bluuebunny/crossref_metadata_2025_split huggingface dataset:
613. The Clinical Spectrum of Curvularia Species: A 20-year Experience at 2 Tertiary Care Hospitals
Authors: Little Jessica S , Nussbaum Eliezer Zachary , Braidt Joseph , Kanjilal Sanjat , Hammond Sarah P 
Published: November 2023

Abstract

Background
Curvularia species are dematiaceous environmental molds that rarely cause disease in humans. Infections may be superficial or invasive and can present as disseminated infection or localized infection including keratitis, invasive fungal sinusitis (IFS), and skin and soft tissue infection (SSTI). Non-pathogenic colonization is also common. The frequency and spectrum of infection has not been well characterized.

Methods
This was a retrospective study of all Curvularia infections at two institutions in Boston, MA between January 1, 2002 and January 1, 2023. Infections were identified using microbiologic culture databases and a research patient data registry. Clinical information was collected. This study was approved by the Massachusetts General Brigham IRB; research was conducted in accordance with the Declaration of Helsinki.

Results
Curvularia species were identified from clinical specimens in 36 patients: 28 pathogenic infections and 8 cases of non-pathogenic colonization. Clinical characteristics of the pathogenic infections are described in Table 1. Of those with infection, 5 were invasive (2 disseminated; 3 localized) and occurred only in immunocompromised hosts (hematologic malignancy n=4, heart transplant n=1). Local invasive disease was characterized by SSTI (n=2) and IFS (n=1). There were 6 SSTI or wound infections without correlative pathology demonstrating tissue invasive disease (3 treated with triazoles; 3 not treated). All cases were identified by culture except one case identified by 28s ribosomal DNA PCR testing. Polymicrobial infection was common with &gt; 50% of pathogenic infections exhibiting cultures with additional bacterial and/or fungal organisms. Antifungal susceptibility testing was performed in most invasive infections; results are shown in Table 2. Invasive infections were treated with both single and dual-agent antifungal regimens (posaconazole n=3; voriconazole and terbinafine n=1; voriconazole and liposomal amphotericin n=1).

Conclusion
Invasive Curvularia infections are rare but mainly occur the immunocompromised, and here manifested as disseminated disease, IFS, and SSTI. Coinfection is common. Non-invasive infections are more frequent (82%) and occur in normal hosts.

Disclosures
Sanjat Kanjilal, MD, MPH, GSK: Advisor/Consultant|Pattern biosciences: Advisor/Consultant|Roche: Honoraria|Uptodate: Royalties Sarah P. Hammond, MD, F2G: Advisor/Consultant|F2G: Grant/Research Support|GSK: Grant/Research Support|Pfizer: Advisor/Consultant|Scynexis: Grant/Research Support|Seres therapeutics: Advisor/Consultant
619. Fungal Species Causing Eumycetoma and Chromoblastomycosis in a Commercial Laboratory, United States
Authors: Smith Dallas J , Gold Jeremy A W , Lockhart Shawn R , Benedict Kaitlin 
Published: November 2023

Abstract

Background
The World Health Organization (WHO) designates the implantation mycoses eumycetoma and chromoblastomycosis as Neglected Tropical Diseases. These infections usually develop after traumatic skin inoculation and primarily occur in resource-limited countries in tropical or subtropical areas. They are difficult to diagnose, may require prolonged antifungal therapy and surgery if not diagnosed early, and cause substantial stigma and morbidity. Understanding the organisms causing these diseases and their epidemiology might help inform best clinical practices in the United States.

Methods
We analyzed Labcorp (a major U.S. commercial laboratory) data sent to CDC’s National Syndromic Surveillance Program. We identified results from cultures ordered during 3/1/2019–3/1/2023 involving fungi known to cause eumycetoma and chromoblastomycosis. Nail and scalp specimens were excluded. We examined patient demographic characteristics, ordering clinical specialty, and species.

Results
We identified 33 eumycetoma and 119 chromoblastomycosis results. For eumycetoma, most patients were aged ≥ 50 years (mean=56, interquartile range 42-69), male (64%), and diagnosed in the South census region (52%). Dermatology ordered 21%; family practitioners ordered 18%. Scedosporium apiospermum species complex was the most common species (94%). Another species identified was Exophiala jeanselmei. For chromoblastomycosis, 31% of results were from patients 45–64 years old; 29% were ≥ 65. Most were male (53%), and results were evenly distributed among the Northeast (33%), South (34%), and West (31%) census regions. Most cultures were ordered by dermatologists (70%). Fifty-two percent of results were Aureobasidium pullulans, 24% were Exophiala (undetermined species), and 12% were Exophiala dermatitidis. Phialophora verrucosa, Fonsecaea pedrosoi, Exophiala jeanselmei, and Exophiala xenobiotica accounted for the other 13%.

