bluuebunny/crossref_metadata_2025_split huggingface dataset:
860. Molecular Characterization of Isolated Staphylococcus aureus Specimens Using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS)
Authors: Dawning Amber , Lin Xiting , Jerris Robert C , Thornton Kevin , Mohamed Noor , Immergluck Lilly 
Published: November 2023

Abstract

Background
Staphylococcus aureus (S. aureus) is a common cause of skin and soft tissue infections (SSTIs). Both the β-lactam resistant form, methicillin resistant S. aureus (MRSA), and non-resistant form, methicillin susceptible S. aureus (MSSA) are associated with disparate infections across age and race; community-associated infections are often due to S. aureus US300. Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) is a used in clinical microbiology laboratories to identify bacterial species, but limited data is available on if this tool can identify different strains of S. aureus. We hypothesize that MALDI-TOF MS can be used to identify strain-specific peaks of S. aureus USA300.

Methods
Children were enrolled from emergency departments and swabbed for S. aureus (anterior nares, axilla, perirectal, oropharyngeal, and wounds) during two time periods (2006-2008 and 2015-2016). MALDI-TOF MS was performed on S. aureus cultured from study participants. Default parameters used for variance stability, smoothing, baseline subtraction, and normalization in R 4.4.3. and MALDIquant v1.22 were applied to raw data. Peak detection and alignment were performed with a signal-to-noise ratio of three and tolerance of 300 ppm. Binning and machine learning algorithms were used to identify intensity differences of each peak identified; significance of peaks was determined using Chi Square statistical analyses, comparing MRSA and MSSA, and then between all S. aureus isolates compared to USA300. Statistical significance was considered with p-value &lt; 0.05 using R and SAS 9.4.

Results
From 57 MRSA and 53 MSSA isolates, 320 peaks were identified. 31 significant peaks were identified, with 14 unique peaks for MRSA and 17 for MSSA. With S. aureus USA300, eight of the 31 peaks remained statistically significant.

Conclusion
MALDI-TOF MS can identify unique peak differences between MRSA and MSSA. This tool can be potentially used to distinguish S. aureus at the strain level in a clinical setting. MALDI-TOF MS can be an impactful and rapid diagnostic tool to detect antibiotic resistance in S. aureus in a clinical setting.

Disclosures
Lilly Immergluck, MD,MS, Melinta: Grant/Research Support|Melinta: Grant/Research Support
861. Development and Clinical Validation of a Custom Modified Two-Tier Testing Algorithm for Serodiagnosis of Lyme Disease
Authors: Gaylord Michelle A , Baranova Danielle , Pride Michael W , Simon Raphael , Anderson Annaliesa S , Kalina Warren Vincent 
Published: November 2023

Abstract

Background
Diagnosis of Lyme Disease has relied on measuring the serological response to Borrelia sp. Over the years the rigor of serological diagnosis has evolved to meet the needs of the clinic and vaccine manufacturers, where the latter require especially sensitive and specific tests to measure efficacy. Likewise, current US guidelines recommend a two-tier testing approach to diagnose Lyme Disease. Among a constellation of commercially available in vitro diagnostics, two highly sensitive immunoassays with Borrelia sp. antigenic diversity were characterized for utility as a custom Modified Two-Tier Testing (MTTT) algorithm. This custom algorithm consists of a first tier assay from Bio-Rad and a second tier assay from Zeus Scientific, and was developed to capture cases of Lyme Disease.

Methods
The BioPlex 2200 Lyme Total assay from BioRad and VlsE1/pepC10 IgG/IgM ELISA from Zeus Scientific were evaluated as the first and second tier assays in the custom MTTT, respectively. The MTTT was clinically assessed for diagnostic accuracy and compared to the highly characterized CDC Pre-Marketing Panel, which is composed of samples from US donors diagnosed with Lyme Disease, “look-alike” diseases or healthy individuals. Other clinically relevant sample populations were benchmarked off the predicate FDA-approved MTTT, also from Zeus Scientific.

