bluuebunny/crossref_metadata_2025_split huggingface dataset:
351. Epidemiology and antifungal susceptibilities of clinically significant filamentous fungi from a tertiary hospital in Singapore from 2018 – 2021
Authors: Huang Wenjie , Tan Mei Gie , Tan Yen Ee 
Published: December 2022

Abstract

Background
Filamentous fungi infections are associated with significant morbidity. Although an increase in antifungal resistance has been reported globally, no data pertaining to Singapore is available. This study investigates the species distribution and antifungal susceptibility profiles of molds isolated from a tertiary hospital in Singapore.

Methods
A retrospective review of fungal cultures with antifungal susceptibility results reported in the laboratory information system from 2018 to 2021 was conducted. Unique isolates per patient were included. Molds were identified primarily by morphology. Molecular studies were used as an adjunct where required. Susceptibility testing was performed via broth microdilution (Sensititre YeastOne) and gradient diffusion (Liofilchem) methods.

Results
125 isolates were analyzed (Table 1). The most common molds recovered were Aspergillus, Fusarium and Mucorales. Aspergillus and Mucorales frequently involved the respiratory tract and skin and soft tissue (SSTI) whereas Fusarium was isolated from SSTI and blood.
Amphotericin B had moderate activity against all molds, with only 11 out of 88 isolates (12.5%) being non-wild type (Table 2). The echinocandins exhibited good activity against Aspergillus and other hyaline molds but not Fusarium and Mucorales. The triazoles were most useful against Aspergillus, with posaconazole demonstrating the lowest geometric mean of 0.067. Fusarium had high MICs when tested against the azoles. Posaconazole was the azole of choice for Mucorales.
Six Aspergillus isolates (all A. fumigatus) were non-wild type when tested against voriconazole, with a MIC &gt;1. Of these six isolates, three were also non-wild type for amphotericin B, with a MIC &gt;2. In particular, one Aspergillus fumigatus complex isolate demonstrated resistance across all tested azoles and sequencing revealed Cyp51 mutations.

Conclusion
Aspergillus species is the most prevalent clinically significant mold in our hospital. Although triazoles and echinocandins exhibit good activity, 13.33% of Aspergillus isolates were non-wild type for amphotericin B. Given the detection of these non-wild type Aspergillus species, susceptibility testing may be indicated in seriously ill patients to aid clinicians in selecting antifungal therapy.

Disclosures
All Authors: No reported disclosures.
355. Outcome of patients with non-COVID-19 related Aspergillosis during the COVID-19 pandemic
Authors: Roman-Montes Carla M , Guzman-Pérez Adriana , Student Medical , Martinez-Gamboa Rosa Areli , Gonzalez Maria Fernanda , Díaz-Lomelí Paulette G , Cervantes Axel , Ponce-de-leon Luis Alfredo , Sifuentes-Osornio José , Rangel-Cordero Andrea 
Published: December 2022

Abstract

Background
In March 2020 our Institution was designated a COVID-19 unit, since the start of 2021 conventional medical attention has been reinstalled and it became a hybrid hospital. Our objective was to compare the outcome of patients with Invasive Aspergillosis (IA) without COVID-19 during the COVID-19 pandemic, compared with past controls from a historical cohort, and describe their clinical characteristics. As a secondary objective, we described the characteristics of other Invasive Fungal Infections (IFI) in a similar patient group.

Methods
Retrospective and descriptive study. The information was obtained from the electronic file. For IFI diagnosis, the EORTC/MSG criteria for proven and probable infection were considered, including the AspiCU modified criteria. The main outcome was death at 6 weeks, time from symptom onset to diagnosis/treatment, and having received antifungal treatment as secondary outcomes. Outcomes were compared to historical IA controls (2:1) from a pre-COVID-19 cohort. The study was approved by the local research and ethics committee.

