bluuebunny/crossref_metadata_2025 huggingface dataset:
430. Tumor microbiota and tumor-infiltrating T cells in the tumor microenvironment of colorectal cancer
Authors: Ugai Satoko , Ugai Tomotaka , Ogino Shuji
Published: January 2025

Background

Recent studies indicate that the gut microbiota influences the immune cell infiltrates in colorectal cancer. For example, a study has shown that the amount of Fusobacterium nucleatum in colorectal carcinoma has been inversely associated with CD3+ cell density in tumor. Evidence also indicates that Bacteroides fragilis may suppress the adaptive T cell response. Based on such biological evidence, we hypothesized that T cell infiltrates might differ by the colorectal tumor tissue microbiota.

Methods

We conducted 16s rRNA sequencing to identify the abundance of 1,518 microbiome species in 861 colorectal cancer patients in the Nurses’ Health Study and the Health Professionals Follow-up Study. Multiplex immunofluorescence combined with digital image analysis and machine learning algorithms was used to measure various T-cell subsets, such as CD3, CD4, and CD8. Spearman correlation test was performed to investigate the association between the abundance of gut microbiota and CD3+, CD3+CD4+, and CD3+CD8+ T-cell densities in the overall tumor region. For the validation, we used tumor microbial data by qPCR.

Results

The strongest negative association was observed between the genus Clostridium and CD3+CD4+ T-cell density (rho = -0.13, p=8.27E-05). Bacteroides fragilis had a statistically significant negative association with CD3+ T-cell density (rho = -0.10, p = 0.0026) and CD3+CD4+ T-cell density (rho = -0.12, p < 0.001). Fusobacterium nucleatum also had a significant negative association with CD3+ T-cell density (rho = - 0.078, p = 0.021) and CD3+CD4+ T-cell density (rho = -0.11, p = 0.0011). These findings were validated by analyses using qPCR data.

Conclusion

We identified tumor microbiota, the abundance of which was inversely associated with tumor-infiltrating T cells in the tumor microenvironment of colorectal cancer. The strongest negative association was observed between Clostridium and CD3+CD4+ cell density. The abundance of Bacteroides fragilis and Fusobacterium nucleatum correlated negatively with the density of CD3+ and CD3+CD4+ cells in colorectal carcinoma tissue. Our findings provide new evidence for microbial-immune interactions in the tumor microenvironment.

Disclosures

All Authors: No reported disclosures
P-1266. Understanding Factors that Influence Patients’ Decision to Seek Care for Flu-Like Symptoms in Emergency Departments During Seasonal Respiratory Viral Surges
Authors: Jacobi-Dorbeck Allison K , Duverna Rose-Alice , Wilson Claire S , McBryde Breana , Rothman Richard E , Saheed Mustapha , Hansoti Bhakti
Published: January 2025

Background

Emergency departments (EDs) are directly impacted by seasonal surges in rates of respiratory viral infection and transmission with increased rates of ED visits for flu-like symptoms. It remains unclear as to why patients assigned lower acuity (level 3,4 and 5) based on standardized triage scoring systems opt to seek care within the emergency department in lieu of alternative healthcare venues for flu-like symptoms. We conducted an exploratory quality improvement study to develop further understanding of patient-related factors for seeking ED care, including patient perception of illness severity, and how this correlated with final ED disposition.

Methods

Patients were recruited from the adult ED using convenience sampling, from 2 major urban hospital centers based on a chief complaint related to flu-like symptoms and a triage score of 3, 4, or 5 (indicating non-emergent clinical status). Patients were asked to complete a structured survey to assess self-perception of current illness severity and reasons for seeking care in the ED. Following survey completion, EMR chart review was performed to collect information about patient’s clinical course, , diagnosis, and disposition.

Results

100 subjects were enrolled; over half (55%, n=55) graded their symptoms as being ‘severe’ or ‘very severe’ on presentation. Survey results demonstrated that desire for fast access to care (n = 80); testing with same-day results (n = 81); and worry that symptoms may evolve into a more serious condition (n = 81) were the top three most commonly reported reasons for seeking care in the ED. 24/100 participants were admitted and 76 were discharged. Rates of self-reported ‘severe’ or ‘very severe’ illness were nearly identical amongst those who were discharged 43/76 (57%) versus those who admitted 12/24 (50%). .

Conclusion

Amongst lower acuity patients presenting to the ED during flu season, the vast majority sough care in the ED due to a desire to be seen quickly and a concern for having serious illness. We observed surprisingly high rates of hospital admission (25%); patients’ perception of having a more severe illness was similar amongst those discharged (versus admitted) suggesting that patients are not able to reliably predict a need for urgent ED evaluation.

Disclosures

Richard E. Rothman, MD, PhD, abbvie: Grant/Research Support|CEPHEID: Advisor/Consultant|CEPHEID: Grant/Research Support|CEPHEID: Honoraria
P-1278. Risk Factors Associated with Post-Treatment Lyme Disease Syndrome: A Prospective Cohort Study on Long Island, NY
Authors: Kenison David , Zamor Rudline G , Bateman Victoria A , Maczaj Brigitte , Nath Sarath , Maramara Bennadette , Lum Michael D , Mordue Dana , Marcos Luis A
Published: January 2025

Background

Lyme disease (LD) is caused by Borrelia burgdorferi transmitted by the Ixodes scapularis tick. Post-treatment Lyme disease syndrome (PTLDS) refers to a condition in which approximately 10-20% of optimally treated LD patients develop persistent symptoms of unknown pathophysiology. The epidemiological data on PTLDS is limited. This study aims to investigate the underlying risk factors associated with PTLDS.Table 1.Patient characteristics in PTLDS developed and PTLDS negative groups and their associated p-values.

