bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-41. Effectiveness of recombinant zoster vaccine against postherpetic neuralgia in a real-world setting
Authors: Zerbo Ousseny , Bartlett Joan , Fireman Bruce , Goddard Kristin , Duffy Jonathan , Glanz Jason , Naleway Allison L , Donahue James , Anderson Tara C , Klein Nicola P 
Published: January 2025

Abstract

Background
Recombinant zoster vaccine (RZV) is highly effective in preventing herpes zoster (HZ). Effectiveness against postherpetic neuralgia (PHN) was nearly 90% in clinical trials but has not been extensively evaluated in real-world settings. The objective of this study was to evaluate real-world RZV effectiveness against PHN overall, by time-since-vaccination, by age, by corticosteroid use, and by time between the two doses.

Methods
\We conducted a prospective cohort study from January 1, 2018 through December 2022 in persons aged ≥ 50 years at 4 healthcare systems in the Vaccine Safety Datalink (VSD) in the US. Using diagnosis codes, we identified PHN cases between 90 and 365 days after an incident HZ episode. We used Cox regression to compare the hazard of PHN in fully (≥30 days after dose 2) and partially (≥30 days after dose 1) vaccinated persons with unvaccinated persons, adjusted for demographics, comorbidities, prior receipt of zoster vaccine live, VSD site and calendar time. Vaccine effectiveness (VE) was calculated as one minus the adjusted hazard ratio.

Results
Of the 45333 incident HZ cases, 2922 (6.4%) were diagnosed with PHN, of which 2775 were unvaccinated. The unadjusted incidence of PHN per 100000 person years was 43.2 among unvaccinated, 17.4 among partially vaccinated, and 7.8 among fully vaccinated persons. After adjustment, VE against PHN of partial vaccination was 68.9% (95% confidence interval [CI] 59.3% – 76.2%) and VE of full vaccination was 87.1% (CI 83.2% - 90.0%). VE of full vaccination was 91.1% during the first year, 89.8% during the second year, and 77.0% after the second year. Among fully vaccinated persons, VE was 93.1% among persons who received their first dose at ages 50-64 years and 85.9% among those who received their first dose at ages ≥65 years; VE was 74.9% in persons who had received corticosteroids within 90 days of vaccination compared to 88.3% in persons who had not. VE was 86.0% in persons who received their second dose within the recommended 6 months after their first dose compared with 91.4% in persons who received their second dose &gt; 6 months.

Conclusion
Two-dose VE against PHN was 87%, which was similar to that of clinical trials. One-dose VE was 69%, underscoring the importance of the second dose. Two-dose VE may have waned after 2 years.

Disclosures
Jason Glanz, PhD, Hillevax: Grant/Research Support Nicola P. Klein, MD, PhD, CSL Seqirus: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support
P-2334. Clesrovimab Binding Site Conservation on the RSV F Protein: An Evaluation of RSV Molecular Sequencing Data from 2019-2023 and GenBank Sequence Analysis
Authors: Fridman Arthur , Love-Gregory Latisha , Railkar Radha , Levitan Diane , Strizki Julie , Vora Kalpit A 
Published: January 2025

Abstract

Background
Clesrovimab is a half-life extended RSV-neutralizing antibody targeting site IV of the RSV fusion protein, that is currently in phase 3 development for the prevention of RSV in infants. As viral sequences drift over time, the possibility for the emergence of viral resistance exists, and the conduct of contemporary global RSV surveillance is important.

Methods
Here, we report the frequency of naturally occurring RSV F gene polymorphisms in the clesrovimab binding site [amino acids (a.a) 426-447] using two approaches. First, a total of 15,527 RSV F protein sequences with a complete extracellular domain were obtained from GenBank (accessed April 2024) for analysis. Sequences were aligned using MUSCLE multiple sequence alignment program. The a.a. frequency at each position was determined as well as the frequency of variants in the clesrovimab binding site. Secondly, we collected RSV positive samples in 2019 through 2023 from individuals of any age in a total of 8 countries (in the northern and southern hemisphere). Next generation sequencing was performed of the RSV F gene and data were analyzed for sequence changes in the clesrovimab binding site.

