Vertical and horizontal dissemination of an IncC plasmid harbouring rmtB 16S rRNA methylase gene, conferring resistance to plazomicin, among invasive ST258 and ST16 KPC-producing Klebsiella pneumoniae

Carbapenem resistance in Klebsiella pneumoniae is a major clinical challenge. Aminoglycosides remain an important asset the current therapeutic arsenal to treat these infections. We examined aminoglycoside phenotypes and genomics collection of 100 invasive KPC-producing K. isolates sequentially collected Brazilian tertiary hospital between 2014 2016. Aminoglycoside susceptibility testing was performed. used combined long-read (MinION) short-read (Illumina) whole-genome sequencing strategy provide genomic picture genes, with particular emphasis on 16S rRNA methyltransferases related plasmids. 68% strains were resistant gentamicin 42% amikacin, 35% both commonly aminoglycosides. identified methyltransferase gene rmtB 30% isolates: 97% (29/30) belonged sequence type 258 (ST258) single isolate emergent ST16 clone. In ST258 located large IncC plasmids 177 kb 174 kb, respectively, highly similar plasmid previously Proteus mirabilis same hospital. Moreover, 99% remained susceptible veterinary-approved drug apramycin, currently under development for human medicine. Such findings geographically temporally suggest combination vertical clonal spread as well horizontal interspecies intraspecies transfer. This broad dissemination endemic setting clones worrisome since it provides most clinically available aminoglycosides, including novel aminoglycoside-modifying enzyme-resistant plazomicin.