bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole-genome sequencing reveals the impact of lipid pathway and APOE genotype on brain amyloidosis
Authors: Patel Maulikkumar , Pottier Cyril , Fan Kang-Hsien , Cetin Arda , Johnson Matthew , Ali Muhammad , Liu Menghan , Gorijala Priyanka , Budde John , Shi Ruyu , Cohen Ann D , Becker James T , Snitz Beth E , Aizenstein Howard , Lopez Oscar L , Morris John C , Kamboh M Ilyas , Cruchaga Carlos
Published: January 2025

Amyloid-PET imaging tracks the accumulation of amyloid beta (Aβ) deposits in the brain. Amyloid plaques accumulation may begin 10 to 20 years before the individual experiences clinical symptoms associated with Alzheimer’s diseases (ad). Recent large-scale genome-wide association studies reported common risk factors associated with brain amyloidosis, suggesting that this endophenotype is driven by genetic variants. However, these loci pinpoint to large genomic regions and the functional variants remain to be identified. To identify new risk factors associated with brain amyloid deposition, we performed whole-genome sequencing on a large cohort of European descent individuals with amyloid PET imaging data (n = 1,888). Gene-based analysis for coding variants was performed using SKAT-O for amyloid PET as a quantitative endophenotype that identified genome-wide significant association for APOE (P = 2.45 × 10−10), and 26 new candidate genes with suggestive significance association (P < 5. 0 × 10−03) including SCN7A (P = 7.31 × 10−05), SH3GL1 (P = 7.56 × 10−04), and MFSD12 (P = 8.51 × 10−04). Enrichment analysis highlighted the lipid binding pathways as associated with Aβ deposition in brain driven by PITPNM3 (P = 4.27 × 10−03), APOE (P = 2.45 × 10−10), AP2A2 (P = 1.06 × 10−03), and SH3GL1 (P = 7.56 × 10−04). Overall, our data strongly support a connection between lipid metabolism and the deposition of Aβ in the brain. Our study illuminates promising avenues for therapeutic interventions targeting lipid metabolism to address brain amyloidosis.
Microbial community dynamics in the soil-root continuum are linked with plant species turnover during secondary succession
Authors: Yan Weiming , Yuan Mengting Maggie , Wang Shi , Sorensen Patrick O , Wen Tao , Xu Yuting , Wang Honglei , Jiao Shuo , Chen Ji , Shangguan Zhouping , Deng Lei , Li Ziyan , Zhong Yangquanwei
Published: January 2025

Grazing exclusion and land abandonment are commonly adopted to restore degraded ecosystems in semiarid and arid regions worldwide. However, the temporal variation in the soil- versus root-associated microbiome over plant species turnover during secondary succession has rarely been quantified. Using the chronosequence restored from fenced grassland and abandoned farmlands on the Loess Plateau of China, we characterized the dynamics of the soil- and root-associated microbiome of host plant with different dominance statuses during secondary succession from 0 to 40 years. Our results revealed that the root microhabitat, the host plant and their interactions were the main contributors to the bacterial community shift (R2 = 15.5%, 8.1% and 22.3%, respectively), and plant interspecies replacement had a greater effect on the shift in the root-associated microbial community than intraspecies replacement did during succession. The root-associated bacterial community of pioneer plants was particularly responsive to succession, especially the endosphere community. Endosphere microbial diversity was positively correlated with host plant coverage change, and the diversity and abundance of taxon recruitment into the endosphere of pioneer plants from the surrounding environment decreased as succession progressed. The community assembly processes also indicated that the endosphere microbiota are strongly selected in younger host plants, whereas stochastic processes dominate in aged host plants. Our study provides evidence of the unique response of the root-associated microbiome to the replacement of plant species during secondary succession, and the function of endosphere microbes should be considered when studying plant–microbe feedback.
Emergence of Crimean-Congo Hemorrhagic fever in India
Authors: Sharma Sakshi , Mohanty Aroop , Sah Ranjit , Luna Camila , Rodriguez-Morales Alfonso J , Özsürekci Yasemin
Published: January 2025

