Epidemiology and antimicrobial resistance of <i>Salmonella enterica</i> serotype Infantis in the United States: infections and emergence of a multidrug-resistant strain during 1979–2022

<i>Salmonella</i> infections are a major cause of human illness in the United States. <i>Salmonella enterica</i> serotype Infantis has re-emerged as a leading serotype with the emergence of a multidrug-resistant <i>S.</i> Infantis strain, designated as REPJFX01 by the Centers for Disease Control and Prevention (CDC). REPJFX01, which typically contains a megaplasmid of emerging <i>Salmonella</i> Infantis (pESI) harbouring multiple resistance genes and a chromosomal <i>gyrA87</i> mutation conferring decreased susceptibility to ciprofloxacin, has caused human infections linked to chicken consumption. The study aimed to describe the epidemiology and antimicrobial resistance of human <i>S.</i> Infantis infections, including the emergence of REPJFX01, in the United States. The study used data from five CDC surveillance systems, with combined years from 1979 through 2022. Negative binomial and logistic regression models were used in the multivariable analyses of surveillance data. In 10 active surveillance sites, the mean annual incidence of human <i>S.</i> Infantis infections was twice as high during 2013–2022 vs. 2003–2012 (adjusted rate ratio = 1.96, 95% CI 1.75–2.20). REPJFX01 infections accounted for nearly one-third of <i>S.</i> Infantis infections during 2018–2022 (vs. 2013–2017, adjusted odds ratio = 2.09, 95% CI 1.56–2.79). <i>Salmonella</i> Infantis infections were more likely among persons who were ≥45 years old, female, from racial and ethnic minority groups, and had <i>Salmonella</i> isolated from urine, than infections with other common serotypes. The increase in <i>S.</i> Infantis infections during 2013–2022 was likely driven by an increase in REPJFX01 infections. Public health strategies to reduce <i>Salmonella</i> contamination of chicken could help prevent human infections.