Dissemination of IMP-6-producing Pseudomonas aeruginosa ST244 in multiple cities in China

  • Y. Chen
  • M. Sun
  • M. Wang
  • Y. Lu
  • Z. Yan


Pseudomonas aeruginosa is an important opportunistic pathogen responsible for nosocomial infections and is currently reported to be a worldwide nosocomial menace. The aim of this study was to investigate the epidemiological traits and the distribution of metallo-β-lactamases (MBLs)-producing P. aeruginosa clinical isolates in ten cities in China between January 2010 and May 2012. Antimicrobial susceptibility was determined by disc diffusion assay and the minimum inhibitory concentrations (MICs) of imipenem and meropenem were also determined by the Etest according to Clinical and Laboratory Standards Institute (CLSI) guidelines. In addition, polymerase chain reaction (PCR) and DNA sequencing were applied to detect bla MBL genes, and their epidemiological relationships were investigated by multilocus sequence typing (MLST). Of 368 P. aeruginosa isolates, MLST analysis identified 138 sequence types (STs), including 122 known and 16 novel STs, and the most frequently detected clone was ST244, followed by ST235. Besides, our study revealed that 25 isolates carried the bla IMP-6 gene and three isolates carried the bla VIM-2 gene, and a probe specific for both genes could be hybridised to an ~1,125-kb fragment in all isolates. Interestingly, all of the bla IMP-6-producing isolates shared an identical ST, ST244, and exhibited a higher level of resistance to several antibiotics. Overall, these observations suggest that P. aeruginosa ST244 carrying the chromosomally located bla IMP-6 gene is widely disseminated in multiple cites in China.


Imipenem Meropenem Colistin Cefepime Multilocus Sequence Typing 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by research grants from the Zhejiang Medical Science and Technology Plan [2013ZB059].

Conflict of interest

None declared.

Ethical approval

Not required.


