- Study 1. The outcomes associated with exposure to different variables will be compared; the targeted exposures will be empirical active antimicrobial therapy, early targeted optimized therapy, and early source control. Antimicrobial regimens will be analysed as empirical (administered before the susceptibility testing is available) and targeted (thereafter) therapy. The primary endpoint "mortality from any cause until day 30" will be analysed using survival methods (Kaplan-Meier, Cox regression). The other primary endpoint "clinical response at TOC" will be analysed as a dichotomous outcome, regression analyses will use the logistic regression model. The analysis of the secondary endpoints will be analogous. Microbiological response at TOC is a polychotomous outcome and will be analysed using multinomial logistic regression. Goodness of fit will be assessed throughout. Variable selection will be based on Akaike's information criterion.