With the rapid spread of multidrug-resistant bacteria, carbapenem-resistant Enterobacteriaceae (CRE) has been reported worldwide as a major concern because of limited treatment options. Carbapenem resistance is mainly due to carbapenem-ase, a carbapenem-degrading enzyme, which is mainly encoded on a plasmid to spread across bacterial species. However, there have been only small-scale attempts to determine the similarities or accommodations of the plasmids disseminating regionwide. We analysed the 230 CRE isolates carrying blaIMP from 43 medical facilities in the northern Osaka area focusing on the plasmids, the main carriers of the drug resistance genes. Combination of whole genome sequencing and Southern blotting revealed the predominant dissemination of blaIMP-6 by the pKPI-6 plasmid among genetically distinct isolates, as well as the emergences of derivatives that acquired various advantages. We iden-tified heteroresistance likely causing stealth transmissions, which was generated by the transcriptional regu-lation of blaIMP-6, stabilization of blaIMP-6 through chromosomal integration, enhanced carbapenem resistance through plasmid multimerization, or broadened antimicrobial resistance due to a single point mutation in blaIMP-6. In this article, I dis-cussed the mechanisms of regional spread of CRE and enhancement of carbapenem resistance providing the insights to prevent their disseminations.