bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-2144. Candida auris skin colonization and the risk of subsequent C. auris bloodstream infection in two teaching hospitals
Authors: Karakosta Polyxeni , Mantzana Paraskevi , Siopi Maria , Meletis Georgios , Tychala Areti , Georgiou Panagiota Christina , Protonotariou Efthymia , Meletiadis Iosif , Skoura Lemonia , Pournaras Spyros 
Published: January 2025

Abstract

Background
Candida auris, an emerging yeast that can cause outbreaks of severe infections in healthcare facilities, has shown an increased spread since the start of the COVID-19 pandemic. This study aimed to investigate the relative risk of subsequent C. auris bloodstream infection (BSI) in patients colonized on their skin by C. auris.

Methods
In this retrospective study, we included all inpatients hospitalized from January 2021 to December 2023, in Intensive Care Units (ICUs) or internal medicine wards of two distant teaching hospitals (Athens: Attikon University Hospital, Thessaloniki: AHEPA University Hospital), who were screened for skin colonization by C. auris and did not have a history of infection or colonisation by C. auris. The axilla and groin served as sampling sites. Screening was performed by selective media and species identification by MALDI-TOF. Patients were followed up for C. auris BSI and relative risk (95% confidence interval) was estimated after adjustment for ICU hospitalization, duration of hospitalization, age and sex.

Results
Of 1445 patients screened, 403 (27.9%) were colonized by C. auris (17.8% non-ICU, 82.2% ICU patients). Among them, 45 (3.1%) subsequently developed C. auris BSI. Skin C. auris colonization was associated with more than a 4-fold higher risk of subsequent C. auris BSI, after adjusted for ICU hospitalization, age, sex and duration of hospital stay [RR (95%CI): 4.27 (2.13-8.57)].

Conclusion
C. auris skin colonization increases significantly the risk of developing C. auris BSI. This underscores the significance of public health monitoring and containment strategies for C. auris. Adhering to infection control protocols is crucial, and healthcare providers should take this into account when deciding on initial treatment, although more comprehensive genome-wide data are necessary to confirm horizontal transmission.

Disclosures
All Authors: No reported disclosures
P-2164. Diagnostic Utility of Plasma Microbial Cell-free DNA Sequencing in Suspected Infective Endocarditis and the Impact on Treatment Decisions
Authors: Kim Myeongji , Damronglerd Pansachee , Ranganath Nischal , Yetmar Zachary , Abu Saleh Omar M , Mahmood Maryam 
Published: January 2025

Abstract

Background
Plasma microbial cell-free DNA (mcfDNA) sequencing, commercially available from Karius® (Redwood City, CA), has been increasingly utilized in diagnosing endovascular infections. The 2023 updated Duke criteria incorporated detection of pathogen via metagenomic sequencing in its microbiologic criteria. We analyzed the clinical impact of mcfDNA sequencing in the diagnosis and treatment of suspected infective endocarditis (IE) cases.

Methods
We performed retrospective review of patients with suspected IE who underwent Karius® test at Mayo Clinic, MN, between 2017 to 2023.

Results
We preformed preliminary analysis of 25 patients. Analysis of baseline characteristics (table 1) revealed that these patients had significant predisposing factors for IE. Before accounting for mcfDNA sequencing, 3 (12%) met criteria for definite IE, 10 (40%) met criteria for possible IE, and 12 (48%) were rejected per 2023 Duke criteria. After incorporating mcfDNA sequencing result, 1 patient who was classified as possible IE was escalated to definite IE. This patient had previous infection of implantable cardioverter-defibrillator (ICD) with Streptococcus dysgalactiae. ICD was removed. She had development of endophthalmitis and stroke, 1 week and 2 weeks after the completion of IV antibiotics, respectively, with echocardiogram showing new tricuspid valve vegetation. Routine work-up was negative despite that she was not on any systemic antibiotics at the time of blood culture collection. mcfDNA sequencing detected Streptococcus dysgalactiae, making definite diagnosis of IE, leading to the physician’s decision to extend the IV antibiotic treatment (treatment escalation). Overall, after mcfDNA sequencing result, treatment decision was not impacted in 14 (56%), ongoing treatment was escalated in 4 (16%), de-escalated in 5 (20%), and antimicrobials was newly initiated in 2 (8%) (figure 1). Positive mcfDNA sequencing result often led to treatment escalation or initiation; negative result often led to treatment de-escalation (figure 2).

