bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-2131. Identification of Non-fumigatus Aspergillus Species in Clinical Samples from Southern California
Authors: Rayens Emily , Skela Jessica , Tartof Sara Y 
Published: January 2025

Abstract

Background
Aspergillus is the causative agent of aspergillosis, with presentations ranging from mild skin infections to disseminated disease affecting the central nervous system. Fungal culture from the infected site is the current recommendation to confirm presence of Aspergillus and to speciate based on morphology. A. fumigatus has historically been identified as the source of most serious infections, but there is emerging concern for invasive disease caused by non-fumigatus­ species, especially those that may carry intrinsic resistance to recommended antifungals. In this descriptive analysis, we reviewed trends in Aspergillus species cultured from a large clinical cohort.Figure 1.Percentage of Positive Aspergillus cultures by specimen origin type over time 2012-2023.

Methods
We identified all positive fungal cultures for at least one Aspergillus species across Kaiser Permanente Southern California hospitals and clinics from January 2012–June 2023. Episodes were defined as a combination of any Aspergillus culture results conducted within 30 days of the first positive Aspergillus culture. Only the first episode for each patient was included in analyses if multiple episodes were identified.Figure 2.Number of positive Aspergillus cultures by species identified and specimen type.

Results
10,777 patients were identified at KPSC with at least one positive Aspergillus culture between 2012 and 2023. Isolates were most frequently identified from samples associated with the respiratory tract and bronchoalveolar lavage fluid. However, the proportion of cutaneous cultures has increased over time and was nearly equal to the number of positive respiratory cultures in 2023 (Figure 1). Aspergillus niger (n=3,772) was the most frequently cultured Aspergillus species overall, with 44.6% of isolates originating from skin, nail, and scalp samples (Figure 2). Aspergillus fumigatus was identified in 40.3% of respiratory sample cultures, followed by Aspergillus niger at 25.7%. Finally, non-fumigatus specimens exhibited seasonal trends in respiratory samples compared to A. fumigatus, peaking in early autumn each year (Figure 3).Figure 3.Number of positive Aspergillus cultures in respiratory samples by reported species by month.

Conclusion
Non-fumigatus species were identified more frequently than A. fumigatus in culture of respiratory and non-respiratory clinical samples. Novel observations of seasonal trends and increasing predominance of non-fumigatus species may indicate a shift in clinical expectations and treatment options during management of aspergillosis.

Disclosures
Emily Rayens, PhD, MPH, GSK: Grant/Research Support|Moderna: Grant/Research Support Sara Y. Tartof, PhD MPH, GSK: Grant/Research Support|Pfizer Inc: Grant/Research Support
P-2132. Comparison of Clinical Characteristics and Risk Factors among Adult Patients with Bloodstream Infections due to candida auris vs other candida Species: a 3-year analysis in a Large Care Tertiary Hospital, Saudi Arabia
Authors: Alasmari Faisal , Wali Asiya , Mukahal Mahmoud , Alsurayhi Seham , Dirar Qais , Tamim Hani 
Published: January 2025

Abstract

Background
Candida auris is considered a serious global threat due to its potential to cause invasive infections, staggering transmissibility and mortality. We evaluated the epidemiologic and clinical features of candida bloodstream infections (BSIs) and explored risk factors associated with C. auris.

Methods
A retrospective review of all candida BSI in patients aged ≥ 18 years were conducted during August 2018 to June 2021. C. auris cases were compared to other Candida species cases. Odds ratio (OR), estimated using stepwise regression analysis, was used to assess the association between risk factors and incidence of C. auris infection.

Results
We identified 137 patients with first episode Candida BSIs. 32% patients were secondary to C. auris and the remaining were due to: C.albicans (20%), C.glabrata (18%), C.Parapsilosis (12%), C.trpicalis (15%), and others (4%). 60% of total cohort were male and their age were more than 55 yearsz. The proportions of patients with underlying diseases e.g. diabetes mellitus, hypertension, cardiovascular diseases, chronic renal diseases and COVID-19 infection were not significantly different. The prevalence of malignancy was significantly higher in non C. auris group (P= 0.01). The following risk factors were independently associated with C. auris BSI: Prior Use of antifungals (OR: 3.60, CI: 1.18-10.98), Previous history of multidrug resistant bacterial infection (OR: 3.37, CI: 1.41-8.06), and intensive care unit stay (OR 8.6, CI 2.61-28.37).

