2012. FilmArray® Measurement of Host Response Signatures Rapidly Discriminates Viral, Bacterial, and Non-Infectious Etiologies of Illness
Session: Poster Abstract Session: Diagnostics: Biomarkers and Novel Approaches
Saturday, October 6, 2018
Room: S Poster Hall
Posters
  • IDWeek 2018 BioFire.pdf (226.0 kB)
  • Background: The inability to reliably discriminate bacterial, viral, and non-infectious illness has led to an epidemic of antibiotic overuse and rising rates of antimicrobial resistance. Host gene expression provides a powerful approach to distinguish infection etiologies and guide appropriate therapy. However, existing platforms for transcriptomic analysis are not amenable for clinical application. The FilmArray platform is a sample-to-answer multiplex RT-PCR system that automates transcriptomic analysis including sample preparation and data analysis. Here we report the validation of a host gene expression FilmArray test to discriminate bacterial, viral, and non-infectious etiologies of illness.

    Methods: Research use only (RUO) FilmArray pouches were manufactured with 45 host response assays previously shown to discriminate bacterial, viral, and non-infectious illness. These pouches were tested on whole blood samples from 226 patients with acute respiratory illness (ARI). Using clinical adjudication as the reference standard, there were 52 bacterial, 100 viral, and 75 non-infectious cases. Quantification cycles were recorded for each assay and normalized to an internal control. A logistic regression model generated probabilities of each condition, which were used to classify subjects.

    Results: Beginning with 100ul of blood, the FilmArray host response panel provided results in ~45 minutes from sample to answer. Overall accuracy for bacterial ARI relative to clinical adjudication was 85% with an area under the receiver operating characteristic curve (AUC) of 0.92. Accuracy and AUC for viral infection were 85% and 0.91, respectively. Ill patients without infection were correctly identified 86% of the time with an AUC of 0.88.

    Conclusion: These results show that the FilmArray system can rapidly measure host gene expression to accurately discriminate bacterial, viral, and non-infectious illness. The development of such a system creates a new option to mitigate inappropriate antibiotic use. It also presents opportunities to use host gene expression as a diagnostic modality for a variety of disease states.

    Ephraim L. Tsalik, MD, MHS, PhD1,2,3, Ricardo Henao, PhD3, Mert Aydin, MSc3, Charles Bullard, MBA3, Jesse Montgomery, PhD4, Jeff Nawrocki, MS4, Maxcén Deneris, AS4, Craig Gritzen, MS4, Jay Jones, MS4, Robert Crisp, PhD4, Micah T. Mcclain, MD, PhD3,5,6, Thomas Burke, PhD3, Geoffrey S. Ginsburg, MD, PhD3,7, Andrew Hemmert, PhD4 and Christopher W Woods, MD, MPH, FIDSA2,3,8, (1)Emergency Department Service, Durham Veterans Affairs Health Care System, Durham, NC, (2)Division of Infectious Diseases and International Health, Department of Medicine, Duke University, Durham, NC, (3)Center for Applied Genomics & Precision Medicine, Duke University, Durham, NC, (4)BioFire Diagnostics, LLC, Salt Lake City, UT, (5)Veterans Affairs Medical Center, Durham, NC, (6)Division of Infectious Diseases, Duke University Medical Center, Durham, NC, (7)Director, Center for Genomic Medicine in the Duke Institute for Genome Sciences & Policy, Duke University, Durham, NC, (8)Section of Infectious Diseases, Durham Veteran's Affairs Medical Center, Durham, NC

    Disclosures:

    E. L. Tsalik, Host Response, Inc.: Founder , Equity .

    R. Henao, None

    M. Aydin, None

    C. Bullard, None

    J. Montgomery, BioFire Diagnostics: Employee , Salary .

    J. Nawrocki, BioFire Diagnostics, LLC.: Employee , Salary .

    M. Deneris, BioFire Diagnostics, LLC.: Employee , Salary .

    C. Gritzen, BioFire Diagnostics, LLC.: Employee , Salary .

    J. Jones, BioFire Diagnostics, LLC.: Employee , Salary .

    R. Crisp, BioFire Diagnostics, LLC: Employee , Salary .

    M. T. Mcclain, None

    T. Burke, None

    G. S. Ginsburg, Host Response Inc: Board Member , Founder , Scientific Advisor and Shareholder , Stock (currently worth < $100) .

    A. Hemmert, BioFire Diagnostics, LLC.: Employee and Investigator , Salary .

    C. W. Woods, Host Response, Inc.: Founder , Equity .

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 3rd with the exception of research findings presented at the IDWeek press conferences.