bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1008. Congenital Cytomegalovirus Infection Screening in the Newborn Nursery: Areas for Improvement in the Absence of Standardized Guidelines
Authors: Abraham Tanya , Desai Ankita P , Minich Nori M 
Published: January 2025

Abstract

Background
Cytomegalovirus (CMV) is the most common viral cause of congenital defects in the U.S. Early identification of congenital CMV (cCMV) infection allows for optimal antiviral treatment which reduces progression of sensorineural hearing loss and improves neurodevelopmental outcomes. There is varying guidance from expert consensus groups ranging from universal screening to selective screening based on clinical features. With conflicting data, many hospitals have no standardized protocol for cCMV screening. This study aims to detail clinical characteristics and outcomes of infants with cCMV in a tertiary medical center prior to implementation of standardized guidelines.

Methods
This was a retrospective case study of newborns who screened positive for CMV between June 2017-July 2022 at Rainbow Babies & Children’s Hospital in Cleveland, Ohio. 1900 newborns less than 21 days old were tested for CMV during this period, and newborns who screened positive for CMV were included (n=18). Clinical characteristics of the patients were described using median and interquartile range for continuous variables and frequency and percentages for categorical variables.

Results
The prevalence rate of cCMV at our center is 9.5 per 1000 live births. The most common associated clinical features were small for gestational age (SGA; n=12), microcephaly (n=9), abnormal neuroimaging findings (n=6), and failed newborn hearing screen (n=4). Two patients had isolated SGA, and neither received treatment nor had clinical sequelae. Saliva PCR tests were used for screening with no confirmatory urine testing. 11 patients received oral valganciclovir with documented side effects of transient neutropenia and transaminitis. 33% of newborns had no infectious disease or audiology follow-up.

Conclusion
Targeted screening practices for cCMV infection in our institution varies between providers. Our center has a prevalence rate slightly above the national average; however, the yield of screening isolated SGA is shown to be low. This study highlights gaps in current cCMV screening including lack of confirmatory urine CMV testing, and infants lost to follow up. System-level interventions including creation of standardized guidelines and provider education are necessary to improve follow-up and outcomes.

Disclosures
All Authors: No reported disclosures
P-1009. Invasive Fungal Disease is Rare in Multiple Myeloma Patients Treated with BCMA CAR-T Therapy
Authors: Pena Angelica Medina , Bridget Kim E , Cirstea Diana , Hammond Sarah P , Little Jessica S 
Published: January 2025

Abstract

Background
B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapy has transformed treatment of relapsed/refractory multiple myeloma (MM). While this innovative therapy may introduce increased risks for infections, little is known about the characteristics and incidence of invasive fungal disease (IFD).Table 1.Institutional protocols for antifungal prophylaxis following immune effector cell therapy.

Methods
We evaluated MM patients treated with first BCMA CAR-T therapy at 2 institutions November 2016 through October 2023. Table 1 summarizes institutional protocols for antifungal prophylaxis for immune effector cell (IEC) therapy. We documented IEC toxicities graded according to ASTCT and Lee Criteria. Proven or probable IFD was recorded from Day 0 through last follow-up, Day 365, or death according to the EORTC/MSGERC consensus criteria.Table 2.Baseline characteristics & immune effector cell toxicity

Results
Among 234 patients in the cohort, median age was 66 years, and 56% were male. Patients had a median of 6 prior therapy lines, and 68% had undergone autologous stem cell transplant (Table 2). The most common IEC toxicity was cytokine release syndrome (CRS), observed in 84.6% of patients, primarily Grade 1-2 (Table 2). Four patients (1.7%) developed proven/probable IFD, including 1 with Candida albicans peritonitis and 3 with invasive aspergillosis. Among these 4 cases, the timing of diagnosis ranged from 6 to 104 days post-CAR-T infusion. All four had CRS/ICANS and received corticosteroids. Outcomes were mixed, with 3 cases reported as severe and 2 deaths within 30 days. One death occurred from Stenotrophomonas sepsis, and isolated cardiac Aspergillus was found incidentally on autopsy. On the second case, pulmonary Aspergillosis was found shortly before transitioning to comfort care due to hemophagocytic lymphohistiocytosis and Staphylococcus aureus pneumonia (Table 3).Table 3.Characteristics of invasive fungal disease

Conclusion
This is the largest study to date to provide details on the incidence and characteristics of IFD in BCMA CAR-T recipients. Here we demonstrate a low incidence of IFD despite a lack of routine antifungal prophylaxis. Nonetheless, these infections may be severe and appear to affect the most vulnerable with IEC toxicities with 50% of affected patients dying with active infection. Larger studies are needed to define underlying risk factors in this population.