Results
A total of 15,495 of 15,527 (99.8%) of sequences analyzed from GenBank were 100% conserved at the clesrovimab binding site. Thirteen clesrovimab epitope variants were found, 7 of which occurred in 2 or more sequences. The most frequent variant occurred in &lt; 0.04% of GenBank sequences. Additionally, a total of 555 RSV viruses (300 RSV A [54%], 255 RSV B [46%]) were analyzed from the molecular surveillance. There were no variants identified in the clesrovimab binding site that met the prespecified study criteria (prevalence over 5% AND a variant allele fraction of &gt;10%).

Conclusion
These data demonstrate that the clesrovimab binding epitope on site IV of the RSV fusion protein is highly conserved. These findings are in line with previous reports on the conserved nature of site IV and support the continued development of clesrovimab for the prevention of RSV disease in infants.

Disclosures
Arthur Fridman, PhD, Merck & Co., Inc.: employee|Merck & Co., Inc.: Stocks/Bonds (Public Company) Latisha Love-Gregory, PhD, Merck & Co., Inc.: Employee|Merck & Co., Inc.: Stocks/Bonds (Public Company) Radha Railkar, PhD, Merck & Co., Inc.: Employee|Merck & Co., Inc.: Stocks/Bonds (Public Company) Diane Levitan, PhD, Merck & Co., Inc.: Employee|Merck & Co., Inc.: Stocks/Bonds (Public Company) Julie Strizki, PhD, Merck & Co., Inc.: Employee|Merck & Co., Inc.: Stocks/Bonds (Public Company) Kalpit A. Vora, PhD, Merck & Co., Inc.: Employee|Merck & Co., Inc.: Stocks/Bonds (Public Company)
P-2335. Comparison of Adverse Drug Effects and Incidence of CMV Infection Between Different Dosing Regimens for Valganciclovir in the Pediatric Solid Organ Transplant Population
Authors: Al Zubaidi Khaled , Huppler Anna R , Jastrow Jena , Groth Shay , Dasgupta Mahua , Yan Ke , Waggoner Winfield S 
Published: January 2025

Abstract

Background
Valganciclovir has become widely used for the prevention of (CMV) infection in solid organ transplant (SOT) patients in both adult and pediatric populations. However, there is no consensus about the optimum dosing regimen in pediatric patients. Our study aims to compare the frequency of side effects and rate of CMV between two commonly used dosing regimens.

Methods
In August 2020, as part of quality improvement initiative our internal SOT guideline for Valganciclovir dosing switched from weight-based (15-25 mg/kg/dose) to the manufacturer recommended dosing based on body surface area and estimated glomerular filtration rate (BSA/eGFR). We retrospectively reviewed medical records of pediatric patients (0-20 years) who underwent SOT (including liver, heart, and kidney) from 2/2015 to 2/2024. The collected data include age, transplanted organ, occurrence of abnormal liver functions (LFT) and neutropenia, and number of episodes of CMV infection during prophylaxis and 6 months post-prophylaxis. Moderate and severe neutropenia were defined as absolute neutrophil count (ANC) 500-1000 and ANC &lt; 500, respectively.

Results
116 pediatric SOT recipients were distributed almost equally between heart (32%), kidney (34%), and liver (34%) transplants. 28/116 (24%) received BSA/eGFR-based dosing. The median duration of prophylaxis was 3.9 months (IQR 2.9-6). The frequency of abnormal LFTs were similar in both dosing groups (64% in the BSA/eGFR group vs 65% in the weight-based group). Moderate neutropenia was more frequent in the BSA/eGFR group (36%) compared to the weight-based group (17%) and severe neutropenia occurred in 11% and 18%, respectively. However, these differences were not significantly different(P=0.11). CMV infection occurred in 27% of total population of patients with no significant difference in breakthrough infection on prophylaxis between the two groups (4% vs 10%, P=0.45).

Conclusion
In pediatric SOT recipients, valganciclovir prophylaxis dosed based on BSA/eGFR or weight had a similar side effect profile for liver toxicity and severe neutropenia. In addition, there was no significant difference in the occurrence of CMV infections between the dosing regimens.