Results
The custom MTTT, described here, was more clinically specific than either test alone and was more clinically sensitive than the only other FDA-approved MTTT. When matched against the FDA-approved predicate method, sensitivity and specificity was 100%. The custom MTTT also detected fewer “look-alike” disease samples than either test alone, or the FDA-approved MTTT. Furthermore, detection of early Lyme Disease in the CDC Pre-Marketing panel was 80% sensitive. In addition, the custom MTTT identified Lyme disease in 98.6% of Lyme Disease samples collected from samples that originated in Europe.

Conclusion
The clinically validated custom MTTT method, described here, has utility as a Lyme Disease diagnostic and is a highly specific tool for assessing efficacy of Lyme Disease vaccines currently in development.

Disclosures
Michelle A. Gaylord, PhD, Pfizer Inc.: Stocks/Bonds Danielle Baranova, PhD, Pfizer Inc: Stocks/Bonds Michael W. Pride, PhD, Pfizer: Stocks/Bonds Raphael Simon, PhD, Pfizer: Stocks/Bonds Annaliesa S. Anderson, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Warren Vincent. Kalina, PhD, Pfizer: Stocks/Bonds
867. Diagnostic test accuracy of TRAIL, IP-10 and C-RP biomarker combination (MeMed BV test) for discrimination of viral vs. bacterial infections among Emergency Department patients with febrile illness: A Systematic Review and Meta-analysis
Authors: Kandula Manasa , Farrell John J 
Published: November 2023

Abstract

Background
Infections (eg. RSV, influenza & Streptococcus pyogenes) have surged following discontinuation of social distancing and masking. Emergency Department (ED) providers feel pressure to prescribe antibiotics for common presentations such as fever for fear of missing a case of Group A Strep, which can lead to antibiotic misuse. Multiplex PCR assays are costly and cultures take 1-2 days to result, and lack sensitivity when antibiotics have already been started. There is a need for a rapid, affordable, and accurate method to distinguish bacterial from viral infections. Some prospective studies have demonstrated that a diagnostic assay that combines CRP with IP-10 and TRAIL can effectively assist ED providers with decisions regarding antibiotic therapy in patients with a febrile illness.

Forrest plot of the individual and composite direct odds ratios (DOT) respectively for the nine studies included in the meta-analysis

Summary Receiver Operating Characteristic (SROC) analysis of the diagnostic accuracy of the MeMed BV test. The SROC analysis was applied to the data which was pooled from all nine studies included in this meta-analysis

Methods
The analysis was registered with PROSPERO prior to following PRISMA-DTA framework, which yielded 9 studies with 4X4 tables for sensitivity, specificity, and diagnostic accuracy of the BV test for bacterial vs. viral infection. Articles were searched in PubMed, Medline, Google Scholar and Ovid. Random effects models were used to calculate pooled proportions. The estimated total effect sizes, test for heterogeneity and moderator effect, and ROC curve are reported using R software.

Results
9 prospective studies were included with a total of 4084 patients (3271 cases and 813 controls). The proportion of the random effect model was 0.841 (95% CI, 0.788 to 0.882). The total effect sizes of all nine studies are shown. The OR of the random effect model is 124.2 (95% CI, 77.3 to 199.4) and p-value &lt; 0.0001, meaning the OR of a positive BV test result among persons with disease was approximately 124 times higher than the OR for a positive test among persons with no disease. The bivariate diagnostic random-effects meta-analysis for viral vs. bacterial infection AUC = 0.973.

Conclusion
Across 9 studies performed over 8 years, the combination of TRAIL, IP-10 and C-RP biomarkers (BV test) accurately distinguished between bacterial and viral infections in patients with febrile illness. The test has the potential to be used to facilitate timely diagnosis and antimicrobial treatment decisions. Further large scale studies are needed to establish its role in antimicrobial stewardship.

Disclosures
All Authors: No reported disclosures
871. Clinical Detection of Intestinal Protozoa in Digitized Modified Trichrome-Stained Stool Specimens using a Deep Convolutional Neural Network Assisted Workflow
Authors: Morris Heather Rose , Pritt Bobbi S , Norgan Andrew 
Published: November 2023

Abstract

Background
Deep convolutional neural networks (DNN) have been successfully applied to the detection and segmentation of objects in gigapixel digital slides. In this study, trained laboratory technologists utilized a DNN-assisted digital workflow (Techcyte, Inc.; Orem, UT) to evaluate clinical stool specimens for the presence and identification of protozoan parasites.

