Novel Approaches for Diagnosing Sepsis in the Critically Ill

Abstract

Accurate and fast diagnostic tests for sepsis are important to improve patient outcomes. This thesis discusses different diagnostic approaches for sepsis. There exists no perfect gold standard for sepsis, which complicates the development of an adequate and consistent definition. We discuss how different applications of the sepsis definitions result in the selection of different patient populations within research. Besides we validate the Septicyte LAB test, which is an RNA-signature that was developed to distinguish infectious from non-infectious inflammation. We validated the test in two patient cohorts and discuss the diagnostic performance of this test in an Intensive Care Setting. Furthermore, we evaluated if routine blood cultures upon ICU admission could improve the diagnosis of bloodstream infections, also when an infection is not immediately evident. At last we devote one chapter on the description of a cohort with E. Coli bacteremias and its serotypes. Currently, an O-polysaccharide vaccine is under development which targets the ten most common E. coli serotypes, and we describe the potential coverage of this vaccine in an ICU population. This thesis was written within the framework of the Molecular Diagnosis and Risk Stratification of Sepsis (MARS) project. This database contains detailed data and biorepository material and was set up to improve our understanding of sepsis.