Methods

This is an ongoing prospective cohort study of 47 adult patients with LD (CDC criteria) who were seen at Stony Brook Medicine in NY since 2021. Demographics, and pertinent epidemiological data, including immunocompromised status, coinfection, diagnosis, past medical history and treatment were collected. Twelve symptoms were assessed using the Visual Analogue Score (VAS) and Fatigue Severity Scores (FSS) at initial presentation and 1, 6- and 12-months post-treatment. PTLDS was defined based on at least one symptom present at 6 months. Continuous variables were described using means and standard deviations; categorical variables were described with frequencies and percentages.Table 2.Symptoms reported by patients at 6 months and average Visual Analogue Scale (VAS) scores for each symptom.

Results

Out of a total of 47 enrolled patients, 44 (female 31%) patients completed their initial VAS. At 6 months, fatigue had the highest frequency (39%). At the initial presentation, median total symptoms scores were 37 for disseminated Lyme (n=14) and 30.5 for erythema migrans (EM) (n=27). Compared to baseline, VAS total symptom scores decreased at 1 month for the disseminated (n=12, median= 6.5) and EM groups (n=25, median= 3.5). VAS total symptom score decreased at 6 months as well for the disseminated (n=10, median= 5.25) and EM groups (n=20, median=3.25). At each visit, the PTLDS group scored higher on the FSS compared to the No PTLDS group, indicating higher levels of fatigue. In both groups, FSS decreased over time.Table 3:Total symptom score at each visit for erythema migrans versus disseminated. P-value calculated comparing LD syndrome disease at each corresponding time point.

Conclusion

A trend of higher total symptom score was observed in disseminated patients compared to erythema migrans at 6 months post-treatment. Fatigue was the most common symptom reported and the PTLDS group consistently reported higher fatigue severity compared to the No PTLDS group.Table 4:Fatigue Severity Score (FSS) and Visual Analogue Fatigue Scale (VAFS) at each visit for PTLDS and No PTLDS patients. P-value calculated comparing PTLDS and No PTLDS at each corresponding time point.

Disclosures

All Authors: No reported disclosures
P-1286. Severe Forms Of Rickettsiosis In Comparison With Non-Severe Forms
Authors: Hammami Fatma , Rekik Khaoula , Smaoui Fatma , Chakroun Amal , Marrakchi Chakib , Koubaa Makram , Jemaa Mounir Ben
Published: January 2025

Background

Rickettsiosis, a relatively benign disease, typically manifests with fever, skin rash, and headache. However, severe forms may occur, changing therefore, the prognosis of the disease. We aimed to study the clinical, biological and therapeutic characteristics of severe forms of rickettsiosis in comparison with non-severe forms.

Methods

We conducted a retrospective study including all patients hospitalized for rickettsiosis in infectious diseases department between 1996 and 2022. The diagnosis was confirmed by serological tests.

Results

We encountered 84 cases of severe rickettsiosis (17.8%) and 388 cases of non-severe forms (82.2%). The median age of patients with severe forms was 47[32-64] years and with non-severe forms was 37[25-53] years (p=0.24). Meningeal syndrome (38.1% vs 8.5%; p< 0.001) and vomiting (58.3% vs 41.9%; p=0.006) were significantly more frequent among severe cases. Maculopapular skin rash (57.1% vs 86.8%; p< 0.001) and arthralgia (58.3% vs 76%; p=0.001) were significantly less frequent among severe cases. Leukocytosis was significantly more frequent among severe forms (36.9% vs 20.6%; p=0.001). Elevated C-reactive protein levels (63.1% vs 66.2%; p=0.582), thrombocytopenia (51.8% vs 59.6%; p=0.19) and hepatic cytolysis (60.7% vs 69.8%; p=0.103) were noted among severe and non-severe forms, with no significant difference. Treatment duration was significantly longer among severe forms (10[7-14] days vs 7[5-10] days; p=0.016).

Conclusion

The diagnosis of severe forms of rickettsiosis should be ruled out in front of meningeal syndrome and vomiting, even in the absence of maculopapular skin rash and arthralgia, especially in the presence of leukocytosis.

Disclosures

All Authors: No reported disclosures
P-1298. Spatiotemporal Dynamics and Risk Factors of Scrub Typhus in 2013–2019 South Korea: a Bayesian Hurdle Model
Authors: Kim Jeehyun , Chun Byung Chul
Published: January 2025

Background

Scrub typhus (ST), also known as tsutsugamushi disease, is a common febrile vector-borne illness in South Korea, with rodents being the main host. Previous studies on vector-borne diseases have often lacked integrated spatiotemporal analyses covering disease dynamics, vectors, and environmental shifts. Therefore, we aimed to comprehensively explore high-risk areas and spatiotemporal trends of ST, incorporating vectors and environmental information.Figure 1.Flowchart of study subject selection. Scrub typhus was diagnosed with A75.3 in ICD-10-CM Code.

Epiweek, epidemiological week. NHIS, National Health Insurance Service in South Korea.

Methods

ST cases were extracted from the 2013–2019 Korea National Health Insurance Service data at 250 municipal levels. Spatial and temporal clusters were assessed using Getis-Ord Gi* and Hot and cold spot trend analyses. Bayesian hurdle models with spatiotemporal interaction terms were employed to identify associations between ST incidence and diverse regional factors, encompassing rodent suitability, as well as human and environmental factors. Stratification by gender and age group (0–19, 20–39, 40–59, 60–79, and ≥80 years) was performed.Figure 2.Scrub typhus incidence per 100,000 population by year.

