149) and with mean age of 61.4, (range: 21 to 96 years old). 43.2% (64/148) of the patients exhibited severe disease, 29.7% (44/148) were recurrent CDI cases, and 19.4% (29/149) died post-infection. Increased fecal levels of S100B (p=0.0006) and IL-6 (p=0.03) were detected in severe disease. Compared to non-severe cases, severe first CDI cases exhibited higher levels of S100B (p=0.002), and IL-6 (p=0.04), while severe recurrent cases showed significantly higher levels of MPO, Lcn2, and calprotectin. In addition, increased levels of MPO, calprotectin, and S100B correlated positively with age. Increased fecal IL-6 (p=0.03) and S100B (p=0.01) were detected in middle-aged (40-64 years old) severe cases. Increased MPO (p=0.02), calprotectin (p=0.01), Lcn2 (p=0.006), and S100B (p=0.02) were also detected in middle-aged and oldest-old severe cases. Furthermore, patients infected by binary positive strains had significantly higher levels of fecal MPO, Lcn2, calprotectin, and IL-6. Recurrent cases also showed higher levels of fecal MPO, Lcn2, and calprotectin compared to first episode CDI cases. Fecal markers of inflammation were independent of gender.

Conclusion

Our findings indicate that fecal S100B is a marker of CDI severity in middle-aged, middle-old, and oldest-old patients independent of gender. Additionally, elevated fecal biomarkers (MPO, Lcn2, calprotectin, S100B, and IL-6) appear to correlate with binary toxin positivity and recurrence.

Disclosures

Jae Hyun Shin, MD, Ferring: Grant/Research Support Cirle A. Warren, MD, Ferring Pharmaceuticals: Site PI for ROAR
P-1858. Exploring the Role of Fatty acid synthase (FASN) Inhibition in Interferon Gamma Mediated Killing of Histoplasma capsulatum
Authors: Nair Resmi , Buesing William , Rossi Diego , Deepe George S
Published: January 2025

Background

Histoplasma capsulatum (Hc) is the leading cause of fungal respiratory infections in the US. Most cases are mild but 20% require hospitalization. Immunosuppression is a major risk factor for disseminated histoplasmosis. The cytokine Interferon gamma (IFN)-γ is crucial for host resistance to Hc. The absence of IFN-γ or its failure to signal affects the host immune response.

Activated CD4+ T cells release IFN-γ to arm macrophages(MΦ) to kill intracellular yeasts. Immunometabolism is a key element in the function of MΦ and fatty acid synthase (FASN) regulates inflammatory responses by these cells. FASN is a large multi-enzyme complex comprised of 6 separate enzymatic grooves that work together to produce 16-carbon chain saturated fatty acid (FA), palmitate, from acetyl-coenzyme A (CoA) and malonyl-CoA(Figure 1). The influence of FASN in the IFN-γ-mediated activation of MΦ remains unclear.

Key inhibitor targets in FASN complex

Methods

Figure 1 shows key inhibitor targets in FASN complex. Bone marrow derived Mφ were used in all experiments with a 2 to 1 yeast to Mφ ratio. IFN-γ induced killing of Hc in mouse Mφ require 48h. We used the tetrazolium salt XTT to assess the Hc viability as this correlates with the colony counts. Controls (Hc in Mφ) are set to 100 %. Toxicity of each inhibitor to Hc and Mφ was studied first.

Mφ were treated with IFN-γ 4hrs before infection and then treated with graded amounts of FASN inhibitors C 75 (inhibits ketoacyl synthase), orlistat (inhibits thioesterase), and TVB-3166 or GSK2194069 (both inhibit ketoacyl synthase) 2hrs before infection with 2x Hc for 48hrs. Intracellular yeast survival at 48hrs was assessed.

Effect of FASN inhibitors on IFN- γ mediated killing of Hc at 48 hrs.

n= 3-10 , mean ±SEM

Results

Pretreatment with the FASN inhibitor C75 reversed the killing activity of IFN- γ. Neither orlistat or inhibitors of ketoacyl reductase modified the impact of IFN-γ. (Figure 2)

Conclusion

The FASN inhibitor C75 reversed the activity of IFN-γ in killing Hc. These results suggest that cholesterol synthesis may be involved in the action of IFN- γ.

Disclosures

All Authors: No reported disclosures
P-1878. Intravenous Ganciclovir Administration Outcomes via an Outpatient Parenteral Antimicrobial Therapy (OPAT) Program
Authors: Patel Dhruv , Mynatt Ryan P , Logan Ashley , Cari Evelyn Villacorta , Mansoor Armaghan-E Rehman
Published: January 2025

Background

Intravenous (IV) ganciclovir is used in the management of herpesvirus infections including cytomegalovirus (CMV). Ganciclovir is usually administered in the inpatient setting given the need for close monitoring of hematologic and renal parameters. This study describes our experience with IV ganciclovir administration in immunocompromised hosts, via an OPAT program at a tertiary academic medical center. Ganciclovir was chosen as choice of therapy either due to concern for GI absorption, or provider preference.

