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  • Possibly harmful systemic response: Two or more of the following:

    • – Fever (oral temperature >38°C [100.4°F]) or hypothermia (oral temperature <36°C [96.8°F])

    • – Tachypnea (>24 breaths/min)

    • – Tachycardia (>90 beats/min)

    • – Leukocytosis (>12,000/μL), leukopenia (<4000/μL), or >10% bands; may have a noninfectious etiology

  • Sepsis (or severe sepsis): Harmful systemic response (including some degree of organ hypofunction) with a proven or suspected microbial etiology

  • Septic shock: Sepsis with hypotension (arterial bp <90 mmHg or 40 mmHg below pt’s normal bp for at least 1 h despite fluid resuscitation) or need for vasopressors to maintain systolic bp ≥90 mmHg or mean arterial bp ≥70 mmHg


  • Blood cultures are positive in 20–40% of sepsis cases and in 40–70% of septic shock cases.

  • For infected pts in ICUs, respiratory infections have been most common (64%). Microbiologic results have revealed that 62% of isolates are gram-negative bacteria (most commonly Pseudomonas spp. and Escherichia coli), 47% are gram-positive bacteria (most commonly Staphylococcus aureus), and 19% are fungi (most commonly Candida spp.), with some cultures being polymicrobial.


  • The incidence of severe sepsis and septic shock in the United States continues to increase, with >750,000 cases each year contributing to >200,000 deaths.

  • Invasive bacterial infections are a prominent cause of death around the world, especially among young children.

  • Sepsis-related incidence and mortality rates increase with age and preexisting comorbidity, with two-thirds of cases occurring in pts with significant underlying disease.

  • The increasing incidence of sepsis has been attributable to the aging of the population, longer survival of pts with chronic diseases, a relatively high frequency of sepsis among AIDS pts, and medical treatments that circumvent host defenses (e.g., immunosuppressive agents, indwelling catheters, and mechanical devices).


Local and Systemic Host Responses

  • Hosts have numerous receptors that recognize highly conserved microbial molecules (e.g., lipopolysaccharide, lipoproteins, double-stranded RNA), triggering the release of cytokines and other host molecules that increase blood flow and neutrophil migration to the infected site, enhance local vascular permeability, and elicit pain.

  • Many local and systemic control mechanisms diminish cellular responses to microbial molecules, including intravascular thrombosis (which prevents spread of infection and inflammation) and an increase in anti-inflammatory cytokines (e.g., IL-4 and IL-10).

Organ Dysfunction and Shock

  • Widespread vascular endothelial injury is believed to be the major mechanism for multiorgan dysfunction.

  • Septic shock is characterized by compromised oxygen delivery to tissues followed by a vasodilatory phase (a decrease in peripheral vascular resistance despite increased levels of vasopressor catecholamines).


  • Hyperventilation that produces respiratory alkalosis

  • Encephalopathy (disorientation, confusion)

  • Acrocyanosis and ischemic necrosis of peripheral tissues (e.g., digits) due to hypotension and DIC

  • Skin: hemorrhagic lesions, bullae, cellulitis, pustules. Skin lesions may suggest specific pathogens; e.g., petechiae and purpura suggest Neisseria meningitidis, and ecthyma gangrenosum ...

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