bluuebunny/crossref_metadata_2025 huggingface dataset:
P-1233. Application of Pharmacometrics in the Personalized Colistin Dosing Recommendation
Authors: Seok Hyeri , Choi Suein , Han Seunghoon , Choi Won Suk , Park Dae Won
Published: January 2025

Background

Colistin is frequently used as a treatment for infections caused by carbapenem-resistant Gram-negative bacteria. Colistin dosing should be adjusted according to the patient's renal function because the prodrug, colistin methanesulfonate (CMS), is partially removed by the kidney. Intensive care unit (ICU) patients may require individualized dosing to prevent nephrotoxicity or treatment failure due to the highly variable pharmacokinetics (PK) of colistin.Figure 1.Example of colistin dosing recommendation program – Patient information input

Methods

Colistin plasma concentration data from ICU patients who received colistin from June 2019 to August 2022 in Korea University Hospital were included in the dataset for this population PK analysis. We developed a population PK model for colistin using ICU patients, and established therapeutic drug monitoring software. A population PK analysis was performed using the first-order conditional estimation method with interaction in non-linear mixed effects modeling. We used the open-source R Shiny program to establish Colistin TDM software. The structural PK model and the final estimates of both fixed-effect and random-effect parameters were translated into an R code.Figure 2.Example of colistin dosing recommendation program – Simulation outputRecommendations provide the loading and maintenance doses based on patient information. Maintenance dose depends on the predicted colistin trough and peak levels, and the interval and infusion time of colistin administration.

Results

We enrolled 176 colistin observations from 22 patients in the dataset. A two-compartment, first-order elimination model best described the PK of Colistin A, one-compartment, first-order elimination model for PK of Colistin B, and one-compartment, first-order elimination model for PK of CMS. In the results from the covariate analysis, GFR estimated by Cockcroft–Gault equation and albumin level was included as a statistically significant covariate of total clearance of CMS, and body weight was selected as a covariate of CMS volume of distribution. The two-compartment structure model for Colistin and CMS, the final estimates of both fixed effects and random effects from the PK model and the log-likelihood Equation (5) for estimating ηi were implemented in R script. A draft version of the software is now available at http://mychloe00.shinyapps.io/colistin_new.

Conclusion

We developed colistin TDM software using PK parameters in ICU patients for individualized colistin administration. Further research is needed to determine whether colistin is actually administered within the therapeutic range through the application of this software.

Disclosures

All Authors: No reported disclosures
P-1240. Optimal Vancomycin Model Selection for Obese Patients Receiving Outpatient Parenteral Antimicrobial Therapy (OPAT)
Authors: Couch Kimberly A , Luu Quyen , Prokesch Richard C , Adams John S , John Joseph F , Van Anglen Lucinda J
Published: January 2025

Background

Optimal OPAT dosing of vancomycin (VAN) is challenging in obese patients. Multiple Bayesian pharmacokinetics (PK) models to aid in AUC estimation exist, including several obesity-specific models. PK population models in the absence of drug serum levels (a priori) are useful to initiate therapy, but once drug serum levels are obtained, model performance is based upon individual patient PK (a posteriori). This study is the first evaluation of the optimal PK model for obese patients receiving OPAT.

Methods

Analysis included all OPAT patients who received VAN in 2022-2023 with at least one therapeutic drug level, and a body mass index (BMI) ≥ 30 kg/m2. Data collection included demographics, anthropometrics, treatment information, laboratory values, and AUC24. Ten PK models were used to predict VAN serum concentrations and calculate AUC24 using a Bayesian dosing software. The performance of each model was assessed using a priori root mean square error (RMSE) and a posteriori RMSE for each model. The average RMSE was also calculated for patients with BMI 30-39.9 kg/m2 and for those ≥40 kg/m2. The model with the best performance for each BMI category was reported.

Results

Of 920 VAN OPAT patients, 420 (45.6%) were identified with a BMI ≥30 kg/m2. Population characteristics are included in Table 1, with 80% having a BMI 30-39.9 kg/m2. Median duration of VAN was 23 days (IQR: 12-35). The RMSE calculations per model and BMI groups are shown in Table 2. Best model fit varied among BMI groups and is indicated in bold type. For RMSE a priori, the Crass model performed the best for BMI 30-39.9 kg/m2 and the UVM model was best for BMI ≥40 kg/m2. The RMSE a posteriori with best performance for BMI 30-39.9 kg/m2 was Thompson capped, with UVM and Goti also performing well. For BMI ≥40 kg/m2, RMSE a posteriori, the Goti model was the best performing.

