Pathophysiology and treatment of gram-negative sepsis

The pathogenesis, clinical presentation, and complications of gram-negative bacterial sepsis are described, and the implications for therapy are reviewed. The sepsis syndrome is a clinically defined condition that involves the physiologic alterations and clinical consequences of the presence of microorganisms or their toxins in the bloodstream or tissues. Gram-negative bacteria produce sepsis and septic shock via the release of the cell-wall component known as endotoxin (lipopolysaccharide). The lipid A moiety, common to gram-negative bacteria, is immunogenic and appears to account for many of the biologic effects of endotoxin. A variety of mediators, including tumor-necrosis factor, are released in response to endotoxin, with resultant diverse effects on host tissues, including organ dysfunction and shock. Adequate treatment requires prompt recognition of infection, especially endotoxemia and sepsis, and the early institution of appropriate therapy. Corticosteroids offer little benefit, and the efficacy of naloxone and nonsteroidal anti-inflammatory drugs has not been determined. Although suitable antimicrobial therapy is necessary to eliminate the offending organisms, antimicrobial agents do not inhibit the effects of the bacterial toxins that are present in sepsis. The outcome of sepsis may be favorably influenced in the future by the use of newer methods of detection and newer treatment modalities, including monoclonal antibodies directed against endotoxin or inhibitors of inflammatory mediators.