Conclusion
The epidemiology of candidemia is changing with non-albicans becoming predominant. Judicious use of all types of antimicrobials including antifungals will help in controlling the emergence of C. auris infection.

Disclosures
All Authors: No reported disclosures
P-2134. Development and Validation of a Quantitative PCR Assay for the Detection of Mucorales in Human Serum Specimens
Authors: Davidson Jerod , Grantham James , Thomas Clayton , Nutt Jamie , Morris Pam , Kockler Zachary , Kleiboeker Steve 
Published: January 2025

Abstract

Background
Mucormycosis are diseases with high morbidity and mortality caused by fungal species belonging to the order Mucorales. The intended use of a Mucorales qPCR assay is as an adjunct to microbiological, clinical, and radiologic means of diagnosing invasive mucormycosis (IM). Serum collection is a non-invasive alternative to BAL and biopsy. Our design process included sequences from all species within the Mucorales genera: Cunninghamella, Lichtheimia, Absidia, Apophysomyces, Mucor, Rhizomucor, Rhizopus and Saksenaea. The Mucorales qPCR assay is designed to detect and quantify Mucorales DNA extracted from human serum.

Methods
Primers and probes were designed to target the 18S regions of Mucorales species. Nucleic acid was extracted using the MagMAX™ Cell-Free DNA Isolation Kit and KingFisher™ Flex system. Amplification and detection were performed using TaqMan™ Fast Universal Master Mix and the Applied Biosystems™ QuantStudio 7 Pro. Quantification was performed using Rhizopus oryzae target-bearing linearized plasmid standards with results reported in copies/mL. Analytical validation was performed by spiking negative human serum with four different Mucorales species’ DNA: Rhizopus oryzae, Rhizomucor miehei, Lichtheimia corymbifera, and Cunninghamella bertholletiae.

Results
The limit of detection was 181 copies/mL, and the lower limit of quantification was determined to be 253 copies/mL as shown in Table 1. Linear regression of dilution data produced an R2=0.997, slope=1.029, and y-intercept=0.212 as show in Figure 1. The Mucorales target detection was 100% (60 of 60) of blinded positive samples with all observed log10 copies/mL results within ±0.5 log10 copies of expected values as shown in Table 2. All (20 of 20) blinded negative samples were negative for Mucorales and positive for Internal Control (IC). Intra-assay precision ranged from 5 – 22 %CV and inter-assay precision ranged from 12 – 17 %CV as Shown in Table 3.

Conclusion
The validated assay described here demonstrates excellent sensitivity, linearity, precision, and accuracy, providing a reliable means of detecting Mucorales DNA in human serum. This assay represents a non-invasive, rapid, and sensitive method to guide clinical decisions on patient populations at high risk of IM.

Disclosures
Jerod Davidson, B.A., Eurofins Viracor: Employee James Grantham, B.S., Eurofins Viracor: Employee Clayton Thomas, B.S., Eurofins Viracor: Employee Jamie Nutt, n/a, Eurofins Viracor: Employee Pam Morris, M.S., PMP, Eurofins Viracor: Employee Zachary Kockler, PhD, Eurofins Viracor: Employee Steve Kleiboeker, PhD, Eurofins: employee|Eurofins: Stocks/Bonds (Public Company)
P-2137. Evaluating the clinical utility of bronchoalveolar lavage polymerase chain reactions for the diagnosis of pulmonary infections in patients with hematological malignancies
Authors: Al-Ghanamah Rakan , Finnigan Katie , Gali Varshini , Kalchiem-Dekel Or , Kamboj Mini , Hohl Tobias M , Babady Esther , Papanicolaou Genovefa , Lee Yeon Joo 
Published: January 2025

Abstract

Background
Invasive pulmonary infections are a significant cause of morbidity and mortality in patients with hematological malignancies and hematopoietic stem cell transplantation (HCT) recipients. A delay in identifying a causative agent may result in late initiation of appropriate treatment and worse outcomes. We explore the diagnostic utility of incorporating commercially available polymerase chain reaction (PCR)-based assays performed on bronchoalveolar lavage (BAL) specimens into evaluating invasive pulmonary infections in patients with hematological malignancies and HCT recipients.

