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Comparison of endotoxin release by different antimicrobial agents and the effect on inflammation in experimental Escherichia coli meningitis.

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 10-fold increase in cerebrospinal fluid concentrations of free (filterable) endotoxin within 2 h of starting treatment. By contrast, free endotoxin concentrations increased almost 100-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.
AuthorsI R Friedland, H Jafari, S Ehrett, S Rinderknecht, M Paris, M Coulthard, H Saxen, K Olsen, G H McCracken Jr
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 168 Issue 3 Pg. 657-62 (Sep 1993) ISSN: 0022-1899 [Print] United States
PMID8354907 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Bacterial Agents
  • Cephalosporins
  • Endotoxins
  • Gentamicins
  • Thienamycins
  • Chloramphenicol
  • Meropenem
  • Cefotaxime
  • cefpirome
Topics
  • Animals
  • Anti-Bacterial Agents (pharmacology)
  • Cefotaxime (pharmacology)
  • Cephalosporins (pharmacology)
  • Chloramphenicol (pharmacology)
  • Endotoxins (cerebrospinal fluid)
  • Escherichia coli Infections (drug therapy, metabolism)
  • Gentamicins (pharmacology)
  • Inflammation (metabolism)
  • Male
  • Meningitis, Bacterial (drug therapy, metabolism)
  • Meropenem
  • Rabbits
  • Thienamycins (pharmacology)

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