Results

Between 2013 and 2019, 95,601 ST patients were reported (male-to-female incidence ratio=0.71:1). ST incidence had positive spatial autocorrelation across South Korea (I=0.600, p=0.01), with spatial expansion from southwestern to northeastern regions. Municipalities with higher rodent suitability (coefficient=0.230, 95% credible interval=0.126–0.333), forest area (coefficient=0.254, 95% credible interval=0.117–0.394), and worse financial independence (coefficient=-0.262, 95% credible interval=-0.326 to -0.198) had higher likelihoods of increased ST incidence, even after adjusting for spatiotemporal autocorrelation. However, significant risk factors varied by age group.Figure 3.Results of hot and cold spot trends by visualizing a space-time cube of scrub typhus incidence per 100,000 population.Colors represent the patterns of hot and cold spot trends, classified as “up trend,” “down trend," or “no significant trend” with 90, 95, and 99% confidence levels.

Conclusion

We elucidated the intricate spatiotemporal dynamics of scrub typhus in South Korea, accounting for factors such as rodent suitability, forest coverage, and economic independence, even after adjusting for spatiotemporal autocorrelation. Our findings lay the groundwork for evidence-based strategies and policies to tackle scrub typhus, integrating a holistic One Health perspective and emphasizing rodent distribution as a key determinant of disease risk.Table.Results of multivariable Bayesian spatiotemporal models on scrub typhus incidence by gender and age group, as expressed via coefficient (95% credible interval)WAIC, Watanabe-Akaike information criterion.

Disclosures

All Authors: No reported disclosures
P-1300. Themes to Support Identification of Emerging Infections Diseases
Authors: Kalvesmaki Andrea F , Peterson Kelly , Dalton Christian , Vuong Joann , Jones Barbara E , Stevens Vanessa W , Jones Makoto
Published: January 2025

Background

Many outbreaks are first recognized by astute clinicians who notice novel disease presentations, even before statistical anomalies are detected . In our efforts to identify COVID-19 cases using automated surveillance, we noted that the tone and content of clinical notes written early in the pandemic were much different than those written later . We investigated the content of early outbreak notes to identify general patterns that might reflect an emerging disease.

Methods

This study seeks to identify themes in a sample of clinical notes from Veteran Administration (VA) data. We used a convenience sample of early COVID-19 , early mpox, and CDC Nationally Notifiable Diseases cases as well as inference from a natural language processing (NLP) classifier that the clinical document mentioned communication with a public health authority (as an indicator of concern). These notes were reviewed by a VA infectious disease expert and a VA medical anthropologist with training in global health, the medical explanatory model, and diagnostic decision-making. Thematic analysis was applied to the notes.

Results

Five main themes were detected in the 100 documents reviewed. 1-Provider discerned something abnormal and included terms such as “unusual presentation”, and “disproportionate” to describe specific symptoms and indicate an element of being surprised. 2-Initiation of protocols for containment or treatment included terms such as “isolate” and “out of concern for… will treat with ” followed by a description of an established protocol for one or more symptoms. 3-Justification of protocol deviation included terms like “insist(ing)” on a type of test or referral to the health authorities. 4-Exposures included terms detailing locations of travel, potentially exposed persons, or locations that may have been sites of initial contraction. 5-Patient voice, as a theme, were described patient fear or agitation.

Conclusion

Unusual cases can prompt documentation of their exceptionality. Similar patterns may be seen in emerging diseases, such as H5N1, perhaps well before statistical increases are detected in the syndromes they cause. In further research, we will expand on this limited sample and explore NLP systems that could be applied to health records to scan for emerging health threats.

Disclosures

All Authors: No reported disclosures
P-1310. From Website to Parasite: An Analysis of the Unregulated Online Helminth Therapy Supply Chain
Authors: Ramirez Liliana J , Danehy Tessa L , Weiss Louis M
Published: January 2025

Background

Previous literature has demonstrated an inverse relationship between the prevalence of parasitic infections and chronic inflammatory diseases such as allergies, inflammatory bowel diseases, and autoimmunity. The “Old Friends” and “Hygiene” Hypotheses posit that in the sanitized society of high-income countries, the lack of allergens and microbiota is causing immune dysregulation. This research has led some individuals to pursue unregulated "helminth therapies" - ingesting parasites to relieve autoimmune symptoms - despite the lack of FDA approval or controlled clinical trials for the marketed products. The growth of an unregulated market, with transactions often conducted via untraceable Bitcoin and without transparency of origin, poses a public health risk that requires awareness among infectious disease specialists.

Methods

The researchers investigated 9 different helminth distributors to determine helminth species offered, origin, price, and “recommended dosage" of helminth therapy through the website Helminth Therapy Wiki. Helminth distributors analyzed include Symmbio, Au NAturel, Nathural, Tanawisa, Helminth Therapy NZ, Biome Restoration Ltd, The Llamas Clinic, YourSymbionts, and Autoimmune Therapies (AIT).

Results

78% of the helminth providers sold Necator americanus, i.e. hookworms (NA), 22% sold Trichuris trichiura, i.e. whipworms (TTO), 22% sold Hymenolepis diminuta, i.e. rat tapeworms (HDC), and 11% sold Trichuris suis, i.e. pig whipworms (TSO). The price of one dose of these various parasites ranged from $120 USD to $1,789 USD, depending on species and provider. “Doses” were highly variable; the dose of NA ranged from 1 - 25 larvae, while TSO ranged from 500 - 2,500 larvae. Many companies used untraceable payment methods and contact preferences to maintain secrecy. Statements on several provider websites used inaccurate marketing, over-promised benefits, and under-emphasized risks.

Conclusion

The unregulated market for helminth therapies poses significant public health and consumer protection issues, given the variability in doses, high costs, and dubious marketing claims. The lack of transparency and medical provider oversight further exacerbates the safety concerns in this market.

