bluuebunny/crossref_metadata_2025_split huggingface dataset:
576. Chandipura virus infection: Time to think beyond Encephalitis?
Authors: Buch Kathan P , Buch Pankaj M 
Published: January 2025

Abstract

Background
Chandipura virus, first isolated in 1965, has caused several outbreaks in India, including significant ones in 2003-2004 in central India and in 2024 in western India. Typically affecting children aged 6-15, recent cases have shown an increase in extra-neurological manifestations.
Baseline characteristics of patients

Methods
This study, conducted at a tertiary care hospital in western India from July 1 to August 13, 2024, examined the epidemiology, clinical profile, and treatment outcomes of patients with Chandipura virus infections. It was a single-center, observational study including all patients with confirmed Chandipura virus infection (RT-PCR positive in CSF or sera).
laboratory characteristics of Patients

Results
Baseline Characteristics: This study involved 51 patients with a mean age of 10.27 (2.32) years, with 55% being male. All the patients were from endemic areas of Gujarat in India. The majority of the patients (90%) were immunocompetent. All cases (100%) were diagnosed positive on RT-PCR of CSF or sera.
Clinical and Laboratory Characteristics:
Common symptoms included fever (100%), headache (70%), altered sensorium (75%), circulatory collapse and shock (35%), and convulsions (25%). Symptoms lasted an average of 5.1 days. Liver dysfunction occurred in 60% of cases, and 19% had acute kidney injury. Abnormal PT, aPTT, and INR levels were found in up to 75% of cases. The main diagnoses were acute viral encephalitis (50%) and encephalitis with MODS due to circulatory collapse (40%).
All 51 patients received standard treatment per Indian government guidelines, including IV fluids, paracetamol, and management of airway, breathing, circulation, intracranial hypertension, and seizures. The median hospital stay was 6 days. Of the 51 patients, 37 died—21 from circulatory collapse and 16 from encephalitic symptoms. The remaining 14 survivors will be monitored for residual neurological issues.

Conclusion
In high-dengue-endemic countries like India, diagnosing CHPV, which can mimic hemorrhagic fever, is challenging. Diagnosis is often delayed, leading to poorer outcomes. Most patients showed symptoms of hemorrhagic fever combined with encephalitic features, highlighting the need for further research on CHPV’s impact on blood vessel endothelial cells.

Disclosures
All Authors: No reported disclosures
94. Efficacy of SCY-247, a Second-generation Triterpenoid Antifungal, in Three Murine Models of Invasive Fungal Infections
Authors: Wring Steve , Borroto-Esoda Katyna , Wiederhold Nathan P , Ibrahim Ashraf S , Angulo David A 
Published: January 2025

Abstract

Background
There are limited treatment options for invasive fungal infections (IFIs) with broad-spectrums of activity that can be delivered both orally and intravenously. SCY-247 is a second-generation novel triterpenoid antifungal in development. It has broad-spectrum activity covering yeasts, molds and dimorphic fungi, including azole- and echinocandin-resistant strains and can be given orally or intravenously. Recent in vivo murine efficacy studies were performed with SCY-247 and results from 3 studies demonstrating activity against Candida and Mucorales are presented.Table 1:Study Methodology Details

Methods
The in vivo activity of SCY-247 was assessed in murine models of invasive candidiasis (IC) caused by C. albicans and C. glabrata and a murine model of pulmonary mucormycosis (PM) caused by R. delemar. In each model, SCY-247 was administered by oral gavage, twice daily (BID), for seven days with doses ranging from 5 to 48 mg/kg. Efficacy endpoints included changes in tissue fungal burden (CFU) and/or survival. Details are shown in Table 1.

Results
SCY-247 demonstrated potent in vivo activity in all three murine IFI models. In each dose-dependent responses based on the primary endpoints of fungal burden and/or survival were observed. Significant reductions in kidney fungal burden vs placebo (P &lt; 0.01) were observed at doses ≥10 mg/kg against C. albicans and at doses ≥16 mg/kg against C. glabrata; significant reductions in lung fungal burden (P &lt; 0.01) were also observed in the C. glabrata model at doses ≥32 mg/kg. Bioanalysis demonstrated SCY-247 preferentially distributed to kidney and lung tissues versus plasma and reductions in C. glabrata fungal burden correlated with dose and exposure. Against pulmonary mucormycosis, treatment with SCY-247 at doses ≥32 mg/kg resulted in prolonged survival (P &lt; 0.05) and reductions in both lung and brain fungal burden vs placebo (P &lt; 0.05).

