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Background Carbapenem-resistant Enterobacterales (CRE) harboring blaKPC have been endemic in Chicago-area healthcare networks for more than a decade. During 2016–2019, a series of regional point-prevalence surveys identified increasing prevalence of blaNDM-containing CRE in multiple long-term acute care hospitals (LTACHs) and ventilator-capable skilled nursing facilities (vSNFs). We performed a genomic epidemiology investigation of blaNDM-producing CRE to understand their regional emergence and spread. Methods We performed whole-genome sequencing on New Delhi metallo-beta-lactamase (NDM)+ CRE isolates from 4 point-prevalence surveys across 35 facilities (LTACHs, vSNFs, and acute care hospital medical intensive care units) in the Chicago area and investigated the genomic relatedness and transmission dynamics of these isolates over time. Results Genomic analyses revealed that the rise of NDM+ CRE was due to the clonal dissemination of an sequence type (ST) 147 Klebsiella pneumoniae strain harboring blaNDM-1 on an IncF plasmid. Dated phylogenetic reconstructions indicated that ST147 was introduced into the region around 2013 and likely acquired NDM around 2015. Analyzing the relatedness of strains within and between facilities supported initial increases in prevalence due to intrafacility transmission in certain vSNFs, with evidence of subsequent interfacility spread among LTACHs and vSNFs connected by patient transfer. Conclusions We identified a regional outbreak of blaNDM-1 ST147 that began in and disseminated across Chicago area post-acute care facilities. Our findings highlight the importance of performing genomic surveillance at post-acute care facilities to identify emerging threats.

Regional Spread of blaNDM-1-Containing Klebsiella pneumoniae ST147 in Post-Acute Care Facilities