Results
From March 2020 to December 2021, 50 IFIs were diagnosed in non-COVID-19 patients, of which 27 (54%) were Invasive Aspergillosis, 10 (20%) Cryptococcosis, 8(16%) histoplasmosis, 4 (8%) mucormycosis, and 1 (2%) Fusariosis. The median age was 44 years (IQR 33-58) and 67% were men. Forty three percent (22/51) had immunosuppression and 35% (18/51) had hematological malignancy, the median time from symptom onset to IFI diagnosis was 30 days (IQR 11-90) and 38% died within 6 weeks. During the pandemic, in Invasive Aspergillosis non COVID-19 patients, the median number of days from symptom onset to start antifungal was 21 (IQR 6-68) vs 5 (IQR 3-10) of IA historic controls (p=0.0005), 81.5% (22/27) vs 93% (50/54) received antifungal treatment (OR 0.88 , 95% CI 0.72-1.0,p=0.13), and IA cases had a mortality of 44% (12/27) vs 41% (22/54) in the historical cohort (p=0.75). We show the IA characteristics in Table 1. Table 1.Clinical characteristics of Patients with Invasive aspergillosis without COVID-19 during COVID-19 pandemic vs historic controlsFigure 1.Invasive fungal infections in non-COVID-19 patients during COVID-19 pandemicFigure 2.Invasive aspergillosis diagnosis methods in non-COVID-19 patients during COVID-19 pandemic
GM: Galactomannan antigen

Conclusion
During the COVID-19 pandemic, patients with IA withouth COVID-19 were diagnosed significantly later. Also, a trend towards increased mortality and lower proportion of antifungal treatment was observed. It is likely a consequence of hospital reconversion during the start of the pandemic.

Disclosures
All Authors: No reported disclosures.
356. Risk Assessment of Pneumocystis jirovecii Pneumonia among Hospitalized Patients with Hypoxic Respiratory Failure - A Proposed Multivariable Calculator Based on Previous Prednisone Equivalent Dose
Authors: Barahona Lilian Vargas , Sillau Stefan , Molina Kyle C , Pedraza-Arévalo Laura C , Scherger Sias , Chastain Daniel B , Shapiro Leland , Franco-Paredes Carlos , Hawkins Kellie , Henao-Martínez Andrés F 
Published: December 2022

Abstract

Background
Corticosteroids increase the risk of Pneumocystis jirovecii pneumonia (PJP). It is unknown how much corticosteroid dose exposure would modify the risk of PJP in different populations. We aim to develop a PJP risk calculator based on the previous dose of corticosteroids and modulated by additional clinical factors.

Methods
A multicenter retrospective case-control study was performed on patients tested for PJP within the UCHealth system from 2000 to 2021. We developed a model for estimating PJP risk based on previous prednisone equivalent daily dose (PEDD) and adjustable for additional clinical variables. PJP was fit to a generalized additive model (GAM), with a spline for prednisone dose and additive covariates for demographics and risk factors. We used a multicenter federated network to calibrate the model to estimate the PJP prevalence among hospitalized patients with hypoxic respiratory failure.

Results
We had a complete sample of 199 patients, 104 cases with PJP, and 95 controls. Patients with HIV (OR: 19 CI: 6.3-60.8, p&lt; 0.0001), diabetes (OR: 4.1 CI: 1.2-14.8, p&lt; 0.0288), and autoimmune disease (OR: 5.2 CI: 1.4-19.2, p&lt; 0.0139) were more likely to have PJP. Patients with preexisting lung disease (OR: 0.3 CI: 0.1-0.6, p&lt; 0.0041) and on PJP prophylaxis (OR: 0.06 CI: 0.02-0.2, p&lt; 0.0001) were less likely to have PJP. 36.8% of controls and 49% of cases were on steroids with a mean PEDD of 15 mg/day and 20.4 mg/day, respectively. We found a prevalence of PJP of 0.126% among hospitalized patients with hypoxic respiratory failure. The developed model can estimate the PJP risk based on a previous PEDD in 32 different clinical combinations: e.g., a PEDD of 20 mg/day would give a calculated annual PJP risk of approximately 1.74% (95% CI: [0.39, 7.42]) if a patient has autoimmune disease only but 6.29% (95% CI: [1.34, 24.91]) if a patient has HIV only (Figure 1). Figure 1.Predicted probability of PJP based on previous prednisone dose among hospitalized patients with hypoxic respiratory failure for three different clinical scenarios

