A Cluster Of Colistin- And Carbapenem-Resistant Klebsiella Pneumoniae Carrying Bla(Ndm-1) And Mcr-8.2

Background. Klebsiella pneumoniae resistant to both carbapenems and colistin imposes severe challenges for management. In this study, we report a cluster of 5 carbapenem-resistant K pneumoniae clinical strains belonging to ST1 and K57 types, 4 of which were also resistant to colistin, from 2 hospitals.Methods. The 5 strains were subjected to whole-genome sequencing (WGS) using the short-read Illumina HiSeq platform, and 2 strains were also selected for long-read WGS using MinION. Clonal relatedness of the 5 strains was determined based on singlenucleotide polymorphisms (SNPs). Conjugation experiments were performed to obtain self-transmissible plasmids.Results. All 5 strains carried the carbapenemase-encoding gene bla(NDM-1), whereas the 4 colistin-resistant strains also harbored a new variant of the mcr-8 colistin resistance gene, namely, mcr-8.2. MCR-8.2 differs from MCR-8.1 by four amino acid substitutions (A51V, A232S, N365Y, and N480K). mcr-8.2 was located on a large, hybrid, nonself-transmissible plasmid containing IncQ, IncR, and IncFII replicons, whereas bla(NDM-1) was carried by self-transmissible IncX3 plasmids. Phylogenetic analysis based on SNPs revealed that the 5 strains were likely to have a common origin.Conclusions. Both the intra- and interhospital transfer of strains carrying mcr-8 and bla(NDM-1) were identified, which represents an emerging threat for clinical management and infection control.