Bacterial vs viral etiology of fever: A prospective study of a host score for supporting etiologic accuracy of emergency department physicians

Background A host-protein score (BV score) that combines the circulating levels of TNF-related apoptosis-inducing ligand (TRAIL), interferon gamma-induced protein 10 (IP-10) and C-reactive protein (CRP) was developed for distinguishing bacterial from viral infection. This study assessed the potential of the BV score to impact decision making and antibiotic stewardship at the emergency department (ED), by comparing BV score’s performance to physician’s etiological suspicion at patient presentation. Methods Rosetta study participants, aged 3 months to 18 years with febrile respiratory tract infection or fever without source, were prospectively recruited in a tertiary care pediatric ED. 465 patients were recruited, 298 met eligibility criteria and 287 were enrolled. ED physician’s etiological suspicion was recorded in a questionnaire. BV score was measured retrospectively with results interpreted as viral, bacterial or equivocal and compared to reference standard etiology, which was adjudicated by three independent experts based on all available data. Experts were blinded to BV scores. Results Median age was 1.3 years (interquartile range 1.7), 39.7% females. 196 cases were reference standard viral and 18 cases were reference standard bacterial. BV score attained sensitivity of 88.9% (95% confidence interval: 74.4–100), specificity 92.1% (88.1–96.0), positive predictive value 53.3% (35.5–71.2) and negative predictive value 98.8% (97.1–100). Positive likelihood ratio was 11.18 (6.59–18.97) and negative likelihood ratio was 0.12 (0.03–0.45). The rate of BV equivocal scores was 9.4%. Comparing physician’s suspicion to BV score and to the reference standard, and assuming full adoption, BV score could potentially correct the physician’s diagnosis and reduce error ~2-fold, from 15.9% to 8.2%. Conclusions BV score has potential to aid the diagnostic process. Future studies are warranted to assess the impact of real-time BV results on ED practice.