O0023: A Host-protein Test, BV, Distinguishes Bacterial from Viral Etiology in Febrile Children Presenting to the Emergency Department and Urgent Care Center with Respiratory Signs or Symptoms

Background: Respiratory tract infections (RTI) represent one of the most common reasons for pediatric Emergency Department (ED) and Urgent Care Center (UCC) visits. The difficulty in determining RTI etiology can lead to sub-optimal patient management, including antibiotic misuse. BV, a score for differentiating between bacterial and viral etiologies, is based on computational integration of the blood levels of three proteins (TRAIL, IP-10, CRP). Here we evaluate its ability to differentiate bacterial from viral infection in children presenting to the ED or UCC with fever and respiratory signs or symptoms.

Methods: The study was a sub-analysis of pediatric patients recruited in the Apollo study (NCT04690569). Children (<=18 years) presenting to the ED or UCC with respiratory signs or symptoms (Figure legend) were included in the analysis. Reference standard was based on adjudication by experts provided with comprehensive patient data including follow-up data but blinded to BV. A bacterial or viral reference standard required that at least 2/3 experts assigned the same etiology label with confidence ≥90% or all 3 assigned with confidence ≥70%. Indeterminate cases did not meet these criteria. BV is indicative of bacterial or viral infection (MeMed BV®). Based on pre-defined score thresholds, 0 ≤ score < 35 indicates viral (or other non-bacterial) infection, 35 ≤ score ≤ 65 indicates equivocal and 65 < score ≤ 100 indicates bacterial infection (or co-infection). BV performance was assessed against the reference standard with indeterminate cases removed. To estimate BV’s potential to influence antibiotic use, we compared the medical decision-making, as documented in the medical record, with medical decision making plus BV. The assumption was that a timely BV result would trigger a change in practice to align with the BV result in cases where the BV and the reference standard were discordant, with no medical decision-making changes occurring with equivocal BV results.

Results: Among 432 children enrolled, 266 presented with respiratory signs or symptoms (Figure). The median age was 2.8 years (interquartile range: 1.5-6.18 years), and 54.1% were admitted with a median duration of 4 days (interquartile range: 3-6 days); see Table. Reference standard outcome: 228 cases were viral and 11 bacterial; 27 were indeterminate. Bacterial diagnoses included: lower respiratory tract infection or pneumonia (n=7), tonsillitis or pharyngitis (n=2), meningitis (n=1) and pyelonephritis (n=1). BV yielded sensitivity of 100.0% (95% confidence interval: 69.2%-100.0%) and specificity of 91.1% (95%CI: 86.5%-94.6%), with 6.3% of equivocal cases. BV potentially reduces antibiotic treatment of viral infections by 3-fold (32.9% to 11%; p=0.034), without causing antibiotic withholding from patients with bacterial infections.

Conclusion: BV exhibited good performance in differentiating bacterial from viral etiology in children presenting with respiratory signs or symptoms. The test has the potential to improve antibiotic use in acute care settings.