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A 76-year-old woman had recurrent urosepsis due to extended-spectrum β-lactamase-positive Escherichia coli. Imipenem resistance was detected after long-term imipenem-meropenem therapy. The carbapenem-hydrolyzing enzyme gene was identified as bla_KPC-3. To our knowledge, this is the first documented case in which carbapenem-resistant E. coli emerged during therapy with imipenem and meropenem, and the first identification of the carbapenem-hydrolyzing enzyme in E. coli isolates.