Molecular epidemiology of carbapenem-resistant Pseudomonas aeruginosa in an endemic area: comparison with global data

  • Theodoros Karampatakis
  • Charalampos Antachopoulos
  • Athanassios Tsakris
  • Emmanuel Roilides
Review

Abstract

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is an endemic problem in certain countries including Greece. CRPA and multidrug-resistant P. aeruginosa (MDRPA) firstly emerged in our region during the 80s, right after the launch of imipenem and meropenem as therapeutic agents against P. aeruginosa infections. The role of outer membrane protein (Opr) inactivation has been known to contribute to imipenem resistance since many years, while efflux overexpression systems have been mainly associated with meropenem resistance. Among carbapenemases, metallo-β-lactamases (MBL) and mostly Verona integron-mediated (VIM) MBL’s have played the most crucial role in CRPA emergence. VIM-2 and VIM-4 producing CRPA, usually belonging to clonal complexes (CC) 111 and 235 respectively, have most frequently been isolated. BlaVIM-2 and blaVIM-4 are usually associated with a class 1 integron. VIM-17 also has appeared in Greece. On the other hand, other VIM subtypes detected in a global level, such as VIM-3, VIM-5, VIM-6, VIM-7, VIM-11, VIM-14, VIM-15, VIM-16 and VIM-18 have not yet emerged in Greece. However, new VIM subtypes will probably emerge in the future. In addition, MBL carbapenemases other than VIM, detected worldwide have not yet appeared. A single CRPA isolate producing KPC has emerged in our region several years ago. The study of the molecular basis of Opr deficiency and efflux overexpression remains a challenge for the future. In this article, we review the molecular epidemiology of CRPA in an endemic area, compared to global data.

Keywords

Pseudomonas aeruginosa Carbapenem resistance Molecular epidemiology Endemic area Greece 

Notes

Acknowledgements

The authors would like to thank Vassiliki Pentsioglou and Georgia Kythreotou for epidemiologic data handling and their valuable collaboration.

Compliance with ethical standards

Conflict of interest

The authors have no relevant affiliation or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter discussed in the manuscript.

Ethical approval

Not applicable.

Informed consent

Not applicable.

