259 Towards precision medicine in sepsis Introduction Sepsis, defined as life-threatening organ dysfunction due to a dysregulated host response to infection [1], is the major cause of mortality from any infectious disease worldwide. Recent US data, from two complementary hospital cohorts, found that sepsis contributed to one in every two to three deaths [2]. Most of these patients already had sepsis at admission [2]. In addition, sepsis is associated with a high rate of late mortality up to two years after hospital discharge, which is not explained by baseline health status [3]. The incidence of sepsis continues to rise, partly due to an ageing population, increased use of immunosuppressive drugs, and antibiotic resistance [4]. Precision medicine provides an opportunity to improve the outcomes of patients with sepsis [5, 6] (see Box 1 for a list of definitions). We aim to summarize the current evidence on precision medicine in sepsis, with an emphasis on translation from theory to clinical practice (Appendix 1). It is intended to provide an overview for clinical microbiologists, pharmacists, infectious disease specialists, physicians on the ward, emergency physicians and intensive care physicians, and all those managing patients with sepsis and/or are involved in research in this field. We provide a section on immune status, dysbiosis of the microbiome and implications in low- and middle-income countries in the Supplementary Electronic Material (SEM 1, 2 and 3). Box 1 - List of definitions Precision medicine – When treatments are optimized for genetics, lifestyle, and environment. Personalized medicine – When treatments prioritize patient needs and preferences. Endotype – Biological subtypes defined by distinct pathophysiologic mechanisms within a phenotype, being clinically observed characteristics that characterize a group of patients within a disease or syndrome such as sepsis. Biomarker - Defined by the National Institutes of Health as a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. Theranostics - The approach to use a biomarker to select a specific therapy and simultaneously measure the response to this treatment. Omics technologies - Omics is the field of study that encompasses genomics, epigenomics, transcriptomics, proteomics and metabolomics. Omics-based technologies characterize and quantify molecules that translate in the structure, function and dynamics of an organism. Synbiotics - A combination of probiotics (living microorganisms) and prebiotics (dietary components that enhance the growth of these microorganisms), used to resupply the gut with beneficial microbes when the microbiome is disturbed due to critical illness or the interventions from clinical care. Adapted from reference [83] 11
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