Comparison of Endotoxin Release by Different Antimicrobial Agents and the Effect on Inflammation in Experimental Escherichia coli Meningitis

Ian R. Friedland, Hamid Jafari, Stuart Ehrett, Stephen Rinderknecht, Maria Paris, Mark Coulthard, Harri Saxen, Kurt Olsen, George H. McCracken

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

In a rabbit Escherichia coli meningitis model, endotoxin liberation and concentrations of leukocytes, tumor necrosis factor (TNF), and lactate were compared after a single intravenous dose of cefotaxime, cefpirome, meropenem, chloramphenicol, or gentamicin. These antibiotics caused a 2- to IO-fold increase in cerebrospinal fluid concentrations of free (filterable) endotoxin within 2 h of starting treatment. By contrast, free endotoxin concentrations increased almost IOO-fold in untreated animals 4 h later as bacteria continued to multiply. An initial enhancement of inflammation in the central nervous system occurred in all treatment groups compared with untreated controls. No significant differences were observed between treatment groups except for lower TNF concentrations in chloramphenicol-treated animals. Antibiotic therapy in E. coli meningitis, irrespective of the agent used, may result in an increase in free endotoxin and enhancement of inflammation, but the amount of endotoxin liberated is considerably smaller than that shed by untreated bacteria.

Original languageEnglish (US)
Pages (from-to)657-662
Number of pages6
JournalJournal of Infectious Diseases
Volume168
Issue number3
DOIs
StatePublished - Sep 1993

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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