Objectives: In patients presenting to the Emergency Department (ED) with infectious symptoms, ruling out sepsis is essential. Procalcitonin (PCT) and presepsin are inflammatory biomarkers suggested for the diagnosis and exclusion of sepsis. Our objective was to test whether these biomarkers, in combination or alone, can rule out sepsis.
Methods: We conducted a single site, prospective pilot observational cohort study of adult ED patients presenting with acute infectious symptoms. Patients were included if they had antibiotics ordered, identification of an infectious source on imaging or laboratory testing, or presence of systemic inflammatory response syndrome. Each participant had blood collected and analyzed on the Pathfast point-of-care analyzer (PHC Corporation, Tokyo, Japan) for presepsin and PCT. Presepsin and PCT results were classified into low-, moderate-, and high-risk based on established cut points. The clinical team was blinded to presepsin and PCT results. The primary outcome was a diagnosis of sepsis. Association of presepsin and PCT with sepsis was assessed using chi-square testing. Negative predictive values (NPV) of presepsin and PCT measures, alone and in combination, for sepsis were calculated with associated 95% confidence intervals.
Results: During the study period, 149 patients were accrued, of which 47.0% were female and 40.9% non-white, with a median age of 64. Among these patients 27.5% (41/149) were diagnosed with sepsis. In patients with low-risk presepsin measures, 5.1% (2/39) had sepsis compared to 35.5% (39/110) in patients with moderate- or high-risk presepsin measures (p < 0.0001). Of the 78 patients with a low-risk PCT, 9.2% (9/98) had sepsis vs 60.4% (29/48) in patients with a moderate- or high-risk PCT (p < 0.0001). In the 36 patients with low-risk measures of both presepsin and procalcitonin, 0% had sepsis compared to 34.5% (38/110) of patients without low-risk measures for both biomarkers (p < 0.0001). The NPV for sepsis was 94.9% (95% CI of 88.0%, 100%) for presepsin, 90.8% (95% CI of 85.1%, 96.5%) for PCT, and 100% (95% CI of 90.3%, 100%) for their combination.
Conclusions: Use of presepsin yielded high negative predictive value for sepsis, especially when used in combination with PCT.
Keywords: Presepsin; Procalcitonin; Sepsis.
Copyright © 2026. Published by Elsevier Inc.