bluuebunny/crossref_metadata_2025 huggingface dataset:
P-1797. Implementation of a Handshake Stewardship Pilot for Inpatient General Medicine Teams at an Academic Medical Center
Authors: Stromberg Joseph , Marx Ashley H , Mavrogiorgos Nikolaos
Published: January 2025

Background

Handshake stewardship is an approach to antimicrobial stewardship that relies on in-person discussions between ASP teams and primary inpatient teams. This model has been implemented in pediatric and intensive care settings, and outcomes have been described in observational studies. In November 2023, UNCMC implemented a handshake stewardship pilot with crossover design for select inpatient general medicine teams.

Methods

Three pairs of matched inpatient general medicine teams at UNCMC were selected, with one team from each pair included in a three month intervention period. After three months, the teams were switched. The intervention consisted of twice weekly meetings of ASP physician and/or pharmacist and primary teams, during which antimicrobial regimens of all patients were reviewed except those with an ID consult. The intervention was delivered via in-person meetings for the two pairs of teams located at UNCMC, and via teleconference for a pair of teams located on a separate campus. The remote teams withdrew from the pilot during the intervention period. Recommendations made were catalogued as iVents in the Epic EMR and electronic surveys were circulated to primary team providers.

Results

287 patients were reviewed across 95 meetings to date, yielding 73 recommendations. Common themes included narrowing coverage and transitioning to oral agents, although in some cases ASP teams recommended broadening therapy or a formal ID consult (Figure 1). 93% of recommendations were implemented. Survey data from 23 participants showed positive attitudes (Figure 2), with many valuing the opportunity to discuss patients that didn’t require a formal ID consult. Survey feedback from the virtual team included frustration with cessation of in-person ID consults at the site (unrelated to this pilot).

Conclusion

Handshake stewardship with in-person meetings has been well-received at UNCMC based on logged interventions and provider surveys, although the virtual component was unsuccessful. A planned crossover comparison between teams and paired controls will be helpful in assessing whether this has had an impact on antimicrobial use. Facilitating successful virtual handshake ASP will require improved coordination of meeting times and ensuring adequate access to in-person ID consults.

Disclosures

All Authors: No reported disclosures
P-1798. Acceptability and Feasibility of Inpatient Group-Level Feedback to Prescribers About Antibiotic Appropriateness for Community-Acquired Pneumonia: A Survey Study
Authors: Chiotos Kathleen , Dutcher Lauren , Lautenbach Ebbing , Neuhauser Melinda M , Hamilton Keith W , Grundmeier Robert , Gerber Jeffrey S , Szymczak Julia E
Published: January 2025

Background

Feedback on antibiotic prescribing is less commonly used in inpatient settings than outpatient. Our objective was to evaluate the acceptability and feasibility of group-level feedback on antibiotic appropriateness for community-acquired pneumonia (CAP) in two United States hospitals.

Methods

We conducted a cross-sectional survey of medicine and pediatrics prescribers who received monthly feedback on antibiotic selection and duration for patients with CAP shared in meetings and by email. The survey was administered from April 2023 to March 2024 and included the validated acceptability of intervention measure (AIM) and feasibility of intervention measure (FIM). Each consists of 4 items scored 1-5 and is reported as a mean total score (5-20), with higher scores indicating greater acceptability and feasibility. Data were analyzed using descriptive statistics.

Results

Of 289 eligible prescribers, 36 (12.5%) completed the survey: 28 (77.8%) physicians and 8 (22.2%) advanced practice providers. Engagement with reports was high: 30/35 (85.7%) looked at the reports, and 22/35 (62.8%) attended meetings discussing the report. The majority (25, 69.4%) liked the feedback reports, while 3 (8.3%) disliked the reports, 4 (11.1%) were unsure and 4 (11.1%) did not recall. The majority (n = 26; 76.5%) trusted the reports accurately captured performance. Thirty-four respondents (94.4%) believed the metrics were clinically meaningful, and the majority found them easy to understand: 34 (94.4%) understood choice, while 36 (100%) understood duration. Twenty respondents (55.6%) believed the reports changed how they prescribed, while 9 (25.0%) were unsure. Sixteen respondents (44.4%) believed the reports changed how their colleagues prescribe, while 17 (47.2%) were unsure. Mean totals (SD; range) for acceptability and feasibility were AIM, 17.2 (3.5; 8-20) and FIM, 17.7 (3.1; 8-20).

Conclusion

Although the low response rate may limit generalizability, inpatient clinicians perceived that group-level feedback on antibiotic appropriateness for inpatients with CAP was acceptable and feasible to implement. Clinicians who responded to the survey understood the metrics, found them clinically meaningful, and some felt they influenced prescribing.

Disclosures

All Authors: No reported disclosures
P-1811. Impact of Hemo-Alert Program on Appropriate Antimicrobial Therapy in Hospitalized Patients with Bacteremia: Results from a Quasi-experimental Study
Authors: Phuetphaichit Siwakan , Kamolvit Witchuda , Samanloh Surangkana , Rattanaumpawan Pinyo
Published: January 2025

Background

Hemo-Alert program is an antimicrobial stewardship strategy, designed to shorten the time to appropriate antimicrobial therapy in bacteremic patients.

