To prevent resistance selection in humans and animals the use of critically important fluoroquinolones and cephalosporins in veterinary medicine needs to be restricted to the necessary minimum. Sepsis is by far the leading indication for these molecules. Despite legislation for cattle limiting the use of critically important antimicrobials, in practice there are several difficulties with the interpretation of terminology like 'urgency criterion' and 'appropriate sampling'. In small animals and horses critically important antimicrobials are among the more frequently used molecules, and formularies and microbiological guidelines are insufficiently followed. In this project we aim to provide the necessary information to rationalise the antimicrobial decision chain for sepsis in an evidence based manner. The target species are calves, foals and dogs, and a first goal is to characterise better the bacteria involved in sepsis and their resistance profile. In addition practically accessible predictive models (scoring systems or decision trees) will be developed assisting the veterinarian to objectively estimate the sepsis risk. The added value of biomarkers in these models will be evaluated. This information will result in a better, more scientifically based formulary and a defined step-by-step guideline to approach sepsis in a more rational way. Finally, the objective is to determine how MALDI-TOF innovations can fasten the diagnostic chain for sepsis. This acceleration would signify an important step towards the final optimum, being an immediate definitive therapy (= therapy supported by an antibiogram and small spectrum) in stead of an empiric therapy (= based on formularies and large spectrum). Through expert consultation the broad support and practical applicability of the developed tools and protocols will be tested. The final deliverables are for each species a direct applicable, practically achievable and evidence based decision tree/ glow diagram supporting veterinarians to use antimicrobials more responsible for sepsis. These tools can be integrated in the national AMCRA guidelines and formularies or can be added in clarification of certain aspects in the current legislation.