, Volume 72, Issue 1, pp 1–16 | Cite as

Plasmid-Mediated Resistance in Enterobacteriaceae

Changing Landscape and Implications for Therapy
Leading Article


Antimicrobial resistance is increasing worldwide, and pathogenic microorganisms that are resistant to all available antimicrobial agents are increasingly reported. Emerging plasmid-encoded extended-spectrum β-lactamases (ESBLs) and carbapenemases are increasingly reported worldwide. Carbapenemase production encoded by genes located on mobile genetic elements is typically accompanied by genes encoding resistance to other drug classes, often but not necessarily located on the same mobile element. Multiple plasmid-mediated mechanisms of resistance against the fluoroquinolones and aminoglycosides have been described, and the combination of plasmid-mediated resistance with chromosomally encoded resistance mechanisms of multiple drug classes now results in strains that are resistant to all of the main classes of commonly used antimicrobial drugs. Clinical studies of antimicrobial therapy and outcome of patients infected with ESBL- or carbapenemase-producing strains of Enterobacteriaceae compared with patients infected with susceptible strains are limited in their design but suggest a worse outcome after infection with resistant strains.

Alternative options for the treatment of infections caused by carbapenem-resistant strains of Enterobacteriaceae are limited. Current strategies include colistin, fosfomycin, tigecycline and temocillin. Although in vitro testing suggests strong activity for each of these drugs against a large proportion of carbapenem-resistant strains of Enterobacteriaceae, clinical evaluations do not provide strong evidence for equivalent or improved outcome. Oral treatment with fosfomycin tromethamine is effective against lower urinary tract infections (UTIs) caused by ESBL-producing Escherichia coli. Intravenous fosfomycin may be beneficial and safe for patients when used as part of a combination therapy in the management of severe infections caused by carbapenem-resistant Klebsiella pneumoniae. Tigecycline is only indicated for the treatment of complicated skin and skin structure infections and complicated intra-abdominal infections in Europe, and is also approved for treatment of community-acquired pneumonia in the US. Clearly, further research on the clinical and safety outcomes in the treatment of multidrug-resistant Enterobacteriaceae with these existing alternative drugs, and the development of new and unrelated drugs, are urgently warranted.



The authors have no conflicts of interest to declare. The authors wish to thank Nguyen Vinh Trung for his contribution to the preparation of table I.


  1. 1.
    Fischbach MA, Walsh CT. Antibiotics for emerging pathogens. Science 2009 Aug 28; 325(5944): 1089–93PubMedCrossRefGoogle Scholar
  2. 2.
    Deleo FR, Otto M, Kreiswirth BN, et al. Community-associated meticillin-resistant Staphylococcus aureus. Lancet 2010 May 1; 375(9725): 1557–68PubMedCrossRefGoogle Scholar
  3. 3.
    Canton R, Coque TM. The CTX-M beta-lactamase pandemic. Curr Opin Microbiol 2006 Oct; 9(5): 466–75PubMedCrossRefGoogle Scholar
  4. 4.
    Poulou A, Spanakis N, Pournaras S, et al. Recurrent healthcare-associated community-onset infections due to Klebsiella pneumoniae producing VIM-1 metallo-beta-lactamase. J Antimicrob Chemother 2010 Dec; 65(12): 2538–42PubMedCrossRefGoogle Scholar
  5. 5.
    Ferech M, Coenen S, Malhotra-Kumar S, et al. European Surveillance of Antimicrobial Consumption (ESAC): outpatient antibiotic use in Europe. J Antimicrob Chemother 2006 Aug; 58(2): 401–7PubMedCrossRefGoogle Scholar
  6. 6.
    Cloeckaert A, Praud K, Lefevre M, et al. IncI1 plasmid carrying extended-spectrum-beta-lactamase gene blaCTX-M-1 in Salmonella enterica isolates from poultry and humans in France, 2003 to 2008. Antimicrob Agents Chemother 2010 Oct; 54(10): 4484–6PubMedCrossRefGoogle Scholar
  7. 7.
    Leverstein-van Hall MA, Dierikx CM, Cohen Stuart J, et al. Dutch patients, retail chicken meat and poultry share the same ESBL genes, plasmids and strains. Clin Microbiol Infect 2011 Jun; 17(6): 873–80CrossRefGoogle Scholar
  8. 8.
    Falagas ME, Karageorgopoulos DE. Pandrug resistance (PDR), extensive drug resistance (XDR), and multidrug resistance (MDR) among Gram-negative bacilli: need for international harmonization in terminology. Clin Infect Dis 2008 Apr 1; 46(7): 1121–2PubMedCrossRefGoogle Scholar
  9. 9.
