Early and adequate antibiotic therapy in the treatment of severe sepsis and septic shock.

Severe sepsis and septic shock are conditions that pose difficult challenges to physicians and the health care system. In the past 10 years, a number of retrospective and prospective observational studies have shed light on the importance of a rapid and systematic approach to treatment of these conditions. A key component is early and appropriate use of antibiotics. Delay of even 6 h can dramatically increase hospital mortality. In addition, multivariate analyses have demonstrated that inappropriate initial antibiotics lead to worse outcomes. The treating physician can rapidly identify risk factors for initial inappropriate antibiotics at the bedside, such as recent antibiotic therapy or recent hospitalization. Organized antibiotic order sets have been shown to significantly improve timely appropriate antibiotic administration in septic patients. Finally, emerging laboratory data suggest that early in the course of septic shock, the pharmacokinetics of common broad spectrum antibiotics may be significantly altered due to increased volumes of distribution having dosing implications for antibiotics in septic shock.