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

Michael Luchi, David C. Morrison, Steven Opal, Ken Y Yoneda, Gus Slotman, Henry Chambers, Harold Wiesenfeld, Jon Lemke, John L. Ryan, David Horn

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

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-α (TNF-α) 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.

Original languageEnglish (US)
Pages (from-to)25-31
Number of pages7
JournalJournal of Endotoxin Research
Volume6
Issue number1
StatePublished - 2000

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Toxicology

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    Luchi, M., Morrison, D. C., Opal, S., Yoneda, K. Y., Slotman, G., Chambers, H., Wiesenfeld, H., Lemke, J., Ryan, J. L., & Horn, D. (2000). A comparative trial of imipenem versus ceftazidime in the release of endotoxin and cytokine generation in patients with Gram-negative urosepsis. Journal of Endotoxin Research, 6(1), 25-31.