DIFFERENTIAL ANTIBIOTIC-INDUCED RELEASE OF ENDOTOXIN FROM GRAM-NEGATIVE BACTERIA

Treatment of log phase cultures of Escherichia coli with cell wall act ive antibiotics results in increased exposure of immunologically react ive lipid A epitopes of lipopolysaccharide (LPS) and release of solubl e LPS into culture supernatants. Comparison of the efficacy of two cel l wall active antibiotics, ceftazidime, a penicillin-binding protein 3 selective antibiotic, and imipenem, a penicillin-binding protein 2 se lective antibiotic, for their relative efficacy in mediating LPS relea se indicated quantitative but not qualitative differences, with the fo rmer antibiotic manifesting a significantly broader range of concentra tions at which LPS release could be demonstrated. Comparison of the re lative efficacy of these two antibiotics in a mouse bacteraemia model in which animals were made hypersensitive to the lethal effects of end otoxin by treatment with D-galactosamine indicated th at the latter an tibiotic may provide a greater level of protection. These studies sugg est that the release of endotoxin mediated by antibiotic treatment may contribute to the pathogenesis of disease in infections due to gram-n egative organisms.