bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1342. LiaX Decreases Killing By β-Lactam Antibiotics: Enterococcal Tolerance Revisited
Authors: Streling Ana , Panesso Diana , Singh Kavindra , Gomez Villegas Sara I , Malikzad Husna , Miller William R , Arias Cesar A 
Published: January 2025

Abstract

Background
Compared to other Firmicutes, enterococci are often tolerant to many antibiotics; combination therapy is used for severe, deep-seated infections. We have previously reported the LiaFSR system, a three-component cell-envelop stress regulatory system, mediates resistance and tolerance to daptomycin (DAP). The main effector, LiaX, harbors distinct N- and C-terminal domains. The N-terminal portion of LiaX is released into the extracellular milieu where it recognizes DAP and other antimicrobial peptides functioning as a sentinel and signal transduction protein to decrease DAP-mediated killing. LiaX likely acts through LiaF, a transmembrane protein necessary for the LiaX effect. We postulated that the LiaX-LiaF relay system may be involved in the β-lactam tolerance shown by E. faecalis (Efs).Figure 1.N-terminal domain of LiaX protects E. faecalis from ampicillin and ceftriaxone.

Methods
We used wild type (WT) Efs OG117 and derivatives: OG117liaF*11-14 (liaF deletion) and OG117 liaF*11-14::liaF (liaF complemented). Ampicillin (AMP) and ceftriaxone (CRO) broth-microdilution MICs were performed. N-terminal LiaX1-275 was expressed in E. coli and purified. Killing assays (5 replicates) with 0.5 X MICs of AMP and CRO were done, with and without LiaX1-275 (80 nM). Bacteria were diluted (∼1x105 CFU/mL) and used to inoculate test media containing antibiotic alone, antibiotic+LiaX1-275, and no antibiotic. After 2-hours of incubation at 37°C, samples were plated on BHI agar for enumeration.

Results
The CRO MICs for WT and complemented strains were 64 μg/mL, whereas it was 2-fold higher (128 μg/mL) for OG117liaF*11-14. All strains showed AMP MICs of 1 μg/mL. In the AMP killing assay, OG117 survival increased with the addition of LiaX1-275 (p &lt; .005). The addition of LiaX1-275 failed to increase survival of OG117liaF*11-14 in the presence of AMP compared to WT (p = 0.4). The survival advantage was restored in the complemented strain (p &lt; .0001). CRO showed a similar trend, i.e., increased survival in OG117 (p &lt; .01) and complemented strain (p &lt; .001), but not in OG117liaF*11-14 (p = 0.29).

Conclusion
We have discovered a novel pathway in Efs for antibiotic tolerance. The LiaF-LiaX signal relay, part of the enterococcal response to antibiotics, boosts organism survival, contributing to tolerance to multiple anti-enterococcal drugs.

Disclosures
William R. Miller, M.D., Merck: Grant/Research Support|UptoDate: Royalties
P-1360. Activity of Cefiderocol against Carbapenem Non-susceptible Enterobacterales, Including Molecularly Characterized Multidrug-resistant Clinical Isolates, Causing Infections in United States Hospitals (2020–2023)
Authors: Mendes Rodrigo E , Hubler Cory , Beekman Danielle , Maher Joshua , Sader Helio S , Castanheira Mariana 
Published: January 2025

Abstract

Background
Cefiderocol (FDC) is a siderophore cephalosporin that hijacks the iron transport system of Gram-negative bacteria to facilitate cell entry. FDC remains stable to hydrolysis in the presence of serine β-lactamases (BL) (e.g. ESBLs, KPC, and OXA-type carbapenemases) and metallo-BL (MBL). FDC and comparator activities were analyzed against carbapenem-nonsusceptible (nonS) Enterobacterales (ENT), including molecularly characterized isolates, collected as part of the SENTRY Antimicrobial Surveillance Program for the US.

Methods
15,147 ENT were collected from 35 sites in 2020–2023. Susceptibility (S) testing was performed by broth microdilution with cation-adjusted Mueller-Hinton broth (CAMHB) for comparators and iron-depleted CAMHB for FDC. CLSI criteria (same as the FDA) were used for FDC; whereas CLSI were applied for comparators, except for colistin (EUCAST). ENT with MIC ≥2 mg/L (nonS by CLSI) for imipenem or meropenem (MER) were screened for BL genes.