CCHF is a tick-borne viral disease with high outbreak potential and no specific treatment or vaccine. It is transmitted via ticks or contact with infected fluids and poses significant risks to healthcare workers and livestock handlers. Prevention relies on strict infection control, public education, and protective measures to reduce transmission.
New-Onset Facial Spasm is associated with Treatment Failure after Radiosurgery in Vestibular Schwannoma
Authors: Wang Sophie Shih-Yüng , van Eck Albertus , Naros Georgios , Horstmann Gerhard , Tatagiba Marcos
Published: January 2025

Background

New-onset facial spasm (NOFS) has been reported to be a post-therapeutic side-effect, when treating vestibular schwannoma (VS) with Radiosurgery (SRS) and has been linked to post-treatment pseudoprogression. The aim of this study was to identify risk factors for developing NOFS after SRS-treatment, and to investigate NOFS as a clinical parameter for radiographic tumor response in VS.

Methods

This study included all consecutive patients of N=1’998 between 2004 and 2020, which were treated with SRS identified by a prospective registry. Patient and tumor characteristics were analyzed (i.e., sex, age, tumor extension and size, intracanalicular extension) were analyzed retrospectively. Statistical testing was performed with R Studio.

Results

The incidence of NOFS was 5% overall. 62% were permanent NOFS, whereas 39% recovered spontaneously between 4 and 34 months, postinterventionally. The incidence of NOFS was unrelated to tumor size – however, previous SRS increased the incidence of NOFS to 20%. In primary SRS therapy, facial spasm was associated with a higher recurrence rate compared to non-NOFS patients in the Kaplan-Meier-Analysis (p<.001),.Tumor control decreased with increasing tumor size. The rate of pseudoprogression was higher in the group of transient NOFS at 39% compared to permanent NOFS 18% (p=.032).

Conclusions

The risk of NOFS was significantly higher in recurrent compared to primary treatment. The majority of NOFS was permanent. The incidence of permanent NOFS was significantly associated with the incidence of tumor recurrence overall. Temporary NOFS was associated with pseudoprogression. Future analysis comparing risk-profile of either treatment option should include facial spasm as a significant VS-related postinterventional symptom.
576. Chandipura virus infection: Time to think beyond Encephalitis?
Authors: Buch Kathan P , Buch Pankaj M
Published: January 2025

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

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 < 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 < 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 < 0.05) and reductions in both lung and brain fungal burden vs placebo (P < 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

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 < 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) ( > 15,000 ng/ml), urine Histoplasma antigen above the LOQ ( > 19 ng/mL), serum beta-D-glucan (BDG) above the LOQ ( > 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 > 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

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

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

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 < 0.001), second surgery < 30 days (p=0.01), primary graft dysfunction (p=0.02), and acute rejection < 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

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< 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

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 < 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
229. IDSA FEATURED ORAL ABSTRACT: MVA-BN Induces a Low Avidity, Non-Durable Humoral Response Against Mpox Virus
Authors: Kottkamp Angelica C , Oom Aaron , Wilson Kesi K , Yonatan Miilani E , Rettig Stephanie , Youn Heekoung , Tuen Michael , Belli Hayley , Zucker Jane R , Rosen Jennifer , Samanovic Marie I , Duerr Ralf , Mulligan Mark J
Published: January 2025

Background

The 2022 global outbreak of clade IIb mpox, the first significant occurrence outside Africa, led to vaccination campaigns using the third-generation orthopoxvirus vaccine modified vaccinia Ankara, Bavarian Nordic (MVA-BN or JYENNEOS vaccine). In the US, a one-fifth dose of an intradermal regimen of the MVA-BN was authorized as a dose-sparing alternative to the two-dose subcutaneous regimen licensed in 2019. During the vaccination campaign, we launched the New York City Observational Study of Mpox Immunity (NYC OSMI) which enrolled participants who received the MVA-BN vaccine during the outbreak in NYC. Here we report the antibody data at one-year post vaccination.