Disclosures
All Authors: No reported disclosures
P-2359. CLEAR Hepatitis C – Development and impact of a regional collaborative to facilitate identification and treatment of patients with Hepatitis C
Authors: Kessell Andrew , Biritwum Madonna A 
Published: January 2025

Abstract

Background
Despite advancements in therapy, hepatitis C continues to significantly impact public health and individual patients. Untreated hepatitis C can lead to liver failure and death. The introduction of oral therapies provides an opportunity to cure patients’ hepatitis C and limit the spread. However, challenges persist in the identification of patients, access to specialists trained in the treatment of hepatitis C and the medication therapy costs. FirstHealth of the Carolinas (FHC) developed partnerships and care pathways within our regional medication community including employed and non-employed physician practices. The principles of the care pathway were, CLEAR Hepatitis C (Figure 1). The purpose of our study was to evaluate the outcomes associated with a comprehensive regional approach to identification and treatment of patients with hepatitis C.
CLEAR Hepatitis C acronym
Outlines care pathway developed for the treatment of hepatitis C

Methods
A retrospective study was conducted at FHC reviewing outcomes associated with the CLEAR Hepatitis C initiative undertaken from September 2023 through April 2024. Data evaluated included: hepatitis C antibody screens conducted by primary care providers, Infectious Disease clinic referrals for hepatitis C treatment, oral therapies prescribed by Infectious Disease providers, patients assisted with medication therapy by specialty pharmacists and pharmacy technicians and patients receiving a curative diagnosis.
CLEAR Hepatitis Results
Results associated with each step of the care pathway.

Results
Primary care provider education and promotion of CLEAR Hepatitis C initiative commenced in November 2023. Comparing the fourth month periods of September-December of 2023 to January-April 2024: the total hepatitis C antibody screens conducted increased from 1169 to 1514 (p &lt; 0.05); Infectious Disease clinic visits with a primary diagnosis of hepatitis C increased from 7 to 18; Prescriptions from Infectious Disease providers increased from 9 to 19; Patients assisted with medication access increased from 6 to 15. During the study period, 4 patients received a curative diagnosis. An additional 8 patients have completed treatment and are awaiting confirmatory lab testing (Figure 2).

Conclusion
Development of a collaborative, integrated hepatitis C care pathway within our regional medical community successfully increased the number of patients identified and treated for hepatitis C in our region.

Disclosures
All Authors: No reported disclosures
P-2361. Real-World Experience of Letermovir for CMV Prophylaxis in Solid Organ Transplant Recipients
Authors: Perez Emily , Cheezem Alexandra , Cabrera-Rios Pierina , Macek Molly , Cano Ennie , Abbo Lilian M , Vu Christine A 
Published: January 2025

Abstract

Background
Valganciclovir is recommended as first-line for cytomegalovirus (CMV) prophylaxis after solid organ transplant, however, its use may be limited by myelosuppression. In 2023, letermovir was approved for CMV prophylaxis in high-risk kidney transplant recipients. The aim of this study was to describe our real-world experience utilizing letermovir for CMV prophylaxis in select solid organ transplant recipients.

Methods
A single-center, retrospective study was conducted in adult solid organ transplant recipients who received letermovir for CMV prophylaxis between December 2022 and March 2024 at the Miami Transplant Institute. We assessed white blood cell count (WBC) recovery following the switch from valganciclovir to letermovir, growth-colony stimulating factor (G-CSF) use, drug interactions, CMV DNAemia, and outpatient accessibility. Data was analyzed using descriptive statistics.

Results
Of the 54 patients included, 31 (57%) received a lung transplant, 22 (41%) received a kidney transplant, and 1 (2%) received a multivisceral transplant. For patients switched from valganciclovir to letermovir, the median WBC change at day 28 was +2.5 k/uL, 95% of patients achieved WBC recovery. Median number of G-CSF doses prior to letermovir was 1 with an average dose of 5.65 mcg/kg. For patients receiving tacrolimus/cyclosporine, 27 (54%) required a dose reduction after starting letermovir. We had 2 cases of breakthrough CMV disease. Of the patients requiring prophylaxis for herpes simplex virus (HSV), 4 (13%) patients were not prescribed acyclovir/valacyclovir. For outpatient accessibility, 27 (59%) of patients required prior authorizations, four (9%) patients were unable to start letermovir due to lack of insurance approval, and 1 (2%) patient discontinued treatment due to ongoing insurance issues.

