Differential antibiotic-induced release of endotoxin from gram-negative bacteria.
Treatment of log phase cultures of Escherichia coli with cell wall active antibiotics results in increased exposure of immunologically reactive lipid A epitopes of lipopolysaccharide (LPS) and release of soluble LPS into culture supernatants. Comparison of the efficacy of two cell wall active antibiotics, ceftazidime, a penicillin-binding protein 3 selective antibiotic, and imipenem, a penicillin-binding protein 2 selective antibiotic, for their relative efficacy in mediating LPS release indicated quantitative but not qualitative differences, with the former antibiotic manifesting a significantly broader range of concentrations at which LPS release could be demonstrated. Comparison of the relative efficacy of these two antibiotics in a mouse bacteraemia model in which animals were made hypersensitive to the lethal effects of endotoxin by treatment with D-galactosamine indicated that the latter antibiotic may provide a greater level of protection. These studies suggest that the release of endotoxin mediated by antibiotic treatment may contribute to the pathogenesis of disease in infectious due to gram-negative organisms.
Bucklin
S E
SE
Department of Microbiology, Molecular Genetics and Immunology, School of Medicine, University of Kansas Medical Center, Kansas City 66160.
Fujihara
Y
Y
Leeson
M C
MC
Morrison
D C
DC
D000818:Animals; D002442:Ceftazidime / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000188:drug therapy*; D005260:Female; D005688:Galactosamine / Q000008:administration & dosage; D015378:Imipenem / Q000494:pharmacology* / Q000627:therapeutic use; D008050:Lipid A / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D051379:Mice; D008826:Microbial Sensitivity Tests
D008050:Lipid A; D008070:Lipopolysaccharides; D015378:Imipenem; D005688:Galactosamine; D002442:Ceftazidime