bluuebunny/crossref_metadata_2025_split huggingface dataset:
1019. Clinical Impact of a Rapid Cerebrospinal Fluid Diagnostic Stewardship Program for Suspected Central Nervous System Infections in Children
Authors: Messacar Kevin , Palmer Claire , Gregoire LiseAnne , Elliott Audrey , Ackley Elizabeth , Tyler Ken , Dominguez Samuel R , Dominguez Samuel R 
Published: December 2021

Abstract

Background
Despite widespread use, the optimal implementation and clinical impact of FilmArray Meningitis Encephalitis Panel (MEP; Table 1) multiplex PCR testing of cerebrospinal fluid (CSF) in children with suspected (CNS) infections is unknown.
Table 1: FilmArray Meningitis Encephalitis Panel Test Characteristics

Methods
A pre-post quasi-experimental cohort study to investigate the impact of implementing MEP using a rapid CSF diagnostic stewardship program was conducted at Children’s Hospital Colorado (CHCO). MEP was implemented with EMR indication selection to guide testing to children meeting approved use criteria: i. infants &lt; 2mo, ii. immunocompromised, iii. encephalitis, iv. &gt; 5 WBCs in CSF. Positive results were communicated with antimicrobial stewardship real-time decision support (Fig 1). All cases with CSF obtained by lumbar puncture (LP) sent to the CHCO microbiology laboratory meeting any of the 4 criteria above were included with pre-implementation controls (2015-2016) compared to post-implementation cases (2017-2018). Primary outcome was time-to-optimal antimicrobials (time from LP to 1st dose of antimicrobials targeted to identified pathogen, or cessation when no treatable pathogen identified).
Figure 1: Rapid Cerebrospinal Fluid Diagnostic Stewardship Program Intervention Design

Results
Post-implementation (n=1127) and pre-implementation (n=1124) group characteristics are in Table 2. Following implementation, MEP was sent in 72% of cases, largely replacing pathogen-specific singleplex CSF testing (Table 3). Time-to-optimal antimicrobials decreased by 10 hours (p&lt; 0.0001; Fig 2). There were no differences in time-to-effective antimicrobials, hospital admissions, antimicrobial starts or length of stay. Time-to-positive CSF results was faster (4.8 vs. 9.6 hrs, p&lt; 0.0001), IV antimicrobial duration was shorter (24 vs 36 hrs, p=0.004) with infectious neurologic diagnoses more frequently identified (15% vs. 10%, p=0.03). Overall, 3% had bacterial and 9% viral CNS infection identified. Enterovirus (n=128) was most common, then HSV (n=28) and parechovirus (n=17) with similar detection rates between groups

Conclusion
Implementation of MEP with a rapid CNS diagnostic stewardship program improved antimicrobial use with faster results shortening empiric therapy. Routine MEP testing in high-yield cases rapidly detects common viral causes and rules out bacterial targets to enable antimicrobial optimization

Disclosures
Samuel R. Dominguez, MD, PhD, BioFire Diagnostics (Consultant, Research Grant or Support)DiaSorin Molecular (Consultant)Pfizer (Grant/Research Support) Samuel R. Dominguez, MD, PhD, BioFire (Individual(s) Involved: Self): Consultant, Research Grant or Support; DiaSorin Molecular (Individual(s) Involved: Self): Consultant; Pfizer (Individual(s) Involved: Self): Grant/Research Support
1020. BioFiring on all Cylinders: Validation of BioFire FilmArray Pneumonia Panel and Determination of Optimal Utility
Authors: Strength Rachel , Bennett Jessica , Patel Jay , Bowden Jarred , Eason Jane V , Thomas-Gosain Neena 
Published: December 2021

Abstract

Background
Respiratory cultures can take up to five days to grow, time that can be crucial in treating patients with serious infections. Newer rapid microbiological identification tests are designed to shorten this delay between specimen collection and test result. The BioFire® FilmArray® Pneumonia Panel is a multiplex PCR panel that can identify 8 viral, 18 bacterial, and 7 resistance gene targets in one hour. In this study, we aimed to calculate the predictive value of this test and its utility in the clinical setting.