Conclusion
Although rare, clinicians should be aware that eumycetoma and chromoblastomycosis can occur in U.S. patients seeking treatment for subcutaneous skin infections. Identifying the epidemiology of causative organisms can inform evidence-based practices for diagnosis and treatment.

Disclosures
All Authors: No reported disclosures
641. Limited Utility of Epstein-Barr Virus (EBV) Surveillance for Predicting Post-Transplant Lymphoproliferative Disorder in EBV Seropositive Adult Lung Transplant Recipients
Authors: Heldman Madeleine R , Chang Yeh-Chung , Saullo Jennifer , Baker Arthur W , Maziarz Eileen K , Tam Patrick C , Messina Julia A , Reynolds John M , Wolfe Cameron R , Alexander Barbara D 
Published: November 2023

Abstract

Background
Post-transplant lymphoproliferative disorder (PTLD), which is often driven by Epstein-Barr virus (EBV), causes significant morbidity and mortality in lung transplant recipients (LTRs). EBV viremia surveillance with reduction of immunosuppression at certain viral load thresholds is a common strategy used to prevent PTLD or mitigate progression of PTLD in pre-clinical stages, but the utility of EBV surveillance in adult seropositive LTRs is poorly understood.

Methods
In a retrospective cohort study of EBV seropositive adults who underwent lung transplant at a single academic center between 1/1/2019-12/31/2020, we compared peak whole blood EBV viral load (VL) among samples collected from 1) LTRs who developed PTLD, before PTLD symptom onset, 2) LTRs who developed PTLD, after PTLD symptom onset and 3) LTRs who did not develop PTLD. LTRs without any recorded EBV VLs were excluded. Patients were followed through 1/31/2023 (maximum 49 months post-transplant). Center protocol recommended quantitative EBV PCRs every 3 months between 3-18 months post-transplant, and as clinically indicated thereafter. Reduction of immunosuppression and evaluation for PTLD was at the discretion of clinicians.

Results
Two-hundred twenty-nine LTRs with a total of 1095 EBV PCRs were included (40% female, median age 65 years at transplant, Table 1). Six (2.6%) LTRs developed biopsy-proven PTLD 8-35 months post-transplant (median 17 months); 5/6 PTLDs were EBV+. Clinical symptoms, rather than an asymptomatic high EBV VL, triggered evaluation for PTLD in all 6 cases. Only one of six LTRs with PTLD had an EBV VL above the assay’s lower limit of quantification before PTLD symptom onset (Figure 1A); among the other 5 LTRs, median time between most recent negative EBV PCR and PTLD symptom onset was 125 days (range 35-216). Peak EBV VL in LTRs with PTLD was significantly higher after PTLD symptom onset than in the asymptomatic period (p=0.016), but peak EBV VL was similar between asymptomatic LTRs who later developed PTLD and LTRs who did not develop PTLD (p=0.62, Figure 1B).

Conclusion
In EBV seropositive adult LTRs , EBV surveillance rarely facilitated PTLD diagnosis and may not be an effective strategy for identifying asymptomatic individuals at high risk for future PTLD.

Disclosures
Arthur W. Baker, MD, MPH, Insmed: Grant/Research Support|Medincell: Advisor/Consultant Eileen K. Maziarz, MD, Karius, Inc: Advisor/Consultant Barbara D. Alexander, MD, F2G Pharmaceuticals: Advisor/Consultant|HealthTrackRx: Advisor/Consultant|HealthTrackRx: Board Member|Leadiaint: Grant/Research Support|Merck: Advisor/Consultant|Scynexis: Grant/Research Support|Thermofisher: Advisor/Consultant
643. Animal Bites Case Surveillance and Rabies Post Exposure Prophylaxis in the Republic of Korea Military, From 2012 to 2019
Authors: Oh Hong Sang , Kim Se-yong , Sung Gyeong-Yong 
Published: November 2023

Abstract

Background
Rabies is a fatal zoonosis on a global scale. In South Korea, no human rabies and animal case has been reported since 2005 and 2014, respectively. Military personnel is frequently exposed to outdoor environment, we hypothesized that their risk of exposure to wild animal is higher than general population. This study aimed to determine the level of rabies risk exposure and the adequacy of treatment by analyzing animal-bitten patients and assessing the status of post-exposure prophylaxis(PEP).