Disclosures

All Authors: No reported disclosures
P-1314. Assessment of the Effect of WHO and USA Antibiotic Awareness Campaigns on Search Engine Queries for Antimicrobial Resistance
Authors: Whitman Melissa , Barajas-Ochoa Aldo , Pedersen Laura
Published: January 2025

Background

Antimicrobial resistance (AMR) is a public health threat according to the World Health Organization (WHO), affecting all countries and at all income levels. Since the WHO’s initial action plan in 2001, multiple campaigns have arisen such as the WHO AMR Awareness Week and the CDC’s U.S. Antibiotic Awareness Week (November 18 to 24). Here, we use Google Trends (GTr) to assess the effects of three awareness campaigns on online search queries related to AMR in the US from their inception to April 2024.

Methods

GTr analyzes a sample of Google® web searches and allows users to make relative comparisons among searched terms by reporting the highest search volume as 100 and all other search volumes as a proportion of 100. Search queries related to AMR and AMR-related campaigns were used in GTr to generate normalized relative search volumes (RSVs) for each term (Table1). AMR-related campaigns' search volumes were compared to other established disease campaigns (Table 2). GTr search data from Jan 1, 2005 to April 20, 2024 was used. Descriptive statistics were used. No inferential statistics were used due to the nature of the data.

Results

When assessing RSVs for AMR-related campaigns, “Antibiotic Awareness week” had the highest RSV and peaked each November after 2017 (Figure 1a). When compared to established campaigns for other diseases, the average RSVs over time for AMR-related campaigns was smaller by a ratio of 8 (prostate cancer) to 219 times (breast cancer) (Figure 1b). Amongst AMR-related terms, “antibiotic resistance” was more searched over other terms and had only a slight increase in RSV over the years (Figure 2a). Notably, RSVs for “antibiotic resistance” each year peaked in Feb-Apr and not in November, the month of the AMR campaign (Figure 2b and 2c).

Conclusion

Despite AMR being one of the most concerning public health threats in the coming decade, public knowledge of this issue trails behind other health related campaigns. RSVs related to AMR did not increase over time despite awareness efforts. Although AMR-related campaigns take place in November, it was not the month with highest RSVs. These findings suggest that more resources may be needed to support the success of these campaign efforts.

Disclosures

All Authors: No reported disclosures
P-1331. Effect of Transfusion-Transmitted Infection Pre-Donation Deferrals on Subsequent Donations in a Military Blood Donation Center
Authors: Kwon Somin , Raiciulescu Sorana , Casleton Brian , Rivera Glorimar , Gella Melita , Winkler Erin , Osuna Angela , Casey Theresa , Yun Heather , Marcus Joseph
Published: January 2025

Background

To minimize the risk of transfusion-transmitted infections (TTI), all prospective blood donors are required to undergo extensive screening via questionnaire and physical exam. Donors who report behaviors or conditions that may increase risk of TTIs are temporarily deferred from donating. In recent years, significant changes to the deferral policy have been instituted to expand the donor eligibility pool and mitigate the blood supply crisis. In this study, we evaluate the impact of deferring donors at increased risk of TTI on future donation attempts to further inform how these policies may affect the military population.

Methods

This retrospective chart review evaluated all blood donors with pre-donation deferrals at a single site between October 2019 to December 2022. Among the fourteen deferral categories, seven were classified as behaviors or conditions that increase risk of TTI including: taking an anti-infective, travel to malaria-endemic area, recent tattoo or piercing, recent sexually transmitted infection (STI), recent COVID-19 infection, man who has sex with men (MSM), or other infectious concern. The rate of donation reattempts within the study period was assessed in donors deferred for TTI risk and compared to that of donors deferred for low hemoglobin matched by sex, age, and BMT status.

Results

6,352 (12.8%) of the 49,613 blood donors identified during the study had a pre-donation deferral. Over half of all deferrals were due to anemia (54.2%) and approximately a tenth for TTI risk (Table 1). We found that donors who were deferred for TTI risk were significantly less likely to attempt redonation during the study period compared to those deferred for anemia (p< 0.001). On multivariate analysis, donors deferred for MSM and travel or residence in a malaria-endemic area were independently associated with a decreased redonation attempt rate and increased time to reattempt (Table 2, Figure 1).

Time to redonation for deferred blood donors with a TTI risk (dark green) or anemia (light blue).

Conclusion

Pre-donation deferrals for TTI risk were associated with a decreased rate of redonation and increased time to reattempt compared to donors deferred for anemia.

Disclosures

All Authors: No reported disclosures
499. Seeing the full picture: Adding discharge antibiotic durations to the dashboard
Authors: Dodds Ashley Elizabeth , Dyer April , Bouchard Jeannette , Johnson Melissa D , Davis Angelina , Anderson Deverick J , Anderson Deverick J , Moehring Rebekah W
Published: January 2025

Background

Antibiotic use (AU) at hospital discharge is often inappropriate and can account for the majority of antibiotic exposure attributed to an admission. Tracking and optimizing discharge antibiotic prescriptions (Rx) can be challenging for antimicrobial stewardship programs (ASPs), as inpatient and outpatient AU are not linked in many electronic health records. Our aim was to establish a routine metric for total antimicrobial durations across a network of hospitals comprising Duke Antimicrobial Stewardship Outreach Network (DASON) and Duke University Health System (DUHS).

Methods

We created a data extract for discharge antibiotic Rx and incorporated this into existing data infrastructure supporting DASON and DUHS hospital-based ASPs. Extracts included discharge antibiotic Rx for agents within the American Hospital Formulary Service (AHFS) category for anti-infectives (8.00). Administration instructions and quantity were used to calculate antibiotic days of therapy (DOT) by agent for discharge Rx. Exclusion criteria were: 1) antiretroviral and anti-COVID medications, 2) Rx that had a paired discontinuation order within the first 24-48 hours 3) Rx with a duration > 30 days, 4) Rx where durations could not be calculated, and 5) non-enteral medications. The clinical reason for use was inferred from most proximal inpatient AU order if prescriber entered indication was available. Total antibiotic duration was determined by adding inpatient DOT and calculated discharge Rx DOT.