Methods
This retrospective study compared BioFire® FilmArray® Pneumonia Panel results to respiratory cultures run at our center from 3/1/2020 to 2/28/2021. For every BioFire sample, a respiratory culture was run concurrently. We examined correlations between these two tests using data collected from the microbiology laboratory and the electronic medical record.

Results
190 BioFire samples from 124 patients were submitted for processing. Of these, 148 samples had a concomitant respiratory culture result that grew organisms that BioFire could detect. BioFire and culture results were compared, and sensitivity and specificity were calculated on a per-sample basis. Sensitivity was calculated at 91%, specificity at 67%, positive predictive value at 46%, and negative predictive value at 96%.
BioFire detected 30 resistance genes total, including mecA/C and MREJ, CTX-M, and KPC. The sensitivity and negative predictive value for BioFire resistance gene detection was 100%. However, specificity was 94-98%, and the positive predictive value ranged between 25-41% when compared to culture.

Conclusion
Despite the promise of faster results and better screening, our data suggests that further study is needed to determine the utility of the BioFire pneumonia panel. The strength of the panel appears to lie in its negative predictive value and sensitivity, but as a positive predictive tool, it is suboptimal.

Disclosures
All Authors: No reported disclosures
1023. Host Gene Expression Biomarkers to Distinguish Between Causes of Acute Respiratory Symptoms in Lung Transplant Recipients
Authors: Steinbrink Julie M , Liu Yiling , Gray Alice , Mohamedaly Omar , Zick Brittany , McClain Micah T 
Published: December 2021

Abstract

Background
Long-term immunosuppression after lung transplantation increases susceptibility to a variety of respiratory infections that are often difficult to diagnose. Host gene expression patterns in circulating leukocytes may provide additional diagnostic information in these settings.

Methods
107 lung transplant recipients (79% with cystic fibrosis) were enrolled at Duke University Medical Center over a 2-year period – 59% with acute respiratory symptoms, the remainder as healthy controls. Whole blood was collected by PAXGene for RNA sequencing. Prior to undergoing biomarker analysis, each case was adjudicated to the appropriate clinical phenotype: bacterial infection, viral infection, allograft rejection, and healthy. Logistic regression models were applied to gene expression data to identify classifiers capable of identifying each etiology.

Results
In lung transplant recipients, 117 genes were upregulated at least 2-fold in the presence of viral infection compared to healthy transplant controls. These genes clustered into expected antiviral pathways, including type I interferon signaling, interferon gamma mediated signaling, and defense response to virus, although the magnitude of gene expression was significantly less than that seen in non-transplant cohorts.
Similar results were seen during bacterial infection (defense response to bacterium, antibacterial humoral response) and rejection (upregulation in defensins DEFA3 and DEFA4). Interestingly, despite the presence of immunosuppression, a previously published gene expression signature of respiratory infection (derived from non-immunosuppressed subjects) was able to differentiate between bacterial and viral infection with 100% accuracy.

Conclusion
Even in the presence of systemic immunosuppression and regardless of presence/absence of cystic fibrosis, core canonical components of the host response to infection and rejection are seen. Gene expression signatures based on these conserved components offer the potential for diagnostic capability in the setting of nonspecific respiratory illness in these vulnerable hosts.

Disclosures
Julie M. Steinbrink, MD, CareDx (Research Grant or Support) Alice Gray, MD, CareDx (Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau)Polarean (Advisor or Review Panel member)
1024. Using DOOR-MAT to Theoretically Compare Three Rapid Diagnostic Tests for Gram-Negative Bloodstream Infections in Immunocompromised Patients
Authors: Groft Lauren , Noval Mandee , Mease James , Kristie Johnson J , Claeys Kimberly C 
Published: December 2021

Abstract

Background
Molecular rapid diagnostic tests (RDTs) for bloodstream infections (BSI) utilize a variety of technologies and differ substantially in organisms and resistance mechanisms detected. RDT platforms decrease time to optimal antibiotics; however, data on RDTs in special populations, such as immunocompromised are extremely limited. This study aimed to compare theoretical changes in antibiotics based on differences in panel identification of organisms and resistance targets among three commercially available RDT panels.

