bluuebunny/crossref_metadata_2025_split huggingface dataset:
347. Azole Activity against Filamentous Fungi Causing Invasive Infections in Patients from ICU and Non-ICU Units (2017-2021)
Authors: Carvalhaes Cecilia G , Rhomberg Paul , Rhomberg Paul , Schaefer Beth A , Pfaller Michael A , Castanheira Mariana 
Published: December 2022

Abstract

Background
Invasive fungal infection (IFI) is associated with high mortality rates in critically ill patients. Appropriate antifungal treatment is crucial for managing IFI. We evaluated the in vitro activity of isavuconazole (ISC), itraconazole (ITC), posaconazole (PSC), and voriconazole (VRC) against contemporary moulds from ICU and non-ICU patients.

Methods
1,226 moulds causing IFI (386/840 from ICU/non-ICU patients, respectively) were consecutively collected (1/patient) in 43 worldwide hospitals from 2017-2021 and susceptibility tested by CLSI broth microdilution. CLSI interpretation criteria were applied. Pneumonia was the predominant infection type among ICU (81.6%) and non-ICU (71.8%) patients.

Results
Aspergillus spp. was the most common mould (87.6%/80.5%). A. fumigatus (AFM; 76.0%/65.4% of Aspergillus), A. section Flavi (ASF; 9.2%/10.9%), and A. section Nigri (ASN; 7.4%/13.6%) were the top 3 Aspergillus groups. ISC inhibited 94.2%/91.2%, 100.0%/98.6%, and 96.0%/96.7% of AFM, ASF, and ASN from ICU/non-ICU, respectively, at the epidemiological cut-off values. Similar activities were noted for ISC, PSC, ITC, and VRC against AFM from ICU (MIC50/90 range, 0.25-1/0.5-1 mg/L) and non-ICU (MIC50/90 range, 0.5-1/0.5-2 mg/L) isolates. No difference in the azole activities was noted against ASF from ICU (MIC50/90 range, 0.5/0.5-1 mg/L) and non-ICU (MIC50/90, 0.5/0.5-1 mg/L) or ASN from ICU (MIC50/90 range, 0.5-2/1-4 mg/L) and non-ICU (MIC50/90 range, 0.5-2/1-4 mg/L) isolates. VRC-non-susceptible (NS) AFM isolates were detected in 9.3% of ICU and 9.0% of non-ICU isolates. Among VRC-NS AFM from ICU/non-ICU, 58.3%/27.5% were wildtype (WT) to ISC, 50.0%/25.0% were ITC-WT, and 75.0%/50.0% remained VRC-WT, respectively. VRC was the most active azole against Scedosporium spp. (SCE) but was less active against Mucorales (MUC) than the other azoles. All azoles showed limited activity against Fusarium spp. (FUS). No difference on azole activities against SCE, MUC, and FUS were noted from ICU and non-ICU isolates.

Conclusion
ISC was active against Aspergillus isolates from ICU and non-ICU, including against VRC-NS AFM from ICU. Azoles displayed similar activity against moulds from ICU and non-ICU units.

Disclosures
Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Paul Rhomberg, BS, MT(ASCP), Cidara: Grant/Research Support|Pfizer: Grant/Research Support Paul Rhomberg, BS, MT(ASCP), Cidara: Grant/Research Support|Pfizer: Grant/Research Support Beth A. Schaefer, BA, MT(ASCP), Pfizer: Grant/Research Support Michael A. Pfaller, MD, Pfizer: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.
352. Evaluation of Serial Serum (1-- &gt;3)-b-D-glucan Assay in Patients with Invasive candidiasis, Pneumocystis Jiroveci Pneumonia and Aspergillosis
Authors: Cari Evelyn Villacorta , Siddiqui Zubair , Leedy Nicole , Fenwick Alexander , Myint Thein 
Published: December 2022

Abstract

Background
Serum (1-- &gt;3)-b-D-glucan (BDG) assay is a noninvasive serological marker that can be used as an adjunct to the diagnosis of invasive candida infections, Pneumocystis jiroveci pneumonia (PJP) as well as aspergillosis. There is limited data in serial monitoring of serum BDG in those fungal infections after treatment was initiated. Figure 1:Serial serum BDG levels of each subject after treatment initiation

Methods
This is a cross-sectional study of subjects with proven fungal infection (invasive candidiasis, aspergillosis or PJP) and with increased serum BDG &gt;500 pg/ml who were admitted to University of Kentucky (UK) hospitals or clinics from 01/2012 to 01/2021. It was approved by institutional IRB. We compared at least two measures of the serum β-D-glucan levels obtained within two to eight weeks after initial diagnosis to evaluate the levels of β-D-glucan during and post-treatment. A decrease in BDG level is defined as any value below 500 pg/ml; normal serum BDG level as &lt; 80 pg/ml.

