Emergence of concurrent infections with colistin-resistant ESBL-positive Klebsiella pneumoniae and OXA-23-producing Acinetobacter baumannii sensitive to colistin only in a Romanian cardiac intensive care unit

  • D. Timofte
  • M. Dan
  • I. E. Maciuca
  • L. Ciucu
  • E. R. Dabija
  • E. Guguianu
  • C. V. Panzaru


We report the emergence and analysis of a cluster of concurrent infections/colonisations with colistin-resistant Klebsiella pneumoniae and OXA-23 carbapenemase-producing Acinetobacter baumannii in patients who had undergone cardiac surgery. We describe the emergence of colistin-resistant K. pneumoniae harbouring bla CTX-M-15, bla SHV-11, bla OXA-1, bla TEM-1 beta-lactamases and aac(6’)-Ib-cr fluoroquinolone resistance. Colistin-resistant K. pneumoniae infections (pneumonia, wound infection, urinary tract infections and bacteraemia) occurred in critically ill patients previously treated with colistin for post-surgery infections with carbapenem-resistant Pseudomonas aeruginosa and/or A. baumannii. Although the cause of death could not be directly attributed to a single pathogen, three patients co-infected/colonised with K. pneumoniae, P. aeruginosa and/or A. baumannii died, whilst a fourth patient who had a mono-microbial infection with colistin-resistant K. pneumoniae only survived. The use of mobile intubation equipment in patients that shared the same ward, the clustering of cases over a short period of time, as well as the pulsed-field gel electrophoresis (PFGE) data all suggest cross-contamination between patients, either through equipment or by staff contact transmission. This report presents the ‘worst-case scenario’ where concurrent infection/colonisation with pathogens exhibiting resistance to different types of last-resort antimicrobials occurred in some of the most debilitated intensive care unit (ICU) patients.


Colistin Acinetobacter Baumannii AmpC Carbapenem Resistance Cardiac Intensive Care Unit 
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 a grant from the Society for General Microbiology (International Development Fund).