    Paterson DL, Doi Y. A step closer to extreme drug resistance (XDR) in gram-negative bacilli. Clin Infect Dis 2007 Nov 1; 45(9): 1179–81PubMedCrossRefGoogle Scholar
  10. 10.
    Carattoli A. Resistance plasmid families in Enterobacteriaceae. Antimicrob Agents Chemother 2009 Jun; 53(6): 2227–38PubMedCrossRefGoogle Scholar
  11. 11.
    Cambray G, Guerout AM, Mazel D. Integrons. Annu Rev Genet 2010; 44: 141–66PubMedCrossRefGoogle Scholar
  12. 12.
    Bush K. Alarming beta-lactamase-mediated resistance in multidrug-resistant Enterobacteriaceae. Curr Opin Microbiol 2010 Oct; 13(5): 558–64PubMedCrossRefGoogle Scholar
  13. 13.
    Bush K, Jacoby GA. Updated functional classification of beta-lactamases. Antimicrob Agents Chemother 2010 Mar; 54(3): 969–76PubMedCrossRefGoogle Scholar
  14. 14.
    Cornaglia G, Giamarellou H, Rossolini GM. Metallo-β-lactamases: a last frontier for β-lactams? Lancet Infect Dis 2011 May; 11(5): 381–93PubMedCrossRefGoogle Scholar
  15. 15.
    Giamarellou H, Poulakou G. Multidrug-resistant Gram-negative infections: what are the treatment options? Drugs 2009 Oct 1; 69(14): 1879–901PubMedCrossRefGoogle Scholar
  16. 16.
    Nordmann P, Cuzon G, Naas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. Lancet Infect Dis 2009 Apr; 9(4): 228–36PubMedCrossRefGoogle Scholar
  17. 17.
    Poirel L, Naas T, Nordmann P. Diversity, epidemiology, and genetics of class D beta-lactamases. Antimicrob Agents Chemother 2010 Jan; 54(1): 24–38PubMedCrossRefGoogle Scholar
  18. 18.
    Ramirez MS, Tolmasky ME. Aminoglycoside modifying enzymes. Drug Resist Updat 2010 Dec; 13(6): 151–71PubMedCrossRefGoogle Scholar
  19. 19.
    Rodriguez-Martinez JM, Cano ME, Velasco C, et al. Plasmid-mediated quinolone resistance: an update. J Infect Chemother 2011 Apr; 17(2): 149–82PubMedCrossRefGoogle Scholar
  20. 20.
    Giske CG, Sundsfjord AS, Kahlmeter G, et al. Redefining extended-spectrum beta-lactamases: balancing science and clinical need. J Antimicrob Chemother 2009 Jan; 63(1): 1–4PubMedCrossRefGoogle Scholar
  21. 21.
    Lahey Clinic. gβ-lactamase classification and amino acid sequences for TEM, SHV and OXA extended spectrum and inhibitor resistant enzymes [online]. Available from URL: http://www.lahey.org/studies [Accessed 2011 Nov 1]
  22. 22.
    Queenan AM, Bush K. Carbapenemases: the versatile beta-lactamases. Clin Microbiol Rev 2007 Jul; 20(3): 440–58PubMedCrossRefGoogle Scholar
  23. 23.
    Livermore DM. Defining an extended-spectrum beta-lactamase. Clin Microbiol Infect 2008 Jan; 14 Suppl. 1: 3–10PubMedCrossRefGoogle Scholar
  24. 24.
    Bush K, Jacoby GA, Amicosante G, et al. Comment on: redefining extended-spectrum beta-lactamases. Balancing science and clinical need. J Antimicrob Chemother 2009 Jul; 64(1): 212–3; author reply 3-5PubMedCrossRefGoogle Scholar
  25. 25.
    Yang Q, Wang H, Sun H, et al. Phenotypic and genotypic characterization of Enterobacteriaceae with decreased susceptibility to carbapenems: results from large hospital-based surveillance studies in China. Antimicrob Agents Chemother 2010 Jan; 54(1): 573–7PubMedCrossRefGoogle Scholar
  26. 26.
    Chihara S, Okuzumi K, Yamamoto Y, et al. First case of New Delhi metallo-beta-lactamase 1-producing Escherichia coli infection in Japan. Clin Infect Dis 2011 Jan; 52(1): 153–4PubMedCrossRefGoogle Scholar
  27. 27.
    Kumarasamy KK, Toleman MA, Walsh TR, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis 2010 Sep; 10(9): 597–602PubMedCrossRefGoogle Scholar
  28. 28.
