bluuebunny/crossref_metadata_2025_split huggingface dataset:
779. Make Micro Cool Again: Implementing a Longitudinal Lab-based Microbiology and Mycology Curriculum to Engage Infectious Diseases Fellows in Hands-On Learning
Authors: Pollock Erin , Keri Vishakh C , Salimnia Hossein , Monday Lea M 
Published: November 2023

Abstract

Background
Microbiology wet labs have been eliminated in many medical schools and infectious diseases (ID) fellows are training in a post-COVID era where hands-on experience is lacking. The IDSA recommends 120 hours of microbiology experience for fellows, but feasibility is limited in centers struggling to retain adequate staff, and technicians are limited in their ability to integrate clinical skills. We aimed to overcome these struggles by implementing a microbiology and mycology curriculum for ID fellows using a case-based approach within the microbiology lab (Fig1).

Methods
In a quasi-experimental study, eight ID fellows from Wayne State University were taught in interactive, 1-hour sessions delivered monthly in the lab over 11 months using existing samples. Planning included a needs assessment, review of in training scores to identify weak spots, and pre-tests to assess baseline knowledge (Fig 1). Sessions topics are shown in Table 1. All sessions were delivered by an ID faculty to ensure homogeneity. Prior to each session, specimens were procured and objectives were outlined and linked to core content areas. An example of the objectives and core content for the hyaline mold session is shown in Table 2. A post-test occurred after session 9. Primary outcome was comparison of de-identified pre and post test scores by Wilcoxon signed-rank test for paired non-parametric data. Fellows experience and feedback for improvement were also collected.

Results
Sessions were performed as described and included hands on activities and a summary handout (Fig 2). Pre versus post test scores showed significant median improvement (65% to 82.5%. p=0.048, table 3). Feedback on the sessions was overwhelmingly positive, with suggestions for encore sessions and request to make a similar parasitology curriculum (Table 4). Sessions became so popular that pharmacists and other trainees began attending. Although not an intended outcome, it was noted that after posting handouts to twitter, fellowship following increased by 250%.

Conclusion
A monthly longitudinal microbiology and mycology curriculum was well received by ID fellows and objectively increased their knowledge. This is the first study attempting to objectively quantify knowledge gained using a hands-on microbiology lab curriculum to teach ID fellows.

Disclosures
All Authors: No reported disclosures
784. Feet First: A Innovative Curriculum for Podiatry Residents on Infectious Disease using Padlet
Authors: Sharma Amit M , Srinivas Sindhu , Wessinger Jaclyn Denise , Nasser Elliane 
Published: November 2023

Abstract

Background
Infectious Disease Rotation is mandatory for Podiatry trainees. Unfortunately, a standardized Infectious Disease rotation is lacking despite the above requirements. Therefore, we performed a nationwide needs assessment for a dedicated podiatry curriculum for Infectious Disease Elective. We also created a curriculum using Padlet to provide education to our trainees.
Results Table Program Characteristics
Podiatry Training Program Characteristics across the nation
Table 2 Curriculum characteristics
Variation in curriculum

Methods
We performed a nationwide survey to assess the current uniformity between podiatric programs regarding their infectious disease rotation. In addition, each podiatric surgical residency program was surveyed to gather data on its current curriculum and evaluation processes. We surveyed Geisinger North East Podiatry Residents to identify the common topics they wanted to learn from their ID rotation and the learning curriculum best suited to their needs. Finally, we devised a novel approach to medical education that leverages educational technology's power to enhance podiatry residents' learning experience. Using Padlet, a versatile and user-friendly platform, this curriculum offers learners an interactive and engaging learning experience featuring lectures, videos, case studies, quizzes, polls, and assignments.

Results
The Northeast region had 38% of programs, followed by the Midwest (26%), Southeast (18%), West (12%), and Southwest (6%). Common regional themes included identifying nosocomial infections, understanding precautions and quarantine for specific infections, and understanding and treating MRSA, VRE, Clostridium difficile, osteomyelitis, and necrotizing fasciitis among Northeast Programs. In the Western region, programs focused on attitudinal assessments detailing the importance of punctuality, self-study and literature review, accepting criticism, quality improvement, willingness to enhance knowledge and practice, and practicing with professionalism. Based upon the discrepancies in the duration of rotation, breadth of topics covered, and lack of uniformity in teaching techniques, we created a curriculum using the Flipped Classroom method and EdTech tools like Padlet. Through Padlet we hope to combine synchronous and asynchronous educational techniques.