Conclusion
SCY-247 demonstrated significant in vivo activity in murine models of invasive candidiasis and pulmonary mucormycosis, and the antifungal responses correlated with dose and exposure.

Disclosures
Steve Wring, PhD, SCYNEXIS, Inc.: Advisor/Consultant Katyna Borroto-Esoda, MS, Scynexis Inc: Advisor/Consultant Nathan P. Wiederhold, PharmD, BioMerieux: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Mycovia: Grant/Research Support|Scynexis: Grant/Research Support|Sfunga: Grant/Research Support Ashraf S. Ibrahim, PhD, SCYNEXIS, Inc.: Advisor/Consultant|SCYNEXIS, Inc.: Grant/Research Support David A. Angulo, MD, SCYNEXIS, Inc.: Board Member|SCYNEXIS, Inc.: SCYNEXIS, INC Officer and Board Member, SCYNEXIS Patents|SCYNEXIS, Inc.: Stocks/Bonds (Public Company)
97. Hemophagocytic Lymphohistiocytosis in Disseminated Histoplasmosis: an Overlooked Diagnosis
Authors: Mandrell Burton , Savenka Tatsiana , Saccente Michael 
Published: January 2025

Abstract

Background
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome involving pathologic excitation of the immune system. Disseminated histoplasmosis (DH) is a known trigger of HLH. However, the prevalence of HLH in DH is not known. Limited data exist on risk factors and outcomes. The goals of this study are to determine the prevalence of HLH among participants with DH, identify risk factors for HLH in this population, and describe the treatment and outcomes of people with DH and HLH.

Methods
We retrospectively identified 110 cases of DH at our institution from 2014 to 2022. The diagnosis of DH required culture of Histoplasma capsulatum from a non-pulmonary site, or non-pulmonary tissue histopathology with yeast identifiable as Histoplasma, or a combination of clinical abnormalities consistent with DH plus detection of Histoplasma antigen in urine or blood (MiraVista Diagnostics). Established HLH-04 criteria defined HLH. Continuous variables are presented as medians with interquartile ranges. Categorical variables are compared with Fisher’s exact test or Mann-Whitney U test. We used odds ratios to identify potential predictors of HLH. P values &lt; 0.05 were considered significant.

Results
Among 110 participants with DH, 22 met criteria for HLH (Table 1). In the subset who were hospitalized, 23.7% (22/93) had HLH. Compared to participants without HLH, the HLH cohort was more likely to have serum ferritin above the limit of quantification (LOQ) ( &gt; 15,000 ng/ml), urine Histoplasma antigen above the LOQ ( &gt; 19 ng/mL), serum beta-D-glucan (BDG) above the LOQ ( &gt; 500 pg/mL), and more likely to be treated in the ICU (Table 2). There was no significant difference in HIV/AIDS status, race, sex, or in-hospital death/transition to hospice. All 22 participants identified with HLH received liposomal amphotericin B. 2 participants with HLH received etoposide, and 1 received IVIG.

Conclusion
Nearly a quarter of participants with DH admitted to our hospital had HLH. This is likely an underestimate because most were not assessed for every HLH criterion. Serum ferritin &gt; 15,000 ng/ml, urine Histoplasma antigen above the LOQ, and serum BDG above the LOQ should prompt investigation for HLH. Further studies are needed to assess optimal treatment strategies in this population.

Disclosures
All Authors: No reported disclosures
98. Multispecies Outbreak of Klebsiella pneumoniae Carbapenemase-3 (KPC-3)-producing Enterobacterales in an Acute Care Hospital – Virginia, 2023-2024
Authors: Langerman Steven D , Rankin Danielle A , Bonnefond Clarissa , Khan Mohammed , Fazal Amara , Grossman Marissa , Bernard Shaina , Stanton Richard A , Gable Paige , Moulton-Meissner Heather , Noble-Wang Judith , Halpin Alison L , Arduino Matthew , Breaker Erin , Ewing Thomas , Masters Thao , Harrington Anthony , Clancy Kristen , Turner Lauren , Lorentz Alexandra , Gali Katelin , Neal Stephanie , Hawker Emily , Rehkopf Kayleigh , Walters Maroya S , Bair Patricia 
Published: January 2025

Abstract

Background
Plasmid-mediated outbreaks have been associated with gaps in infection control (IC) and environmental reservoirs such as sink drains. In October 2023, the Virginia Department of Health (VDH) identified a cluster of four Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella variicola urinary tract infections among patients at Acute Care Hospital A (ACH A). VDH and CDC collaborated to investigate the source and prevent further transmission.

