Impact of Different Classes of Antimicrobial Agents on Plasma Endotoxin Activity

Abstract

To investigate the influence of different classes and doses of antibiotics on endotoxin release in gram-negative infection in a rat model of intra- abdominal infection. Immediately after intraperitoneal inoculation of Escherichia coli (5 x 10(7) colony-forming units/kg), anesthetized Wistar rats were treated with a single intravenous dose of an antimicrobial agent: cefotaxime (40 mg/kg), ciprofloxacin (3 mg/kg or 6 mg/kg), imipenem (7 mg/kg or 14 mg/kg), or gentamicin (5 mg/kg). An untreated control group received 0.9% sodium chloride instead of antibiotic. Plasma endotoxin activity, blood bacteria count, and mean arterial pressure were monitored at 60-minute intervals for 5 hours. At the end of the experiment, lavage was performed to determine the bacteria count in the peritoneal cavity. In the untreated group, the blood bacteria count increased rapidly. Five hours after therapy, the plasma endotoxin activity in the cefotaxime group was higher by a factor of 3.6 than in the untreated group. Compared with the cefotaxime group, endotoxin activity was approximately 26% lower in the ciprofloxacin (3 mg/kg) group, 35% lower in the imipenem groups, and 38% lower in the gentamicin group. The lowest endotoxin levels were in the high-dose ciprofloxacin group. Bacteria counts in the peritoneal cavity were lowest in the gentamicin and high-dose ciprofloxacin groups. Except in the high-dose ciprofloxacin group, the endotoxin increase in the therapy groups was associated with a significant (P < .05) decrease in mean arterial pressure. In the early phase of therapy, antibiotic-induced endotoxin release is influenced by the mode of action of the agent class. This is not the sole influence in every class. With quinolones, this effect is also influenced considerably by dosage, ie, by pharmacodynamics.