Distribution of podiatry training programs across the United States

Conclusion
Edtech tools like Padlet can help provide quality education effectively to podiatry trainees.
Padlet Snapshot

Disclosures
All Authors: No reported disclosures
806. Candida Gut Colonization in Critically Ill Patients
Authors: Adelman Max W , Tran Truc T , Detranaltes Andrea M , Rydell Kirsten B , Atterstrom Rachel , Schettino Marissa G , Amaya Abigail A , Malikzad Husna , Virk Muhammad H , Jones Mary N , Deyanov Alex E , Perez Jose C , Corry David B , Lorenz Michael C , de Paula Baptista Rodrigo , Arias Cesar A 
Published: November 2023

Abstract

Background
Candida spp. colonization is a risk factor for candidemia in intensive care unit (ICU) patients. Recent data suggest that the epidemiology of Candida infections is shifting away from C. albicans, but prospective data on the epidemiology of Candida spp. gut colonization are limited.

Methods
We conducted a prospective cohort study of adult patients admitted to an ICU at a tertiary care hospital. Patients had stool samples collected twice weekly for up to four weeks or until ICU discharge. A convenience sample of stool samples was plated on CHROMagar Candida Plus for 48 hours. Colonies of different morphologies were isolated on Sabouraud dextrose agar and identified with MALDI-ToF.

Results
A total of 102 patients were included in the cohort. We performed screening for stool Candida colonization in 12 patients: 8 (67%) men, median age 65 (IQR 54.5-68.5). Three (25%) were in shock and eight (67%) required mechanical ventilation on ICU admission. In-hospital mortality was 25%. Seven patients (58%) were colonized with Candida at ≥1 time point (Figure 1). Of 30 total time points tested (median per patient=2, range 1-5), 15 (50%) were positive for Candida spp. Most time points (9/15, 60%) were positive for C. glabrata; 4/15 (27%) were positive for both C. glabrata and C. albicans. A minority (1/15; 7%) were positive for C. albicans and C. parapsilosis alone, respectively. None had C. auris colonization. Most colonization was persistent: Of 6 colonized patients with ≥1 time point tested, 5 (83%) were colonized at multiple timepoints. Eleven patients had data collected on anti-fungal administration during the study period, and five of these received an antifungal (Figure 1). Of these five, three (60%) had no Candida colonization. One lost C. albicans colonization but had persistent C. glabrata colonization despite azole therapy, and another developed C. parapsilosis colonization despite azole and amphotericin administration.
Figure 1.
Results of serial stool samples tested for Candida colonization per individual patient.

Conclusion
Most ICU patients in this study had Candida spp. gut colonization, commonly with intrinsically azole-resistant C. glabrata. This study is limited by small sample size, and further data are needed to determine the clinical impact of antifungal-resistant Candida in ICU patients at high risk of candidemia.

Disclosures
All Authors: No reported disclosures
808. Outcomes of Invasive Candidiasis Stratified by Antifungal Therapy
Authors: Box Maggie , Anwar Lara , Molina Kyle 
Published: November 2023

Abstract

Background
IDSA guidelines for invasive candidiasis recommend echinocandins (ECH) as first-line agents for initial therapy, with fluconazole (FLU) as an acceptable alternative. Transitioning from an ECH to FLU is also recommended in clinically stable patients with FLU susceptible isolates. All-cause mortality is high for candidemia, typically due to medical comorbidities in patients who develop candidiasis. The objective of this study is to report outcomes of invasive candidiasis stratified by antifungal therapy received, comparing micafungin (MIC), fluconazole, and micafungin to fluconazole step down therapy.

Methods
This multicenter, retrospective study was conducted at Scripps Health from 6/1/2019 – 6/30/2022. Adult patients with culture confirmed invasive candidiasis were included. Patients were excluded if they were pregnant, care was withdrawn within 7 days of treatment initiation, or had prolonged course of therapy due to uncontrolled source. The primary endpoint was 28-day mortality based on antifungal therapy. Secondary outcomes included time-to-death among and duration of therapy trends.

Results
A total of 95 patients were included. Candida glabrata was most frequently isolated (43.2%) followed by Candida albicans (36.8%). There was no difference in 28-day mortality among patients receiving fluconazole only (15.4%, n = 13), micafungin only (20.5%, n = 44), micafungin only due to fluconazole resistance (12.5%, n = 8), and micafungin to fluconazole step down therapy (13.3%, n = 30), p = 0.849. Among patients who died, there was no difference in time-to-death between groups (p = 0.678) or mortality by organism (C. albicans 37.5%, p = 0.952 and C. glabrata 43.8%, p = 0.958). Six patients with non-C. albicans isolates that were susceptible dose-dependent (SDD) to FLU were successfully treated with FLU step-down therapy with a dose/MIC ratio of &gt; 100.