Methods

Eligible subjects were all hospitalized patients with at least one positive hemoculture. The standard of care included a prompt notification of positive hemoculture via a phone call. However, the final identification and susceptibility results need to be individually retrieved. The Hemo-alert program included a prompt notification of final identification and susceptibility results via a direct SMS to physician and by placing results on patient’s medical chart. Appropriateness of antimicrobial therapy was determined by two independent infectious disease specialists. Antimicrobial therapy for colonization, too-broad or too-narrow regimen were considered inappropriate.

Results

There were 150 subjects in the pre-implementation group and 150 subjects in the post-implementation group. Approximately half of both groups (pre vs. post; p-value) were male (50.7% vs. 48.7%; p=0.73) with a comparable mean age (66.14±17.13 vs. 68.57±14.41; p=0.18). The three leading causative pathogens were Escherichia coli (24.0% vs. 26.7%; p=0.60), followed by Klebsiella pneumoniae (14.0% vs. 16.7%; p=0.52), and Staphylococcus aureus (9.3% vs. 10.7%; p=0.70). The proportion of appropriate antimicrobial therapy within the first 72 hours was significantly higher in the post-implementation group (22.7% vs. 34.0%; p=0.03). Good clinical response was significantly higher in the post-implementation group (74.0% vs. 85.3%; p=0.02). Furthermore, the 28-day mortality was comparable between the two groups (24.0% vs. 18.0%; p=0.20).

Conclusion

Our study confirmed the positive impact of the Hemo-Alert program on the appropriateness of antimicrobial therapy and treatment response among bacteremic patients.

Disclosures

All Authors: No reported disclosures
P-1817. Reducing The Use of Piperacillin/Tazobactam for Common Infections – A Danish Quality Improvement Study
Authors: Hagen Trine L
Published: January 2025

Background

During a 4-year period we noticed a doubling of Piperacillin/Tazobactam (PIT) consumption in our hospital, which was not supported by the local antibiotic guideline. This quality improvement study aimed to study prescription behavior. We hypothesized that an intervention might increase guideline adherence, thus decreasing the use of PIT as first line treatment for common infections.

Methods

Baseline data on PIT consumption were collected from April 2022 to March 2023 as defined daily doses (DDD)/100 bed-days. We collected baseline data on guideline adherence from January to March 2023 and performed an audit by reviewing patient charts. A multifaceted intervention was carried out from April 1st to December 31st, 2023, consisting of teaching sessions, feedback to prescribers, discouraging use of urinary dipsticks, creating pocket guidelines, and revision of the antibiotic guideline.

Inclusion criteria: Immuno-competent patients ≥ 18 years being prescribed PIT for community-acquired infections. Patients with immunosuppression or at risk of hospital-acquired infection were excluded.

We compared the number of PIT prescriptions between baseline and intervention by using unpaired t-tests. Change in adherence to guidelines was tested using the Chi-squared test.

The primary outcome was reduction in PIT use and secondary outcome was increased guideline adherence.

Results

Three-hundred and sixty-nine patients were included. During the intervention, we observed a 26% decrease in PIT use (DDD/100 bed days) and 41% reduction in the number prescribed PIT doses/week. Correctly prescribed PIT doses increased from 49.6% to 53.8% after the intervention. The correct prescriptions were differentiated between senior (75%), junior (57.7%) and locum doctors (43.5%).

Conclusion

By using a multifaceted intervention strategy to encourage prescribers to follow local guidelines, we observed a substantial reduction in the use of PIT for community-acquired infections in immuno-competent patients. Forming a formal antimicrobial stewardship team may play an important role in maintaining vigilance towards antibiotic prescribing behavior.

Disclosures

All Authors: No reported disclosures
P-1823. Development of a Nocardia Reporter Strain to Study Cell-type Specific Phagocytosis and Killing in vivo
Authors: Abers Michael S , Finin Peter M , Ma Li , Zelazny Adrian , Boshoff Helena , Barry Clifton E , Holland Steven M , Lionakis Michail S
Published: January 2025

Background

Nocardia infections are associated with substantial morbidity and mortality. Little is known about how the immune system defends against Nocardia.

Methods

Nocardia was transformed to contain a genomic copy of mScarlet. The cell wall was then labelled with AlexaFluor633 (AF633) to generate dually labelled (mScarlet+ AF633+) Nocardia. Cybb knockout (KO) mice (chronic granulomatous disease or CGD) and wildtype (WT) controls were inoculated with 5-10 million colony forming units (CFU) via oropharyngeal aspiration. High-dimensional flow cytometry (HDFC) and bacterial burden were determined in lung and bronchoalveolar lavage (BAL) fluid obtained 24 hours post-infection. Phagocytic index (PI) was defined as % of cells that are AF633+ cells. Killing capacity (KI) was defined as % of AF633+ cells that are mScarlet–.

Results

Live cultures of dually labelled Nocardia were positive for both mScarlet and AF633. mScarlet but not AF633 fluorescence decreased to undetectable levels upon killing of Nocardia. HDFC demonstrated that alveolar macrophages (AM), interstitial macrophages (IM), neutrophils, monocytes, and type 2 dendritic cells (cDC2) are the primary cell types that interact with Nocardia in vivo. PI was highest in AM and IM. PI was greater in cells from BAL versus lung (P< 0.01) while the opposite was true for other cell types. KI was lower in neutrophils versus other cell types (P< 0.05). Mortality and bacterial burden in lung were higher in CGD mice compared to WT controls (P< 0.01 for both comparisons). CGD mice demonstrated reduced PI in neutrophils, AM, IM (P< 0.05 for both). KI was impaired in AM and neutrophils.