Results
1.4% (207/15,147) isolates were carbapenems-nonS, and among these 57.5% (119/207) carried carbapenemases. Class A blaKPC (72.3%; 86/119) prevailed, followed by class B MBL genes (17.6%; 21/119) and class D blaOXA-48 variants (5.9%; 7/119). FDC (96.6–98.3%S) had MIC50 of 0.5 mg/L and MIC90 of 4 mg/L against carbapenem-nonS and carbapenemase-carrying isolates; other agents had S of 6.7–86.5% (Table). FDC (100%S) and β-lactam-β-lactamase inhibitor (BL/BLI) combinations (96.6–100%S) were active against ENT carrying class A carbapenemases, whereas only FDC (MIC50/90, 2/4 mg/L; 95.2%S) had activity against those carrying class B genes. FDC and ceftazidime-avibactam (CAZ-AVI) were active (100%S for both) against ENT carrying class D genes. FDC (MIC50/90, 0.25/4 mg/L; 92.1%S), MER-vaborbactam (MIC50/90, 0.25/4 mg/L; 92.1%S) and CAZ-AVI (MIC50/90, 0.5/8 mg/L; 94.7%S) were most active against carbapenem-nonS, but carbapenemase-negative ENT.

Conclusion
FDC activity against carbapenem-nonS ENT collected in the US. FDC activity was consistent across different genotypes, including against isolates carrying carbapenemase genes, where approved BL/BLI combinations showed limited activity. These data demonstrate FDC as an important option for the treatment of infections caused by carbapenem-nonS ENT.

Disclosures
Rodrigo E. Mendes, PhD, GSK: Grant/Research Support
P-1380. Congenital Syphilis at Los Angeles General Medical Center, 2022-2023
Authors: Villarreal Diana , Lewis Katherine , Cielo Mikhaela , Klausner Jeffrey 
Published: January 2025

Abstract

Background
Congenital syphilis cases in the United States have increased 10-fold in the last decade. At Los Angeles General Medical Center (LAGMC), a large public hospital in Los Angeles, infants born to mothers with untreated syphilis during pregnancy continue to rise. We reviewed all the cases of neonatal congenital syphilis in 2022 and 2023 to describe sociodemographic and clinical characteristics and management history.

Methods
A search of the LAGMC Electronic Health Records uncovered all infant RPR test results in 2022 and 2023. Once case-patients were identified, we abstracted relevant information related to maternal health and infection history along with the infant medical history into a Redcap database. Statistical analysis was performed.

Results
Thirty-six infants were born to mothers with a history of inadequately treated syphilis in pregnancy. Compared to women who were adequately treated before or during pregnancy (n=62), women that were not adequately treated were more likely to have methamphetamine use (72% vs. 41%, p=0.004), cocaine use (19% vs. 2%, p=0.005), opiate use (34% vs. 9%, p=0.002), or no prenatal care (41% vs. 8%, p ≤ 0.001). Of the 12 infants with probable congenital syphilis, two infants had an abnormal physical exam. One infant had an RPR &gt; 4-fold the mother’s RPR. Four infants had bony changes on long bone radiography. Of the 36 exposed infants, 20 had successful lumbar punctures. Five met criteria for probable congenital syphilis from elevated CSF protein alone, with normal cell counts and non-reactive VDRL. Two infants had positive CSF VDRL.

Conclusion
Overall, 2 infants out of 12 with probable congenital syphilis were symptomatic at the time of birth, and the other 10 were identified from laboratory and radiographic evaluation. Sixteen infants did not have a successful lumbar puncture, but results of the lumbar puncture did not change treatment choice. Our review also identified maternal substance use and no prenatal care as risk factors for inadequate treatment of syphilis before or during pregnancy.

Disclosures
Jeffrey Klausner, MD MPH, Direct Diagnostics: Advisor/Consultant
P-1381. Gender-based Testing Differences for Chlamydia trachomatis and Neisseria gonorrhoeae in Military Service Members
Authors: Aleman-Reyes David Manuel , Aden James , Arroyo Cazurro Miguel A , Marcus Joseph 
Published: January 2025

Abstract

Background
Chlamydia trachomatis and Neisseria gonorrhoeae infections impose a significant burden to the military, due to its young, sexually active population. In previous studies, female service members had 3-5 times the rate of both these infections as compared to men for unclear reasons. The purpose of this study was to investigate if gender-based differences in infection rates for chlamydia and gonorrhea may be due to gender-based differences in testing practices.
Demographic Information of 1620 Military Service Members Tested for Chlamydia trachomatis and Neisseria gonorrhoeae at Brooke Army Medical Center and Wilford Hall Ambulatory Surgical Center June-September 2023

Methods
A retrospective chart review was conducted on military service members who underwent testing for chlamydia and gonorrhea at Joint Base San Antonio between June and September 2023. The local electronic health record database was queried to determine patient demographics (age, gender, race, ethnicity, rank, military branch), clinical setting and indications for testing.