Conclusion
There was no difference in 28-day mortality or time-to-death between patients who received fluconazole versus micafungin for invasive candidiasis. Fluconazole step down therapy (including oral) is a viable option for patients who are candidates, including non-C. albicans SDD organisms.

Disclosures
All Authors: No reported disclosures
809. Empiric Antifungal Therapy Is Not Associated with Improved Survival Outcome among Intensive Care Units (ICU) Patients
Authors: Wong Lauren , Zelenkov Dimitar , Campion Maureen , Foong Kap Sum , Doron Shira , Vazquez Gabriela Andujar 
Published: November 2023

Abstract

Background
In recent years, ICU at Tufts Medical Center (TMC) have a higher utilization rate of antifungal agents compared to nationwide ICU data reported to the National Health and Safety Network. The role of empiric antifungal therapy in reducing ICU patient mortality remains controversial. Prudent use of antifungals is needed to mitigate the risk of further antifungal resistance development. Our study aimed to evaluate empiric antifungal use among ICU patients and its association with ICU 30-day all-cause mortality.

Methods
We conducted a retrospective study of all adult ICU patients at TMC who had received fluconazole (F) or micafungin (M) between August 2022 and February 2023. We collected demographics, comorbidities, Candida score, indication for empiric antifungal therapy, use of mechanical ventilation (MV) and broad spectrum antibiotic use. Univariable and multivariable logistic regression analyses were conducted to identify predictors associated with ICU 30-day all-cause mortality among ICU patients who received antifungal therapy.

Results
A total of 77 ICU patients received antifungal treatment, (F: 22 patients, M: 55 patients). The median treatment duration was the same for both therapies, 2 days [1-4]. Only 4 (5%) of patients had positive blood cultures for Candida sp. The median Candida score was 3 [2-4]. Antifungal therapy was initiated for suspected infection in 52 (68%) of patients per prescriber orders indications. The majority of patients were ventilated (63, 81.8%), of these, 15 (23.8%) were on extracorporeal membrane oxygenation. The 30-day all-cause mortality was 58 (75%). Multivariable logistic regression analysis showed antifungal therapy for ≥ 48 hours was not associated with improved ICU mortality (adjusted odds ratio, 0.276; 95% confidence interval, 0.31-2.44). Chronic heart failure was associated with an increased risk for ICU mortality (adjusted odds ratio, 19.91; 95% confidence interval, 1.32-299.72).

Conclusion
A high 30-day all-cause mortality among ICU patients who received empiric antifungal treatment was observed. Similar to national trends, the incidence of fungemia was low despite moderate candida scores. Empiric antifungal therapy ≥48 hours was not associated with improved mortality outcome in this population.

Disclosures
Maureen Campion, PharmD, BCIDP, Shinoigi: Speaker
812. Bacterial endosymbionts are frequently found among Mucorales clinical isolates. Should we screen for their presence in patients with Mucormycosis?
Authors: Leon Dora Edith Corzo , Harrison Jamie , Uehling Jessie , López-Jácome Luis Esaú , Borman Andy , Ballou Elizabeth 
Published: November 2023

Abstract

Background
Soil-associated Mucorales fungi frequently host bacterial endosymbionts that produce damaging endotoxins important for plant pathology. Our work and clinical reports suggest an important and unanticipated role for endosymbionts in human disease. The endosymbiont Mycetohabitants rhizoxinica was associated with bacteriemia in an immunocompromised individual where its host Rhizopus microsporus caused mucormycosis. Our data demonstrate the endosymbiont Ralstonia pickettii can impact virulence of its R. microsporus host. Together, these data suggest Mucorales endosymbionts can influence both fungal and bacterial infections; however, their frequency and diversity in Mucormycosis is unknown. This project investigates the frequency and diversity of bacterial endosymbionts in Mucorales clinical isolates.

Methods
Mucorales isolates from mucormycosis patients via the UK National Mycology Reference Laboratory and the Instituto Nacional de Rehabilitacion, Mexico, were identified by ITS1/2 PCR or MALDI-TOF. Fungal isolates (YPG agar, 5 days, 30 oC) were subjected to phenol/chloroform DNA extraction. Bacterial presence was assessed by 16s RNA PCR, and resulting bands identified by nanopore sequencing. In parallel, WGS of total DNA confirmed bacterial presence and identity. Bacteria were also physically isolated from homogenized fungal mycelia (nutrient broth, 80rpm, 37oC, 4 days) harvested under sterile conditions. Bacteria from supernatants (LB, Blood agar, 30 and 37 oC ± 5% CO2, 4-10 days) were identified by 16s RNA PCR and Nanopore sequencing.