Methods
Retrospective cohort of immunocompromised patients treated for gram-negative BSI at University of Maryland Medical Center from January 2018 to September 2020. Immunocompromised was defined as active hematologic or solid tumor malignancy at time of BSI diagnosis, history of hematopoietic stem cell transplantation (HSCT) or solid organ transplantation (SOT), or absolute neutrophil count (ANC) &lt; 1000 cells/mm3 at any time 30 days prior to BSI diagnosis. Verigene BC-GN was performed as standard of care. GenMark ePlex BCID and BioFire FilmArray BCID 2 results were assigned based on respective identifiable organism panels.
An infectious diseases clinician blinded to final antimicrobial susceptibility testing (AST) results used RDT results to assign antibiotic treatments for each platform. Decisions were referenced against a priori DOOR-MAT matrices. A partial credit scoring system (0 to 100) was applied to each decision based on final AST results. The mean and standard deviation (SD) were compared across panels using One-Way Repeated Measures ANOVA with modified Bonferroni for multiple comparisons.

Results
A total of 146 patients met inclusion. Baseline characteristics are summarized in Table 1. The mean (SD) DOOR-MAT scores for the three RDT panels were: 86.1 (24.4) Verigene BC-GN vs. 88.5 (22.2) GenMark BCID vs. 87.2 (24.4) BioFire BCID 2. There was no statistically significant difference between the panels for DOOR-MAT score (P=0.6).
Table 1. Baseline Patient Characteristics and Organism Identification

Conclusion
Within an immunocompromised patient population, differences in organism identification between three commercially available RDT panels did not impact theoretical antibiotic prescribing.

Disclosures
J. Kristie Johnson, PhD, D(ABMM), GenMark (Speaker’s Bureau) Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau)
1025. Prediction of Intravenous Immunoglobulin Resistance and Coronary Artery Dilatation in Kawasaki Disease: a Multicenter Study from Oman
Authors: Al Mwaiti Fatma , Alhinai Zaid , AlAbrawi Safiya , mamari Asmhan A L , Abdwani Reem , Senidi Khalfan Al 
Published: December 2021

Abstract

Background
Prediction of intravenous immunoglobulin (IVIG) resistance and coronary artery dilatation continues to be a challenge in the management of Kawasaki disease. Significant differences exist among different populations.

Methods
Children &lt; 13 years of age who presented to the two main tertiary care hospitals in Oman (Royal Hospital and Sultan Qaboos University Hospital) between 2008 and 2019 with a diagnosis of Kawasaki disease were included. Diagnosis was confirmed and clinical, laboratory and echocardiography data was systematically collected and checked for accuracy. The primary outcome was the presence of IVIG resistance or coronary artery dilatation at the 6-week follow-up. Bivariate analysis was used to identify significant predictors of the primary outcome, followed by multivariable logistic regression to determine independent predictors. The Muscat Index of Kawasaki disease Severity (MIKS) score was created based on the results.

Results
156 children with Kawasaki disease were included. Median age was 2.1 years (IQR 0.9-3.8), and 64% were males. All patients received IVIG, 26 (17%) received steroids, and one received infliximab. Coronary dilatation was identified in 41 (26%) patients on initial echocardiogram, and 26 (18%) at the 6-week follow-up visit. Variables significantly associated with the primary outcome were age ≤15 months (P=0.031), hemoglobin (P=0.009), WBC count (P=0.002), absolute neutrophil count (P=0.006), and CRP ≥150 mg/L (P=0.015). These variables in addition male gender (P=0.058), ALT &gt;80 IU/L (P=0.10) and serum sodium (P=0.10), were entered into multivariable logistic regression. A predictive model based on CRP ≥150 mg/L (LR=2.2, P=0.049), male gender (LR=2.1, P=0.095) and WBC (LR=1.1, P=0.017) resulted, and it was used as basis for the MIKS score (Table 1). The MIKS score performed favorably to the Kobayashi score in its sensitivity to predict the primary outcome and its separate components (Table 2). Combining the MIKS score with other high-risk criteria had a sensitivity of 95% in predicting the primary outcome and a specificity of 56%.
Table 1. Calculation of the Muscat Index of Kawasaki disease Severity (MIKS) score

Table 2. Sensitivity, specificity and P value for the Kobayashi, MIKS, and combined high risk criteria in predicting IVIG resistance, coronary dilatation at 6 weeks, separately or in combination, among patients with Kawasaki disease. MIKS: Muscat Index of Kawasaki disease Severity. *High risk: presence of coronary artery dilatation on initial echocardiogram or age &lt;1&gt;

Conclusion
The MIKS score predicts IVIG resistance and coronary artery dilatation in Kawasaki disease in our setting, with favorable performance compared to the Kobayashi score.