References

  1. 1.
    Ruhnke M, Arnold R, Gastmeier P (2014) Infection control issues in patients with haematological malignancies in the era of multidrug-resistant bacteria. Lancet Oncol 15(13):e606–e619.  https://doi.org/10.1016/S1470-2045(14)70344-4 PubMedCrossRefGoogle Scholar
  2. 2.
    Borgatta B, Lagunes L, Imbiscuso AT, Larrosa MN, Lujan M, Rello J (2017) Infections in intensive care unit adult patients harboring multidrug-resistant Pseudomonas aeruginosa: implications for prevention and therapy. Eur J Clin Microbiol Infect Dis.  https://doi.org/10.1007/s10096-016-2894-3
  3. 3.
    Kahan FM, Kropp H, Sundelof JG, Birnbaum J (1983) Thienamycin: development of imipenen-cilastatin. J Antimicrob Chemother 12(Suppl D):1–35PubMedCrossRefGoogle Scholar
  4. 4.
    Birnbaum J, Kahan FM, Kropp H, MacDonald JS (1985) Carbapenems, a new class of beta-lactam antibiotics. Discovery and development of imipenem/cilastatin. Am J Med 78(6A):3–21PubMedCrossRefGoogle Scholar
  5. 5.
    Yourassowsky E, Van der Linden MP, Lismont MJ, Crokaert F, Glupczynski Y (1989) Bactericidal activity of meropenem against Pseudomonas aeruginosa. J Antimicrob Chemother 24(Suppl A):169–174PubMedCrossRefGoogle Scholar
  6. 6.
    Tsuji M, Ishii Y, Ohno A, Miyazaki S, Yamaguchi K (1998) In vitro and in vivo antibacterial activities of S-4661, a new carbapenem. Antimicrob Agents Chemother 42(1):94–99PubMedPubMedCentralGoogle Scholar
  7. 7.
    Wexler HM (2004) In vitro activity of ertapenem: review of recent studies. J Antimicrob Chemother 53(Suppl 2):ii11–ii21.  https://doi.org/10.1093/jac/dkh204 PubMedGoogle Scholar
  8. 8.
    Buscher KH, Cullmann W, Dick W, Wendt S, Opferkuch W (1987) Imipenem resistance in Pseudomonas aeruginosa is due to diminished expression of outer membrane proteins. J Infect Dis 156(4):681–684PubMedCrossRefGoogle Scholar
  9. 9.
    Margaret BS, Drusano GL, Standiford HC (1989) Emergence of resistance to carbapenem antibiotics in Pseudomonas aeruginosa. J Antimicrob Chemother 24(Suppl A):161–167PubMedCrossRefGoogle Scholar
  10. 10.
    Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, Harbarth S, Hindler JF, Kahlmeter G, Olsson-Liljequist B, Paterson DL, Rice LB, Stelling J, Struelens MJ, Vatopoulos A, Weber JT, Monnet DL (2012) Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 18(3):268–281.  https://doi.org/10.1111/j.1469-0691.2011.03570.x PubMedCrossRefGoogle Scholar
  11. 11.
    Buehrle DJ, Shields RK, Clarke LG, Potoski BA, Clancy CJ, Nguyen MH (2017) Carbapenem-resistant Pseudomonas aeruginosa bacteremia: risk factors for mortality and microbiologic treatment failure. Antimicrob Agents Chemother 61(1).  https://doi.org/10.1128/AAC.01243-16
  12. 12.
    Kohler T, Michea-Hamzehpour M, Epp SF, Pechere JC (1999) Carbapenem activities against Pseudomonas aeruginosa: respective contributions of OprD and efflux systems. Antimicrob Agents Chemother 43(2):424–427PubMedPubMedCentralGoogle Scholar
  13. 13.
    Poole K, Krebes K, McNally C, Neshat S (1993) Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J Bacteriol 175(22):7363–7372PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Castanheira M, Deshpande LM, Costello A, Davies TA, Jones RN (2014) Epidemiology and carbapenem resistance mechanisms of carbapenem-non-susceptible Pseudomonas aeruginosa collected during 2009-11 in 14 European and Mediterranean countries. J Antimicrob Chemother 69(7):1804–1814.  https://doi.org/10.1093/jac/dku048 PubMedCrossRefGoogle Scholar
  15. 15.
    Riera E, Cabot G, Mulet X, Garcia-Castillo M, del Campo R, Juan C, Canton R, Oliver A (2011) Pseudomonas aeruginosa carbapenem resistance mechanisms in Spain: impact on the activity of imipenem, meropenem and doripenem. J Antimicrob Chemother 66(9):2022–2027.  https://doi.org/10.1093/jac/dkr232 PubMedCrossRefGoogle Scholar
  16. 16.
    Yong D, Toleman MA, Bell J, Ritchie B, Pratt R, Ryley H, Walsh TR (2012) Genetic and biochemical characterization of an acquired subgroup B3 metallo-beta-lactamase gene, blaAIM-1, and its unique genetic context in Pseudomonas aeruginosa from Australia. Antimicrob Agents Chemother 56(12):6154–6159.  https://doi.org/10.1128/AAC.05654-11 PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Nascimento AP, Ortiz MF, Martins WM, Morais GL, Fehlberg LC, Almeida LG, Ciapina LP, Gales AC, Vasconcelos AT (2016) Intraclonal genome stability of the Metallo-beta-lactamase SPM-1-producing Pseudomonas aeruginosa ST277, an endemic clone disseminated in Brazilian hospitals. Front Microbiol 7:1946.  https://doi.org/10.3389/fmicb.2016.01946 PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Wendel AF, Kolbe-Busch S, Ressina S, Schulze-Robbecke R, Kindgen-Milles D, Lorenz C, Pfeffer K, MacKenzie CR (2015) Detection and termination of an extended low-frequency hospital outbreak of GIM-1-producing Pseudomonas aeruginosa ST111 in Germany. Am J Infect Control 43(6):635–639.  https://doi.org/10.1016/j.ajic.2015.02.024 PubMedCrossRefGoogle Scholar
