Tracking bla _KPC Plasmid Dissemination within and between Enterobacterales across Michigan Over a Decade

bla _KPC is endemic among Enterobacterales in the USA. While present on diverse plasmids, bla _KPC burden is often associated with the clonal spread of multi-drug resistant (MDR) epidemic lineages. In this study we sought to determine the relative contributions of clonal spread and plasmid transfer to bla _KPC burden across Michigan healthcare facilities over a decade. To this end we performed whole-genome sequencing of 1,058 KPC-producing isolates collected from 47 Michigan healthcare facilities between 2013 and 2022, including long-read sequencing for 527 isolates to enable precise plasmid tracking. Analysis with MOB-suite identified 64 distinct KPC plasmid types (“secondary clusters”), with the AK975 broad-host range plasmid being the most prevalent, found in 27% of isolates, spanning 20 species and 92 sequence types. Among genomes with AK975, 30% were from epidemic and 70% non-epidemic lineages, highlighting its broad role in regional bla _KPC spread. Epidemic lineages of various species constituted 46% of the study population. Epidemic lineages differed in their primary plasmids, and even within epidemic lineages there were clonal expansions with distinct bla _KPC plasmids, including in some cases AK975. These findings highlight two patterns of KPC spread: transmission of epidemic lineages harboring broad-range and lineage-specific KPC plasmids; and broader spread of AK975 among diverse species. Traditional surveillance studies often focus on common MDR lineages, potentially overlooking rare species and lineages that mediate the spread of plasmid-borne antimicrobial resistance (AMR) genes. Here we show how longitudinal studies tracking plasmids across species are essential to understand the pathways leading to AMR infections in hospitals.