    Poirel L, Hombrouck-Alet C, Freneaux C, et al. Global spread of New Delhi metallo-β-lactamase 1 [letter]. Lancet Infect Dis 2010 Dec; 10(12): 832PubMedCrossRefGoogle Scholar
  29. 29.
    Poirel L, Lagrutta E, Taylor P, et al. Emergence of metallo-beta-lactamase NDM-1-producing multidrug-resistant Escherichia coli in Australia. Antimicrob Agents Chemother 2010 Nov; 54(11): 4914–6PubMedCrossRefGoogle Scholar
  30. 30.
    Struelens MJ, Monnet DL, Magiorakos AP, et al. New Delhi metallo-beta-lactamase 1-producing Enterobacteriaceae: emergence and response in Europe. Euro Surveill 2010 Nov 18; 15(46): 19716PubMedGoogle Scholar
  31. 31.
    Nordmann P, Poirel L, Toleman MA, et al. Does broad-spectrum beta-lactam resistance due to NDM-1 herald the end of the antibiotic era for treatment of infections caused by Gram-negative bacteria? J Antimicrob Chemother 2011 Apr; 66(4): 689–92PubMedCrossRefGoogle Scholar
  32. 32.
    Castanheira M, Deshpande LM, Mathai D, et al. Early dissemination of NDM-1- and OXA-181-producing Enterobacteriaceae in Indian hospitals: report from the SENTRY Antimicrobial Surveillance Program, 2006–2007. Antimicrob Agents Chemother 2011 Mar; 55(3): 1274–8PubMedCrossRefGoogle Scholar
  33. 33.
    Livermore DM, Walsh TR, Toleman M, et al. Balkan NDM-1: escape or transplant? [letter]. Lancet Infect Dis 2011 Mar; 11(3): 164PubMedCrossRefGoogle Scholar
  34. 34.
    Sidjabat H, Nimmo GR, Walsh TR, et al. Carbapenem resistance in Klebsiella pneumoniae due to the New Delhi Metallo-beta-lactamase. Clin Infect Dis 2011 Feb; 52(4): 481–4PubMedCrossRefGoogle Scholar
  35. 35.
    Mulvey MR, Grant JM, Plewes K, et al. New Delhi metallo-beta-lactamase in Klebsiella pneumoniae and Escherichia coli, Canada. Emerg Infect Dis 2011 Jan; 17(1): 103–6PubMedCrossRefGoogle Scholar
  36. 36.
    Yong D, Toleman MA, Giske CG, et al. Characterization of a new metallo-beta-lactamase gene, bla(NDM-1), and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 2009 Dec; 53(12): 5046–54PubMedCrossRefGoogle Scholar
  37. 37.
    Pfeifer Y, Witte W, Holfelder M, et al. NDM-1-producing Escherichia coli in Germany. Antimicrob Agents Chemother 2011 Mar; 55(3): 1318–9PubMedCrossRefGoogle Scholar
  38. 38.
    Poirel L, Fortineau N, Nordmann P. International transfer of NDM-1-producing Klebsiella pneumoniae from Iraq to France. Antimicrob Agents Chemother 2011 Apr; 55(4): 1821–2PubMedCrossRefGoogle Scholar
  39. 39.
    Poirel L, Revathi G, Bernabeu S, et al. Detection of NDM-1-producing Klebsiella pneumoniae in Kenya. Antimicrob Agents Chemother 2011 Feb; 55(2): 934–6PubMedCrossRefGoogle Scholar
  40. 40.
    Samuelsen O, Thilesen CM, Heggelund L, et al. Identification of NDM-1-producing Enterobacteriaceae in Norway. J Antimicrob Chemother 2011 Mar; 66(3): 670–2PubMedCrossRefGoogle Scholar
  41. 41.
    Poirel L, Al Maskari Z, Al Rashdi F, et al. NDM-1-producing Klebsiella pneumoniae isolated in the Sultanate of Oman. J Antimicrob Chemother 2011 Feb; 66(2): 304–6PubMedCrossRefGoogle Scholar
  42. 42.
    Leverstein-Van Hall MA, Stuart JC, Voets GM, et al. Global spread of New Delhi metallo-beta-lactamase 1. Lancet Infect Dis 2010 Dec; 10(12): 830–1CrossRefGoogle Scholar
  43. 43.
    Hammerum AM, Toleman MA, Hansen F, et al. Global spread of New Delhi metallo-beta-lactamase 1. Lancet Infect Dis 2010 Dec; 10(12): 829–30PubMedCrossRefGoogle Scholar
  44. 44.
    Koh TH, Khoo CT, Wijaya L, et al. Global spread of New Delhi metallo-beta-lactamase 1 [letter]. Lancet Infect Dis 2010 Dec; 10(12): 828PubMedCrossRefGoogle Scholar
  45. 45.