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Papp-Wallace KM, Endimiani A, Taracila MA, Bonomo RA (2011) Carbapenems: past, present, and future. Antimicrob Agents Chemother 55(11):4943–4960CrossRefPubMedCentralPubMedGoogle Scholar
  2. 2.
    McKenna M (2013) Antibiotic resistance: the last resort. Nature 499(7459):394–396CrossRefPubMedGoogle Scholar
  3. 3.
    Kontopoulou K, Protonotariou E, Vasilakos K, Kriti M, Koteli A, Antoniadou E, Sofianou D (2010) Hospital outbreak caused by Klebsiella pneumoniae producing KPC-2 beta-lactamase resistant to colistin. J Hosp Infect 76(1):70–73CrossRefPubMedGoogle Scholar
  4. 4.
    Tóth A, Damjanova I, Puskás E, Jánvári L, Farkas M, Dobák A, Böröcz K, Pászti J (2010) Emergence of a colistin-resistant KPC-2-producing Klebsiella pneumoniae ST258 clone in Hungary. Eur J Clin Microbiol Infect Dis 29(7):765–769CrossRefPubMedGoogle Scholar
  5. 5.
    Mammina C, Bonura C, Di Bernardo F, Aleo A, Fasciana T, Sodano C, Saporito MA, Verde MS, Tetamo R, Palma DM (2012) Ongoing spread of colistin-resistant Klebsiella pneumoniae in different wards of an acute general hospital, Italy, June to December 2011. Euro Surveill 17(33):9–14Google Scholar
  6. 6.
    Marchaim D, Chopra T, Pogue JM, Perez F, Hujer AM, Rudin S, Endimiani A, Navon-Venezia S, Hothi J, Slim J, Blunden C, Shango M, Lephart PR, Salimnia H, Reid D, Moshos J, Hafeez W, Bheemreddy S, Chen T-Y, Dhar S, Bonomo RA, Kaye KS (2011) Outbreak of colistin-resistant, carbapenem-resistant Klebsiella pneumoniae in metropolitan Detroit, Michigan. Antimicrob Agents Chemother 55(2):593–599CrossRefPubMedCentralPubMedGoogle Scholar
  7. 7.
    Suh J-Y, Son JS, Chung DR, Peck KR, Ko KS, Song J-H (2010) Nonclonal emergence of colistin-resistant Klebsiella pneumoniae isolates from blood samples in South Korea. Antimicrob Agents Chemother 54(1):560–562CrossRefPubMedCentralPubMedGoogle Scholar
  8. 8.
    Clinical and Laboratory Standards Institute (CLSI) (2011) Performance standards for antimicrobial susceptibility testing; Twenty-first informational supplement, vol 31, no 1. CLSI document M100-S21Google Scholar
  9. 9.
    Dallenne C, Da Costa A, Decré D, Favier C, Arlet G (2010) Development of a set of multiplex PCR assays for the detection of genes encoding important beta-lactamases in Enterobacteriaceae. J Antimicrob Chemother 65(3):490–495CrossRefPubMedGoogle Scholar
  10. 10.
    Corvec S, Caroff N, Espaze E, Giraudeau C, Drugeon H, Reynaud A (2003) AmpC cephalosporinase hyperproduction in Acinetobacter baumannii clinical strains. J Antimicrob Chemother 52(4):629–635CrossRefPubMedGoogle Scholar
  11. 11.
    Pérez-Pérez FJ, Hanson ND (2002) Detection of plasmid-mediated AmpC beta-lactamase genes in clinical isolates by using multiplex PCR. J Clin Microbiol 40(6):2153–2162CrossRefPubMedCentralPubMedGoogle Scholar
  12. 12.
    Nordmann P, Poirel L, Carrër A, Toleman MA, Walsh TR (2011) How to detect NDM-1 producers. J Clin Microbiol 49(2):718–721CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Woodford N, Ellington MJ, Coelho JM, Turton JF, Ward ME, Brown S, Amyes SGB, Livermore DM (2006) Multiplex PCR for genes encoding prevalent OXA carbapenemases in Acinetobacter spp. Int J Antimicrob Agents 27(4):351–353CrossRefPubMedGoogle Scholar
  14. 14.
    Park CH, Robicsek A, Jacoby GA, Sahm D, Hooper DC (2006) Prevalence in the United States of aac(6’)-Ib-cr encoding a ciprofloxacin-modifying enzyme. Antimicrob Agents Chemother 50(11):3953–3955CrossRefPubMedCentralPubMedGoogle Scholar
  15. 15.
    Mugnier P, Poirel L, Pitout M, Nordmann P (2008) Carbapenem-resistant and OXA-23-producing Acinetobacter baumannii isolates in the United Arab Emirates. Clin Microbiol Infect 14(9):879–882CrossRefPubMedGoogle Scholar
  16. 16.
    Turton JF, Gabriel SN, Valderrey C, Kaufmann ME, Pitt TL (2007) Use of sequence-based typing and multiplex PCR to identify clonal lineages of outbreak strains of Acinetobacter baumannii. Clin Microbiol Infect 13(8):807–815CrossRefPubMedGoogle Scholar