Disclosures
All Authors: No reported disclosures
1026. Following the Hoof Prints: Detecting Coxiella and Brucella infections with A Plasma-based Microbial Cell-Free DNA Next-generation Sequencing Test
Authors: Degner Nicholas R , Castillo-Galvan Ricardo , Alexander Jose , Arun Aparna , de Vries Christiaan R , Macintyre Ann , Perkins Bradley , Ahmed Asim A , Smollin Matthew 
Published: December 2021

Abstract

Background
Coxiella burnetii and Brucella spp. are zoonotic bacterial pathogens responsible for Q fever and Brucellosis, respectively. Both pathogens have a global distribution and Brucellosis is the most common zoonosis in the world. However, the CDC reports only 80-120 cases of human brucellosis and ~150 cases of acute Q fever annually. The diagnosis of these infections can be limited by: (1) their difficulty to culture; (2) the insensitivity and nonspecificity of serology; (3) the clinical overlap with other infections; and (4) the unreliability of epidemiological exposure history for these zoonoses. Unbiased microbial cell free DNA (mcfDNA) next-generation sequencing (NGS) offers a potential solution to overcome these limitations.

Methods
The Karius TestTM (KT) developed and validated in Karius’s CLIA certified/CAP accredited lab in Redwood City, CA detects mcfDNA in plasma. After mcfDNA is extracted and NGS performed, human reads are removed, and remaining sequences are aligned to a curated database of &gt; 1500 organisms. McfDNA from organisms present above a statistical threshold are reported and quantified in molecules/µL (MPM). KT detections of Coxiella and Brucella were reviewed from August 2017 - present; clinical information was obtained with test requisition or consultation upon result reporting.

Results
KT detected 8 cases of Coxiella burnetii (1735 MPM +/- 3000) and 5 cases of Brucella melitensis (avg 296 MPM +/- 223) (Table 1), representing approximately 1-2% of all detections in the US during this period. All of the Coxiella detections were in adults (100% male) with 5 cases of fever of unknown origin, 2 cases of culture-negative endocarditis and one case of endovascular graft infection. Brucella detections occurred in 3 adults and 2 children (60% male), 3 with exposure to unpasteurized dairy and included 3 cases of spine infection (2 vertebral osteomyelitis, 1 epidural abscess).

Conclusion
Open-ended, plasma-based mcfDNA NGS provides a rapid, non-invasive test to diagnose diverse clinical manifestations of zoonotic infections such as Q fever and Brucellosis against competing broad differential diagnoses. Furthermore, these cases highlight the potential of the KT to diagnose infections caused by fastidious/unculturable pathogens with cryptic clinical presentations.

Disclosures
Nicholas R. Degner, MD, MPH, MS, Karius Inc. (Employee, Shareholder) Ricardo Castillo-Galvan, MD MPH, Karius Inc. (Consultant) Jose Alexander, MD, D(ABMM), FCCM, CIC, SM, MB(ASCP), BCMAS, Karius (Employee) Aparna Arun, MD, Karius (Employee) Ann Macintyre, DO, Karius, Inc. (Employee) Bradley Perkins, MD, Karius, Inc. (Employee) Asim A. Ahmed, MD, Karius, Inc. (Employee) Matthew Smollin, PharmD, Karius, Inc. (Employee)
1028. Performance and Patient Acceptability Evaluation of the Chembio DPP® HIV-Syphilis Assay in an Emergency Department
Authors: Maliszewski Kendall N , Hsieh Yu-Hsiang , Myer Deanna , Perez Danielle A , Gaydos Charlotte A , Manabe Yukari C , Ricketts Erin , Rothman Richard E 
Published: December 2021

Abstract

Background
Emergency departments (EDs) serve as sentinel settings for diagnosing sexually transmitted infections (STIs), including HIV and syphilis. We aimed to assess performance and patient acceptability of a point-of-care (POC) test, the Chembio Dual Path Platform (DPP®) HIV-Syphilis Assay, in an urban ED in Baltimore.

