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Volume 6, Issue 1

Population structure of KPC carbapenemase-producing in a long-term acute-care rehabilitation facility: identification of a new lineage of clonal group 101, associated with local hyperendemicity Open Access

Abstract

In this work, we used a whole-genome sequencing (WGS) approach to study the features of KPC-producing (KPC-Kp) spreading in a large Italian long-term acute-care rehabilitation facility (LTACRF), and to track the dynamics of dissemination within this setting. Thirty-eight, non-replicated, KPC-Kp isolates from colonized patients (either already colonized at admission or colonized during admission), collected during 2016, were subjected to antimicrobial-susceptibility testing and WGS. All isolates were resistant to β-lactams, with the exception of ceftazidime/avibactam (97.4 % susceptible). The second most effective agent was fosfomycin, followed by colistin, trimethoprim/sulfamethoxazole, gentamicin and amikacin (92.1, 86.8, 60.5, 44.7 and 50 % of susceptibility, respectively). A large proportion of isolates (=18/38, 47.4%) belonged to clonal group (CG) 101, and most of them (=15) to a new sequence type (ST) designated as ST2502. All the CG101 isolates had a capsule locus type KL17. The ST2502 harboured the genes encoding for the yersiniabactin siderophore and the ArmA methylase, conferring high-level resistance to aminoglycosides. The second most represented lineage of isolates (16/38, 42.1%) belonged to ST512 of CG258. Analysing WGS data, we were able to ascertain the common origin of some isolates imported from other hospitals, and to track several clusters of in-LTACRF cross-transmissions. The results revealed that, in peculiar epidemiological settings such as LTACRF, new KPC-Kp clones different from those prevailing in acute-care hospitals and associated with uncommon resistance and virulence determinants can successfully emerge and disseminate.

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  • Published Online:
Keyword(s): Klebsiella pneumoniae , KPC-type carbapenemases , molecular epidemiology , sequence type 101 and virulence determinants
Funding
This study was supported by the:
  • Don Carlo Gnocchi Foundation (Award project N. 1345)
    • Principle Award Recipient: Gian Maria Rossolini
© 2020 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution NonCommercial License.
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2020-01-02
2024-04-27
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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]
     [Google Scholar]
  2. Kadri SS, Adjemian J, Lai YL, Spaulding AB, Ricotta E et al. Difficult-to-treat resistance in gram-negative bacteremia at 173 US hospitals: retrospective cohort analysis of prevalence, predictors, and outcome of resistance to all first-line agents. Clin Infect Dis 2018; 67:1803–1814 [View Article]
     [Google Scholar]
  3. Gomez-Simmonds A, Uhlemann A-C. Clinical implications of genomic adaptation and evolution of carbapenem-resistant Klebsiella pneumoniae . J Infect Dis 2017; 215:S18–S27 [View Article]
     [Google Scholar]
  4. David S, Reuter S, Harris SR, Glasner C, Feltwell T et al. Epidemic of carbapenem-resistant Klebsiella pneumoniae in Europe is driven by nosocomial spread. Nat Microbiol 19: [View Article]
     [Google Scholar]
  5. Broberg CA, Palacios M, Miller VL. Klebsiella: a long way to go towards understanding this enigmatic jet-setter. F1000Prime Rep 2014; 6:64 [View Article]
     [Google Scholar]
  6. Conte V, Monaco M, Giani T, D'Ancona F, Moro ML et al. Molecular epidemiology of KPC-producing Klebsiella pneumoniae from invasive infections in Italy: increasing diversity with predominance of the ST512 clade II sublineage. J Antimicrob Chemother 2016; 71:3386–3391 [View Article]
     [Google Scholar]