Disclosures
Diana Cirstea, MD, Sanofi: Advisor/Consultant Sarah P. Hammond, MD, Cidara: Grant/Research Support|F2G: Grant/Research Support|GSK: Grant/Research Support|Melinta: Advisor/Consultant|Pfizer: Advisor/Consultant|Roche: Advisor/Consultant|Scynexis: Grant/Research Support|Seres Therapeutics: Advisor/Consultant
P-1023. Prevalence and distribution of fungal microorganisms among cutaneous specimens submitted to community microbiology laboratories
Authors: Yeung Eugene 
Published: January 2025

Abstract

Background
Not much is known about the local prevalence of cutaneous fungal infections in Canada because these data are not readily available. Knowing the distribution of microorganisms in local settings may help developing guidance for empiric therapy, especially for immunocompromised patients whose cutaneous fungal infections could turn into systemic infections. The current retrospective study aimed to establish the prevalence and distribution of fungal microorganisms among patients who had specimens submitted to community microbiology laboratory for cutaneous fungal culture workups.

Methods
LifeLabs regional microbiology laboratories, connected with 129 collection centers in urban and rural communities in British Columbia, provided reports of isolated fungus from hair, nail, and skin scraping specimens from 1 January 2022 to 31 December 2022. Culture followed by microscopy and/or MALDI-TOF mass spectrometry was routinely used to isolate and identity microorganisms, but nucleic-acid testing was added to help identification if needed.

Results
Among the 20652 cutaneous specimens submitted in a year, 3665 of them were reported to have microorganism growth. The most reported microorganism was Trichophyton species (43.8%), followed by Penicillium species (5.8%), Candida albicans (4.2%), Aspergillus species (3.6%), and Fusarium species (2.8%). Of note, other than Trichophyton species, the other two main dermatophytes Microsporum species and Epidermophyton species accounted for only 0.2% and 0.1% of the positive specimens, respectively. Pseudomonas aeruginosa was incidentally identified in 2.9% of the positive specimens in the fungal culture workups.

Conclusion
Trichophyton species was the most reported microorganism among the hair, nail, and skin scrapping specimens submitted for cutaneous fungal culture workups from communities in British Columbia. Pseudomonas infections, which could present as chloronychia, folliculitis, ecthyma gangrenosum, could be considered in the differential diagnoses of cutaneous fungal infections. The current data will help clinicians to determine the empiric therapy needed based on each patient’s clinical situation.

Disclosures
All Authors: No reported disclosures
P-1024. Fungal Pneumonia and Severe Neutropenia: Risk Factors for Increased 90 Day Mortality
Authors: Handley Guy , Greene John , Cannella Anthony P , Velez Ana , Shah Shivan , Katzman Ju Hee , Pasikhova Yanina 
Published: January 2025

Abstract

Background
Invasive fungal infections (IFI) carry a high mortality risk in hematologic malignancy; the majority being pulmonary infections. Diagnosis is based on consensus definitions of host factors, clinical features and mycologic evidence. In previous studies, increased mortality is associated with delays in therapy and failure of neutrophil recovery; however, use of salvage posaconazole may have improved outcomes. We sought to identify risk factors associated with higher 90-day mortality in these patients.

Methods
Patients at an NCI designated comprehensive cancer center from 06/2021 – 07/2023 with hematologic malignancy, severe neutropenia and a diagnosis of IFI and receiving posaconazole for treatment with verified therapeutic drug monitoring were identified. Demographic, clinical and laboratory data were evaluated to identify risk factors for increased mortality within 90 days of diagnosis of pulmonary IFI. The diagnosis was based on international consensus definitions.

