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.