Results

Data from calendar year 2023 was available for 20 hospitals in DASON/DUHS. Of the initial 307,825 Rx identified, 255,543 Rx in 194,428 patients remained after applying exclusion criteria. Of interest, 83,276 (27%) patients received a discharge antibiotic Rx despite no record of inpatient AU. Data for the top 20 agents with a discharge Rx are shown in the Table; narrow spectrum agent use was common. Much of the total antibiotic course was prescribed post-discharge (range 27-90%). Genitourinary and skin/soft tissue infection (SSTI) were the most common Rx indications (Figure).

Conclusion

Antibiotics prescribed at discharge remains an important stewardship target. Data regarding AU at discharge can be combined with inpatient AU for routine monitoring to facilitate ASP interventions at TOC.

Disclosures

Elizabeth Dodds Ashley, PharmD, MHS, HealthtrackRx: Advisor/Consultant|UpToDate: Royalties Melissa D. Johnson, PharmD MHS AAHIVP, Biomeme: Licensed Technology|Scynexis, Inc: Grant/Research Support|UpToDate: Author Royalties Rebekah W. Moehring, MD, MPH, FIDSA, FSHEA, UpToDate, Inc.: Author Royalties
P-1336. Building Connections: Rise in Construction Projects correlated with New Cluster of Infantile Botulism in North Texas
Authors: Evans Amanda S , Wood William
Published: January 2025

Background

Regional clustering of infantile botulism is well documented in throughout the United States. We report a new cluster of cases in Northeast Texas.

Methods

We performed a single center retrospective chart review of all patients with suspected and confirmed infant botulism admitted to Children’s Medical Center Dallas from January 1, 2010 through December 31, 2023. Environmental conditions near each patient’s home prior to hospitalization were analyzed. County level data on annual birth, population, and death rates was collected from The United States Census Bureau. Construction permit data from Tyler, Texas was analyzed.

Results

46 infants with suspected infant botulism presented to care and received botulism immune globulin from 2010-2023. 3 infants were excluded due to alternative neurologic diagnosis. Features of cohort (N=43) without alternative diagnosis included in Table 1. 39 infants without honey exposure were included in environmental analysis: Group 1: 2010-2016 (N=8 infants), and Group 2: 2017-2023 (N=31 infants). The mean number of yearly residential construction permits issued (235.0 vs 352.7, p=0.01) and projects finalized (208.6 vs 333.5, p=0.01) increased from 2010-2016 to 2017-2022. The mean number of yearly commercial construction permits issued (40.1.0 vs 14.5, p=< 0.01) and projects finalized (36.9 vs 17.5, p=0.01) decreased between 2010-2016 as compared to 2017-2022. A sudden cessation of infantile botulism cases occurred during the COVID-19 pandemic that appears to coincide with delays in construction projects being complete. There were no significant differences between the 2 cohorts in environmental changes near the patient’s home address: temperature, precipitation, wind speed or direction, soil moisture, or drought index (Table 2). Specific humidity was significantly higher (p=0.01) in the 30-60 days before admission for patients presenting 2017-2023 as compared to 2010-2016 (-0.53 g/kg vs 0.70 g/kg).

Conclusion

Changes in local construction patterns are associated with a notable increase in infantile botulism cases in Northeast Texas over the past 14 years. Changes in environmental conditions do not appear to play a large role in this increasing case count.

Disclosures

All Authors: No reported disclosures
P-1339. Navigating Antibiotic Susceptibility Testing: The Antibiotic Breakpoint Explorer (ABE 1.0)
Authors: Craney Arryn , Lau Suetping , Jones Addae , Mandal Sanjay
Published: January 2025

Background

The landscape of antibiotic susceptibility testing has evolved significantly, with constant revisions to antibiotic breakpoint definitions by key standard-setting bodies: the Clinical and Laboratory Standards Institute (CLSI), the Food and Drug Administration (FDA), and the European Committee on Antimicrobial Susceptibility Testing (EUCAST). These changes reflect advances in scientific understanding, emerging resistance patterns, and the need for harmonization across international guidelines. However, staying abreast of these evolving breakpoints can be challenging for healthcare professionals. The Antibiotic Breakpoint Explorer 1.0 (ABE 1.0) is an innovative tool that simplifies antibiotic susceptibility testing interpretation with current 2024 breakpoint interpretive criteria.

Methods

Antibiotic breakpoints for minimum inhibitor concentration (MIC) were consolidated from the CLSI, FDA and EUCAST websites for current 2024 breakpoint interpretative criteria for 15 Gram-negative pathogens and 30 antibiotics from 10 antibiotic classes (Table 1). ABE 1.0 was programmed using Python 3.12.2 and the Streamlit package. ABE 1.0 is hosted as a web-based tool hosted at www.petrifiedbugs.com. The initial beta version of the program is accessible at https://newbreak-hxdfezfsrkpuusfjpfkrby.streamlit.app/

Results

By consolidating breakpoint information from CLSI, FDA, and EUCAST guidelines for the top 15 Gram-negative pathogens, ABE 1.0 provides a simple user-friendly web-based tool to help users make informed decisions regarding antibiotic therapy and resistance management for 30 key clinically used antibiotics (Figure 1).

Conclusion

ABE 1.0 addresses the challenge of navigating antibiotic breakpoints by offering a user-friendly platform that consolidates antibiotic breakpoint information from CLSI, FDA, and EUCAST guidelines into a single, easily accessible resource.

