The role of monoclonal antibodies in the management of gram-negative sepsis. Experience with the E5 antibody.
Immunologic targeting of the mediators of sepsis is a new approach to reducing mortality associated with this often-fatal complication. When sepsis is due to infection with a gram-negative pathogen, endotoxin plays a key role in its pathogenesis. Antiendotoxin antibody E5 binds endotoxin from a broad spectrum of clinically relevant gram-negative bacteria and reduces mortality from endotoxemia and bacteremia in animal models. It seems to be safe to administer to patients with suspected gram-negative sepsis; fewer than 2% of patients experienced allergic-type reactions, a frequency similar to that seen with third-generation cephalosporins. When administered in a dose of 2 mg/kg daily for two days, E5 reduces mortality and improves the outcome of multi-organ failure in patients with gram-negative sepsis, especially when administered before the development of refractory shock. Patients with sepsis of other etiology have not been shown to benefit from antiendotoxin immunotherapy. E5 antibody appears to be an effective agent for the adjunctive treatment of gram-negative sepsis. Further evaluation of E5 antibody is warranted in the treatment of patients with neutropenia, burns, and shock.
Gorelick
K J
KJ
Genelabs, Inc., Redwood City, California.
Chmel
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004731:Endotoxins / Q000276:immunology; D004926:Escherichia coli / Q000276:immunology; D016905:Gram-Negative Bacterial Infections / Q000628:therapy*; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D012772:Shock, Septic / Q000628:therapy; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D004731:Endotoxins; D008070:Lipopolysaccharides; C044101:endotoxin, Escherichia coli