This study determined the phylogenetic groups and virulence factors of 37 Escherichia coli isolates producing types of CTX-M compared with those of 19 isolates producing different types of extended-spectrum -lactamases (ESBLs) in a well-defined North American population. Most CTX-M-14 producers (97%) were from phylogenic group D; 67% of the CTX-M-15 producers were from group B2. A single CTX-M-14-producing strain belonged to clonal group A. There were significant prevalence differences for individual virulence factors among CTX-M producers and nonproducers; however, aggregate virulence factor scores were similar. CTX-M producers more commonly caused repeat urinary tract infections. Our results indicate that CTX-M type predicts phylogenetic background, and the virulence potential of ESBL-producing E. coli isolates is a complex issue, requiring further study and ongoing surveillance.Enterobacteriaceae, especially Klebsiella spp. producing extended-spectrum -lactamases (ESBLs), such as SHV and TEM types, have been recognized since the 1980s as a major cause of hospital-acquired infections (3). However, during the late 1990s and 2000s, Enterobacteriaceae (mostly Escherichia coli) producing novel ESBLs, the CTX-M enzymes, have been identified, from both the hospital and community settings (26). Surveys from several countries, including Canada (25), Spain (27), and the United Kingdom (31) show that CTX-M-producing E. coli strains isolated from community sites, exhibited coresistance to trimethoprim-sulfamethoxazole, tetracycline, gentamicin, and ciprofloxacin, further limiting therapeutic options.Phylogenetic analyses have shown that E. coli strains fall into four main phylogenetic groups (A, B1, B2, and D) (10). Virulent extraintestinal strains derive mainly from group B2 and, to a lesser extent, group D, whereas most commensal strains derive from groups A and B1 (11). Most virulence factors are concentrated predominantly either within group B2 or jointly within groups B2 and D, although certain factors are concentrated significantly in group D but not in group B2, while others are distributed across the population without a significant concentration in either group B2 or group D. These diverse patterns suggest more complex evolutionary histories for the various virulence factors present in E. coli. Fluoroquinolone-resistant E. coli isolates causing urinary tract infections (UTIs) most often belong to the low-virulence phylogenetic groups A and B1 (12) or group D (14). Such resistant strains typically exhibit a decreased prevalence of certain virulence factors and a seemingly reduced invasive capacity (30). We studied a well-defined population from North America to determine the virulence-associated traits of E. coli isolates from community and hospital source specimens. Specifically, isolates producing types of CTX-M -lactamases were compared, according to phylogenetic group and virulence factor profile, with E. coli isolates producing different types of well-characterized ESBLs.