bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1246. Effect of BV100 on the Pharmacokinetics of Midazolam and its metabolite 1-hydroxymidazolam in healthy volunteers
Authors: Delique Pierre , Husband Lisa , Kemmer Christian , Lakner Geza , Dale Glenn 
Published: January 2025

Abstract

Background
We identified rifabutin as having potent antibacterial activity towards Acinetobacter baumannii under iron limiting conditions. BV100 (rifabutin for infusion) is under development for the treatment of serious infections due to A. baumannii
A single center, open-label, 3-period fixed-sequence, phase I clinical drug-drug interaction study was conducted to evaluate the effect of BV100 on the pharmacokinetics (PK) of midazolam and its metabolite 1-hydroxymidazolam on healthy subjects.

Methods
The study included nonchildbearing females and males aged 18 to 55. The study was divided in three periods : On Day 1 (Period 1), each participant received a single 5 mg oral dose of midazolam syrup. After a 24-hour washout on Day 2, BV100 was given as a 300 mg intravenous infusion over 2 hours every 12 hours for 8 doses from Day 3 to Day 6 (Period 2). On Day 7 (Period 3), the 9th dose of BV100 was administered alongside a single 5 mg oral dose of midazolam. PK parameters for midazolam and its metabolite were assessed in plasma samples on Day 1 after midazolam administration alone and on Day 7 after midazolam administration following 8 BV100 doses from Day 3 to Day 6.

Results
No deaths, no SAEs, or other significant AEs occurred during this study. All 23 study subjects were eligible for safety analysis. Sixteen out of 23 subjects completed all 3 periods of the study. No clinically relevant effects of BV100 on clinical laboratory profiles (haematology, biochemistry, haemostasias, urinalysis) or vital signs (blood pressure, heart rate, respiration rate, body temperature) were observed in this study.
Midazolam and 1-OH-midazolam plasma concentrations were higher when administered alone on Day 1 (Cmax = 33.36 ng/mL; AUC0-tlast = 99.20 h*ng/mL) compared to co-administration with BV100 on Day 7 (Cmax = 25.43 ng/mL; AUC0-tlast = 50.81 h*ng/mL). The elimination parameters indicate faster elimination for both midazolam and its metabolite on Day 7 compared to Day 1.

Conclusion
BV100 is considered a mild and weak inducer of midazolam according to EMA and FDA criteria, respectively. Multiple 300 mg IV doses of BV100, administered with and without midazolam to healthy subjects, were safe and well tolerated.

Disclosures
All Authors: No reported disclosures
432. High-fat diet changed Salmonella infection patten associated with increasing intestinal permeability and altering gut microbiota
Authors: Zhao Xu , lei Chen , Guo Xiaohan 
Published: January 2025

Abstract

Background
The impact of a High-fat diet (HFD) on gut microbiota may influence host susceptibility to pathogen infection. Here we utilized a HFD-induced dysbiosis mice model to investigate how HFD alters gut microbiota, thereby affecting the pattern of Salmonella infection.

Methods
The mice was fed with HFD or Grain-based chow (GBC) for 3 weeks, then orally gavaged with 106 CFU S. enteritis to induce colitis. The survival rate, fecal bacterial counting, liver and spleen bacterial burden and cytokine detection were performed to compare the difference of two groups. Moreover, FTIC-Dextran method was used to investigate the intestinal permeability of HFD or GBC feeding mice. Finally, antibiotics cocktail pretreatment was performed to investigate the effect of HFD on gut microbiota.

Results
When the mice were performed gavage with 106 CFU S. enteritis, the mortality of HFD mice (100%) was significantly higher than GBC mice (50%) (P=0.0225). Interestingly, the results displayed the fecal colonization amount of mice in GBC group was higher than HFD group. However, the bacterial burden of liver and spleen in HFD group was significantly higher than in GBC group (Fig. 1). The result showed the pro-imflammatory cytokine (TNF-α, IL-6 and IL-1β) concentration of HFD was higher than GBC mice, regardless of serum, spleen and colon (Fig. 2). Using FTIC-Dextran method to investigate the intestinal permeability, the results showed HFD decreased intestinal mucosal permeability. Meanwhile, Western results showed HFD reduced intestinal Occludin expression, which is an important component of the intestinal tight junction (Fig. 3). Finally, Antibiotics cocktail pretreatment was performed to destroy mice gut microbiota, the results showed the survival curve and fecal bacerial counting of group HFD+Antibiotics and GBC+Antibiotics was identical. It is implied that depleting gut microbiota with antibiotics rendered the mice equally susceptible to Salmonella infection, irrespective of their diets (Fig. 4).