Methods
170 patients were enrolled via convenience sampling from Oct 2019 – March 2020 and Jan 2021 – June 2021. Patients eligible were &lt; 70 yrs, men who have sex with men, pregnant without care, had STI concerns, or history of drug use. Subjects received standard of care (SOC) HIV and syphilis testing under institutional laboratory algorithms. Subjects were then tested with the finger-stick POC test and completed a survey, both before and after the POC test to assess subjects’ attitudes about the POC test.

Results
Comparing the SOC and POC results, 165/170 (97.1%) were test concordant. 3 syphilis POC results were false negative, but reported successful treatment over 10 years prior to enrollment (treponemal antibody remains after treatment). 1 HIV result was false negative and 1 was false positive. Overall the sensitivity and specificity of the HIV POC test were 96.8% (95%CI: 83.3%, 99.9%) and 99.3% (95% CI: 96.1%, 100%), and for syphilis were 85.7% (95%Cl: 63.7%, 97.0%) or 100% (95%CI: 81.5%, 100%), if excluding 3 persons having been successfully treated, and 100% (95% CI: 97.6%, 100%) respectively.
The pre-test survey found 67% and 77% of participants were comfortable with a finger-stick test and agreed the POC test result would be as good as the SOC test result, which increased to 96% and 86% in the post-test, respectively, (p&lt; 0.05). At post-test, 86% reported they would feel confident to perform this test at home and 81% would use it at least once per year if it were available. 97% reported they were more likely to seek treatment if receiving a positive result during their ED visit and 91% reported it would reduce their stress/anxiety if receiving a negative test result in the ED.

Conclusion
Our findings demonstrated satisfactory performance and high patient acceptability of the Chembio DPP® HIV-Syphilis Assay. Given the test is FDA approved, implementation studies are needed to determine whether adoption of this POC test will benefit patients and be consistent with ED workflows.

Disclosures
Richard E. Rothman, PhD, MD, Chem bio (Grant/Research Support)
1029. Torus Synestia Nucleic Acid Analysis Platform for Fast, High Multiplex Analysis of Nucleic Acids With Single-Nucleotide Discrimination Level
Authors: Rockwood Tyler , Sullivan Andrew , Gandhi Jahnavi , Gruszka Sarah , Turczyk Brian , Khodakov Dmitriy 
Published: December 2021

Abstract

Background
Nucleic acid amplification testing (NAAT) is an essential tool both for biomedical research and for clinical molecular diagnostics. Currently, there are multiple NAAT platforms available, each offering certain performance and utility advantages and disadvantages as compared to each other. Next generation NAAT platforms aim to deliver increased target detection sensitivity and specificity, low limits of target detection, quantitative high multiplex target capacity, rapid time to results, and simple sample-to-answer workflow.

Methods
Here we describe the Torus Synestia System, a NAAT platform capable of rapid, highly multiplexed amplification and detection of both DNA and RNA targets. The platform comprises a small, portable (~ 2kg) amplification and detection device and a disposable single-use cartridge housing a PCR amplification chamber with an integrated label-free microarray for real-time data acquisition and interpretation. The platform offers a 30-min turnaround time with a detection limit of 10 DNA/RNA molecules per assay and single nucleotide discrimination.

Results
We demonstrate the Synestia System performance and utility with three distinct molecular applications: 1) detection of 20 genetic loci and 30 single nucleotide polymorphisms in human genomic DNA; 2) detection and genotyping of 43 unique bacterial species associated with human urinary tract infections; and 3) detection and profiling human respiratory viral pathogens including SARS-CoV-1/2, seasonal coronaviruses, Influenza A/B, and human respiratory syncytial viruses. In addition, the single-nucleotide specificity of our label-free microarray probes allowed for robust identification and discrimination of newly emerging SARS-CoV-2 lineages, such as B.1.1.7 (a.k.a. UK), B.1.351 (a.k.a. South African), P.1 (a.k.a. Brazilian), and B.1.617 (a.k.a. Indian).

Conclusion
The Torus Synestia System has broad applicability in both clinical and research environments. We are confident that the Torus Synestia System will revolutionize syndromic diagnostics at the point of care (PoC) and lead to improved response times during future epidemic and pandemic pathogen outbreaks.

Disclosures
All Authors: No reported disclosures