A total of 148 E. coli strains displaying reduced susceptibility to ciprofloxacin (MIC > 2 g/ml) and causing uncomplicated urinary tract infections in eight European countries during 2003 to 2006 were studied. Their phylogenetic groups, biochemical profiles, and antibiotic susceptibilities were determined. Determination of the O:H serotype, pulsed-field gel electrophoresis (PFGE), randomly amplified polymorphic DNA (RAPD) PCR, and multilocus sequence typing provided additional discrimination. The majority (82.4%) of the microorganisms (122/148) carried resistance to two or more additional drugs, with the pattern ciprofloxacin-trimethoprim-sufamethoxazole-tetracycline-ampicillin being the most represented (73 strains out of 148; 49.3%). Extended-spectrum beta-lactamase production was detected in 12/148 strains (8.1%), with CTX-M-15 being the most-common enzyme. Six strains out of the whole collection studied (4.0%) contained a qnrB-like gene. Overall, 55 different PFGE or RAPD PCR profiles could be distinguished, indicating a substantial heterogeneity. However, about one-third (51/148) of the strains belonged to two clonal groups: O15:K52:H1 (phylogenetic group B2, lactose-nonfermenting variant, ciprofloxacin MIC of 16 g/ml) and O25:H4 sequence type 131 (ST-131) (phylogenetic group D, ciprofloxacin MIC of >32 g/ml). With the exception of Poland, strains of these two groups were isolated in samples from all participating countries but more frequently in samples from Spain and Italy. In some representative strains of the two main clonal groups, alterations in GyrA and ParC were the basic mechanism of fluoroquinolone resistance. In some members of the O25:H4 ST-131 group, displaying a ciprofloxacin MIC of >32 g/ml, additional OmpF loss or pump efflux overexpression was found. In the Mediterranean area, strains belonging to these two clonal groups played a major role in determining the high rate of fluoroquinolone-resistant E. coli strains observed in the community.Uncomplicated urinary tract infections (UTIs) are among the most prevalent infectious diseases mainly affecting women. Between one-quarter and one-half of all women experience a UTI at some time (27).The overall etiology has not changed in recent years, and Escherichia coli remains by far the most-common uropathogen, accounting for Ͼ80% of all positive cultures (19). However, the management of these infections is becoming complicated due to the emergence of resistance to several first-line antimicrobial agents in this primary pathogen (13).In fact, in E. coli bacteria, ampicillin and sulfamethoxazoletrimethoprim resistance rates have reached 20% to 50% worldwide. In Europe, increasing percentages of ciprofloxacinresistant mutants have been observed in the community in Spain, Portugal, and Italy (10,18).The results of a recent surveillance survey, the ARESC (Antimicrobial Resistance Epidemiological Survey on Cystitis) study, have shown high rates (Ͼ10%) of ciprofloxacin-resistant E. coli in Spain, Italy, and Russia and the emergence of this problem in all c...