Results
In total, 27 Mucorales isolates (R. arrhizus/delemar n=7; R. microsporus n=6; Lichtheimia corymbifera n=4; L. ramosa n=3; Mucor circinelloides n=4; others n=3) were evaluated for bacteria presence. 17/27 (62%) were 16s RNA positive. Culture identified 6 bacterial species (R. pickettii, Niallia circulans, Peribacillus simplex, Roseomonas mucosa, Micrococcus luteus, Staphylococcus pasteuri). Mucorales isolates originated from cutaneous 11/27 (41%); respiratory 8/27 (29%); and sinus-orbital diseases 7/27 (26%).

Conclusion
The presence of bacterial endosymbionts in clinical isolates of Mucorales is frequent, diverse and can potentially influence fungi in causing disease among individuals at risk.

Disclosures
All Authors: No reported disclosures
814. Impact of Testing Turnaround Times on Clinical Outcome in Hospitalized Patients with Histoplasmosis and Blastomycosis
Authors: Dalton Liam , Richards Blair , Miceli Marisa H 
Published: November 2023

Abstract

Background
Patients (pt) with histoplasmosis (histo) and blastomycosis (blasto) requiring hospitalization have unacceptably high mortality rates. In part, this is due to a delay in diagnosis. Serum (S) and urine (U) antigen (Ag) testing are often crucial for timely antifungal therapy. Clinical observations suggested delays in ordering samples to be sent to reference labs upon admission and prolonged turnaround time (TAT) for test results can lead to delays in starting therapy and poor outcomes. We sought to determine the impact of TAT for histo and blasto Ag testing on clinical outcomes of hospitalized patients (pt) at our institution.

Methods
Retrospective evaluation of all adult inpatients with histo or blasto diagnosed by positive U or S Ag tests from 1/1/15-12/31/22 was conducted. TAT from admission to result (TAT-AR) and from sample collection to result (TAT-CR) for the earliest positive test were calculated. Clinical data, including treatment & outcomes were collected. Only pt who received antifungal therapy or had a postmortem diagnosis were included. The relationship between TAT-AR and TAT-CR and outcome was evaluated.

Results
Of 39 pt (mean age 47±19 yr), 26 (67%) were men and 33 (85%) were immunocompromised: solid organ transplant recipients, 15; hematologic malignancy, 3; autoimmune/inflammatory disease on treatment, 12; others, 3. Thirty-five pt had pulmonary (8) or disseminated histo (27); 4 had disseminated blasto. Nine pt (23%) died within 4 months of diagnosis, including 8 pt with histo and 1 with blasto. Mean TAT-AR for these 9 deceased pt was 14.7± 19.5 days (d) vs 6.1±3.1 d for 30 survivors (p=.02). Mean TAT-CR for these 9 deceased pt was 5.4±1.5 d vs 3.9±1.3 d for 30 survivors (p=.003). Of the 32 pt who required IV amphotericin B (29) or died before any antifungal therapy was given (3), mean TAT-CR was 5.4±1.5 d for those who died vs 3.7±1.1 d for those who survived (p=.0013). ICU transfers, 30-d readmissions, and length of stay were not impacted by TAT-AR or TAT-CR.

Conclusion
Delays in TAT for initiating testing and obtaining results were associated with increased mortality of hospitalized pt with newly diagnosed histo or blasto. These findings highlight the importance of early testing and timely test results to guide treatment for hospitalized pt with these diseases.

Disclosures
Marisa H. Miceli, MD, Astellas: Advisor/Consultant|F2G: Grant/Research Support|Scynexis: Advisor/Consultant|Scynexis: Grant/Research Support
818. Therapeutic Drug Monitoring of Triazole Antifungals for Coccidioidal Meningitis
Authors: Fang Michelle , Torres Bianca , Kooner Lovedip , Dunn Chelsea , Redgrave Jessica , Kuran Rasha , Heidari Arash , Johnson Royce H 
Published: November 2023

Abstract

Background
Coccidioidal meningitis (CM) is a potentially devastating manifestation of disseminated infection caused by Coccidioides spp., generally requiring lifelong therapy with triazole antifungals (TA). Given the complexity of assessing treatment response in coccidioidomycosis, which can be impacted by host immune response, pharmacokinetics, antifungal pharmacodynamics, and medication adherence, therapeutic drug monitoring (TDM) of TA therapy, which is not currently common practice for most TA, has been proposed to improve clinical evaluation of such variables. Consistent TDM is anticipated to increase the probability of a successful CM treatment outcomes.