Conclusion

Use of a dually labelled Nocardia reporter strain demonstrated cell-type specific defects in both phagocytosis and killing of Nocardia in CGD mice. This might explain the underlying predisposition to nocardiosis seen in humans with CGD. Ongoing studies aim to elucidate the molecular basis for the susceptibility to nocardiosis in humans and mice with CGD.

Disclosures

All Authors: No reported disclosures
P-1827. Novel Evaluation System for Aspergillus fumigatus Interactions with Human Cells via Combination of Imaging and Electrical Impedance
Authors: Kakuno Shigeki , Shibata Wataru , Umeyama Takashi , Miyazaki Yoshitsugu , Kakeya Hiroshi
Published: January 2025

Background

Aspergillus fumigatus is a major fungal pathogen causing pulmonary aspergillosis, an important disease associated with transplantation and immunosuppression. However, the interactions between A. fumigatus and human cells are not well understood. This study evaluated the interaction of A. fumigatus with THP-1 macrophages and A549 lung epithelial cells using fluorescence imaging and electrical impedance measurements to monitor fungal growth and cellular damage continuously.Figure 1.Schematic diagram of the relationship between electrical impedance and cell damage

Methods

The experimental setup used xCELLigence eSight (Agilent) and a specialized 96-well plate with electrodes at the bottom to measure impedance changes as cells adhered or detached (Figure 1). THP-1 and A549 cells were cultured, then infected with fluorescent A. fumigatus conidia. In addition, antifungal drugs (micafungin, caspofungin, voriconazole, isavuconazole, amphotericin B) were added to this experimental system at broth microdilution method and tested.Figure 2.Macrophage and A. fumigatus (MOI 4.0) in relation to each antifungal agentA:Voriconazole(VRCZ), B : Amphotericin B (AMPH-B)

Results

Results showed A. fumigatus filament growth leading to decreased impedance indicative of cell damage in both cell types, with faster damage at higher conidial loads. Fluorescence showed echinocandins inhibited hyphal growth but did not prevent impedance drops. Voriconazole and isavuconazole prevented impedance drops at clinically relevant concentrations (Figure 2A). Amphotericin B caused rapid impedance drops at high doses, suggesting direct cytotoxicity (Figure 2B).

Conclusion

A549 epithelial cells survived longer than macrophages, suggesting they play a defensive role against A. fumigatus. Impedance changes correlated with visual antifungal effects for azoles and amphotericin B but not echinocandins. This system enables evaluating fungal-host interactions using different cell types and fungi. Combining impedance with fluorescence imaging provides a comprehensive and objective assessment of antifungal activity and cellular responses.

Disclosures

Hiroshi Kakeya, MD, PhD, Asahikasei Phrma: Honoraria|GSK: Honoraria|MSD: Honoraria|Pfizer: Honoraria|Shionogi: Honoraria|Sumitomo Parma: Honoraria
P-1833. Acute Virulence Expression and Evolution of Artificial Airway Adapted Pseudomonas aeruginosa
Authors: Rapsinski Glenn J , Cooper Vaughn , Kozemchok Anna
Published: January 2025

Background

Mechanical ventilation is life-saving and may be lifelong in medically complex children with tracheostomy tubes (TT). Ventilator-associated infections (VAI), a common complication of mechanical ventilation, result in an estimated $1.25 billion per year of healthcare costs. Pseudomonas aeruginosa (Pa) frequently colonizes TT and endotracheal tubes and is a leading cause of VAI. Despite the importance of VAI, little is known about how Pa establishes colonization, limiting our ability to improve management. We hypothesize that Pa adaptively evolves to reduce its potential for acute virulence to facilitate colonization.

Methods

Convenience samples of Pa isolates from patients requiring endotracheal tubes or TT were collected from the UPMC Children’s Hospital of Pittsburgh microbiology lab. Isolates were screened for virulence factors including proteases, rhamnolipids, twitching motility, lysis and sheen, amino acid auxotrophy, and mucoid colony morphology. Isolate infectivity was tested on a in vitro primary human cell epithelial model. DNA was extracted from longitudinal isolates for whole genome sequencing.

Results

One hundred thirty-five isolates from 124 unique patients were screened for acute and chronic virulence phenotypes in a cross-sectional study. Low protease production, rhamnolipid production, and reduced twitching motility were more frequently present in respiratory isolates compared to skin and soft tissue infection (SSTI) isolates. Lysis and sheen were present in approximately one-third of respiratory isolates, similar to SSTI isolates. In longitudinal specimens from 23 patients, 95% of patients maintained their Pa genotype over time and representation from all three clades (PAO1, PA14, and PA7) of Pa were detected, with the PAO1 clade containing most isolates. Whole genome sequencing revealed mutations in global virulence regulators. Respiratory isolates had reduced infectious capabilities in an epithelial cell infection model.

Conclusion

These data suggest that isolates from mechanically ventilated patients are diverse between patients, maintained within a given patient over time, and have lower virulence expression than Pa isolates from other sites.