Methods
Slides were prepared from 142 stool specimens by spreading a thin layer of concentrated stool onto a slide, staining with modified-trichrome, and coverslipping with permanent mounting medium. Slides were then scanned using a NanoZoomer 360 digital slide scanner (Hamamatsu Photonics K.K., Japan) at 40x apparent magnification and prospectively analyzed by the Techcyte DNN. Objects of interest were identified and classified by the DNN (protozoa, leukocytes, erythrocytes) and presented to a laboratory technologist for interpretation. (See example image below.) DNN-assisted results were compared to those from conventional microscopic examination. To determine analytical sensitivity, slides were prepared from serial, 2-fold dilutions of 3 unique stool specimens (6 slides at each dilution/specimen) and analyzed by the DNN-assisted method and conventional microscopy.
Example of Techcyte DNN analysis review screen
Objects of interest most likely to be significant are presented to the technologist for review in an intuitive web-based format. Parasites are confirmed as present or absent by a trained technologist after reviewing these images.

Results
Digital analysis was highly reproducible, showing 100% slide level agreement (positive/negative) within and between runs using positive and negative slides. There was 98.7% and 98.3% positive and negative agreement, respectively, between conventional and DNN-assisted results. Of the 142 slides conventional microscopy detected parasites in 82, while the DNN-assisted method detected 83. The DNN-assisted method also detected more slides with leukocytes (29 vs 24) and erythrocytes (12 vs 8). All discrepant results were confirmed by repeat conventional microscopy. Analytical sensitivity of the DNN-assisted method was equivalent or superior to conventional microscopy review, detecting down to 1:64 dilutions in 6/6 slides per specimen (conventional = 1:32 to 1:64), extending for some slides to detection at dilutions of 1:2048.

Conclusion
The DNN-assisted method facilitates rapid screening of negative specimens, while providing sensitive and accurate detection and classification of protozoa.

Disclosures
All Authors: No reported disclosures
874. Rapid Prediction of Antibiotic Susceptibility in Blood Stream Infections Using Direct Sequencing from Blood Cultures Coupled with Neighbour-Typing Prediction Algorithms.
Authors: Purssell Andrew , Carroll Amanda C , Puchacz Natalia , Mortimer Leanne , MacFadden Derek 
Published: November 2023

Abstract

Background
Increasing rates of antimicrobial resistance in Gram-negative (GN) bacteria make empiric treatment challenging. Culture-based techniques form the basis of pathogen and antibiotic susceptibility determination yet are limited by long turn-around-times that can prolong the time a patient remains on inappropriate therapy. Direct sequencing of positive blood cultures coupled with neighbour-typing prediction algorithms could help anticipate antibiotic susceptibility and improve selection of empiric therapy. We sought to develop a rapid metagenomic diagnostic workflow and evaluate its performance for blood stream infections.

Methods
We developed a metagenomic workflow for pathogen identification and prediction of antibiotic susceptibilities outlined in Figure 1. We performed Nanopore-based metagenomic sequencing on positive blood cultures from critically ill patients admitted to a quaternary care center. Isolates belonging to six common GN blood stream pathogens were subjected to a rapid lineage-based prediction algorithm (RASE) that predicts antibiotic susceptibility against a reference set of local isolates. We calculated test performance of predictions compared to phenotypic susceptibility testing. Impact of prediction on post-test probability was calculated for each agent and in aggregate benchmarked against minimum susceptibility thresholds for empiric treatment of 80% for mild infections and 90% for moderate-severe infections.

