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Sepsis is a heterogeneous syndrome characterized by widespread inflammation and potential organ harm initiated by a microorganism. Although gram-positive and gram-negative bacteria account for the majority of cases, fungi, viruses, mycobacteria, rickettsiae, and protozoans can trigger sepsis. Invasion of the blood is not necessary to develop or identify sepsis, which is determined by the host response to the infectious insult. As sepsis severity increases, a multifactorial series of events lead to impairments in oxygen delivery, secondary to macro- and microvascular malperfusion, as well as direct cellular damage secondary to inflammation. Eventually, multisystem organ failure occurs, and mortality is high.

The varying clinical presentation, differences in coding, and methodologic differences between studies lead to a wide range of estimates of the annual incidence of severe sepsis, ranging from 300 to 1000 cases/ 100,000 persons per year.1 Over 500,000 patients each year present to the ED with suspected severe sepsis, the largest group of all sepsis patients hospitalized. The incidence is increasing and is multifactorial in origin; a key component of this increase relates to an aging patient population, which is not surprising given the fact that sepsis incidence increases >100-fold with age (0.2 per 1000 in children age 10 to 14 years to 26.2 per 1000 in those >85 years of age).2

The mean ED length of stay of a patient with sepsis is 5 hours. Once admitted, more than half of patients with severe sepsis will require care in an intermediate or intensive care unit,2 where it represents the leading cause of death. Despite advances in care, mortality rates from severe sepsis remain high, with approximately 20% dying3 during hospitalization in optimal clinical trial scenarios4,5; this rate approaches 50% when considering the sicker subset of those with septic shock.6 These mortality rates exceed many other high-visibility acute care conditions such as acute myocardial infarction,7 massive pulmonary embolism,8 and cerebrovascular accident.9 Morbidity is high and prolonged, and a long-term deficit in cognition and functioning is common.10 Finally, sepsis care is costly; estimates from 10 years ago suggest a mean case cost of $22,100 with annual national costs reaching $16.7 billion,2 figures that have certainly increased in the last decade.

Since 1987, gram-positive bacteria outside of the surgical setting are the predominant pathogens of sepsis.11 With the rise of antimicrobial resistance, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and other multidrug-resistant organisms are more common.12 Similarly, the incidence of fungi as the source has risen, particularly in immunosuppressed patients. The most likely causative microorganism varies based on the likelihood of exposure to drug-resistant microorganisms (due to recent healthcare exposures) and the anatomic site of infection, with pneumonia, intra-abdominal, urinary, and skin/soft tissue being the most common locations.

Sepsis syndromes are a continuum, with specific definitions regularly updated to include children13,14 (Table 1). Although the definitions provide ...

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