Conclusion
Our findings reveal a significant increase in Salmonella infection-induced mortality associated with HFD. HFD increased host susceptibility to Salmonella infection maybe due to HFD increasing intestinal permeability and altering gut microbiota.

Disclosures
All Authors: No reported disclosures
P-1279. Understanding Vaccine Hesitancy and Health Literacy among Parents in the United States
Authors: Eiden Amanda , Wang Dong , Zheng Yi , Frew Paula 
Published: January 2025

Abstract

Background
Vaccination effectively prevents diseases and reduces the health system burden. However, vaccine hesitancy persists and affects vaccination uptake. We aim to better understand the level of vaccine hesitancy and its associated factors among parents.

Methods
A cross-sectional survey was conducted (January 2022) among 692 parents with children under 18 years old in the US. Demographic characteristics were described by level of vaccine hesitancy. Logistic regression models were fitted to assess the associations of vaccine hesitancy towards children’s vaccines with factors related to literacy, information seeking behavior, attitudes and beliefs, and access to care. We compared vaccine hesitancy levels across vaccine preventable diseases using Chi-Square tests. Odds ratios (OR) with their 95% confidence intervals (CI) and p-values were reported.

Results
Overall, more hesitant parents were more likely to be younger, male, and Hispanic. After adjusting for age, gender, race/ethnicity, education, income, and region, parents more familiar with children’s vaccines had lower odds of being hesitant (OR= 0.82, 95% CI: 0.69 - 0.97). Open discussion with healthcare professionals, trust in vaccination authorities, belief that vaccines benefit children, and easy access to pharmacy were significantly associated with less hesitancy. Higher odds of being hesitant were observed among parents who were more cautious in decision-making or had information seeking challenges, and those who had concerns regarding vaccine safety, efficacy, associated side effects, or frequent vaccine schedules. Parents were more hesitant towards seasonal vaccines (e.g., COVID-19, influenza) compared to routine vaccines (e.g., tetanus-containing, MMR).

Conclusion
This study informs public health entities and medical practitioners where to target positive vaccine-related messaging and resources to enhance parental vaccine literacy and build trust in vaccines.

Disclosures
Amanda Eiden, PhD, MBA, MPH, Merck & Co., Inc.: Stocks/Bonds (Private Company) Dong Wang, PhD, Merck & Co., Inc.: Stocks/Bonds (Private Company) Yi Zheng, PhD, MPH, Merck & Co., Inc.: Stocks/Bonds (Private Company) Paula Frew, PhD, MA, MPH, Merck & Co., Inc.: Stocks/Bonds (Private Company)
P-1280. Vaccinating Your Child During an Emergency Is More Important Than Ever: A Randomized Controlled Trial on Message Framing Among Ukrainian Refugees in Poland
Authors: Kleszczewska Dorota , Sochoń-Latuszek Agnieszka , Winters Maike , Lewtak Katarzyna , Nurzhynska Anastasiia , Yoruk Kseniia , Kukuła Katarzyna , Bahruddinov Mutribjon , Kusek Aleksandra , Dzielska Anna , Maciejewski Tomasz , Mazur Joanna , Melchinger Hannah , Kinsman John , Christie Sarah , Omer Saad 
Published: January 2025

Abstract

Background
Since February 2022, millions of Ukrainian women and children have fled their home country. Evidence suggests that vaccination coverage among Ukrainian refugee children is sub-optimal. We therefore tested the effect of three messages on mothers’ intention to vaccinate their children, and on scheduling a vaccination appointment.

Methods
The UNICEF-funded project (SBC office) 'Say Yes to Vaccinations’ conducted an online randomized controlled trial among Ukrainian refugee mothers residing in Poland who had at least one child under 7 years of age. Participants were randomized to 1 of 3 intervention groups or to the control group. Intervention messages encouraged vaccination with a specific frame: 1) trust in the Polish healthcare system, 2) ease of access to vaccination, 3) risk aversion (highlighting the vulnerability to diseases due to emergency). Primary outcomes included intention to get a child vaccinated in Poland and clicking on a link to schedule a vaccination appointment.

