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This study analyzes the epidemiology of hospital and community-acquired infections caused by Escherichia coli. The antimicrobial resistance pattern was used to characterize the isolates, and a prospective observational study was performed to assess the relationship between antimicrobial use and bacterial resistance. The study was conducted during a 3-month period in a 1,200-bed tertiary care hospital in Nantes, France. An E. coli infection was diagnosed in 3.8% of the patients (507 of 13,384) admitted to the hospital between 1 January and 31 March 1996. Of the 507 isolates, 205 (40.4%) were resistant to at least one antimicrobial; 40% were resistant to amoxicillin, 30% to amoxicillin/clavulanate, 38% to ticarcillin, and 16% to trimethoprim-sulfamethoxazole, while resistance to other antimicrobials was low. Prior receipt of antimicrobial and/or immunosuppressive therapy was significantly associated with infection caused by a resistant organism.