  19. 19.
    Sun F, Zhou D, Wang Q, Feng J, Feng W, Luo W, Zhang D, Liu Y, Qiu X, Yin Z, Chen W, Xia P (2016) The first report of detecting the blaSIM-2 gene and determining the complete sequence of the SIM-encoding plasmid. Clin Microbiol Infect 22(4):347–351.  https://doi.org/10.1016/j.cmi.2015.12.001 PubMedCrossRefGoogle Scholar
  20. 20.
    Mataseje LF, Peirano G, Church DL, Conly J, Mulvey M, Pitout JD (2016) Colistin-nonsusceptible Pseudomonas aeruginosa sequence type 654 with blaNDM-1 arrives in North America. Antimicrob Agents Chemother 60(3):1794–1800.  https://doi.org/10.1128/AAC.02591-15 PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Maltezou HC (2009) Metallo-beta-lactamases in Gram-negative bacteria: introducing the era of pan-resistance? Int J Antimicrob Agents 33(5):405 e401–405 e407.  https://doi.org/10.1016/j.ijantimicag.2008.09.003 CrossRefGoogle Scholar
  22. 22.
    Hagihara M, Crandon JL, Urban CM, Nicolau DP (2013) KPC presence in Pseudomonas aeruginosa has minimal impact on the in vivo efficacy of carbapenem therapy. Antimicrob Agents Chemother 57(2):1086–1088.  https://doi.org/10.1128/AAC.01748-12 PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Sevillano E, Gallego L, Garcia-Lobo JM (2009) First detection of the OXA-40 carbapenemase in P. aeruginosa isolates, located on a plasmid also found in A. baumannii. Pathol Biol 57(6):493–495.  https://doi.org/10.1016/j.patbio.2008.05.002 PubMedCrossRefGoogle Scholar
  24. 24.
    Tada T, Shimada K, Satou K, Hirano T, Pokhrel BM, Sherchand JB, Kirikae T (2017) Metallo-beta-lactamases (DIM-1, NDM-1, VIM-2) and a 16S rRNA methyltransferase (RmtB4, RmtF2) producing Pseudomonas aeruginosa in Nepal. Antimicrob Agents Chemother.  https://doi.org/10.1128/AAC.00694-17
  25. 25.
    Legakis NJ, Aliferopoulou M, Papavassiliou J, Papapetropoulou M (1982) Serotypes of Pseudomonas aeruginosa in clinical specimens in relation to antibiotic susceptibility. J Clin Microbiol 16(3):458–463PubMedPubMedCentralGoogle Scholar
  26. 26.
    Fyfe JA, Harris G, Govan JR (1984) Revised pyocin typing method for Pseudomonas aeruginosa. J Clin Microbiol 20(1):47–50PubMedPubMedCentralGoogle Scholar
  27. 27.
    Yan JJ, Hsueh PR, Ko WC, Luh KT, Tsai SH, Wu HM, Wu JJ (2001) Metallo-beta-lactamases in clinical Pseudomonas isolates in Taiwan and identification of VIM-3, a novel variant of the VIM-2 enzyme. Antimicrob Agents Chemother 45(8):2224–2228.  https://doi.org/10.1128/AAC.45.8.2224-2228.2001 PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Levesque C, Piche L, Larose C, Roy PH (1995) PCR mapping of integrons reveals several novel combinations of resistance genes. Antimicrob Agents Chemother 39(1):185–191PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Cuenca FF, Pascual A, Martinez Marinez L, Conejo MC, Perea EJ (2003) Evaluation of SDS-polyacrylamide gel systems for the study of outer membrane protein profiles of clinical strains of Acinetobacter baumannii. J Basic Microbiol 43(3):194–201.  https://doi.org/10.1002/jobm.200390022 PubMedCrossRefGoogle Scholar
  30. 30.
    Yoneda K, Chikumi H, Murata T, Gotoh N, Yamamoto H, Fujiwara H, Nishino T, Shimizu E (2005) Measurement of Pseudomonas aeruginosa multidrug efflux pumps by quantitative real-time polymerase chain reaction. FEMS Microbiol Lett 243(1):125–131.  https://doi.org/10.1016/j.femsle.2004.11.048 PubMedCrossRefGoogle Scholar
  31. 31.
    Mahenthiralingam E, Campbell ME, Foster J, Lam JS, Speert DP (1996) Random amplified polymorphic DNA typing of Pseudomonas aeruginosa isolates recovered from patients with cystic fibrosis. J Clin Microbiol 34(5):1129–1135PubMedPubMedCentralGoogle Scholar
  32. 32.
    Kaufmann ME (1998) Pulsed-field gel electrophoresis. Methods Mol Med 15:33–50.  https://doi.org/10.1385/0-89603-498-4:33 PubMedGoogle Scholar
  33. 33.
    Poirel L, Naas T, Nicolas D, Collet L, Bellais S, Cavallo JD, Nordmann P (2000) Characterization of VIM-2, a carbapenem-hydrolyzing metallo-beta-lactamase and its plasmid- and integron-borne gene from a Pseudomonas aeruginosa clinical isolate in France. Antimicrob Agents Chemother 44(4):891–897PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    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):5644–5649.  https://doi.org/10.1128/JCM.42.12.5644-5649.2004 PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Giske CG, Libisch B, Colinon C, Scoulica E, Pagani L, Fuzi M, Kronvall G, Rossolini GM (2006) Establishing clonal relationships between VIM-1-like metallo-beta-lactamase-producing Pseudomonas aeruginosa strains from four European countries by multilocus sequence typing. J Clin Microbiol 44(12):4309–4315.  https://doi.org/10.1128/JCM.00817-06 PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Giamarellou H, Touliatou K, Koratzanis G, Petrikkos G, Kanellakopoulou K, Lelekis M, Pagona A, Tsagarakis J, Symeonides J, Falagas M (1986) Nosocomial consequences of antibiotic usage. Scand J Infect Dis Suppl 49:182–188PubMedGoogle Scholar
