Kinetics of endotoxin release during antibiotic therapy for experimental gram-negative bacterial sepsis.

For study of the kinetics of endotoxin release from bacterial cells during therapy for gram-negative bacterial sepsis, serial blood samples were obtained from rabbits with Escherichia coli sepsis that were treated with either antibiotic or placebo. The concentrations of viable bacteria, free endotoxin, and total endotoxin in each blood sample were quantitated. In animals treated with placebo the concentration of free endotoxin was proportional to the level of bacteremia. In contrast, in animals treated with antibiotic the plasma levels of free endotoxin increased 10- to 2,000-fold, in spite of decreasing levels of bacteremia. Free endotoxin that was present in the plasma following antibiotic treatment appeared to be derived in part from the breakdown of circulating bacteria and in part from the disintegration of bacteria in tissues other than the blood. The results of this study demonstrate that significant amounts of endotoxin are released from bacterial cells following administration of antibiotics in vivo.