bluuebunny/crossref_metadata_2025_split huggingface dataset:
484. Vaginal Candida albicans: High Frequency of In-vitro Fluconazole Resistance in a Select Clinical Population.
Authors: Agrawal Pranjal , Yazdy Golsa M , Ghanem Khalil G , Handa Victoria L , Sobel Jack D , Zhang Sean , Tuddenham Susan 
Published: December 2022

Abstract

Background
In vitro fluconazole resistance in vaginal C. albicans has rarely been reported in the U.S. Little is known about the characteristics of patients who demonstrate fluconazole resistance vs. sensitivity, or how likely resistant strains are to persist over time. Hence we sought to describe patterns of fluconazole resistance in clinician ordered vaginal cultures positive for C. albicans at our center. We compared patient characteristics between those with fluconazole sensitive versus resistant isolates.

Methods
We conducted a chart review of patients with clinician ordered vaginal cultures positive for C. albicans undergoing fluconazole susceptibility testing in our medical center’s clinical mycology lab from January 2017 to April 2021. Patient characteristics were compared using chi-square and ANOVA tests and correlated to fluconazole resistance with logistic regression models.

Results
Of N=92 patients with vaginal C. albicans, 3.3% were sensitive dose-dependent (SDD: minimal inhibitory concentration (MIC) =4) to fluconazole, and 30.4% were resistant (R: MIC &gt; =8). Amongst those with at least 2 previous episodes of vulvovaginal candidiasis (VVC) in the past 6 months (N=45), 50% had R and 6.5% had SDD isolates. Compared to those with sensitive (S: MIC &lt; =2) isolates, patients with SDD or R were younger and more likely to have the following characteristics: Black race, bacterial vaginosis (BV) in the past year, high or multi-dose azole treatment, fluconazole suppressive therapy in the past 6 months, and more VVC and BV episodes in the previous 6 months (Table 1). Of N=10 patients who had a follow-up culture with initial R isolates, 28.6% had a sensitive C. albicans vaginal isolate.

Conclusion
The frequency of C. albicans vaginal isolates with in vitro resistance to fluconazole in this study was high. Our findings highlight the importance of obtaining cultures and sensitivity testing in patients with recurrent or refractory VVC. However, resistant vaginal strains may not necessarily persist over time. Future, larger studies on those with recurrent VVC are needed to verify factors associated with fluconazole resistance, how frequently azole-resistant strains persist over time, and how well in vitro resistance correlates to in vivo treatment response.

Disclosures
Susan Tuddenham, MD, MPH, Luca Biologics: Advisor/Consultant|Medscape/WebMD: Honoraria|UpToDate: Royalties.
495. Enterovirus Genotype Specific Immune Response in Cerebrospinal Fluid of Infected Infants
Authors: Shore Kayla , Sasidharan Anjana , Lee Brian R , Hassan Wail M , Harrison Christopher J , Selvarangan Rangaraj 
Published: December 2022

Abstract

Background
Non-polio Enteroviruses (EV) are important neonatal CNS pathogens. Multiple EV genotypes have been detected in pediatric CSF, e.g. Echovirus (E) 6 and E30. CSF innate immune responses to EV genotypes remain poorly defined. Most data are from EV-A71 or E30 CNS infections and do not compare responses between these or other EV types. We sought to better define innate immune responses to EV genotypes in CSF.

Methods
Salvaged standard of care CSF samples from ≤6 month olds (real time EV PCR(+) or EV PCR(-) controls) from Jan 2010 - Dec 2020 were tested in duplicate on a 21- cytokine bead panel (MilliporeSigma). EV positive samples were previously genotyped by sequencing the viral capsid gene. Cytokine levels calculated from the standard curve were compared by Kruskal-Wallis and post-hoc analysis (GraphPad Prism 8.4.3). Natural partitioning of participants was explored using principal component analysis and cluster analysis (IBM SPSS v27). The utility of cytokine signatures in predicting EV status was explored using discriminant analysis and ROC analysis (IBM SPSS v27).