Results
A total of 3768 patients were identified. 2148 female basic trainees who underwent mandatory entry screening were excluded, leaving 1620 (43%) patients for analysis. The cohort was predominantly female (67.5%) and enlisted (84.2%) with a median age of 27. Male patients were more likely to be tested for patient driven factors, such as symptoms (41.2%) or patient request (24.5%). Female patients were most frequently tested due to clinical algorithm (53.0%). Tested male patients were more likely to have a positive result than female patients for both chlamydia (8.7% vs 3.9%, p=&lt; 0.001) and gonorrhea (2.8% vs 0.4%, p=&lt; 0.001) (Table).

Conclusion
Although women were more frequently tested for chlamydia and gonorrhea infections, male service members had significantly higher positivity rates, with more patient-driven indications for testing. This study implies the higher positivity rates in female patients compared to the male patients that has been previously reported is at least partially due to a testing bias.

Disclosures
All Authors: No reported disclosures
P-1395. Safety and Effectiveness of LC16m8 for Pre-Exposure Prophylaxis Against mpox in High-Risk Population: An Open-Label Randomized Trial
Authors: Okumura Nobumasa , Morino Eriko , Nomoto Hidetoshi , Yanagi Mashiho , Takahashi Kozue , Iwasaki Haruka , Uemura Yukari , Shimizu Yosuke , Mizushima Daisuke , Fukushima Kazuaki , Kinai Ei , Shiojiri Daisuke , Itoda Ichiro , Onoue Yasuhiko , Kobori Yoshitomo , Nakamura Fukumi , Tokita Daisuke , Sugiura Wataru , Ohmagari Norio , Ujiie Mugen 
Published: January 2025

Abstract

Background
Since May 2022, the incidence of mpox cases has surged outside endemic regions. Although vaccination remains pivotal in mpox prevention, data on LC16m8, a third-generation smallpox vaccine, are scant. We provided LC16m8 pre-exposure prophylaxis opportunities to high-risk individuals, including those with HIV, and conducted a randomized controlled trial to assess LC16m8’s effectiveness in mpox prevention and safety.

Methods
Our multicenter randomized open-label trial enrolled men and women aged ≥18 years at high mpox risk who provided written consent. Participants were randomly assigned 1:1 to early or late vaccination groups, receiving vaccinations approximately 70 days apart. Primary endpoint: vaccine effectiveness (VE) against mpox development between early and late vaccinations. VE against severe mpox, symptoms, “take” incidence, and adverse events were secondary endpoints.

Results
A total of 1,135 participants were recruited; 570 and 565 were assigned to early and late vaccination groups, respectively; 530 and 476 were vaccinated. Median age: 41 years; 99.7% were male; 89.7% Japanese; and 34.4% HIV-infected. No mpox cases occurred during the observation period, precluding VE calculation. “Take” rates: 90.3% (HIV-infected), 94.6% (uninfected). Adverse events related to the study were observed in 96.6% and 98.0% of the HIV-infected and uninfected participants, respectively. No fatal adverse events were observed; serious adverse events (SAE): 0.6% (HIV-infected), 0.5% (uninfected). One HIV-uninfected participant reported pulmonary embolism and deep vein thrombosis as a causally undeniable SAE. Local skin reactions: 96.6% (HIV-infected), 97.9% (uninfected); systemic reactions: 63.6% (HIV-infected), 64.2% (uninfected).

Conclusion
LC16m8’s effectiveness in mpox prevention remains inconclusive. Yet, its use in well-controlled HIV-infected and -uninfected individuals showed no significant safety concerns, suggesting potential for targeted vaccination strategies in at-risk groups.

Disclosures
All Authors: No reported disclosures
P-1396. Compliance Rates to Updated CDC Guidelines and an Automatic Communication Intervention Following Positive Sexually Transmitted Infection Results in the Emergency Department
Authors: Taweh Noor , Cahill Patrick , Chhabra Jyoti 
Published: January 2025

Abstract

Background
The emergency department (ED) remains at the forefront of the growing sexually transmitted infection (STI) epidemic. Despite being a critical leverage point for STI management, current practices can be incongruent with recent 2021 CDC STI Guidelines. The transitory role of the ED poses challenges to establishing follow-up. We sought to assess the degree of deviation from CDC STI guidelines in the Hartford Hospital ED and optimize management by having positive STI tests automatically routed to the outpatient infectious disease (ID) clinic for follow-up.

