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(Table 325-1) Animals mount both local and systemic responses to microbes that traverse their epithelial barriers and enter underlying tissues. Fever or hypothermia, leukocytosis or leukopenia, tachypnea, and tachycardia are cardinal signs of the systemic response. To date, attempts to devise precise definitions for the harmful systemic reaction to infection (“sepsis”) have not resulted in a clinically useful level of specificity, in part because the systemic responses to infection, trauma, and other major stresses can be so similar. In general, when an infectious etiology is proven or strongly suspected and the response results in hypofunction of uninfected organs, the term sepsis (or severe sepsis) should be used. Septic shock refers to sepsis accompanied by hypotension that cannot be corrected by the infusion of fluids.


image The systemic response to any class of microorganism can be harmful. Microbial invasion of the bloodstream is not essential because local inflammation can also elicit distant organ dysfunction and hypotension. In fact, blood cultures yield bacteria or fungi in only ~20–40% of cases of severe sepsis and 40–70% of cases of septic shock. In a prevalence study of 14,414 patients in intensive care units (ICUs) from 75 countries in 2007, 51% of patients were considered infected. Respiratory infection was most common (64%). Microbiologic results were positive in 70% of individuals considered infected; of the isolates, 62% were gram-negative bacteria (Pseudomonas species and Escherichia coli were most common), 47% were gram-positive bacteria (Staphylococcus aureus was most common), and 19% were fungi (Candida species). This distribution is similar to that reported a decade earlier from eight academic centers in the United States (Table 325-2). In patients whose blood cultures are negative, the etiologic agent is often established by culture or microscopic examination of infected material from a local site; specific identification of microbial DNA or RNA in blood or tissue samples is also used. In some case series, a majority of patients with a clinical picture of severe sepsis or septic shock have had negative microbiologic data.


Severe sepsis is a contributing factor in >200,000 deaths per year in the United States. The incidence of severe sepsis and septic shock has increased over the past 30 years, and the annual number of cases is now >750,000 (~3 per 1000 population). Approximately two-thirds of the cases occur in patients with significant underlying illness. Sepsis-related incidence and mortality rates increase with age and preexisting comorbidity. The rising incidence of severe sepsis in the United States has been attributable to the aging of the population, the increasing longevity of patients with chronic diseases, and the relatively high frequency with which sepsis has occurred in patients with AIDS. The widespread use of immunosuppressive drugs, indwelling catheters, and mechanical devices has also played a role. In the aforementioned international ICU prevalence study, the case–fatality rate among infected ...

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