Results
Data from 72 CSF with E6 (N=16), E9 (N= 9), E18 (N=9), and E30 (N=21) showed significant differences among EV genotypes vs. controls for 20 cytokines (IL-17 was excluded). Significant differences in cytokine levels in EV CSF vs controls were seen: E6 for all 20 cytokines; E9 for Fractalkine, IP10, and MCP1; E18 for Fractalkine and MCP1; E30 19 cytokines (not GM-CSF). PCA revealed only minor overlap of controls and EV positives; EV types overlapped, except E30, differing most from E9 and E18 but overlapping E6. The most important type-differentiating cytokines by PCA were MCP1, Fractalkine, IL-8, and IL-10. Patterns in DA resembled PCA; controls clearly separated from EV CSF, E30 being the most distinct. Overall, the discriminant model correctly classified EV type or controls at a 63% rate - highest for controls (94.1%) and E30 (74.1%). In the DA model, the most important cytokines were IP-10, IL-2, IL-1Ra, and Fractalkine. Discriminant scores had the largest area under the curve (AUC), 0.990. Among cytokines, IFNa2 had the largest AUC, 0.987.

Conclusion
Preliminary data show significant EV-genotype differences in innate immune response to CNS infections. Cytokine patterns may serve as a key predictor for discerning EV genotypes.

Disclosures
Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: Grant/Research Support Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support.
503. Lack of coronary aneurysms during Kawasaki Disease (KD) correlates with higher levels of autoantibodies to both full form and spliced variant of immune regulator EDIL-3 (Del-1)
Authors: Ross Welliver R , Prakash Aviraag Vijaya , Hicar Mark D 
Published: December 2022

Abstract

Background
Kawasaki disease is a rare multisystem inflammatory condition that mainly affects children under the age of 5 years. Current theory of the pathogenesis is that an infectious stimulus triggers an autoimmune reaction in a genetically susceptible child. Recent studies demonstrated an association with autoantibody response to EDIL3 (also known as DEL-1) in children with KD. EDIL3 is an extracellular matrix protein which is expressed both in macrophages and vascular endothelium. EDIL3, has an anti-inflammatory role by preventing leucocyte migration to inflammatory sites. Del-1 has two expression variants and genetic variants of Del-1 have been associated with the risk of intracranial aneurysms. Due to the physiologic plausibility for a role during KD, we chose to assess if autoantibodies against EDIL3 are seen in a larger cohort of children with KD and to assess if responses correlated to aneurysm formation.

Methods
We assessed plasma samples from a cohort of febrile children, including Kawasaki disease with ELISA assay using recombinant EDIL3 using ELISAs.

Results
Time course samples of KD (pre-IVIG, post-IVIG and convalescent) from two different patient cohorts showed that there is increased autoantibody levels against EDIL3 in the post-IVIG samples, which is consistent with the commonality of antibodies. Contrary to prior findings, in comparison to febrile controls, autoantibodies were not higher in children with Kd. Correlation with signs of cardiac inflammation showed lower autoantibody levels.

Conclusion
Auto-antibodies to EDIL3 are common in febrile children and, like other autoantibodies, are seen in IVIG formulation. Lower levels of these may be a susceptibility marker for KD or may be sequestered during aneurysm formation.

Disclosures
All Authors: No reported disclosures.
512. The relationship of Clostridioides difficile in-vitro antibiotic resistance, prior exposure to antibiotics and ribotype: A single center study
Authors: Alsoubani Majd , Thorpe Cheleste M , Walk Seth , McDermott Laura A , Snydman David R 
Published: December 2022

Abstract

Background
Antibiotic exposure is the most important risk factor for Clostridioides difficile associated diarrhea (CDAD). Little information has been reported on the relationship between prior antibiotic exposure, antibiotic resistance of C. difficile, and isolate ribotype.

Methods
C. difficile isolates were collected from the stools of patients with CDAD. Isolates were ribotyped by PCR-based fragment analysis. Susceptibility testing was performed using Clinical & Laboratory Standards Institute (CLSI) recommended methods. MIC results were interpreted using European Committee on Antimicrobial Susceptibility Testing (EUCAST) epidemiologic cut off values or the CLSI breakpoints. Demographic data and antibiotic exposure in the 30 days period prior to C. difficile isolation were collected via retrospective chart review.

