The management of a patient with severe sepsis is first to diagnose the infection, to collect samples immediately after diagnosis and to initiate promptly broad-spectrum antibiotic treatment. The choice of empirical antimicrobial therapy should be based on host characteristics, site of infection, local ecology and the pharmacokinetics and pharmacodynamics of the antibiotics. In severe infection, guidelines recommend the use of a combination of antibiotics. After results of cultures are obtained, treatment should be re-evaluated to either de-escalate or escalate the antibiotics. This is associated with optimal costs, decreased incidence of superinfection and reduced development of antimicrobial resistance. All these steps should be based on written protocols, and compliance to these protocols should be monitored continuously in order to detect violations and implement corrective procedures.