IMPACT OF DIFFERENT CLASSES OF ANTIMICROBIAL AGENTS ON PLASMA ENDOTOXIN ACTIVITY

Objective: To investigate the influence of different classes and doses of antibiotics on endotoxin release in gram-negative infection in a r at model of intraabdominal infection. Design: Immediately after intrap eritoneal inoculation of Escherichia coli (5 X 10(7) colony-forming un its/kg), anesthetized Wistar rats were treated with a single intraveno us dose of an antimicrobial agent: cefotaxime (40 mg/kg), ciprofloxaci n (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 in stead 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 determin e the bacteria count in the peritoneal cavity. Results: In the untreat ed group, the blood bacteria count increased rapidly. Five hours after therapy, the plasma endotoxin activity in the cefotaxime group was hi gher by a factor of 3.6 than in the untreated group. Compared with the cefotaxime group, endotoxin activity was approximately 26% lower in t he ciprofloxacin (3 mg/kg) group, 35% lower in the imipenem groups, an d 38% lower in the gentamicin group. The lowest endotoxin levels were in the high-dose ciprofloxacin group. Bacteria counts in the peritonea l cavity were lowest in the gentamicin and high-dose ciprofloxacin gro ups. Except in the high-dose ciprofloxacin group, the endotoxin increa se in the therapy groups was associated with a significant (P<.05) dec rease in mean arterial pressure. Conclusions: In the early phase of th erapy, 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.