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We report for the first time the isolation of CTX-M-15-producing Escherichia coli strains belonging to sequence type (ST) 410, ST224, and ST1284 in commercial swine in Brazil. The bla_CTX-M-15 gene was located on F-::A9::B1 and C1::A9::B1 IncF-type plasmids, surrounded by a new genetic context comprising the IS26 insertion sequence truncated with the ISEcp1 element upstream of bla_CTX-M-15. These results reveal that commercial swine have become a new reservoir of CTX-M-15-producing bacteria in South America.