Conclusion
Previous corticosteroid dose alone is inadequate to inform of an increased risk of PJP. A multivariable calculator incorporating the absence or presence of additional traditional risk factors could optimally stratify the PJP risk. Future directions include validating the findings in external cohorts and modeling PJP risk in the ambulatory setting to inform the need for PJP prophylaxis.

Disclosures
All Authors: No reported disclosures.
362. Association of Eosinophilia with Parasites in Rhode Island Refugees, 2015 - 2020
Authors: Teferi Maranatha , Osorio Marcela , Marin Benjamin Gallo , Ding Ann , Michelow Ian C 
Published: December 2022

Abstract

Background
There are sparse data reporting the rates of potentially pathogenic parasites in asymptomatic, newly arrived refugees to the United States. Untreated parasitic infections can have significant health consequences including anemia, malnutrition, infertility, urinary tract malignancy, and death, among others. Eosinophilia may serve as a biomarker for certain parasites, but its reliability is debated. We hypothesized that detection of eosinophilia in refugees to Rhode Island would be useful for guiding management in this vulnerable population.

Methods
A retrospective chart review was performed on all adult and pediatric refugees who had their initial refugee intake clinic visit at Lifespan’s Center for Primary Care Refugee Clinic, Hasbro Children Hospital’s Refugee Clinic, or Medicine-Pediatrics Refugee Clinic, all in Rhode Island, from January 2015 to December 2020. Patients who had delayed intakes or were originally evaluated in other states were not eligible. Data were systematically collated in RedCap and descriptive statistics were performed.

Results
Charts of 955 refugees were reviewed retrospectively, of which 143 did not meet eligibility criteria and were excluded. Overall, 505 (62.2%) patients were from Africa, 242 (29.8%) from Asia, 32 (3.9%) from the Americas, 32 (3.9%) from Europe, and 1 (0.1%) from Australia. Among the 812 individuals included, 147 (18.1%) patients had eosinophil counts &gt; 500/uL, of whom 113 (76.9%) had mild (450-1499/uL), 30 (20.4%) had moderate (1500-4999/uL), and 4 (2.7%) had severe eosinophilia (⪰ 5000/uL). The majority of patients with or without eosinophilia originated from Africa.
Prevalence of symptoms (Table 1) ranged from 0% (bloody stools) to 17.6% (abdominal pain). Overall, &gt; 50% of refugees tested positive for a parasite by various methods (Table 2). Serology did not distinguish between acute or past infection. One patient (0.7%) was diagnosed with Plasmodium falciparum malaria. Table 1.Symptoms at Initial Encounter Among Patients With Eosinophilia (n=68)Table 2.Lab Values Among Patients with Eosinophilia (n=147)

Conclusion
Eosinophilia was common in both adult and pediatric asymptomatic refugees in Rhode Island who had parasites detected by various tests. Therefore, we conclude that routine testing for eosinophilia may inform treatment of potentially dangerous parasites in the absence of symptoms.

Disclosures
All Authors: No reported disclosures.
363. Autoimmune Sensory Neural Hearing Loss Apparently Triggered by Neurocysticercosis
Authors: Davies Evan , Arabshahi Alidad , Lateef Hamza A 
Published: December 2022

Abstract

Background
Meniere’s disease (MD) occurs when an abnormal amount of fluid causes increased pressure in the inner ear or labyrinth. People with Meniere's can experience symptoms including vertigo, tinnitus, hearing loss, and a feeling of fullness in the ear. Various triggers for MD have been recognized and range from smoking and alcohol consumption to recent viral illness, allergies and anxiety. We present the case of a 37 year old Hispanic male, who presented with dizziness and tinnitus, which progressed to include left sided sensorineural hearing loss and he was diagnosed with Meniere’s Disease, later found to be triggered by Neurocystercercosis.

