Discriminating Bacterial and Viral Infection Using a Rapid Host Gene Expression Test∗

Ephraim L. Tsalik, Ricardo Henao, Jesse L. Montgomery, Jeff W. Nawrocki, Mert Aydin, Emily C. Lydon, Emily R. Ko, Elizabeth Petzold, Bradly P. Nicholson, Charles B. Cairns, Seth W. Glickman, Eugenia Quackenbush, Stephen F. Kingsmore, Anja K. Jaehne, Emanuel P. Rivers, Raymond J. Langley, Vance G. Fowler, Micah T. McClain, Robert J. Crisp, Geoffrey S. GinsburgThomas W. Burke, Andrew C. Hemmert, Christopher W. Woods

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


OBJECTIVES: Host gene expression signatures discriminate bacterial and viral infection but have not been translated to a clinical test platform. This study enrolled an independent cohort of patients to describe and validate a first-in-class host response bacterial/viral test. DESIGN: Subjects were recruited from 2006 to 2016. Enrollment blood samples were collected in an RNA preservative and banked for later testing. The reference standard was an expert panel clinical adjudication, which was blinded to gene expression and procalcitonin results. SETTING: Four U.S. emergency departments. PATIENTS: Six-hundred twenty-three subjects with acute respiratory illness or suspected sepsis. INTERVENTIONS: Forty-five-transcript signature measured on the BioFire FilmArray System (BioFire Diagnostics, Salt Lake City, UT) in ∼45 minutes. MEASUREMENTS AND MAIN RESULTS: Host response bacterial/viral test performance characteristics were evaluated in 623 participants (mean age 46 yr; 45% male) with bacterial infection, viral infection, coinfection, or noninfectious illness. Performance of the host response bacterial/viral test was compared with procalcitonin. The test provided independent probabilities of bacterial and viral infection in ∼45 minutes. In the 213-subject training cohort, the host response bacterial/viral test had an area under the curve for bacterial infection of 0.90 (95% CI, 0.84-0.94) and 0.92 (95% CI, 0.87-0.95) for viral infection. Independent validation in 209 subjects revealed similar performance with an area under the curve of 0.85 (95% CI, 0.78-0.90) for bacterial infection and 0.91 (95% CI, 0.85-0.94) for viral infection. The test had 80.1% (95% CI, 73.7-85.4%) average weighted accuracy for bacterial infection and 86.8% (95% CI, 81.8-90.8%) for viral infection in this validation cohort. This was significantly better than 68.7% (95% CI, 62.4-75.4%) observed for procalcitonin (p < 0.001). An additional cohort of 201 subjects with indeterminate phenotypes (coinfection or microbiology-negative infections) revealed similar performance. CONCLUSIONS: The host response bacterial/viral measured using the BioFire System rapidly and accurately discriminated bacterial and viral infection better than procalcitonin, which can help support more appropriate antibiotic use.
Original languageEnglish (US)
Pages (from-to)1651-1663
Number of pages13
JournalCritical Care Medicine
StatePublished - Jan 1 2021
Externally publishedYes

Bibliographical note

Generated from Scopus record by KAUST IRTS on 2023-02-15

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine


Dive into the research topics of 'Discriminating Bacterial and Viral Infection Using a Rapid Host Gene Expression Test∗'. Together they form a unique fingerprint.

Cite this