IntroductionSalmonella entericais a major cause of foodborne illness in the United States. A multi-drug resistant (MDR) emergentSalmonellaInfantis (ESI) with a megaplasmid (pESI) was first identified in Israel and Italy and subsequently reported worldwide. The ESI clone carrying an extended spectrum β-lactamaseblaCTX-M-65 on a pESI-like plasmid and a mutation in thegyrA gene has recently been found in the United States in poultry meat.MethodsWe analyzed the phenotypic and genotypic antimicrobial resistance, genomics and phylogeny of 200S. infantisisolates from animal diagnostic samples.ResultsOf these, 33.5% were resistant to at least one antimicrobial and 19.5% were multi-drug resistant (MDR). Eleven isolates from different animal sources were phenotypically and genetically similar to the ESI clone. These isolates had a D87Y mutation in thegyrA gene conferring reduced susceptibility to ciprofloxacin and harbored a combination of 6–10 resistance genes:blaCTX-M-65,aac(3)-IVa,aadA1,aph(4)-Ia,aph(3′)-Ia,floR,sul1,dfrA14,tetA, andfosA. These 11 isolates carried class I and class II integrons and three virulence genes: sinH, involved in adhesion and invasion,ybtQ andybtP, associated with iron transport. These isolates were also closely related to each other (separated by 7 to 27 SNPs) and phylogenetically related to the ESI clone recently found in the U.S.DiscussionThis dataset captured the emergence of the MDR ESI clone in multiple animal species and the first report of a pESI-like plasmid in isolates from horses in the U.S.