Disclosures

All Authors: No reported disclosures
P-1834. An Enteric Bacterial Infection Disrupts Brain Homeostasis and Induces Chronic Neuroinflammation by Breaching the Gut-Brain Axis in 3xTg-AD Transgenic Mice
Authors: Park Gwoncheol , Kadyan Saurabh , Hochuli Nathaniel , Nagpal Ravinder
Published: January 2025

Background

In previous studies, we found that an enteric infection caused by Klebsiella pneumoniae (Kpn) not only disturbs the balance of gut microbiome but also translocates to the brain, leading to inflammation and impairments in neurobehavior.

Methods

Triple-transgenic (3xTg-AD) mice were split into three categories: those infected with Kpn (Kpn group), a subset of Kpn mice treated with antibiotics to induce dysbiosis (Kpn+Ab group), and a control group receiving no treatment (TgCt group). Metabolomic and inflammation profiles of gut, serum, and brain samples collected six weeks after infection were evaluated using NMR-based metabolomic analysis and transcriptomics analysis conducted with the NanoString nCounter system.

Results

Significant shifts were observed in gut metabolites, while serum metabolites showed minor changes, particularly with an upward trend in branched-chain amino acids in Kpn-treated mice. In the gut, an inflammatory response was evident, characterized by the increased expression of inflammatory genes such as Cd14, Ptgs2, and Il6st. Transcriptomic analysis of the brain revealed disrupted homeostasis, with heightened neuropathological processes, including oxidative stress and cytokines, and reduced structural and anti-pathological functions, particularly notable in the Kpn+Ab group. Specifically, genes associated with inflammation and neurodegeneration, such as Il1r1 and Ptgs2, were upregulated in the Kpn+Ab group, suggesting a chronic inflammatory state potentially worsening neuropathology. Indeed, elevated levels of total tau were observed in the brains of Kpn+Ab mice. Furthermore, dysregulation in redox signaling linked to the malate-aspartate shuttle was evident, as indicated by increased levels of aspartate and N-acetylaspartate alongside decreased serine concentrations.

Conclusion

The results indicate that Kpn enteric infection leads to persistent inflammation in both the gut and the brain, disrupting essential pathways for brain homeostasis. This disruption may contribute to the buildup of AD pathologies and impairments in neurobehavioral function.

Disclosures

All Authors: No reported disclosures
P-1852. Investigating the infant gut microbiome in relation to R21/Matrix-M™ vaccine immunogenicity and efficacy
Authors: Datoo Mehreen S , Yen Sandi , Edwards Nick , Traore Ousmane , Some Athanase , Natama Hamtandi M , Johnson Jethro , Hill Adrian V S , Tinto Halidou
Published: January 2025

Background

R21/Matrix-M™ malaria vaccine was recently licensed in young children following good vaccine efficacy and induction of high titre antibody responses to the central repeat (NANP) of the P. falciparum circumsporozoite protein. Variability in NANP responses and efficacy was noted in the populations assessed and according to age.

Links between the gut microbiome and the immune system mean early life gut microbiome is an important consideration when understanding vaccine responses. We investigated the relationship of these and participant factors with the gut microbiome in Burkinabe infants in the R21/Matrix-M™ phase IIb trial.

Methods

A phase IIb double-blind, randomised controlled trial assessing safety, immunogenicity and efficacy of R21/Matrix-M™ in 5-17 month olds took place in Nanoro, Burkina Faso from 2019 to 2023. Rectal swabs were collected at baseline and a year later, for both malaria vaccine (n=223) and control participants (n=77). Participant factors (i.e. age, gender, feeding, number of siblings, and Z-score), malaria episodes, and anti-NANP antibody responses were measured. Microbiome was assessed using 16S rRNA gene sequencing. Microbiome alpha- and beta- diversity were characterized, and microbial abundances were analysed using univariate and multivariate models.

Results

Participant microbiomes showed two discernible compositional phenotypes at baseline and follow-up timepoints. The microbiome of majority of participants (93%) were predominantly Firmicutes (39%) and Bacteroidetes (37%) and low in Proteobacteria (13%). However, a subset of participants (7%) had microbiomes that were mainly Proteobacteria (63%). Within-individual alpha-diversity significantly varied with age, but not other participant factors. Relative abundances of certain bacteria were associated with age. Microbial abundances will be analysed and presented against antibody responses, as well as the number of clinical malaria episodes in the first two years.

Conclusion

We describe the microbiome of Burkinabe infants within the context of R21/Matrix-M™ malaria vaccination. This dataset provides insight into a previously underrepresented population during early life, which is a key window for immunological and microbiome development.

Disclosures

Adrian V S Hill, PhD, Serum Institute of India: Grant/Research Support|Serum Institute of India: I am named as a co-inventor on patent applications related to R21
P-1854. Children with Congenital Heart Disease and PICS (Persistent Inflammation, Immunosuppression, and Catabolism Syndrome) Demonstrate Both Pro- and Anti-Inflammatory Cytokine Profiles
Authors: Beneschott Natalya M , Yoder Sandy M , Brady Eric , Williams Amanda K , Buddy Creech C
Published: January 2025

Background

Patients with chronic critical illness have variable recovery from acute events, such as surgery or sepsis, and experience dysregulated inflammation, blunted immune responses, and recurrent infections. The development of persistent inflammation, immunosuppression, and catabolism syndrome (PICS) increases the risk of healthcare associated infections, poor wound healing, and indolent organ failure. The pathophysiology of PICS has not been characterized in critically ill pediatric populations, particularly those with congenital heart disease (CHD).

