Relevance of antimicrobial agent-induced endotoxin release from in vitro cultured Escherichia coli and in vivo experimental infection with Gram-negative bacilli

Abstract

In vitro exposure of Gram-negative bacilli (GNB) to antimicrobial agents may induce endotoxin (ET) release, that may cause various reactions in vivo resulting in endotoxic shock. We used the antimicrobial agents, flomoxef (FMOX) and gentamicin (GM), to investigate the kinetics of ET released from in-vitro-cultured Escherichia coli and to examine the ET effect on tumor necrosis factor (TNF) production by macrophages. In a rabbit model of E. coli peritonitis, we measured plasma ET, TNF and blood bacterial counts under the administration of FMOX or GM. In our in vitro experiment, ET levels under FMOX were significantly higher than those under GM, and ET induced TNF production in a dose-dependent manner. However, in vivo, plasma ET, TNF, and blood bacterial counts under antimicrobial agents were significantly lower than those of the controls, and those under FMOX treatment did not differ from those under GM treatment. Thus, ET release may not be a critical problem in GNB infections if appropriate antimicrobial agents are administered.