1887

Abstract

Carbapenemase-producing Enterobacteriaceae (CPE) have emerged as a global threat to public health and clinical practice.

In Thailand, reports describing CPEs carrying and -like genes have been increasing recently; however, data on detailed plasmid analysis and temporal shift of sequence type and carbapenemase type are limited.

In this study, we analysed whole-genome sequencing (WGS) data of clinically isolated carbapenemase-producing (CPKP) to reveal the molecular epidemiology of CPKP in a tertiary-care hospital in Bangkok, Thailand.

Seventy-seven non-duplicated CPKP isolates collected during 2013–2016 were examined for their drug-resistance genes, sequence types and phylogenetic relationships.

All the tested isolates possessed carbapenemase gene(s), and the major type of carbapenemase gene in 2014–2015 was , whereas isolates in 2016 harboured more than . Other carbapenemase gene variants, such as , , , and were detected in some CPKP isolates. Furthermore, this study revealed that CPKP co-harbouring two genes, and or , emerged during this period. Notably, such isolates co-carrying the two carbapenemase genes emerged in three different sequence types, even in a single hospital, and then spread clonally. The WGS of CPKP revealed a temporal shift of the predominant carbapenemase genes from to along with a variation in other carbapenemase gene types within a span of 4 years.

Our findings suggest that a substantial change in CPE types occurred in Thailand and potentially in Southeast Asian countries.

Funding
This study was supported by the:
  • Japan Agency for Medical Research and Development (Award 21wm0125010h0001)
    • Principle Award Recipient: YukihiroAkeda
  • Japan Agency for Medical Research and Development (Award 21wm0225013h0502)
    • Principle Award Recipient: TetsuyaIida
  • Japan Agency for Medical Research and Development (Award JP18fm0108003)
    • Principle Award Recipient: ShigeyukiHamada
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.001711
2023-06-09
2024-04-29
Loading full text...

Full text loading...