Methods

The PICASSO study is an ongoing, observational cohort study of immunologic dysregulation in children with CHD who undergo cardiopulmonary bypass for surgical repair. Three groups were defined in this preliminary analysis. Children with uncomplicated post-operative courses served as control participants. Group 1 includes children who underwent CHD repair and were anticipated to have prolonged recovery (n=6), and Group 2 includes children with culture-confirmed, post-operative infection (n=2). PICS was defined as having at least 2 of the following criteria: lymphocyte count < 1500 cells/mL, CRP > 10 mg/dL, and albumin < 3 mg/dL. Blood samples were collected weekly for up to one month in Groups 1 and 2; controls had one sample collected at discharge. Plasma cytokines were measured using a 25-plex panel (Human Immunotherapy Fixed Panel, Luminex®).

Results

Thirty-four samples from 15 patients were analyzed. Plasma cytokines analysis across groups is shown in Figure 1. While come cytokines were more abundant in Group 1 compared to Group 2 and controls (e.g., IL-9 and IP-10), no significant differences were observed. Next, we compared cytokine levels in participants with (n=4) and without PICS (n=11). Both IL-1Ra and IP-10 were increased among children with PICS (p=0.007 and p=0.012, respectively).

Conclusion

In a preliminary analysis of the first 15 patients in the cohort, children with CHD and PICS demonstrate increased plasma levels of both pro-inflammatory (IP-10) and anti-inflammatory (IL-1Ra) cytokines that mirror the clinical phenotype of PICS. Ongoing analysis includes immunophenotyping and immunometabolic profiling of peripheral blood mononuclear cells.

Disclosures

C. Buddy Creech, MD, MPH, CommenseBio: Advisor/Consultant|GSK: Advisor/Consultant|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant
P-1856. Difference in T-cell responses to influenza internal proteins according to HLA type
Authors: Cho Yoon Kyung , Kang Hyun Mi , Kang Kyu Ri , Kang Jin Han
Published: January 2025

Background

Gene variants in HLA are known to influence the degree of immune responses to influenza vaccines leading to varying immunogenicity among different populations. Universal influenza vaccines that contain internal proteins which elicit immunogenicity to various influenza strains are under development, and in order to provide the best protection for vaccine recipients, this study aimed to investigate difference in T-cell responses to influenza internal proteins according to HLA type.

Methods

In the murine challenge model, HLA-A*02:01 and HLA-A*11:01 transgenic mice were immunized with a seasonal influenza vaccine and then injected intramuscularly with two doses of one the following internal proteins: nucleoprotein (NP), nonstructural protein 1 (NS1), nonstructural protein 2 (NS2), matrix protein 1 (M1), matrix protein 2 (M2), and polymerase acidic protein (PA)). The mice were then challenged with A/Cambodia/e0826360/2020 (H3N2) virus.

Results

The NS1NS2 protein showed 0% survival in the A*11:01 type but a high immune response in the HLA-A*02:01 type. In the chemokine/cytokine analyses, the PA_A2.1 group followed by NS1NS2_A2.1, M1M2_A2.1, and M1M2_A11.1 showed the highest positive scores for cytokines MIP-1a, RANTES, IFN-γ, KC, and MCP-1. Furthermore, the PA_A11.1 group showed statistically valid IFN-γ and CD8+ T cell percentages in the lungs, whereas in the spleen, the PA_A2.1 group showed high percentages.

Conclusion

Internal proteins that showed adequate immune responses in HLA-A*02:01 type was NS1NS2, and M1M2 showed adequate responses in both HLA-A*02:01 and HLA-A*11:01 type.

Disclosures

All Authors: No reported disclosures
P-1889. Penicillin Allergy and Its Impact on Clinical Outcomes in OPAT Patients: A Retrospective Cohort Study
Authors: Jafar Maher , McSweeney Kristen , Liu Fang-yu , Erdil Rachel , Vindenes Tine , Doron Shira , Foong Kap Sum
Published: January 2025

Background

10% of the U.S. population is labeled as allergic to penicillin, with higher rates among women and older adults. These individuals often experience worse clinical outcomes. Despite the extensive use of Outpatient Parenteral Antimicrobial Therapy (OPAT), data on the prevalence of penicillin allergy in this population and its impact on clinical outcomes are scarce. Our study aims to address this knowledge gap by assessing rates of penicillin allergy in OPAT patients and its associations with OPAT-related clinical outcomes.

Table 1

Comparison of characteristics and complications among OPAT patients considering penicillin allergy status

Methods

We conducted a retrospective cohort study at Tufts Medical Center, including all patients aged ≥18 years discharged on OPAT between April 2022 and October 2022. Data on demographics, penicillin allergy status, complications, and outcomes were extracted through chart reviews. The primary outcomes were: (1) rates of penicillin allergy, and (2) association between penicillin allergy and OPAT complication rate (line- or antibiotic-related), OPAT extension, 30-day ED visits, and readmission rates. We used a multivariable logistic regression model to examine these associations, adjusting for age, sex, race, ethnicity, and Charlson comorbidity index. Two-sided p values were considered statistically significant at .05.