Methods
Case report based on chart review.

Results
The patient's laboratory work up was positive for anti-HSP antibody and he had an abnormal electrocochleography, left greater than right. His vestibulonystagmogram was positive for both central and peripheral findings and bithermal caloric irrigations suggested abnormal peripheral function with a 57% weakness in the left ear.
The patient was also referred to rheumatology and neurology. Neurodiagnostic work up included an MRI which revealed a post inflammatory calcification in the right parietal lobe and patient was presumed to have neurocystercercosis. He was treated with steroids, betahistine, and a low salt diet for his MD.

Conclusion
To our knowledge, this is the first reported case in the literature of Meniere’s disease that may have been triggered by or concurrent with neurocysticercosis. This highlights the importance of a thorough work up to look for neurologic comorbidity for patients presenting with Meniere’s disease.
Neurocystercercosis is typically seen developing countries and is caused by the larval form of the parasite Taenia solium infecting the central nervous system. It commonly presents with seizures and such a manifestation associated with Meniere’s disease has not been previously reported.

Disclosures
All Authors: No reported disclosures.
368. Successful treatment of resistant visceral leishmania with repeated trial of Liposomal Amphotericin B- A Case Report
Authors: Mendiratta Ayushi , Adhikari Ramesh , Jagirdhar Gowthami Sai Kogilathota , Tirupathi Raghavendra , Kashyap Rahul , Sagar Vinay 
Published: December 2022

Abstract

Background
Although visceral leishmaniasis is endemic in various parts of India, management is still a challenge due to multiple drug resistance. Here we describe a case of a 50 years old female who was diagnosed with visceral leishmaniasis at a tertiary care hospital in northern parts of India and was managed with a repeated trial of liposomal Amphotericin B.

Methods
Case Discussion: The patient presented in the outpatient department with recurrent fever, mild intermittent abdominal discomfort associated with generalized weakness for the past one month. On per abdomen examination the patient had splenomegaly with spleen palpable 8 cm below the left costal margin. Blood investigations were suggestive of pancytopenia (leukocyte of 1800/cumm, Hemoglobin 7 g/dl, Platelet count: 80,000/cumm) along with severe neutropenia (Absolute neutrophil count: 400/cumm) . The CT abdomen showed massive splenomegaly (23 cm) with mild hepatomegaly . Leishmania Immunoglobulin G was positive. Bone marrow biopsy revealed hyperproliferative marrow with plasmacytosis (12-15%). Bone marrow Leishman-Donovan bodies were negative. Serum immunofixation was negative for M spike and serum light chain assay was also negative. She was managed with liposomal Amphotericin B (3mg/kg) for 7 days and was subsequently discharged. After 3 months, the patient again presented with continuous fever, lethargy, running nose, palpitations. Her blood work-up revealed severe pancytopenia again. She was tested for Leishmania anti- rk39 antibody, which was positive. She was given a repeat trial of Liposomal Amphotericin B with a different regimen-3 mg/kg dose on Day 1 to 5, followed by 6th dose on Day 14, followed by 7th dose on Day 21, as per the FDA approved regimen. Patient recovered well. The most recent total leukocyte counts eventually improved to 4800 with normal differential count. Platelets increased to 180,000, Hemoglobin was around 10.8g/dl and spleen was non palpable on physical examination.

Results
Treatment of leishmania can become complicated due to resistance to various drugs especially when a single agent is being given.

Conclusion
But in resource limited countries different regimens of liposomal amphotericin B can be tried which might be helpful due to speedy clinical recovery and cost effectiveness.