Conclusion

Obesity models provided good performance for a priori predictions and performed similarly to non-obese models in a posteriori predictions. This research supports use of both obesity and non-obesity models for VAN PK in OPAT.

Disclosures

Joseph F. John, Jr., MD, FACP, FIDSA, MicroGenDx: Advisor/Consultant Lucinda J. Van Anglen, PharmD, Cumberland Pharmaceuticals: Grant/Research Support|Ferring Pharmaceuticals: Grant/Research Support|Novartis Pharmaceuticals: Grant/Research Support|Takeda Pharmaceuticals: Grant/Research Support
P-1245. Optimizing Antibiotic Dosing in Burn Patients: Real-Time Therapeutic Drug Monitoring for Enhanced Therapeutic Efficacy
Authors: Paulson Shon , Biju Sanju
Published: January 2025

Background

Burn patients often receive antibiotic therapy, but optimal dosing can be challenging due to variability in pharmacokinetics. This study aimed to assess the accuracy of antibiotic dosing in burns and the impact of real-time dose adjustment via therapeutic drug monitoring (TDM).

Methods

Given the challenges in predicting pharmacokinetics in burn patients, we conducted a 3-year prospective, monocentric, randomized, controlled trial to assess antibiotic dosing accuracy and the effect of systematic therapeutic drug monitoring (TDM) with same-day real-time dose adjustment to maintain therapeutic antibiotic concentrations. Forty-three consecutive burn patients receiving antibiotics were screened at a tertiary care hospital in India. Forty met the inclusion criteria; one declined participation, and another withdrew consent, leaving 21 patients each in the intervention and standard-of-care groups. A total of 38 infection episodes were analysed.

Results

Before the intervention, only 35 out of 67 (52%) initial trough concentrations were within the therapeutic range. No significant difference was found between groups in the initial trough concentrations (adjusted hazard ratio = 1.39 [95% CI, 0.81 to 2.39], P = 0.227) or the time to achieve the target concentration. However, due to real-time dose adjustments, the intervention group showed a higher proportion of trough concentrations within the predefined range (38/51 [74.5%] versus 33/58 [56.9%]; adjusted odds ratio [OR] = 2.34 [95% CI, 1.17 to 4.81], P = 0.018), spent more days within the target range (157 days/245 days on antibiotics [64.1%] versus 138 days/253 days on antibiotics [54.5%]; adjusted OR = 1.64 [95% CI, 1.16 to 2.32], P = 0.005), and had fewer subtherapeutic trough concentrations (19/88 [21.6%] versus 32/99 [32.3%]; adjusted OR = 0.47 [95% CI, 0.26 to 0.87], P = 0.015). No significant difference in infection outcomes was observed between the study groups.

Conclusion

Systematic TDM with same-day real-time dose adjustment was effective in achieving and maintaining therapeutic antibiotic concentrations in burn patients, minimizing both over- and underdosing.

Disclosures

All Authors: No reported disclosures
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

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

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

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

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

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

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 < 0.01), especially for extraintestinal amebiasis (prevalence rate ratio = 0.35; 95% CI, 0.22-0.57; P < 0.01) compared with intraintestinal amebiasis (prevalence rate ratio = 0.81; 95% CI, 0.71-0.93; P < 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

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

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

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
P-1355. Trends in Carbapenemase and Co-carbapenemase Production among Enterobacterales in Latin America: SMART 2018-2022
Authors: Wise Mark G , Polis Thales , Siddiqui Fakhar , Young Katherine , Motyl Mary , Sahm Daniel F
Published: January 2025

Background

The proliferation of carbapenemases in many geographies has compromised the effectiveness of the carbapenem class of antimicrobials and constitutes a major clinical problem. However, carbapenems paired with β-lactamase inhibitors, like imipenem/relebactam (IMR), can restore their activity against isolates carrying some types of carbapenemases. We evaluated trends in carbapenemase and co-carbapenemase production among Enterobacterales collected as part of the SMART surveillance program in Latin America.

Methods

In 2018-2022, 47 clinical labs in 11 countries in Latin America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico, Panama, Peru, Puerto Rico, Venezuela) each collected up to 250 consecutive Gram-negative pathogens per year from patients with bloodstream, intraabdominal, respiratory tract, and urinary tract infections. MICs were determined using CLSI broth microdilution and interpreted with 2024 CLSI breakpoints. Most imipenem (IPM) nonsusceptible non-Morganellaceae Enterobacterales and ceftolozane/tazobactam (C/T) nonsusceptible Enterobacterales were screened for β-lactamases genes.