Disclosures

Arryn Craney, PhD D(ABMM), MiraVista Diagnostics: Employee; Salary
P-1340. Genetic Factors Associated with Cefepime and Piperacillin/Tazobactam Resistance in Clinical Extended-Spectrum Beta-Lactamase-Producing Enterobacterales from the Intensive Care Unit
Authors: Hokunson Todd W , Hernandez Erica , Annavajhala Medini K , Uhlemann Anne-Catrin , Gomez-Simmonds Angela
Published: January 2025

Background

Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBLE) are common pathogens in intensive care units (ICUs) causing infection at a range of body sites. While carbapenems are considered first-line agents, non-carbapenem beta-lactams such as piperacillin/tazobactam (TZP) and cefepime (FEP) are often used to treat non-severe ESBLE infections. Few studies have examined the molecular epidemiology and mechanisms of TZP and FEP resistance in non-bloodstream ESBLE isolates (e.g. urine, respiratory tract).

Methods

We screened Enterobacterales isolates collected between 2015-2019 for the ESBL gene blaCTX-M using multiplex PCR and performed nanopore sequencing positive isolates (n=164). FEP and TZP susceptibilities were determined by broth microdilution (BMD). We assessed the impact of genetic factors such as the location and genetic context of blaCTX-M, other beta-lactamase gene presence, and porin gene disruption on TZP and FEP MICs (Figure 1); univariable and multivariable logistic regression were used to test their association with FEP and TZP resistance.

Results

Most isolates belonged to Klebsiella pneumoniae (47%) or Escherichia coli(45%) and were highly clonally diverse. blaCTX-M-15 was the most common blaCTX-M allele (78%) followed by blaCTX-M-27 (15%). 47% of isolates demonstrated FEP resistance (MIC50/90 8/64 µg/mL), which was significantly associated with blaCTX-M allele, location, and copy number and narrow-spectrum β-lactamase co-carriage. Only 10% of isolates were resistant to TZP (MIC50/90 4/16 µg/mL), which did not appear to be modulated by presence of blaCTX-M. In multivariable analyses, FEP resistance was independently associated with blaCTX-M copies (OR 5.21, 95% CI 1.7-24.6, p=0.01) and association with truncated ISEcp1 (OR 12.9, 95% CI 3.1-65, p< 0.001); TZP resistance was associated with organism (OR 5.82 for K. pneumoniae versus E. coli, 95% CI 1.3-43.8, p=0.04), presence of blaOXA-1 (OR 5.2, 95% CI 1.3-35.9, p=0.04), and porin gene disruption (OR 6.5, 95% CI 1.3-32.3, p=0.02).

Conclusion

In summary, TZP resistance was uncommon and appeared to be independent of blaCTX-M carriage. TZP may be an appropriate treatment for nonbloodstream ESBLE infections in the ICU and should be evaluated further in clinical studies.

Disclosures

All Authors: No reported disclosures
P-1350. Novel mutations in PBP1 and AcrB associated with methicillin resistance in clinical isolates of S. aureus lacking mec variants
Authors: Mancera Maria Alejandra , Matiz Juan , Leal Castro Aura Lucia , de Paula Baptista Rodrigo , Rincon Sandra , Carvajal Lina Paola , Celis Ramirez Adriana Marcela , Reyes Jinnethe
Published: January 2025

Background

Methicillin-resistant S. aureus (MRSA) is a major global pathogen. In the absence of mecA and mecC, methicillin resistance has been associated with genetic changes, such as PBP1 to PBP4 (Penicillin-Binding Protein) and GdpP (c-di-AMP phosphodiesterase) mutations. However, this unusual genotype has not been reported in Colombia. Here, the aim was to characterize the genetic determinants in two methicillin-resistant clinical isolates of S. aureus lacking mec variants in Colombia.

Table 1

Genetic changes associated with methicillin resistance lacking mec variants in SaA and SaB isolates.

Methods

One isolate (SaA) was recovered in 2015 from a urine culture and the second (SaB) was obtained in 2016 from a peritoneal fluid secretion. OXA susceptibility was assessed via broth microdilution according to CLSI M100 guidelines, and species confirmation and mecA detection were performed using multiplex PCR. Genome characterization by Illumina Whole Genome Sequencing was conducted to evaluate the presence of mec variants (A, B, or C) and determinants associated with OXA resistance lacking mec variants (mutations in PBP1 to PBP4, pbp4 promoter, GdpP, and AcrB).

Results

Both isolates were identified as MRSA (OXA MIC of 16 ug/mL) but lacked mecA by PCR. In addition, genomic characterization showed that SaA (ST-5/CC-5/agr-III) and SaB (ST-765/CC-30/agr-I) do not harbor any mec variants. Moreover, the bla operon was complete in SaB, whereas was absent in SaA. Notably, we found genetic changes in SaA and SaB previously associated with methicillin resistance lacking mec (Table 1), some of which were common in both isolates (PBP1: N118D, PBP3: T438S and PBP4: T409A). Mutations in PBP2 were only detected in SaB. Remarkably, novel mutations, such as D604G in PBP1 and AcrB mutations (T52S, A282T, P285S, A577T, A677V, A711T, and V747I) were identified (Table 1).

Conclusion

Novel mutations in PBP1 and AcrB were found in clinical isolates of MRSA lacking mec variants, as well as previously documented genetic changes. This emergent unusual genotype needs further investigation.

Disclosures

All Authors: No reported disclosures
P-1364. Cefiderocol Activity against Pseudomonas aeruginosa Clinical Isolates Carrying Metallo-β-lactamase Genes in United States and European Hospitals (2020–2023)
Authors: Mendes Rodrigo E , Beekman Danielle , Karr Maura , Kimbrough Hank , Hubler Cory , Sader Helio S , Castanheira Mariana
Published: January 2025

Background

Cefiderocol (FDC) is a siderophore cephalosporin that uses the iron transport systems of Gram-negative bacteria to optimize cell entry. FDC is stable to hydrolysis by serine and metallo-β-lactamases (MBL). FDC and comparator activities were analyzed against P. aeruginosa (PSA) carrying MBL genes, as part of the SENTRY Antimicrobial Surveillance Program.

