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

• Published in: Journal of global antimicrobial resistance. Vol. 24; pp. 183 - 189
• Main Authors: Roch, Mélanie, Sierra, Roberto, Sands, Kirsty, Martins, Willames M.B.S., Schrenzel, Jacques, Walsh, Timothy R., Gales, Ana C., Andrey, Diego O.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01-03-2021; Elsevier
• Subjects: 16S rRNA methyltransferase; Aminoglycosides; Apramycin; KPC-producing Klebsiella pneumoniae; Plazomicin; rmtB; Aminoglycosides; KPC-producing Klebsiella pneumoniae; rmtB; Plazomicin; Apramycin; 16S rRNA methyltransferase
• ISSN: 2213-7165; 2213-7173
• DOI: 10.1016/j.jgar.2020.12.006

•High prevalence of 16S methyltransferase rmtB in KPC-producing Klebsiella pneumoniae.•Invasive KPC-producing K. pneumoniae isolates showed high aminoglycoside resistance rates.•rmtB dissemination via ST258 high-risk clone and horizontal transfer within K. pneumoniae.•A similar rmtB plasmid in Proteus mirabilis and K. pneumoniae.•K. pneumoniae harbouring rmtB and blaKPC-2 remained susceptible to apramycin.
Carbapenem resistance in Klebsiella pneumoniae is a major clinical challenge. Aminoglycosides remain an important asset in the current therapeutic arsenal to treat these infections. We examined aminoglycoside resistance phenotypes and genomics in a collection of 100 invasive KPC-producing K. pneumoniae isolates sequentially collected in a Brazilian tertiary hospital between 2014 and 2016.
Aminoglycoside susceptibility testing was performed. We used a combined long-read (MinION) and short-read (Illumina) whole-genome sequencing strategy to provide a genomic picture of aminoglycoside resistance genes, with particular emphasis on 16S rRNA methyltransferases and related plasmids.
68% of the strains were resistant to gentamicin and 42% to amikacin, with 35% resistant to both of these commonly used aminoglycosides. We identified the 16S rRNA methyltransferase gene rmtB in 30% of these isolates: 97% (29/30) belonged to sequence type 258 (ST258) and a single isolate to the emergent ST16 clone. In ST258 and ST16 the rmtB gene was located on large IncC plasmids of 177 kb and 174 kb, respectively, highly similar to a plasmid previously identified in Proteus mirabilis in the same hospital. Moreover, 99% of the isolates remained susceptible to the veterinary-approved drug apramycin, currently under clinical development for human medicine.
Such findings in geographically and temporally related isolates suggest a combination of vertical clonal spread as well as horizontal interspecies and intraspecies plasmid transfer. This broad rmtB dissemination in an endemic setting for KPC-producing clones is worrisome since it provides resistance to most clinically available aminoglycosides, including the novel aminoglycoside-modifying enzyme-resistant plazomicin.