Methods

We initiated the New York City Observational Study of Mpox Immunity (NYC OSMI), a longitudinal study involving 171 MVA-BN vaccinees, some with prior smallpox vaccination and mpox convalescents. Study participants had blood drawn prior to vaccination, after one dose, and after two doses. We performed Immunofluorescence-based Mpox virus (MPXV) clade IIb microneutralization assays, Multiplexed immunoassay for binding antibodies and avidity, and Anti-MPXV H3 Enzyme-Linked Immunosorbent Assay (ELISA). Paired measurements in figures were analyzed by Wilcoxon matched-pairs signed rank test. Comparisons of multiple sample groups in figures were conducted by Kruskal-Wallis test with Dunn’s method for multiple comparisons. Linear mixed-effects regressions (LMER) were used to model neutralizing titer durability with repeated measurements.

Results

Our findings indicate that neutralizing titers in naïve individuals return to baseline in less than a year, while those with prior smallpox vaccination maintain elevated titers. Both groups generate robust IgG responses against MPXV H3 and A35, but the response in naïve vaccinees, characterized by lower avidity, is short-lived.

Conclusion

These results highlight the necessity for further investigation into MVA-BN's long-term protection, potential need for booster doses, and the development of next-generation orthopoxvirus vaccines.

Disclosures

Mark J. Mulligan, M.D., HilleVax: Advisor/Consultant|Meissa Vaccines: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi: Grant/Research Support
293. Association of a Hospital Stress Indicator with Device Associated Infections
Authors: Parriott Andrea , Barahmani Nadia , Epson Erin
Published: January 2025

Background

Hospital surges during the COVID-19 pandemic provided an opportunity to assess the effects of strained hospital resources on patient safety outcomes and identify predictors of resilience. We sought to examine the relationship between a composite indicator of hospital stress and device-associated infections (DAI) including central-line associated bloodstream infections (CLABSI) and catheter-associated urinary tract infections (CAUTI) in California acute-care hospitals.

Methods

We used data from the California Hospital Association daily survey to create a composite variable indicating hospital stress. Hospitals were considered stressed on a given day if they reported patients in surge beds, ventilated COVID-19 patients in the emergency department, or a critical staffing shortage. We matched data from the National Healthcare Safety Network (NHSN) on CLABSI and CAUTI occurring between June 2020 and December 2021 to inpatient discharge data from the California Office of Healthcare Access and Information (HCAI) by sex, birthdate, admission date, and hospital. Patients were considered exposed to hospital stress if the hospital was stressed on any day between their admission and infection onset or discharge. We used propensity score weighting for risk adjustment for patient characteristics including month of admission, age, sex, race, expected payer, principal diagnosis, type of admission (emergency/urgent, trauma, or elective) and comorbidities from linked HCAI records (Table 1). Odds ratios were calculated using logistic regression with the generalized estimating equation to account for clustering within facilities.

Results

2,843 CLABSI and 2,870 CAUTI were successfully matched to patient records. Forty seven percent of patients were exposed to hospital stress. Risk-adjusted odds ratios were between 2 and 3 and significant at α=0.05 for all DAI, CLABSI, and CAUTI (Table 2).

Conclusion

These findings validate that our measure of hospital stress was associated with increased risk of individual patient-level DAIs in 2020-2021. Further research will focus on generalizing results beyond 2020-2021 and assessing facility-level factors that mitigate the stress-patient outcome association.

Disclosures

All Authors: No reported disclosures
P-815. Clinical Impact of BioFire® Blood Culture Identification 2 Implementation in Patients with Staphylococcal Bacteremia
Authors: Duell Colin , Ackley Tyler , Linder Kristin E , Kuti Joseph L , Castle Alivia , Li Rosanna
Published: January 2025

Background

The BioFire® Blood Culture Identification 2 (BCID2) PCR panel aids in rapid identification of blood pathogens, including coagulase-negative Staphylococci (CoNS) and methicillin susceptible Staphylococcus aureus (MSSA). BCID2 was implemented at all Hartford HealthCare hospitals in September 2022. The objective of this study was to evaluate how BCID2 impacted vancomycin use, clinical outcomes, and pharmacist intervention.

