bluuebunny/crossref_metadata_2025_split huggingface dataset:
160. RSV Pre-F IgG levels in pediatric hematopoietic stem cell transplant (HCT) and leukemia/lymphoma patients
Authors: Murray Alastair , Clark Erica , Chu Helen Y , Englund Janet A 
Published: January 2025

Abstract

Background
Hematopoietic stem cell transplant (HCT) patients are at increased risk of morbidity from RSV infection. Vaccines and monoclonal antibodies directed against the RSV pre-fusion surface protein are now licensed for protection of infants against RSV. Analysis of RSV-specific antibody seroprevalence in pediatric HCT and oncology patients will help identify those who may benefit from receipt of an RSV monoclonal antibody, such as nirsevimab, for protection against severe disease.Table 1.Demographic information by patient cohort

Methods
This prospective study collected deidentified serum samples from pediatric (age 0-24 years) HCT patients (n = 10), pediatric leukemia and lymphoma (LL) patients (without blood transfusion &lt; 60 days) (n = 10) and general pediatric patients without immunocompromising conditions or respiratory illness evaluated in the emergency room (n = 10) in Seattle, WA, USA. Samples were collected at time of transplant between February-April 2024 and concurrently collected from the two other cohorts. Samples were tested for quantitative RSV pre-fusion IgG concentration using an ELISA assay. One LL patient received nirsevimab (excluded from analysis). Values were natural log-transformed before all statistical processes and comparisons were performed by ANOVA testing.Figure 1.RSV Pre-fusion IgG concentration by patient cohort

Results
Mean age was similar among HCT and general pediatrics cohorts (12.2 years versus 12.8) and slightly younger among the LL cohort (8.8) (ANOVA, p = 0.38) (Table 1). Mean log antibody concentration was similar across all three cohorts (BMT: 10.3 AU/mL, LL: 9.9, general pediatric: 10.5), (ANOVA, p = 0.62) (Figure 1). Mean log antibody concentration was also similar by age group (0-5 years: 10.1 AU/mL, 6-12 years: 10.2, 13-24 years: 10.4), (ANOVA, p = 0.33) (Figure 2).Figure 2.RSV Pre-fusion IgG concentration by patient age

Conclusion
RSV pre-fusion IgG concentration was comparable across cohorts of pediatric HCT patients, leukemia/lymphoma and general pediatric patients. Further study enrollment is ongoing to capture changes in antibody level over the course of a respiratory viral season, along with assessment of RSV neutralizing antibody, which may provide a more robust correlate of protection. This information may inform the need for further clinical trial prophylaxis studies, given the vulnerability to RSV disease in these patient populations.

Disclosures
Helen Y. Chu, MD, MPH, Abbvie: Advisor/Consultant|Merck: Advisor/Consultant|Vir: Advisor/Consultant Janet A. Englund, MD, Abbvie: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Advisor/Consultant|Pfizer: Board Member|Pfizer: Grant/Research Support|Pfizer: Speaker at meeting|SanofiPasteur: Advisor/Consultant|Shinogi: Advisor/Consultant
210. Implementation of a Pharmacist Driven Beta-lactam Therapeutic Drug Monitoring Program with Daily Result Reporting: Initial Experiences and Challenges Faced
Authors: Pan Samantha , Weslander Erin , Fierak Sarah , Galvin Shannon , Rhodes Nathaniel J 
Published: January 2025

Abstract

Background
Beta-lactam (BL) antibiotics are a cornerstone of treatment for patients with serious infections. Individualized BL dosing using therapeutic drug monitoring (TDM) is an emerging approach to address variability in BL exposure that adversely impacts PK/PD; however, challenges can emerge when implementing TDM programs in the real-world. We sought to characterize the implementation of a BL TDM program by describing initial successes and challenges.

Methods
In September 2023, we implemented a front-line pharmacist driven BL TDM clinical protocol (Figure 1) with daily result reporting for the following BLs: cefepime (FEP), meropenem (MEM), and piperacillin-tazobactam (TZP). Patients with FEP, MEM, and TZP plasma TDM data analyzed between September 26th, 2023 and March 31st, 2024 were included. TDM results were interpreted using Bayesian analysis (InsightRX). For each TDM event, we characterized ordering provider specialty, whether or not TDM was performed per protocol, whether or not changes were made in response to TDM results, Bayesian model fitness, treatment indication, culture information, and PK/PD target attainment [including predicted steady state trough concentration (Ctrss) and fT&gt; 1xMIC and fT&gt; 4xMIC].

