Rapid diagnosis of sepsis and bloodstream infections

Abstract

Sepsis accounts for approximately 20% of global mortality and a substantial healthcare cost. Delayed or missed diagnoses of sepsis and poorly targeted treatment of sepsis-causing bloodstream infections are key contributors to this high mortality. Clinical diagnosis and monitoring of sepsis is based on several host-response measures related to organ system dysfunction. Owing to the low concentration of pathogens in bloodstream infections, identification of the causative pathogen generally requires blood culture over the course of hours to days. This necessitates the use of broad-spectrum antibiotics before culture results are available, which is a major risk factor for the development of antimicrobial resistance. In this Review, we describe the current standards for diagnosis of sepsis and summarize the technologies in use for detection of pathogens and host-response biomarkers in blood. We then identify key challenges in rapid diagnosis and discuss how ideal diagnostics for bloodstream infections could be achieved. Sepsis causes approximately 20% of global mortality and targeted treatment of causative bloodstream infection is limited by slow and insensitive pathogen detection, leading to delayed diagnosis and the overuse of broad-spectrum antibiotics that fuel antimicrobial resistance. This Review describes the measurement of host-response biomarkers for the detection and diagnosis of sepsis and addresses the need for sensitive and scalable approaches to bypass time-consuming blood culture.