Results

Of the 29,419 Enterobacterales collected, 6669 tested non-susceptible to IPM or C/T; of these, 4474 (67.1%) were characterized molecularly. KPC was the most frequently observed carbapenemase each year, ranging from 40.8% of the characterized isolates in 2021 to 31.1% in 2022, exhibiting an overall slight decreasing trend (Fig. 1). In contrast, the rate of NDM detection increased annually, ranging from 2.0% of the characterized isolates in 2018 to 20.8% in 2022. Rates of detection of other carbapenemases, including OXA-48-like, VIM, IMP and GES remained low and relatively stable over the studied time frame. Detection of carbapenemase co-carriers peaked in 2021 (3.5%), with isolates harboring NDM & KPC the most common genotype (Fig. 2).

Conclusion

KPC was the most commonly encountered carbapenemase among Enterobacterales in Latin America from 2018-2022, suggesting agents that retain potency against KPC-carrying Enterobacterales, like IMR, remain appropriate therapies. However, the increasing trend of NDM detection in this region is of concern as it severely limits treatment options.

Disclosures

Daniel F. Sahm, PhD, Pfizer, Inc.: Advisor/Consultant
P-1358. Understanding Fungal Infections and Trends in Fungal Resistance: A Single Center Evaluation
Authors: Islam Nuzhat , Haste Nina , Kline Ahnika , Abeles Shira
Published: January 2025

Background

Invasive fungal infections cost the US health care system billions and are challenging to treat. In 2021 alone, the CDC estimates that fungal infections contributed to over $7 billion in direct medical costs and over 7,000 deaths in the US. The most common agents used to treat clinical fungal infections are azoles. However, antifungal resistance is on the rise. Exposure to agricultural fungicides has been identified as likely contributing to increased resistance to medical azoles, as there has been incidence of infection with azole-resistant fungi in patients who were azole-naïve. Furthermore, in vitro studies have demonstrated that fungi exposed to agricultural azoles develop cross-resistance to medical azoles. This study aims to describe retrospective antifungal susceptibility trends for medical azoles in patients at UCSD Health and agricultural azole use in San Diego and Imperial Counties.

Methods

Chart review was used to obtain sensitivity data (minimum inhibitory concentrations or MICs) for non-Candida fungal isolates sent for susceptibility testing from UCSD Health patients from January 2016 through February 2024. Data on fungal isolates including species, date of isolate collection, susceptibility data, and patient zip code were collected. Agricultural azole use data is publicly available from the California Department of Pesticide Regulation and was analyzed for azoles applied in San Diego and Imperial Counties from 2016 to 2021.

Results

189 fungal isolates from 170 patients were included in the analysis. Fusarium demonstrated high resistance to common medical azoles which did not change over time. A. fumigatus also exhibited minimal change in MICs for itraconazole and posaconazole but showed possible increase in MICs over time for voriconazole and isavuconazole. Imperial County had an 8 to 10-fold higher use of agricultural azoles compared to San Diego County.

Conclusion

Fusarium demonstrated resistance to all common medical azoles. There may be a possible increase in resistance of A. fumigatus to voriconazole and isavuconazole over time, however this is limited by small sample size. This study highlights the need for increased antifungal susceptibility testing at UCSD Health.

Disclosures

Nina Haste, PharmD, PhD, Novartis: Spouse is an employee
P-1369. Impact of the E152K Mutation in Resistance to Taniborbactam and Evolutionary Advantages of NDM-9
Authors: Vila Alejandro J , Delmonti juliana , Zuccato Francesco G , Pennesi Jazmin , Parodi Clarisa , Drusin Salvador I , Moreno Diego , Bonomo Robert A , Gonzalez Lisandro
Published: January 2025

Background

NDM is one of the most prevalent carbapenemases worldwide. Boronate-based inhibitors able to target Metallo−β-lactamases, MBLs, such as taniborbactam (TAN) and xeruborbactam (XER), are promising new drugs. However, NDM-9, the third most widespread variant of NDM-1 is refractory to the action of TAN. The E152K substitution in NDM-9 disrupts an attractive electrostatic interaction between the Glu residue in NDM-1 and the side chain of the inhibitor. We aimed to explore how the E152K was selected before the clinical use of TAN and its possible evolutionary pathways.

