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

Department of Medicine, Division of Infectious Diseases, University of Kansas Medical Center, Kansas City, Kansas, USA, mluchi{at}kumc.edu

David C. Morrison

Office of Research Administration, St Luke's Hospital, Kansas City, Missouri, USA

Steven Opal

Brown University School of Medicine, Memorial Hospital, 111 Brewster Street, Pawtucket, Rhode Island, USA

Ken Yoneda

Pulmonary Critical Care Medicine, Davis Medical Center, University of California, Sacramento, California, USA

Gus Slotman

Department of Surgery, Cooper Hospital/Rutgers University Medical Center, Camden, New Jersey, USA

Henry Chambers

San Francisco General Hospital, San Francisco, California, USA

Harold Wiesenfeld

Department of OB/GYN/RS, Magee Women's Hospital, Pittsburgh, Pennsylvania, USA

Jon Lemke

Department of Preventive Medicine and Environmental Health, University of Iowa College of Medicine, Iowa City, Iowa, USA

John L. Ryan

Genetics Institute, Cambridge, Massachusetts, USA

David Horn

Bristol-Myers-Squibb, Plainsboro, New Jersey, USA

Urosepsis Study Group

Evidence from in vitro experiments and animal and human studies indicate that antibiotic therapy may induce the release of endotoxin from the outer membrane of Gram-negative bacteria. Antibiotics that bind preferentially to penicillin-binding protein-2 (PBP-2) —such as imipenem — are associated with little release of endotoxin, while antibiotics that preferentially bind to PBP-3 — such as ceftazidime — are associated with far greater release of endotoxin. We conducted a randomized, multicenter, double-blind study comparing imipenem to ceftazidime in patients with urinary tract infections caused by Gram-negative bacilli associated with signs and symptoms of systemic inflammation. A total of 33 patients were randomized to receive either imipenem (n = 14) or ceftazidime (n = 19) for initial treatment for urosepsis. No differences in plasma endotoxin, interleukin-6 (IL-6), tumor necrosis factor- (TNF-) or urine endotoxin, IL-6 or IL-8 levels were found between the two treatment groups within the first 8 h after antibiotic administration. We conclude that, if differences exist with respect to endotoxin release by these two antimicrobial agents, these differences are not readily demonstrable in this clinical study with carefully defined patients with Gram-negative urinary tract infections.

Journal of Endotoxin Research, Vol. 6, No. 1, 25-31 (2000)
DOI: 10.1177/09680519000060010401


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