Sepsis is the ultimate clinical expression of the deleterious clash between the host immune response and invasive microorganisms.(72,73) At the beginning of the twentieth century, infections were by far the most common causes of death of Americans. By the beginning of the twenty-first century, the average lifespan of United States citizens had increased by over 30 years, with infections now accounting for a small minority of death.(74,75) Despite advances in public health, sanitation, vaccines, and antituberculosis chemotherapy and other antimicrobial agents, sepsis continues to account for an increasing number of deaths in critically ill patients. Future advances are anticipated when the genomics era and the promise of systems biology and personalized medicine are fully realized in the next few decades. A remarkable history of scientific inquiry into the fundamental nature of microbes and immune defenses preceded much of the current advances in the treatment of infectious diseases. Much work remains before the benefits of these discoveries can be thoughtfully applied to the management of severe sepsis and septic shock worldwide.
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