Integrated Epidemiologic and Genomic Surveillance of Carbapenemase-Producing Enterobacterales in a Regional Healthcare Network

Background Carbapenemase-producing Enterobacterales (CPE) pose a persistent challenge across interconnected healthcare networks. Although epidemiologic risk factors for CPE colonization are well described, evidence integrating patient-level risk profiling with regional genomic surveillance remains limited. Methods We conducted a multicenter study integrating epidemiologic risk factor analysis with regional genomic surveillance across three acute-care hospitals and six long-term care facilities in Gangwon Province, Korea. A matched case-control study of 908 patients screened for CPE at admission between August 2024 and June 2025, including 445 CPE-colonized patients and 463 non-colonized controls, identified independent predictors of CPE colonization using multivariable logistic regression. Whole-genome sequencing of 242 CPE isolates collected across the regional healthcare network was performed to characterize circulating lineages, resistance determinants, and genetic connectivity among facilities. Results Significant predictors of CPE colonization included prior hospitalization, prior CPE colonization or infection, and prior room sharing with a CPE-colonized or infected patient within the previous year; recent exposure to carbapenems, glycopeptides, penicillins, or proton pump inhibitors; recent indwelling device use; and the presence of wound drainage or respiratory secretions at the time of screening. Genomic surveillance revealed a regionally structured CPE population dominated by Klebsiella pneumoniae . The KPC-producing ST307 clone was widely distributed across multiple facilities, while additional lower-frequency lineages, including ST11 and ST16, highlighted the genomic diversity of the regional CPE population. A single ST23-1LV isolate carrying blaKPC and multiple hypervirulence-associated loci was identified, representing a potential convergence of carbapenem resistance and hypervirulence. Regional variation in lineage composition suggested heterogeneous dissemination dynamics, whereas SNP-based genetic linkage patterns indicated putative interfacility circulation across the healthcare network. Conclusions CPE dissemination within this regional healthcare network was associated with both identifiable high-risk patient populations and persistent circulation of KPC-producing Klebsiella pneumoniae ST307. These findings support coordinated regional approaches integrating risk-based screening, interfacility information sharing, and genomics-informed surveillance to strengthen future CPE prevention and control efforts.