Point-of-care Monitoring of the Host-Pathogen Interaction during Infection

Modern battlefield medicine has improved the rate of salvage of life and limb at the expense of a greater burden of hospitalizations for acute traumatic injuries and surgical care. The inflammation that accompanies the normal recovery from such tissue trauma is often clinically indistinguishable from early sepsis. This uncertainty can lead to delayed treatment with antibiotics and to substantially increased mortality rates. It can also lead to unnecessary treatment with antibiotics, with substantially increased morbidity, cost, and antimicrobial resistance. In several recent high-profile manuscripts, we published on the development and validation of three sets of biomarkers for sepsis that use gene expression profiling of the host immune response. For any patient with acute inflammation, these host-response gene sets can (1) determine whether an infection is present, (2) determine whether an infection is bacterial or viral, and (3) risk-stratify patients (predict 30-day mortality). This proposal aims to translate these biomarkers into one single point-of-care diagnostic for bacterial sepsis. To do this, we are partnering with a company whose device can rapidly quantitate multiple gene expression targets in multiplex with high accuracy at low cost. The final sepsis diagnostic will fill an unmet critical need in both defense and civilian applications.