Despite the recent global spread of CTX-M β-lactamases in Escherichia coli isolates from community-acquired urinary tract infections (CA-UTIs), their dissemination has been little studied in developing countries. In a 2-year prospective study, we documented the prevalence of extended-spectrum β-lactamases (ESBLs) in E. coli that were responsible for CA-UTIs in Phnom-Penh, Cambodia. Ninety-three E. coli strains were included. We observed a high prevalence of resistance to amoxicillin (88.2% of strains), cotrimoxazole (75.3%), ciprofl oxacin (67.7%), gentamicin (42.5%), and third-generation cephalosporins (37.7%). A total of 34 strains carried ESBLs, all of which were CTX-M type. CTX-M carriage was associated with resistance to fl uoroquinolones and aminoglycosides. Using repetitive extragenic palindromic-PCR, we identifi ed 4 clusters containing 9, 8, 3, and 2 strains. The prevalence of CTX-M β-lactamases has reached a critical level in Cambodia, which highlights the need for study of their spread in developing countries.