Methods
This study was conducted from January 1, 2012, to December 31, 2019, in 18 military hospitals across the country. The patients with animal bite-related diagnoses were included in the study. The diagnoses were made based on the ICD-10 code related to animal bite. We excluded patients with human bites, insect bites, and snake bites. Cases of repeated visits for additional vaccination were excluded as duplicate cases.

Results
A total of 330 cases of animal bites were included. No human rabies was reported. 297 (90%) were military personnel, with a males (92.1%) and a mean age of 32±11 years. The most frequent site of bite was the hands and fingers (69.7%), followed by the legs (12.4%) and arms (3.9%). Dogs were responsible for 44.8% of bites, followed by cats (38.5%) and mice (5.8%). Empirical antibiotic was administered to 58.5%, while tetanus vaccination was given to 22.1%. In terms of PEP, the matching rate with domestic health authorities’ standards was 62.1%. Category II was the most common criteria for bite injuries (71.5%), according to the World Health Organization(WHO)’s criteria.

Conclusion
Dogs and cats are the most frequently bitten animals, as in previous studies, and hands and fingers, were the most frequently bitten. We postulate that bites occur mainly during contact with animals using hands, suggesting that precaution is necessary. PEP requires immediate medical attention, however 43.7% of patients visited hospitals more than 24 hours after the bite, indicating a need to improve awareness of the disease. PEP was not performed in 15.1% of cases despite meeting domestic standards, and 37.3% in the WHO’s criteria. These emphasize that efforts should be needed to provide appropriate PEP that meets the relevant criteria and minimize unnecessary use of medical resources.

Disclosures
All Authors: No reported disclosures
644. "Impact of heat inactivation and freeze-thaw cycles on detection of influenza A and influenza B antigens and RNA when assessing novel multiplex diagnostic assays"
Authors: Rao Anuradha , Bowers Heather , Sabino Courtney , McLendon Kaleb , Morales Evelyn , Solis Zianya , Greenleaf Morgan , Sullivan Julie , Lai Eric , Damhorst Gregory L , Lam Wilbur A , Bassit Leda 
Published: November 2023

Abstract

Background
Advances in diagnostics since the emergence of COVID-19 has resulted in easy availability of rapid antigen tests (RAT). Building on this, multiplex tests for simultaneous detection of Flu A, Flu B, and SARS-CoV-2 are being evaluated as part of NIH’s Rapid Acceleration of Diagnostics (RADx) program. Critically important for assay development and assessment are viral panels prepared under validated conditions to evaluate new tests. These panels may contain live virus or may be inactivated to promote biosafety. They also may undergo freeze-thaw cycles during storage and transport. We characterized the effect of heat inactivation (HI) on detection of Flu A and B using two RATs, and the effect of freeze-thaw cycles on a point-of-care (PoC) molecular assay already on the market.

Methods
Panels were prepared by serially diluting Flu A or B strains obtained from BEI Resources. Both live and HI panels were prepared. HI was achieved in-house (60°C, 30 minutes). Panels with and without HI were used to assess two RATs by performing triplicate tests and determining limit of detection (LOD) as the lowest TCID50 at which 3 of 3 replicates were positive. Additionally, a molecular-based PoC assay was evaluated by recording cycle threshold (Ct) values before and after freeze-thaw of specimens. All assays were performed according to the manufacturer’s instructions.

Results
Both RATs detected Flu A with similar sensitivity (2-fold increase in LOD) before and after heat inactivation (Figure 1), whereas Flu B was not detected by either RAT after heat inactivation. These results were consistent across both RATs and two strains of each virus. Live Flu A and B were stable and consistently detected up to four freeze-thaw cycles in the molecular assay with minor attrition of Ct values (Figure 2).
Results of LOD characterization for two independent RATs with influenza A and B with and without heat inactivation.
Correlation of Flu A and Flu B Ct values for fresh samples versus after four cycles of freeze thaw measured using a PoC molecular assay.