  7. Mezzatesta ML, Gona F, Caio C, Adembri C, Dell'utri P et al. Emergence of an extensively drug-resistant ArmA- and KPC-2-producing ST101 Klebsiella pneumoniae clone in Italy. J Antimicrob Chemother 2013; 68:1932–1934 [View Article]
     [Google Scholar]
  8. Bonura C, Giuffrè M, Aleo A, Fasciana T, Di Bernardo F et al. An update of the evolving epidemic of bla KPC carrying Klebsiella pneumoniae in Sicily, Italy, 2014: emergence of multiple non-ST258 clones. PLoS One 2015; 10:e0132936 [View Article]
     [Google Scholar]
  9. Del Franco M, Paone L, Novati R et al. Molecular epidemiology of carbapenem resistant Enterobacteriaceae in Valle d'Aosta region, Italy, shows the emergence of KPC-2 producing Klebsiella pneumoniae clonal complex 101 (ST101 and ST1789). BMC Microbiol 2015; 15:260
     [Google Scholar]
  10. Wyres KL, Hawkey J, Hetland MAK, Fostervold A, Wick RR et al. Emergence and rapid global dissemination of CTX-M-15-associated Klebsiella pneumoniae strain ST307. J Antimicrob Chemother 2019; 74:577–581 [View Article]
     [Google Scholar]
  11. Hayden MK, Lin MY, Lolans K, Weiner S, Blom D et al. Prevention of colonization and infection by Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae in long-term acute-care hospitals. Clin Infect Dis 2015; 60:1153–1161 [View Article]
     [Google Scholar]
  12. Marchaim D, Chopra T, Bogan C, Bheemreddy S, Sengstock D et al. The burden of multidrug-resistant organisms on tertiary hospitals posed by patients with recent stays in long-term acute care facilities. Am J Infect Control 2012; 40:760–765 [View Article]
     [Google Scholar]
  13. Lin MY, Lyles-Banks RD, Lolans K, Hines DW, Spear JB et al. The importance of long-term acute care hospitals in the regional epidemiology of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae . Clin Infect Dis 2013; 57:1246–1252 [View Article]
     [Google Scholar]
  14. Rossini A, Di Santo SG, Libori MF, Tiracchia V, Balice MP et al. Risk factors for carbapenemase-producing Enterobacteriaceae colonization of asymptomatic carriers on admission to an Italian rehabilitation hospital. J Hosp Infect 2016; 92:78–81 [View Article]
     [Google Scholar]
  15. Prabaker K, Lin MY, McNally M, Cherabuddi K, Ahmed S et al. Transfer from high-acuity long-term care facilities is associated with carriage of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae: a multihospital study. Infect Control Hosp Epidemiol 2012; 33:1193–1199 [View Article]
     [Google Scholar]
  16. Arena F, Vannetti F, Di Pilato V, Fabbri L, Colavecchio OL et al. Diversity of the epidemiology of carbapenemase-producing Enterobacteriaceae in long-term acute care rehabilitation settings from an area of hyperendemicity, and evaluation of an intervention bundle. J Hosp Infect 2018; 100:29–34 [View Article]
     [Google Scholar]
  17. CLSI. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically, Approved Standard M07, 11th edn. Wayne, PA: Clinical and Laboratory Standards Institute; 2018
     [Google Scholar]
  18. Camarlinghi G, Parisio EM, Antonelli A, Nardone M, Coppi M et al. Discrepancies in fosfomycin susceptibility testing of KPC-producing Klebsiella pneumoniae with various commercial methods. Diagn Microbiol Infect Dis 2019; 93:74–76 [View Article]
     [Google Scholar]
  19. 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]
  20. Wyres KL, Wick RR, Gorrie C, Jenney A, Follador R et al. Identification of Klebsiella capsule synthesis loci from whole genome data. Microb Genom 2016; 2:e000102 [View Article]
     [Google Scholar]
  21. Wick RR, Wyres KL, Gorrie CL, Judd LM, MMC L et al. Genetic diversity, mobilisation and spread of the yersiniabactin-encoding mobile element ICEKp in Klebsiella pneumoniae populations. Microb Genom 2018; 4:mgen.0.000196
     [Google Scholar]
  22. Poirel L, Jayol A, Nordmann P. Polymyxins: antibacterial activity, susceptibility testing, and resistance mechanisms encoded by plasmids or chromosomes. Clin Microbiol Rev 2017; 30:557–596 [View Article]