Conclusion
This study supports the use of letermovir to prevent CMV infection in high- and intermediate-risk transplant recipients. Most patients who were switched from valganciclovir experienced WBC recovery. Our more notable findings were the challenges faced with prescribing letermovir. Early pharmacy engagement may be necessary to help address barriers related to cost, insurance coverage, drug-drug interactions, and reinforce concomitant prescribing of HSV prophylaxis.

Disclosures
All Authors: No reported disclosures
P-89. Daptomycin Compared to Vancomycin for the Treatment of Osteomyelitis: a national VA cohort study
Authors: Moenster Ryan P , Linneman Travis W , Eaton Daniel 
Published: January 2025

Abstract

Background
Daptomycin (DPT) has been used as an alternative to vancomycin (VCM) for the treatment of osteomyelitis (OM), but few studies have compared their efficacy in this infection.

Methods
This was a retrospective evaluation of all patients within the Veteran’s Affairs (VA) Health Care System between the ages of 18 and 89 who were treated for OM with at least 21-days of either intravenous (IV) VCM or DPT between 1 January 2009 and 1 January 2020. The diagnosis of OM was identified by a primary ICD-9 (730.0-730.99) or ICD-10 (M86.0-M86.9) discharge code around the time of VCM or DPT administration. Additionally, records were verified to ensure no patient had received more than 6 days of the other therapy.
The primary outcome was clinical failure, which was a composite of retreating with antibiotics for at least 14 days within the 6-months after initial treatment was completed, surgical procedures related to OM in the 6-months after treatment was completed, or all cause 30-day readmission while on antibiotic therapy for the incident case of OM.
Two additional, nested cohorts were analyzed. A cohort matched based on age, race, sex, body mass index, and Charlson Comorbidly Index, and a cohort analyzed using average effect on treatment (ATT).

Results
Five thousand, four hundred twenty-six patients were included (4777 VCM, 649 DPT). The primary outcome of composite clinical failure occurred in 63.4% (412) of DPT patients and 57.2% (2731) of VCM patients (p &lt; 0.001). In the adjusted cohort, DPT was not associated with failure (OR 1.173, 95% CI 0.978-1.407), but overall retreatment (1-180 days after completion of initial therapy) and early retreatment (1-25 days after completion of initial therapy) were more likely in DPT treated patients (OR 1.23 (95% CI 1.026-1.475) and OR 1.242 (95% CI 1.092-1.414), respectively). In the ATT analysis composite failure was not associated with DPT, but overall retreatment and early retreatment were (OR 1.263 (95% CI 1.014-1.574) and OR 1.247 (95% CI 1.068-1.455), respectively).

Conclusion
In this large, retrospective cohort of veteran’s receiving treatment for OM more patients receiving DPT experienced composite failure compared to those treated with VCM. The difference appears driven by DPT failure within the first 25 days after treatment completion.

Disclosures
All Authors: No reported disclosures
P-109. A Phase I First-in-Human Study to Evaluate the Safety and Pharmacokinetic (PK) Properties of the Intravenously (IV) Administered OMN6, A Novel Antimicrobial Peptide Targeting Acinetobacter baumannii (AB), in Adults including Older Healthy Volunteers (HVs) Subjects
Authors: Shusterman Muratov Bella , Maximov Shelly , Stark Yafit , Zazoun Jonathan , Michaeli Janna , Dogterom Peter , Abd-Elaziz Khalid , Shorr Andrew , Cohen Kutner Moshik , Bachnoff Niv 
Published: January 2025

Abstract

Background
Acinetobacter baumannii (AB) is an opportunistic Gram-negative pathogen ranked 1st on the World Health Organization (WHO) Priority Pathogen list, that causes severe infections among elderly patients in intensive care units. Given the accelerating pace of global population aging, the burden of diseases including multi-drug resistant AB (MDRAB) infections is increasingly falling on elderly adults. Due to both elevated mortality rates associated with AB and the lack of effective treatments in older adults, there is a critical unmet need to develop new effective and safe anti-infectives. OMN6 is a novel, biochemically-engineered antimicrobial peptide, with a unique mechanism of action, which is being developed for the treatment of severe AB infections including carbapenem-resistant AB and MDRAB.