Results
We performed metagenomic sequencing and RASE analysis on twelve unique GN blood culture samples with predictions available in 2.5 hours. Across all organisms and antibiotics tested, sensitivity and specificity were 0.87 (95% CI 0.76-0.94) and 0.56 (95% CI 0.31-0.78) although these values approached one for some agents. Impact of RASE predictions on probability of susceptibility is shown in Figure 2. For all antibiotics combined, baseline susceptibility was 79% but improved to 88% or reduced to 47% when RASE predicted a susceptible or resistant phenotype respectively, an effect echoed by specific agents tested.
Probability of susceptibility to specific agents or in aggregate after prediction of a susceptible or resistant phenotype by RASE. This was benchmarked against minimum susceptibility thresholds for empiric treatment of 80% for mild infections and 90% for moderate-severe infections.

Conclusion
We developed a novel metagenomic diagnostic workflow for rapidly predicting antibiotic susceptibility of common GN blood stream pathogens that could improve early selection of empiric therapy.

Disclosures
All Authors: No reported disclosures
878. Clinical impact of plasma cell-free metagenomic next-generation sequencing: A retrospective cohort study
Authors: Vasishta Shilpa , Vo Christopher , Neogi Sushrita , Alahmdi Bayan , Sullivan Timothy , Gitman Melissa R 
Published: November 2023

Abstract

Background
Plasma cell-free metagenomic next-generation sequencing (cf-mNGS) offers potential for rapid, noninvasive diagnosis of complex infections, though clinical impact remains incompletely characterized. Here, we describe impacts on diagnosis and antimicrobial management among patients evaluated with plasma cf-mNGS.

Methods
Patients evaluated with plasma cf-mNGS (Karius®) in the Mount Sinai Health System from January 1, 2019 to December 23, 2022 were included. Cases were each reviewed independently in the medical record by two investigators using a standardized data collection form with discrepancies adjudicated collectively. Data were analyzed descriptively.

Results
Plasma cf-mNGS was sent for 37 patients of whom 29 (78%) were immunocompromised. 26 (70%) had prior invasive diagnostics. Median time from admission to NGS was 15 days. NGS was positive in 24 cases (65%), with results reflecting 20 bacterial infections, 9 viral, and 4 fungal (14 monomicrobial, 10 polymicrobial). Results were deemed clinically relevant in 18 cases (49%) including 12 positive and 6 negative tests. Testing led to antimicrobial changes in 11 cases (30%), discontinuation in 3 cases (8%), and no change in 23 cases (62%). After plasma cf-mNGS (compared with prior), fewer patients received 3 or 4 antimicrobials, while more received 0, 1, or 2 antimicrobials (Fig. 1A); fewer patients received combined antibiotic/antifungal therapy, while more received no antimicrobials or antifungal therapy alone; there was no change in use of antibiotic therapy alone (Fig. 1B). Final diagnoses included 15 bacterial infections (41%), 9 fungal (24%), 0 viral, and 7 noninfectious conditions (19%). Final diagnoses were attributed to NGS in 6 cases (16%), other diagnostics in 9 cases (24%), and both NGS and other diagnostics in 6 cases (16%); in the latter group, NGS provided a diagnosis prior to another study in 3 cases by intervals of 13, 19, and 72 days, respectively.

A. Changes in number of antimicrobials, B. Changes in classes of antimicrobials

Conclusion
Plasma cf-mNGS, as an adjunct to traditional methods, may provide unique or expedited diagnosis of bacterial or fungal infections, accelerate diagnosis of noninfectious conditions, or inform changes in broad-spectrum antimicrobial regimens. Continued study is warranted to delineate clinical impact and optimal use of plasma cf-mNGS.

Disclosures
All Authors: No reported disclosures
882. Gender Disparities in Faculty Rank and Mentorship opportunities Within a Sample of US Academic Infectious Disease Divisions
Authors: Hollenberg Benjamin , Cawcutt Kelly , Marcelin Jasmine R , Zimmer Andrea J , Cortes-Penfield Nicolas W 
Published: November 2023

Abstract

Background
Gender inequities in promotion within academic medicine, including academic infectious diseases (ID), are well-documented. Effective mentorship is a key component of career advancement and data show that same-gender mentorship can be valuable for women junior faculty learning to navigate academia. We compared the gender, bibliometrics, and mentorship opportunity distributions of ID faculty at each academic rank (instructor vs assistant, associate, or full professor) across several US medical centers.

