Prospective Validation of a Rapid Host Gene Expression Test to Discriminate Bacterial from Viral Respiratory Infection

Emily R. Ko, Ricardo Henao, Katherine Frankey, Elizabeth A. Petzold, Pamela D. Isner, Anja K. Jaehne, Nakia Allen, Jayna Gardner-Gray, Gina Hurst, Jacqueline Pflaum-Carlson, Namita Jayaprakash, Emanuel P. Rivers, Henry Wang, Irma Ugalde, Siraj Amanullah, Laura Mercurio, Thomas H. Chun, Larissa May, Robert W. Hickey, Jacob E. LazarusShauna H. Gunaratne, Daniel J. Pallin, Guruprasad Jambaulikar, David S. Huckins, Krow Ampofo, Ravi Jhaveri, Yunyun Jiang, Lauren Komarow, Scott R. Evans, Geoffrey S. Ginsburg, L. Gayani Tillekeratne, Micah T. McClain, Thomas W. Burke, Christopher W. Woods, Ephraim L. Tsalik

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Importance: Bacterial and viral causes of acute respiratory illness (ARI) are difficult to clinically distinguish, resulting in the inappropriate use of antibacterial therapy. The use of a host gene expression-based test that is able to discriminate bacterial from viral infection in less than 1 hour may improve care and antimicrobial stewardship. Objective: To validate the host response bacterial/viral (HR-B/V) test and assess its ability to accurately differentiate bacterial from viral infection among patients with ARI. Design, Setting, and Participants: This prospective multicenter diagnostic study enrolled 755 children and adults with febrile ARI of 7 or fewer days' duration from 10 US emergency departments. Participants were enrolled from October 3, 2014, to September 1, 2019, followed by additional enrollment of patients with COVID-19 from March 20 to December 3, 2020. Clinical adjudication of enrolled participants identified 616 individuals as having bacterial or viral infection. The primary analysis cohort included 334 participants with high-confidence reference adjudications (based on adjudicator concordance and the presence of an identified pathogen confirmed by microbiological testing). A secondary analysis of the entire cohort of 616 participants included cases with low-confidence reference adjudications (based on adjudicator discordance or the absence of an identified pathogen in microbiological testing). Thirty-three participants with COVID-19 were included post hoc. Interventions: The HR-B/V test quantified the expression of 45 host messenger RNAs in approximately 45 minutes to derive a probability of bacterial infection. Main Outcomes and Measures: Performance characteristics for the HR-B/V test compared with clinical adjudication were reported as either bacterial or viral infection or categorized into 4 likelihood groups (viral very likely [probability score 0.73]) and compared with procalcitonin measurement. Results: Among 755 enrolled participants, the median age was 26 years (IQR, 16-52 years); 360 participants (47.7%) were female, and 395 (52.3%) were male. A total of 13 participants (1.7%) were American Indian, 13 (1.7%) were Asian, 368 (48.7%) were Black, 131 (17.4%) were Hispanic, 3 (0.4%) were Native Hawaiian or Pacific Islander, 297 (39.3%) were White, and 60 (7.9%) were of unspecified race and/or ethnicity. In the primary analysis involving 334 participants, the HR-B/V test had sensitivity of 89.8% (95% CI, 77.8%-96.2%), specificity of 82.1% (95% CI, 77.4%-86.6%), and a negative predictive value (NPV) of 97.9% (95% CI, 95.3%-99.1%) for bacterial infection. In comparison, the sensitivity of procalcitonin measurement was 28.6% (95% CI, 16.2%-40.9%; P
Original languageEnglish (US)
JournalJAMA network open
Volume5
Issue number4
DOIs
StatePublished - Apr 14 2022
Externally publishedYes

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

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