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coli that breach a sterile barrier to cause extraintestinal infections. This question has become more complicated by the advent of whole genome sequencing (WGS) that has raised a new question about the taxonomic characterization of E. coli based on traditional clinical microbiologic and phylogenetic methods. This review discusses how molecular epidemiologic approaches have been used to address these questions, and how answers to these questions may contribute to our better understanding of the epidemiology of infections caused by E. col