1887

Journal of Medical Microbiology logo

Volume 71, Issue 12

High prevalence of ArmA-16S rRNA methyltransferase among aminoglycoside-resistant bloodstream isolates Open Access

Abstract

Aminoglycosides are used for the treatment of carbapenemase-producing (CPK) infections. 16S rRNA methyltransferases (RMTs) confer resistance to all aminoglycosides and are often cocarried with NDM.

There is a dart of studies looking at the aminoglycoside resistance mechanisms for invasive CPK isolates, particularly in OXA-48 endemic settings.

We aimed to determine the prevalence of RMTs and their association with beta lactamases and MLSTs amongst aminoglycoside-resistant CPK bloodstream isolates in an OXA-48 endemic setting.

CPK isolates (=181), collected as part of a multicentre cohort study, were tested for amikacin, gentamicin and tobramycin susceptibility using custom-made sensititre plates (GN2XF, Thermo Fisher Scientific). All isolates were previously subjected to whole-genome sequencing. Carbapenemases, RMTs, MLSTs and plasmid incompatibility groups were detected on the assembled genomes.

Of the 181 isolates, 109(60 %) were resistant to all three aminoglycosides, and 96 of 109(88 %) aminoglycoside-resistant isolates carried an RMT (85 ArmA, 10 RmtC, 4 RmtF1; three isolates cocarried ArmA and RmtC). Main clonal types associated with ArmA were ST2096 (49/85, 58 %) and ST14 (24/85, 28 %), harbouring mainly OXA-232 and OXA-48 +NDM, respectively. RmtC was cocarried with NDM (5/10) on ST395, and NDM +OXA-48 or NDM +KPC (4/10) on ST14, ST15 and ST16. All RMT producers also carried CTX-M-15, and the majority cocarried SHV-106, TEM-150 and multiple other antibiotic resistance genes. The majority of the isolates harboured a combination of IncFIB, IncH and IncL/M type plasmids. Non-NDM producing isolates remained susceptible to ceftazidime-avibactam.

Aminoglycoside resistance amongst CPK bloodstream isolates is extremely common and mainly driven by clonal spread of ArmA carried on ST2096 and ST14, associated with OXA-232 and OXA48 +NDM carriage, respectively.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): 16S rRNA methyltransferase , aminoglycoside resistance , ArmA , bloodstream , carbapenem-resistant , Klebsiella pneumoniae , NDM , OXA-232 and OXA-48
Funding
This study was supported by the:
  • Pfizer Foundation (Award 56644459)
    • Principle Award Recipient: DavidL. Paterson
© 2022 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001629
2022-12-20
2024-05-04
Loading full text...

Full text loading...

/deliver/fulltext/jmm/71/12/jmm001629.html?itemId=/content/journal/jmm/10.1099/jmm.0.001629&mimeType=html&fmt=ahah