Results
Eighty-two BL TDM levels were obtained in 47 patients. FEP was most frequently monitored (70.7%). Model fit was good or intermediate in &gt; 95% of cases (Table 1). The most common treatment indications were HAP/VAP (n=12, 25.5%), surgical prophylaxis (n=6, 12.8%), bone/joint (n=6, 12.8%), and CNS infection (n=6, 12.8%) (Table 2). Dose adjustments were made in 34% (n=16) of patients. In 57.4% of patients the level order or dose-adjustment deviated from recommended protocols. Targets of 100% fT&gt; MIC and 100% fT&gt; 4xMIC were achieved in 91.5% and 61.7% of patients, respectively (Table 3). Ctrss was above goal in 21% of patients.

Conclusion
We found that &gt; 90% of patients undergoing BL TDM achieved 100% fT&gt; MIC, whereas nearly 40% failed to achieve 100% fT&gt; 4xMIC at baseline, and &gt; 20% had a Ctrss exceeding safety goals. BL TDM resulted in dose or agent change over 60% of the time, but protocol deviations in dose adjustment were common. The frequency of interventions observed underscores the potential clinical impact of BL TDM on a broader scale when daily reporting is available.

Disclosures
Nathaniel J. Rhodes, PharmD MS, Apothecademy, LLC: Advisor/Consultant
297. Comparative In Vitro Microbiologic Activity of Two Antimicrobial Intravenous Connectors
Authors: Truong Y Lan , Rosenblatt Joel , Gerges Bahgat Z , Jiang Ying , Raad Issam I 
Published: January 2025

Abstract

Background
Intravenous (IV) connectors are ubiquitous access junctions in vascular access circuits. In accessing IV connectors (IVCs) for infusions, they become vulnerable to microbial contamination and colonization. Antimicrobial IVCs are treated with antimicrobial agents to resist microbial colonization. In this in vitro study, we compared the microbiologic efficacy of IVCs treated with silver and with a novel coating of Minocycline (M), Rifampin (R) and Chlorhexidine (C).
MRC vs Silver Antimicrobial IV Connectors: 7-Day Microbiologic Challenge Test
Colonization of MRSA, P. aeruginosa, and C. albicans on silver and MRC IVCs following 7 days of elution. Non-antimicrobial IVCs were used as positive controls. Data is presented as the median CFU/connector from six replicates; bars indicate the range.

Methods
M, R, and C were spray coated onto IVCs in sequential laminate layers to produce MRC IVCs. Commercially available silver IVCs were purchased (Antimicrobial Microclave Connector, ICU Medical Inc., San Clemente, CA). MRC and silver IVCs were immersed separately in tubes filled with 50% serum + 50% saline to simulate elution of the coatings. After 7 days elution (typical interval of use prior to replacement of IV connectors), eluted connectors were exposed to challenge inocula (5x105 CFU/mL) of key CLABSI clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), multidrug-resistant Pseudomonas aeruginosa (PA), and Candida albicans (CA) for 24 hours at 37C. The number of viable colonizing microbes (CFU/connector) were enumerated by sonication, serial dilution, plating, and counting. Non-coated IVCs were positive controls.
Log10 Reduction of MRC and Silver IV Connectors vs Positive Control
Log10 reduction of the median number of CFU/connector recovered from six replicates following colonization of MRSA, P. aeruginosa, and C. albicans to silver IVCs and MRC IVCs.

Results
Figure 1 presents the median number of CFU/connector with range bars indicating the highest and lowest number of viable colonies recovered from six replicates after 7 days of elution and following 24-hour microbial challenges with MRSA, PA, and CA. Table 1 shows the median log reductions between positive control and coated connectors with p-values comparing MRC and silver IVCs calculated by Wilcoxon rank sum test.

Conclusion
The absence of microbial colonization of the MRC IVCs demonstrates the efficacy and durability of the novel MRC coating. The silver IVC was unable to fully eradicate biofilms of any of the tested pathogens. MRC IVCs were superior to silver IVCs (p&lt; 0.05) for all pathogens tested. MRC-coated IVCs merit further testing in vitro and in vivo for their potential to prevent CLABSI.