Results
A total of 39 patients were identified. 18 (46.2%) were diagnosed with acute myeloid leukemia and 13 (33.3%) had undergone bone marrow transplantation. Median time from diagnosis to treatment initiation was 2 days and 17 (43.6%) patients received combination therapy with multiple antifungal agents. Bronchoscopy with bronchoalveolar lavage was performed in 34 (87.2%) and of those a microbiologic diagnosis found in 5 (14.7%). Day 90 mortality was 56.0% (n=14). Survivors were more likely to have initiation of antifungal therapy within 7 days (96.0% vs 64.3%, p=0.016) and received liposomal amphotericin B as part of their initial therapy (72.0% vs 42.9%, p=0.009). Patients receiving corticosteroids or who failed to have neutrophil recovery tended to have higher mortality, but this did not achieve statistical significance. Combination therapy and receipt of granulocyte or granulocyte-macrophage colony-stimulating factors were not associated with improved day 90 mortality.

Conclusion
Early recognition and initiation of antifungal therapy in high-risk neutropenic patients with hematologic malignancy with IFI and initial therapeutic regimens including liposomal amphotericin B may be associated with improved outcomes.

Disclosures
All Authors: No reported disclosures
P-1046. Isavuconazonium Utilization in Pediatric Patients at a Free-Standing Children’s Hospital
Authors: Orbach Regina , Bee Jessica , Legaspi Jamie 
Published: January 2025

Abstract

Background
Isavuconazonium sulfate is a newer triazole antifungal used for the treatment of invasive aspergillosis and mucormycosis. In December 2023, the FDA expanded approval for isavuconazonium sulfate (Cresemba) to include pediatric patients 1 year and older. The most common adverse effect requiring monitoring is hepatotoxicity. Routine therapeutic drug monitoring is not recommended for most patients but may be considered if there is a concern for toxicity, therapeutic failure, or impaired drug absorption. With limited published data in pediatric patients, our aim is to evaluate the use of isavuconazonium at Children's Hospital Los Angeles (CHLA) and assess safety and tolerability in our patient population.

Methods
A retrospective chart review was performed to evaluate utilization of isavuconazonium from 01/01/2023 – 12/31/2023 at CHLA. Demographic data, Infectious Diseases consultation, indication for therapy, liver function before and during treatment, and serum drug level results were collected and analyzed.

Results
A total of 54 patient encounters included an isavuconazonium order during the review period. All study patients had a primary diagnosis of leukemia or stem cell transplant (SCT), the most common (45%) being Acute Lymphoblastic Leukemia (ALL). 3 patients had mildly elevated liver function tests (LFTs) at baseline, and 6 total patients developed grade 3 or 4 liver toxicity during therapy. The most common indication for treatment was empiric or definitive treatment of invasive fungal infection, with 15 (28%) and 20 (37%) patients, respectively. 19 patients (35%) received off-label prophylaxis for invasive fungal infection due to contraindications to alternative antifungal agents. 33 of 54 patients had at least one serum trough level measured at steady state. Although a therapeutic target range is not well established, 26 patients (79%) achieved levels within typical expected range of 1-5 mg/L. Of 3 patients with trough level &lt; 1 mg/L, 2 were determined to be due to non-adherent to outpatient therapy.

Conclusion
Based on serum drug levels and LFT results collected for routine therapeutic monitoring, isavuconazonium appears well-tolerated for treatment or prophylaxis of invasive fungal infection in our immunocompromised pediatric population.

Disclosures
All Authors: No reported disclosures
P-1047. The Epidemiology of Sporotrichosis: Clinical Features, Risks Factors and Associated Mortality, a Global Research Network Analysis
Authors: Schapiro Samantha , Pulciano Nicholas , Galindo Julian , Martínez Andrés F Henao , Thompson George R , Chastain Daniel B 
Published: January 2025

Abstract

Background
Sporotrichosis is a fungal infection affecting thousands in South America, yet is uncommon globally, where it is not a reportable disease. This leads to a limited understanding of its epidemiology and clinical features.
The study aimed to identify and characterize the clinical features, geographic distribution, risk factors, and outcomes of sporotrichosis across a multicenter United States (US)-based network to improve diagnostic and treatment strategies.

Methods
The study used the TriNetX global research network database to identify patients with sporotrichosis defined by ICD-10-CM code B42. A manual chart review was conducted to verify the reliability of the code in 60 patients. Data collected included demographics, comorbidities, lab results, and outcomes. The primary outcome was mortality and hospitalization. Bivariate analysis was performed to compare survivors with non-survivors in one year.