Results
Of a total of 490 C. difficile isolates, 335 (67.3%) isolates were resistant to one or more antibiotics (Table 1). Patients who had higher Charlson Comorbidity Score (CCI) and who had hospital associated CDAD were more likely to receive antibiotics (Table 2). Moxifloxacin resistance was significantly associated with prior fluoroquinolone exposure (OR 2.5, CI 95% 1.5-4.1). Fluoroquinolone use was associated with vancomycin resistance (OR 2.7, CI 95% 1.3-5.6) and rifampin resistance (OR 1.9, CI 95% 1.2-3). Infection with a clindamycin resistant isolate was more likely to be hospital acquired (p = 0.006). We identified 54 different ribotypes (Figure 1). Prior treatment with aminopenicillins increased the odds of acquiring ribotype 053-163 (OR 2.9, 95% CI 1.0-8.2) and ribotype 002 (OR 3.2; CI 95% 1.0-10) (Table 3). .Prior treatment with cephalosporins had an increased risk of 014-020 (OR 2.0, CI 95% 1.2-3.3); prior treatment with carbapenems was associated with ribotype 106 (OR 2.3, CI 95% 1.2-4.4). Isolation of ribotype 027 following prior treatment to fluroquinolones was marginally significant (p = 0.054).

Conclusion
Specific antibiotic exposure may select for infection by specific C. difficile ribotypes, which can often lead to infection with resistant strains. Prior fluoroquinolone treatment, in particular, was associated with an increased risk of isolating multi-drug resistant strains.

Disclosures
Cheleste M. Thorpe, MD, Actelion: Grant/Research Support|Deinove: Advisor/Consultant|General Mills: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Grant/Research Support|Summit: Advisor/Consultant|Summit: Grant/Research Support David R. Snydman, MD, Merck: Advisor/Consultant|Merck and Company: Grant/Research Support|Prolacta: Advisor/Consultant|Prolacta: Grant/Research Support|Seres: Advisor/Consultant|Seres Health: Grant/Research Support|Summit Plc: Grant/Research Support|Takeda: Advisor/Consultant|Takeda: Grant/Research Support|Visterra: Advisor/Consultant.
518. Characterization of colistin-resistant (COL-R) Acinetobacter baumannii calcoaceticus complex (ABC) isolates from a recent, global Phase 3 trial (ATTACK)
Authors: Moussa Samir , McLeod Sarah , Miller Alita 
Published: December 2022

Abstract

Background
Due to the lack of effective therapies, last-resort agents such as colistin are more frequently being used to treat drug-resistant ABC infections. Consequently, COL-R ABC is becoming more common, with some countries such as Greece reporting rates of &gt;50%1. The efficacy and safety of sulbactam-durlobactam (SUL-DUR) was recently compared to COL, both on a background of imipenem/cilastatin therapy, in patients with ABC infections, including those caused by multidrug-resistant strains. SUL-DUR was non-inferior to colistin with respect to 28-day all-cause mortality (19 vs. 32.3%). SUL-DUR therapy resulted in higher clinical cure rates and significantly improved safety compared to COL. Here, we describe COL-R ABC in ATTACK.

Methods
Antibiotic susceptibility was determined by broth microdilution according to CLSI guidelines at IHMA, Inc. COL-R was defined as MIC ≥ 4 µg/ml. Next generation sequencing was performed using Nextera® libraries on an Illumina MiSeq system (San Diego, CA) at JMI Laboratories. Assembly and analysis were performed using CLC Genomics Workbench.

Results
17% (30 of 175) baseline ABC isolates from m-MITT (microbiologically modified Intent-to-Treat) patients were COL-R. All were extensively drug-resistant2 and 26 were pan-drug resistant (PDR). Two additional ABC isolates became COL-R in patients with pneumonia who received COL therapy; neither patient survived to 28 days. Most came from 5 clinical sites: Hungary (N = 9), Russia (N = 7), Greece (N = 6), Israel (N = 4) and Turkey (N = 2). No COL-R ABC was found in China or the Americas. Sequencing analysis on selected isolates suggested sites in Hungary and Russia had clonal outbreaks, whereas others were non-clonal but closely related ( &gt;99%). SUL-DUR was highly active in vitro against COL-R ABC isolates, with an MIC50/90 of 2/4 µg/ml. Of the 22 patients with COL-R ABC infections treated with SUL-DUR, 17 (77%) survived to 28 days with clinical and microbiological cure at test-of-cure (TOC).