Disclosures
All Authors: No reported disclosures.
380. A molecular epidemiological exploration of reduced vancomycin susceptibility in Clostridioides difficile
Authors: Eubank Taryn A , Dureja Chetna , Hurdle Julian G , Garey Kevin W , Gonzales-Luna Anne J 
Published: December 2022

Abstract

Background
Use of vancomycin to treat Clostridioides difficile infection (CDI) has increased following recent IDSA/SHEA treatment guideline updates, applying a selection pressure for resistance development. We previously demonstrated acquired mutations in VanSR two-component system led to constitutive vanG expression and improved in vitro C. difficile survival in physiologic vancomycin concentrations. We aim to describe the molecular epidemiology of reduced vancomycin susceptibility in clinical isolates during a period of high vancomycin use.

Methods
A cohort study was performed including adult patients hospitalized with CDI in two health systems (14 hospitals) in the Houston Area between 2017-2021. (Stool transport) C. difficile were ribotyped by fluorescent PCR and susceptibility tested by agar dilution in accordance with CLSI standards. Reduced vancomycin susceptibility was defined by minimum inhibitory concentrations (MICs) &gt;2 mg/L. Sanger sequencing was conducted on a subgroup of isolates to identify VanSR mutations. Analysis using Chi square was performed using IBM SPSS Statistics (v 28.0.1.0).

Results
A total of 36% (165/465) of isolates exhibited reduced vancomycin susceptibility (MIC50 = 2 mg/L, MIC90 = 4 mg/L, range 0.5-16 mg/L), of which 348 were ribotyped. A significantly higher proportion of ribotype (RT) 027 isolates demonstrated reduced vancomycin susceptibility (83%) compared to other common ribotypes (30%); p&lt; 0.001). No differences based on collection year (p=0.3) or healthcare system (p=0.08) were observed. Overall, 11% (7/56) of isolates exhibiting mutations in VanS (n=1), VanR (n=5), or both (n=1). VanSR mutations were present in 47% (7/15) of those with MICs &gt;2mg/L vs 0% (0/41) of those with MICs ≤2 mg/L (p&lt; 0.001).

Conclusion
A high proportion of clinical C. difficile isolates exhibited elevated MICs to vancomycin, which was most common in RT027 isolates. Mutations in the vanG regulator, VanSR, correlated with elevated MICs in a subgroup of isolates. Future research is needed to expand upon molecular mechanisms and clinical implications of reduced vancomycin susceptibility.

Disclosures
Kevin W. Garey, PharmD, MS, Acurx Pharmaceuticals: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support|Seres Therapeutics: Grant/Research Support|Summit Pharmaceuticals: Grant/Research Support.
392. Guideline adaptation of fidaxomicin as first-line therapy for Clostridioides difficile infection in institutions across the United States
Authors: Basir Angela , Bradley Nicole , Lee Yuman 
Published: December 2022

Abstract

Background
In 2021, Clostridioides difficile infection (CDI) treatment guidelines were updated to recommend fidaxomicin over oral vancomycin as first-line therapy in initial and recurrent CDI episodes. Prior to this update, fidaxomicin use in management of CDI was limited, as cheaper alternatives were recommended as first-line therapy. The purpose of this study was to assess the guideline adaptation of fidaxomicin as first-line therapy in CDI management in institutions across the United States (US) and to identify barriers to its use.

Methods
An electronic survey was distributed to members of the American Society of Health-System Pharmacists in April 2022. Baseline demographics, current practices, and barriers to fidaxomicin use were collected. Results were analyzed using descriptive statistics. Fisher’s Exact Test was used to compare categorical variables.