References

  1. Rodríguez-Baño J, Gutiérrez-Gutiérrez B, Machuca I, Pascual A. Treatment of infections caused by extended-spectrum-beta-lactamase-, AmpC-, and carbapenemase-producing enterobacteriaceae. Clin Microbiol Rev 2018; 31:e00079-17 [View Article]
     [Google Scholar]
  2. Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D et al. Infectious diseases society of America guidance on the treatment of extended-spectrum β-lactamase producing enterobacterales (ESBL-E), carbapenem-resistant enterobacterales (CRE), and Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa). Clin Infect Dis 2021; 72:1109–1116 [View Article]
     [Google Scholar]
  3. Serio AW, Keepers T, Krause KM. Plazomicin is active against metallo-β-lactamase-producing enterobacteriaceae. Open Forum Infect Dis 2019; 6:fz123 [View Article]
     [Google Scholar]
  4. Ramirez MS, Tolmasky ME. Aminoglycoside modifying enzymes. Drug Resist Updat 2010; 13:151–171 [View Article]
     [Google Scholar]
  5. Doi Y, Wachino JI, Arakawa Y. Aminoglycoside resistance: the emergence of acquired 16S ribosomal RNA methyltransferases. Infect Dis Clin North Am 2016; 30:523–537 [View Article]
     [Google Scholar]
  6. Yang W, Hu F. Research updates of plasmid-mediated aminoglycoside resistance 16S rRNA methyltransferase. Antibiotics 2022; 11:906 [View Article]
     [Google Scholar]
  7. Nafplioti K, Souli M, Adamou P, Moraitou E, Giannopoulou P et al. Characterization of 16S rRNA methylase genes in Enterobacterales and Pseudomonas aeruginosa in Athens Metropolitan area, 2015-2016. Eur J Clin Microbiol Infect Dis 2021; 40:111–121 [View Article] [PubMed]
     [Google Scholar]
  8. Shen X, Liu L, Yu J, Ai W, Cao X et al. High prevalence of 16S rRNA methyltransferase genes in carbapenem-resistant Klebsiella pneumoniae clinical isolates associated with bloodstream infections in 11 Chinese teaching hospitals. Infect Drug Resist 2020; 13:2189–2197 [View Article]
     [Google Scholar]
  9. Isler B, Özer B, Çınar G, Aslan AT, Vatansever C et al. Characteristics and outcomes of carbapenemase harbouring carbapenem-resistant Klebsiella spp. bloodstream infections: a multicentre prospective cohort study in an OXA-48 endemic setting. Eur J Clin Microbiol Infect Dis 2022; 41:841–847 [View Article]
     [Google Scholar]
  10. ThermoFischer 2018 https://assets.thermofisher.com/TFS-Assets/MBD/brochures/Sensititre-Plate-Guide-Booklet-EN.pdf
  11. Anonymous European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2021. Breakpoint tables for interpretation of MICs and zone diameters, version 11.0. n.d https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_11.0_Breakpoint_Tables.pdf
  12. Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 2012; 19:455–477 [View Article]
     [Google Scholar]
  13. Treangen TJ, Ondov BD, Koren S, Phillippy AM. The harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes. Genome Biol 2014; 15:524 [View Article]
     [Google Scholar]
  14. Yu G, Smith DK, Zhu H, Guan Y, Lam T-Y. Ggtree: an r package for visualization and annotation of phylogenetic trees with their covariates and other associated data. Methods Ecol Evol 2017; 8:28–36
     [Google Scholar]
  15. Arca-Suárez J, Rodiño-Janeiro BK, Pérez A, Guijarro-Sánchez P, Vázquez-Ucha JC et al. Emergence of 16S rRNA methyltransferases among carbapenemase-producing Enterobacterales in Spain studied by whole-genome sequencing. Int J Antimicrob Agents 2022; 59:106456 [View Article]
     [Google Scholar]
  16. Galani I, Nafplioti K, Adamou P, Karaiskos I, Giamarellou H et al. Nationwide epidemiology of carbapenem resistant Klebsiella pneumoniae isolates from Greek hospitals, with regards to plazomicin and aminoglycoside resistance. BMC Infect Dis 2019; 19:167 [View Article]
     [Google Scholar]
  17. Fournier C, Poirel L, Despont S, Kessler J, Nordmann P. Increasing trends of association of 16S rRNA methylases and carbapenemases in Enterobacterales clinical isolates from Switzerland, 2017-2020. Microorganisms 2022; 10:615 [View Article]
     [Google Scholar]
  18. Taylor E, Sriskandan S, Woodford N, Hopkins KL. High prevalence of 16S rRNA methyltransferases among carbapenemase-producing Enterobacteriaceae in the UK and Ireland. Int J Antimicrob Agents 2018; 52:278–282 [View Article] [PubMed]
     [Google Scholar]
  19. Berçot B, Poirel L, Ozdamar M, Hakko E, Türkoglu S et al. Low prevalence of 16S methylases among extended-spectrum-beta-lactamase-producing Enterobacteriaceae from a Turkish hospital. J Antimicrob Chemother 2010; 65:797–798 [View Article] [PubMed]
     [Google Scholar]
  20. Castanheira M, Deshpande LM, Woosley LN, Serio AW, Krause KM et al. Activity of plazomicin compared with other aminoglycosides against isolates from European and adjacent countries, including Enterobacteriaceae molecularly characterized for aminoglycoside-modifying enzymes and other resistance mechanisms. J Antimicrob Chemother 2018; 73:3346–3354 [View Article] [PubMed]
     [Google Scholar]
  21. Al-Marzooq F, Ngeow YF, Tay ST. Emergence of Klebsiella pneumoniae producing dual carbapenemases (NDM-1 and OXA-232) and 16S rRNA methylase (armA) isolated from a Malaysian patient returning from India. Int J Antimicrob Agents 2015; 45:445–446 [View Article] [PubMed]
     [Google Scholar]
  22. Rahman M, Shukla SK, Prasad KN, Ovejero CM, Pati BK et al. Prevalence and molecular characterisation of New Delhi metallo-β-lactamases NDM-1, NDM-5, NDM-6 and NDM-7 in multidrug-resistant Enterobacteriaceae from India. Int J Antimicrob Agents 2014; 44:30–37 [View Article] [PubMed]
     [Google Scholar]
  23. KAUoSa T. A fatal outbreak of hypervirulent and multidrug resistant clone (ST2096) of Klebsiella pneumoniae silently transmitting in A Saudi Arabia western region hospital: A clinical and molecular surveillance study; 2020 https://www.ncbi.nlm.nih.gov/bioproject/?term=prjeb36683
  24. Pitout JDD, Peirano G, Kock MM, Strydom K-A, Matsumura Y. The global ascendency of OXA-48-type carbapenemases. Clin Microbiol Rev 2019; 33:e00102-19 [View Article]
     [Google Scholar]
  25. Fursova NK, Astashkin EI, Gabrielyan NI, Novikova TS, Fedyukina GN et al. Emergence of five genetic lines ST395(NDM-1), ST13(OXA-48), ST3346(OXA-48), ST39(CTX-M-14), and novel ST3551(OXA-48) of multidrug-resistant clinical klebsiella pneumoniae in russia. Microb Drug Resist 2020; 26:924–933
     [Google Scholar]
  26. Gao H, Liu Y, Wang R, Wang Q, Jin L et al. The transferability and evolution of NDM-1 and KPC-2 co-producing Klebsiella pneumoniae from clinical settings. EBioMedicine 2020; 51:102599 [View Article] [PubMed]
     [Google Scholar]
  27. Partridge SR, Kwong SM, Firth N, Jensen SO. Mobile genetic elements associated with antimicrobial resistance. Clin Microbiol Rev 2018; 31:e00088-17 [View Article]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001629
Loading
High prevalence of ArmA-16S rRNA methyltransferase among aminoglycoside-resistant Klebsiella pneumoniae bloodstream isolates
J. Med. Microbiol. 71, 001629 (2022); https://doi.org/10.1099/jmm.0.001629
/content/journal/jmm/10.1099/jmm.0.001629
/content/journal/jmm/10.1099/jmm.0.001629
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error