Conclusion
A notable number of ABC infections in ATTACK were COL-R, most of which were PDR but susceptible to SUL-DUR at ≤ 4 µg/ml. If approved, SUL-DUR could be an effective treatment for patients with these types of infections.
1. Nowak (2017) JAC, 72, 3277–3282
2. Magiorakis (2012) CMI,18, 268-81

Disclosures
Samir Moussa, PhD, Entasis Therapeutics: Employee|Entasis Therapeutics: Stocks/Bonds Sarah McLeod, PhD, Entasis Therapeutics: Employee|Entasis Therapeutics: Stocks/Bonds Alita Miller, PhD, Entasis Therapeutics: Ownership Interest|Entasis Therapeutics: Stocks/Bonds.
530. Characterization of the Proteomic Changes via SARS-CoV-2 Infection or Vaccination in the COVID-19 Community Research Partnership (CCRP)
Authors: DeWitt Michael E , Herrington David M , Williamson John C , Seals Austin L , Wierzba Thomas F , Binek Aleksandra , Van Eyk Jennifer , Sanders John W 
Published: December 2022

Abstract

Background
There remain important gaps in knowledge concerning the effects of SARS-CoV-2 infection or vaccination on the human blood proteome.

Methods
The CCRP is a longitudinal surveillance study with information on SARS-CoV-2 infections, vaccinations and associated humoral immune responses in over 37,000 individuals. We selected a sample of blood spots cards (n=510) from serum antibody studies obtained between October 2020 and April 2021 for mass spectrometry proteomics analysis covering 540 unique plasma proteins. We analyzed the quantified protein differences based on dried blood samples obtained before and after infection or vaccination among previously non-infected individuals (immune naïve) after adjustment for batch effects, age, sex, or prior diagnosis of cancer, cardiovascular or autoimmune disease, or diabetes. The majority of infected individuals were minimally symptomatic. Differentially expressed proteins were considered significant with an FDR adjusted p-value of &lt; 0.05 and log2 fold change (L2FC) &gt;0.2.

Results
We found 11 and 12 proteins differentially expressed proteins in the naïve/infected and naïve/vaccinated people respectively, of which 10 were shared. Hepatocyte growth factor receptor (HGF) was upregulated (L2FC 0.24; p &lt; 0.001) only in those who were infected while fibrillarin (L2FC -0.24; p&lt; 0.001) and lambda-crystallin homolog (L2FC -0.29, p &lt; 0.001) were downregulated only in the vaccinated samples (Fig 1). The remaining DE protein were associated with a wide array of functions including metabolic, cytostructural, extracellular matrix and DNA regulatory processes.

Conclusion
We found changes in the proteome both from infection and vaccination. HGF, elevated in the infected, has been associated with endothelial inflammation, upregulation of pro-inflammatory cytokines to reduce lung fibrosis and is known to promote tissue repair. Fibrillarin, downregulated in the vaccinated, has been associated with higher rates of bacterial and viral clearance, inflammation reduction, and increased cell survival. These findings suggest detectable complex inflammation from mild to moderate infections. Further investigation is required to understand the mechanism of action and clinical implication of these findings.

Disclosures
All Authors: No reported disclosures.
536. Evaluation of the Clinical Utility of Universal Polymerase Chain Reaction Testing
Authors: Donkin Joshua D , Emery Rebecca P , Polega James , Behenna Curtis J , Caulfield Adam J , Simeunovic Gordana 
Published: December 2022

Abstract

Background
Despite advances in microbiologic techniques, for patients with complex infections it often remains a challenge to identify the causative infectious pathogen. Traditional cultures (Cx) may fail to grow microorganisms due to inadequate sampling, prior antibiotic use, or the inherent insensitivity of culture methods for fastidious pathogens. Molecular tests allow for the detection of microbial nucleic acids directly from clinical specimens and do not require the presence of viable organisms for identification. Universal polymerase chain reaction testing (UPCR) is offered though the University of Washington Department of Laboratory Medicine and Pathology as a metagenomic approach using broad-range PCR primers followed by sequencing to hypothetically identify any pathogen present. The testing is composed of 3 separate tests for bacterial (BUPCR), fungal (FUPCR), and acid-fast (AFUPCR) organisms. The utility of UPCR has not been formally evaluated. Our objective is to describe the diagnostic utility of UPCR by comparing Cx and UPCR results, and their impact on management. Figure 1:Introduction - Types of Universal PCR Testing

Methods
We retrospectively collected data on UPCR and culture results and changes in antimicrobial therapy based on UPCR results for all patients with at least 1 UPCR test done during the 2-year study period.

