bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1247. Cerebrospinal Fluid Penetration of Multiple Antibiotics in Patients With Intracranial Hemorrhage: A Prospective, Observational, Clinical Study
Authors: Tseng Yu-Ju , Chen Yi-hsuan , Lan Yi-Xuan , Wu Chien-Chih , Luh Hui-Tzung 
Published: January 2025

Abstract

Background
External ventricular drains (EVD) are used for acute hydrocephalus in intracranial hemorrhage(ICH), potentially causing ventriculostomy-associated cerebrospinal fluid infection (VAI). Variable meningeal inflammation in VAI can result in unpredictable antibiotic penetration in cerebrospinal fluid (CSF). This observational study aimed to assess CSF penetration of intravenous antibiotics for suspected VAI treatment in neurosurgical patients.
Time to concentrations in CSF and plasma among the patients.
The figure presented the concentrations of blood and cerebrospinal fluid (CSF) measured at different time points for each patient. REVD right-sided external ventricular drain. LEVD left-sided external ventricular drain.

Methods
Adults with EVD for ICH who were receiving antibiotics, including vancomycin, ceftazidime, cefepime and meropenem, for VAI from January 2023 to April 2024 in two north Taiwan medical centers were enrolled in this study. The primary outcome was the area under the concentration (AUC) ratio between CSF and plasma (AUCCSF/plasma). Factors influencing CSF concentration was also investigated. In addition, the probability of target attainment (PTA) of anti-Pseudomonal antibiotics were calculated.
A summary of the permeability of vancomycin into the cerebrospinal fluid in this study.
ARC augmentation renal clearance. L Left-side external ventricular drain R Right-side external ventricular drain.
a. AUC was calculated from the first observation point to the last observation point.
b. It was resistant to vancomycin.

Results
A total of 9 patients (6 male) with VAI were enrolled, and contributed 7 vancomycin, 3 ceftazidime, 2 cefepime and 2 meropenem treatment courses. One patient provided two courses. The ranges of AUCCSF/plasma for vancomycin, ceftazidime, cefepime, or meropenem were as follows 0.85-15.61%, 6.74-15.61%, 0.16-128.73%, and 0.09-13.24%, respectively. The CSF to plasma concentration ratio at the end of vancomycin infusion and at the middle of dosing interval showed good correlation with AUCCSF/plasma (Spearman's coefficient 0.8 and 0.783, p-value ≦0.01) For ceftazidime, both CSF and plasma achieved at least 98% fT &gt;MIC=8 under 2 gram every 8 hours regimen. For meropenem, the fT &gt;MIC=2 for CSF and plasma were 0-100 % and 95.7-99.8% under 2 gram every 8 hours regimen, respectively. For cefepime, the fT &gt;MIC=16 for CSF and plasma were 0-100% and &gt;97%, respectively.

Conclusion
This is the first study to report real-world data of antibiotic CSF penetration in neurosurgical population in Taiwan. Ceftazidime showed adequate penetration and achieved sufficient PTA in the CSF. Additionally, the single-point ratio of vancomycin at the end of infusion and during the mid-dosing interval may serve as a surrogate for AUCCSF/plasma.

Disclosures
All Authors: No reported disclosures
P-1249. Analysis of Drug Interaction Between Valproic acid and Carbapenems
Authors: Cho Youngmin , Moon Hyejeong , Park Jaemin , Kim Chang , Han Ji Yeon , Kim Hun Min , Choi Yunsang , Choi Seong Jin , Moon Song Mi , Song Kyoung-Ho , Kim Eu Suk , Kim Hong Bin , Lee Woo-Jin , Yun Chang-Ho , Yoon Seonghae , Chung Jae-Yong , Lee Joon Hee , Park Jeong Su , Heo Eunjeong , Kim hyung-Sook , Lee Hyunju 
Published: January 2025

Abstract

Background
Carbapenems are broad spectrum antibiotics widely used for treatment of various infectious disease such as pneumonia, sepsis, and urinary tract infection. Carbapenems have been linked to a possible drug interaction which can lead to subtherapeutic levels of valproate and increase the risk of patients experiencing seizures. In this study, we reviewed cases of concomitant use of valproic acid and carbapenems, and investigated the impact of drug-drug interactions and effects.