Conclusion
In challenging cases of suspected IE, mcfDNA sequencing led to alteration of antimicrobial treatment in 44% of cases. Further data collection and final analysis will include larger number of patients.

Disclosures
All Authors: No reported disclosures
P-2192. Hepatitis C Virus Re-infection in the Direct-Acting Antiviral Era within the US Veterans Health Administration
Authors: Gregoire Bruce , Maier Marissa , Beste Lauren , Matelski Alexander , Cartwright Emily J , Lowy Elliott , Morgan Timothy R , Varley Cara D , Ross David 
Published: January 2025

Abstract

Background
Background and Aims: Hepatitis C virus (HCV) treatment with direct-acting antivirals (DAA) results in a sustained virologic response (SVR) in &gt;90% of individuals (1). Limited prior data describes persons who achieve SVR and later develop recurrent viremia. We identify a cohort with HCV viremia after SVR, detail their risk factors for repeat viremia, and describe the time interval to repeat viremia
Characteristics of Veterans with recurrent HCV viremia (n= 1129)

Methods
We identified individuals in the Veterans Health Administration in care during 2021-2022 who received DAAs between January 1, 2014 and December 31, 2022, achieved SVR, and developed repeat viremia. We performed a manual chart review of a randomly selected subset of patients (10%) who were adjudicated into four categories defined as: (1) definite reinfection (HCV genotype change after SVR), (2) presumed reinfection (injection drug use, HIV pre-exposure prophylaxis receipt, new HIV or hepatitis B diagnoses, or incarceration between SVR and repeat viremia), (3) false positive result based on clinician assessment, or (4) neither (possible late relapse).
Adjudication as confirmed reinfection, probable reinfection, false positive, or neither based on chart review, N = 110
SVR = sustained virologic response; EOT = end of treatment; PrEP = pre-exposure prophylaxis VL = viral load.

Results
Among the 1,129 individuals in the cohort, median time to viremia after SVR was 23 months (IQR 9 – 42 months). Of the 110 individuals randomly selected for chart review, 25.5% (28/110) were definite reinfections, 25.5% (28/110) presumed reinfections, 11.8% (13/110) false positives, and 37.3% (41/110) did not meet any of the above criteria and were considered possible late relapses. Overall, 56/110 (50.9%) had a genotype change or known risk factor for reinfection, with IDU being the most common risk factor (27/110), followed by incarceration (10/110).
Time to repeat viremia

Conclusion
Our study found the median time to repeat viremia is 1.9 years with 75% of individuals developing repeat viremia within 3.6 years. In detailed chart review of a random subset of individuals with repeat viremia, half had confirmed or probable reinfection, and a clinically significant minority were false positive. After EMR review, over one third had no identified risk factor for repeat viremia.
(1) Nguyen V, et al. JAMA Netw Open. 2022;5(12).

Disclosures
All Authors: No reported disclosures
P-2193. The Importance of Telemedicine to the Linkage to Care and Treatment of Hepatitis C in West Virginia
Authors: Mulango Isabelle , Bryan Nicole , Guilfoose John A , Burner Kayleigh , Reece Becky , Thompson Jesse M 
Published: January 2025

Abstract

Background
West Virginia (WV) is entirely located within the Appalachian region and most of the population resides in rural areas. It is currently ranked 2nd in the nation for acute Hepatitis C infections due to the opioid crisis that has devastated the state. The use of direct-acting antivirals (DAA) for Hepatitis C treatment revolutionized care with cure rates near 100%. However, access to treatment remains low, particularly in rural areas such as WV. We implemented telemedicine visits in our Hepatitis C clinic to address this need. Here, we describe the impact of these delivery systems on engagement in care for this population.