Results
367 UPCR tests were performed over 24 months on 155 patients. From 367 tests, 119 were FUPCR, 111 AFUPCR, and 137 BUPCR.
32/155 (20.6%) patients had positive UPCR. 25/32 were BUPCR and 7/32 were FUPCR. No AFUPCR was positive.
In 8/155 (5.2%) patients management was changed based on UPCR results: Positive UPCR results directed treatment in 5 patients: 4 patients had positive UPCR and negative culture, and 1 had both UPCR and Cx positive but for different organisms. In all 5 therapy was changed in favor of UPCR result. All 5 tests were BUPCR.Negative UPCR led to antimicrobial discontinuation in 3 patients.
11/155 (7.1%) patients had negative UPCR and positive Cx, 10 of which were BUPCR and 1 AFUPCR. These results did not change management. Figure 2:Results – Type of Tissue and Test ResultsFigure 3:Results – Universal PCR Test Type and ResultsFigure 4:Results - Summary

Conclusion
Based on the real-world experience, UPCR results have limited impact on antimicrobial management in our institution. Further studies may try to identify clinical scenarios where UPCR may be of better clinical utility.

Disclosures
All Authors: No reported disclosures.
540. Impact on Clinical Decision Making of Microbial Broad Range Metagenomic Cell-Free DNA at a Single Academic Medical Center, a Retrospective Study
Authors: Olthoff Michael C , Kobayashi Takaaki , Parsons Meredith , Ford Bradley A , Prasidthrathsint Kunatum , Non Lemuel R , Diekema Daniel , Ince Dilek , Salinas Jorge 
Published: December 2022

Abstract

Background
Broad-range metagenomic cell-free DNA testing (Karius®) can identify a variety of pathogens from a single blood sample to help in diagnosis of deep seated and bloodstream infections. Few studies have evaluated the impact of Karius testing on clinical decision making when compared to more conventional diagnostic methods.

Methods
We performed a retrospective cohort study of adult patients who had Karius tests at University of Iowa Hospitals and Clinics between 01/2020 and 10/2021. Chart review was conducted to obtain patient characteristics and clinical course including patient age, immunocompromising conditions, involvement of Infectious Disease (ID) consultant, reason for the test, and final diagnosis. Results of the Karius tests and conventional tests were compared for concordance. Clinical impact and change in management due to Karius testing were determined using previously established criteria outlined by Hogan et al.(Clin Infect Dis. 2021 Jan 27;72(2):239-245)

Results
Out of 26 patients who had Karius testing, 20 patients (77%) had an immunocompromising condition, the most common of which was hematologic malignancy (17 patients, 65%). Twenty-four patients (92%) had received a formal ID consultation prior to the test. The most common finding prior to testing was the presence of pulmonary infiltrates on imaging (20 patients, 77%). Karius testing was positive in 18/26 cases (69%). Organisms detected by Karius and conventional testing were concordant in 9/18 cases (50%). Karius test result had a positive clinical impact in 3 cases (12%), an indeterminant impact in 1 case (3%) and no impact in 22 cases (85%). Reasons for a positive impact are as follows: 1 case with initiation of antituberculosis therapy due to earlier diagnosis of tuberculosis, 1 case with de-escalation of antifungal therapy based on negative Karius results, and 1 case of clearance for urgent lung transplantation based on negative Karius results in the setting of mobile echo density on echocardiogram in the absence of other stigmata of endocarditis.

Conclusion
The impact of Karius testing on patient management appears limited. Further studies will be needed to identify patient populations or disease factors in which this testing have clinical impact.

Disclosures
All Authors: No reported disclosures.