Methods
We reviewed medical records, directly observed IC practices (e.g., hand hygiene, sink hygiene, environmental cleaning), performed active surveillance in units with cases, and collected environmental samples. Clinical and environmental isolates harboring KPC underwent short-read whole-genome sequencing (WGS); long-read WGS was performed on a subset of isolates. We defined a case as K. variicola or other Enterobacterales with an IncN plasmid marker and blaKPC-3, blaTEM-1, dfrA14, and qnrS antimicrobial resistance genes from any specimen source in an ACH A patient.

Results
From August 4, 2023 to February 11, 2024, we identified 18 cases from 17 patients (urine: 11, rectal swab: 6, tracheal aspirate: 1 [Figure 1]). Organisms identified included K. variicola (14), Escherichia coli (2), K. oxytoca (1), and K. aerogenes (1). We observed gaps in hand hygiene adherence, disposal of antibiotics in handwashing sinks, storage of patient care supplies in sink splash zones, and gaps in environmental cleaning. KPC-producing K. variicola was recovered from a sink drain and an aerator in two sinks in one patient room. Clinical and environmental K. variicola isolates varied from 0-10 single nucleotide variants over 93.5% of a 5.3 Mbp core genome. The E. coli, K. oxytoca, and K. aerogenes cases had sequence overlaps of 92.5-100% with the IncN plasmid isolated from a clinical K. variicola (Figure 2).

Conclusion
Detection of KPC in an uncommon organism, K. variicola, led to the discovery of an outbreak of multiple Enterobacterales strains harboring a common plasmid. Clonal expansion and plasmid-mediated spread across species can occur in parallel in patients and environmental reservoirs. Facilities experiencing an increase in detection of a carbapenemase across multiple organisms should consider the potential for a plasmid outbreak.

Disclosures
All Authors: No reported disclosures
158. Hepatitis B Screening Among Persons With HIV Receiving Care from the U.S. Department of Veterans Affairs
Authors: Stone Stephen , Lee Rachel R , Beste Lauren , Lowy Elliott , Ross David , Weintrob Amy , Denyer Rachel V 
Published: January 2025

Abstract

Background
In the United States, around 8% of persons with HIV (PWH) are coinfected with Hepatitis B (HBV), influencing antiretroviral choice and conferring higher mortality. Despite recommendations for universal HBV screening in PWH, small US and international studies found 52-68% were ever screened. National US data on HBV screening in PWH that could inform quality improvement efforts is lacking.
Hepatitis B Screening in Persons with HIV Receiving Care in the US Veterans Health Administration

Methods
We used the Veterans Health Administration (VHA) Corporate Data Warehouse to conduct a service evaluation of longitudinal operational data collected during routine care in the integrated electronic health record. We assessed the proportion of PWH receiving HIV care through VHA (at least one encounter in the current or previous year) who have complete HBV serologic screening, defined as at least one result for each of hepatitis B surface antigen (sAg), core antibody (cAb) and surface antibody (sAb). We conducted two multivariate logistic regressions on complete HBV serologic screening using (1) demographic and comorbidity variables, and (2) geographic and facility variables.
Hepatitis B Screening Amongst Persons with HIV by Geographic and Facility Factors

Results
Of 30,412 PWH receiving VHA care, 24,913 (81.9%) had complete HBV serologic screening. Adjusted odds ratios (AOR) for complete HBV screening were significantly higher in PWH who were black or Hispanic, born from 1961 onwards, were homeless, or had comorbidities such as hepatitis C, mental health and substance use disorders, as shown in Table 1, but did not differ significantly by sex. AOR for complete HBV screening were significantly lower for PWH seen at rural and lower complexity (smaller) facilities as shown in Table 2. Among non-immune PWH without hepatitis B (sAg negative, no prior reactive sAg), 55% subsequently received at least 1 dose of hepatitis B vaccine after a median 370-day interval (IQR 75-1512) as shown in Figure 1.
Time to Administration of At Least One Dose Of Hepatitis B Vaccine in Persons with HIV with Negative Hepatitis B Surface Antigen Lacking Prior Positive Surface Antibody Results.