Methods
This was a retrospective, observational study of 342 patients from October 31st, 2021 to August 18th, 2023. Pre-intervention, ED providers were solely responsible for reviewing results and contacting patients to return for treatment. An intervention was initiated on October 31st, 2022, whereby positive STI test results from the ED were automatically rerouted to the ID clinic EPIC inbox, eliminating the modulatory role of ED providers. Manual chart review was conducted to evaluate compliance to CDC guidelines and parameters before and after the intervention, including the rate of referral to and follow-up with ID.

Results
Significant deviations from CDC guidelines were observed: 78.8% of practitioners took inadequate sexual history, 95.0% did not order comprehensive STI screening (gonorrhea, chlamydia, HIV, and syphilis), and only 60.8% initiated empiric antibiotic therapy. Of those, only 71.6% were guideline-based therapies. This intervention was successful in decreasing the proportion of patients lost to follow-up; Prior to intervention, 3.9% of patients were seen in the ID clinic for follow-up which increased to 15.3% after intervention (p &lt; 0.001).

Conclusion
Although guidelines were updated almost 3 years ago, current practices remain incongruent with recommendations. Automatically rerouting positive STI results resulted in a higher rate of follow-up. We propose other hospital systems utilize a similar automatized system to minimize gaps in care and reduce burden on strained ED systems.

Disclosures
All Authors: No reported disclosures
P-1437. Racial Disparities in Inpatient Antibiotic Prescribing for Community-Acquired Pneumonia
Authors: Rock Matthew , Hamilton Keith W , Momplaisir Florence , Cressman Leigh , Lautenbach Ebbing , Dutcher Lauren 
Published: January 2025

Abstract

Background
Racial disparities have been reported in antibiotic prescribing for certain inpatient and outpatient conditions, but it remains unknown if antibiotic prescribing for inpatients with community-acquired pneumonia (CAP) have similar patterns despite long-standing guidelines for CAP treatment regimens. We evaluated racial disparities in antibiotic prescribing for inpatients with CAP at three hospitals within a health system.

Methods
We conducted a retrospective cohort study with data from the electronic health record using two binary metrics to evaluate differences in the appropriateness of antibiotic selection and duration by race. The cohort included non-ICU inpatients from 1/1/2019-12/31/2021 with a diagnosis of CAP based on ICD-10-CM code who received a systemic antibiotic within 48 hours of admission. We used multivariable logistic regression to determine the association of race with prescribing (selection and duration in separate models), adjusting for variables such as hospital, admitting service, age, sex, Charlson Comorbidity Index (CCI), and area deprivation index.

Results
Patient demographics are described in Table 1. Of 2,524 CAP episodes, subjects were prescribed an appropriate empiric antibiotic for an appropriate duration in 42.6% of cases. The rate of appropriate selection was 83%, while the rate of prescribing for the appropriate duration was 53% (Table 2). In the multivariable model, the following were associated with appropriate selection: hospital, lower CCI, and admitting service; race was not associated with antibiotic selection. Black race, hospital, lower CCI, and admitting service were associated with appropriateness of antibiotic duration. (Table 3).

Conclusion
While patient race was not independently associated with the likelihood of appropriate antibiotic selection, it was associated with a higher likelihood of appropriate duration. Importantly, the distribution of patient race differed significantly between hospitals and in both models we found that hospital site was associated with antibiotic prescribing appropriateness. Future research is required to explore the systems-level mechanisms creating these differences in order to ameliorate disparities.

Disclosures
All Authors: No reported disclosures
P-1438. Health-Related Social Needs and Guardian Adversity in Outpatient Pediatric Infectious Diseases
Authors: Day Melissa E , Choony Chitravati , Duan Qing , Burkhardt Mary Carol , Klein Melissa , Beck Andrew F , Schlaudecker Elizabeth P 
Published: January 2025

Abstract

Background
Infectious Diseases (ID) outpatient settings do not routinely screen for psychosocial needs of patients and families that may exacerbate infectious processes or challenge traditional treatment. We assessed the prevalence of health-related social needs (HRSN), guardian adverse childhood experiences (ACEs), and neighborhood-level socioeconomic deprivation in two pediatric outpatient ID clinics.