  37. 37.
    Giamarellou H, Sfikakis P, Voutsinas D, Galanakis N, Daikos GK (1986) Evaluation of imipenem/cilastatin against nosocomial infections and multiresistant pathogens. J Antimicrob Chemother 18(Suppl E):175–179PubMedCrossRefGoogle Scholar
  38. 38.
    Giamarellou H (1986) Aminoglycosides plus beta-lactams against gram-negative organisms. Evaluation of in vitro synergy and chemical interactions. Am J Med 80(6B):126–137PubMedCrossRefGoogle Scholar
  39. 39.
    Giamarellou H, Petrikkos G (1987) Ciprofloxacin interactions with imipenem and amikacin against multiresistant Pseudomonas aeruginosa. Antimicrob Agents Chemother 31(6):959–961PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Voutsinas D, Mavroudis T, Avlamis A, Giamarellou H (1989) In-vitro activity of meropenem, a new carbapenem, against multiresistant Pseudomonas aeruginosa compared with that of other antipseudomonal antimicrobials. J Antimicrob Chemother 24(Suppl A):143–147PubMedCrossRefGoogle Scholar
  41. 41.
    Giamarellos-Bourboulis EJ, Grecka P, Giamarellou H (1995) Comparative in vitro killing activity of meropenem versus imipenem against multiresistant nosocomial Pseudomonas aeruginosa. J Chemother 7(3):179–183.  https://doi.org/10.1179/joc.1995.7.3.179 PubMedCrossRefGoogle Scholar
  42. 42.
    Anderson DL (2006) Doripenem. Drugs Today 42(6):399–404.  https://doi.org/10.1358/dot.2006.42.6.985634 PubMedCrossRefGoogle Scholar
  43. 43.
    Giamarellou H, Kanellakopoulou K (2008) Current therapies for pseudomonas aeruginosa. Crit Care Clin 24(2):261–278, viii.  https://doi.org/10.1016/j.ccc.2007.12.004 PubMedCrossRefGoogle Scholar
  44. 44.
    Poulakou G, Giamarellou H (2008) Doripenem: an expected arrival in the treatment of infections caused by multidrug-resistant Gram-negative pathogens. Expert Opin Investig Drugs 17(5):749–771.  https://doi.org/10.1517/13543784.17.5.749 PubMedCrossRefGoogle Scholar
  45. 45.
    Tassios PT, Gennimata V, Maniatis AN, Fock C, Legakis NJ (1998) Emergence of multidrug resistance in ubiquitous and dominant Pseudomonas aeruginosa serogroup O:11. The Greek Pseudomonas aeruginosa study group. J Clin Microbiol 36(4):897–901PubMedPubMedCentralGoogle Scholar
  46. 46.
    Legakis NJ, Koukoubanis N, Malliara K, Michalitsianos D, Papavassiliou J (1987) Importance of carbenicillin and gentamicin cross-resistant serotype 0:12 Pseudomonas aeruginosa in six Athens hospitals. Eur J Clin Microbiol 6(3):300–303PubMedCrossRefGoogle Scholar
  47. 47.
    Doring G, Horz M, Ortelt J, Grupp H, Wolz C (1993) Molecular epidemiology of Pseudomonas aeruginosa in an intensive care unit. Epidemiol Infect 110(3):427–436PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Pradella S, Pletschette M, Mantey-Stiers F, Bautsch W (1994) Macrorestriction analysis of Pseudomonas aeruginosa in colonized burn patients. Eur J Clin Microbiol Infect Dis 13(2):122–128PubMedCrossRefGoogle Scholar
  49. 49.
    Tassios PT, Gennimata V, Spaliara-Kalogeropoulou L, Kairis D, Koutsia C, Vatopoulos AC, Legakis NJ (1997) Multiresistant Pseudomonas aeruginosa serogroup O:11 outbreak in an intensive care unit. Clin Microbiol Infect 3(6):621–628PubMedCrossRefGoogle Scholar
  50. 50.
    Pitt TL, Livermore DM, Pitcher D, Vatopoulos AC, Legakis NJ (1989) Multiresistant serotype O 12 Pseudomonas aeruginosa: evidence for a common strain in Europe. Epidemiol Infect 103(3):565–576PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Senda K, Arakawa Y, Ichiyama S, Nakashima K, Ito H, Ohsuka S, Shimokata K, Kato N, Ohta M (1996) PCR detection of metallo-beta-lactamase gene (blaIMP) in gram-negative rods resistant to broad-spectrum beta-lactams. J Clin Microbiol 34(12):2909–2913PubMedPubMedCentralGoogle Scholar
  52. 52.
    Senda K, Arakawa Y, Nakashima K, Ito H, Ichiyama S, Shimokata K, Kato N, Ohta M (1996) Multifocal outbreaks of metallo-beta-lactamase-producing Pseudomonas aeruginosa resistant to broad-spectrum beta-lactams, including carbapenems. Antimicrob Agents Chemother 40(2):349–353PubMedPubMedCentralGoogle Scholar
  53. 53.