Results
3,282 women entered the survey, 1,233 did not meet the inclusion criteria. A total of 1,910 Ukrainian mothers completed the study, 33% had fully vaccinated children. The mothers who read the risk aversion message were significantly more likely to intend to get their children vaccinated in Poland (AOR 2.35; 95% CI 1.25-4.42). 31% of the participants in the risk aversion intervention groups clicked on the link to make the appointment compared with 25% in the control group, which translated into an AOR of 1.53 (95% CI 1.12-2.09). The messages focused on trust and ease of access did not result in increased vaccination intention or clicking on the link. Getting vaccination information from social media was associated with increased vaccination intention (AOR 1.91; 95% CI 1.21-3.00), not trusting anyone for vaccination information, however, was associated with decreased vaccination intentions (AOR 0.34; 95% CI 0.11-1.00).

Conclusion
We found that framing a pro-vaccination message around risk aversion resulted in increased intention to vaccinate and more clicks on a vaccination scheduler. Health workers who interact with Ukrainian refugees could use the risk aversion frame when communicating around vaccination, highlighting the vulnerable situation faced by refugees.

Disclosures
Saad Omer, MBBS MPH PhD, Meta: Advisor/Consultant|Meta: Grant/Research Support
433. Impact of Antibiotics on the Gut Microbiota: Comparisons Using Model-Based Analyses
Authors: Olivares Carlos , de Gunzburg Jean , Ruppe Etienne , Andremont Antoine , Corbel Tanguy , Ferreira Stéphanie , Guedj Jérémie , Burdet Charles 
Published: January 2025

Abstract

Background
Antibiotic (AB) treatments shift the gut microbiota composition according to their spectrum of activity, posology and intestinal excretion rate. We compared the impact of various ABs on gut microbiota bacterial diversity.

Methods
We used data from 2 RCTs, DAV-132-CL1004 and DAV-132-CL1006 (sponsor Da Volterra), where respectively 143 and 144 healthy volunteers (HV) were randomly assigned to receive a 5-day IV treatment with moxifloxacin (MXF, 400mg OAD, CL1004) or with ceftriaxone (CRO,1 g once a day), ceftazidime/avibactam (CEF/AVI, 2g/0.5g every 8 hours (q8h)), piperacillin/tazobactam (PIP/TZB, 4g/0.5g q8h) (CL1006). Some HV were also treated for 7 days with several doses of DAV132, a charcoal-based adsorbent that captures AB residuals in the late ileum and colon (2g-36g/day). Plasma and fecal concentrations of AB were measured longitudinally. Gut microbiota bacterial diversity was determined by 16S rRNA gene profiling. A pharmacokinetic (PK) model was adapted to predict plasma and feces AB concentrations over time, and a pharmacodynamic (PD) model of indirect response was used to characterize the effects of fecal drug on the bacterial diversity. In the parameter asymptotic distribution we simulated 1000 PK and PD profiles for each antibiotic with various treatment durations (3 to 14 days) and computed several PK & PD indices.

Results
Following a 5-day treatment, the median [IQR] time for AB fecal concentrations to decrease below the limit of quantification after the last administration varied between antibiotics: CRO, 5.1 days [3.5;7.0]; CEF, 5.0 [3.2;8.5]; PIP, 2.5 [1.4;5.6]; and MXF, 11.5 [10.0;13.0].
The global impact on the diversity was highest for MXF and lowest for CRO: median AUC of the change from baseline of the Shannon index (SI) between baseline and day 42 of 13.2 [7.9;20.4] for MXF, 10.9 [0.6;20.4] for PIP, 10.1 [4.6;18.3] for CEF and 2.1 [0.8;5.0] for CRO. The maximal variation from baseline of the SI was observed for PIP (-27.3% [-37.0%;-1.9%]).
Impact increased for all AB when longer treatment durations were simulated.

Conclusion
AB alter the intestinal microbiota diversity to various degrees, both within and between AB families. Such studies comparing the impact of AB on the gut microbiota may help in driving stewardship.

Disclosures
All Authors: No reported disclosures
P-1292. Impact of Discontinuation of Serum Antibody Test Reagents on the Diagnosis of Amebiasis in Japan (2013-2022)
Authors: Hadano Yoshiro , Mori Hirotake , Ohno Satoshi 
Published: January 2025

Abstract

Background
Amebiasis, a notifiable infectious disease in Japan, had shown an increasing trend in reported cases until 2017 when the insurance-covered serum antibody testing reagent was discontinued. This change raised concerns about the subsequent decline in reported cases. Our study aimed to investigate the impact of discontinuing serum antibody test reagent production on amebiasis diagnosis trends.

