Although in certain countries in Europe fosfomycin trometamol (FT) has been used for many years, in Turkey FT has become available in recent years. FT has a broad-spectrum activity against most of gram-positive and gram-negative bacteria. In this study, we aimed to evaluate the effect of FT, a new alternative antimicrobial agent in the treatment of patients with Escherichia coli related uncomplicated lower urinary tract infection (UTI). For this purpose, between May 2007-July 2008, FT susceptibility of 771 nonduplicate E. coli strains, isolated from urine samples of patients with uncomplicated lower UTI (bacteria > or = 10(5) cfu/mL), was determined by disk diffusion method according to Clinical and Laboratory Standarts Institute (CLSI) criteria. Simultaneously, extended-spectrum beta-lactamase (ESBL) detection was performed by double disk synergy test in all isolates. Among all E. coli isolates, FT resistance rate was 0.4% (3/771) and ESBL positivity was 19.5% (150/771). The rates of ESBL producing strains isolated from inpatients and outpatients were 34.1% (70/205) and 14.1% (80/566), respectively, and the difference was found statistically significant (p = 0.0001). Although resistance to FT was not detected in non-ESBL producing E. coli isolates (n = 621), FT resistance rate was 2% (3/150) in ESBL producers. As far as the current literature was concerned this was the largest scale study investigating the activity of FT in Turkey. Resistance to antimicrobials that had been used frequently as therapeutic options for the treatment of E. coli related UTIs, has been increasing. In the present study high susceptibility rates to FT was determined for urinary E. coli isolates. In conclusion, these data suggest that FT may be a good alternative for the treatment of uncomplicated UTIs as a first line antimicrobial agent.