Methods
Patients with hematological malignancies and HCT recipients who underwent a bronchoscopy 1/2020 - 1/2024 with at least one PCR assay (Aspergillus, Mucorales, and Nocardia) sent to Viracor (Lenexa, KS) were included. Multiple bronchoscopies were captured if performed ≥6 weeks apart. “Proven” and “Probable” invasive fungal infection (IFI) were defined as per EORTC/MSG 2020 guidelines. Pulmonary infection was defined by clinical findings, galactomannan antigen (GMA) testing, culture from BAL, histopathology if a biopsy was performed, and radiology imaging studies. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PCRs and BAL GMA were tested for probable and proven IFI and pulmonary nocardia infection.

Results
Figure 1 describes the study cohort. Fifty-eight of 134 (43.3%) received HCT (Table 1). The sensitivity, specificity, PPV, and NPV for BAL PCRs, and BAL GMA are provided in Table 2. Figure 2 shows diagnosis by standard of care and BAL PCRs. Among 19 patients with positive BAL GMA, 4 were positive with culture. Two patients were negative for BAL GMA and BAL Aspergillus PCR, but culture was positive for A. fumigatus. Culture was negative for all pulmonary mucor, and culture was positive for all pulmonary nocardia.

Conclusion
Aspergillus PCR has lower sensitivity & NPV, and higher specificity & PPV compared to BAL GMA. The sensitivity of Mucorales and Nocardia PCRs was 42.9% and 100%, respectively. The specificity of Mucorales and Nocardia PCRs were 98.2% and 98.8%, respectively. Our study suggests PCRs from BAL can be helpful as an adjunct tool in diagnosing invasive pulmonary infections in highly immunocompromised patients.

Disclosures
Genovefa Papanicolaou, MD, AlloVir: Advisor/Consultant|AlloVir: Data safety monitoring committee|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Investigator|Symbio: Advisor/Consultant Yeon Joo Lee, MD, MPH, AiCuris: institutional research support for clinical trials|Karius: institutional research support for clinical trials|Merck: Grant/Research Support|Scynexis: institutional research support for clinical trials
P-2139. Evaluation of a Multiplex Real-time PCR for the Detection and Differentiation of Sporothrix schenckii and Sporothrix brasiliensis
Authors: López Cano Luisa F , Gade Lalitha , Litvintseva Anastasia P , Sexton Joseph 
Published: January 2025

Abstract

Background
Sporothrix spp is a thermally dimorphic fungi known to cause subacute or chronic subcutaneous lesions in humans and animals and is the cause of increasing public health concern due to spread of feline-associated cases.Figure 1.Limit of detection and genomic DNA standard curve of S. schenckii and S. brasiliensis

Methods
A recently described Real-time PCR assay targeting the β-tubulin gene to detect and differentiate two related species, S. schenckii and S. brasiliensis, was evaluated and adapted by adding lambda primers and probe for internal control amplification. Isolates, fresh tissues and suspected sporotrichosis Formalin-Fixed, Paraffin Embedded (FFPE) tissues from humans and animals were received in the Mycotic Diseases Branch laboratory at the U.S. Centers for Disease Control and Prevention (CDC) for the routine fungal identification by conventional PCR and sequencing, using the primers D1/D2, ITS5/ITS4 and ITS3/ITS4. Ten-fold serial dilutions from 1 ng/μl to 1 fg/μl of DNA were tested with 20 replicates to establish limit of detection (LOD), and DNA from four fresh tissues extracted on three different days was used to assess reproducibility.Table 1.Ct values and coefficient of variation (CV) of the reproducibility test using fresh tissues on three different days

Results
The assay was tested with 55 S. brasiliensis, 19 S. schenckii, and 85 isolates from other clinically relevant fungi, showing 100% concordance with sequencing methods. The test was also able to amplify S. schenckii DNA from 10 fresh tissues, which were previously confirmed by culture and sequencing as S. schenckii (100% sensitivity), with Ct values ranging from 19 to 38. Among 9 FFPE samples, S. schenckii was amplified in 6 samples (67% sensitivity) with Ct values ranging from 29 to 38. LOD was 1pg/μl of DNA. Results of the 20 replicates showed that at this concentration all the DNAs had a positive signal for both targets (fig 1). For reproducibility, the results showed consistent Ct values over the 3 days of the test with the four fresh tissue samples with a coefficient of variation (CV) of 4% (table 1).