References

  1. Logan LK, Weinstein RA. The epidemiology of carbapenem-resistant Enterobacteriaceae: the impact and evolution of a global menace. J Infect Dis 2017; 215:S28–S36 [View Article] [PubMed]
    [Google Scholar]
  2. Pitout JDD, Nordmann P, Poirel L. Carbapenemase-producing Klebsiella pneumoniae, a key pathogen set for global nosocomial dominance. Antimicrob Agents Chemother 2015; 59:5873–5884 [View Article] [PubMed]
    [Google Scholar]
  3. Lee C-R, Lee JH, Park KS, Kim YB, Jeong BC et al. Global dissemination of carbapenemase-producing Klebsiella pneumoniae: epidemiology, genetic context, treatment options, and detection methods. Front Microbiol 2016; 7:895 [View Article] [PubMed]
    [Google Scholar]
  4. Queenan AM, Bush K. Carbapenemases: the versatile beta-lactamases. Clin Microbiol Rev 2007; 20:440–458 [View Article] [PubMed]
    [Google Scholar]
  5. Xu Y, Gu B, Huang M, Liu H, Xu T et al. Epidemiology of carbapenem resistant Enterobacteriaceae (CRE) during 2000-2012 in Asia. J Thorac Dis 2015; 7:376–385 [View Article] [PubMed]
    [Google Scholar]
  6. Hsu L-Y, Apisarnthanarak A, Khan E, Suwantarat N, Ghafur A et al. Carbapenem-resistant Acinetobacter baumannii and Enterobacteriaceae in South and Southeast Asia. Clin Microbiol Rev 2017; 30:1–22 [View Article] [PubMed]
    [Google Scholar]
  7. Laolerd W, Akeda Y, Preeyanon L, Ratthawongjirakul P, Santanirand P. Carbapenemase-producing carbapenem-resistant Enterobacteriaceae from Bangkok, Thailand, and their detection by the Carba NP and modified Carbapenem inactivation method tests. Microb Drug Resist 2018; 24:1006–1011 [View Article] [PubMed]
    [Google Scholar]
  8. Takeuchi D, Kerdsin A, Akeda Y, Sugawara Y, Sakamoto N et al. Nationwide surveillance in Thailand revealed genotype-dependent dissemination of carbapenem-resistant Enterobacterales. Microb Genom 2022; 8:000797 [View Article] [PubMed]
    [Google Scholar]
  9. Boonyasiri A, Jauneikaite E, Brinkac LM, Greco C, Lerdlamyong K et al. Genomic and clinical characterisation of multidrug-resistant carbapenemase-producing ST231 and ST16 Klebsiella pneumoniae isolates colonising patients at Siriraj hospital, Bangkok, Thailand from 2015 to 2017. BMC Infect Dis 2021; 21:142 [View Article] [PubMed]
    [Google Scholar]
  10. Wick RR, Judd LM, Gorrie CL, Holt KE. Unicycler: resolving bacterial genome assemblies from short and long sequencing reads. PLoS Comput Biol 2017; 13:e1005595 [View Article] [PubMed]
    [Google Scholar]
  11. Kaas RS, Leekitcharoenphon P, Aarestrup FM, Lund O. Solving the problem of comparing whole bacterial genomes across different sequencing platforms. PLoS One 2014; 9:e104984 [View Article] [PubMed]
    [Google Scholar]
  12. Letunic I, Bork P. Interactive Tree Of Life (iTOL): an online tool for phylogenetic tree display and annotation. Bioinformatics 2006; 23:127–128 [View Article] [PubMed]
    [Google Scholar]
  13. Page AJ, Taylor B, Delaney AJ, Soares J, Seemann T et al. SNP-sites: rapid efficient extraction of SNPs from multi-FASTA alignments. Microb Genom 2016; 2: [View Article]
    [Google Scholar]
  14. Croucher NJ, Page AJ, Connor TR, Delaney AJ, Keane JA et al. Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins. Nucleic Acids Res 2015; 43:e15 [View Article] [PubMed]
    [Google Scholar]
  15. Brettin T, Davis JJ, Disz T, Edwards RA, Gerdes S et al. RASTtk: a modular and extensible implementation of the RAST algorithm for building custom annotation pipelines and annotating batches of genomes. Sci Rep 2015; 5:8365 [View Article] [PubMed]
    [Google Scholar]
  16. Li X-P, Sun R-Y, Song J-Q, Fang L-X, Zhang R-M et al. Within-host heterogeneity and flexibility of mcr-1 transmission in chicken gut. Int J Antimicrob Agents 2020; 55:105806 [View Article] [PubMed]
    [Google Scholar]
  17. Peirano G, Bradford PA, Kazmierczak KM et al. Importance of Clonal complex 258 and IncFK2-Like Plasmids among a global collection of Klebsiella pneumoniae with blaKPC. Antimicrob Agents Chemother 2017; 61:e02610–16 [View Article]
    [Google Scholar]
  18. Wong JLC, Romano M, Kerry LE, Kwong H-S, Low W-W et al. OmpK36-mediated Carbapenem resistance attenuates ST258 Klebsiella pneumoniae in vivo. Nat Commun 2019; 10:3957 [View Article] [PubMed]
    [Google Scholar]
  19. David S, Wong JLC, Sanchez-Garrido J, Kwong H-S, Low WW et al. Widespread emergence of OmpK36 loop 3 insertions among multidrug-resistant clones of Klebsiella pneumoniae. PLoS Pathog 2022; 18:e1010334 [View Article] [PubMed]
    [Google Scholar]
  20. Chen Y-T, Lin A-C, Siu LK, Koh TH. Sequence of closely related plasmids encoding blaNDM-1 in two unrelated Klebsiella pneumoniae isolates in Singapore. PLoS One 2012; 7:e48737 [View Article] [PubMed]
    [Google Scholar]
  21. Netikul T, Sidjabat HE, Paterson DL, Kamolvit W, Tantisiriwat W et al. Characterization of an IncN2-type blaNDM-₁-carrying plasmid in Escherichia coli ST131 and Klebsiella pneumoniae ST11 and ST15 isolates in Thailand. J Antimicrob Chemother 2014; 69:3161–3163 [View Article] [PubMed]
