Distinct origins and transmission pathways of bla KPC Enterobacterales across three U.S. states

Background Carbapenem-resistant Enterobacterales (CRE) are among the most concerning antibiotic resistance threats due to high rates of multidrug resistance, transmissibility in healthcare settings, and high mortality rates. We evaluated the potential for regional genomic surveillance to track bla KPC -carrying CRE (KPC-CRE) transmission across healthcare facilities in three U.S. states. Methods Clinical isolates were collected from Connecticut (CT; 2017-2018), Minnesota (MN; 2012-2018), and Tennessee (TN; 2016-2017) through the U.S. Centers for Disease Control and Prevention’s Multi-site Gram-negative Surveillance Initiative and additional surveillance. KPC-CRE isolates were whole-genome sequenced, and case report data on patient comorbidities, healthcare utilization, and interfacility patient transfer were extracted. Findings In CT, most KPC-CRE isolates showed evidence of importation from outside the state, with limited local transmission. In MN, cases were mainly from sporadic importation and transmission of bla KPC -carrying Klebsiella pneumoniae (KPC-Kp) ST258, and clonal expansion of an imported epidemic lineage of bla KPC -carrying Enterobacter hormaechei (KPC-Ec) ST171 primarily at a single focal facility and its satellite facilities. In TN, KPC-Kp ST258, and more recently emerged KPC-Kp ST307 and KPC-Eh ST114 were most common, with largely non-overlapping facility networks mediating the spread of ST258 versus ST307 and ST114. Conclusions The underlying processes driving KPC-CRE burden can differ substantially across regions, and different STs can spread via distinct pathways within a region. Integrating genomic and epidemiological data from regional surveillance, and information on interfacility patient transfers, can provide insights to target interventions.