Wirkungssteigerung von Fosfomycin durch Zusatz von Glukose-6-Phosphat bei intraperitoneal infizierten Mäusen

Abstract

The increase of antimicrobial activity of Fosfomycin by glucose-6-phosphate (G-6-P) has often been demonstrated by in vitro studies. However, this effect was never sufficiently established in vivo. Our study was carried out in order to investigate the effects of the addition of G-6-P to Fosfomycin in white mice (strain G.P. of N.I.H.), which were intraperitoneally infected with a strain of S. typhimurium (10³ c.f.u/0.5 ml i.p.). One and six hours after the infection, 0.1 ml consisting of increasing doses of G-6-P (0, 5, 25, 50, 250 and 500 μg/g) and decreasing doses of Fosfomycin (15.6, 7.8, 3.9, 1.95, 0.98 and 0.49 μg/g) were applied i.m., using 10 animals for each combination. Tables 1 and 2 show the results of this therapy with regard to the reduction of the ED₅₀ of Fosfomycin. It can be seen that the addition of 25 μg G-6-P/g body-weight significantly reduces the ED₅₀ within the first days (Tab. 1), while doses of 50 and more μg G-6-P/g significantly reduce the ED₅₀ during the whole investigation period (Tab. 2). These results justify the proposal to use a combination of Fosfomycin and G-6-P in clinical studies for the treatment of human infections.