Methods
The First in Human Phase 1 OMN6 clinical trial was a single center, double-blind, placebo-controlled, randomized, single ascending total daily dose study, conducted in healthy volunteers. 5 single ascending total daily doses were tested; 5 cohorts in adults aged 18-59 years, and 1 cohort of older adults aged ≥ 60 years. Adults aged 18-59 years received doses ranging from 7.5 to 100 mg OMN6 as a 3-hour single IV infusion, while 50 mg was administered to both age groups (N=8/cohort). Safety and tolerability assessments, and pharmacokinetic (PK) blood sampling occurred at pre-defined timepoints. All blood samples for PK evaluation were analyzed with a validated LC/MS/MS assay. PK parameters of 50 mg OMN6 in both age groups were compared.

Results
No serious adverse events (SAEs) were reported in either adults or older adults and all dose levels were considered safe and well tolerated.
Upon a single infusion administration, mean PK results demonstrated dose-proportionality for Cmax and near dose-proportionality for AUCinf. The OMN6 PK profiles in adults and older adults at the 50 mg dose indicated a similar pattern. The mean AUCinf and Cmax for adults and older adults, were 1289 and 1211 h*ng/mL; and 502 and 470 ng/mL, respectively.

Conclusion
OMN6 had a favorable safety, tolerability, and PK profile that was similar in adults across all age groups. These positive results support advancing OMN6 to Phase 2 clinical trials, including subjects aged ≥ 60 years.

Disclosures
Andrew Shorr, MD, MPH, MBA, Basilea: Advisor/Consultant|Basilea: Grant/Research Support
P-128. Evaluating dopamine agonists to confer colonization resistance against bacterial enteric infection: population-based propensity-matched cohort study
Authors: Birabaharan Morgan , Kaelber David C , Mehta Sanjay R 
Published: January 2025

Abstract

Background
Uncovering gut microbiota mechanisms can afford new preventive therapies against enteric infection amidst the antimicrobial resistance crisis. Recent groundbreaking work in mice models suggest microbial-mediated metabolism of diet-derived tryptophan helps confer colonization resistance against enteric pathogens via agonism of dopamine receptors. This study aims to assess the risk of bacterial enteric infection in restless leg syndrome patients using a dopamine agonist (ropinirole) compared to a voltage-gated calcium channel modulator (gabapentin).Table 1:Characteristics of the ropinirole and gabapentin cohorts before and after propensity score matching

Methods
The TriNetX Analytics Platform containing 89 million unique patients from 63 health care organizations was used. These data represent 27% of the US population from all 50 states, and includes persons from diverse geographic, age, race, ethnicity, income, and insurance groups. Persons &gt;18 years of age diagnosed with restless leg syndrome and prescribed ropinirole or gabapentin between Jan 2018- Jan 2023 were included as the study and control cohort, respectively. Individuals who received both ropinirole and gabapentin were excluded. The two cohorts were propensity score matched for age, sex, race, ethnicity, social determinants of health, obesity, ischemic heart disease, type 2 diabetes mellitus, hypertension, hyperlipidemia, human immunodeficiency virus and organ transplant status. Using the matched cohorts, we calculated the relative risk of first-ever and recurrent bacterial enteric infection 1-year after index events in the respective cohorts.

Results
We identified 38,122 and 82,961 persons with restless leg syndrome receiving ropinirole or gabapentin, respectively. After 1:1 propensity matching, demographic and clinical characteristics were balanced (SD &lt; 0.1) (Table 1). Ropinirole compared to gabapentin use among persons with restless leg syndrome was associated with decreased 1-year risk of both recurrent (RR 0.85, 95% CI 0.74-0.98) and new-onset bacterial enteric infection (RR 0.77, 95% CI 0.65-0.92).

Conclusion
This study found that persons with restless leg syndrome receiving dopamine-agonist (ropinirole) compared to voltage-gated calcium channel modulator therapy (gabapentin) was associated with reduced risk of recurrent and new-onset bacterial enteric infection.

Disclosures
David C. Kaelber, MD, PhD, MPH, FAAP, FACP, FACMI, FAMIA, Dynavax Technologies Corporation: Advisor/Consultant