    Gibb AP, Tribuddharat C, Moore RA, Louie TJ, Krulicki W, Livermore DM, Palepou MF, Woodford N (2002) Nosocomial outbreak of carbapenem-resistant Pseudomonas aeruginosa with a new bla(IMP) allele, bla(IMP-7). Antimicrob Agents Chemother 46(1):255–258PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Lauretti L, Riccio ML, Mazzariol A, Cornaglia G, Amicosante G, Fontana R, Rossolini GM (1999) Cloning and characterization of blaVIM, a new integron-borne metallo-beta-lactamase gene from a Pseudomonas aeruginosa clinical isolate. Antimicrob Agents Chemother 43(7):1584–1590PubMedPubMedCentralGoogle Scholar
  55. 55.
    Xiong J, Hynes MF, Ye H, Chen H, Yang Y, M'Zali F, Hawkey PM (2006) bla(IMP-9) and its association with large plasmids carried by Pseudomonas aeruginosa isolates from the People’s Republic of China. Antimicrob Agents Chemother 50(1):355–358.  https://doi.org/10.1128/AAC.50.1.355-358.2006 PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Poirel L, Nordmann P (2002) Acquired carbapenem-hydrolyzing beta-lactamases and their genetic support. Curr Pharm Biotechnol 3(2):117–127PubMedCrossRefGoogle Scholar
  57. 57.
    Cornaglia G, Mazzariol A, Lauretti L, Rossolini GM, Fontana R (2000) Hospital outbreak of carbapenem-resistant Pseudomonas aeruginosa producing VIM-1, a novel transferable metallo-beta-lactamase. Clin Infect Dis 31(5):1119–1125.  https://doi.org/10.1086/317448 PubMedCrossRefGoogle Scholar
  58. 58.
    Corvec S, Poirel L, Decousser JW, Allouch PY, Drugeon H, Nordmann P (2006) Emergence of carbapenem-hydrolysing metallo-beta-lactamase VIM-1 in Pseudomonas aeruginosa isolates in France. Clin Microbiol Infect 12(9):941–942.  https://doi.org/10.1111/j.1469-0691.2006.1532_1.x PubMedCrossRefGoogle Scholar
  59. 59.
    Tsakris A, Pournaras S, Woodford N, Palepou MF, Babini GS, Douboyas J, Livermore DM (2000) Outbreak of infections caused by Pseudomonas aeruginosa producing VIM-1 carbapenemase in Greece. J Clin Microbiol 38(3):1290–1292PubMedPubMedCentralGoogle Scholar
  60. 60.
    Mavroidi A, Tsakris A, Tzelepi E, Pournaras S, Loukova V, Tzouvelekis LS (2000) Carbapenem-hydrolysing VIM-2 metallo-beta-lactamase in Pseudomonas aeruginosa from Greece. J Antimicrob Chemother 46(6):1041–1042PubMedCrossRefGoogle Scholar
  61. 61.
    Lee K, Lim JB, Yum JH, Yong D, Chong Y, Kim JM, Livermore DM (2002) bla(VIM-2) cassette-containing novel integrons in metallo-beta-lactamase-producing Pseudomonas aeruginosa and Pseudomonas putida isolates disseminated in a Korean hospital. Antimicrob Agents Chemother 46(4):1053–1058PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Sofianou D, Tsakris A, Skoura L, Douboyas J (1997) Extended high-level cross-resistance to antipseudomonal antibiotics amongst Pseudomonas aeruginosa isolates in a university hospital. J Antimicrob Chemother 40(5):740–742PubMedCrossRefGoogle Scholar
  63. 63.
    Pournaras S, Tsakris A, Maniati M, Tzouvelekis LS, Maniatis AN (2002) Novel variant (bla(VIM-4)) of the metallo-beta-lactamase gene bla(VIM-1) in a clinical strain of Pseudomonas aeruginosa. Antimicrob Agents Chemother 46(12):4026–4028PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Tsakris A, Tassios PT, Polydorou F, Papa A, Malaka E, Antoniadis A, Legakis NJ (2003) Infrequent detection of acquired metallo-beta-lactamases among carbapenem-resistant Pseudomonas isolates in a Greek hospital. Clin Microbiol Infect 9(8):846–851PubMedCrossRefGoogle Scholar
  65. 65.
    Giske CG, Rylander M, Kronvall G (2003) VIM-4 in a carbapenem-resistant strain of Pseudomonas aeruginosa isolated in Sweden. Antimicrob Agents Chemother 47(9):3034–3035PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Libisch B, Gacs M, Csiszar K, Muzslay M, Rokusz L, Fuzi M (2004) Isolation of an integron-borne blaVIM-4 type metallo-beta-lactamase gene from a carbapenem-resistant Pseudomonas aeruginosa clinical isolate in Hungary. Antimicrob Agents Chemother 48(9):3576–3578.  https://doi.org/10.1128/AAC.48.9.3576-3578.2004 PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Libisch B, Muzslay M, Gacs M, Minarovits J, Knausz M, Watine J, Ternak G, Kenez E, Kustos I, Rokusz L, Szeles K, Balogh B, Fuzi M (2006) Molecular epidemiology of VIM-4 metallo-beta-lactamase-producing Pseudomonas sp. isolates in Hungary. Antimicrob Agents Chemother 50(12):4220–4223.  https://doi.org/10.1128/AAC.00300-06 PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Giakkoupi P, Petrikkos G, Tzouvelekis LS, Tsonas S, Legakis NJ, Vatopoulos AC, Group WGS (2003) Spread of integron-associated VIM-type metallo-beta-lactamase genes among imipenem-nonsusceptible Pseudomonas aeruginosa strains in Greek hospitals. J Clin Microbiol 41(2):822–825PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Poirel L, Lambert T, Turkoglu S, Ronco E, Gaillard J, Nordmann P (2001) Characterization of class 1 integrons from Pseudomonas aeruginosa that contain the bla(VIM-2) carbapenem-hydrolyzing beta-lactamase gene and of two novel aminoglycoside resistance gene cassettes. Antimicrob Agents Chemother 45(2):546–552.  https://doi.org/10.1128/AAC.45.2.546-552.2001 PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Pournaras S, Maniati M, Petinaki E, Tzouvelekis LS, Tsakris A, Legakis NJ, Maniatis AN (2003) Hospital outbreak of multiple clones of Pseudomonas aeruginosa carrying the unrelated metallo-beta-lactamase gene variants blaVIM-2 and blaVIM-4. J Antimicrob Chemother 51(6):1409–1414.  https://doi.org/10.1093/jac/dkg239 PubMedCrossRefGoogle Scholar