  1. 1.
    Wolter DJ, Lister PD (2013) Mechanisms of beta-lactam resistance among Pseudomonas aeruginosa. Curr Pharm Des 19(2):209–222PubMedCrossRefGoogle Scholar
  2. 2.
    Queenan AM, Bush K (2007) Carbapenemases: the versatile beta-lactamases. Clin Microbiol Rev 20(3):440–458PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Edelstein MV, Skleenova EN, Shevchenko OV, D’Souza JW, Tapalski DV, Azizov IS, Sukhorukova MV, Pavlukov RA, Kozlov RS, Toleman MA, Walsh TR (2013) Spread of extensively resistant VIM-2-positive ST235 Pseudomonas aeruginosa in Belarus, Kazakhstan, and Russia: a longitudinal epidemiological and clinical study. Lancet Infect Dis 13(10):867–876PubMedCrossRefGoogle Scholar
  4. 4.
    Edalucci E, Spinelli R, Dolzani L, Riccio ML, Dubois V, Tonin EA, Rossolini GM, Lagatolla C (2008) Acquisition of different carbapenem resistance mechanisms by an epidemic clonal lineage of Pseudomonas aeruginosa. Clin Microbiol Infect 14(1):88–90PubMedCrossRefGoogle Scholar
  5. 5.
    Hammami S, Gautier V, Ghozzi R, Da Costa A, Ben-Redjeb S, Arlet G (2010) Diversity in VIM-2-encoding class 1 integrons and occasional bla(SHV2a) carriage in isolates of a persistent, multidrug-resistant Pseudomonas aeruginosa clone from Tunis. Clin Microbiol Infect 16(2):189–193PubMedCrossRefGoogle Scholar
  6. 6.
    Szabó D, Szentandrássy J, Juhász Z, Katona K, Nagy K, Rókusz L (2008) Imported PER-1 producing Pseudomonas aeruginosa, PER-1 producing Acinetobacter baumanii and VIM-2-producing Pseudomonas aeruginosa strains in Hungary. Ann Clin Microbiol Antimicrob 7:12PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Viedma E, Juan C, Villa J, Barrado L, Orellana MA, Sanz F, Otero JR, Oliver A, Chaves F (2012) VIM-2-producing multidrug-resistant Pseudomonas aeruginosa ST175 clone, Spain. Emerg Infect Dis 18(8):1235–1241PubMedPubMedCentralGoogle Scholar
  8. 8.
    Spilker T, Coenye T, Vandamme P, LiPuma JJ (2004) PCR-based assay for differentiation of Pseudomonas aeruginosa from other Pseudomonas species recovered from cystic fibrosis patients. J Clin Microbiol 42(5):2074–2079PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Clinical and Laboratory Standards Institute (CLSI) (2012) Performance standards for antimicrobial susceptibility testing; Twenty-second informational supplement. CLSI document M100-S22. CLSI, Wayne, PAGoogle Scholar
  10. 10.
    Ellington MJ, Kistler J, Livermore DM, Woodford N (2007) Multiplex PCR for rapid detection of genes encoding acquired metallo-beta-lactamases. J Antimicrob Chemother 59(2):321–322PubMedCrossRefGoogle Scholar
  11. 11.
    Lee K, Lim YS, Yong D, Yum JH, Chong Y (2003) Evaluation of the Hodge test and the imipenem-EDTA double-disk synergy test for differentiating metallo-beta-lactamase-producing isolates of Pseudomonas spp. and Acinetobacter spp. J Clin Microbiol 41(10):4623–4629PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Curran B, Jonas D, Grundmann H, Pitt T, Dowson CG (2004) Development of a multilocus sequence typing scheme for the opportunistic pathogen Pseudomonas aeruginosa. J Clin Microbiol 42(12):5644–5649PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG (2007) Clustal W and Clustal X version 2.0. Bioinformatics 23(21):2947–2948PubMedCrossRefGoogle Scholar
  14. 14.
    Jolley KA, Feil EJ, Chan MS, Maiden MCJ (2001) Sequence type analysis and recombinational tests (START). Bioinformatics 17(12):1230–1231PubMedCrossRefGoogle Scholar
  15. 15.
    Héritier C, Poirel L, Aubert D, Nordmann P (2003) Genetic and functional analysis of the chromosome-encoded carbapenem-hydrolyzing oxacillinase OXA-40 of Acinetobacter baumannii. Antimicrob Agents Chemother 47(1):268–273PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Walsh TR, Toleman MA, Poirel L, Nordmann P (2005) Metallo-beta-lactamases: the quiet before the storm? Clin Microbiol Rev 18(2):306–325PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Yano H, Kuga A, Okamoto R, Kitasato H, Kobayashi T, Inoue M (2001) Plasmid-encoded metallo-beta-lactamase (IMP-6) conferring resistance to carbapenems, especially meropenem. Antimicrob Agents Chemother 45(5):1343–1348PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Jeong JH, Shin KS, Lee JW, Park EJ, Son S-Y (2009) Analysis of a novel class 1 integron containing metallo-beta-lactamase gene VIM-2 in Pseudomonas aeruginosa. J Microbiol 47(6):753–759PubMedCrossRefGoogle Scholar
  19. 19.
    Samuelsen O, Toleman MA, Sundsfjord A, Rydberg J, Leegaard TM, Walder M, Lia A, Ranheim TE, Rajendra Y, Hermansen NO, Walsh TR, Giske CG (2010) Molecular epidemiology of metallo-beta-lactamase-producing Pseudomonas aeruginosa Isolates from Norway and Sweden shows import of international clones and local clonal expansion. Antimicrob Agents Chemother 54(1):346–352PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Valenza G, Joseph B, Elias J, Claus H, Oesterlein A, Engelhardt K, Turnwald D, Frosch M, Abele-Horn M, Schoen C (2010) First survey of metallo-beta-lactamases in clinical isolates of Pseudomonas aeruginosa in a German university hospital. Antimicrob Agents Chemother 54(8):3493–3497PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Lee K, Park AJ, Kim MY, Lee HJ, Cho J-H, Kang JO, Yong D, Chong Y; KONSAR group (2009) Metallo-beta-lactamase-producing Pseudomonas spp. in Korea: high prevalence of isolates with VIM-2 type and emergence of isolates with IMP-1 type. Yonsei Med J 50(3):335–339Google Scholar
  22. 22.
    Tada T, Miyoshi-Akiyama T, Shimada K, Shimojima M, Kirikae T (2013) IMP-43 and IMP-44 metallo-beta-lactamases with increased carbapenemase activities in multidrug-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother 57(9):4427–4432PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Livermore DM (2002) Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: our worst nightmare? Clin Infect Dis 34(5):634–640PubMedCrossRefGoogle Scholar
  24. 24.
    Kidd TJ, Ritchie SR, Ramsay KA, Grimwood K, Bell SC, Rainey PB (2012) Pseudomonas aeruginosa exhibits frequent recombination, but only a limited association between genotype and ecological setting. PLoS One 7(9):e44199PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Empel J, Filczak K, Mrówka A, Hryniewicz W, Livermore DM, Gniadkowski M (2007) Outbreak of Pseudomonas aeruginosa infections with PER-1 extended-spectrum beta-lactamase in Warsaw, Poland: further evidence for an international clonal complex. J Clin Microbiol 45(9):2829–2834PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Maatallah M, Cheriaa J, Backhrouf A, Iversen A, Grundmann H, Thuy D, Lanotte P, Mastouri M, Elghmati MS, Rojo F, Mejdi S, Giske CG (2011) Population structure of Pseudomonas aeruginosa from five Mediterranean countries: evidence for frequent recombination and epidemic occurrence of CC235. PLoS One 6(10):e25617PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Ryoo NH, Lee K, Lim J-B, Lee YH, Bae IK, Jeong SH (2009) Outbreak by meropenem-resistant Pseudomonas aeruginosa producing IMP-6 metallo-beta-lactamase in a Korean hospital. Diagn Microbiol Infect Dis 63(1):115–117PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Medical Examination CenterThe First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhouChina
  2. 2.Department of Clinical LaboratoryThe First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhouChina

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