Nontyphoidal Salmonella (referred to as Salmonella hereafter) is a leading cause of foodborne bacterial enteric disease in the United States, affecting an estimated 1.3 million people each year (Scallan Walter et al., 2025). Chicken is a major source of foodborne salmonellosis; in 2022, 20% of domestically acquired foodborne salmonellosis was attributed to chicken based on outbreak data (IFSAC, 2024). Salmonella enterica serotype Infantis (Infantis) is the sixth most frequently reported serotype among cases monitored by the Centers for Disease Control and Prevention’s (CDC) Foodborne Diseases Active Surveillance Network (FoodNet) (Shah et al., 2024). Although most Infantis infections are sporadic (not associated with outbreaks), Infantis outbreaks linked to chicken during 2012–2021 had a high burden of illness with an increased outbreak trajectory in terms of outbreak associated illnesses (Marshall et al., 2024); as of 2023, Infantis outbreaks linked to chicken had a low burden with decreasing trajectory (CDC, 2025). A study comparing trends in the incidence of human Infantis infection with Infantis prevalence in chicken at processing suggested that the increase in human Infantis infection was likely due to non-chicken transmission pathways (Powell and Williams, 2024).

A multidrug-resistant (MDR) strain of Infantis was first detected in a U.S. resident in 2012; this resident reported traveling to Peru prior to illness onset. Since then, reports of illness from this strain have increased to approximately 500 culture-confirmed illnesses annually during 2018–2024. Although Infantis is only the 6^th most common serotype causing human illness (Shah et al., 2024), interest in this serotype is high due to the frequency of MDR. The persisting strain, identified as REPJFX01, is monitored by the CDC as a reoccurring, emerging, or persisting (REP) strain and varies in genetic diversity beyond the typical outbreak strain (CDC, 2024d). Most REPJFX01 isolates have a chromosomal mutation in the gyrA gene and a pESI-like megaplasmid that carries resistance to multiple antimicrobials, including several that are recommended for first-line or alternative treatment (CDC, 2024d, Tate et al., 2017). Although most people with salmonellosis recover without antibiotics, resistance is concerning because, if treatment is needed, infections resulting from REPJFX01 may not be treatable with antibiotics commonly recommended for Salmonella. Additionally, resistance genes and mutations on mobile plasmids such as pESI can more easily spread to other bacteria, including human and animal pathogens.

REPJFX01 illnesses have historically been linked to international travel and chicken. Local, state, federal health, and regulatory partners investigated 11 outbreaks of REPJFX01 illness during 2016–2023 and identified chicken products as the suspected or confirmed source in three of six outbreaks with a known source. A chicken-associated outbreak of REPJFX01 has not been identified since 2019. (CDC, 2024d, Hutchinson et al., 2018). REPJFX01 has been isolated from the primary U.S. meat and poultry commodities (beef, pork, turkey, chicken), but it is most often isolated from chicken products (CDC, 2024d). Other potential reservoirs of REPJFX01 (i.e., other food, animal, and environmental samples) are not as routinely sampled and reported to PulseNet. Consequently, more than 93% of the >7000 non-clinical REPJFX01 isolates submitted to CDC were from poultry or poultry products (CDC, 2024d), most of which were collected by the USDA due to the Agency’s extensive poultry sampling programs (USDA-FSIS, 2021a).

Because there may be different transmission pathways for different strains of Infantis, we aimed to examine the emergence and trends of REPJFX01 in humans and chickens to assess whether these trends coincide.

During 2003–2023, there were 3,307 reported REPJFX01 human infections; 3,297 human isolates underwent WGS and 10 were not sequenced but met the REPJFX01 definition based on resistance and PFGE pattern Supplementary Data 1. The first identified human REPJFX01 infection occurred in 2012, and by 2019, REPJFX01 accounted for approximately 30% of all human clinical Infantis isolates (Figure 1). There were 516 REPJFX01 chicken carcass isolates; all underwent WGS. REPJFX01 was first isolated from a chicken carcass sample in 2016, and by 2019, REPJFX01 accounted for >90% of all Infantis isolated from chicken carcass samples (Figure 1).

We found that the increase in U.S. illnesses due to REPJFX01 coincided with the emergence of REPJFX01 in U.S. chicken carcasses in 2016, and both REPJFX01 illnesses and carcasses have increased since 2016. Combined with findings from surveillance, outbreak investigations, and evidence that REPJFX01 emerged as a leading strain in retail chicken since 2016 (Brown et al., 2018, CDC, 2024d, McMillan et al., 2022, Tyson et al., 2021), our analysis suggests that chicken is likely an important reservoir.

MDR Infantis strains with a pESI-like plasmid, such as REPJFX01, are not unique to the United States. These MDR Infantis strains likely originated in South America and have been isolated from humans, animals, and the environment around the world (Alvarez et al., 2023, Georganas et al., 2024, Guzinski et al., 2023, Li et al., 2024, Mattock et al., 2024). Although there are several reservoirs for MDR Infantis (CDC, 2024d), it has spread rapidly among chickens globally (Alvarez et al., 2023, Kim et al., 2024, Tate et al., 2017, Tyson et al., 2021). In a systematic review, broilers and chicken meat were found to be the primary sources for MDR Infantis strains (Alvarez et al., 2023). The pESI plasmid has multiple characteristics that contribute to the selection and persistence of this strain in chickens, including fimbria and siderophores, resistance genes, and a higher tolerance to hydrogen peroxide (McMillan et al., 2024, McMillan et al., 2020, Tate et al., 2017).

