Whole-genome sequence analyses revealed the presence of ( = 31), ( = 8), ( = 1), or ( = 1) in extensively drug-resistant and pandrug-resistant organisms isolated from in-patients in 10 private hospitals (2012 to 2013) in Durban, South Africa. Two novel NDM-1-encoding plasmids from were circularized by PacBio sequencing. In p19-10_01 [IncFIB(K); 223.434 bp], was part of a Tn-like structure (16.276 bp) delineated by IS The multireplicon plasmid p18-43_01 [IncR_1/IncFIB(pB171)/IncFII(Yp); 212.326 bp] shared an 80-kb region with p19-10_01, not including the -containing region. The two plasmids were used as references for tracing NDM-1-encoding plasmids in the other genome assemblies. The p19-10_01 sequence was detected in ( = 7) only, whereas p18-43_01 was tracked to ( = 4), ( = 1), ( = 11), spp. ( = 7), and ( = 1), revealing horizontal spread of this -bearing plasmid structure. Global phylogeny showed clustering of the (18/20) isolates together with closely related carbapenemase-negative ST101 isolates from other geographical origins. The South African isolates were divided into three phylogenetic subbranches, where each group had distinct resistance and replicon profiles, carrying either p19-10_01, p18-10_01, or pCHE-A1 (8,201 bp). The latter plasmid carried and within an integron mobilization unit. Our findings imply independent plasmid acquisition followed by local dissemination. Additionally, we detected carried by pPKPN4 in (ST14) and contained by a pNDM-MGR194-like genetic structure in (ST167), adding even more complexity to the multilayer molecular mechanisms behind nosocomial spread of carbapenem-resistant in Durban, South Africa.