Table 2

Association of documented penicillin allergy and complications related to OPAT

Results

A total of 231 patients received OPAT; 39 (17.9%) had documented penicillin allergy. Females and white patients had higher rates of penicillin allergy compared to their counterparts; 24.4% vs 12.4% and 19.1% vs 9.4%, respectively (Table 1). In the final multivariable logistic regression model, penicillin allergy status was not associated with OPAT extension (adjusted odds ratios[aOR] 0.83; 95% confidence interval[CI] 0.36-1.89), OPAT-related complications (aOR 1.04; 95%CI 0.42-2.57), 30-day ED visits (aOR 0.38, 95%CI 0.05-3.13), and 30-day readmissions (aOR 0.24; 95%CI 0.03-1.87) (Table 2).

Conclusion

Our findings suggest that the rates of PCN allergy were higher than in hospital settings (∼15%), but these do not significantly influence the OPAT clinical outcomes. However, neither group met the required 248 subjects to reliably detect a 10% increase in complication rates, limiting the significance of the findings. Further research with a larger sample size is needed to validate these findings.

Disclosures

Shira Doron, MD, Medtronic: Expert Testimony|Sunovion: Advisor/Consultant|Vertex: Speaker
P-1890. Implementation and outcomes of a fully remote tele-ID and tele-OPAT program at a regional medical center
Authors: Davis Matthew R , Shah Neel , Maurer Stephen M , Neils Megan Gray , Khan Nazia
Published: January 2025

Background

Infectious diseases (ID) consult services and outpatient parenteral antimicrobial therapy (OPAT) programs have traditionally been restricted to well-equipped academic medical centers. However, the integration of telehealth technologies into ID specialty care now allows for the expansion of ID expertise to underserved medical communities, including non-academic medical centers, and community and rural hospitals. Our initiative pioneered a comprehensive tele-ID service, encompassing both inpatient consultations and a tele-OPAT service for post-discharge management. Herein, we describe the program structure and outcomes from the first year of our integrated tele-ID and tele-OPAT program, implemented at a 144-bed community hospital in Vermont.

Methods

The program featured an inpatient tele-ID consult service supported by local nurse tele-presenters who would facilitate physical exams for a remote ID physician using videoconferencing technology. Patients deemed appropriate for OPAT were referred to the remote tele-OPAT team which consisted of a nurse coordinator, an ID pharmacist, and the current ID physician attending the inpatient service. The nurse coordinator's responsibilities included communicating with the local case management team, home health, and post-discharge facilities to ensure orders were placed, and communications were triaged for the tele-OPAT team. The ID pharmacist reviewed OPAT regimens for appropriateness and monitored outpatient labs for safety and dose adjustments. Tele-OPAT patients were seen locally by the ID physician in a pre-existing clinic with the assistance of a nurse tele-presenter.

Results

Ninety patients were enrolled in the tele-OPAT program in the first twelve months. Of these, 62 (68.9%) completed therapy without adverse event (AE) or 30-day readmission. 30-day readmission occurred in 14 patients (15.6%) and 20 patients (22.2%) had a documented AE during therapy, with 10 patients (11.1%) experiencing line-related issues.

Conclusion

Our telehealth initiative successfully expanded ID expertise to an underserved community hospital, with a majority of patients completing therapy without AEs or readmissions, demonstrating the efficacy and safety of remote ID consultations and tele-OPAT services.

Disclosures

All Authors: No reported disclosures
P-1897. Quality Improvement Initiative: Quantifying and Reducing Anti-infective Pharmaceutical Waste at a Tertiary Care Pediatric Hospital
Authors: Doshi Shreya M , Esadah Esther , Yoko-Uzomah Johnny , Howard Erica , Shapiro Craig A , Dassner Aimee
Published: January 2025

Background

Pediatric hospitals have reported thousands of doses and dollars’ worth of waste from anti-infective drugs (anti-microbial, anti-fungal, anti-viral) every year. This has an environmental impact due to pharmaceutical waste incineration resulting in greenhouse gas emissions and contributes to drug shortages. Anti-infective drugs are prepared in advance for routine administration. When an order is modified or cancelled it cannot be used for another patient and gets discarded. The goal of this study was to calculate the anti-infective waste at our tertiary care pediatric hospital, to understand the key drivers and design education and QI interventions to reduce wasted doses.Figure 1:Fish bone diagram highlighting the reasons for waste

Methods

Pharmacy data for waste reviewed (06/2022-03/2024). The reasons for wasted doses determined by point prevalence review of 75 charts on a single hospital day. PDSA 1 included creation of additional batch processing timings. PDSA 2 included education of providers on teams with high amounts of wasted orders held in 02/2024. Pharmacy leaders reminded teams daily on rounds about stop dates.Figure 2:Key driver diagram

Results

Total waste - 79,525 doses at a cost of $407,072 were wasted due to order changes in 2023. Top wasted anti-infectives include ampicillin-sulbactam, cefepime, cefazolin, ceftriaxone, vancomycin, and piperacillin-tazobactam.