Disclosures
All Authors: No reported disclosures
300. Clinical Experience with 16S Ribosomal RNA Gene PCR and Sequencing of Normally Sterile Body Fluids and Tissues in Pediatric Patients
Authors: Li Guyu , Reis Christopher , Kruc Rebecca M , Streck Nicholas , Ristagno Elizabeth H , Zhang Ziyuan , Wolf Matthew , Gaensbauer James , Patel Robin 
Published: January 2025

Abstract

Background
16S ribosomal RNA (rRNA) gene PCR and sequencing may serve as an adjunctive diagnostic tool in complex infections, identifying bacteria in patients on antibiotics whose cultures may be negative. Data on the optimal clinical settings for utilizing this type of testing are limited. This study reviews a single center's 16S rRNA PCR/sequencing experience in children to identify clinical syndromes and optimize specimen choice for higher yield, leading to testing of appropriate patients.

Methods
A retrospective study was performed at Mayo Clinic, Rochester involving children aged 0 to 18 years whose normally sterile tissue or fluid samples underwent 16S rRNA gene PCR/sequencing. The assay involved an up-front real-time PCR assay, reported as negative or submitted to Sanger or next-generation sequencing depending on Ct values. Data was collected on patient characteristics and results of 16S rRNA gene PCR/sequencing and conventional tests. Impact on clinical decision-making was assessed as to whether the advanced molecular diagnostic changed antimicrobial therapy.

Results
A total of 162 tests were performed on 124 patients, including 47% females (58/124) with a median age of 9.6 (range, 2.2-15.0) years. Overall, 33/162 (20%) of tests were positive in 24/124 (19%) patients. 58% of positive tests (19/33) were from samples with negative bacterial cultures. Cerebrospinal fluid was the most common specimen tested (n=38; 31%). Positive results were more likely from fluid compared to tissue samples (OR [95% CI]: 3.1 [1.3, 7.1], p=.007; OR [95% CI]: 0.3 [0.1, 0.8], p=.007, respectively). Testing was positive in 5/10 (50%) pleural fluids tested, a higher positivity rate than any other specimen type (OR [95% CI]: 5 [1.3, 19.0], p=.011). No significant changes in antibiotics were made within 24 hours of reporting positive 16S rRNA gene PCR/sequencing results.

Conclusion
This study highlights the importance of selecting appropriate sample types for 16S rRNA gene PCR/sequencing in pediatric patients. The assay is most likely to yield positive results in children with pleural effusion and in other fluid samples such as subdural and synovial fluid. Further implementation science research is needed to achieve impact on clinical practice.

Disclosures
Robin Patel, MD, a patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic, a: See above|MicuRx Pharmaceuticals and BIOFIRE: Grant/Research Support|PhAST, Day Zero Diagnostics, Abbott Laboratories, Sysmex, DEEPULL DIAGNOSTICS, S.L., Netflix, Oxford Nanopore Technologies and CARB-X: Advisor/Consultant|Up-to-Date and the Infectious Diseases Board Review Course.: Honoraria
306. Patient-Derived Airway Organoids: a Pre-clinical Platform to Model RSV Infection
Authors: Merenda Alessandra , Ehsani Nilofar , Gkogkou Foteini , Pott Johanna , Bezhaeva Taya , Vries Robert G J , Boj Sylvia F 
Published: January 2025

Abstract

Background
HUB’s patient-derived organoids (PDOs) are novel “mini-organs in a dish” derived from adult epithelial stem cells which form 3D structures and resemble the architecture and physiology of the tissue of origin. Airway PDOs represent a valuable model for investigating the pathogenesis of respiratory infections and testing strategies to prevent or treat such diseases. Because in vivo pathogens attack the luminal surface of the epithelium, HUB has established monolayers from lung PDOs, where the luminal side is accessible for mimicking host-pathogen interactions.
Viruses such as the Respiratory Syncytial Virus (RSV) are associated with severe respiratory illnesses, especially in children and older adults. RSV uses the fusion protein, F protein, which can interact with the intercellular adhesion molecule-1 (ICAM-1) to facilitate cell entry, rendering both molecules appealing targets for inhibiting RSV infection.