Methods
We conducted a retrospective review of clinic visits at the West Virginia University hospital in Morgantown providing care for individuals with Hepatitis C. Data on adult clinic visits from January 1, 2018 to December 31, 2023 were abstracted from the electronic medical record (EMR) and analyzed by chi-square analysis.

Results
We analyzed a total of 7,811 visits and 2,471 patients. Most of the patients were male (58%, P&lt; 0.001). Ages ranged from 19-87 years old (41 ± 13). The majority of the patients identified as white (92%, P&lt; 0.001), consistent with the racial make-up of the state. 72% of the visits were in-person, compared to 22% telephone and 6% video visits (P&lt; 0.001). 58% of the visits were for return patients vs 42% new visits (P &lt; 0.001). Only 34% of the new patient visits were completed, 25% were cancelled and 41% were no-showed. More telephone visits and video visits were completed (80.8% and 48.9%) than in-person visits (31.9%). The majority of patients were located &gt;25 miles away from the clinic for most visits (66%, P&lt; 0.001). Completion rate for these individuals in-person, telephone and video visits were 32%, 81% and 49%, respectively (P&lt; 0.001).

Conclusion
Here, we show that the use of telemedicine was more successful in engaging rural Appalachian patients with Hepatitis C in care compared to in-person visits. Specifically, telephone visits. This finding is likely explained by the limited access to high-speed internet in these areas. Telemedicine services should be increased to expand Hepatitis C care to rural populations.

Disclosures
All Authors: No reported disclosures
P-2234. Real World Impact of Metagenomic Next-Generation Sequencing Compared to Standard Infectious Diagnostic Workup
Authors: Ackling Taylor , Lee Helen , Nam Hannah H 
Published: January 2025

Abstract

Background
Metagenomic next-generation sequencing (mNGS) is a new, promising diagnostic tool for infectious diseases (ID). Of these mNGS tests, cell-free DNA (cfDNA) sequencing is one of the first commercially available and most common send-out tests by academic medical centers in the US. Unlike standard microbiology and serology diagnostic tests, cfDNA utilizes blood samples to measure plasma microbial cell-free DNA to detect over 1,000 pathogens. However, there is significant cost associated with the testing. Currently, there is a lack of a standardized approach for how to interpret cfDNA results with limited publications clearly defining its clinical impact and utility.

Methods
We conducted a retrospective, descriptive study in an academic medical center of patients for whom cfDNA test was performed between January 2021 and September 2023 to determine its clinical impact and utility. The primary outcome of this study is the clinical impact of the cfDNA test categorized as positive, negative, indeterminate, or no impact. Positive impact is defined as leading to a new or earlier diagnosis compared to standard infectious workup, or escalation/de-escalation to appropriate antimicrobial agents. Negative impact is defined as leading to unnecessary treatment or additional diagnostic testing. Indeterminate impact is defined as patient mortality before test results. Secondary outcomes include disease-state indications for cfDNA testing. Clinical impact was adjudicated by an internal ID expert.

Results
There was a total of 150 cfDNA tests included amongst 121 patients during the study period. Pneumonia (52%) was the leading indication for testing, followed by febrile neutropenia (16%), endovascular infections (9.3%), and fevers of unknown origin (9.3%). Based on preliminary analysis, 25/150 (16.7%) resulted in a positive impact, 1/150 (0.67%) resulted in a negative impact, and 110/150 (72%) had no impact on diagnosis or antimicrobial use. 14/150 (9.3%) tests were indeterminate. Of the cfDNA tests resulting in positive impact, 65.3% led to the initiation of new antibiotics.

Conclusion
cfDNA testing may be useful in detecting new pathogens not found on standard workup, however, we found that it did not have a clinical impact in most cases in which it was utilized.

