Prospective Validation of a Rapid Host Gene Expression Test to Discriminate Bacterial From Viral Respiratory Infection.
Abstract
<h4>Importance</h4>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.<h4>Objective</h4>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.<h4>Design, setting, and participants</h4>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.<h4>Interventions</h4>The HR-B/V
test quantified the expression of 45 host messenger RNAs in approximately 45 minutes
to derive a probability of bacterial infection.<h4>Main outcomes and measures</h4>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 <0.19], viral likely [probability score of 0.19-0.40],
bacterial likely [probability score of 0.41-0.73], and bacterial very likely [probability
score >0.73]) and compared with procalcitonin measurement.<h4>Results</h4>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 < .001), the specificity
was 87.0% (95% CI, 82.7%-90.7%; P = .006), and the NPV was 87.6% (95% CI, 85.5%-89.5%;
P < .001). When stratified into likelihood groups, the HR-B/V test had an NPV of 98.9%
(95% CI, 96.1%-100%) for bacterial infection in the viral very likely group and a
positive predictive value of 63.4% (95% CI, 47.2%-77.9%) for bacterial infection in
the bacterial very likely group. The HR-B/V test correctly identified 30 of 33 participants
(90.9%) with acute COVID-19 as having a viral infection.<h4>Conclusions and relevance</h4>In
this study, the HR-B/V test accurately discriminated bacterial from viral infection
among patients with febrile ARI and was superior to procalcitonin measurement. The
findings suggest that an accurate point-of-need host response test with high NPV may
offer an opportunity to improve antibiotic stewardship and patient outcomes.
Type
Journal articleSubject
Antibacterial Resistance Leadership GroupHumans
Bacteria
Bacterial Infections
Virus Diseases
Fever
Gene Expression
Adult
Child
Female
Male
Procalcitonin
COVID-19
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https://hdl.handle.net/10161/24951Published Version (Please cite this version)
10.1001/jamanetworkopen.2022.7299Publication Info
Ko, Emily R; Henao, Ricardo; Frankey, Katherine; Petzold, Elizabeth A; Isner, Pamela
D; Jaehne, Anja K; ... Antibacterial Resistance Leadership Group (2022). Prospective Validation of a Rapid Host Gene Expression Test to Discriminate Bacterial
From Viral Respiratory Infection. JAMA network open, 5(4). pp. e227299. 10.1001/jamanetworkopen.2022.7299. Retrieved from https://hdl.handle.net/10161/24951.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
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.
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
Gayani Tillekeratne
Assistant Professor of Medicine
Global healthAntimicrobial resistance/ stewardshipAcute respiratory tract infections Emerging
infections/ dengue
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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