Results
The study included 2,124 patients with sporotrichosis, with a manual chart diagnosis validation rate of 95%. The average age was 52, with 56% women and 40% Caucasian. Common comorbidities were neoplasms, diabetes mellitus (DM), and chronic obstructive pulmonary disease (COPD). Most cases were unspecified, but among those with a specified subtype, lymphatic was the most common (9.4%), followed by disseminated (1.1%). Itraconazole was the most common first-line treatment. The one-year mortality was 17% (Table 1). The Southeast had the most frequent cases in the US (Figure 1). Age, unmarried marital status, and location in south or international regions were significantly associated with mortality. Higher ferritin levels, lower hematocrit, and higher leukocyte count also indicated increased mortality (Table 2). There were 17 patients with both sporotrichosis and HIV; 82% were men with an average age of 56. The average CD4 count was 65.5, with a one-year mortality of 17.6% (Table 3).

Conclusion
Patients with sporotrichosis had low rates of extracutaneous disease. Age, unmarried marital status, geographic location, and specific comorbidities such as neoplasms, DM, and COPD are significant factors affecting sporotrichosis survival. Despite their compromised immune status, patients with HIV did not have worse outcomes than the general sporotrichosis population.

Disclosures
George R. Thompson, III, MD, Astellas: Advisor/Consultant|Cidara: Advisor/Consultant|Cidara: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Pfizer: Advisor/Consultant
389. Trends in HIV-Related Mortality Among Reproductive-Aged Women in the United States
Authors: Ali Shah M Danial , Aslam Sadaf , Rybolt Lauren E , Fatima Abeer , Sherbuk Jacqueline E , Somboonwit Charurut 
Published: January 2025

Abstract

Background
Despite advancements in HIV treatment, there remains a significant gap in understanding mortality rates among reproductive-aged women with HIV in the United States. To enhance evidence-based interventions, this study aims to delineate mortality trends from 1999-2020, focusing on demographic characteristics such as age, race, and geographic regions.
HIV-related AAMRs per 100,000 individuals stratified by race in women aged 15-44 in the United States, 1999 to 2020.

Methods
This study involved a retrospective analysis using the CDC WONDER database, extracting data via ICD-10 codes B20-B24 to identify HIV-related deaths among women aged 15-44 from 1999 to 2020. We analyzed demographic disparities in HIV mortality rates over time based on age, ethnicity, and geographic regions using systematic database analysis. Results are presented as age-adjusted mortality rate (AAMR) and 95% confidence interval (CI). These were calculated by standardizing HIV-related deaths in the United States in 2000.
HIV-related AAMRs per 100,000 individuals stratified by state in in the United States among women aged 15-44 from 1999 to 2020.

Results
Between 1999 and 2020, a total of 29,358 women aged 15-44 died from HIV in the US (AAMR = 2.2 per 100,000; 95%CI: 2.2-2.2). The crude mortality rate declined from 4.2 in 1999 to 2.1 in 2020. The overall decline in mortality rates masked disparities: Non-Hispanic Black women experienced the highest AAMR (11.3), while Hispanics, though initially higher, saw the most substantial decrease in mortality rates (1.4). Geographical analysis revealed the South as the most affected region (3.5), accounting for 58.3% of deaths, with urban areas presenting higher mortality rates than rural ones (2.4 and 1.4). Notably, older age groups (35-44) accounted for the majority of deaths (67.1%)
HIV-related AAMRs per 100,000 individuals among women aged 15-44 from 1999 to 2020 in the United States census regions. *=significant at p &lt; 0.05; confidence interval does not include zero

Conclusion
HIV-related mortality among reproductive-aged women decreased nationally from 1999 to 2020, yet disparities persist. Our analysis emphasizes the disproportionate impact of HIV-related deaths on non-Hispanic Black women and those residing in the Southern United States, suggesting the need for region and population-specific public health interventions. This highlights the need to improve access to care, particularly in urban areas, and target age-specific prevention programs to further reduce mortality rates. Improving timely diagnosis and addressing the stigma surrounding HIV among women is vital to reduce mortality in this demographic.
HIV-related crude mortality percentage stratified by different variables in women aged 15-44 in the United States, 1999 to 2020

Disclosures
All Authors: No reported disclosures
P-1057. Leveraging A Global-Scale Atlas of Phage Host Interactions to Discover Novel Precision Antimicrobials
Authors: Bryson Sam , Auch Benjamin , Grove Jonas , Nelson Bradley J , Glidden Demi , Reister Emily , Liachko Ivan 
Published: January 2025

Abstract

Background
A growing global antimicrobial resistance (AMR) crisis fueled by the overuse of traditional antibiotics has created an urgent need not only for new antimicrobials, but entirely new approaches for sustained therapeutic development against existing and emerging pathogens. Endolysins (lysins) have demonstrated both efficacy and safety as precision antimicrobials that overcome the resistance problem posed by most other antibiotic modalities. However, due to the difficulty of identifying new sources of lysins, development has been slow.