Results
Of 26 subjects included in this cohort, 14 (51.8%) subjects had invasive candidiasis, six (22.2%) subjects had PJP, and six (22.2%) subjects had invasive aspergillosis. Twelve patients did not have a repeat BDG level after at least two separate levels with &gt;500 pg/ml. Ten (38.5%) subjects had a decline in BDG level 2-3 weeks after starting treatment. Serum BDG level did not return to within normal limits at week 4 of treatment except one patient.
A repeat serum BDG level was seen decline at three weeks of treatment in four of six (66.6%) subjects with PJP, six weeks of treatment in three of six (50.0%) subjects with invasive aspergillosis and 8 weeks of treatment in six of 14 (42.8%) patients with invasive candidiasis. Two subjects had persistent elevation of BDG 8 weeks after treatment. (Figure 1)

Conclusion
Serial serum BDG level was not routinely done for monitoring the treatment response in this cohort. There was no linear decline in serum BDG level even after appropriate treatment in invasive fungal infections. A decline in serum BDG level was best observed among subjects with PJP pneumonia. It appears that the duration of a decline in serum BDG level was shorter in patients with PJP and longer in patients with invasive candidiasis.

Disclosures
All Authors: No reported disclosures.
358. Surveillance of Activity of Antifungals: Data from the Analysis of Resistance in Antifungals (ARIA) 2020 Study
Authors: Hawser Stephen , Kothari Nimmi , Lemos Bárbara 
Published: December 2022

Abstract

Background
ARIA is a new annual global surveillance initiative collecting yeast and fungal isolates from worldwide designed to determine resistance to antifungal agents and trends over time. The ARIA program was developed in 2020 to provide a repository of recent clinical fungal isolates with known susceptibility profiles and to monitor resistance trends over time. ARIA reports the susceptibility patterns of its earliest data concerning echinocandins, second-generation triazoles, and fluconazole against clinical Candida albicans, non-albicans strains including C. auris, Aspergillus and Fusarium isolates from worldwide sources.

Methods
Isolates were collected from hospital worldwide during 2020, shipped to a central laboratory and re-identified by MALDI-TOF or molecular methods. MIC tests were performed by broth microdilution method in line with CLSI susceptibility testing standards. Percentage of susceptibility was calculated according to CLSI breakpoints. Antifungals tested were amphotericin B (AMB), anidulafungin (ANID), fluconazole (FLU), isavuconazole (ISA), micafungin (MIC), posaconazole (POS), and voriconazole (VOR). All testing was performed according to CLSI M27-A4 and M38-A2 methodologies.

Results
See table.

Conclusion
Ongoing antifungal resistance surveillance like the ARIA program is of utmost importance in order to monitor the efficacy of traditional empirical therapy and for the development of novel antifungal agents. This repository and ongoing ARIA program will provide a resource to better support the biopharmaceutical industry’s goals to develop new and more potent antifungal agents.

Disclosures
All Authors: No reported disclosures.
364. Diagnosis of Amebic Liver Abscess by a Commercial Multiplex Stool Amplification Assay. A Potentially Useful Alternative in Limited-Resources Settings.
Authors: Murillo Jorge , Torres Jaime , Baquero Julio , Leal Vanessa , Jimenez Ana , Martinez Elena , Garcia Chloris 
Published: December 2022

Abstract

Background
Amoebic liver abscess (ALA) is caused by the protozoan parasite Entamoeba histolytica. Clinical and radiological features of ALA often mimic those of pyogenic liver abscess (PLA). Currently, differential diagnosis between ALA and PLA relys on microscopic examination, anti-amoebic IgG serology, and culture of aspirate for pyogenic organisms. Therefore, there is a need for new, rapid and more accurate microbiological methods for diagnosing ALA. Unfortunately, with few exceptions, available reports involved the use of inhouse or laboratory-tailored polymerase chain reaction (PCR) assays.
We herein report our recent experience with the successful use of a commercial multiplex, nested PCR assay designed for stool, in the diagnosis of two cases of ALA.

