Ultrastructure and Viability of K. pneumoniae Treated with Fosfomycin

The effect of Fosfomycin on K. pneumoniae ATCC 10031 was studied. The morphology on the electron microscopical level and the viability were markedly altered after application of 6 micrograms/ml and 60 micrograms/ml of Fosfomycin, respectively. These were chosen because they can be attained in man by oral or parenteral administration. Until 30 min after the administration of 6 micrograms/ml, and 10 min after administration of 60 micrograms/ml the turbidity increased in the same range as in the control. Thereafter the turbidity decreased but did not fall below its minimal values; after application of 6 micrograms/ml of Fosfomycin the OD remained at higher levels than after applying 60 micrograms/ml of Fosfomycin, at all corresponding times. The number of viable cells, after application of 6 micrograms/ml of Fosfomycin, was maximally reduced for 70% of the value at the time of administration. 60 micrograms/ml quickly impaired the ability of reproduction. Consequently, the CFU were reduced continuously, e.g. by 80% after 30 min and by more than 99% after 180 min. The finestructural alterations were characterized by loss of contrast and regular shape. The occurrence of protruded protoplasts and defects in the cell wall indicate the action of Fosfomycin on the bacterial envelope, preferably on the peptidoglycan layer.