Abstract
Mortality and morbidity in severe sepsis and septic shock remain high despite significant advances in critical care. Efforts to improve outcome in septic conditions have focused on targeted, quantitative resuscitation strategies utilizing intravenous fluids, vasopressors, inotropes, and blood transfusions to correct disease-associated circulatory dysfunction driven by immune-mediated systemic inflammation. This review explores an alternate paradigm of septic shock in which microbial burden is identified as the key driver of mortality and progression to irreversible shock. We propose that clinical outcomes in severe sepsis and septic shock hinge upon the optimized selection, dosing, and delivery of highly potent antimicrobial therapy.