Illness due to MDR Infantis with a pESI-like plasmid is a public health concern. Globally, these infections have been associated with increased virulence (Alvarez et al., 2023, Fenske et al., 2023, Tyson et al., 2021). In the United States, a recent study did not classify Infantis as a higher virulence serotype (Fenske et al., 2023), and serotypes other than Infantis (e.g., Enteritidis and Typhimurium) have a much higher overall burden (~1% of Salmonella uploads to PulseNet are REPJFX01). However, public health surveillance data show that the hospitalization rate for REPJFX01 infection is comparable to that of other serotypes classified as having higher virulence, like S. Enteritidis and S. Typhimurium (all ~30%) (CDC, 2024d, CDC, 2024e). Additionally, MDR Infantis is more likely to result in extraintestinal infections compared with non-MDR Infantis (CDC, 2024d, Fenske et al., 2023). Also, the antibiotic resistance carried by these isolates is concerning because it can complicate treatment when treatment is needed (Shane et al., 2017), and the plasmid and resistance genes can spread to other Salmonella serotypes and pathogens (FDA, 2022, Li et al., 2024, Tate et al., 2017, Tyson et al., 2021).

Poultry is a leading source of Salmonella foodborne illness in the United States. People can become infected with Salmonella when handling raw chicken, eating undercooked chicken, or eating other foods and beverages that are contaminated by raw chicken or its juices (CDC, 2024c). There is evidence from US outbreak investigations and the international literature that chicken consumption is a transmission pathway for (sometimes severe) human MDR Infantis illness (Alvarez et al., 2023, CDC, 2024d). Also, REPJFX01 has spread rapidly in chickens in the United States (Tyson et al., 2021). Most REPJFX01 isolates from non-human sources reported to PulseNet were from chicken product samples (CDC, 2024d), and in our study, REPJFX01 accounted for 21% of all Salmonella and 97% of all Infantis isolated from chicken carcasses in 2023. However, not all potential reservoirs for REPJFX01 are as robustly sampled (e.g., water, wildlife and other environmental sources). REPJFX01 illnesses have not been linked to contact with live animals, such as backyard chickens, but two Infantis isolates with gyrA mutations were isolated from backyard poultry compost during a study of backyard and commercial broiler production systems in the Southeastern United States (Parzygnat et al., 2025).

Salmonella prevention measures are important to prevent salmonellosis in humans. However, Salmonella strains carrying a pESI plasmid may be harder to prevent in chicken environments; their characteristics (e.g., oxidizer tolerance, fimbriae that increase epithelial attachment, increased biofilm production) can make standard cleaning and disinfection protocols less effective (McMillan et al., 2024, Newton et al., 2020). Disinfecting feeder lines and external areas and applying bacteriophages after cleaning and before disinfection were shown to effectively reduce MDR Infantis in commercial broiler facilities (Newton et al., 2020, Sevilla-Navarro et al., 2024). Furthermore, consumers can prevent REPJFX01 and other Salmonella infections by keeping raw meat and poultry separate from ready-to-eat food, by washing hands and food contact surfaces after handling raw poultry, and by using a food thermometer to ensure poultry is cooked to an internal temperature of 165°F (CDC, 2024a).

This study has several limitations. First, our analysis of human REPJFX01 infections was limited to culture-positive infections reported to PulseNet. Ill persons with REPJFX01 who did not seek medical care or did not have their diagnosis culture-confirmed do not appear in the PulseNet database. We also may have missed some REPJFX01 infections because not all Salmonella isolates underwent WGS, particularly before 2019. We calculated a sensitivity of 99.9% and specificity of 98.7% of resistance to nalidixic acid for REPJFX01 isolates compared with other Infantis isolates (Table A.2), and few isolates that did not undergo sequencing had nalidixic acid resistance and a PFGE that mapped to REPJFX01, suggesting that such cases were likely rare. Second, travel history was not routinely reported to CDC, so we were unable to exclude all international travelers from our analyses; the sensitivity analysis excluding patients with known international travel found similar results to the main analysis. Third, our analysis focused only on REPJFX01 isolated from chicken, although other non-human sources have been reported to PulseNet. Furthermore, we limited our analysis of REPJFX01 prevalence to chicken carcass isolates because chicken carcass sampling methods were more consistent throughout the study period, isolates were routinely submitted to PulseNet, and our sensitivity analysis found similar results when using chicken product data. Lastly, our analysis only establishes a correlation between trends in human infections and chicken carcass prevalence and consequently does not show causation and should not be used to infer attribution. Further research to attribute REPJFX01 illnesses to food sources and more robust sampling and inclusion of non-chicken isolates in PulseNet would be useful to assess chicken consumption as a potential transmission pathway and contextualize it alongside other sources potentially contributing to the overall burden of REPJFX01 human illness.

Although there are likely multiple sources for REPJFX01 infection, the increase in REPJFX01 burden in human illness is highly correlated and concurrent with the increase in prevalence on chicken carcasses. This important MDR strain should be considered in Salmonella prevention strategies. Consumers can prevent REPJFX01 by practicing safe food handling and cooking practices.