Results
Based on 63 responses, majority of institutions (41/63, 65%) did not recommend use of fidaxomicin as first-line therapy for CDI. While most hospitals reported having institution specific CDI guidelines (48/63, 76%), over half of institutions with CDI guidelines still recommended oral vancomycin as first-line therapy (26/48, 54%). None of the institutions without CDI guidelines (0/15, 0%) recommended use of fidaxomicin as first-line therapy and majority of them (12/15, 80%) did not have fidaxomicin on formulary or restricted its use to ID services. Recommendation of fidaxomicin as first-line therapy was significantly higher in institutions with CDI guidelines versus those without (46% vs 0%, Fisher’s Exact 0.0006, p&lt; 0.05).
Approximately 92% (58/63) of respondents reported at least 1 barrier to using fidaxomicin, with 39.6% (25/63) reporting 2 or more barriers to use. Barriers identified were cost (55/63, 87.3%), lack of formulary inclusion (14/63, 22.2%), lack of provider familiarity (13/63, 20.6%) and inability of patients to afford upon discharge (7/63, 11.1%).

Conclusion
Majority of institutions do not currently recommend use of fidaxomicin as first-line therapy for CDI despite the recent guideline updates. Institutions with CDI treatment guidelines were more likely to recommend use fidaxomicin as first-line therapy. Cost and lack of formulary inclusion were cited as the most frequent barriers to fidaxomicin use.

Disclosures
All Authors: No reported disclosures.
400. Rehospitalization of Patients for Recurrent Clostridioides difficile Infection
Authors: Drwiega Emily , Johnson Stuart , Skinner Andrew M 
Published: December 2022

Abstract

Background
Clostridioides difficile infection (CDI) is an important cause of morbidity and mortality, especially in patients with recurrent episodes and those requiring re-hospitalization. Decreasing recurrent CDI (rCDI) and re-hospitalization for rCDI are important outcomes. The purpose of our study was to evaluate the impact of specialty care from an infectious disease (ID) or gastroenterology (GI) provider, either during the admission of the primary episode or in a follow-up appointment within 30 days.

Methods
This was a single-center, retrospective, chart review at a tertiary medical center. All hospitalized patients with a positive stool test for C. difficile (CD) (GI panel PCR, FilmArray, Biofire, or CD PCR, Xpert CD assay, Cepheid) with or without an ICD-10 code Enterocolitis due to CD (A04.7, A04.71, A04.72) from January 2018 through December 2018 were reviewed. Demographic and clinical data at the time of diagnosis and up to 90 days after discharge were collected.

Results
Our criteria identified 602 patients. We excluded 27 patients who died while hospitalized and 104 patients classified as colonized from analysis. Most patients (410/471, 87%) were determined to have a primary CDI episode. After discharge, 57 (14%) patients developed rCDI and 40 patients (10%) died within 90 days of discharge. Among those with rCDI, 40% (23/57) of patients had to be re-hospitalized due to their recurrence. Those re-hospitalized for rCDI developed their recurrence sooner (40% within 45 days, p &lt; 0.005) compared to patients with rCDI that were not re-hospitalized (Figure). ID/GI evaluated 173 of 471 (37%) patients during the index hospitalization or on hospital follow-up. Among patients evaluated by ID/GI, 10.4% had rCDI compared to the 13.8% with no ID/GI intervention. (p=NS). Only 3.5% (6/173) of patients evaluated by ID/GI were re-hospitalized vs 5.7% (17/298) of patients without ID/GI evaluation. (p=NS)
Time to CDI recurrence in re-hospitalized patients

Conclusion
In our study, 40% of patients who had rCDI had to be readmitted for their rCDI. Recurrence occurred significantly earlier in patients who were re-hospitalized. Patients evaluated by ID or GI had a decreased rate of re-hospitalization. Inpatient consultation and timely follow up of hospitalized CDI patients should be studied prospectively to determine the impact on rCDI re-hospitalization.

Disclosures
Stuart Johnson, M.D., Ferring Pharmaceuticals: Membership on Ferring Publication Steering Committee|Ferring Pharmaceuticals: Employee|Summit Plc: Advisor/Consultant.