Comparative study of fosfomycin activity in Mueller-Hinton media and in tissues

Fosfomycin utilizes two uptake systems as ways of entry into microorganisms: the L-a-glycerophosphate and the hexose phosphate transport system. The latter is inducible by glucose-6-phosphate. The relationship between glucose-6-phosphate (concentration range 0-100 mg/l) and the susceptibility of Staphylococcus aureus was studied in Mueller-Hinton broth. An almost maximal enhancement of fosfomycin activity was found at 25 mg/l glucose-6-phosphate. Fosfomycin activity against Staph. aureus, Escherichia coli, Proteus mirabilis, Enterobacter cloacae, Klebsiella spp., Serratia spp., and Pseudomonas aeruginosa was studied by use of the broth and the agar dilution method, in the presence and absence of glucose-6-phosphate (25 mg/l). The minimum inhibitory concentrations (MICs) of fosfomycin against Staph. aureus Streptococcus faecalis, E. coli, Ent. cloacae, Pr. mirabilis, and Ps. aeruginosa were estimated in particle free supernatants of 25% tissue homogenates (liver, kidney, lung, heart) and in parallel in Mueller-Hinton broth. With few exceptions the MICs in Mueller-Hinton broth (with glucose-6-phosphate) were similar to those found in tissues (no glucose-6-phosphate added).