Investigations on the bactericidal activity of fosfomycin using the membrane filter-agar dilution method and the time-kill technique.

Minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) for a 99% and a 99.9% kill can be reproducibly determined for fosfomycin by the agar dilution procedure when placing the inoculum on top of membrane filters. In 88.7% (85%) of 80 bacterial strains (Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus) examined we found a 99% (99.9%) kill at concentrations higher than the respective MIC by up to one dilution step. For 5% (10%), the bactericidal concentrations were more than two steps higher. Both the MIC and the MBC were influenced by the culture medium. The influence of the medium on fosfomycin activity was also shown by the time-kill curves. In nutrient broth, Mueller-Hinton broth, Iso-Sensitest broth and human plasma water (with and without glucose-6-phosphate) we found different killing rates, different killing maxima and different times of regrowth of the cultures. The bactericidal activity of fosfomycin against Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, and Pseudomonas aeruginosa ATCC 27853 was more pronounced in plasma water, nutrient broth, and Mueller-Hinton broth than in Iso-Sensitest broth.