[Improvement of the therapeutic efficacy of fosfomycin by addition of glucose-6-phosphate in the treatment of intraperitoneally infected mice (author's transl)].
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 (10(3) 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 micrograms/g) and decreasing doses of Fosfomycin (15.6, 7.8, 3.9, 1.95, 0.98 and 0.49 micrograms/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 micrograms G-6-P/g body-weight significantly reduces the ED50 within the first days (Tab. 1), while doses of 50 and more micrograms 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.