Methods

9,573 PSA were collected from 36 sites in the US and 43 sites in Europe (EU) in 2020–2023. Susceptibility (S) testing used broth microdilution with cation-adjusted Mueller-Hinton broth (CAMHB) for comparators and iron-depleted CAMHB for FDC. CLSI/EUCAST breakpoints were used for FDC; whereas CLSI were applied for comparators (EUCAST for colistin [COL]). Isolates with MIC ≥4 mg/L (nonS by CLSI) for imipenem or meropenem were screened for β-lactamase genes.

Results

Carbapenem-nonS PSA comprised 23.4% (2,236/9,573) of isolates, with 22.3% (980/4,400) and 24.3% (1,256/5,173) originating from US and EU sites, respectively (Table). 5.5% (124/2,236) of PSA carried MBL, and these PSA were mostly from EU (94.4%). FDC (98.3–99.4%S) had MIC50 of 0.12 mg/L and MIC90 of 0.5 mg/L against carbapenem-nonS PSA from the US and EU, whereas other agents had lower S (80.9–90.2%), except for COL (99.7–99.8%S). Aztreonam-avibactam inhibited only 48.4% and 57.6% of carbapenem-nonS PSA from the US and EU at MIC of ≤8 mg/L, respectively. FDC (MIC50/90, 0.25/2 mg/L; 94.4–96.0%S) had activity against the MBL-carrying PSA subset; in contrast, other agents had off-scale MIC90 (i.e. >8 mg/L), except for COL (100%S). All PSA carrying blaIMP and blaVIM were susceptible to FDC (MIC90/100, 1/2 mg/L), whereas higher FDC MIC (MIC50/90, 2/16 mg/L; 57.1–64.3%S) were noted against blaNDM-carrying PSA.

Conclusion

FDC showed potent activity against carbapenem-nonS PSA clinical isolates from US and EU hospitals, including isolates carrying MBL genes, whereas newly launched BL/BLI didn’t show activity. FDC should be considered as an important option for the treatment of infections caused by these resistant subsets for which antibiotic treatment option are limited.

Disclosures

Rodrigo E. Mendes, PhD, GSK: Grant/Research Support
P-1368. High prevalence of class 1 integrons in carbapenem resistant Enterobacterales in Taiwan
Authors: Lee Susan Shin-Jung , Hsia Hui-Ling , Lee Yi-ting , Lin Hsi-Hsun
Published: January 2025

Background

The prevalence of integron in carbapenem resistant Enterobacterales is not well studied. This study aimed to investigate the prevalence and resistance gene cassettes of class 1 integron in carbapenem resistant Enterobacterales.Fig. 1.Integron gene expression in Carbapenem-resistant Enterobacterales (CRE)(N=101).

Methods

In total, 101 carbapenem resistant Enterobacterales strains were collected

through 2020 to2023. Genomic DNA was extractedand PCR method was performed for detection of class 1 integron gene cassettes. Sequences were performed by an automatic sequencer with Applied Biosystems 3730xl and alignment in GenBank.Figure 2.Resistance gene cassettes of Integron(+) in carbapemase-producing and non-carbapenemase producing carbapenem-resistant Klebsiella pneumoniae

Results

The prevalence of class 1 integron cassette of all Carbapenem resistant Enterobacterales (CRE) was 79.21% (80/101), and was high as 83% (44/53) in carbapenem resistant Klebsiella pneumoniae.The most common resistant gene cassettes wer edfrA12-aadA2 (20 %), following by dfrA17-aadA5 (17.5%) and aadA2 (11.25%). No carbapenemase gene was detected in class 1 integron gene cassettes. However, acriflavine resistance B (AcrB) gene, which is a multiple efflux transporter, wasdetected in 4 strains.Table 1.The expression patterns of integron genes (+) and integron genes (-) cassettes in different Carbapenem-resistant Enterobacterales (CRE).

Conclusion

Our study revealed high prevalence of type I integron gene cassettes in carbapenemase resistance Enterobacterales. The role of AcrB gene need to be further studied.

Disclosures

All Authors: No reported disclosures
P-1383. Gap in Doxy PEP Prescription for People Living With HIV Compared with PrEP Users in a Primary Care Practice
Authors: Asiago-Reddy Elizabeth , Himat Nabeil , Myers Courtney
Published: January 2025

Background

Use of 200mg of doxycycline as post-exposure prophylaxis within 72 hours of a condomless sexual encounter (Doxy PEP) has been shown to reduce the risk of key sexually transmitted infections (STIs). Doxy PEP is effective both for people living with HIV (PLH) as well as those who do not have HIV. The goal of this analysis was to describe uptake of Doxy PEP in a primary care practice in Syracuse, NY, a Northeastern U.S. city serving a large population of PLH as well as people prescribed pre-exposure prophylaxis (PrEP) for HIV prevention.

Methods

Data were abstracted from the electronic medical record. Patients who were seen for HIV or PrEP care between 1 Jan and 31 December, 2023 who were transgender women (TGW) or cisgender men self-identified as gay, bisexual, or “other” sexual orientation (MSM) and had been diagnosed with chlamydia, gonorrhea or syphilis during 2023 were analyzed. Doxy PEP discussion and prescription were determined through medication review and office notes up through the first quarter of 2024. Factors associated with providers recommending and/or prescribing doxy PEP were evaluated using bivariable and multivariate logistic regression.

