Toward a holistic approach for diagnosing sepsis in the emergency department

Sepsis is an important healthcare issue worldwide due to the unfavorable clinical outcome and the increasing risk of antimicrobial resistance caused by inappropriate usage of antimicrobials. According to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), sepsis is currently defined as a life-threatening organ dysfunction caused by deregulated host response to an infection. This updated definition has contributed to revolutionizing our current understanding of sepsis, emphasizing the central pathogenetic role of the non-homeostatic host response to microorganisms rather than the infection per se. As a result, “bloodstream infection” is no longer being used synonymously to sepsis. Although blood culture has been considered the gold standard for diagnosing sepsis for decades, the accuracy of this technique remains limited due to the low diagnostic sensitivity with high false negative rates in patients undergoing antimicrobial therapy, and in patients with severe localized infections or in noninfectious cause of sepsis. Also, preanalytical factors and possible contamination further limit the reliability of blood cultures. Recent evidence suggests that an increased concentration of some innovative sepsis biomarkers, especially procalcitonin and presepsin, more reliably reflects the systemic host response to infection. Recent evidence suggests that the measurement of such sepsis biomarkers in addition to blood culture or molecular biology further improves the diagnostic management of patients with possible sepsis. The current article aims to propose a “holistic” approach to sepsis diagnostics, encompassing a reasonable combination of clinical signs and symptoms, sepsis biomarkers and microbiological tests