    Qi Y, Wei Z, Ji S, et al. ST11, the dominant clone of KPC-producing Klebsiella pneumoniae in China. J Antimicrob Chemother 2011 Feb; 66(2): 307–12PubMedCrossRefGoogle Scholar
  46. 46.
    Souli M, Galani I, Antoniadou A, et al. An outbreak of infection due to beta-Lactamase Klebsiella pneumoniae carbapenemase 2-producing K. pneumoniae in a Greek University Hospital: molecular characterization, epidemiology, and outcomes. Clin Infect Dis 2010 Feb 1; 50(3): 364–73PubMedCrossRefGoogle Scholar
  47. 47.
    Gaibani P, Ambretti S, Berlingeri A, et al. Rapid increase of carbapenemase-producing Klebsiella pneumoniae strains in a large Italian hospital: surveillance period 1 March-30 September 2010. Euro Surveill 2011; 16(8): 19800PubMedGoogle Scholar
  48. 48.
    Zacharczuk K, Piekarska K, Szych J, et al. Emergence of Klebsiella pneumoniae coproducing KPC-2 and 16S rRNA methylase ArmA in Poland. Antimicrob Agents Chemother 2011 Jan; 55(1): 443–6PubMedCrossRefGoogle Scholar
  49. 49.
    Poirel L, Lienhard R, Potron A, et al. Plasmid-mediated carbapenem-hydrolysing beta-lactamase KPC-2 in a Klebsiella pneumoniae isolate from Switzerland. J Antimicrob Chemother 2011 Mar; 66(3): 675–6PubMedCrossRefGoogle Scholar
  50. 50.
    Marchaim D, Chopra T, Pogue JM, et al. Outbreak of colistin-resistant, carbapenem-resistant Klebsiella pneumoniae in metropolitan Detroit, Michigan. Antimicrob Agents Chemother 2011 Feb; 55(2): 593–9PubMedCrossRefGoogle Scholar
  51. 51.
    Kitchel B, Rasheed JK, Patel JB, et al. Molecular epidemiology of KPC-producing Klebsiella pneumoniae isolates in the United States: clonal expansion of multilocus sequence type 258. Antimicrob Agents Chemother 2009 Aug; 53(8): 3365–70PubMedCrossRefGoogle Scholar
  52. 52.
    Cuzon G, Ouanich J, Gondret R, et al. Outbreak of OXA-48-positive carbapenem-resistant Klebsiella pneumoniae isolates in France. Antimicrob Agents Chemother 2011 May; 55(5): 2420–3PubMedCrossRefGoogle Scholar
  53. 53.
    Goren MG, Chmelnitsky I, Carmeli Y, et al. Plasmidencoded OXA-48 carbapenemase in Escherichia coli from Israel. J Antimicrob Chemother 2011 Mar; 66(3): 672–3PubMedCrossRefGoogle Scholar
  54. 54.
    Nordmann P, Poirel L, Carrer A, et al. How to detect NDM-1 producers. J Clin Microbiol 2011 Feb; 49(2): 718–21PubMedCrossRefGoogle Scholar
  55. 55.
    Cohen Stuart J, Leverstein-Van Hall MA. Guideline for phenotypic screening and confirmation of carbapenemases in Enterobacteriaceae. Int J Antimicrob Agents 2010 Sep; 36(3): 205–10PubMedCrossRefGoogle Scholar
  56. 56.
    Hirsch EB, Tam VH. Detection and treatment options for Klebsiella pneumoniae carbapenemases (KPCs): an emerging cause of multidrug-resistant infection. J Antimicrob Chemother 2010 Jun; 65(6): 1119–25PubMedCrossRefGoogle Scholar
  57. 57.
    Tato M, Morosini M, Garcia L, et al. Carbapenem heteroresistance in VIM-1-producing Klebsiella pneumoniae isolates belonging to the same clone: consequences for routine susceptibility testing. J Clin Microbiol 2010 Nov; 48(11): 4089–93PubMedCrossRefGoogle Scholar
  58. 58.
    Kahlmeter G. Breakpoints for intravenously used cephalosporins in Enterobacteriaceae: EUCAST and CLSI breakpoints. Clin Microbiol Infect 2008 Jan; 14 Suppl. 1: 169–74PubMedCrossRefGoogle Scholar
  59. 59.
    Chau TT, Campbell JI, Galindo CM, et al. Antimicrobial drug resistance of Salmonella enterica serovar typhi in Asia and molecular mechanism of reduced susceptibility to the fluoroquinolones. Antimicrob Agents Chemother 2007 Dec; 51(12): 4315–23PubMedCrossRefGoogle Scholar
  60. 60.
