Background: It is prudent to develop biomarkers that enhance the differentiation between viral and bacterial infection in order to support expeditious and judicious antimicrobial implementation in emergency department admissions. Human neutrophilic peptides 1-3 (HNP1-3) are the major neutrophilic peptides with potent antimicrobial activity. Methods: We tested the performance of the plasma HNP1-3 test in a prospective observational cohort of children admitted to the emergency department for fever. We validated this test with traditionally used biomarkers and final diagnoses. An expert panel reviewed the patient’s data and gave a final diagnosis. The final diagnosis was classified as definite, probable, or possible. Results: A total of 111 children (98 with fever and 13 control) were recruited: 55% male, mean age 6.3 years. Plasma HNP1-3 levels were higher with bacterial infections: 10,428 (5789–14,866) vs. 7352 (3762–10,672) pg/mL, p = 0.007. HNP1-3 were negatively correlated with age: r = −0.207, p = 0.029. Of the different categorical variables tested, only c-reactive protein (CRP) (≥42.3 mg/dL), neutrophil count (≥10.2), and age (odds ratio = 1.185, p = 0.013 and 95%CI = 1.037–1.354) had significant diagnostic capability for bacterial disease prediction. Conclusions: Due to its low diagnostic value in febrile patients, the HNP1-3 value is not currently recommended to support pathogen differentiation in children in an emergency setting. Further studies are needed to support its clinical use.
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