  71. 71.
    Toleman MA, Rolston K, Jones RN, Walsh TR (2004) blaVIM-7, an evolutionarily distinct metallo-beta-lactamase gene in a Pseudomonas aeruginosa isolate from the United States. Antimicrob Agents Chemother 48(1):329–332PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Pasteran F, Faccone D, Petroni A, Rapoport M, Galas M, Vazquez M, Procopio A (2005) Novel variant (bla(VIM-11)) of the metallo-{beta}-lactamase bla(VIM) family in a GES-1 extended-spectrum-{beta}-lactamase-producing Pseudomonas aeruginosa clinical isolate in Argentina. Antimicrob Agents Chemother 49(1):474–475.  https://doi.org/10.1128/AAC.49.1.474-475.2005 PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Bahar G, Mazzariol A, Koncan R, Mert A, Fontana R, Rossolini GM, Cornaglia G (2004) Detection of VIM-5 metallo-beta-lactamase in a Pseudomonas aeruginosa clinical isolate from Turkey. J Antimicrob Chemother 54(1):282–283.  https://doi.org/10.1093/jac/dkh321 PubMedCrossRefGoogle Scholar
  74. 74.
    Pournaras S, Maniati M, Spanakis N, Ikonomidis A, Tassios PT, Tsakris A, Legakis NJ, Maniatis AN (2005) Spread of efflux pump-overexpressing, non-metallo-beta-lactamase-producing, meropenem-resistant but ceftazidime-susceptible Pseudomonas aeruginosa in a region with blaVIM endemicity. J Antimicrob Chemother 56(4):761–764.  https://doi.org/10.1093/jac/dki296 PubMedCrossRefGoogle Scholar
  75. 75.
    Zappas S, Giakkoupi P, Vourli S, Hadjichristodoulou C, Polemis M, Tzouvelekis LS, Avlami A, Vatopoulos A, Daikos GL, Petrikkos G (2008) Epidemiology of metalloenzyme-producing Pseudomonas aeruginosa in a tertiary hospital in Greece. J Chemother 20(3):307–311.  https://doi.org/10.1179/joc.2008.20.3.307 PubMedCrossRefGoogle Scholar
  76. 76.
    Falagas ME, Bliziotis IA, Kasiakou SK, Samonis G, Athanassopoulou P, Michalopoulos A (2005) Outcome of infections due to pandrug-resistant (PDR) Gram-negative bacteria. BMC Infect Dis 5:24.  https://doi.org/10.1186/1471-2334-5-24 PubMedPubMedCentralCrossRefGoogle Scholar
  77. 77.
    Siarkou VI, Vitti D, Protonotariou E, Ikonomidis A, Sofianou D (2009) Molecular epidemiology of outbreak-related pseudomonas aeruginosa strains carrying the novel variant blaVIM-17 metallo-beta-lactamase gene. Antimicrob Agents Chemother 53(4):1325–1330.  https://doi.org/10.1128/AAC.01230-08 PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Pournaras S, Ikonomidis A, Markogiannakis A, Spanakis N, Maniatis AN, Tsakris A (2007) Characterization of clinical isolates of Pseudomonas aeruginosa heterogeneously resistant to carbapenems. J Med Microbiol 56(Pt 1):66–70.  https://doi.org/10.1099/jmm.0.46816-0 PubMedCrossRefGoogle Scholar
  79. 79.
    Ikonomidis A, Tsakris A, Kantzanou M, Spanakis N, Maniatis AN, Pournaras S (2008) Efflux system overexpression and decreased OprD contribute to the carbapenem heterogeneity in Pseudomonas aeruginosa. FEMS Microbiol Lett 279(1):36–39.  https://doi.org/10.1111/j.1574-6968.2007.00997.x PubMedCrossRefGoogle Scholar
  80. 80.
    Castanheira M, Toleman MA, Jones RN, Schmidt FJ, Walsh TR (2004) Molecular characterization of a beta-lactamase gene, blaGIM-1, encoding a new subclass of metallo-beta-lactamase. Antimicrob Agents Chemother 48(12):4654–4661.  https://doi.org/10.1128/AAC.48.12.4654-4661.2004 PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Toleman MA, Simm AM, Murphy TA, Gales AC, Biedenbach DJ, Jones RN, Walsh TR (2002) Molecular characterization of SPM-1, a novel metallo-beta-lactamase isolated in Latin America: report from the SENTRY antimicrobial surveillance programme. J Antimicrob Chemother 50(5):673–679PubMedCrossRefGoogle Scholar
  82. 82.
    Lee K, Yum JH, Yong D, Lee HM, Kim HD, Docquier JD, Rossolini GM, Chong Y (2005) Novel acquired metallo-beta-lactamase gene, bla(SIM-1), in a class 1 integron from Acinetobacter baumannii clinical isolates from Korea. Antimicrob Agents Chemother 49(11):4485–4491.  https://doi.org/10.1128/AAC.49.11.4485-4491.2005 PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Maniati M, Ikonomidis A, Mantzana P, Daponte A, Maniatis AN, Pournaras S (2007) A highly carbapenem-resistant Pseudomonas aeruginosa isolate with a novel blaVIM-4/blaP1b integron overexpresses two efflux pumps and lacks OprD. J Antimicrob Chemother 60(1):132–135.  https://doi.org/10.1093/jac/dkm126 PubMedCrossRefGoogle Scholar