    Strahilevitz J, Engelstein D, Adler A, et al. Changes in qnr prevalence and fluoroquinolone resistance in clinical isolates of Klebsiella pneumoniae and Enterobacter spp. collected from 1990 to 2005. Antimicrob Agents Chemother 2007 Aug; 51(8): 3001–3PubMedCrossRefGoogle Scholar
  61. 61.
    Wang A, Yang Y, Lu Q, et al. Presence of qnr gene in Escherichia coli and Klebsiella pneumoniae resistant to ciprofloxacin isolated from pediatric patients in China. BMC Infect Dis 2008 May 22; 8: 68PubMedCrossRefGoogle Scholar
  62. 62.
    Higgins PG, Fluit AC, Schmitz FJ. Fluoroquinolones: structure and target sites. Curr Drug Targets 2003 Feb; 4(2): 181–90PubMedCrossRefGoogle Scholar
  63. 63.
    Jacoby GA. Mechanisms of resistance to quinolones. Clin Infect Dis 2005 Jul 15; 41 Suppl. 2: S120–6PubMedCrossRefGoogle Scholar
  64. 64.
    Robicsek A, Jacoby GA, Hooper DC. The worldwide emergence of plasmid-mediated quinolone resistance. Lancet Infect Dis 2006 Oct; 6(10): 629–40PubMedCrossRefGoogle Scholar
  65. 65.
    Lahey Clinic. qnr numbering and sequence [online]. Available from URL: http://www.lahey.org/qnrstudies [Accessed 2011 Nov 1]
  66. 66.
    Strahilevitz J, Jacoby GA, Hooper DC, et al. Plasmid-mediated quinolone resistance: a multifaceted threat. Clin Microbiol Rev 2009 Oct; 22(4): 664–89PubMedCrossRefGoogle Scholar
  67. 67.
    Briales A, Rodriguez-Martinez JM, Velasco C, et al. In vitro effect of qnrA1, qnrB1, and qnrS1 genes on fluoroquinolone activity against isogenic Escherichia coli isolates with mutations in gyrA and parC. Antimicrob Agents Chemother 2011 Mar; 55(3): 1266–9PubMedCrossRefGoogle Scholar
  68. 68.
    Allou N, Cambau E, Massias L, et al. Impact of low-level resistance to fluoroquinolones due to qnrA1 and qnrS1 genes or a gyrA mutation on ciprofloxacin bactericidal activity in a murine model of Escherichia coli urinary tract infection. Antimicrob Agents Chemother 2009 Oct; 53(10): 4292–7PubMedCrossRefGoogle Scholar
  69. 69.
    Robicsek A, Strahilevitz J, Jacoby GA, et al. Fluoroquinolone-modifying enzyme: a new adaptation of a common aminoglycoside acetyltransferase. Nat Med 2006 Jan; 12(1): 83–8PubMedCrossRefGoogle Scholar
  70. 70.
    Kim HB, Wang M, Park CH, et al. oqxAB encoding a multidrug efflux pump in human clinical isolates of Enterobacteriaceae. Antimicrob Agents Chemother 2009 Aug; 53(8): 3582–4PubMedCrossRefGoogle Scholar
  71. 71.
    Yamane K, Wachino J, Suzuki S, et al. New plasmid-mediated fluoroquinolone efflux pump, QepA, found in an Escherichia coli clinical isolate. Antimicrob Agents Chemother 2007 Sep; 51(9): 3354–60PubMedCrossRefGoogle Scholar
  72. 72.
    Vien le TM, Abuoun M, Morrison V, et al. Differential phenotypic and genotypic characteristics of qnrS1-harboring plasmids carried by hospital and community commensal enterobacteria. Antimicrob Agents Chemother 2010 Apr; 55(4): 1798–802Google Scholar
  73. 73.
    Liu JH, Deng YT, Zeng ZL, et al. Coprevalence of plasmid-mediated quinolone resistance determinants QepA, Qnr, and AAC(6′)-Ib-cr among 16S rRNA methylase RmtB-producing Escherichia coli isolates from pigs. Antimicrob Agents Chemother 2008 Aug; 52(8): 2992–3PubMedCrossRefGoogle Scholar
  74. 74.
    Cavaco LM, Aarestrup FM. Evaluation of quinolones for use in detection of determinants of acquired quinolone resistance, including the new transmissible resistance mechanisms qnrA, qnrB, qnrS, and aac(6′)Ib-cr, in Escherichia coli and Salmonella enterica and determinations of wild-type distributions. J Clin Microbiol 2009 Sep; 47(9): 2751–8PubMedCrossRefGoogle Scholar
  75. 75.
