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COMPARATIVE STUDY OF ENDOTOXIN RELEASE FOLLOWING THERAPY WITH AN AMINOGLYCOSIDE VERSUS A THIRD GENERATION CEPHALOSPORIN

In order to determine if the rate of endotoxin Liberation following antibiotic therapy of gram-negative bacterial sepsis is related to the antibiotic class administered, sepsis was induced in 12 rabbits by intraperitoneal injection of E. coli K1. Blood was sampled just prior to and 1/2 hour and hourly following antibiotic administration. Bacteremia was measured by quantitative culture. Plasma endotoxin levels before and after passage through a 0.45 micron filter were quantitated by Limulus lysate assay. Two hours after infection rabbits received either 2.5 mg/kg of gentamicin or 100 mg/kg of moxalactam intravenously. Both groups of rabbits developed similar mean levels of bacteremia and free endotoxin prior to antibiotic therapy. However, beginning within 1/2 hour after antibiotic administration and continuing for 4 hours, two to ten-fold higher mean levels of free (filterable) endotoxin were present in the moxalactam-treated rabbits as compared to the gentamicin-treated rabbits (p <.05 for each sample time). These higher mean levels of free endotoxin occurred in the moxalactam group although there was no significant difference in the mean rates of bacterial killing. Assessment of the clinical significance, if any, of the observed difference in rates of endotoxin liberation following aminoglycoside therapy versus third generation cephalosporin therapy will require further studies employing biochemical and physiological measurements.