Methods
This study assessed the effect of Rilematovir, an RSV antiviral agent that inhibits the viral F protein and prevents cell fusion in RSV-infected PDOs. To this end, airway PDO-derived monolayers were pre-treated with different concentrations of the inhibitor before infection with RSV. Transepithelial electrical resistance (TEER) and monolayer integrity were monitored daily, and the viral titre was quantified by real-time quantitative PCR (RT-qPCR) at different time points post-infection (PI). The production of IP-10 and CXCL2, two inflammatory cytokines released upon infection, was also measured 7 days PI.

Results
Our data revealed that when no inhibitor treatment was applied, the viral titre increased gradually, indicating that RSV could infect and propagate in airway PDO monolayers. Notably, monolayers treated with F protein inhibitors showed a significant decrease in viral titre. This viral titre decrease was accompanied by a total reduction of IP-10 and CXCL2, suggesting a potential role for F-protein inhibition in modulating RSV infection.

Conclusion
Overall, this study confirms that airway PDO-derived monolayers are innovative models to study viral infections and investigate potential targets to prevent or treat such infections. These findings could potentially lead to significant advancement in the field of respiratory infections.

Disclosures
All Authors: No reported disclosures
P-830. Comparison of Oral Antibiotic Use and Hospital Readmission Among People Who Use Drugs with Staphylococcus aureus Bacteremia and Before Medically Advised Discharge During Two Time Periods
Authors: Anam Karim Farzana , Sikka Monica K , Streifel Amber C , Strnad Luke , Sukerman Ellie 
Published: January 2025

Abstract

Background
Recent studies suggest the benefit to salvage oral (PO) antibiotics to support people who use drugs (PWUD) with serious bacterial infections who leave before medically advised (BMA) prior to completing antibiotics. We compared the use of PO antibiotics in PWUD with S. aureus bacteremia (SAB) discharged BMA before versus after the implementation of a multidisciplinary discharge planning conference for PWUD requiring long-term antibiotics and publication of recent literature suggesting the benefit of PO antibiotics for patients leaving BMA.

Methods
We performed a retrospective chart review of PWUD with SAB admitted to a 500-bed teaching hospital over two time periods: 1/1/16 to 12/31/17 (group A) and 7/1/21 to 7/31/23 (group B). We compared 30 and 90-day readmission, PO and IV antibiotic recommendations, prescriptions, and percent of prescriptions dispensed.

Results
There were 21 patients in group A and 20 in group B. Univariable analysis showed no significant difference in the groups (Table 1). The incidence of 30 and 90-day readmission was similar (48% vs 50%, p=0.65) and (57% vs 65%, p=0.85), respectively. Long-acting antibiotics were administered on BMA discharge in 1 patient in group A and 8 in group B. PO antibiotic/s were prescribed on BMA discharge for 33% in group A and 50% in group B. While no patients in Group A filled their prescriptions, 35% in Group B did. When incorporating PO treatment that was dispensed and long-acting antibiotics administered, only 5% (1/21) in group A received treatment on BMA discharge compared to 75% (15/20) in group B.

Conclusion
There was an improvement in providing recommendations and prescriptions for PO antibiotics as well as long-acting injectable antibiotics to provide treatment in situations of BMA discharge. These results suggest an impact of the publication of recent literature and our multidisciplinary discharge planning conference but still highlight room for improvement in recommending and prescribing PO antibiotics for PWUD with SAB who leave the hospital BMA. The lack of benefit in readmissions is likely due to the small sample size and limited duration of follow-up.

Disclosures
Monica K. Sikka, MD, F2G: Grant/Research Support
P-836. Non-Beta Lactam Agents for Definitive Treatment of Ampicillin-Susceptible Enterococcus Bacteremia: A Single Center Experience
Authors: Kang HeeEun , khan Asif , Kim Justin J , Martin Isabella W , Zuckerman Richard A 
Published: January 2025

Abstract

Background
Enterococcus bacteremia (EB) is a serious infection with high morbidity and mortality. While anti-enterococcal beta-lactams (BL) remain the mainstay of therapy against ampicillin-susceptible (AS) EB, non-beta-lactam (NBL) antimicrobial agents are also used to treat ASEB. Few studies evaluate NBL use for definitive therapy of ASEB.
CONSORT flow diagram of patients included in study.

