Activity of the trometamol salt of fosfomycin in an in vitro model of the treatment of bacterial cystitis.
The response to trometamol fosfomycin of four strains of Escherichia coli was studied in an in vitro model in which the hydrokinetic aspects of the treatment of bacterial cystitis can be stimulated. Two strains of E. coli that were fully susceptible to fosfomycin, and a strain of intermediate susceptibility responded well to relatively low concentrations of the trometamol salt: doses achieving peak concentrations of 50 or 250 mg/l suppressed bacterial growth for at least 18 h; however, the emergence of resistance was completely suppressed only when a peak concentration of 2500 mg/l was achieved in the bladder model. A strain of E. coli that was fully resistant to fosfomycin in conventional minimum inhibitory concentration titrations responded to the highest dosage used, but this did not prevent further resistance from emerging. These results were obtained in the absence of the potentiating agent, glucose-6-phosphate, which is commonly used in susceptibility tests of fosfomycin. The implications of the results for fosfomycin dosage in bacterial cystitis and for the interpretation of susceptibility tests is discussed.
D000284:Administration, Oral; D003556:Cystitis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004926:Escherichia coli / Q000187:drug effects; D004927:Escherichia coli Infections / Q000188:drug therapy*; D005578:Fosfomycin / Q000627:therapeutic use*; D006801:Humans; D008826:Microbial Sensitivity Tests; D014325:Tromethamine / Q000627:therapeutic use*
D004338:Drug Combinations; D014325:Tromethamine; D005578:Fosfomycin