The C-terminal dynamics that tags protein degradation is quenched in apo-NDM-9

The C-terminal dynamics that tags protein degradation is quenched in apo-NDM-9

Methods

Minimum inhibitory concentrations of ceftazidime in Escherichia coli cells expressing NDM variants were determined in Luria Bertani (LB) media with increasing concentrations of dipicolinic acid (DPA). NDM-1 and NDM-9 were expressed in E. coli BL21(DE3) pLysS and purified by affinity chromatography. Site-directed mutagenesis was performed. Steady-state catalytic parameters were determined by initial rate measurements and/or by analysis of the progress curves, measured in HEPES buffer, pH 7.5 at 25°C. Deletion mutants in E. coli were obtained by CRISPR. NMR spectra were run in a 700 MHz Bruker spectrometer. Docking simulations were performed by using Glide.Figure 2.Protein levels in the periplasm of E. coli cells expressing different NDM variants as measured by immunoblotting upon zinc starvation.

Results

NDM-9 is able to confer higher resistance to ceftazidime than NDM-1 under zinc deprivation since apo-NDM-9 is more stable against the periplasmic proteases. NMR reveals that the C-terminal stretch recognized by the protease Prc is more rigid in apo-NDM-9, protecting this variant towards degradation. Despite this, E152K substitution is present only in NDM-9. We obtained new variants of more frequent substitutions such as M154L and A233V. The two double variants and the triple variant were generated. These combinations gave rise to NDM variant hyper-stable against degradation, which also showed resistance to TAN, as supported by docking experiments.

Conclusion

Resistance to TAN exhibited by NDM-9 is a secondary gain-of-function elicited by the E152K substitution, that represents a clinical threat since it stabilizes the protein under zinc limiting conditions. The finding of new combinations on the genetic background of NDM-9 giving resistance to TAN suggests that NDM-9 can further evolve by acquiring more mutations.

Disclosures

All Authors: No reported disclosures
P-1370. Molecular Bases and Mechanistic Insights of NDM-mediated Resistance to Cefiderocol
Authors: Vila Alejandro J , Warecki Brenda A , Mojica Maria F , Tomatis Pablo , Bethel Christopher , Rodriguez Magdalena , Ono Daisuke , Bahr Guillermo , Drusin Salvador I , Moreno Diego , Mahler Graciela , Bonomo Robert A
Published: January 2025

Background

Cefiderocol (FDC) is a novel cephalosporin with a siderophore-mimicking moiety that favors uptake into the periplasm through iron transporters. FDC was reported as the only cephalosporin refractory to hydrolysis by metallo-β-Lactamases (MBLs). However, resistance to FDC has been reported due to substitutions in the iron transporter coupled to the expression of the MBLs NDM-1 and NDM-5. In contrast, resistance emergence involving other MBLs such as VIM or IMP are not known. We aimed to identify the interaction of FDC with NDM and other MBLs.Table 1.Kinetic parameters of FDC hydrolysis by different MBLsNDM variants show considerable activity in FDC hydrolysis. In contrast, VIM-2 and IMP-1 show poor activity.

Methods

MICs values of FDC against Escherichia coli DH10B cells expressing different MBLs cloned into a pHSG298 vector were determined by the microdilution method in iron-depleted cation-adjusted Mueller-Hinton broth. NDM-1, NDM-5, IMP-1 and VIM-2 were expressed in E. coli BL21(DE3) pLysS and purified by affinity chromatography. Steady state catalytic parameters were determined by initial rate measurements measured in HEPES buffer, pH 7.5 at 25°C. NMR spectra were run in a 700 MHz Bruker spectrometer. Stopped-flow data were acquired in an Applied Photophysics spectrophotometer.

Mechanism of MBL-mediated resistance to FDC

Under high levels of NDM expression, the enzymatic activity counter the cefiderocol action, confering bacterial resistance against this antibiotic.

Results

MIC values of FDC in E. coli cells expressing NDM variants were 2 μg/ml, similar to NDM-1. Steady-state kinetic measurements showed that NDM-1 and NDM-5 hydrolyze FDC efficiently, with kcat/KM values of 1.9 and 1.2 x10^6 M-1s-1, respectively. In contrast, IMP-1 and VIM-2 displayed poor catalytic efficiencies (Table 1). Electrospray ionization mass spectrometry (ESI-MS) revealed that FDC forms an adduct with MBLs, which is significantly more stable in the case of IMP-1 and VIM-2. Stopped flow experiments under pre-steady state conditions show that both IMP-1 and VIM-2 form a stable adduct with FDC, that results in enzyme inhibition. Instead, NDM-1 is poorly inhibited since the formed adduct is less stable. NMR experiments confirmed the formation of an hydrolysis product and adduct.