Methods

This is a retrospective, single-center review of patients discharged on IV ganciclovir via OPAT from August 2019 to December 2023. Patient demographics, underlying diagnoses, indication for ganciclovir, duration of therapy, treatment outcomes and adverse events were collected.

Results

We included 18 patients whose mean age was 58.6 (SD±12.4) years, with ten (55.6%) being male. The most common underlying immunocompromising condition was receipt of a transplanted organ in 15 (83.3%) patients, including five and ten recipients of hearts and kidneys, respectively. The mean duration of therapy was 25 (SD±11) days. In our cohort, 13 were treated for CMV disease as follows; 11 patients with gastrointestinal involvement and two patients with encephalitis/retinitis. Four patients had isolated viremia and one patient was treated for Epstein Barr Virus encephalitis. A majority (13 patients, 72.2%) transitioned to valganciclovir on completion of parenteral therapy for secondary prophylaxis or to continue induction therapy.

The most common adverse event was worsening cytopenia in four (22.2%) patients, one of whom had baseline leukopenia. Neutropenia was documented in three patients, and one patient had thrombocytopenia. One (5.6%) patient developed acute kidney injury (AKI) through their treatment, requiring dose modification.

Conclusion

Ganciclovir is a viable option for outpatient parenteral therapy in the treatment of CMV disease where an extended duration of IV therapy is required. In our cohort of 18 immunocompromised patients, only one had early discontinuation of therapy due to ganciclovir-related AKI. Close monitoring of labs through an established OPAT protocol is needed for successful completion of therapy.

Disclosures

All Authors: No reported disclosures
P-1884. Evaluation of Outpatient Parenteral Antimicrobial Therapy Practices within a Large Healthcare System
Authors: Beran Christina , Kim Chungyun , Wings Emily , Pallotta Andrea , Shrestha Nabin K
Published: January 2025

Background

The practice of outpatient parenteral antimicrobial therapy (OPAT) has challenges such as reduced control and monitoring in the outpatient setting. Lack of availability of OPAT lab monitoring is associated with poorer outcomes. This study sought to describe the operations and practices of an OPAT program within a large health system to identify clinical and operational opportunities for workflow improvement.

Laboratory monitoring completion over proportion of OPAT courses

Methods

This was a retrospective cohort study of patients receiving OPAT in a large healthcare system from January 1, 2022 to December 31, 2022. After excluding OPAT courses initiated in the outpatient setting and courses less than 7 days long, 200 OPAT courses for patients greater than 18 years of age were selected, using a random sample generator, from the Cleveland Clinic OPAT registry. Events were followed until the OPAT end date or 30 days, whichever occurred sooner. The relationship between lab monitoring completion within 24 hours of scheduled date and detection of clinically significant lab abnormalities (CSLAs) was examined using linear regression. Secondary outcomes included the rate of emergency department (ED) visits and readmissions.

Cumulative incidence of ED visits by target lab monitoring level

Results

The mean age (SD) of included patients was 63 years (27) and 64% were male. Fewer than half the OPAT courses had 80% or higher lab monitoring completion (Figure 1). Detected CSLAs are shown in Table 1. In a linear regression model adjusted for high-risk medications, the number of CSLAs detected per OPAT course increased by 0.003 (95% C.I. 0.002 – 0.004) per unit increase in percentage lab monitoring completion (p < 0.001). ED visit within 30 days was 11% (Figure 2) and readmission within 30 days was 23% (Figure 3). Reasons for readmission included non-OPAT-related (53%, n=24 of 45), infection-related (40%, n=18 of 45), and adverse OPAT drug effects (9%, n=4 of 45).

Cumulative incidence of readmissions by target lab monitoring level

Conclusion

This study showed a substantial gap in lab completion and a significant association between lab monitoring completion and detection of CSLAs, thereby demonstrating clinical and operational opportunity for OPAT workflow improvement with monitoring and follow-up actions. A multidisciplinary OPAT team with clearly defined roles may enhance safety, effectiveness, and efficiency within the program.

Detection of Clinically Significant Lab Abnormalities

Disclosures

Andrea Pallotta, PharmD, Astra Zeneca: Advisor/Consultant|Viiv: Advisor/Consultant
P-1885. Continuous Infectious Diseases Coverage by Merging with a Hospitalist Practice in a Small Community Hospital System
Authors: Wang Michael , Aleksoniene Kristina , Tompkins Jason , Douce Richard , Froggatt John , Harrison Mark
Published: January 2025

Background

There is a severe shortage of infectious diseases (ID) physicians in the United States, with > 80% counties without an ID physician. Insufficient compensation is a contributing factor, with many internal medicine graduates practicing as hospitalists. Based on community needs, we merged the ID practice into the hospitalists group to create an ID-Hospitalist position.

