E5 Murine Monoclonal Antiendotoxin Antibody in Gram-Negative SepsisA Randomized Controlled Trial

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Abstract
While knowledge and understanding of gram-negative sepsis have grown over the last 20 years, the ability to treat it successfully has not changed substantially.1 Despite the introduction of more potent antibiotics and more sophisticated life-support technology, an estimated 200,000 Americans develop gram-negative sepsis each year with reported mortality rates of 30% to 65%.2-5 The prime initiator of gram-negative sepsis is endotoxin, the lipopolysaccharide component of the bacterial outer membrane.6-8 Endotoxin triggers the production of proinflammatory monokines (eg, tumor necrosis factor) which in turn stimulate a variety of proinflammatory and anti-inflammatory mediator cascades that result in the systemic signs and organ dysfunction that characterize clinical sepsis.9 Accordingly, it has been hypothesized that agents that bind endotoxin may mitigate the subsequent cascade, resulting in a decrease in the clinical manifestations of sepsis and improvement in outcome.1,10,11