Conclusion
Our data provide insight into current HBV screening practices for PWH in a nationwide US health system. Overall HBV screening rates were high, but 18.1% of PWH had incomplete HBV screening with cAb most frequently missing. Lower odds of HBV screening in smaller facilities and rural populations underscore the need for tailored strategies to ensure equitable access. Our data will inform quality improvement efforts to enhance screening practices for HBV among Veterans living with HIV.

Disclosures
All Authors: No reported disclosures
162. Comparison of Clinical Risk Factors, Outcomes and Molecular Epidemiology of ESBL and non-ESBL Enterobacterales Bacteremia in Solid Organ Transplant Recipients
Authors: Hanna Zachary W , Birk Navina K , Alangaden George J , Suleyman Geehan , Kaur Jagjeet , Ramesh Mayur 
Published: January 2025

Abstract

Background
Infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales are associated with adverse outcomes in recipients of solid organ transplants (SOTr). This study aims to elucidate the risk factors, outcomes, and molecular epidemiology associated with ESBL Enterobacterales bacteremia (ESBL EB) in abdominal SOTr.Table 1:Risk Factors, Clinical Characteristics and Outcomes

Methods
This observational cohort study was performed on abdominal SOTr with ESBL EB (cases) and non-ESBL EB (controls) at Henry Ford Health between August 2014 and February 2023. We performed whole genome sequencing on all blood isolates; sequencing libraries were created using +QIAGEN QIAseq FX DNA Library Kit according to manufacturer’s instructions and sequenced on Illumina NextSeq 2000. Fastq files were used to determine the distribution of traits and resistance genes using the 1928 Platform. Demographic, risk factors, clinical characteristics, outcomes and molecular sequence data were evaluated. Primary outcome was 30-day mortality.Figure 1:Percentage of E. coli isolates with resistome mutations

Results
56 patients were included: 31 (55%) cases and 25 (45%) controls. Liver and kidney transplant recipients were 28 (58%) and 18 (32%). Median age was 65 years and 54% were female. Risk factors for ESBL EB included liver transplant recipients (p &lt; 0.001), second surgery &lt; 30 days (p=0.01), primary graft dysfunction (p=0.02), and acute rejection &lt; 3 months prior to BSI (p=0.001) (Table 1). Both 30-day (p=0.001) and 90-day (p=0.015) mortality were higher in the ESBL EB group. ST131 (57%) and ST410 (21%) were the predominant sequence types identified in ESBL E. coli isolates. Among ESBL K. pneumoniae, ST16, ST39, ST45, and ST219 were common. Resistome analysis identified β-lactam mutations in all isolates (figure 1 and figure 2). Additional resistance genes that were not phenotypically expressed in ESBL isolates were identified.Figure 2:Percentage of K. pneumoniae isolates with resistome mutations

Conclusion
Our study demonstrates the high mortality associated with ESBL EB in SOTr and highlights the risk factors and molecular characteristics of these infections. Clinical significance of the additional resistance genes identified needs further investigation. These findings provide insights for targeted management strategies in this high-risk population.

Disclosures
Mayur Ramesh, MD, AstraZeneca: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant
203. Screening and Targeted Prophylaxis for Clostridioides Difficile Infection: STOP-CDI
Authors: Ziegler Matthew J , Anesi Judith , Tolomeo Pam C , Glaser Laurel , Cowden Laura , Cressman Leigh , Huang Elizabeth , Patel Alexa , Lautenbach Ebbing , Kelly Brendan 
Published: January 2025

Abstract

Background
Patients receiving immunosuppression for oncology treatment and transplantation are at highest risk for developing hospital-onset C.difficile infection (HO-CDI). We studied a prophylactic enteral vancomycin intervention implemented to reduce HO-CDI during high-risk inpatient admissions among immunocompromised patients.