    Wachino J, Shibayama K, Kurokawa H, et al. Novel plasmid-mediated 16S rRNA m1A1408 methyltransferase, NpmA, found in a clinically isolated Escherichia coli strain resistant to structurally diverse aminoglycosides. Antimicrob Agents Chemother 2007 Dec; 51(12): 4401–9PubMedCrossRefGoogle Scholar
  76. 76.
    Kang HY, Kim KY, Kim J, et al. Distribution of conjugative-plasmid-mediated 16S rRNA methylase genes among amikacin-resistant Enterobacteriaceae isolates collected in 1995 to 1998 and 2001 to 2006 at a university hospital in South Korea and identification of conjugative plasmids mediating dissemination of 16S rRNA methylase. J Clin Microbiol 2008 Feb; 46(2): 700–6PubMedCrossRefGoogle Scholar
  77. 77.
    Yu FY, Yao D, Pan JY, et al. High prevalence of plasmid-mediated 16S rRNA methylase gene rmtB among Escherichia coli clinical isolates from a Chinese teaching hospital. BMC Infect Dis 2010; 10: 184PubMedCrossRefGoogle Scholar
  78. 78.
    Zhou Y, Yu H, Guo Q, et al. Distribution of 16S rRNA methylases among different species of Gram-negative bacilli with high-level resistance to aminoglycosides. Eur J Clin Microbiol Infect Dis 2010 Nov; 29(11): 1349–53PubMedCrossRefGoogle Scholar
  79. 79.
    Aubron C, Poirel L, Fortineau N, et al. Nosocomial spread of Pseudomonas aeruginosa isolates expressing the metallo-beta-lactamase VIM-2 in a hematology unit of a French hospital. Microb Drug Resist 2005 Fall; 11(3): 254–9PubMedCrossRefGoogle Scholar
  80. 80.
    Bratu S, Brooks S, Burney S, et al. Detection and spread of Escherichia coli possessing the plasmid-borne carbape-nemase KPC-2 in Brooklyn, New York. Clin Infect Dis 2007 Apr 1; 44(7): 972–5PubMedCrossRefGoogle Scholar
  81. 81.
    Carrer A, Poirel L, Yilmaz M, et al. Spread of OXA-48-encoding plasmid in Turkey and beyond. Antimicrob Agents Chemother 2010 Mar; 54(3): 1369–73PubMedCrossRefGoogle Scholar
  82. 82.
    Goldfarb D, Harvey SB, Jessamine K, et al. Detection of plasmid-mediated KPC-producing Klebsiella pneumoniae in Ottawa, Canada: evidence of intrahospital transmission. J Clin Microbiol 2009 Jun; 47(6): 1920–2PubMedCrossRefGoogle Scholar
  83. 83.
    Oteo J, Hernandez-Almaraz JL, Gil-Anton J, et al. Outbreak of vim-1-carbapenemase-producing Enterobacter cloacae in a pediatric intensive care unit. Pediatr Infect Dis J 2010 Dec; 29(12): 1144–6PubMedCrossRefGoogle Scholar
  84. 84.
    Wendt C, Schutt S, Dalpke AH, et al. First outbreak of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae in Germany. Eur J Clin Microbiol Infect Dis 2010 May; 29(5): 563–70PubMedCrossRefGoogle Scholar
  85. 85.
    Woodford N, Tierno Jr PM, Young K, et al. Outbreak of Klebsiella pneumoniae producing a new carbapenem-hydrolyzing class A beta-lactamase, KPC-3, in a New York Medical Center. Antimicrob Agents Chemother 2004 Dec; 48(12): 4793–9PubMedCrossRefGoogle Scholar
  86. 86.
    Pitout JD, Laupland KB. Extended-spectrum beta-lactamase-producing Enterobacteriaceae: an emerging public-health concern. Lancet Infect Dis 2008 Mar; 8(3): 159–66PubMedCrossRefGoogle Scholar
  87. 87.
    Coque TM, Novais A, Carattoli A, et al. Dissemination of clonally related Escherichia coli strains expressing extended-spectrum beta-lactamase CTX-M-15. Emerg Infect Dis 2008 Feb; 14(2): 195–200PubMedCrossRefGoogle Scholar
  88. 88.
    Samuelsen O, Naseer U, Tofteland S, et al. Emergence of clonally related Klebsiella pneumoniae isolates of sequence type 258 producing plasmid-mediated KPC carbapenemase in Norway and Sweden. J Antimicrob Chemother 2009 Apr; 63(4): 654–8PubMedCrossRefGoogle Scholar
  89. 89.
