A comparative trial of imipenem versus ceftazidime in the release of endotoxin and cytokine generation in patients with Gram-negative urosepsis

Evidence from ill vitro experiments and animal and human studies indicate t hat antibiotic therapy may induce the release of endotoxin from the outer m embrane of Gram-negative bacteria. Antibiotics that bind preferentially to penicillin-binding protein-2 (PBP-2) -such as imipenem - are associated wit h little release of endotoxin, while antibiotics that preferentially bind t o PBP-3 - such as ceftazidime - are associated with far greater release of endotoxin. We conducted a randomized, multicenter, double-blind study compa ring imipenem to ceftazidime in patients with urinary tract infections caus ed by Gram-negative bacilli associated with signs and symptoms of systemic inflammation. A total of 33 patients were randomized to receive either imip enem (n = 14) or ceftazidime (n = 19) for initial treatment for urosepsis. No differences in plasma endotoxin, interleukin-6 (IL-6), tumor necrosis fa ctor-alpha (TNF-alpha) or urine endotoxin, IL-6 or IL-8 levels were found b etween the two treatment groups within the first 8 h after antibiotic admin istration. We conclude that, if differences exist with respect to endotoxin release by these two antimicrobial agents, these differences an not readil y demonstrable in this clinical study with carefully defined patients with Gram-negative urinary tract infections.