  17. 17.
    Towner KJ (2009) Acinetobacter: an old friend, but a new enemy. J Hosp Infect 73(4):355–363CrossRefPubMedGoogle Scholar
  18. 18.
    Blot S, Vandewoude K, Colardyn F (2003) Nosocomial bacteremia involving Acinetobacter baumannii in critically ill patients: a matched cohort study. Intensive Care Med 29(3):471–475PubMedGoogle Scholar
  19. 19.
    Robenshtok E, Paul M, Leibovici L, Fraser A, Pitlik S, Ostfeld I, Samra Z, Perez S, Lev B, Weinberger M (2006) The significance of Acinetobacter baumannii bacteraemia compared with Klebsiella pneumoniae bacteraemia: risk factors and outcomes. J Hosp Infect 64(3):282–287CrossRefPubMedGoogle Scholar
  20. 20.
    Falagas ME, Bliziotis IA, Siempos II (2006) Attributable mortality of Acinetobacter baumannii infections in critically ill patients: a systematic review of matched cohort and case–control studies. Critical Care 10(2):R48Google Scholar
  21. 21.
    Marchaim D, Perez F, Lee J, Bheemreddy S, Hujer AM, Rudin S, Hayakawa K, Lephart PR, Blunden C, Shango M, Campbell ML, Varkey J, Manickam P, Patel D, Pogue JM, Chopra T, Martin ET, Dhar S, Bonomo RA, Kaye KS (2012) “Swimming in resistance”: Co-colonization with carbapenem-resistant Enterobacteriaceae and Acinetobacter baumannii or Pseudomonas aeruginosa. Am J Infect Control 40(9):830–835CrossRefPubMedCentralPubMedGoogle Scholar
  22. 22.
    Potron A, Kalpoe J, Poirel L, Nordmann P (2011) European dissemination of a single OXA-48-producing Klebsiella pneumoniae clone. Clin Microbiol Infect 17(12):E24–E26CrossRefPubMedGoogle Scholar
  23. 23.
    Nielsen JB, Skov MN, Jørgensen RL, Heltberg O, Hansen DS, Schønning K (2011) Identification of CTX-M15-, SHV-28-producing Klebsiella pneumoniae ST15 as an epidemic clone in the Copenhagen area using a semi-automated Rep-PCR typing assay. Eur J Clin Microbiol Infect Dis 30(6):773–778CrossRefPubMedGoogle Scholar
  24. 24.
    Cai Y, Chai D, Wang R, Liang B, Bai N (2012) Colistin resistance of Acinetobacter baumannii: clinical reports, mechanisms and antimicrobial strategies. J Antimicrob Chemother 67(7):1607–1615CrossRefPubMedGoogle Scholar
  25. 25.
    Ben-David D, Masarwa S, Navon-Venezia S, Mishali H, Fridental I, Rubinovitch B, Smollan G, Carmeli Y, Schwaber MJ; Israel PACF CRKP (Post-Acute-Care Facility Carbapenem-Resistant Klebsiella pneumoniae) Working Group (2011) Carbapenem-resistant Klebsiella pneumoniae in post-acute-care facilities in Israel. Infect Control Hosp Epidemiol 32(9):845–853CrossRefPubMedGoogle Scholar
  26. 26.
    Consales G, Gramigni E, Zamidei L, Bettocchi D, De Gaudio AR (2011) A multidrug-resistant Acinetobacter baumannii outbreak in intensive care unit: antimicrobial and organizational strategies. J Crit Care 26(5):453–459CrossRefPubMedGoogle Scholar
  27. 27.
    Giamarellou H, Poulakou G (2009) Multidrug-resistant Gram-negative infections: what are the treatment options? Drugs 69(14):1879–1901CrossRefPubMedGoogle Scholar
  28. 28.
    Kempf M, Rolain J-M (2012) Emergence of resistance to carbapenems in Acinetobacter baumannii in Europe: clinical impact and therapeutic options. Int J Antimicrob Agents 39(2):105–114CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • D. Timofte
    • 1
    • 4
    • 5
  • M. Dan
    • 2
  • I. E. Maciuca
    • 1
    • 4
  • L. Ciucu
    • 2
  • E. R. Dabija
    • 2
  • E. Guguianu
    • 4
  • C. V. Panzaru
    • 2
    • 3
  1. 1.School of Veterinary ScienceUniversity of Liverpool, Leahurst CampusNestonUK
  2. 2.Institute of Cardiovascular DiseasesIasiRomania
  3. 3.University of Medicine and Pharmacy “Grigore T. Popa”IasiRomania
  4. 4.Faculty of Veterinary MedicineUniversity of Agronomical Sciences and Veterinary MedicineIasiRomania
  5. 5.Institute of Infection and Global HealthUniversity of LiverpoolLiverpoolUK

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