PDSA 1 (Addition of batches for batch processing timing) & PDSA 2 (Provider education and awareness) showed significant reduction in waste per 1,000 doses as highlighted in figure 4.Figure 3:Reasons for waste on chart review of 75 patients

Conclusion

Education around medication waste was created through this QI Initiative and was well received. Using the data collected, IT and pharmacy workflow interventions are being developed and will be evaluated including standardized dosing, 48 hour hard-stops for sepsis rule outs.A key intervention we are currently working on (PDSA 3) is to reduce the time gap between discharge of the patient and when the orders are discontinued on the EMR (identified during chart review). For our hospital this time gap was found to be 6.5 hours which results in large amounts of waste. Calculating environmental impact & Green House Gas emissions from the pharmaceutical waste (by measuring weight in kg) is another impact assessment metric we are working on.Figure 4:Run-chart of baseline waste data with the two PDSA cyclesA decrease in the center line was observed following PDSA 1 that was sustained for greater than 6 months

Disclosures

All Authors: No reported disclosures
P-1912. Characteristics and Outcomes of Matched Vaccinated and Unvaccinated Patients Hospitalized for Covid-19 in 27 Hospitals During Brazil's Delta and Omicon Waves
Authors: Moraes Eduardo V , Pires Magda Carvalho , Costa Amanda A A , Tupinambás Unaí , Marcolino Milena S
Published: January 2025

Background

Brazil faced significant challenges during the COVID-19 pandemic, emerging as one of the most affected countries globally in the number of cases and deaths. In January 2021, the country began the national vaccination campaign against COVID-19. Currently, about 80.2% of Brazilians over six months of age are fully vaccinated.

Few population-based studies have compared clinical characteristics and outcomes among patients hospitalized for COVID-19 concerning vaccination status. This knowledge gap was even greater when an attempt was made to match vaccinated versus unvaccinated individuals to control for confounders. Therefore, this study aimed to compare the clinical characteristics and outcomes of matched vaccinated and unvaccinated COVID-19 in hospital patients.

Flowchart of COVID-19 patients included in the study.

Methods

This retrospective multicenter cohort study included adult COVID-19 patients, with a laboratory-confirmed diagnosis, from 27 hospitals, admitted from March/2021 to August/2022. Clinical characteristics, vaccination status, and outcomes were collected from medical records. Vaccinated and unvaccinated patients were compared in a matched analysis, using the propensity score model that included age, sex, hospital, and comorbidities (hypertension, diabetes mellitus, obesity [body mass index > 30kg/m2], heart failure, and chronic kidney disease).

Results

From 3,188 patients, 1,963 (61.6%) were unvaccinated and 1,225 (38.4%) fully vaccinated. Among these, we matched 771 vaccinated with 771 unvaccinated. Vaccinated had lower rates of mortality (17.6% vs. 29.7%), invasive mechanical ventilation (IMV-17.5% vs. 33.0%), non-invasive mechanical ventilation (NIMV- 10.0% vs. 20.2%), intensive care unit admission (ICU- 29.8% vs. 44.0%) vasoactive drugs use (20.5% vs. 30.9%), dialysis (8.0% vs. 13.7%), p < 0.001 for all, and thrombosis (3.7% vs. 7.5% p=0.002).

Conclusion

This study suggests considerable benefits of vaccination for patients hospitalized with COVID-19. Fully vaccinated patients experienced lower mortality rates and lower severity disease with fewer ICU admissions, and shorter hospital lengths of stay. These findings confirm that prior vaccination reduces the risk of death and alters the disease trajectory in hospital settings.

Disclosures

All Authors: No reported disclosures
P-1922. Liver Function Test Abnormalities near Admission Predict Mortality for Patients with COVID-19: A Single-Center Study
Authors: Hirashima Lucia Cabrejos , Naiman Nicole , Jain Mamta K
Published: January 2025

Background

Early data from the COVID-19 pandemic shows patients commonly present with abnormal liver function tests (LFTs) upon admission. This phenomenon is multifactorial and is associated with increased in-hospital mortality and disease severity. There is limited data describing COVID-19 LFT derangements in the United States, and few comparisons of LFT derangements between variants.

Methods

This is a retrospective cohort study that includes non-pregnant adults admitted at Parkland Health and Hospital System from 03/01/2020 to 12/31/2021 with laboratory confirmed or ICD-10-documented COVID-19. We examine the association of LFT derangement (within 24 hours of admission) and mortality using multivariate logistic regression adjusting for baseline demographics, comorbidities, oxygen requirement, and lab values previously reported to be associated with COVID-19 mortality. We also examine this association after excluding patients with prior liver disease, viral hepatitis, and use of remdesivir prior to measuring LFTs. Finally, we compare LFT derangement patterns between variants (defined by date).Table 2.Multivariate logistic regression of liver function tests as predictors for mortality

Results

In our cohort of 3587 patients, over 93% had an available LFT. Abnormalities of aspartate aminotransferase (AST) and alkaline phosphatase (AP) are more prevalent in the deceased group (Table 1). Multivariate logistic regression shows that severely elevated AST and abnormal AP are consistently associated with mortality, while severely elevated alanine aminotransferase (ALT) is associated with mortality only in patients with no prior liver disease, viral hepatitis or remdesivir use (Table 2). Our analysis reveals significant differences in the frequency of AST and ALT abnormalities based on the variant, with the delta variant showing the highest occurrence of abnormalities. However, we do not find a significant difference in mortality between variants (Table 3).Table 3.Distribution of liver function tests and mortality rate by SARS-CoV-2 variant

Conclusion

This study highlights the consistent association between elevated LFTs at admission and mortality in COVID-19 patients, suggesting close monitoring by clinicians. It also demonstrates that COVID-19 is a systemic illness. Further studies are warranted to elucidate variant-specific differences in the association between LFT derangements and mortality.