Conclusion
Pre-treatment and storage of testing material plays a crucial role in the assessment of diagnostic tests used for Flu A and B detection. Loss of reactivity in Flu B antigen tests after inactivation suggests that heating may denature a critical epitope recognized by immunoassays. Selection of live versus HI samples and degradational effects of freeze thaw cycles must be considered by laboratorians and engineers creating or validating diagnostic tests.

Disclosures
All Authors: No reported disclosures
651. Implementing a Multiplex-PCR Test for the Diagnosis of Acute Gastroenteritis in Hospitalized Children, Are All Enteric Viruses the Same?
Authors: Danino Dana , Hazan Guy , Mahajna Rufaida , Khalde Firas , Farraj Lama , Shemer-Avni Yonat , Greenberg David , Hershkovitz Eli , Givon-Lavi Noga , Faingelernt Yaniv 
Published: November 2023

Abstract

Background
Multiplex-PCR for the diagnosis of acute gastroenteritis (AGE) has allowed for rapid detection of multiple pathogens simultaneously but poses challenges in distinguishing between shedding and disease-causing pathogens. We aimed to evaluate the epidemiology of viral AGE and compare clinical characteristics among the 5 most common viruses.

Methods
SUMC is the only hospital in southern Israel serves a population of ∼97,500 children &lt; 5 years. Rotavirus vaccine was added to the national immunization program in 2010 and vaccine coverage (3 doses) reached 70% in 2 years. All rectal swabs for multiplex-PCR targeting; rotavirus, norovirus, adenovirus 40,41, astrovirus and sapovirus collected from diarrheic children &lt; 5 years, December 2017 - March 2022, were included. Detection of the same virus within 2 months was considered a single episode. The clinical analysis included all episodes with single-virus detection and negative stool bacterial PCR (Figure 1).

Results
Of the 5,151 rectal swabs collected, 1,934 (37.5%) were positive for at least one virus, with 245 (12.6%) showing multiple virus detection. Norovirus and rotavirus were the most prevalent (Figure 1). No clear seasonality was observed for AGE viruses in 2018-19. However, during the 2nd year of the COVID-19 pandemic, an unusual surge in warm months was observed, first attributed to rotavirus and later to norovirus (Figure 2). Of the single-virus AGE episodes with negative bacterial PCR, 34.6% and 5.9% presented with mucus and bloody stool, respectively, and 29.3% were treated with antibiotics. No significant differences in rotavirus vaccination rates were found between rotavirus and other viruses. Children infected with astrovirus and sapovirus had higher rates of hospital-acquired AGE and immunodeficiency (P&lt; 0.05) (Table), while children with rotavirus had higher dehydration severity and metabolic acidosis (P&lt; 0.05) (Figure 3).

Conclusion
37.5% of all rectal swabs from diarrheic hospitalized children &lt; 5 years were positive for enteric virus, 12.6% with multiple detection. Rotavirus remained significant and the most severe despite vaccination efforts. Our findings highlight the importance of continuous surveillance in the context of multiplex PCR testing for accurate management and future prevention methods.

Disclosures
Dana Danino, Dr. MD, Pfizer: Grant/Research Support David Greenberg, Professor MD, GSK: Advisor/Consultant|GSK: Honoraria|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria
657. Impact of Oral Vancomycin Duration on Clostridioides difficile Recurrence in Patients Requiring Concurrent Systemic Antibiotics
Authors: Marsh Kassandra , Kwiatkowski Diana , Dubrovskaya Yanina , Katz Alyson , Papadopoulos John , So Jonathan , Major Vincent J , Sommer Philip , Hochman Sarah , Arnouk Serena 
Published: November 2023

Abstract

Background
IDSA guidelines for the treatment (TX) of Clostridioides difficile infection (CDI) do not provide specific guidance for total duration of oral vancomycin (VAN) TX in patients requiring prolonged concomitant systemic antibiotics (cABX), as limited evidence exists.

Methods
This was a retrospective study of adult patients with an initial episode of CDI from 2017 to 2022 at NYU Langone Health. Patients were included if they received CDI TX with oral VAN (without fidaxomicin or oral metronidazole) and &gt; 72 hours of cABX (categorized as high, medium or low CDI risk). Prescribing of VAN TX was described as standard duration (SD; ≤ 14 days) vs prolonged duration (PD; &gt; 14 days). The primary outcome was CDI recurrence within 8 weeks of TX completion. Secondary outcomes included risk factors for recurrence, and VAN-resistant Enterococci (VRE) isolation and all-cause mortality at 6 months.