Disclosures
All Authors: No reported disclosures
P-2237. Mortality and Causative Pathogens of Sepsis Differ by Molecular Phenotype in a Secondary Analysis of MARS
Authors: Bartek Brian , Maddali Manoj , van Amstel Rombout B E , van der Poll Tom , Cremer Olaf , Consortium Mars , Bos Lieuwe D J , Sinha Pratik , Calfee Carolyn S 
Published: January 2025

Abstract

Background
Heterogeneity of host response has been a barrier to identifying novel therapies in sepsis. Two molecular phenotypes of critical illness, called the Hyperinflammatory and Hypoinflammatory, have been identified in multiple cohorts of sepsis and ARDS ( &gt;12,000 patients), with divergent biology, clinical course, and responses to therapy1. We evaluated whether these phenotypes were identifiable in MARS-- a large observational cohort of critically ill patients-- and whether the pathogens present in each phenotype differed.

Methods
MARS recruited critically ill patients from two Dutch ICUs. Only patients meeting sepsis or ARDS diagnostic criteria were included for this analysis. We applied latent class analysis (LCA) to vital signs, clinical laboratory values, and protein biomarkers from Day 1 of ICU admission in 1,485 patients. LCA models with 1-5 classes were fitted. We assigned class membership using the best fitting model and compared characteristics between classes. The present classes’ overlap with prior phenotypes was evaluated by comparison to an extensively validated parsimonious model,2 trained previously to classify molecular phenotypes.

Results
A two-class model best fit the cohort (VLMR p&lt; .001), and the parsimonious model and multivariate profiles suggested high overlap (AUC=.929) with previously described ‘Hypoinflammatory’ (Class 1; n=895) and ‘Hyperinflammatory’ (Class 2; n=590) phenotypes (Figure 1). Bacteremia was more prevalent in the Hyperinflammatory phenotype (27.2% vs 7.8%; p&lt; .001), with Enterobacteriaceae as the most prevalent species. For primary infection sites, lower respiratory tract was more common in the Hypoinflammatory (56% vs 36%) and abdomen more common in the Hyperinflammatory phenotype (26% vs 9%). Mortality was significantly higher in the Hyperinflammatory phenotype at both 30 days (OR=2.54, CI95%= 2.003—3.235 ) and 90 days (OR=2.41, CI95% = 1.925—3.016; both p&lt; .001).

Conclusion
In MARS, we identified the previously described Hypo- and Hyperinflammatory phenotypes with divergent host response, pathogen profiles, and outcomes. These findings suggest that host phenotype signatures in part may be driven by sites of infection and pathogen species.

Disclosures
Lieuwe D.J. Bos, MD-PhD, Astra Zeneca: Advisor/Consultant|CSL Behring: Advisor/Consultant|Impentri: Advisor/Consultant|Novartis: Advisor/Consultant|Scailyte: Advisor/Consultant|Sobi: Advisor/Consultant Pratik Sinha, MBChB/PhD, AstraZeneca: Advisor/Consultant|Prenosis Inc: Board Member Carolyn S. Calfee, MD, Cellenkos: Advisor/Consultant|Gen1e Life Sciences: Advisor/Consultant|Janssen: Advisor/Consultant|NGMBio: Advisor/Consultant|Santhera: Advisor/Consultant|Vasomune: Advisor/Consultant
P-2241. Monocyte Distribution Width (MDW) as a Biomarker to Distinguish Septic Shock with Bacteremia from Cardiogenic Shock
Authors: Goldner Kaylie Christine , DeWitt Michael E , Maves Ryan C 
Published: January 2025

Abstract

Background
Shock is associated with high mortality in intensive care units with resultant urgency for rapid diagnosis. The monocyte distribution width (MDW) is a biomarker that is elevated in sepsis and septic shock and is readily obtained from routine leukocyte differential testing. It is unknown whether MDW is also elevated in other kinds of shock. The purpose of this study was to evaluate the potential of MDW to discriminate between cardiogenic and septic shock.
Boxplot of the MDW values by those with cardiogenic shock vs those with septic shock (A). The receiver operator curves for the prediction of septic shock (B) and cardiogenic shock (C) using MDW cut-off values, resulting in an AUC of 0.892.

Methods
This study was a single-center retrospective analysis of adult patients admitted between 1/31/2023 and 12/27/2023 with either cardiogenic shock requiring inotropic or mechanical support or septic shock with bacteremia requiring vasopressor support derived from EHR database search for diagnosis codes. All patients required hemodynamic support and were excluded if any confounding immunosuppressive medications or conditions (e.g., advanced HIV infection, transplant, active malignancy on treatment) were present. Patients with cardiogenic shock were excluded if concomitant infection at the time of admission was identified. MDW was collected at the time of initial presentation.
Study population demographics and results by shock category.

Results
171 patients met inclusion criteria: 81 with septic shock and 90 with cardiogenic shock. 56.7% of patients with cardiogenic shock received empiric antibiotics on admission. The MDW was significantly higher in the septic shock group. Using estimated cut-off values of MDW &gt; 21.53 for septic shock and MDW &lt; 28.99 for cardiogenic shock each produced an AUC (area under the curve) of 0.892. Elevated SOFA score, elevated WBC, and female sex were associated with increased odds of septic shock. Adding the WBC count to MDW in the logistic regression for septic shock only minimally improved the AUC.

Conclusion
MDW may be a useful tool in stratifying the risk of septic or cardiogenic shock. MDW above 28.99 supports a diagnosis of septic shock with bacteremia while MDW below 21.53 supports a diagnosis of non-septic shock; values from 21.53-28.99 are less predictive. A low MDW in patients with shock may exclude the need for empiric antibiotics and improve stewardship. Further work is needed to better characterize the performance of this assay in other populations and shock phenotypes.

Disclosures
Ryan C. Maves, MD, AiCuris: Grant/Research Support|Biotest: Grant/Research Support|GeoVax: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Honoraria|Sound Pharmaceuticals: Grant/Research Support
P-2244. Prevalence of Antifungal Allergies in the General Population
Authors: Shiferaw Meron , Donnelley Monica , Thompson George R 
Published: January 2025

Abstract

Background
The use of antifungal agents continues to increase yearly and coincides with the growing immunocompromised patient population. Therapy may be prescribed as prophylaxis or treatment in fungal disease care. The emergence of novel fungal pathogens, antifungal resistant species, and infection control concerns pose challenges to antifungal agents' use. However patient tolerability remains a significant issue and documented allergic reactions to antifungal agents have not previously been reported.
Primary Outcome
1.7 million patients assessed for reported antifungal allergy

Methods
A multi-site, population health, retrospective cohort review was conducted including all healthcare sites within the University of California system. All inpatient and outpatients with an antifungal allergy reported in 2023 were included. Specifically, patients reporting an allergy to a systemic antifungal agent or with a general antifungal allergy ICD-10 T36.7. The following systemic antifungals were included: fluconazole, voriconazole, isavuconazole, posaconazole, itraconazole, amphotericin B formulations, micafungin, caspofungin, anidulafungin, and/or flucytosine. The primary outcome of this study was the rate of reported antifungal allergy among a general population. Secondary outcome, the incidence of antifungal allergies among patients with documented administration of antifungal agent.
Baseline Characteristics

Results
During the study period 1,704,176 patients were screened for reported antifungal allergy, and 2598 patients exhibited a documented antifungal allergy. An allergy to a specific antifungal agent was reported in 2203 patients, while 395 patients reported an unspecified antifungal allergy. From greatest to least reported: fluconazole 1,591 (0.093%), general antifungal allergy 395 (0.023%), triazole 361 (0.021%), itraconazole 145 (0.009%), amphotericin 110 (0.006%), flucytosine less than 10 (0.001%) (Table 1). Secondary outcome 9,976 patients received an antifungal agent and 496 reported an antifungal allergy.
Table 1

Conclusion
This is the first study to report antifungal allergy rates in the general population. It assessed over 1.7 million patients and found the allergy rate to be low at 0.15%. Future work evaluating the utility of skin testing, cross-allergenicity, and desensitization strategies should be performed.
Secondary Outcome

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