Methods
Two severely ill adult Latin American migrants presented with fever, malaise, non-bloody diarrhea, abdominal pain and leukocytosis. CT scans revealed single large hypodense, inflammatory, liver cystic lesions.

Results
Necrotic material obtained by needle aspiration under guidance and stool samples were processed by FilmArray Gastrointestinal Panel (BioFire Diagnostics, Salt Lake City), designed to detect 13 bacterial, 5 viral and 4 parasitic pathogens, both amplified only for E. hystolitica DNA. ELISA serology for amoeba was also positive. Bacterial cultures were sterile. Treatment with Metronidazole and paromomycin resulted in complete recovery.

Conclusion
Analysis of liver abscess content using a commercially available, multiplex, nested PCR assay designed for stool, may represent a convenient alternative to currently available diagnostic methods, providing rapid results and allowing for immediate choosing of specific therapy targeting single pathogens on more rational basis.
Since there are several commercially available multiplex PCR panels containing primers for E. histolytica, their use for evaluation of liver abscess samples has some theoretical advantages for the diagnosis of ALA, such as simplicity, ample availability, rapid processing time and capacity to exclude simultaneously several potential pathogens. Nevertheless, further testing is necessary to validate their use in liver abscess diagnosis and define their false positivity and negativity rates.

Disclosures
All Authors: No reported disclosures.
365. Hospitalizations Associated with Strongyloidiasis in the United States, 2003-2018
Authors: Inagaki Kengo , Bradbury Richard S , Hobbs Charlotte V 
Published: December 2022

Abstract

Background
Strongyloides stercoralis is considered to be historically endemic in Appalachia and the American South, but recent surveillance data, especially data evaluating strongyloidiasis associated with hospitalization, are lacking in most parts of the US.

Methods
We performed a population-based retrospective analysis on strongyloidiasis using the National Inpatient Sample from 2003-2018. Geographic distribution of strongyloidiasis associated hospitalization was assessed. Logistic regression was used to identify risk factors associated with strongyloidiasis.

Results
We identified 6931 hospitalizations associated with strongyloidiasis during the study period (11.8 per million hospitalizations). The rate of strongyloidiasis was highest in the US Northeast region including the Middle Atlantic division (47.1 cases per million population, adjusted odds ratio, aOR: 2.00 [95% confidence interval, CI: 1.58-2.53]), and the East South Central division (27.5 cases per million population, adjusted odds ratio, aOR: 2.77 [95% confidence interval, CI: 2.02-3.80]) (Figure 1, Figure 2). Older age, male sex, non-white race/ethnicity particularly Hispanic and Asian, non-private insurance, and residence in neighborhoods with low median income were also associated with strongyloidiasis (Table, Figure 2). Immunocompromising conditions, particularly human immunodeficiency virus infection, were present in 41.3% of hospitalizations with strongyloidiasis (Table). In-hospital death was seen in 7.8% of cases with strongyloidiasis-associated hospitalization.

Conclusion
Strongyloidiasis-associated hospitalization is rare in the U.S. but can be associated with mortality. It occurs more frequently in poor and marginalized populations. Immunocompromised conditions were common among hospitalized patients with strongyloidiasis. Enhanced surveillance efforts are needed to inform health policies for improving the health of at-risk populations.

Disclosures
Charlotte V. Hobbs, MD, Biofire (Biomerieux): Advisor/Consultant.
366. Optimization of a Surrogate Assay for Efficacy of a Malaria Transmission Blocking Vaccine
Authors: Meehan Cristina , Meehan Cristina , Duffy Patrick , Renn Jonathan , Zaidi Irfan 
Published: December 2022

Abstract

Background
An estimated 241 million malaria cases and 627,000 malaria deaths occurred worldwide in 2020. Efforts to develop a higher efficacy malaria vaccine are a global priority, but parasites pose a complex biological puzzle for vaccine development. Innovative vaccine strategies include transmission blocking vaccines (TBV) that target the mosquito stages of parasite development to interrupt parasite transmission. The current leading TBV called Pfs230D1-EPA targets Pfs230, a Plasmodium falciparum gamete surface protein that mediates binding of microgametes to red blood cells. Antibodies against Pfs230 bind and lyse gametes in a complement-dependent manner to block transmission.