Methods
The electronic medical records of patients treated with carbapenems and valproic acid at Seoul National University Bundang Hospital from 2017 to 2022 were reviewed.

Results
During the study period, a total of 183 patients were prescribed concomitantly with valproic acid and carbapenems. The average age was 64 years, 172 (94%) were &gt;18 years of age and 11 (6%) were ≤ 18 years. The most common reason for carbapenem prescription were urinary tract infection (48.1%), pneumonia (38.3%), sepsis (24.6%), and intra-abdominal infection (5.5%). Among carbapenems, ertapenem was most common by 61.8%, followed by meropenem (39.9%), and imipenem (3.3%). Of the total cases, valproic acid monotherapy accounted for 42.6% and concomitant use with other anticonvulsants accounted for 57.4%. During concomitant use of carbapenem and valproic acid, 35.0% of patients were consulted to the infectious diseases or neurology departments about drug interactions, and 44.8% monitored the therapeutic drug concentration. During the concomitant treatment, valproic acid dosage was increased in 19.1% and other anticonvulsants were added in 12.0%. Seizure occurred in 15 cases (8.2%) of the total cases.

Conclusion
As a result of investigating drug-drug interactions between carbapenem and valproic acid, serum concentrations of valproic acid were significantly decreased, some of which actually led to convulsions. Care should be taken when administering carbapenem to patients receiving valproic acid. If concomitant administration is unavoidable, it is important to monitor serum concentrations and consider alternative anticonvulsants. Continuing education and monitoring of therapeutic drug concentrations are required for the concomitant administration of carbapenem antibiotics and valproic acid.

Disclosures
All Authors: No reported disclosures
P-1252. Individualizing Antibiotic Therapy: Pharmacokinetic Approach to Evaluate and Optimize dosing of Meropenem in Critically Ill Sepsis Patients
Authors: Dhandapani Shakthivel 
Published: January 2025

Abstract

Background
The optimization of antibiotic dosing poses a considerable challenge, particularly in cases of Sepsis with acute renal impairment requiring continuous renal replacement therapy (CRRT). This study centers on the widely prescribed broad-spectrum beta-lactams, specifically meropenem, recognizing its extensive use in severe and complex clinical scenarios. The primary objectives of this study is to formulate new guidelines facilitating dose individualization, thus enhancing therapeutic outcomes for this critical population.
Meropenem dosing recommendations for sepsis shock patients with acute renal impairment

Methods
Three studies were conducted based on specific hypotheses. The initial study involved a comprehensive systematic literature review aimed at critically evaluating the existing evidence regarding the dosing regimens of meropenem. Subsequently, Studies 2 and 3 were undertaken as observational, prospective, open-labeled, multicenter pharmacokinetic investigations within the Intensive Care Unit of a prominent tertiary care hospital in Coimbatore, India. The study cohort comprised thirty patients administered with meropenem experiencing septic shock with acute renal impairment requiring continuous renal replacement therapy. Population Pharmacokinetic models were meticulously developed, validated, and subjected to Monte Carlo simulations for comprehensive analysis.

Results
A comprehensive literature review exposed the limitations of current dosing recommendations, pointing to varied sickness severities, renal function levels, admission diagnostics, CRRT settings, and disparate pharmacokinetic (PK) methodologies. For meropenem, a crucial relationship between 24-hour urine output and total clearance emerged. Oligoanuric patients (&lt; 100mL/24h) displayed a 30% decrease in total clearance compared to those with preserved diuresis ( &gt;500mL/24h). Monte Carlo simulations supported tailored dosing recommendations, addressing bacterial susceptibility and patient diuresis status.

Conclusion
For optimal antibiotic dosing, our findings highlight the importance of considering clinical and demographic factors, including 24-hour urine output and patient weight. These insights can be implemented at the bedside to help navigate the complexities of antibiotic optimization within the Intensive Care Unit.

Disclosures
All Authors: No reported disclosures
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

Abstract

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 &lt; 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

Abstract

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

Abstract

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

Abstract

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&lt; 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&lt; 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

Abstract

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