Conclusion

Our results indicate that NDM-1 and NDM-5 hydrolyze FDC efficiently, in contrast to the poor activity of IMP-1 and VIM-2. These findings support the observation that clinical resistance is linked to overexpression of NDM variants and not to IMP-1 and VIM-2. This may guide the use of FDC against a specific group of MBLs and justifies pairing with an MBL inhibitor.

Disclosures

All Authors: No reported disclosures
P-1374. Syphilis in an American Indian Population: A Descriptive Analysis of Cases
Authors: Blair Andrea L , Comiford Ashley L , Mera Jorge
Published: January 2025

Background

Syphilis, a sexually transmitted infection, caused by the bacterium Treponema subspecies pallidum. Because of its numerous varied clinical presentations, it has earned the term "the great imitator and mimicker." Between 2017 and 2021, syphilis rates in the US increased by 72%, and Oklahoma cases increased by 223%. Further, American Indian/Alaska Natives (AI/AN) are disproportionately burdened by the increase in syphilis rates.

The objective of this presentation is to describe demographic characteristics of AI individuals diagnosed with syphilis between 2016 and 2023 within the Cherokee Nation Health Services (CNHS) system.

Methods

We extracted patient data collected through the CNHS electronic health record system. Individuals were included in this analysis if they had a positive syphilis result from January 1, 2016 through July 1, 2023. We analyzed the data using descriptive statistics including counts and percentages.

Results

Over the study period, 375 individuals were diagnosed with syphilis. The majority of individuals were 34 years or younger (61.5%), 50% of were female, 69.3% had a non-emergency or urgent care healthcare visit within the previous 12 months. About 45% had insurance, and 84% were single. Nearly 85% of individuals resided in a county with a Cherokee Nation clinic and 53.3% received treatment documented in the EHR. Most individuals were diagnosed during the COVID-19 pandemic (75.2%) and 45.1% were diagnosed through the emergency or urgent care departments. About 13% had a diagnosis of HCV, 30% had more than one other STI, and 16% of individuals received HIV PrEP treatment.

Conclusion

In the Cherokee Nation, syphilis primarily affects women of childbearing age, with a significant portion diagnosed in urgent care and emergency department settings, yet only 53% receive treatment. Investigating the reasons behind such low treatment rates and devising interventions to enhance them will be pivotal in curbing the surge in syphilis cases. Crucially, identifying demographic and other pertinent factors that could pinpoint those vulnerable to syphilis is imperative. Further research should concentrate on delineating risk factors for syphilis in this demographic and implementing preventive measures accordingly.

Disclosures

All Authors: No reported disclosures
P-1375. Evaluation of Comprehensive STI Screening in the Emergency Department Setting
Authors: Sciarra Braden , Frasca Katherine , Montague Brian T
Published: January 2025

Background

Sexually transmitted infections (STI) are a common reason for emergency department (ED) evaluation. Patients diagnosed with or suspected to have an STI are also at risk for other STIs, and should be screened in accordance with Center for Disease Control (CDC) recommendations.Figure 1:Percentage of HIV screenings among ED patients tested for STIs

Methods

This study is a retrospective analysis of comprehensive STI screening conducted at eleven freestanding emergency departments associated with an academic referral center. Individuals tested for gonorrhea, chlamydia, and syphilis between 1/1/2019 and 12/31/2023 in the emergency department were evaluated for the completion of appropriate comprehensive STI screening, defined as the completion of HIV co-testing during the same ED encounter. Additional evaluation of HIV testing was also completed in higher risk individuals that tested positive for gonorrhea and/or chlamydia.Figure 2:Percentage of HIV screenings among ED patients testing positive for gonorrhea or chlamydia

Results

The analysis showed that comprehensive STI screening in the emergency department was completed in only 2.9% of the 10,895 patients that were screened for gonorrhea, chlamydia, or syphilis. The rate of comprehensive STI screening in the emergency department was 2.6% among the 2,082 patients that tested positive for gonorrhea and/or chlamydia.

Conclusion

The CDC recommends HIV screening for all persons that present for evaluation of possible sexually transmitted infections. Our analysis of individuals undergoing STI screening in the ED demonstrates a significant gap in HIV screening, including amongst higher risk individuals that have tested positive for gonorrhea and/or chlamydia. Based on these results, a comprehensive STI screening educational tool was developed within the electronic medical record to increase comprehensive STI screening. Further analysis of these interventions will be studied in the future.

Disclosures

Brian T. Montague, DO MS MPH, Regeneron: Grant/Research Support