Methods
We retrospectively analyzed amebiasis cases from January 2013 to December 2022 using the National Center for Epidemiology of Infectious Diseases system. We employed Poisson analysis to assess weekly amebiasis case trends before and after the discontinuation period, which we divided into pre discontinuation (2013-2017), discontinuation (2018-2019), and COVID-19 pandemic (2020-2022) phases.

Results
A total of 8,907 cases of amebiasis were reported during the study period. The average weekly number of cases was 20.4 in 2014-2017, 16.4 in 2018-2019, and 10.7 in 2020-2022. After adjusting for the effects of the COVID-19 pandemic, the frequency of diagnosis decreased during the discontinuation period (prevalence rate ratio = 0.76; 95% CI, 0.66-0.86; P &lt; 0.01), especially for extraintestinal amebiasis (prevalence rate ratio = 0.35; 95% CI, 0.22-0.57; P &lt; 0.01) compared with intraintestinal amebiasis (prevalence rate ratio = 0.81; 95% CI, 0.71-0.93; P &lt; 0.01).

Conclusion
After adjusting for the effects of the COVID-19 pandemic, the number of reported amebiasis cases per week significantly decreased after discontinuation of the serum antibody test reagent, even during the COVID-19 pandemic phase in Japan. To ensure accurate diagnosis, the availability of antibody reagents for serum testing, covered by insurance, should be encouraged.

Disclosures
Satoshi Ohno, M.D. Ph.D., Otsuka Pharmaceutical Factory: Advisor/Consultant
P-1294. Examining the Utility of Education Alongside Low-Barrier Community Vaccination Clinics in Increasing Influenza Immunization Uptake Within Vulnerable Black Communities
Authors: Abdul-Mutakabbir Jacinda , Abdul-Mutakabbir Raheem , Casey Samuel 
Published: January 2025

Abstract

Background
Amidst the coronavirus disease (COVID-19) pandemic, vaccination rates for other preventable diseases, including influenza, have drastically declined across the US non-Hispanic Black population. Systemic injustice and decades of medical mistreatment have been cited as critical factors. Addressing gaps in health literacy and accessibility has been shown to promote trust and improve vaccine uptake. In this study, we aimed to utilize a multifaceted approach to investigate barriers to influenza vaccination and to promote equitable influenza immunization uptake across San Bernardino County, CA (SBC) Black communities.

Methods
The intervention commenced from August to December 2023 and included a 45-minute vaccine education session followed by a community vaccination clinic. The intervention occurred one weekend per month at a pre-identified church location within SBC. Participants 18 years and older were invited to take two optional surveys before and after the education session to assess the impact of knowledge on health behaviors. Demographic data, including social vulnerability, were collected for all survey participants and those immunized in the clinic.

Results
127 individuals completed the pre-survey, and 109 individuals completed the post-survey. Survey data revealed that 86% of the participants identified as Black, 75% were age 55 or older, and 98% resided in a highly vulnerable area. We identified significant positive knowledge changes when comparing baseline vaccine literacy to the knowledge gained following the presentation, particularly in areas surrounding vaccine recommendations for adults 65 years or older. Notably, 47.2% of the participants stated they were “extremely likely” to be vaccinated against influenza before receiving education. Following education, 75.4% of participants noted they were “extremely likely” to be vaccinated and 78.5% were “extremely likely” to recommend the vaccine. 96 vaccine doses (40 influenza and 56 COVID-19) were given, and 33% were co-administered.

Conclusion
Our results indicate that providing education alongside vaccination can impact vaccine uptake in Black communities. Further research is needed to determine best practices for addressing limitations in vaccine uptake within minoritized populations.

Disclosures
Jacinda Abdul-Mutakabbir, PharmD,MPH, CSL Sequiris: Advisor/Consultant|CSL Sequiris: Honoraria|GSK: Advisor/Consultant|GSK: Honoraria|Novavax: Advisor/Consultant|Novavax: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria
P-1299. Epidemiology of Invasive Meningococcal Disease in the United States: Review of Recent Data and Identified Risk Factors
Authors: Presa Jessica , Spitz Daniel , Palmer Paul , Snow Vincenza , Dooling Kathleen 
Published: January 2025

Abstract

Background
Although relatively rare, invasive meningococcal disease (IMD) is distinguished by its unpredictable epidemiology, rapid clinical progression, and often severe or fatal outcomes. IMD risk peaks in infants and young children, with secondary peaks in adolescents/young adults and sometimes older adults. Overall IMD has been declining in the United States and elsewhere since the year 2000, with historic lows during the COVID-19 pandemic; however, widespread post-pandemic rebounds stress the ongoing public health threat of IMD.
In the United States, IMD is a notifiable condition tracked by the Centers for Disease Control and Prevention (CDC) in part using the National Notifiable Diseases Surveillance System (NNDSS). A comprehensive enhanced meningococcal disease surveillance (EMDS) program was implemented in 2015.
Presa_Figure
N/A

Methods
We compiled annual NNDSS and EMDS data and searched published literature for analyses of US IMD data to review recent IMD epidemiology and associated risk factors.