Methods
Using a cross-sectional study design, we approached English- and Spanish-speaking guardians of outpatient ID patients at two campuses. Guardians completed a HRSN screen (evaluating food/housing insecurity, transportation access, and mental health concerns) and the 10-question ACEs questionnaire (evaluating traumatic childhood experiences of guardians). Responses were entered into REDCap. We geocoded street addresses to identify census tract-level socioeconomic deprivation index (SDI) scores, with higher scores indicating more deprivation. We quantified individual HRSN items, total ACE scores, and SDI measures. We extracted clinical/demographic information from patient charts. Descriptive analyses were pursued. ANOVA analyses explored associations with psychosocial needs and SDI scores.Figure 1.Association of SDI score and Food Insecurity Over the Past 12 Months.

Results
To date, 221 caregivers have been surveyed, and results are described in Table 1. Most children identified as White, non-Hispanic, and English-speaking. Many families reported any food insecurity (15%), regular caregiver depressive symptoms (20%), and recent anxiety (70%). Four percent lived in an unsteady place, and 5% had transportation issues that affected access to medical care. Firearms were present in 35% of homes. Nineteen percent of guardians had high ACEs (≥4). The mean SDI score was 0.32 (range 0.11-0.71), similar to our institution’s primary service area. Higher SDI scores were associated with more food insecurity over the past 12 months (Figure 1, p&lt; 0.001) and the past week (Figure 2, p=0.01).Figure 2.Association of SDI Score and Food Insecurity Over the Past Week.

Conclusion
Guardians of children receiving ID outpatient care reported HRSNs and ACEs. SDI score may be a useful adjuvant to screening to identify more efficiently those at risk for challenges like food insecurity. Outpatient ID settings can identify and help mitigate these concerns in clinical encounters.

Disclosures
Elizabeth P. Schlaudecker, MD, MPH, Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant
P-1445. Evaluation of Achievement of Metabolic Goals in People with Human Immunodeficiency Virus (HIV) in the Illinois Department of Corrections (IDOC)
Authors: Khair Nivan , Vu Amber , Ruiz Jonathan M , Drwiega Emily N , Patel Mahesh C , Borgetti Scott , Badowski Melissa E 
Published: January 2025

Abstract

Background
The UIC-IDOC clinic is an interdisciplinary telemedicine clinic addressing HIV care needs of individuals in custody. The UIC-IDOC care team makes recommendations to medical providers regarding disease states outside of HIV. HIV contributes to increases in cardiovascular (CV) risk, along with diabetes (DM), hypertension (HTN), and hyperlipidemia (HLD). Managing comorbidities in patients with HIV (PWH) can lead to an overall reduction in CV risk. The goal of this study was to provide evidence that follow-up with IDOC telemedicine clinic had positive outcomes on achieving metabolic goals in individuals in custody.

Methods
This was a pilot retrospective cohort study evaluating the effectiveness of an interdisciplinary approach in achieving A1C, blood pressure, or lipid panels among PWH in custody. Adults diagnosed with HIV, on antiretroviral therapy (ART), and with a diagnosis of DM, HTN, and HLD were included between 1/1/2021 and 6/30/2022. The primary outcome evaluated the achievement of metabolic goals within 1 year compared to baseline, while the secondary outcome assessed medication optimization to guideline-recommended therapy for any diagnoses above.

Results
102 patients were included. Baseline characteristics are presented in Table 1. Notably, most PWH reported ART adherence and achieved viral suppression. For the primary outcome, there was no difference in the achievement of metabolic goals 1-year post-follow-up for all disease states, DM (p=0.347), HTN (p=0.833), and HLD (p=0.935). For our secondary outcome, there was a significant difference in the optimization of hypertensive medications by the last visit, Table 2.

Conclusion
Findings from this study offer insights into optimizing HIV care delivery within correctional settings and enhancing outcomes for this patient population. Based on this data, recommendations being made by the UIC-IDOC telemedicine clinic may not be consistently implemented. However, our study shows an interdisciplinary clinic's role in the medication management of individuals in custody and the potential to assist in reducing cardiovascular risk in PWH, especially in people with HTN. Furthermore, a high degree of viral suppression was demonstrated for this study which may predict adherence to medications for metabolic diagnoses.

Disclosures
Scott Borgetti, MD, GSK: Grant/Research Support