Diagnostic accuracy and added value of infection biomarkers in patients with possible sepsis in the emergency department

Abstract

Background: Biomarkers for early recognition of infection are warranted. The hypothesis of this study was that calprotectin, C-reactive protein (CRP), IL-6 and procalcitonin (PCT), alone or in combination, provide clinically useful information to the clinicians for early identification of infection in patients with possible sepsis in the emergency department (ED). Biomarker dynamics in the first week of hospitalization were explored.

Methods: Adult patients in rapid response teams in the ED were included in a prospective observational study (n = 391). Patients who received antibiotics after biomarker availability were excluded. The ED clinician (EDC) decision whether to start antibiotics was registered. Calprotectin, CRP, IL-6, and PCT were analyzed in blood samples drawn within 15 min after ED arrival and in a subgroup for 1 week. Infection likelihood was evaluated post hoc.

Results: In identifying patients with infection, CRP (area under the receiver operating characteristic curve [AUC], 0.913) and IL-6 (AUC, 0.895) were superior to calprotectin (AUC, 0.777) and PCT (AUC, 0.838). The best regression model predicting infections included EDC, CRP, and IL-6. Using optimal cutoff values, CRP and IL-6 in combination reached 95% positive and 90% negative predictive values for infection. The EDC undertreated or overtreated 65 of 391 patients (17%), and CRP and IL-6 optimal cutoff values could correct this in 32 of 65 patients (49%). Longitudinal samples revealed that IL-6 peaked in the ED, whereas CRP and PCT peaked later.

Conclusion: C-reactive protein and IL-6 were superior to calprotectin and PCT for recognizing infection in patients with possible sepsis in the ED. Combining these two biomarkers with different dynamics improved recognition of infection and could aid clinical management in rapid response teams in the ED.