  84. 84.
    Fiett J, Baraniak A, Mrowka A, Fleischer M, Drulis-Kawa Z, Naumiuk L, Samet A, Hryniewicz W, Gniadkowski M (2006) Molecular epidemiology of acquired-metallo-beta-lactamase-producing bacteria in Poland. Antimicrob Agents Chemother 50(3):880–886.  https://doi.org/10.1128/AAC.50.3.880-886.2006 PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Horianopoulou M, Legakis NJ, Kanellopoulou M, Lambropoulos S, Tsakris A, Falagas ME (2006) Frequency and predictors of colonization of the respiratory tract by VIM-2-producing Pseudomonas aeruginosa in patients of a newly established intensive care unit. J Med Microbiol 55(Pt 10):1435–1439.  https://doi.org/10.1099/jmm.0.46713-0 PubMedCrossRefGoogle Scholar
  86. 86.
    Schneider I, Keuleyan E, Rasshofer R, Markovska R, Queenan AM, Bauernfeind A (2008) VIM-15 and VIM-16, two new VIM-2-like metallo-beta-lactamases in Pseudomonas aeruginosa isolates from Bulgaria and Germany. Antimicrob Agents Chemother 52(8):2977–2979.  https://doi.org/10.1128/AAC.00175-08 PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Castanheira M, Bell JM, Turnidge JD, Mathai D, Jones RN (2009) Carbapenem resistance among Pseudomonas aeruginosa strains from India: evidence for nationwide endemicity of multiple metallo-beta-lactamase clones (VIM-2, -5, -6, and -11 and the newly characterized VIM-18). Antimicrob Agents Chemother 53(3):1225–1227.  https://doi.org/10.1128/AAC.01011-08 PubMedCrossRefGoogle Scholar
  88. 88.
    Castanheira M, Bell JM, Turnidge JD, Mendes RE, Jones RN (2010) Dissemination and genetic context analysis of bla(VIM-6) among Pseudomonas aeruginosa isolates in Asian-Pacific Nations. Clin Microbiol Infect 16(2):186–189.  https://doi.org/10.1111/j.1469-0691.2009.02903.x PubMedCrossRefGoogle Scholar
  89. 89.
    Mazzariol A, Mammina C, Koncan R, Di Gaetano V, Di Carlo P, Cipolla D, Corsello G, Cornaglia G (2011) A novel VIM-type metallo-beta-lactamase (VIM-14) in a Pseudomonas aeruginosa clinical isolate from a neonatal intensive care unit. Clin Microbiol Infect 17(5):722–724.  https://doi.org/10.1111/j.1469-0691.2010.03424.x PubMedCrossRefGoogle Scholar
  90. 90.
    Souli M, Galani I, Giamarellou H (2008) Emergence of extensively drug-resistant and pandrug-resistant Gram-negative bacilli in Europe. Euro Surveill 13(47)Google Scholar
  91. 91.
    Tsakris A, Poulou A, Kristo I, Pittaras T, Spanakis N, Pournaras S, Markou F (2009) Large dissemination of VIM-2-metallo-{beta}-lactamase-producing pseudomonas aeruginosa strains causing health care-associated community-onset infections. J Clin Microbiol 47(11):3524–3529.  https://doi.org/10.1128/JCM.01099-09 PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Meletis G, Exindari M, Vavatsi N, Sofianou D, Diza E (2012) Mechanisms responsible for the emergence of carbapenem resistance in Pseudomonas aeruginosa. Hippokratia 16(4):303–307PubMedPubMedCentralGoogle Scholar
  93. 93.
    Miyakis S, Pefanis A, Tsakris A (2011) The challenges of antimicrobial drug resistance in Greece. Clin Infect Dis 53(2):177–184.  https://doi.org/10.1093/cid/cir323 PubMedCrossRefGoogle Scholar
  94. 94.
    Liakopoulos A, Mavroidi A, Katsifas EA, Theodosiou A, Karagouni AD, Miriagou V, Petinaki E (2013) Carbapenemase-producing Pseudomonas aeruginosa from Central Greece: molecular epidemiology and genetic analysis of class I integrons. BMC Infect Dis 13:505.  https://doi.org/10.1186/1471-2334-13-505 PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Gilarranz R, Juan C, Castillo-Vera J, Chamizo FJ, Artiles F, Alamo I, Oliver A (2013) First detection in Europe of the metallo-beta-lactamase IMP-15 in clinical strains of Pseudomonas putida and Pseudomonas aeruginosa. Clin Microbiol Infect 19(9):E424–E427.  https://doi.org/10.1111/1469-0691.12248 PubMedCrossRefGoogle Scholar
  96. 96.
    Guzvinec M, Izdebski R, Butic I, Jelic M, Abram M, Koscak I, Baraniak A, Hryniewicz W, Gniadkowski M, Tambic Andrasevic A (2014) Sequence types 235, 111, and 132 predominate among multidrug-resistant pseudomonas aeruginosa clinical isolates in Croatia. Antimicrob Agents Chemother 58(10):6277–6283.  https://doi.org/10.1128/AAC.03116-14 PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Nemec A, Krizova L, Maixnerova M, Musilek M (2010) Multidrug-resistant epidemic clones among bloodstream isolates of Pseudomonas aeruginosa in the Czech Republic. Res Microbiol 161(3):234–242.  https://doi.org/10.1016/j.resmic.2010.02.002 PubMedCrossRefGoogle Scholar
  98. 98.
    Meletis G, Oustas E, Botziori C, Kakasi E, Koteli A (2015) Containment of carbapenem resistance rates of Klebsiella pneumoniae and Acinetobacter baumannii in a Greek hospital with a concomitant increase in colistin, gentamicin and tigecycline resistance. New Microbiol 38(3):417–421PubMedGoogle Scholar