Methods
A single-center retrospective study identified all ASEB episodes between 1/1/2016-12/31/2021 (Figure 1). Patient, microbiological, infection, treatment and outcomes were compared between those who received NBL versus BL for ASEB. Multivariable logistic regression analysis was used to determine factors associated with NBL use.
Baseline characteristics of patients treated with non-beta-lactam vs beta-lactam for definitive therapy for ampicillin-susceptible Enterococcus bacteremia.

Results
158 episodes of ASEB in 153 patients were included (Table 1). 43 episodes (27%) were treated with NBL for definitive therapy. Factors associated with NBL therapy were younger age (58 vs 66 years old, p=0.02), reported history of any penicillin allergy (42% vs 9%, p&lt; 0.01) and serious penicillin allergy (14% vs 1%, p&lt; 0.01), history of cancer (37% vs 17%, p=0.01), end-stage renal disease (ESRD; 23% vs 3%, p&lt; 0.01), unknown source of bacteremia (24% vs 8%, p&lt; 0.01), polymicrobial bacteremia (40% vs 16%, p&lt; 0.01), lack of metastatic foci of infection (12% vs 31%, p=0.02), and lack of endocarditis (7 vs 23%, p=0.02). Combination therapy was used in 23% of those treated with BL therapy compared to no patients receiving NBL therapy (p&lt; 0.01).
For NBL vs BL therapy, there was no difference between all-cause 30-day mortality, all-cause 90-day mortality, or 30-day relapse rate.
In a multivariable logistic regression model (Table 2), NBL therapy was more likely in those with: younger age (AOR 0.95, p=0.001), any penicillin allergy (AOR 5.76, p=0.001), history of cancer (AOR 5.23, p=0.001), ESRD (AOR 11.70, p=0), and polymicrobial bacteremia (AOR 4.20, p=0.001).
Factors associated with use of non-beta-lactam antibiotic for definitive therapy of ampicillin-susceptible Enterococcus bacteremia: multivariable analysis.

Conclusion
NBL was used as definitive treatment in 27% of ASEB. Penicillin allergy, access and dosing for patients on hemodialysis, younger host, and polymicrobial infection are factors associated with NBL use. This real-life experience suggests NBL can be successfully used to treat non-severe ASEB. Further studies are needed to determine the efficacy and stewardship implications of NBL use for ASEB.

Disclosures
All Authors: No reported disclosures
P-871. Outcome of Ceftriaxone resistant, Escherichia-coli and Klebsiella spp. bacteremia comparing Carbapenem and Beta-lactam/Beta-lactamase inhibitors in a public sector hospital from Pakistan
Authors: Samar Rohama , Rani Beena , Babar Zaheer Udin , Nasim Asma , Dodani Sunil 
Published: January 2025

Abstract

Background
Carbapenem are recommended for the treatment of Ceftriaxone (CRO) resistant Enterobacterales, however, there are concerns of cost and resistance. Our aim is to compare the outcome of CRO resistant E-coli and Klebsiella bacteremia between Carbapenem and Beta-lactam/beta-lactamase inhibitors (BL/BLI).

Methods
A prospective cohort study conducted from October 2021 to June 2022. All adult patients with E coli or Klebsiella spp. bacteremia, CRO resistant and sensitive to both BL/BLI and Carbapenem were included. The patients were divided into BL/BLI and Carbapenem groups. Demographics, clinical features, comorbidities, laboratory parameters and intensive care unit stay were compared. Outcomes were bacteriological clearance, clinical success and all-cause mortality at day 14 of bacteremia.

Results
A total of 156 patients, 93(59.6%) in BL/BLI and 63(40%) in Carbapenem group were included. There was no difference in co-morbidities, risk factors and severity of disease. The 14 day all-cause mortality was 14.1%. No statistically significant difference was found between BL/BLI and Carbapenem group regarding bacteriological clearance (p=0.27) and mortality (p=0.95). The Carbapenem group had less clinical success rate (69.8% vs 82.8%, p=0.057),however not statistically significant.

Conclusion
BL/BLIs were as effective as Carbapenem in microbiological clearance, clinical success and mortality in CRO resistant E-coli and Klebsiella bacteremia.

Disclosures
All Authors: No reported disclosures