Conclusion
This multiplex Real-time PCR assay successfully detected DNA from the S. brasiliensis and S. schenckii isolates as well as S. schenckii from fresh and FFPE tissues. Our results demonstrate this molecular assay performs well and could be a helpful molecular tool to support rapid identification and differentiation at species level from cultures and primary human and animal specimens.

Disclosures
All Authors: No reported disclosures
P-2142. Cross-Reactivity of Fungal Enzyme Immunoassays (EIA): Implications for Clinical Diagnosis in Patients with Autoimmune Disease
Authors: Craney Arryn , Carlson Kendra , Seyfried Kyla , Witt John , Hanzlicek Andrew , Barros Nicolas , Wheat Lawrence J 
Published: January 2025

Abstract

Background
The immune system exhibits remarkable discriminatory power, distinguishing between self and non-self to mount protective responses against infections. In clinical diagnostics targeting dimorphic fungi, this immunological discrimination is leveraged to detect specific antibodies indicative of disease states. However, reliance on immune modulation for diagnostic purposes presents inherent challenges due to the intricate nature of antigen-antibody interactions. This complexity is particularly pronounced in patients with a history of autoimmune disorders, where the risk of false positive results in immunoassays is heightened due to the dysregulated immune response characteristic of autoimmune conditions.

Methods
We assessed the potential for cross-reactivity of serum samples from patients with autoimmune disease in dimorphic fungal Enzyme Immunoassays (EIAs) by analyzing a cohort of clinical serum samples sourced from the Florida region, which is non-endemic for dimorphic fungal diseases. Samples were commercially sourced as remnant-banked serum samples (Medix Biochemica, Florida, USA). 25 serum samples obtained from distinct patients were subjected to testing using Coccidioides, Blastomyces, and Histoplasma EIA (MiraVista Diagnostics, Indiana, USA). This ncluded 5 individuals devoid of autoimmune disorders, cohorts of 5 patients each diagnosed with Rheumatoid Arthritis and Multiple Sclerosis, and 10 patients with Systemic Lupus Erythematosus. Samples were tested in triplicate.

Results
Preliminary findings from our study unveiled nuanced levels of cross-reactivity across the dimorphic fungal EIAs utilized for the three autoimmune disorders examined. Depending on the specific dimorphic fungal EIA assay and autoimmune disorder, approximately 10–30% of serum samples from patients tested intermediate or weakly positive in the respective fungal EIAs. All control patient samples tested negative.

Conclusion
These preliminary findings underscore the complexity of diagnosing dimorphic fungal infections, highlighting the significance of the patient's immune status as a confounding factor. Clinical practitioners should consider the possibility of autoimmunity when encountering weakly positive or intermediate dimorphic fungal EIA results.

Disclosures
Arryn Craney, PhD D(ABMM), MiraVista Diagnostics: Employee; Salary Kendra Carlson, n/a, MiraVista Diagnostics: Employee; Salary Kyla Seyfried, n/a, MiraVista Diagnostics: Employee; Salary John Witt, n/a, MiraVista Diagnostics: Employee; Salary Andrew Hanzlicek, DVM, MiraVista Diagnostics: Employee; Salary Nicolas Barros, MD, MiraVista Diagnostics: Advisor/Consultant Lawrence J. Wheat, MD, MiraVista Diagnostics: Employee; Salary|MiraVista Diagnostics: Ownership Interest
P-2147. Incidence of Invasive Fungal Infection in Venetoclax-based Regimens for AML/MDS Patients on Micafungin Prophylaxis
Authors: Texidor Williams Monier , Amaya Lee , Gauthier Timothy , Andia Marco Ruiz 
Published: January 2025

Abstract

Background
Combining venetoclax with a hypomethylating agent (HMA) is standard of care in Acute Myeloid Leukemia (AML) ineligible for intensive chemotherapy. However, this agent is associated with prolonged neutropenia, potentially increasing the risk of invasive fungal infections (IFI). The necessity of antifungal prophylaxis in this context remains unclear, particularly in regions like the southeastern United States, where the humid climate may contribute to higher overall rates of IFIs.