Results
After screening 1,350 patients, 218 were included (PD n=140, SD n=78). The median age was 65 years (IQR 54-72), the median Charlson comorbidity index was 4 (2-6), 52% were immunocompromised, 32% required intensive care unit admission, and 66% received high-risk ABX with no differences between groups for any baseline characteristic. Non-severe, severe, and fulminant CDI occurred in 39%, 36%, and 25%, respectively. Patients who received PD had significantly more carbapenem use (37% vs 21%, p=0.011), a longer duration of ABX overlap with VAN TX (11 [7-16] vs 8 [6-11] days, p&lt; 0.001), and more infectious disease consultation (69% vs 54%, p=0.023). After ABX completion, 147 (67%) patients continued VAN TX for a median of 7 (5-10) days, and 30 (14%) patients continued VAN prophylaxis for a median of 6 (5-14) days. Recurrence occurred in 20 (9%) patients, isolation of VRE in 14 (6%), and mortality in 21 (10%), with no statistical differences between SD and PD arms. Stopping VAN prior to completion of ABX was identified as a risk factor for recurrence on univariate analysis (OR 4.25, 95%CI 1.214-14.880, p=0.037).

Conclusion
Our findings suggest that in this high-risk cohort, continuation of VAN after completion of systemic antibiotics may decrease risk of recurrence. Prospective studies are needed to determine optimal VAN TX durations and alternative strategies to reduce CDI recurrence in patients who require cABX.

Disclosures
All Authors: No reported disclosures
663. Epidemiology and outcomes of recurrent C. difficile infection among hematopoietic cell transplant recipients
Authors: Sanchez Eduardo , Krantz Elizabeth M , Pergam Steven A , Liu Catherine , Tverdek Frank P , Escobar Zahra 
Published: November 2023

Abstract

Background
Recent updates in Clostridioides difficile infection (CDI) treatment guidelines among hematopoietic cell transplant (HCT) recipients recommend fidaxomicin as first line therapy as it reduces the risk of recurrent CDI. We aimed to characterize HCT recipients with CDI and describe their clinical outcomes, including incidence of recurrent CDI.

Methods
This retrospective cohort study included patients ≥18 years old who underwent HCT at Fred Hutchinson Cancer Center from January 2012 to December 2021 and were diagnosed with CDI between day -7 and day +100 relative to HCT (Figure 1). Chart review was conducted to capture demographic, clinical and outcome data, including data on episodes of recurrent CDI. Recurrent CDI was defined as a new episode of symptoms consistent with CDI and a positive CDI test within 12 weeks after completing primary treatment. We computed the cumulative incidence of recurrent CDI, with treatment completion for the initial CDI as time zero and death before recurrent CDI as a competing risk.

Results
Of 3479 HCT recipients, 416 (12%) patients had CDI at a median of 5 days from HCT (Table 1). The most common underlying malignancies were acute leukemia and multiple myeloma; 248 (59%) patients received an allogeneic HCT. All but one patient were treated with metronidazole or oral vancomycin. Within 14 days of CDI, 38 (32%) patients of 119 diagnosed as outpatients required hospitalization and 3 (0.7%) of 410 not in the intensive care unit (ICU) required ICU level of care (Table 2); 10 (2%) died within 30 days of CDI diagnosis. Of 381 patients eligible for analysis of CDI recurrence, 30 patients had recurrent CDI at a median of 57 days (range, 1, 93) follow-up, for a cumulative incidence of 10% at 12 weeks (95% confidence interval, 7%, 14%, Figure 2). In the 14 days after CDI recurrence, 2 (10%) of 21 had a new hospital admission; none died within 30 days.

Conclusion
The majority of HCT recipients in our cohort developed CDI early posttransplant; serious complications and deaths were uncommon. The incidence of recurrent CDI was low and may not warrant use of fidaxomicin for all initial CDI episodes in this population. Further work identifying HCT subgroups at higher risk of recurrent CDI may help to target fidaxomicin use to those most likely to benefit.

Disclosures
Steven A. Pergam, MD, MPH, Cidara: Investigator in clinical trials|F2G: Investigator in clinical trials|Global Life Technologies: Grant/Research Support|Symbio: Investigator in clinical trials Catherine Liu, MD, Pfizer: Site Investigator|SNIPR BIOME: Advisor/Consultant