PREVENTION OF ENDOTOXIN EFFECTS IN A GRAFT-NEGATIVE SEPTICEMIA MODEL WITH POLYMYXIN B

Abstract

The antibiotic polymyxin B sulfate has been shown to neutralize endotoxin lethality in chick embryos and adrenalectomized mice and to prevent endotoxin induced leukopenia, thrombocytopenia disseminated intravascular coagulation and renal cortical necrosis in rabbits. In this study, the anti-endotoxin effect of polymyxin B was investigated in experimentally induced septicemia in rabbits. The Pasteurella multocida organisms were sensitive to the antibacterial action of penicillin, but not to polymyxin B. Twenty-five animals pretreated with polymyxin showed positive blood cultures and significantly reduced plasma endotoxin levels (Limulus test) with normal white blood cell and platelet counts when analyzed six hours after the injection of live organisms. Polymyxin therapy, given after the animals had established endotoxemia-septicemia, reduced the plasma endotoxin levels and improved the survival, but had no effect on the leukopenia and thrombocytopenia. Forty-seven control animals treated only with saline revealed the characteristic findings of positive blood cultures, high endotoxin activity levels, severe leukopenia and thrombocytopenia and a high mortality rate. The best survival data were obtained in rabbits who were treated with both penicillin and polymyxin. The data suggests that polymyxin B is effective in neutralizing the endotoxin effects from live organisms and that the timing of polymyxin treatment is of critical importance.