271 Towards precision medicine in sepsis Molecular signatures should be evaluated to distinguish sterile, non-infectious systemic inflammatory states from systemic infection. Physicians should carefully evaluate patient-related factors when prescribing antibiotic treatment. Local antimicrobial resistance data should be taken into account as part of good antibiotic stewardship, when an initial empirical antibiotic regimen is started. When confronted with septic shock patients in need of vasopressors, it is imperative to start antimicrobials quickly. One should avoid the risk of delay in treatment, for instance due to pathogen identification or antibiotic susceptibility assessment, in this subset of patients. It is essential to educate all healthcare workers for rapid diagnosis, team working and personalized management. Perspectives Pathogen detection will remain most critical during the acute phases of sepsis for early targeted antimicrobial therapy. It implies the need for the development of ultra-rapid tests (under 30 minutes) at the patient’s bedside for both microorganism identification and resistance detection. Microbial load (quantitative mass or pathogen burden) is an important parameter that will require more attention. The load predicts outcome, risk of death and failure of antibiotics and need to drain the primary site, and helps to distinguish colonization versus infection using samples taken from mucosal surfaces (sputum BAL, gastrointestinal tract etc.). Rapid measures of bacterial load need to be improved and are a priority for the future. Data on the monitoring of hospitalized patients should be integrated into a continuous assessment of vital signs and oxygen saturation for early detection of sepsis. An electronic alert should be able to detect deterioration and notify health care providers. This technology already exists and is largely implemented on ICUs, but these big data processes also need to become standard practice on general wards. As for care of patients with cancer, the advent of NGS technologies may be the next step of precision medicine in sepsis. In contrast to cancer, sepsis is a rapidly evolving process and the NGS-based tests need to be performed in a short time period, directly from clinical specimens, and should be optimized to be faster, simple-to-use and cost-effective. To restore the microbiome after antibiotic treatment or to promote a functional microbiome, novel strategies are being evaluated. The indications for (modified) fecal microbiota transplantation (FMT) are currently broadening. However, the use of certain strains or (next generation) probiotics may be more feasible as future therapies to restore ‘healthy’ microbiomes in the critically ill. The rapid development of omics-based technologies has shifted the focus from traditional biomarkers to genome-wide blood gene expression profiles, in addition to compartment specific protein and metabolite profiles. Big data analyses to identify these genotypes and associations will increase the need for the expertise of computational biologists in the sepsis field. Identifying drug-response phenotypes is a priority. The further development of specific sepsis signatures or endotypes will have a major impact on future clinical trial design in sepsis and sepsis management in general. Challenges in trial design, clinical trial ethics and study execution remain before precision medicine becomes the norm in patients presenting with sepsis. 11
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