Methods
We randomly selected five academic medical centers from the US World News & Reports top 100 medical school rankings that had ID division websites including a faculty listing with ranks and years since graduation. We recorded each physician faculty’s rank and gender based on the written biography, using a validated tool (genderize.io) to determine gender if not given, and collected each faculty’s traditional bibliometric data via Google Scholar.

Results
We included 221 faculty (107 women) from five ID divisions (mean 44 faculty). Women accounted for 5/12 (42%) of instructors, 62/109 (57%) of assistant professors, 19/44 (43%) of associate professors, and 21/56 (38%) of full professors. Junior faculty women (instructor or assistant) had a median 0.6 potential same-gender senior mentors per mentee within their divisions versus 1.1 for men; associate professor women had a median 1.0 potential same-gender senior mentor per mentee versus 1.7 for men. Measures of academic productivity, such as annual publications, citations, and h-index growth since graduation from fellowship were similar between men and women.

Conclusion
Our findings support published studies demonstrating lower proportions of women in successively senior positions within academic ID divisions despite similar scholarly activity and suggest that fewer within-institution opportunities for senior mentorship might be a contributing factor.

Disclosures
Andrea J. Zimmer, MD, Allovir: Grant/Research Support
889. The age of RSV cases changes consistently over the course of annual epidemics: potential insights into RSV transmission dynamics based on surveillance data from seven countries.
Authors: Casalegno Jean-Sebastien , Rodrigues Ana Paula , Lee Vernon , Cohen Cheryl , Sue Huang Q , Caicedo Alfredo Bruno , Guiomar Raquel , Ang Li Wei , Cook Tim , de Mora Domenica , Bangert Mathieu , Kramer Rolf , Staadegaard Lisa , Heemskerk Susanne , van Summeren Jojanneke , Meijer Adam , Paget John , Caini Saverio , Teirlinck Anne 
Published: November 2023

Abstract

Background
RSV infections affects people of all ages but the seasonality of RSV among different age groups have not been thoroughly examined. In this study, we investigated changes in the age distribution of RSV cases during the course of annual epidemics.

Methods
We analyzed surveillance data (2008-2019) from the Netherlands, the city of Lyon (France), Portugal, Singapore, Ecuador, South Africa, and New Zealand using the Global Epidemiology of RSV (GERi) study database. We defined annual RSV seasons as the period from July to June in the Northern hemisphere, or the calendar year in the tropics and Southern hemisphere. Within each season, we divided the data into “epidemic quartiles”, corresponding to each quartile of RSV cases in the season. We used multilevel multinomial logistic regression models with season as the higher-level variable to assess whether the likelihood of RSV cases being aged &lt; 1 year or ≥5 years (vs. those aged 1 to &lt; 5 years) changed over time during the season.

Results
A total of 27,391 RSV cases were included. Across all countries, the odds of RSV cases being aged &lt; 1 year (vs. 1 to &lt; 5 years) were significantly higher in the fourth epidemic quartile compared to the first quartile; the relative risk ratio (RRR) ranged between 1.35 in Lyon, France, and 2.56 in the Netherlands. Similarly, the odds of RSV cases being aged ≥5 years (vs. 1 to &lt; 5 years) were significantly higher in the fourth epidemic quartile compared to the first quartile (except in Singapore); the RRR ranged from 1.75 in Ecuador to 6.70 in Lyon, France. The results were consistent when stratifying the data by level of care (primary vs. secondary) or using a lower cut-off of six months of age.

Conclusion
The age distribution of RSV cases changes over the course of a season, with infants (&lt; 1 year) and older children (≥5 years), adults, and elderly people constituting a higher proportion of RSV cases in the later phases of annual epidemics. These findings provide potential insights into the transmission dynamics of RSV and may inform prevention and control measures, e.g. the implementation of targeted age-specific interventions. Funding: This research was funded by a collaborative agreement with Sanofi / AstraZeneca and is part of the RODEO research program for RSV disease.

Disclosures
Mathieu Bangert, PhD, Sanofi: Staff member Rolf Kramer, n/a, Sanofi: Stocks/Bonds John Paget, n/a, Sanofi Pasteur: Grant/Research Support