Results
The NNDSS and EMDS reported similar numbers of IMD cases during 2016‒2021, with EMDS providing more updated serogroup information (Figure). NNDSS data indicate more cases in 2023 than in any of the 7 years prior, with this rebound intensifying thus far in 2024; the CDC estimates there will be more cases in 2024 than the 422 seen in 2023 (35% serogroup Y). Serogroup Y ciprofloxacin and/or penicillin resistance rose from 22.8% in 2019 to 65.4% in 2021. Surveillance data and additional analyses point to increased IMD incidence associated with college vs no college attendance (1.6- to 3.1-fold during 2016‒2019), Black vs White race (1.1- to 2.4-fold, 2016‒2020), Medicaid vs commercial insurance (1.8- to 3.0-fold, 2016‒2019), homelessness vs non-homelessness (13.8- to 30.2-fold, 2016‒2019), men having vs not having sex with men (5.4-fold, 2015‒2016), and HIV vs no HIV infection (6.2-fold; 2009‒2019).

Conclusion
US IMD is rebounding after major COVID-associated declines. Established risk factors (eg, smoking, sharing food, dormitory living) and related behaviors (eg, vaping, overnight camp attendance) may be influencing IMD surges as post-COVID socialization increases. Comprehensive understanding of US epidemiology is crucial for optimizing vaccination strategies. Funding: Pfizer.

Disclosures
Jessica Presa, MD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Daniel Spitz, PharmD, Pfizer Inc: Employee Paul Palmer, PhD, Pfizer Inc: Employee Vincenza Snow, MD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company) Kathleen Dooling, MD, Pfizer: Employee|Pfizer: Stocks/Bonds (Public Company)
500. Finding AP Gap: An Assessment of Antibiotic Use in Acute Pancreatitis
Authors: Brassell Emily , Son Andrea H , Hecker Michelle T 
Published: January 2025

Abstract

Background
American Gastroenterology Association (AGA) guidelines recommend against the use of prophylactic antibiotics for acute pancreatitis. Antibiotic therapy is recommended for culture-proven infection in pancreatic necrosis or when infection is strongly suspected (e.g. gas in collection, bacteremia, sepsis, or clinical deterioration). Carbapenems, metronidazole, third or fourth generation cephalosporins, and fluoroquinolones are preferred agents. Data to support use of piperacillin/tazobactam also exists. There is limited data evaluating adherence to these guidelines.Table 1:Baseline Characteristics

Methods
This was a retrospective cohort study of adult patients hospitalized in The MetroHealth System from January 1, 2021 through December 31, 2022 who received antibiotics for a diagnosis of acute pancreatitis. Exclusion criteria included multiple indications for antibiotics or antibiotics given in the emergency department (ED) only. Only the first hospitalization per patient was included. The primary outcome was the percentage of encounters for which antibiotic use was adherent to AGA guidelines. Secondary outcomes included descriptions of antibiotic choice/duration and microbiologic results.Table 2:Antibiotic Use

Results
Of 538 inpatient encounters with a diagnosis of acute pancreatitis, antibiotics for any indication were prescribed in 322 (60%). For the 83 unique patient encounters meeting inclusion criteria, antibiotic use was not adherent to AGA guidelines in 49 (59%). Table 1 compares characteristics of patients in whom antibiotic therapy was adherent vs non-adherent. Carbapenems, piperacillin/tazobactam, cephalosporins, and vancomycin were prescribed for pancreatitis during 42%, 51%, 41%, and 25% of encounters respectively (table 2). The average duration of antibiotics for all study patients was 8.5 days. Microbiologic testing was performed in 64 (77%) patients with no MRSA isolated in any cultures (Table 3).Table 3:Microbiologic Results

Conclusion
Antibiotic use in more than half of patients was not adherent to AGA guidelines. Carbapenems, piperacillin/tazobactam, and cephalosporins were commonly used. Vancomycin was often used, although no MRSA was isolated. Significant opportunities for antimicrobial stewardship for acute pancreatitis exist.

Disclosures
All Authors: No reported disclosures