Fosfomycin trometamol: historical background and clinical development.

A brief historical review of the clinical development of fosfomycin is given. Fosfomycin has attracted great interest because of its broad spectrum of activity and excellent tolerability. However, some problems have arsen because of the rapid emergence of resistant strains, and the poor bioavailability by oral route. Fosfomycin trometamol (a salt of fosfomycin with tromethamine) overcomes this difficulty: in fact when given by oral route it reaches very high and persistent urinary concentrations (up to 48 h). This behaviour allows a long-lasting bactericidal activity in urine to be obtained and the emergence of resistant variants to be prevented. These characteristics allowed proposing the drug for the "single dose therapy" of lower uncomplicated urinary tract infections. The clinical trials confirmed that this assumption was correct, demonstrating the excellent therapeutic activity of the drug in this indication.