     [Google Scholar]
  23. Seemann T. 2018; Snippy: fast bacterial variant calling from NGS reads. https://github.com/tseemann/snippy
  24. Nguyen L-T, Schmidt HA, von Haeseler A, Minh BQ. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol Biol Evol 2015; 32:268–274 [View Article]
     [Google Scholar]
  25. Hadfield J, Croucher NJ, Goater RJ, Abudahab K, Aanensen DM et al. Phandango: an interactive viewer for bacterial population genomics. Bioinformatics 2018; 34:292–293 [View Article]
     [Google Scholar]
  26. ECDC Risk Assessment on the Spread of Carbapenemase-Producing Enterobacteriaceae (CPE) Through Patient Transfer Between Healthcare Facilities, with Special Emphasis on Cross-Border Transfer Stockholm: European Centre for Disease Prevention and Control; 2011
     [Google Scholar]
  27. Ministero della Salute Circolare Ministeriale ‘Sorveglianza e Controllo delle Infezioni da Batteri Produttori di Carbapenemasi (CPE)’. Rome: Ministero della Salute; 2013
  28. Esposito EP, Cervoni M, Bernardo M et al. Molecular epidemiology and virulence profiles of colistin-resistant Klebsiella pneumoniae blood isolates from the hospital agency "Ospedale dei Colli," Naples, Italy. Front Microbiol 2018; 16:1463
     [Google Scholar]
  29. Villa L, Feudi C, Fortini D, Brisse S, Passet V et al. Diversity, virulence, and antimicrobial resistance of the KPC-producing Klebsiella pneumoniae ST307 clone. Microb Genom 2017; 3:mgen.0.000110 [View Article]
     [Google Scholar]
  30. Mammina C, Palma DM, Bonura C, Anna Plano MR, Monastero R et al. Outbreak of infection with Klebsiella pneumoniae sequence type 258 producing Klebsiella pneumoniae carbapenemase 3 in an intensive care unit in Italy. J Clin Microbiol 2010; 48:1506–1507 [View Article]
     [Google Scholar]
  31. Richter SN, Frasson I, Franchin E, Bergo C, Lavezzo E et al. KPC-mediated resistance in Klebsiella pneumoniae in two hospitals in Padua, Italy, June 2009-December 2011: massive spreading of a KPC-3-encoding plasmid and involvement of non-intensive care units. Gut Pathog 2012; 4:4 [View Article]
     [Google Scholar]
  32. Giani T, Arena F, Vaggelli G, Conte V, Chiarelli A et al. Large nosocomial outbreak of colistin-resistant, carbapenemase-producing Klebsiella pneumoniae traced to clonal expansion of an mgrB deletion mutant. J Clin Microbiol 2015; 53:3341–3344 [View Article]
     [Google Scholar]
  33. Calia C, Pazzani C, Oliva M, Scrascia M, Lovreglio P et al. Carbapenemases-producing Klebsiella pneumoniae in hospitals of two regions of Southern Italy. APMIS 2017; 125:491–498 [View Article]
     [Google Scholar]
  34. Giani T, Antonelli A, Caltagirone M, Mauri C, Nicchi J et al. Evolving beta-lactamase epidemiology in Enterobacteriaceae from Italian nationwide surveillance, October 2013: KPC-carbapenemase spreading among outpatients. Euro Surveill. 2017; 22:30583 [View Article]
     [Google Scholar]
  35. Sotgiu G, Are BM, Pesapane L, Palmieri A, Muresu N et al. Nosocomial transmission of carbapenem-resistant Klebsiella pneumoniae in an Italian university hospital: a molecular epidemiological study. J Hosp Infect 2018; 99:413–418 [View Article]
     [Google Scholar]
  36. Wu KM, Li LH, Yan JJ, Tsao N, Liao TL et al. Genome sequencing and comparative analysis of Klebsiella pneumoniae NTUH-K2044, a strain causing liver abscess and meningitis. J Bacteriol 2009; 191:4492–4501 [View Article]
     [Google Scholar]
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Population structure of KPC carbapenemase-producing Klebsiella pneumoniae in a long-term acute-care rehabilitation facility: identification of a new lineage of clonal group 101, associated with local hyperendemicity
M Gen 6, e000308 (2020); https://doi.org/10.1099/mgen.0.000308
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