    [Google Scholar]
  22. Hao Y, Shao C, Geng X, Bai Y, Jin Y et al. Genotypic and phenotypic characterization of clinical Escherichia coli sequence type 405 carrying IncN2 plasmid harboring blaNDM-1. Front Microbiol 2019; 10:788 [View Article]
    [Google Scholar]
  23. Abe R, Akeda Y, Takeuchi D, Sakamoto N, Sugawara Y et al. Clonal dissemination of carbapenem-resistant Klebsiella pneumoniae ST16 co-producing NDM-1 and OXA-232 in Thailand. JAC Antimicrob Resist 2022; 4:dlac084 [View Article] [PubMed]
    [Google Scholar]
  24. Sakamoto N, Akeda Y, Sugawara Y, Takeuchi D, Motooka D et al. Genomic characterization of carbapenemase-producing Klebsiella pneumoniae with chromosomally carried bla NDM-1. Antimicrob Agents Chemother 2018; 62:e01520–18 [View Article]
    [Google Scholar]
  25. Doi Y, O’Hara JA, Lando JF, Querry AM, Townsend BM et al. Co-production of NDM-1 and OXA-232 by Klebsiella pneumoniae. Emerg Infect Dis 2014; 20:163–165 [View Article] [PubMed]
    [Google Scholar]
  26. Doi Y, Hazen TH, Boitano M, Tsai Y-C, Clark TA et al. Whole-genome assembly of Klebsiella pneumoniae coproducing NDM-1 and OXA-232 carbapenemases using single-molecule, real-time sequencing. Antimicrob Agents Chemother 2014; 58:5947–5953 [View Article]
    [Google Scholar]
  27. Kwon T, Jung Y-H, Lee S, Yun M-R, Kim W et al. Comparative genomic analysis of Klebsiella pneumoniae subsp. pneumoniae KP617 and PittNDM01, NUHL24835, and ATCC BAA-2146 reveals unique evolutionary history of this strain. Gut Pathog 2016; 8:34 [View Article] [PubMed]
    [Google Scholar]
  28. Liu Y, Feng Y, Wu W, Xie Y, Wang X et al. First report of OXA-181-producing Escherichia coli in China and characterization of the isolate using whole-genome sequencing. Antimicrob Agents Chemother 2015; 59:5022–5025 [View Article]
    [Google Scholar]
  29. Sugawara Y, Akeda Y, Hagiya H, Sakamoto N, Takeuchi D et al. Spreading patterns of NDM-producing Enterobacteriaceae in clinical and environmental settings in Yangon, Myanmar. Antimicrob Agents Chemother 2019; 63:e01924–18 [View Article]
    [Google Scholar]
  30. Castanheira M, Doyle TB, Collingsworth TD, Sader HS, Mendes RE. Increasing frequency of OXA-48-producing Enterobacterales worldwide and activity of ceftazidime/avibactam, meropenem/vaborbactam and comparators against these isolates. J Antimicrob Chemother 2021; 76:3125–3134 [View Article]
    [Google Scholar]
  31. Emeraud C, Birer A, Girlich D, Jousset AB, Creton E et al. Polyclonal dissemination of OXA-232 carbapenemase-producing Klebsiella pneumoniae, France, 2013-2021. Emerg Infect Dis 2022; 28:2304–2307 [View Article] [PubMed]
    [Google Scholar]
  32. Paveenkittiporn W, Lyman M, Biedron C, Chea N, Bunthi C et al. Molecular epidemiology of carbapenem-resistant Enterobacterales in Thailand, 2016-2018. Antimicrob Resist Infect Control 2021; 10:88 [View Article] [PubMed]
    [Google Scholar]
  33. Tunyong W, Arsheewa W, Santajit S, Kong-Ngoen T, Pumirat P et al. Antibiotic resistance genes among carbapenem-resistant Enterobacterales (CRE) Isolates of Prapokklao Hospital, Chanthaburi Province, Thailand. Infect Drug Resist 2021; 14:3485–3494 [View Article] [PubMed]
    [Google Scholar]
  34. Nulsopapon P, Nasomsong W, Pongchaidecha M, Changpradub D, Juntanawiwat P et al. The synergistic activity and optimizing doses of tigecycline in combination with aminoglycosides against clinical carbapenem-resistant Klebsiella pneumoniae isolates. Antibiotics 2021; 10:736 [View Article] [PubMed]
    [Google Scholar]
  35. Meletis G, Chatzidimitriou D, Malisiovas N. Double- and multi-carbapenemase-producers: the excessively armored bacilli of the current decade. Eur J Clin Microbiol Infect Dis 2015; 34:1487–1493 [View Article] [PubMed]
    [Google Scholar]
  36. Lutgring JD, Zhu W, de Man TJB, Avillan JJ, Anderson KF et al. Phenotypic and genotypic characterization of Enterobacteriaceae producing oxacillinase-48-like carbapenemases, United States. Emerg Infect Dis 2018; 24:700–709 [View Article] [PubMed]
    [Google Scholar]
  37. Lee H, Shin J, Chung Y-J, Park M, Kang KJ et al. Co-introduction of plasmids harbouring the carbapenemase genes, blaNDM-1 and blaOXA-232, increases fitness and virulence of bacterial host. J Biomed Sci 2020; 27:8 [View Article]
    [Google Scholar]
  38. Kazi M, Shetty A, Rodrigues C. The carbapenemase menace: do dual mechanisms code for more resistance?. Infect Control Hosp Epidemiol 2015; 36:116–117 [View Article] [PubMed]
    [Google Scholar]
  39. Meletis G. Carbapenem resistance: overview of the problem and future perspectives. Ther Adv Infect Dis 2016; 3:15–21 [View Article] [PubMed]
    [Google Scholar]
  40. Bulik CC, Nicolau DP. Double-carbapenem therapy for carbapenemase-producing Klebsiella pneumoniae. Antimicrob Agents Chemother 2011; 55:3002–3004 [View Article]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.001711
Loading
/content/journal/jmm/10.1099/jmm.0.001711
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
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