Methods
Here, we are exploiting a panel of human monoclonal antibodies (hmAb) generated from human volunteers who received Pfs230D1-EPA formulated in Alhydrogel or AS01 adjuvants, to develop a competitive ELISA platform. This assay will quantify epitope-specific serum antibodies along with their features and effector functions, expanding the conventionally used functional assay of standard membrane feeding (SMFA).

Results
The competitive ELISA is being developed with single-chain variable fragments (ScFv) to define epitope-specific binding of antibodies in sera from vaccinated individuals. Sera of human volunteers from trials in Mali, Africa will be assayed to assess epitope-specific serum antibody binding that is competed off in the presence of saturating levels of ScFv. Preliminary optimization of the competitive assay has shown concentration-dependent epitope-specific competition between ScFv and hmAbs and confirmation of ScFv binding to Pfs230D1 antigen.

Conclusion
Further optimization of this assay will characterize the complement-binding and isotype/subclass-specific features of epitope-specific antibodies. These efforts will lay the foundations for standardized assays that can assess correlates of vaccine efficacy and durability of this leading TBV.

Disclosures
All Authors: No reported disclosures.
370. Toxoplasma gondii IgG Seropositivity is Associated with Increased Schizophrenia, Hospitalization, and 1-year Mortality— a Multicenter Research Network Study
Authors: Montalbano Gabrielle E , Reno Elaine , Rossetto Marika , Zhang Alexander , Kung Vanessa , Franco-Paredes Carlos , Vargas Barahona Lilian , Chastain Daniel B , Montoya Jose G , Henao-Martínez Andrés F 
Published: December 2022

Abstract

Background
Despite Toxoplasma seropositivity found in about one-third of the global population, we lack information about the clinical outcomes of patients with past exposure to this parasite without the manifested disease. We aim to evaluate 1-year mortality and mental health diagnosis in patients with Toxoplasma IgG seropositivity.

Methods
We queried a federated national multicenter network to validate mortality risk differences between Toxoplasma IgG seropositive and seronegative patients from 2010 to 2021, excluding patients with active disease. We used propensity score matching to assess independent mental health outcomes and mortality risk 1-year after serology.

Results
We found 6244 patients with Toxoplasma IgG positivity without toxoplasmosis and 29,179 patients with negative Toxoplasma IgG. Patients with positive Toxoplasma IgG were slightly older (46.1 ± 17 vs. 45±16.5, p&lt; 0.0001) and more likely to be Hispanic (15% vs. 12%, p&lt; 0.0001). Toxoplasma gondii IgG seropositivity was more often present in patients with neoplasms (25% vs 22%, &lt; 0.0001), type 2 diabetes mellitus (13% vs 12%, p=0.0284), and less likely in transplant recipients (7% vs. 8%, p=0.0015), and liver cirrhosis (5% vs 7%, p. &lt; 0.0001). Propensity score matching to 6099 seronegative patients adjusted for age, gender, race, ethnicity, heart disease, transplant, neoplasm, and cirrhosis found that seropositive patients had an increased risk of 1-year mortality (OR: 1.2, CI: 1.06-1.4, p=0.0036) (Figure 1), hospitalization (OR:1.2, CI: 1.1-1.3, p&lt; 0.0001) and schizophrenia (OR: 1.4, CI: 1.01-1.8, p=0.04). An increased risk was not seen with bipolar disorder (OR: 0.86, CI: 0.66-1.15, p=0.3206). Figure 1.Kaplan-Meier survival analysis comparing the survival probability of patients without toxoplasmosis with a positive toxoplasma IgG (purple line) to those with a negative Toxoplasma IgG (green line)

Conclusion
Toxoplasma IgG seropositivity without clinical disease is associated with an increased risk of one-year mortality, hospitalization, and schizophrenia diagnosis. Further prospective studies are needed to clarify the association of Toxoplasma exposure with schizophrenia and worse outcomes.

Disclosures
All Authors: No reported disclosures.
372. Analysis of the reliability of rapid diagnostic tests for varicella patients, including breakthrough cases
Authors: Higashimoto Yuki , Hattori Fumihiko , Kawamura Yoshiki , Kozawa Kei , Enya Yasuko , Ihira Masaru , Yoshikawa Tetsushi 
Published: December 2022

Abstract

Background
In the era of universal varicella vaccination, diagnosis of varicella is challenging, especially for breakthrough cases. We sought to clarify the reliability of direct varicella-zoster virus (VZV) loop-mediated isothermal amplification (LAMP) and DermaQuick® VZV using the immunochromatography technique as rapid diagnostic tests for varicella. In addition, the usefulness of saliva as a sample type for direct LAMP was also investigated.