  99. 99.
    Karampatakis T, Geladari A, Politi L, Antachopoulos C, Iosifidis E, Tsiatsiou O, Karyoti A, Papanikolaou V, Tsakris A, Roilides E (2017) Cluster-distinguishing genotypic and phenotypic diversity of carbapenem-resistant Gram-negative bacteria in solid-organ transplantation patients: a comparative study. J Med Microbiol.  https://doi.org/10.1099/jmm.0.000541
  100. 100.
    Geladari A, Karampatakis T, Antachopoulos C, Iosifidis E, Tsiatsiou O, Politi L, Karyoti A, Papanikolaou V, Tsakris A, Roilides E (2017) Epidemiological surveillance of multidrug-resistant gram-negative bacteria in a solid organ transplantation department. Transpl infect Dis.  https://doi.org/10.1111/tid.12686
  101. 101.
    Villegas MV, Lolans K, Correa A, Kattan JN, Lopez JA, Quinn JP, Colombian Nosocomial Resistance Study G (2007) First identification of Pseudomonas aeruginosa isolates producing a KPC-type carbapenem-hydrolyzing beta-lactamase. Antimicrob Agents Chemother 51(4):1553–1555.  https://doi.org/10.1128/AAC.01405-06 PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Correa A, Montealegre MC, Mojica MF, Maya JJ, Rojas LJ, De La Cadena EP, Ruiz SJ, Recalde M, Rosso F, Quinn JP, Villegas MV (2012) First report of a Pseudomonas aeruginosa isolate coharboring KPC and VIM carbapenemases. Antimicrob Agents Chemother 56(10):5422–5423.  https://doi.org/10.1128/AAC.00695-12 PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Tofas P, Samarkos M, Piperaki ET, Kosmidis C, Triantafyllopoulou ID, Kotsopoulou M, Pantazatou A, Perlorentzou S, Poulli A, Vagia M, Daikos GL (2017) Pseudomonas aeruginosa bacteraemia in patients with hematologic malignancies: risk factors, treatment and outcome. Diagn Microbiol Infect Dis.  https://doi.org/10.1016/j.diagmicrobio.2017.05.003
  104. 104.
    Beris FS, Akyildiz E, Ozad Duzgun A, Say Coskun US, Sandalli C, Copur Cicek A (2016) A novel integron gene cassette harboring VIM-38 metallo-beta-lactamase in a clinical Pseudomonas aeruginosa isolate. Ann Lab Med 36(6):611–613.  https://doi.org/10.3343/alm.2016.36.6.611 PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Wang M, Borris L, Aarestrup FM, Hasman H (2015) Identification of a Pseudomonas aeruginosa co-producing NDM-1, VIM-5 and VIM-6 metallo-beta-lactamases in Denmark using whole-genome sequencing. Int J Antimicrob Agents 45(3):324–325.  https://doi.org/10.1016/j.ijantimicag.2014.11.004 PubMedCrossRefGoogle Scholar
  106. 106.
    Zafer MM, Amin M, El Mahallawy H, Ashour MS, Al Agamy M (2014) First report of NDM-1-producing Pseudomonas aeruginosa in Egypt. Int J Infect Dis 29:80–81.  https://doi.org/10.1016/j.ijid.2014.07.008 PubMedCrossRefGoogle Scholar
  107. 107.
    Shu JC, Kuo AJ, Su LH, Liu TP, Lee MH, Su IN, Wu TL (2017) Development of carbapenem resistance in Pseudomonas aeruginosa is associated with OprD polymorphisms, particularly the amino acid substitution at codon 170. J Antimicrob Chemother.  https://doi.org/10.1093/jac/dkx158
  108. 108.
    Chalhoub H, Saenz Y, Rodriguez-Villalobos H, Denis O, Kahl BC, Tulkens PM, Van Bambeke F (2016) High-level resistance to meropenem in clinical isolates of Pseudomonas aeruginosa in the absence of carbapenemases: role of active efflux and porin alterations. Int J Antimicrob Agents 48(6):740–743.  https://doi.org/10.1016/j.ijantimicag.2016.09.012 PubMedCrossRefGoogle Scholar
  109. 109.
    Xiong J, Deraspe M, Iqbal N, Krajden S, Chapman W, Dewar K, Roy PH (2017) Complete genome of a Panresistant Pseudomonas aeruginosa strain, isolated from a patient with respiratory failure in a Canadian Community Hospital. Genome Announc 5(22).  https://doi.org/10.1128/genomeA.00458-17
  110. 110.
    Lapuebla A, Abdallah M, Olafisoye O, Cortes C, Urban C, Landman D, Quale J (2015) Activity of imipenem with relebactam against Gram-negative pathogens from New York City. Antimicrob Agents Chemother 59(8):5029–5031.  https://doi.org/10.1128/AAC.00830-15 PubMedPubMedCentralCrossRefGoogle Scholar
  111. 111.
    Zhanel GG, Chung P, Adam H, Zelenitsky S, Denisuik A, Schweizer F, Lagace-Wiens PR, Rubinstein E, Gin AS, Walkty A, Hoban DJ, Lynch JP 3rd, Karlowsky JA (2014) Ceftolozane/tazobactam: a novel cephalosporin/beta-lactamase inhibitor combination with activity against multidrug-resistant gram-negative bacilli. Drugs 74(1):31–51.  https://doi.org/10.1007/s40265-013-0168-2 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Infectious Diseases Unit, 3rd Department of Pediatrics, Medical Faculty, School of Health Sciences, Hippokration General HospitalThessalonikiGreece
  2. 2.Microbiology DepartmentNational and Kapodistrian University School of MedicineAthensGreece

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