Results

A total of 602 MSM and 25 TGW were seen in the practice during 2023; 117 (18.7%) were diagnosed with at least one STI, specifically syphilis [37; (31.6%)], chlamydia [33 (28.2%)], gonorrhea [23 (19.7%)] or more than 1 of these [24 (20.5%)]. A total of 46 (39.3%) patients were prescribed doxy PEP; 11 (9.3%) declined, and 60 (51.3%) had no documented discussion or prescription. Most 35 (76.1%) prescriptions were in the 1st quarter of 2024; average days between STI diagnosis and doxy PEP prescription was 200 days. On multivariate analysis (MVA), only PrEP vs. HIV was associated with prescription (OR 13.3 p< 0.0001; this held even after excluding 4th quarter STI diagnoses to account for less frequent follow up of PLH vs. PrEP users (OR 17.5, p=0.001). Doxy PEP prescription was not associated with age, race or ethnicity, type or site of STI, provider, or time (days) since STI diagnosis.

Conclusion

Doxy PEP is a valuable tool for reducing STIs; it may be underutilized in people living with HIV despite ongoing risk, and methods to encourage prescription for PLH are warranted.

Disclosures

Elizabeth Asiago-Reddy, MD, Abbvie: Grant/Research Support|GSK/Viiv: Grant/Research Support|Pfizer: Grant/Research Support|Theratechnologies, Inc.: Grant/Research Support
504. Missed opportunities for HIV Prevention and Treatment in People Hospitalized with Serious Injection Related Infections: The CHOICE+ Cohort
Authors: Bryan Nicole , Traver Edward C , Kattakuzhy Sarah , Carpenter Joseph E , Catalanotti Jillian S , Raman Sumitha , Fujita Ayako W , Kuo Irene , Steck Alaina , Rosenthal Elana S , Reece Becky
Published: January 2025

Background

Harm reduction for persons who inject drugs (PWID) has many components, including HIV testing and Pre-exposure Prophylaxis (PrEP). However, despite the increasing evidence of effectiveness, PrEP remains highly underutilized in these patients at high-risk for infection and subsequent transmission risk to others. Our aim is to identify the gaps in HIV prevention care among a hospitalized PWID population.Table 1:Demographics and Clinical Characteristics

Methods

CHOICE+ is a multisite retrospective cohort study of adults hospitalized with infectious complications of active injection opioid use between 1/1/2018 and 3/31/2022 at four US medical centers. Data were collected by abstraction of the electronic medical record and analyzed by chi-square and multivariate logistic regression.Table 2:Multivariate Analysis of Factors Associated with HIV Screening

Results

1168 (74%) adults with unknown HIV status underwent HIV screening during sentinel admission. For risk comparison, 48% of this cohort had active HCV infection. HIV screening was less likely to occur in PWID who were male (69% vs 78% females), Black (51% vs 78% White), hospitalized < 3 days (56%), on non-medical services (62% vs 75%), and without ID consult (56% vs 79%). Only 3 participants were referred for PrEP, and only 4 initiated PrEP within 1 year of discharge. Additionally, nearly half (49%) of this HIV (-) cohort did not have follow up HIV screening. There were 79 HIV (+) individuals: 66 known HIV (+) and 13 new diagnoses. Forty-five (57%) were on anti-retroviral therapy during hospitalization, 28 (35%) had CD4 < 200, 47 (59%) had detectable viral load, and 49 (62%) were referred for HIV care. However, only 37% were confirmed linked to care. Of those in care, 59% were virally suppressed within 12 months.Table 3:HIV Prevention Outcomes among HIV negative group within 12 months

Conclusion

In a cohort of high-risk PWID hospitalized with infectious complications of substance use, there were low rates of HIV screening, PrEP initiation, and referrals for treatment in HIV (-) individuals. The lack of PrEP initiation in this study is unsurprising; however, the absence of referring patients suggests a lack of awareness of increased PrEP availability. More concerning are the gaps in HIV screening among this high-risk cohort. Clinicians must capitalize on opportunities to provide this population with tools to reduce their risks, which includes HIV screening and PrEP.Figure 1:HIV Care Cascade

Disclosures

Elana S. Rosenthal, MD, Gilead Sciences: Grant/Research Support|Merck: Grant/Research Support
P-1386. Developing a Diagnostic Strategy for the Diagnosis of Bacterial Vaginosis: A Shift from Subjective to Objective Approach
Authors: Grover Pragati , Sethi Sunil , Dadwal Rajneesh , Sehgal Amit , Saini Aastha , Bagga Rashmi , Chopra Seema , Angrup Archana
Published: January 2025

Background

Bacterial vaginosis (BV), a polymicrobial syndrome of unclear etiology is a major public health problem. The current diagnostic approaches lack standardisation and are not easily reproducible. We aim to develop a diagnostic modality to enhance the accurate diagnosis of BV.

Methods

385 vaginal samples were categorised into BV positive (n=108), BV negative (n=208) and intermediate group (n=69). The positive and negative samples were then subjected to qualitative and quantitative PCR. The two pathogens targetted were Fannyhessea vaginae and Gardenerella vaginalis.

Standardisation real time PCR: CP value and Tm value for Gardnerella vaginalis

Results

PCR detection as compared to Nugent criteria yielded a sensitivity of 96% and specificity of 82.9%, positive predicitive value (PPV) of 68.5% and negative predicitive value (NPV) of 98.2%. In contrast, molecular quantification of the two bacteria together had highest specificity (99.52%) with excellent PPV of 98.1%. Although, with a low sensitivity (48.1%) and NPV (78%).

Conclusion

All women in reproductive age group should be screened for BV using qualitative PCR targeting Fannyhessea vaginae and Gardenerella vaginalis together. In symptomatic women, the use of quantitative PCR can provide a consistent diagnosis of BV. Thus this objective diagnostic strategy can play a pivotal role in prevention, early diagnosis, treatment initiation and cure of BV.

Disclosures

All Authors: No reported disclosures