    Walsh TR, Weeks J, Livermore DM, et al. Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: an environmental point prevalence study. Lancet Infect Dis 2011 May; 11(5): 355–62PubMedCrossRefGoogle Scholar
  90. 90.
    Dortet L, Radu I, Gautier V, et al. Intercontinental travels of patients and dissemination of plasmid-mediated carbapenemase KPC-3 associated with OXA-9 and TEM-1. J Antimicrob Chemother 2008 Feb; 61(2): 455–7PubMedCrossRefGoogle Scholar
  91. 91.
    Wernli D, Haustein T, Conly J, et al. A call for action: the application of the international health regulations to the global threat of antimicrobial resistance. PLoS Med 2011 Apr; 8(4): e1001022PubMedCrossRefGoogle Scholar
  92. 92.
    Ramphal R, Ambrose PG. Extended-spectrum beta-lactamases and clinical outcomes: current data. Clin Infect Dis 2006 Apr 15; 42 Suppl. 4: S164–72PubMedCrossRefGoogle Scholar
  93. 93.
    Pena C, Gudiol C, Calatayud L, et al. Infections due to Escherichia coli producing extended-spectrum beta-lactamase among hospitalised patients: factors influencing mortality. J Hosp Infect 2008 Feb; 68(2): 116–22PubMedCrossRefGoogle Scholar
  94. 94.
    Gudiol C, Tubau F, Calatayud L, et al. Bacteraemia due to multidrug-resistant Gram-negative bacilli in cancer patients: risk factors, antibiotic therapy and outcomes. J Antimicrob Chemother 2011 Mar; 66(3): 657–63PubMedCrossRefGoogle Scholar
  95. 95.
    Ortega M, Marco F, Soriano A, et al. Cefotaxime resistance and outcome of Klebsiella spp bloodstream infection. Eur J Clin Microbiol Infect Dis. Epub 2011 Apr 21Google Scholar
  96. 96.
    Marchaim D, Gottesman T, Schwartz O, et al. National multicenter study of predictors and outcomes of bacteremia upon hospital admission caused by Enterobacteriaceae producing extended-spectrum beta-lactamases. Antimicrob Agents Chemother 2010 Dec; 54(12): 5099–104PubMedCrossRefGoogle Scholar
  97. 97.
    Marchaim D, Navon-Venezia S, Schwaber MJ, et al. Isolation of imipenem-resistant Enterobacter species: emergence of KPC-2 carbapenemase, molecular characterization, epidemiology, and outcomes. Antimicrob Agents Chemother 2008 Apr; 52(4): 1413–8PubMedCrossRefGoogle Scholar
  98. 98.
    Daikos GL, Petrikkos P, Psichogiou M, et al. Prospective observational study of the impact of VIM-1 metallo-beta-lactamase on the outcome of patients with Klebsiella pneumoniae bloodstream infections. Antimicrob Agents Chemother 2009 May; 53(5): 1868–73PubMedCrossRefGoogle Scholar
  99. 99.
    Falagas ME, Kasiakou SK. Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections. Clin Infect Dis 2005 May 1; 40(9): 1333–41PubMedCrossRefGoogle Scholar
  100. 100.
    Montero M, Horcajada JP, Sorli L, et al. Effectiveness and safety of colistin for the treatment of multidrug-resistant Pseudomonas aeruginosa infections. Infection 2009 Oct; 37(5): 461–5PubMedCrossRefGoogle Scholar
  101. 101.
    Garonzik SM, Li J, Thamlikitkul V, et al. Population pharmacokinetics of colistin methanesulfonate and formed colistin in critically ill patients from a multicenter study provide dosing suggestions for various categories of patients. Antimicrob Agents Chemother 2011 Jul; 55(7): 3284–94PubMedCrossRefGoogle Scholar
  102. 102.
    Falagas ME, Giannopoulou KP, Kokolakis GN, et al. Fosfomycin: use beyond urinary tract and gastrointestinal infections. Clin Infect Dis 2008 Apr 1; 46(7): 1069–77PubMedCrossRefGoogle Scholar
  103. 103.
    Van Pienbroek E, Hermans J, Kaptein AA, et al. Fosfomycin trometamol in a single dose versus seven days nitrofurantoin in the treatment of acute uncomplicated urinary tract infections in women. Pharm World Sci 1993 Dec 17; 15(6): 257–62PubMedCrossRefGoogle Scholar
  104. 104.
    Knottnerus BJ, Nys S, Ter Riet G, et al. Fosfomycin tromethamine as second agent for the treatment of acute, uncomplicated urinary tract infections in adult female patients in the Netherlands? J Antimicrob Chemother 2008 Aug; 62(2): 356–9PubMedCrossRefGoogle Scholar
  105. 105.