Methods

This was a multi-center, retrospective study of adult patients admitted to Hartford HealthCare hospitals with MSSA or CoNS positive blood cultures. The primary endpoint, days of vancomycin therapy, was compared between the pre- (3/7/22 – 9/7/22) and post-BCID2 periods (10/7/22 – 4/7/23). Secondary endpoints included duration of MSSA positive blood cultures, intensive care unit (ICU) length of stay, hospital mortality, and pharmacist interventions accepted.

Results

Of the 617 patients included in the primary analysis, MSSA bacteremia accounted for 37.0% (110/297) and 31.6% (101/320) of the patients in the pre- and post-BCID2 group, respectively (p=0.178). The median duration of vancomycin was 1.3 and 0.3 days in the pre- and post-BCID2 group, respectively (absolute difference, 1.0 days; p< 0.001). The duration of MSSA BSI was 3.1 and 2.4 days in the pre- and post-BCID2 group, respectively (absolute difference, 0.7 days; p=0.096). Hospital mortality was not different between periods [7.1% (21/297) vs 10.6% (34/320), p=0.16]. In patients with MSSA bloodstream infection (BSI), ICU LOS was 4.4 days shorter in the post-BCID2 period (7.8 vs 3.4 days, p< 0.001). Pharmacists successfully intervened to reduce vancomycin duration in 7.1% (21/297) and 16.3% (52/320) of patients in the pre- and post-BCID2 group, respectively (p< 0.001).

Conclusion

BCID2 implementation shortened the duration of vancomycin in patients with MSSA or CoNS bacteremia and facilitated pharmacist intervention to stop vancomycin in non-pathogenic CoNS positive blood cultures or switch to MSSA-targeted therapy in MSSA BSI. These data support BCID2 as a critical tool to improve appropriate antibiotic selection and shorten the time to safer and more effective treatment for patients with CoNS and MSSA bacteremia.

Disclosures

Joseph L. Kuti, PharmD, Abbvie: Advisor/Consultant|bioMerieux: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi Inc: Advisor/Consultant|Shionogi Inc: Grant/Research Support|Shionogi Inc: Honoraria|Venatorx: Grant/Research Support
P-817. Can We Stop Taking Follow-Up Blood Cultures for Brucella Melitensis in Hospitalized Adults?
Authors: Grupel Daniel , Cherniak Meir , Cohen Matan
Published: January 2025

Background

Brucella melitensis is an important zoonotic pathogen causing human disease worldwide. Blood cultures are often essential in establishing the diagnosis in hospitalized patients.

The need for repeated blood cultures is well established in gram-positive bacteremia and is still debated in gram-negative bacteremia. There is scant data regarding the need for repeated blood cultures in brucellosis. Follow-up blood cultures (FUBCs) may direct physicians to cryptogenic focal infection but are also associated with multiple venipunctures, prolonged hospitalization, and contamination. Moreover, repeatedly positive blood cultures can cause clinicians to pursue excessive workups.

Methods

We retrospectively collected data on all positive cultures growing Brucella sp. collected between 1/10 and 12/22 in adults at the Hadassah Medical Center campuses.

The primary outcome was brucellosis relapse or treatment failure. Hospitalization resource utilization, treatment modifications and length of stay were also recorded.

Three groups were defined- patients with 1) a single blood culture positive for Brucella without FUBC; 2) a first positive blood culture with negative FUBCs; and 3) positive FUBCs. Subgroup analysis was performed according to the positivity of the last culture taken during hospitalization.

Results

We found 525 cultures taken from 176 patients positive for Brucella sp. 68 patients met the exclusion criteria. 7.5% of the cohort had a single culture, 17.8% had negative FUBCs, and 74.8% had positive FUBCs.

No significant difference was observed in the primary outcome between the groups with positive or negative FUBCs (15.8% and 11.3%, respectively, p=0.695). The clinical presentation, length of stay, number of imaging modalities used, and rates of treatment modification also did not differ between the groups (Table 1).

Conclusion

In our brucellosis cohort, FUBC positivity was not associated with an increased rate of complications or adverse events despite similar baseline characteristics and clinical course.

