Antibiotic-Induced Endotoxin Release in Patients with Gram-Negative Urosepsis: A Double-Blind Study Comparing Imipenem and Ceftazidime

The clinical significance of differences between antibiotics in endotoxin-liberating potential is unknown. Thirty patients with gram-negative urosepsis were randomized between imipenem and ceftazidime, which have, respectively, a low and a high endotoxin-liberating potential in vitro. In patients treated with ceftazidime, a slower defervescence was noticed. After 4 h of treatment, the blood endotoxin level decreased in all 3 endotoxemic patients receiving imipenem, whereas it increased in 2 of the 4 endotoxemic patients receiving ceftazidime, and in ceftazidime-treated patients, the endotoxin level in urine decreased less than in imipenem-treated subjects. Serum and urine cytokine levels increased 10%-40% after 4 h of ceftazidime treatment compared with no increase in the imipenem-treated patients (P > .05). Endotoxin release during antibiotic killing in vitro, assessed for all microorganisms, was 10-fold higher with ceftazidime (P < .001). These results indicate that differences between antibiotics in endotoxin release may affect the inflammatory response during treatment.