Methods
The STOP-CDI intervention was implemented on 11/2021 at the Hospital of the University of Pennsylvania. Patients admitted for solid-organ transplant, autologous stem cell transplant, CART, or treatment for leukemia were screened for colonization with
C.difficile. Colonized patients were placed in contact isolation and were recommended oral vancomycin prophylaxis for a duration of 10 days or until discharge. Patients were compared to concurrent controls and historical controls in the two years prior to implementation of the STOP-CDI intervention. Concurrent controls were eligible for screening, but research staff were not available to perform screening. The primary study outcome was the development of HO-CDI, defined as a positive clinical diagnostic test after hospital day 3 but prior to discharge. Secondary outcomes included 90 day CDI, stool output, length of stay, VRE infection, and mortality. The impact of the STOP-CDI intervention was assessed using logistic and Poisson regression, with propensity-score weighting calculated using inpatient treatment category.

Results
Between 11/2021 and 12/2023, 692 patients were screened for C.difficile, 11% were colonized. Characteristics of those enrolled and matched controls are displayed in Table 1. Compared to matched controls, the odds of HO-CDI was significantly lower in the intervention group (OR 0.21, P&lt; 0.001) with a number needed to screen of 31 (Figure 1). We also identified significant reductions in 90-day HO-CDI, stool output, and length of stay (Table 2). There was no detected difference in VRE infection or mortality.

Conclusion
The STOP-CDI intervention was effective at reducing HO-CDI, LOS, and symptoms of C.difficile in this high-risk cohort. Future work will assess the ability of a targeted screening and prophylaxis approach to reduce transmission of C.difficile on units and its utility in other patient populations.Figure 1.Number Needed to Screen to Prevent One Hospital-Onset C.difficile Infection.

Disclosures
All Authors: No reported disclosures
205. Utilization of the Four Themes of the CDC/ATSDR SVI Interactive Map in Assessing Initial Clostridioides difficile Infection Outcomes
Authors: Afable Timothy , Zhou Anna , Tan Karen , Abdul-Mutakabbir Jacinda C 
Published: January 2025

Abstract

Background
Social determinants of health (SDoH) (e.g., education, clean water, health care access) are external factors shown to impact health outcomes. Inequities in SDoH have been hypothesized to contribute to poorer Clostridioides difficile infection (CDI) outcomes. The Centers for Disease Control’s (CDC) Social Vulnerability Index (SVI) is a composite measure of neighborhood (census tract) based on four major themes: socioeconomic status (SES), housing characteristics (H&C), race/ethnicity (REM) status, and housing and transportation (H&T). There is a cessation of literature that describes the impact of each SVI theme on CDI outcomes. The objective of this study was to utilize the four themes of the CDC SVI to determine the impact of SDoH on initial CDI severity and all-cause mortality outcomes.

Methods
Adult patients admitted to Loma Linda University Medical Center (LLUMC) with an initial episode of CDI between January 2020 to June 2021 were included. Patient residential addresses were collected and input into the CDC/ATSDR SVI Interactive Map. Vulnerability groups were congregated into 2 main subgroups [patients with SVI scores of &lt; 0.4999 are grouped as low vulnerability (LV) and patients with SVI scores of ≥ 0.5 are grouped as high vulnerability (HV)].

Results
206 patients were included, and those with an overall HV SVI score were more likely to have a higher all-cause mortality rate and to present with severe or fulminant initial CDI compared to those with a LV score. The frequency of initial severe CDI was 3x greater for the SVI themes of SES and H&C [61/206 (29.61%) vs 19/206 (9.22%)] in patients with a HV score compared to those with LV scoring. Further, patients who presented with an HV score for the H&T theme were more likely to present with initial severe (26.21% vs 12.62%) or fulminant CDI (13.11% vs 5.34%) versus those with a LV score. When considering the REM status theme, the initial fulminant CDI diagnosis was about 37x greater among individuals with a HV score (17.96% vs 0.49%) and mortality 9x greater when compared to those with LV scoring (8.74% vs 0.97%).

Conclusion
HV scores across SES, H&C, REM status, and H&T correlate with increased CDI severity and mortality rates. Further research and targeted interventions should be identified.

Disclosures
Anna Zhou, PharmD, Melinta Therapeutics: Honoraria Jacinda C. Abdul-Mutakabbir, PharmD, MPH, CSL Sequiris: Advisor/Consultant|CSL Sequiris: Honoraria|GSK: Advisor/Consultant|GSK: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria