bluuebunny/crossref_metadata_2025 huggingface dataset:
P-1943. Risk Factors for Coronavirus disease 2019 (COVID-19)-Associated Pulmonary Aspergillosis (CAPA) in Critically Ill Patients: The Predictive Value of KL-6 for CAPA and Mortality
Authors: Lee Seung Min , Kim Si-Ho , Jeon Cheon-Hoo , Wi Yu Mi
Published: January 2025

Background

Coronavirus Disease 2019 (COVID-19) is an acute respiratory viral illness that can be complicated by secondary invasive fungal infections, such as COVID-19-Associated Pulmonary Aspergillosis (CAPA). Krebs von den Lungen-6 (KL-6), a mucinous high-molecular-weight glycoprotein found on the surface of type II alveolar epithelial cells, has been known as a biomarker indicative of respiratory epithelial damage. This study aims to evaluate the risk factors for CAPA in critically ill COVID-19 patients, with a focus on the predictive value of KL-6.

Overall 30-day survival rates between patients with and without CAPA

Methods

This single-center retrospective cohort study included critically ill COVID-19 patients (those requiring high-flow respiratory support or mechanical ventilation) admitted from January 2021 through June 2023. CAPA diagnosis was established based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. The study investigated factors associated with CAPA and compared overall 30-day mortality for patients with and without CAPA.

Results

Among 238 critically ill COVID-19 patients, 25 (10.5%) were diagnosed with CAPA. Notably, patients with CAPA exhibited significantly higher median serum peak levels of KL-6 (787.4 vs. 290.2 U/mL, P< 0.001), with a cutoff value of 392.9 U/mL determined by the Youden index. Multivariable analysis revealed that a peak KL-6 level ≥ 392.9 U/mL was strongly associated with CAPA (adjusted odds ratio 8.62, 95% confidence interval [CI] 2.43-31.69). Additionally, inotropics/vasopressor support, diabetes mellitus, and tocilizumab were identified as factors associated with the development of CAPA. The overall 30-day mortality was significantly higher in patients with CAPA (60.8%) compared to those without (45.2%) (P=0.020), with the difference persisting after adjustment (adjusted hazard ratio 2.06, 95% CI 1.05-4.03). Furthermore, along with older age, lacticemia, and diabetes mellitus, elevated KL-6 was also associated with increased mortality.

Conclusion

Our study suggests that KL-6 may be a significant predictor of both the development of CAPA and mortality among critically ill patients with COVID-19.

Disclosures

All Authors: No reported disclosures
P-1952. SARS-CoV-2 Self-Testing Modalities Demonstrate Concerning Inaccuracies Among Rural, Minority Populations: The ALL-IN SC Study
Authors: Meyer Madeleine M , Self Stella C W , Daguise Virginie , Nolan Melissa
Published: January 2025

Background

At-home, diagnostic self-test assays provide a unique opportunity to reduce healthcare disparities by providing low-cost, immediate access to disease testing. Despite their utility, their real-world accuracy is unknown. Therefore, this study aimed to evaluate multiple testing modalities among diverse, marginalized populations in a large, multi-year, state-wide randomized controlled trial.

Methods

From 2022 to 2023, 2,195 individuals participated in testing events across South Carolina, USA. Participants provided medical personnel collected samples for gold standard laboratory comparison and were assigned to one of three groups for a matching self-test comparison. These groups were 1) no assistance self-test (only provided manufacturer self-test instructions), 2) unassisted hybrid (collected their own samples according to manufacturer instructions and mailed-in samples to laboratory), and 3) assisted (medical personnel verbally explained the manufacturer’s instructions). A robust statistical analysis plan was executed; however, only the results from multivariate regression are described here.

Results

Participants in the unassisted groups were significantly more likely to have an incorrect self-test result. Conversely, participants with assistance were 32% more likely to have a correct self-test result, regardless of testing modality (saliva, dried blood spot, nasal swab). Self-collection of saliva samples to send to a laboratory for testing had the highest odds of inaccuracy (OR=9.21, p-value < 0.001). Self-collection of dried blood spot samples sent for laboratory testing had the lowest odds of inaccuracy (OR=1.52, p-value< 0.021). Demographic risk factors varied by testing modality, with females, black, and lower income participants statistically more likely to have inaccurate testing results. Select infection symptoms at the time of testing also increased the odds of inaccuracy.

Conclusion

This study provides critical evidence that self-tests are a viable option for addressing health care access disparities, but telemedicine and/or community assistance programs must also be provided to ensure tests are conducted and interpreted correctly.

Disclosures

All Authors: No reported disclosures
P-1967. Characteristics of the first immunocompromised patients to receive Sipavibart as an early access treatment for COVID-19 pre-exposure prophylaxis in France
Authors: Loubet Paul , Gaborit Benjamin , Salpin Mathilde , Gardeney Hélène , Benotmane Iliès , Systchenko Thomas
Published: January 2025

Background

Immunocompromised patients account for a large proportion of COVID-19 hospitalizations and deaths, even in the most recent periods, despite having received several COVID-19 vaccine doses. Monoclonal antibodies effectively prevented COVID-19 in the general population in randomized control trials and the immunocompromised population in real-world studies. Unfortunately, the emergence of new variants precluded their use. Sipavibart (AZD3152) is an investigational long-acting monoclonal antibody designed to provide broad coverage across Omicron and ancestral viral variants currently being studied in the SUPERNOVA prevention trial. France was the first country to grant Sipavibart as a COVID-19 pre-exposure prophylaxis treatment in immunocompromised individuals with an early access authorization in December 2023.

Methods

We performed a retrospective multicentric study in France, including the first consecutive patients to receive one intramuscular dose of Sipavibart in January and February 2024, to collect their characteristics and COVID-19-related medical history.

Results

Overall, we included 47 patients with a median age of 61 years (IQR:64—69) and 64% male. The three main immunosuppressive conditions were Stem cell transplants (38%), solid organ transplants (32%), and immune-based therapies (mostly Rituximab) (19%) for chronic inflammatory diseases or haematologic malignancies. Nearly half had hypogammaglobulinemia and 71% had at least another key comorbidity (Table 1). 15% and 11% had a history of severe and persistent COVID-19, respectively. The median number of COVID-19 doses was 4 (IQR 3-6), and nearly one-third had previously received previous generation of monoclonal antibodies for COVID-19 prophylaxis (Casirivimab/imdevimab or Tixagevimab/Cilgavimab). SARS-CoV-2 serology results before Sipavibart administration were available in 11 patients (without Immunoglobulins substitution). The median anti-Spike IgG titers was 30 UI/L (IQR 0-179).

Conclusion

The first patients to receive Sipavibart in France had different profiles, but they were all highly immunocompromised with frequently associated hypogammaglobulinemia and other chronic conditions.

Disclosures

Paul LOUBET, MD, PhD, Astrazeneca: Advisor/Consultant|Gilead: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant Iliès Benotmane, n/a, Astrazeneca: Advisor/Consultant|Astrazeneca: Board Member
P-1974. Surface Protein Profiling of Extracellular Vesicles: A Novel Biomarker Approach for Long COVID Diagnosis?
Authors: Ikeda Gentaro , Jagannathan Prasanna , Leki Mario , Inoue Hiroyuki , El Kamari Vanessa , Dadhania Arya V , Miglis Mitchell , Shafer Robert W , Geng Linda N , Yang Phillip C , Bonilla Hector F
Published: January 2025

Background

Extracellular vehicles (EVs) are lipid bilayer vesicles secreted by all cell types into the circulation. EVs carry an array of biomolecules indicative of their origin cells and act as cargo vesicles capable of delivering proteins, mitochondria, and viral particles. However, whether long COVID affects the profile of plasma EVs remains unknown.

Methods

Plasma samples were selected from the Stanford repositories of Long COVID participants—seventy-six plasma samples from patients with documented SARS-CoV-2 infection. Twenty-five participants had full recovery (10 months post-infection, Stanford Lambda Trial), 24 patients with Long COVID with CFS phenotype and 27 with ME/CFS from the Stanford Long COVID clinic. Plasma EVs were isolated using size-exclusion columns (qEV, Izon Science). The positivity for surface markers and mitochondrial membrane potentials of the plasma EVs were evaluated by flow cytometry. Samples were stained with pre-titrated volumes of the following fluorochrome-conjugated monoclonal antibodies: CD45 leukocytes, CD3/T cells, CD20/B cells, CD14/Monocytes, CD16/NK cells, CD144/endothelial cells, CD41a/Platelets, CD56/neural cell adhesion molecule (NCAM), and Mitotracker deep red/mitochondrial membrane potential.

Results

The total EV counts and the proportion of mitochondria-positive were decreased in Long COVID group compared to the COVID recovery group (5.02 x 106 vs. 1.92 x 107 /mL, and 42.7 vs. 56.7%, respectively). Compared with the recovery group, Monocyte and NK cell-derived EVs were significantly increased, whereas Endothelial cell-derived EVs were decreased in the Long COVID group. The EVs from the Long COVID group consistently exhibited lower positivity of mitochondrial membrane potential regardless of the parental cells. No difference was observed in plasma EVs derived from NCAM positive cells. NK cell proportion is the only difference between LC/CSF and CSF (P= 0.046).

Conclusion

Patients with Long COVID showed alterations in plasma EV profiles. These findings may offer insights into the pathogenesis of long COVID.

Disclosures

All Authors: No reported disclosures
P-1978. Long-Term Mast Cell Activation Patterns in Systemic and Tissue-Resident Compartments Following COVID-19: Insights from a 2-Year Post-Infection Study
Authors: Augustin Max , Picard Lea Katharina , Zenev Elisabeth , Ball Melanie , Rostocki Isabella , Pracht Elisabeth , Rauschning Dominic , de Silva Ute Sandaradura , Lin Ting-Huee , Petschnak Sophia , Kirschner Harald , Stingl Michael , Komenda-Lett Martin , Födinger Manuela , Wenisch Christoph , Lehmann Clara , Zoufaly Alexander
Published: January 2025

Background

The pathogenesis of Post-COVID syndrome (PCS) following mild coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) remains unclear. In particular, the involvement of activated mast cells (MC) in the highly angiotensin converting enzyme 2 (ACE2) expressing small bowel, the largest lymphoid organ, might be significant in PCS pathogenesis. This study aimed to elucidate the role of activated MC, residual SARS-CoV-2 spike (S) protein and zonulin (a marker for impaired intestinal integrity), in the context of PCS, examining peripheral blood (PB) and terminal ileum (TI) 2 years post-infection.

Methods

In this cross-sectional, controlled study, paired PB and TI samples were obtained from 21 SARS-CoV-2 convalescents with (PCS+) and 11 without PCS (PCS−). CD117+CD25+ activated MC and residual S protein were assessed using fluorescent immunohistochemistry on sections of the the ileal tissue from the gut. Tryptase, zonulin and S protein were quantified in serum by enzyme-linked immunosorbent assay (ELISA). Flow cytometry assessed frequencies of T-cells (CD3+CD4+ (TCD4), CD3+CD8+ T-cells (TCD8)) and CCR7±CD27± memory subsets (TCM: T central memory, TEM: T effector memory) on mononuclear cells of PB and TI.

Results

Among PCS+ and PCS−, median follow up was 22 and 18 months post-infection, 81% and 73% were female, and 57% and 55% had pre-existing conditions of which arterial hypertension, chronic lung disease and diabetes mellitus were the most frequent. Compared to PCS−, PCS+ expressed significantly more MC (p< 0.0001) in ileal sections, along with elevated levels of tryptase (p=0.0196) and zonulin (p=0.024) in PB. S protein, by contrast, was undetectable in PB of PCS+ and PCS− even 2 years post-infection. In TI however, the frequency of tissue-resident S protein-infected cells was significantly higher in PCS+ compared to PCS− (p=0.0135). Interestingly, systemic tryptase levels correlated positively to elevated TCM in TI (r=0.7407, p=0.0034).

Conclusion

Elevated MC activity and S protein in the TI, along with increased tryptase and zonulin levels in PB, indicate ongoing immune activation and intestinal damage in the TI of PCS+. Understanding the role of tissue-resident MC in PCS pathogenesis could lead to targeted therapies.

Disclosures

All Authors: No reported disclosures
P-1987. Effectiveness of Tixagevimab-Cilgavimab as Pre-Exposure Prophylaxis in Patients Undergoing Hematopoietic Cell Transplant or Chimeric Antigen Receptor T-cell Therapy
Authors: Juneja Arjun , Armistead Paul , Thakkar Astha , Ptachcinski Jonathan , Herman Catherine A
Published: January 2025

Background

Tixagevimab-cilgavimab (tixa-cil), was approved for emergency use authorization by the FDA in December of 2021 for pre-exposure prophylaxis of the COVID-19 virus in immunocompromised populations due to concerns about vaccine efficacy. Data regarding real world efficacy of tixa-cil in preventing SARS-CoV-2 infection in immunocompromised patients is limited.Table 1Patient Demographics

Methods

We conducted a retrospective analysis of all patients who had received hematopoietic cell transplantation (HCT) or chimeric antigen receptor T-cell (CAR-T cell) therapy between 12/1/2021-12/1/2022 at the University of North Carolina Bone Marrow Transplant and Cellular Therapy Program and were eligible to receive tixa-cil as pre-exposure prophylaxis. Patient demographics, underlying malignancy type, COVID-19 vaccine status, data and number of tixa-cil injections, cellular infusion type, presence of GVHD, adverse events, and cause of death if related to COVID-19 were all collected.Table 2Therapeutic Agents Used For Treatment of COVID-19

Results

Of 184 eligible patients, 113 (61%) received at least one tixa-cil injection. Forty-five cases of either documented or reported COVID-19 infection following cell infusion (including 8 recurrent infections) were identified. Of the 113 patients who received tixa-cil, 14 (12%) had a documented positive COVID test within 6 months. In comparison, 23 (32%) of the 71 patients who did not receive tixa-cel had a documented positive COVID test, (p=0.0013, Fisher’s exact test), OR=0.2951. Of 13 COVID-related hospitalizations, only one occurred in a patient who received tixa-cil, (p=0.0048, Fisher’s exact), OR=0.0641.

Number of Patients with Documented COVID Infections Who Did and Did Not Receive Tixa-Cil

Conclusion

Our findings indicate that tixa-cil was effective as pre-exposure prophylaxis in reducing SARS-CoV-2 infection and disease severity in a highly immunocompromised patient population. While the FDA removed authorization for ongoing use of tixa-cil in January 2023 due to its ineffectiveness against the Omicron variants, our data suggest that mAbs are highly effective in providing protective passive immunity to patients at risk of impaired vaccination responses. Pemibivart, a new anti-SARS-CoV-2 spike protein mAb, was recently authorized by the FDA. Our results suggest a clinical benefit for this therapy; however, real world studies will be needed to determine actual efficacy.

Number of Patients Hospitalized Related to COVID Infection Who Did and Did Not Receive Tixa-Cil

Disclosures

Jonathan Ptachcinski, PharmD, Johnson & Johnson: Company Employee
P-2012. Predicting Persistent SARS-CoV-2 Shedding in Immunocompromised Patients: A Probability-Based Approach
Authors: Chang Eui Jin , Kim Jun-Won , Jang Choi-Young , Kang Sung Woon , Kim Ji Yeon , Bae Seongman , Jung Jiwon , Kim Min Jae , Chong Yong Pil , Lee Sang-Oh , Choi Sang-Ho , Kim Yang Soo , Yang Jeong-Sun , Kim Kyung-Chang , Lee Joo-Yeon , Yun Sung-Cheol , Kim Sung-Han
Published: January 2025

Background

Prolonged SARS-CoV-2 shedding frequently occurs in immunocompromised patients, making the determination of their isolation periods challenging. This study aims to estimate the probability of viral clearance in immunocompromised patients, stratified by elapsed days and other relevant variables.

Figure 1

The estimated probability of viral clearance along days, stratified by SARS-CoV-2 PCR Ct value and immunocompromised conditions

Methods

This prospective study was conducted at Asan Medical Center, a 2,732-bed tertiary teaching hospital in the Republic of Korea, from January 2022 to May 2023 during the prevalence of the Omicron variant. We enrolled immunocompromised patients, defined as 'moderately or severely immunocompromised' according to CDC guidelines. All participants, diagnosed with COVID-19 via nasopharyngeal swab PCR, provided weekly respiratory specimens for viral load measurement using real-time RT-PCR. Positive samples underwent viral culture. The Cox time-varying proportional hazard model was applied to identify significant predictors of viral culture negative conversion, employing backward elimination for model refinement. Analyses were conducted using R software, version 4.3.2, and included the assessment of viral copy number dynamics and treatment effects on viral shedding probabilities.

Baseline characteristics of the immunocompromised patients

Results

In a cohort of 70 immunocompromised patients, 48 (68.6%) had hematologic malignancies and 22 (31.4%) underwent solid organ transplants. Univariate and multivariate analyses revealed that the use of B-cell depleting agents, CAR T-cell therapy, and viral copy number significantly influenced viral culture negative conversion. These findings were incorporated into a refined model to predict viral shedding probabilities. Patients with a history of both B-cell depleting agents and CAR T-cell therapy exhibited the lowest negative conversion rates, with median durations of viral shedding from 76 days to undeterminable depending on SARS-CoV-2 Ct values. In contrast, patients receiving neither treatment showed markedly faster viral clearance, typically within one to two months after COVID-19 diagnosis, regardless of Ct values.

Predictive factors for viral culture negative conversion in the immunocompromised patients

Conclusion

Ending the isolation of immunocompromised patients with COVID-19 should be determined individually, based on the viral copy number at specific time points and treatment conditions.

Table 3

Probability of culture-negative conversion among immunocompromised patients based on treatments received, days elapsed after diagnosis, and SARS-CoV-2 PCR results

Disclosures

All Authors: No reported disclosures
P-13. Awareness, Attitudes, Knowledge and Barriers Related to Adult Pneumococcal Vaccination among Internal Medicine Residents and Fellows in University Hospital, Thailand
Authors: Roongjiraroj Thanasate , Phuensan Pawat
Published: January 2025

Background

Pneumonia is the leading cause of global mortality with Streptococcus pneumoniae as a leading pathogen in high-risk adults. Although vaccination is crucial for preventing pneumococcal infections, its uptake remains suboptimal in Thailand. Internists, pivotal in managing such patients, are at the forefront of promoting vaccination. Therefore, this study aimed to explore factors related to physicians’ pneumococcal vaccine administration among high-risk adults in university hospital in Thailand.

Methods

This web-based survey cross-sectional study was conducted at King Chulalongkorn Memorial Hospital, Bangkok, Thailand (university hospital). Participants were residents and fellows in Department of Medicine. The questionnaire included demographic data and vaccine-related inquiries in various aspects including awareness, attitudes, and knowledge towards pneumococcal vaccination.

Results

The study involved 93 participants. Demographic data was presented in table 1. Awareness of pneumococcal vaccination was generally high and attitudes were positive. Overall, participants showed a good knowledge of pneumococcal infection, but participants with lower rate of vaccination administration had significant lower knowledge than participants with higher rate of vaccination administration (table 2). Key barriers to vaccination included limited access to advice and recording systems, cost issues, and a lack of specialized consultation. Potential quality improvement strategies were electronic vaccination record, easy-to-access guideline, and vaccine consultation clinic.

Conclusion

This study emphasizes the importance of addressing barriers like limited access to vaccination advice and recording systems, cost issues, and a lack of specialized consultation. Implementing targeted interventions and raising knowledge and awareness of vaccination are key steps toward reducing the burden of pneumococcal infections. These results would lead to improvement of residency and fellowship training program and vaccination practice in our hospital.

Disclosures

Pawat Phuensan, MD, MSc, GSK: Grant/Research Support|GSK: Honoraria|MSD: Honoraria|Pfizer: Grant/Research Support|Pfizer: Honoraria|Siam Pharmaceutical: Grant/Research Support|Takeda: Honoraria
P-2129. Analytical Validation of a Next-Generation Sequencing Assay for the Detection of Microbial Pathogens in Human Plasma
Authors: Bacon Curtis , Bixler Ellis , Cowden Scott , Nutt Jamie , Kleiboeker Steve
Published: January 2025

Background

Fungal and acid-fast bacteria (AFB) infections can be a serious complication for immunosuppressed patients. Identification of the pathogen involved in invasive fungal/AFB infections (IFIs) can allow for reduced time to initiation of the appropriate targeted therapy through elimination of ineffective therapies. Current fungal/AFB diagnostics suffer from low sensitivity/specificity, invasiveness (e.g., biopsy or antigen), have long turnaround times (e.g., culture), and/or require an a priori hypothesis regarding the causative pathogen (e.g., PCR based methods). To overcome shortcomings in fungal/AFB diagnostics, an unbiased next-generation sequencing (NGS) approach can be utilized to characterize pathogen cfDNA present in a patient blood sample.

Methods

Sequencing of IFIs through hybrid capture has the potential to detect a broad range of pathogens yet can still specifically target the most clinically relevant. Compared to standard whole-genome sequencing methods, hybrid capture followed by NGS can be more specific and sensitive due to an enrichment step using probes specific to cfDNA targets of interest. This additional enrichment step can result in more sequencing reads being dedicated to cfDNA derived from pathogens of interest rather than to cfDNA derived from non-relevant organisms. Here is described a hybrid capture assay that uses >30,000 probes to detect >600 Fungal and select AFB species in plasma.

Results

Cutoffs for target coverage and kmers/million were established through ROC analysis of 170 contrived plasma samples resulting in an analytical specificity of ∼96% and a sensitivity of ∼1,200 molecules/mL. 98% of the 40 contrived samples used for accuracy were correctly identified while 100% intra- and 93%-inter assay precision was achieved. In silico validation demonstrated the assay’s ability to detect closely related species unable to be tested at the bench. Several species have been detected in the initial clinical samples received thus far, however, all have been below the reportable cutoff values.

Conclusion

The analytical validation described here demonstrates the analytical performance of hybrid capture in human plasma.

Disclosures

Curtis Bacon, PhD, Eurofins Viracor: employee Ellis Bixler, n/a, Eurofins Viracor: Employee Scott Cowden, n/a, Eurofins Viracor: Employee Jamie Nutt, n/a, Eurofins Viracor: Employee Steve Kleiboeker, PhD, Eurofins: employee|Eurofins: Stocks/Bonds (Public Company)
P-2140. Clinical Review of Respiratory Tract Infections Caused by Exophiala dermatitidis Misidentified as genus Rhodotorula: Case Series
Authors: Setoguchi Daichi , Iwanaga Naoki , Hirayama Tatsuro , Yoshida Masataka , Takeda Kazuaki , Ide Shotaro , Tashiro Masato , Takazono Takahiro , Kosai Kosuke , Izumikawa Koichi , Yanagihara Katsunori , Mukae Hiroshi
Published: January 2025

Background

Exophiala dermatitidis is a black fungus isolated from wet environments such as soil and baths. Human infections have been reported chiefly as skin and soft tissue infections, and respiratory infections have been extremely rare. The fungus is dimorphic and known to be yeast-like in culture, changing to filamentous fungi over time. The fungus is often misidentified as yeast during the first few days of culture, and preliminary experiments have shown that it can be misidentified as Rhodotorula spp. by commercially available yeast identification kits.

Methods

Genetic identification was performed using 44 strains isolated from airway specimens over the past 11 years from July 2012 to September 2023, except for one difficult to culture, by determining the sequence of the ITS and D1/D2 regions. Cases genetically identified with E. dermatitidis were examined retrospectively for clinical information except for seven cases identified of the same cases.

Results

Of the 43 strains identified genetically, 22 were identified as E. dermatitidis, indicating that they were misidentified in approximately 50% of the cases; analysis of the clinical information of the 15 cases identified as E. dermatitidis and for which a retrospective search was possible showed that chronic lower respiratory tract infection or pneumonia due to E. dermatitidis was definite in six cases, active infection was possible in five cases and airway colonization only in four cases. Comorbidities included pulmonary non-tuberculosis mycobacterium (NTM) in five cases, chronic progressive pulmonary aspergillosis (CPPA) in three cases, and pulmonary nocardiosis in one case, suggesting concurrent chronic pulmonary infections due to other microbes. Steroid and immunosuppressive agent use was observed in ten cases. Five of the six definite cases responded to azoles, and one case resolved spontaneously with only a reduction of the immunosuppressive drugs. Drug sensitivity testing showed that all cases were resistant to Candin and sensitive to azoles and polyenes.

Conclusion

E. dermatitidis is a dimorphic fungus that is time-consuming to culture and may have been underestimated previously, misidentified as Rhodotorula spp. In addition to NTM and CPPA, E. dermatitidis might be differentiated in chronic lung infections.

Disclosures

Hiroshi Mukae, M.D., Ph.D., AstraZeneca: Lecture fees|Gilead Sciences: Lecture fees|GSK: Lecture fees|MSD: Advisor/Consultant|MSD: Lecture fees|Pfizer: Lecture fees|Shionogi & Co., Ltd.: Advisor/Consultant|Shionogi & Co., Ltd.: Grant/Research Support|Shionogi & Co., Ltd.: Lecture fees
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

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

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

Background

Background and Aims: Hepatitis C virus (HCV) treatment with direct-acting antivirals (DAA) results in a sustained virologic response (SVR) in >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

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< 0.001). Ages ranged from 19-87 years old (41 ± 13). The majority of the patients identified as white (92%, P< 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< 0.001). 58% of the visits were for return patients vs 42% new visits (P < 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 >25 miles away from the clinic for most visits (66%, P< 0.001). Completion rate for these individuals in-person, telephone and video visits were 32%, 81% and 49%, respectively (P< 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

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

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 ( >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< .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< .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< .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

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 > 21.53 for septic shock and MDW < 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