Methods
A retrospective, observational cohort study evaluated patients admitted to Baptist Health Baptist Hospital in Miami, Florida, from January 2019 to January 2023 who received venetoclax and an HMA with/without low-dose cytarabine for AML/MDS. Exclusions included incomplete first cycle, active IFI treatment, absence of antifungal prophylaxis, or initiation of venetoclax at an outside institution. The primary endpoint was 90-day IFI incidence using 2022 EORTC criteria. The secondary endpoints were complete response (CR) per ELN 2022 guidelines, 1-year mortality, and 90-day count recovery.

Results
Among 102 patients evaluated, the mean±SD age was 73±9 years. Twenty-seven patients (27%) had relapsed refractory disease, and 42 (41%) received prior chemotherapy. Overall, 57% presented with de novo AML/MDS; 13 treated specifically for MDS. Micafungin was the predominant inpatient prophylaxis agent (95%), while posaconazole (40%) and fluconazole (37%) were the predominant prophylaxis agents prescribed at discharge. IFI incidence at 90 days was 7%, consisting mostly of possible IFI (6/7). CR was achieved in 61% of patients, and 1-year mortality was 32%. 90-day neutrophil recovery occurred in 62% (63/102), while platelet recovery occurred in 66% (65/99).

Conclusion
Our findings suggest that micafungin as primary antifungal prophylaxis in AML/MDS patients receiving venetoclax-based regimens demonstrates a comparable incidence of IFI at 90 days to previous studies reporting similar outcomes.

Disclosures
Timothy Gauthier, PharmD, BCPS, BCIDP, AbbVie Pharma: Advisor/Consultant|Antimicrobial Therapy, Inc: Advisor/Consultant|Ferring Pharma: Advisor/Consultant|Firstline Mobile Health: Advisor/Consultant|Gilead Pharma: Advisor/Consultant|GoodRx: Advisor/Consultant|GSK Pharma: Advisor/Consultant|Melinta Pharma: Advisor/Consultant|Pattern Biosciences: Advisor/Consultant|Pfizer Pharma: Advisor/Consultant|ProCE: Honoraria|WWW.LearnAntibiotics.com: Ownership Interest
P-2148. Prospective Study on Microbiological Profile of Fungal Isolates and its Antibiogram in a Tertiary care hospital in South India
Authors: Velmani Vaishnavi , Radhakrishnan Sriram , Muppa Leena , Dorairajan Sureshkumar 
Published: January 2025

Abstract

Background
Fungal infections are increasingly recognized as significant causes of morbidity and mortality, particularly in immunocompromised individuals. Despite their importance, there is limited data on the microbiological profile and antimicrobial resistance patterns of fungal isolates in South India. This prospective study aims to fill this gap by characterizing fungal isolates and determining their antibiograms in a tertiary care hospital, providing crucial insights for clinical management and infection control strategies.

Methods
A Prospective Observational Study was done under the guidance of an Infectious diseases Specialist by collecting the culture positive fungal isolates from the Microbiology department for the 1 year duration of April 2023 to March 2024. Data including patient age, gender, specimen, type of fungus isolated, its sensitivity pattern, average time required for identification of the species and requirement of ICU admission were analyzed. The three classes of antifungals including polyenes, azoles and echinocandins were included. Data was entered and analyzed using Microsoft excel.

Results
A total of n=62 fungal isolates were isolated. The average age of the patients was 49 years with a higher prevalence in male (n=42) compared to females (n=20). Fungal species have been isolated more commonly from blood samples followed by urine samples, tissues, body fluids. In all the cases tested, Azoles, Polyenes and Echinocandins were susceptible in 57%, 76% and 80% of the cases respectively. Average time taken for identification of the subspecies was 124 hrs (∼ 5 days). Candida auris was the most common isolate found, which developed complete resistance to azoles, partially to polyenes, while echinocandin has been found to be a reliable drug of choice. The spectrum and efficacy of Echinocandins were higher compared to azoles and polyenes.

Conclusion
Candida auris was found as the most resistant species and echinocandins have been found as a reliable drug of choice compared to Azoles and Polyenes antifungals. This study highlights the need for rapid diagnostic procedures for rapid identification of the species grown in the culture, thereby enabling rational antifungal therapy. As long as the reporting time delays, initiation of right antifungal therapy also delays.

Disclosures
All Authors: No reported disclosures