Methods

Corewell Health South is based in Berrien County, which is in Southwest Michigan, population 152,261, and includes large rural populations and several federally funded clinics. The hospital includes 2 acute care facilities, including 220-bed and 76 bed hospitals. In 2002, the ID physicians began seeing patients as hospitalists at a Long-Term Acute Care Hospital. An ID physician assumed the role of Hospitalist Director in 2005 and second physician became co-director in 2008. At that time, the ID service adopted a 7 day on-7 day off schedule and included primary hospitalist patients.

Results

Since 2011, the ID-Hospitalist group has had continuous coverage with at least 3 Full time and 1 part-time ID-Hospitalists. Coverage (2.63/100,000) exceeds the national average of 1.79/100,000 by 84%. All service weeks are based on a 7 day on-7 day off schedule. In 2013, the outpatient ID clinic was resumed after a 5-year hiatus and is Ryan White Funded. A clinic day is built into the 7-day work week. Over the last 22 years, the group has included 6 ID physicians, which include 5 American graduates and 1 international graduate. In surveying the group, 83% expressed that pay was a factor in working as an ID/Hospitalist. 67% reported more free time and improved work-life balance. 67% preferred doing ID only, although the majority enjoyed hospitalist practice.

Perceived weaknesses included overextension of responsibilities and a de-emphasis on the ID service in favor of hospitalist responsibilities. Another limitation included inconsistent coverage at the smaller hospital, increasing the reliance on telephone consultations.

Conclusion

Merging an ID practice into a hospitalist group has been effective in sustaining an ID service. Strengths included stable salary support and ability to perform other administrative or clinical tasks. Weakness included a multitasking of duties. This may serve as a model for resource limited settings.

Disclosures

All Authors: No reported disclosures
P-1894. Evaluation of an Outpatient Parenteral Antimicrobial Therapy (OPAT) Program Performance Against Published Key Performance Indicators (KPIs)
Authors: Slain Nicole , Mynatt Ryan P , Logan Ashley , Burgess Donna R , Clemons Alisha , Mansoor Armaghan-E Rehman , Ruf Kathryn , Cari Evelyn Villacorta
Published: January 2025

Background

Current OPAT guidelines emphasize identifying, reporting and improving key antimicrobial use and care coordination decisions. There is no clear guidance on benchmarking or consensus reporting recommendations. We examined our OPAT program’s performance against data published from Great Britain’s National Outcomes Registry System (NORS) as well as a meta-analysis on catheter related thrombosis (CRT) in OPAT (Figure 1).

Methods

Adult patients receiving OPAT from infectious diseases (ID) ambulatory and inpatient consult teams from June 2021 to July 2022 were included. Patient demographics, admission data, and OPAT outcomes were recorded as part of routine pharmacist workflow. Data were compared against those reported via the NORS registry as well as a meta-analysis evaluating CRT. Specific comparisons relative to reported rates and ranges were made in key clinical areas including infection type, clinical outcomes, OPAT completion, VAD events, adverse drug events (ADEs) and medication-related events. Given limitations to available published data, a statistical comparison was not performed.

Results

Overall, 913 OPAT episodes were identified. Infections observed at our institution were more invasive and required longer treatment durations (Table 1). Outcomes were known in 798 (87.4%) patients, with improvement/cure reported in 689 (86.3%) in comparison to 92.4% (number not reported) in the NORS registry (Table 2). Institutional performance relative to VAD-related events was within the ranges observed by both NORS (1.4 per 1000 OPAT days vs. 1.4 per 1000 OPAT days [reported range: 0.11 – 10.4]) and meta-analysis (Table 3). These rates remained comparable when further classified as either infection-related or CRT. In our OPAT cohort, rates of catheter removal events and medication errors were rare, occurring in 0.5 and 0.6 events per 1000 OPAT days, respectively. These were novel OPAT metrics not reported in the comparator registry.

Conclusion

Compared to the NORS national registry, infections managed with OPAT at our institution were more deep-seated and required longer durations of therapy. However, our reported clinical outcomes at the end of therapy remained comparable and were within reported ranges.