    Roussos N, Karageorgopoulos DE, Samonis G, et al. Clinical significance of the pharmacokinetic and pharmacodynamic characteristics of fosfomycin for the treatment of patients with systemic infections. Int J Antimicrob Agents 2009 Dec; 34(6): 506–15PubMedCrossRefGoogle Scholar
  106. 106.
    Gardiner D, Dukart G, Cooper A, et al. Safety and efficacy of intravenous tigecycline in subjects with secondary bacteremia: pooled results from 8 phase III clinical trials. Clin Infect Dis 2010 Jan 15; 50(2): 229–38PubMedCrossRefGoogle Scholar
  107. 107.
    Tasina E, Haidich AB, Kokkali S, et al. Efficacy and safety of tigecycline for the treatment of infectious diseases: a meta-analysis. Lancet Infect Dis 2011 Nov; 11(11): 834–44PubMedCrossRefGoogle Scholar
  108. 108.
    Gupta ND, Smith RE, Balakrishnan I. Clinical efficacy of temocillin. J Antimicrob Chemother 2009 Aug; 64(2): 431–3PubMedCrossRefGoogle Scholar
  109. 109.
    Livermore DM, Warner M, Mushtaq S, et al. What remains against carbapenem-resistant Enterobacteriaceae? Evaluation of chloramphenicol, ciprofloxacin, colistin, fosfomycin, minocycline, nitrofurantoin, temocillin and tigecycline. Int J Antimicrob Agents 2011 May; 37(5): 415–9PubMedCrossRefGoogle Scholar
  110. 110.
    Falagas ME, Maraki S, Karageorgopoulos DE, et al. Antimicrobial susceptibility of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Enterobacteriaceae isolates to fosfomycin. Int J Antimicrob Agents 2010 Mar; 35(3): 240–3PubMedCrossRefGoogle Scholar
  111. 111.
    Falagas ME, Kastoris AC, Kapaskelis AM, et al. Fosfomycin for the treatment of multidrug-resistant, including extended-spectrum beta-lactamase producing, Enterobacteriaceae infections: a systematic review. Lancet Infect Dis 2010 Jan; 10(1): 43–50PubMedCrossRefGoogle Scholar
  112. 112.
    Kelesidis T, Karageorgopoulos DE, Kelesidis I, et al. Tigecycline for the treatment of multidrug-resistant Enterobacteriaceae: a systematic review of the evidence from microbiological and clinical studies. J Antimicrob Chemother 2008 Nov; 62(5): 895–904PubMedCrossRefGoogle Scholar
  113. 113.
    Adams-Haduch JM, Potoski BA, Sidjabat HE, et al. Activity of temocillin against KPC-producing Klebsiella pneumoniae and Escherichia coli. Antimicrob Agents Chemother 2009 Jun; 53(6): 2700–1PubMedCrossRefGoogle Scholar
  114. 114.
    Rodriguez-Villalobos H, Bogaerts P, Berhin C, et al. Trends in production of extended-spectrum beta-lactamases among Enterobacteriaceae of clinical interest: results of a nationwide survey in Belgian hospitals. J Antimicrob Chemother 2011 Jan; 66(1): 37–47PubMedCrossRefGoogle Scholar
  115. 115.
    Paul M, Bishara J, Levcovich A, et al. Effectiveness and safety of colistin: prospective comparative cohort study. J Antimicrob Chemother 2010 May; 65(5): 1019–27PubMedCrossRefGoogle Scholar
  116. 116.
    Falagas ME, Rafailidis PI, Ioannidou E, et al. Colistin therapy for microbiologically documented multidrug-resistant Gram-negative bacterial infections: a retrospective cohort study of 258 patients. Int J Antimicrob Agents 2010 Feb; 35(2): 194–9PubMedCrossRefGoogle Scholar
  117. 117.
    Cai Y, Wang R, Liang B, et al. Systematic review and meta-analysis of the effectiveness and safety of tigecycline for treatment of infectious disease. Antimicrob Agents Chemother 2011 Mar; 55(3): 1162–72PubMedCrossRefGoogle Scholar
  118. 118.
    Cai Y, Wang R. Tigecycline: benefits and risks. Lancet Infect Dis 2011 Nov; 11(11): 804–5PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2012

Authors and Affiliations

  1. 1.Department of Global Health, Academic Medical CenterUniversity of AmsterdamAmsterdamthe Netherlands
  2. 2.Department of Medical Microbiology, Academic Medical CenterUniversity of AmsterdamAmsterdamthe Netherlands
  3. 3.Oxford University Clinical Research UnitHo Chi Minh CityVietnam
  4. 4.Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical CenterUniversity of AmsterdamAmsterdamthe Netherlands

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