Disclosures

Mamta K. Jain, MD, MPH, Abbvie: Grant/Research Support|Gilead Sciences: Grant/Research Support|Laurent: Grant/Research Support
P-1926. Once Is Enough, Two Is Too Much: Unraveling Predictors of COVID-19 Readmission among Previously Hospitalized Patients
Authors: Colaneri Marta , Canuti Marta , Torrigiani Ginevra , Dall’Olio Lucia , Bobbio Chiara , Baldi Sante Leandro , Nobili Alessandro , Puoti Massimo , Marchetti Giulia , Latronico Nicola , Plebani Pierluigi , Raviglione Mario , Gori Andrea , Ojeda Fernandez Maria Luisa , Baviera Marta , Tettamanti Mauro , Leoni Olivia , Fortino Ida , Bandera Alessandra
Published: January 2025

Background

While risk factors for COVID-19 hospitalization are well characterized, only a few studies investigated those associated with hospital re-admission after SARS-CoV-2 re-infections, since most are focused-on re-admission because of all-causes. Our aim was to identify co-morbidities and other risk factors associated with a second COVID-19 hospitalization.

Study flowchart and timeline

Methods

Administrative database from the Lombardy Welfare Directorate was used to detect patients hospitalized for COVID-19 for a first time between 1st Feb 2020 to 31st Aug 2021. Information on demographic variables, hospital records and drug prescriptions were collected. The population comprised the re-hospitalized individuals, who were readmitted for COVID-19 at least 3 months after their initial hospital admission, likely because of a different SARS-CoV-2 infection and the non-re-hospitalized subjects. Follow-up observation lasted until the re-hospitalization, death or the end of study period. Adjusted hazard ratio (CI, 95%) was performed to assess the association between risk factors and re-hospitalization with a competing risk analysis.

Multivariable analysis with competing risk, where death after 3 months is the competing risk for re-hospitalization due to COVID-19.

Results

From a total of 98,369 patients hospitalized for COVID-19, 25,776 (26.2%) died within three months and 610 (0.6%) were re-hospitalized for a likely new SARS-CoV-2 infection (Figure 1). Re-hospitalized patients were mostly male (61.3%) and were 72.2 years on average.

The strongest risks for re-hospitalization in patients with a new episode of COVID-19 were kidney and liver diseases. However, a significant association for this risk was also observed for age, males, immune suppression, cerebro-vascular and cardio-vascular diseases, lung disease, diabetes, and some medications (Table 1).

Conclusion

We demonstrated that vulnerability due to multimorbidity and chronic conditions, such as kidney and liver disfunction, may diminish the ability to withstand physiological challenges, elevating the risk of re-hospitalization. The fact that the elderly, immune suppressed individuals, or those with chronic conditions may survive an initial hospitalization does not safeguard them from further admissions. We emphasized the importance of targeted interventions and heightened clinical vigilance for these high-risk patient populations.

Disclosures

All Authors: No reported disclosures
P-1929. Impact of the COVID-19 Pandemic on the Risk Factors and Outcomes Associated with Candidemia
Authors: Endashaw Melat , Dykes Austin , Clark Rachael , Warrayat Laila , Deng Shiyuan , Chen Xianyan , Henao Martínez Andrés F , Chastain Daniel B
Published: January 2025

Background

Cases of candidemia surged during the COVID-19 pandemic, possibly due to the intensive treatments used in critically ill patients. This study aims to explore the impact of the pandemic on risk factors and clinical outcomes associated with candidemia.

Methods

We retrospectively analyzed patients ≥ 18 years diagnosed with candidemia at a single facility in Albany, Georgia, between January 2017 and May 2023. Patients were categorized into three groups based on their COVID-19 status and admission date (January 21, 2020, marking the first US case): 1) pre-pandemic (before January 21, 2020), 2) pandemic with COVID-19 (after January 21, 2020), and 3) pandemic without COVID-19 (after January 21, 2020). We compared risk factors for candidemia and in-hospital mortality across these groups.

Results

A total of 89 patients were included, with 44% pre-pandemic and 56% during the pandemic (half with COVID-19) (Table 1). Baseline characteristics were similar, except for a higher median number of comorbidities in the pre-pandemic group (p=0.008). Notably, the COVID-19 group had a significantly higher proportion of patients with no comorbidities (12%) compared to the pre-pandemic (0%) and pandemic without COVID-19 (4%) groups (p=0.01). Patients with COVID-19 were predominantly diagnosed with candidemia in the ICU (92%) compared to pre-pandemic (49%) and pandemic without COVID-19 (44%) groups (p< 0.001). Additionally, mechanical ventilation and vascular catheters were more frequent in the COVID-19 group (88% and 96%, respectively) compared to the pre-pandemic (31% and 62%) and pandemic without COVID-19 (40% and 68%) groups (p< 0.001 for both) (Table 2). While immunosuppressive medications were uncommon, glucocorticoid use was significantly higher in the COVID-19 group (76%) compared to the pre-pandemic (18%) and pandemic without COVID-19 (24%) groups (p=0.008). In-hospital mortality was highest among patients with COVID-19 (76%) compared to patients before the pandemic (44%) and those without COVID-19 during the pandemic (32%) (p< 0.005).

Conclusion

Patients with COVID-19 displayed a higher prevalence of candidemia risk factors and significantly worse clinical outcomes, including higher in-hospital mortality, compared to the other groups.

Disclosures

All Authors: No reported disclosures