Discriminating Bacterial and Viral Infection Using a Rapid Host Gene Expression Test.
Abstract
<h4>Objectives</h4>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.<h4>Design</h4>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.<h4>Setting</h4>Four U.S. emergency departments.<h4>Patients</h4>Six-hundred
twenty-three subjects with acute respiratory illness or suspected sepsis.<h4>Interventions</h4>Forty-five-transcript
signature measured on the BioFire FilmArray System (BioFire Diagnostics, Salt Lake
City, UT) in ~45 minutes.<h4>Measurements and main results</h4>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.<h4>Conclusions</h4>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.
Type
Journal articleSubject
Antibacterial Resistance Leadership GroupHumans
Bacterial Infections
Virus Diseases
Clinical Laboratory Techniques
Adult
Middle Aged
Emergency Service, Hospital
Female
Male
Transcriptome
Biomarkers
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https://hdl.handle.net/10161/23936Published Version (Please cite this version)
10.1097/ccm.0000000000005085Publication Info
Tsalik, Ephraim L; Henao, Ricardo; Montgomery, Jesse L; Nawrocki, Jeff W; Aydin, Mert;
Lydon, Emily C; ... Antibacterial Resistance Leadership Group (2021). Discriminating Bacterial and Viral Infection Using a Rapid Host Gene Expression Test.
Critical care medicine, 49(10). pp. 1651-1663. 10.1097/ccm.0000000000005085. Retrieved from https://hdl.handle.net/10161/23936.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Thomas Burke
Manager, Systems Project
Vance Garrison Fowler Jr.
Florence McAlister Distinguished Professor of Medicine
Determinants of Outcome in Patients with Staphylococcus aureus Bacteremia Antibacterial
ResistancePathogenesis of Bacterial Infections Tropical medicine/International Health
Geoffrey Steven Ginsburg
Adjunct Professor in the Department of Medicine
Dr. Geoffrey S. Ginsburg's research interests are in the development of novel paradigms
for developing and translating genomic information into medical practice and the integration
of personalized medicine into health care.
Ricardo Henao
Associate Professor in Biostatistics & Bioinformatics
Emily Ray Ko
Assistant Professor of Medicine
Clinical and translational research, COVID-19 therapeutics, clinical biomarkers for
infectious disease.
Micah Thomas McClain
Associate Professor of Medicine
Ephraim Tsalik
Adjunct Associate Professor in the Department of Medicine
My research at Duke has focused on understanding the dynamic between host and pathogen
so as to discover and develop host-response markers that can diagnose and predict
health and disease. This new and evolving approach to diagnosing illness has the
potential to significantly impact individual as well as public health considering
the rise of antibiotic resistance.
With any potential infectious disease diagnosis, it is difficult, if not impossible,
to determine at the time of pre
Christopher Wildrick Woods
Wolfgang Joklik Distinguished Professor of Global Health
1. Emerging Infections 2. Global Health 3. Epidemiology of infectious diseases
4. Clinical microbiology and diagnostics 5. Bioterrorism Preparedness 6. Surveillance
for communicable diseases 7. Antimicrobial resistance
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