Disclosures

Alisha Clemons, APRN, Gilead Sciences: Honoraria
P-1904. The Interaction of Serum Biomarkers and Lymphopenia on Pulmonary COVID-19 Illness Progression in Hospitalized Patients
Authors: Benitez Gregorio , Kaczynski Matthew , Vassilopoulos Stephanos , Vassilopoulos Athanasios , Shehadeh Fadi , Tashima Karen T , Mylonakis Eleftherios
Published: January 2025

Background

Low absolute lymphocyte count (ALC) as well as elevated levels of plasma nucleocapsid antigen (N-antigen) and C-reactive protein (CRP) are independently associated with COVID-19 clinical outcomes. We evaluated the potential additive interaction of these three prognostic markers on the progression of pulmonary COVID-19 illness.

Methods

We utilized publicly available data to perform a secondary analysis of hospitalized adults who enrolled into the Therapeutics for Inpatients with COVID-19 platform trial (NCT04501978). Plasma N-antigen level > 1000 ng/L, CRP level > 75 mg/L, and ALC < 1.5x109/L, all measured at baseline, were the three prognostic markers of interest. The outcome of interest was worsened pulmonary status, dichotomized as either worse or same/better than baseline status on a 7-point ordinal scale, at day 5. Estimated coefficients from modified multivariable Poisson regression were utilized to calculate risk ratios. We then calculated relative excess risk due to interaction (RERI) to evaluate departure from additivity. We present a measure of excess risk due to the respective two-way interactions when one of the markers is absent (RERI2), a measure of excess risk due to the three-way interaction (RERI3), and a total summation of excess risk (TotRERI).

Results

A total of 2,478 enrolled patients were included in our complete-case analysis (Figure 1). The interaction of low ALC, elevated plasma N-antigen level and elevated CRP level on worsened pulmonary status at day 5 may be super-additive (TotRERI = 0.88, 95% confidence interval (CI): -0.71 – 2.48) (Table 1). This 88% excess risk of worsened pulmonary status is mainly due to the explicit three-way interaction (RERI3: 1.56, 95% CI: -0.77 – 3.89). Sensitivity analysis utilizing multiple imputation to address missing data revealed similar estimates: TotRERI: 0.87 (95% CI: -0.79 – 2.53) and RERI3: 1.70 (-0.74 – 4.14).

Conclusion

Our data suggest that the interaction of low ALC, elevated plasma N-antigen level and elevated CRP level may be associated with excess risk of worsened pulmonary COVID-19 illness among hospitalized patients. Further evaluation regarding the interaction of prognostic markers in identifying patients at high-risk of pulmonary deterioration is supported.

Disclosures

Eleftherios Mylonakis, MD, PhD, BARDA: Grant/Research Support|Basilea: Advisor/Consultant|Chemic Labs/KODA Therapeutics: Grant/Research Support|Cidara: Grant/Research Support|Leidos Biomedical Research Inc./NCI: Grant/Research Support|NIH SciClone Pharmaceuticals: Grant/Research Support|NIH/NIAID: Grant/Research Support|NIH/NIGMS: Grant/Research Support|Pfizer: Grant/Research Support|Regeneron Pharmaceuticals, Inc.: Grant/Research Support
P-1927. Utilization of Patient Characteristics and the Area Deprivation Index (ADI) To Evaluate Referral Patterns for Long COVID at a Tertiary-Care Veterans Affairs (VA) Medical Center
Authors: Brennan Martha , Wilson Brigid , Stiefel Usha
Published: January 2025

Background

The COVID-19 pandemic disproportionally affected socioeconomically disadvantaged communities, with corollary expectation of increased impact of post-acute sequelae in this population. We established a subspecialty Long COVID Clinic (LCC) at VA Northeast Ohio to care for patients with post-acute sequelae of COVID-19 in 2023. The LCC was advertised system-wide to providers via email and videoconference presentations, and to patients via the facility website. After the first 1/2 year of implementation, an analysis of patients and of referral adequacy in meeting the needs of the catchment area was undertaken.

Methods

The Area Deprivation Index (ADI) uses census data to rank US neighborhoods by socioeconomic disadvantage and can be a tool in refining delivery of services or healthcare. Neighborhoods are ranked nationally and within-state (state deciles 1-10, with 10 indicating greatest disadvantage). In addition to other health factors, national and state ADI indices were obtained for each patient seen in our LCC between March 2023 and April 2024.

Results

70 unique patients (mean age 63) were seen via referral in the 1st 8 months of the LCC (Fig 1). These were 13 (19%) women, 55 (79%) men, 2 (1%) transgender, 10 (14%) Black and 54 (77%) White. The most common comorbidities were psychiatric (57%), hypertension (44%) and cardiac (40%) (Fig 1). The most common presenting complaints were fatigue (73%), exercise intolerance (72%), and dyspnea (52%) (Fig 2). ∼1/4 of LCC patients had experienced severe COVID-19 (Fig 3). The average in-state ADI decile was 5 (range, 1-10).

Conclusion

Disclosures

All Authors: No reported disclosures