Bacteremia versus endotoxemia in experimental mouse leukopenia - Role of antibiotic chemotherapy

Imipenem and ceftazidime have different specificities for penicillin-binding proteins and cause a differential release of lipopolysaccharide (LPS) from gram-negative bacteria in vitro. In studies in mice made leukopenic by the administration of cyclophosphamide, the innate relative resistance to the lethal effects of LPS was not significantly changed, but these animals became highly sensitized to bacterial infection. When leukopenic mice were challenged with graded doses of Escherichia coli O111:B4, an LD(50) was achieved at a dose of similar to 10(6) cfu, Administration of either antibiotic resulted in a shift in the LD(50) of similar to 500-fold, in contrast to D-galactosamine-treated LPS-sensitized mice, in which a < 10-fold increase in the LD(50) was observed with antibiotic therapy, Further, if mice were made LPS-sensitive with D-galactosamine, no differences between leukopenic and normal mice were noted with antibiotic therapy.