Furthermore, the groups with FUBCs did not fare differently than those without FUBCs.

With the caveats of an observational study, these data suggest that discontinuing FUBCs in hospitalized brucellosis patients should be considered as it seems reasonable and safe.

Disclosures

All Authors: No reported disclosures
P-824. A Tertiary Care Hospital's Eight-Year Experience with Acinetobacter Bloodstream Infections in the Pediatric Population
Authors: Erci Ece , Avcu Gulhadiye , Bilen Nimet Melis , Arslan Sema Yıldırım , Guner Gizem , Özkaya Pınar Yazıcı , Cilli Feriha , Sahbudak Bal Zumrut
Published: January 2025

Background

Acinetobacter spp has emerged as an important nosocomial pathogen causing life-threatening infections in hospitalized patients. Since carbapenem-resistant Acinetobacter bloodstream infections have been increasingly reported in the pediatric population worldwide in recent years, we aimed to evaluate the clinical characteristics and identify possible risk factors in hospitalized patients with carbapenem-resistant bloodstream infections.

Methods

We retrospectively analyzed the results of blood-stream infections caused by Acinetobacter spp. in hospitalized children between 2014-2022. Demographic features and clinical and laboratory findings were evaluated.

Results

Bloodstream infections due to Acinetobacter spp. were detected in 70 hospitalized children. Carbapenem resistance was present in 38 (54.2%) of the patients. The mean age of patients with carbapenem-resistant (CR) Acinetobacter bloodstream infection (21 males and 17 females) was 5.7±0.95 years and 3.9±0.74 years in the carbapenem-susceptible (CS) group (13 males and 19 females) (p< 0.005). The most common pathogen in the CR group (97.4%) and CS group (56.3%) was Acinetobacter baumannii. While 15.3% of the CR patients were previously healthy, 3.1% of the CS group had no history of previous diseases. The most important predisposing risk factors for the development of carbapenem resistance were invasive mechanical ventilation (p< 0.005), previous antibiotic use (p< 0.005), and history of meropenem use (p< 0.005). Combination therapy was initiated in 64.6% of patients in the CR group and 53.1% in the CS group. The most frequently used antibiotic regimens in the CR group were meropenem-colistin (15.8%), colistin-amikacin (10.5%), and colistin-sulfamethoxazole and trimethoprim (SMZ-TMP) (7.9%). The mean treatment duration for the groups was 13.3±0.98 days for the CR group and 11.3±1 days for the CS group (p:0.523). The infection-related mortality rates for the CR and the CS groups were 36.8% and 21.9%, respectively, and there was no statistically significant difference between the groups (p:0.136).

Conclusion

Our single-center experience aims to emphasize the importance of rational antibiotic use and enhance the awareness of clinicians about the increasing carbapenem resistance.

Disclosures

All Authors: No reported disclosures
P-825. Short Versus Long Treatment Duration for Streptococcal Bloodstream Infections
Authors: Spivak Emily S , Gray Julie , Zhang Chong , Earl Ali
Published: January 2025

Background

The rise in antibiotic resistance, antimicrobial-related harms and emerging data have prompted a shift towards shorter antibiotic durations. However, there is a lack of data to inform durations of therapy for Streptococcal bloodstream infections (BSI). The need for clearer guidance led us to compare outcomes between short and long antibiotic durations for uncomplicated Streptococcal BSI with the goal of informing local and national practice.

Effects of Long vs. Short Antibiotic Durations

Methods

This was a retrospective cohort study of unique adult patients admitted to University of Utah from January 1, 2014 to July 15, 2023 with uncomplicated Streptococcal BSI, defined as negative follow-up blood cultures, clinical resolution by day 3, absence of metastatic foci, source control if indicated, and no other complications. We used inverse probability of treatment weighting to estimate the average treatment effects (ATE) of in vitro active antibiotics administered for > 10 days (long duration) versus < 10 days (short duration), adjusting for pretreatment variables. The primary outcome was a composite of recurrent bacteremia, all-cause mortality, and readmissions at 30 days from end of treatment (EOT). Secondary outcomes were 90-day all-cause mortality and recurrent bacteremia from EOT.

