Early Biomarkers in Sepsis: Can We Diagnose Before It’s Too Late? – A Review on CRP, Procalcitonin, Presepsin, IL-6, and Novel Biomarkers

Abstract

Sepsis remains a leading cause of morbidity and mortality worldwide, with early diagnosis critical for improving outcomes. Conventional biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) aid in diagnosis but lack sufficient sensitivity and specificity, particularly in culture-negative cases. Emerging biomarkers, including interleukin-6 (IL-6), pentraxin 3 (PTX3), suPAR, and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), provide additional insight but are limited when used alone. Presepsin (sCD14-ST), a cleavage fragment of CD14, rises within 2–3 hours of infection and shows strong diagnostic and prognostic value. Evidence from emergency department studies demonstrates higher sensitivity and specificity for presepsin compared to PCT, especially in culture-negative sepsis. Combined use of presepsin with PCT enhances diagnostic yield and supports a multimarker strategy. Despite promising findings, assay variability and influence of renal dysfunction remain challenges. Future multicenter studies are needed to establish standardized cut-offs and validate its integration into clinical practice.