Biomarkers Update on Management of Sepsis

Abstract

Background: Emergency department (ED) overcrowding is a major global health challenge and is associated with increased morbidity and mortality, particularly in septic patients. Delays in diagnosis and treatment contribute to adverse outcomes.

Objective: This review summarizes recent evidence on novel sepsis biomarkers and their role in improving early recognition, risk stratification, and prognosis in ED settings.

Methods: Evidence from international studies, clinical trials, and biomarker research presented in Singapore (October 2025) was analyzed, focusing on procalcitonin (PCT), presepsin, bio-adrenomedullin (bio-ADM), proenkephalin (PenKid), and dipeptidyl peptidase 3 (DPP3).

Results: PCT and Presepsin demonstrated superior specificity for bacterial infections compared to conventional markers. bio-ADM levels correlated with endothelial dysfunction and predicted septic shock. PenKid was validated as an early predictor of acute kidney injury (AKI), independent of comorbidities. DPP3 was identified as a harmful mediator released during cellular damage, strongly associated with circulatory failure and mortality. Clinical trials such as ALBIOS, FROG-ICU, and AdrenOSS confirmed their prognostic and therapeutic implications.

Conclusion: A multimarker approach that combines traditional and emerging biomarkers may enhance sepsis management in overcrowded EDs, enabling timely interventions and improving patient outcomes. Further validation is required before routine clinical implementation.