Results

209 patients met criteria for inclusion. The median duration in the long and short groups were 15 (IQR, 14-17) and 8 days (IQR, 7-9.75), respectively. In the propensity score weighted analysis (Table 1), the ATE of long versus short duration was not significant on the composite primary outcome (21% vs 22%; OR= 0.81 [95% CI: 0.34 to 1.91], p=0.62) or any secondary outcomes.

Conclusion

We found no appreciable difference in outcomes between patients treated with >10 days of antibiotics compared to those treated with <10 days for uncomplicated Streptococcal BSI. Given low absolute rates of mortality and recurrent bacteremia, paired with no appreciable difference related to treatment duration, it is reasonable to recommend shorter durations. Given limitations of this retrospective analysis, future research is needed to confirm our findings; however, our data could inform antimicrobial stewardship interventions aimed at decreasing treatment durations for uncomplicated Streptococcal BSI.

Disclosures

All Authors: No reported disclosures
P-827. Epidemiology of Favorable vs. Unfavorable Outcomes in Hospitalized Patients with S. aureus Bacteremia in the US: A Multicenter Retrospective Cohort Study
Authors: Zilberberg Marya D , Nathanson Brian H , Wagenaar Rolf J , Posthumus Jan , Shorr Andrew
Published: January 2025

Background

The incidence of Staphylococcus aureus bacteremia (SAB) remains ∼25 cases/100,000 population, and methicillin-resistant S. aureus (MRSA) causes ∼1/2 of all SAB. Historically, mortality has served as the primary gauge for SAB’s outcomes, potentially neglecting other important unfavorable outcomes (UO) that contribute to its morbidity. We developed a multifaceted definition for UOs in SAB and examined their prevalence and early predictors.

Methods

We included adult hospitalized patients with at least one positive blood culture (BC) for S. aureus in a large US database (∼300 hospitals, 2020-2022). We defined UO as at least one of the following: hospital mortality, antibiotic escalation, persistently positive BCs, prolonged post-infection length of stay (LOS), or readmission within 30 days after discharge. All other outcomes were classified as favorable (FO). We used descriptive statistics to compare patients with UO and FO, and applied multiple regression models to identify factors associated with UOs.

Results

Among 4,080 patients with SAB, 2,427 (59.5%) suffered an UO. The most common UOs were disease worsening and need for vasopressors (Figure 1). Those with UOs were more likely to be non-White and suffered from a higher co-morbidity burden (Table 1). During hospitalization and prior to the onset of SAB, those with UOs more frequently required an ICU stay and dialysis. The majority of SABs were community-onset, and similarly distributed in the groups. UOs occurred in 66.1% of patients with MRSA vs. 55.2% with MSSA. Vancomycin was the leading empiric drug administered, followed by cefazolin. Daptomycin was used infrequently, and the rate of delayed therapy was low. The unadjusted post-infection hospital LOS and costs were significantly higher with UOs (Table 1). The variables with the highest odds ratios predicting an UO were the presence of septic shock on admission, empiric treatment with daptomycin, and the presence of complicated SAB (Table 3).

Conclusion

UOs occur frequently in SABs. A broader perspective exploring issues other than mortality demonstrates the substantial implications of SAB both for patients and healthcare systems. Select clinical variables are associated with UOs, some of which may not be modifiable.

Disclosures

Marya D. Zilberberg, MD, MPH, Basilea Pharmaceutica International Ltd, Allschwil, Switzerland: Grant/Research Support Brian H. Nathanson, Ph.D., MERCK: Advisor/Consultant Rolf J. Wagenaar, MS, Basilea: Advisor/Consultant Jan Posthumus, PhD, MBA, Basilea Pharmaceutica International., Alschwil Ltd: Honoraria|Basilea Pharmaceutica International., Alschwil Ltd: Stocks/Bonds (Public Company) Andrew Shorr, MD, MPH, MBA, Basilea: Advisor/Consultant|Basilea: Grant/Research Support