Methods
This is a retrospective review of patients with CM who received adjunctive TA TDM at the Valley Fever Institute at Kern Medical from November 2019 to December 2022. Approval and a waiver of consent were obtained from the Institutional Review Board. The combination of a patient and TA was considered a unique therapy regimen, with each TA course evaluated separately for patients who received multiple triazoles over the course of their CM treatment. The primary endpoint was improvement in the cerebrospinal fluid (CSF) score, which was derived from the Mycoses Study Group scoring system for meningeal disease, over the available follow-up period.Table 1.CSF Score (based on the Mycoses Study Group scoring system for meningeal disease)

Results
Twenty-seven TA regimens were found to be eligible for inclusion in this study, with fluconazole comprising the majority of these courses (52%) and the remainder divided between isavuconazole (22%), voriconazole (11%), itraconazole (7%), and posaconazole (7%). Of the serum triazole levels obtained, 34% were considered to be therapeutic, 45% were subtherapeutic, and 21% were supratherapeutic. Greater improvements were noted in CSF scores of TA regimens with the higher serum levels compared to TA regimens resulting in lower serum levels (see figure 1).
Figure 1. CSF Scores on Fluconazole: Lowest vs. Highest Quartile
CSF scores of fluconazole regimens resulting in the lowest quartile (Q1, n=4) of serum fluconazole levels over 24 months were compared to regimens resulting in the highest quartile (Q4, n=4) of serum levels. A decrease in the CSF score generally represent improvement in meningeal disease.

Conclusion
TA TDM is expected to advantage the care of patients with CM. The possible correlation between higher TA serum levels and improvements in CSF parameters shown in this study emphasizes the potential role of TDM for maximizing TA efficacy in CM, in addition to discernment of medication nonadherence or suboptimal pharmacokinetics.

Disclosures
All Authors: No reported disclosures
819. Experience with Isavuconazole Use for Treatment of Invasive Fungal Infections
Authors: Gow-Lee Vanessa , Chesdachai Supavit , Harris Courtney E , Abu Saleh Omar M 
Published: November 2023

Abstract

Background
The treatment of invasive fungal infections (IFI) is often complicated by drug-drug interactions, toxicities, and host comorbidities. Isavuconazole (ISA) has a favorable side effect profile and has FDA approval for invasive aspergillosis and mucormycosis, but there are fewer data on its efficacy for other microbes and non-pulmonary infections. We report our experience of ISA in IFI treatment, with a particular focus on non-pulmonary sites and other microbial etiologies.

Methods
We identified patients who received ISA as part of IFI treatment from 1/1/2015–4/1/2020 at Mayo Clinic. We categorized them by organ involvement and by pathogens, and identified patterns of ISA use and clinical outcomes.

Results
A total of 131 patients were identified. Similar to the existing literature, the majority were pulmonary infections (60%), with 12% invasive sinus infection, 12% central nervous system (CNS) infection, and 7% fungemia. Aspergillus was the most common pathogen (39%), yeast comprised 19%, dimorphic fungi 15%, Mucormycosis 12%, phaeohyphomycosis 5%, and other molds 3%.
ISA was used as secondary/salvage therapy in 89% of cases. The response rate varied by organ involvement and pathogen. ISA had complete/partial resolution or achieved stability in 57% of fungemia cases, 63% of invasive sinus infections, 64% of pulmonary infections, and 73% of CNS infections. Aspergillus species had a 67% response rate, with 72% response in yeast infections, 65% rate in dimorphic fungi, 53% for mucormycosis, and 86% in dematiaceous molds.

Conclusion
Although limited by a small sample size, the subgroup review based on organ site and microbial etiology did seem to show roughly similar results to approved uses. The CNS infections treated with ISA were particularly of interest, given the limited options available with reliable CNS penetration.
The current available literature has little to say on the efficacy of ISA in these off-label uses, with the majority being similar case series. This report highlights the importance of prospective trials comparing ISA to other antifungals in a greater variety of indications to better identify when this better-tolerated agent can be safely used.

Disclosures
Courtney E. Harris, MD, Dynamed: Advisor/Consultant