Methods
Between April 2019 and January 2021, 46 patients suspected VZV infection were enrolled in this study. Written informed consent was obtained from the parents of all participants. This study was approved by the institutional review board of Fujita Health University (No. 15–247). Samples were collected from skin eruptions using two different swabs. one swab which was soaked in 1 mL of isotonic saline was used for direct VZV LAMP and the other swab which was immersed in 500 µL of DermaQuick® VZV reaction buffer was used for DermaQuick® VZV. The isotonic saline solution used to wash the oral swab sample was used for direct VZV LAMP. The DNA extracted from the solutions were used for real-time PCR analysis.

Results
Thirty one patients (67.3%) were diagnosed with varicella based on real-time PCR of skin swabs. Direct LAMP of skin swabs was positive in 29 (63.0%) of 46 patients. DermaQuick® VZV was positive in 25 (54.3%) of 46 patients. The sensitivity for direct LAMP of skin swabs, DermaQuick® VZV, direct LAMP of oral swabs, and real-time PCR of oral swabs was 93.6% (95% confidence interval [CI], 79.3–98.9%), 80.7% (95% CI, 63.7–90.8%), 48.3% (95% CI, 32.0–65.1%), and 74.2% (95% CI, 56.8–86.3%), respectively. The sensitivity and specificity of real-time PCR for DNA extracted from oral swabs was 74.2% (95% CI, 56.8–86.3%) and 93.3% (95% CI, 79.8–99.7%), respectively.

Conclusion
Although DermaQuick® VZV is the most convenient point-of-care test for varicella, the sensitivity and specificity of this method were slightly lower than those of direct VZV LAMP.

Disclosures
All Authors: No reported disclosures.
385. Impact of the COVID-19 Pandemic First Wave on Clostridioides difficile Infection
Authors: Mendo-Lopez Rafael , Pacheco Lauren , Villafuerte-Galvez Javier A 
Published: December 2022

Abstract

Background
Clostridioides difficile infection (CDI) is the leading cause of nosocomial diarrhea and a costly burden on the healthcare system. The COVID-19 pandemic brought enhanced infection control measures that could hypothetically decrease CDI transmission. Nonetheless, diarrhea secondary to COVID-19 and increased usage of broad-spectrum antibiotics could potentially increase testing for or frequency of CDI. We aimed to assess variations in CDI testing and frequency during the first surge of the COVID-19 pandemic in a tertiary community medical center in the Southern United States.

Methods
Records from adult patients were retrospectively reviewed at Princeton Baptist Medical Center, Birmingham, AL. Three groups spanning equal time periods were created based on the CDC COVID-19 rate curves for Alabama: PPG (pre-pandemic, 03/01/2020 to 05/31/2020), PG (pandemic, 06/01/2020 to 08/31/2020), and SCG (seasonal control, 06/01/2019 to 08/31/2019). We included patients ≥ 18 years old and excluded readmissions and follow-up visits. We determined the frequency, testing rates, and positivity rates for CDI in each group to assess their differences. Also, we measured the rate of coinfection between C. difficile and SARS-CoV-2. CDI cases were defined as positive toxin enzyme-linked immunosorbent assay (EIA) and glutamate dehydrogenase (GDH), or positivity of either in addition to positive nucleic acid amplification test (NAAT). Differences in frequencies and rates across groups were compared with Fisher exact test.

Results
Overall, 7,252 hospitalized patients and 29,671 outpatients were included (Figure 1). No outpatient CDI cases were detected. Outpatient testing rates were: PPG 3 (0.05%), PG 4 (0.05%), and SCG 9 (0.06%). Among inpatients, 3,912 (53.9%) were female with a mean ± SD age of 61.2 ± 17.5 years. Overall, CDI frequency, testing rates, and positivity rates did not vary significantly among all groups (Table 1). Among those tested, the only case of C.difficile/SARS-CoV-2 coinfection corresponded to PPG. Figure 1:Patient distributionTable 1:Frequency of CDI and COVID-19 infection in inpatients

Conclusion
There were no statistically significant differences in CDI frequency, or positivity rate between the pre-pandemic, pandemic, and seasonal control groups for inpatients. No CDI cases were detected in outpatients. This is likely due to a low testing rate in our population.

Disclosures
All Authors: No reported disclosures.