Methods
We have adapted a unique genomic technology, proximity ligation sequencing, to harness the vast genetic diversity of microbial viruses (phages) to discover large-numbers of protein-based interventions against microbes. Proximity-guided metagenomics allows us to pinpoint the microbial targets of phages in situ, recovering the genomes of both microbe and phage without culturing or isolation of either party. Inherently, each lytic phage genome encodes one or more more proteins (endolysins) which can lyse their host cell. Each of these proteins represents a powerful tool in the targeted destruction of a selected organism, and because we know which species of microbe each phage infects, we can identify candidate lysins from proximity-guided metagenomic data alone.

Results
As part of our global-scale metagenomics project, we used our ProxiMeta platform to recover the target-resolved genomes of hundreds of thousands of phages across the tree of life. We will share published and unpublished work describing our discovery and evaluation of these lysins, and their applications in selectively killing microbes involved in human disease.

Conclusion
Phage genomes from metagenomic databases are a rich source of antimicrobial proteins that can be developed into novel antimicrobial agents.

Disclosures
All Authors: No reported disclosures
P-1073. Developing Vaccines and Antibodies Targeting Conserved Peptidoglycan, Lipoteichoic Acid, and Lipopolysaccharide Epitopes to Combat Antimicrobial Resistance
Authors: Sei Clara J , Rikhi Nimisha , Kroscher Kellie , Schuman Richard F , Muema Kevin , Assiaw-Dufu Aba , Fischer Gerald W 
Published: January 2025

Abstract

Background
Antimicrobial resistance (AMR) poses a significant global health threat, driving the urgent need for non-antibiotic therapies such as vaccines and monoclonal antibodies (mAbs). Targeting conserved epitopes on gram-positive and gram-negative bacteria, including mycobacteria will be important for developing strategies against AMR. Key epitopes, including Peptidoglycan (PGN), Lipoteichoic acid (LTA), and Lipopolysaccharide (LPS) are crucial in this context. In this study, we illustrate the efficacy of a mAb directed against ultrapure PGN from Staphylococcus aureus (SA), alongside the capabilities of polyclonal serum antibodies induced by a multi-epitope composite peptide vaccine comprised of PGN, LTA, and LPS epitopes.

Methods
MAb MD11 was produced from a mouse immunized subcutaneously with ultrapure PGN from SA and the mAb specificity identified using ultrapure PGN and a synthetic PGN peptide in a competitive inhibition assay. Additionally, polyclonal serum antibodies were derived from ICR mice immunized subcutaneously on days 0, 21, and 35 with 20 µg of multi-epitope composite peptide vaccine LPS.PGN.LTA05, formulated with AddaVax™ adjuvant. IgG1 titers to the immunogens and whole bacteria: SA, Staphylococcus epidermidis, Mycobacterium smegmatis, Escherichia coli, B. subtilis, Grp. B Streptococcus and killed Mycobacterium tuberculosis (MTB) were analyzed by ELISA.

Results
MAb MD11 recognized and opsonized various gram-positive bacteria, including mycobacteria. PGN peptide competitively inhibited binding of MD11 to Ultrapure PGN, indicating specificity of MD11 to PGN epitope. Robust and broad polyclonal serum IgG1 antibodies recognizing both gram-positive and gram-negative bacteria, including mycobacteria were generated by the multi-epitope composite peptide vaccine.

Conclusion
Anti-PGN mAb MD11 was broadly reactive to gram-positive bacteria. Polyclonal serum antibodies showed broad reactivity across both gram-positive and gram-negative bacteria, including mycobacteria. Developing vaccines and antibodies that target conserved bacterial epitopes may provide important strategies for prevention and treatment of bacterial infections, particularly for immunocompromised individuals, and could offer a useful approach to combat AMR.

Disclosures
All Authors: No reported disclosures