Nano Research

, Volume 10, Issue 2, pp 520–533 | Cite as

Catheters coated with Zn-doped CuO nanoparticles delay the onset of catheter-associated urinary tract infections

  • Yakov Shalom
  • Ilana Perelshtein
  • Nina Perkas
  • Aharon GedankenEmail author
  • Ehud BaninEmail author
Research Article


Catheter-associated urinary tract infections (CAUTIs) are among the most common bacterial infections associated with medical devices. In the current study, the synthesis, coating, antibiofilm properties, and biocompatibility of urinary catheters coated with Zn-doped CuO (Zn0.12Cu0.88O) nanoparticles (NPs) were examined. The doped NPs were synthesized and subsequently deposited on the catheter by the sonochemical method. The coated catheters displayed high antibiofilm activity and promising biocompatibility, as indicated by low in vitro cytotoxicity, negligible associated cytokine secretion, and absence of detectable irritation. The biocompatibility and ability of the Zn-doped CuO coating to inhibit biofilm formation were also evaluated in vivo using a rabbit model. Rabbits catheterized with uncoated catheters scored positive for CAUTI by day 4 of the experiment. In contrast, rabbits catheterized with Zn-doped CuO-coated catheters did not exhibit CAUTI until day 7 or remained completely uninfected for the whole duration of the 7-day experiment. Furthermore, the in vivo biocompatibility assays and examinations supported the biosafety of Zn-doped CuO-coated catheters. Taken together, these data highlight the potential of Zn-doped CuO nanocomposite as effective antibiofilm compound.


antibiofilm urinary tract infection catheter nanoparticle coating metal oxide 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.



This project was partially funded by a Kamin research grant from the Israeli Ministry of Economy to Ehud Banin. We also thank the Dyna and Fala Weinstock Foundation and the Douer Family Foundation for their support. We are grateful to Dr. Gal Yerushalmi and Yana Belnik for fruitful discussions and assistance in the preparation of the manuscript. We thank Yossi Lavie from Harlan for technical assistance and Dr. Abraham Nyska for histopathological analysis. We thank Katya Gotlib for technical assistance in the HRSEM.

Supplementary material

12274_2016_1310_MOESM1_ESM.pdf (705 kb)
Catheters coated with Zn-doped CuO nanoparticles delay the onset of catheter-associated urinary tract infections


  1. [1]
    Antibiotic Resistance Threats; U.S. Department of Health and Human Services: Washington, D.C., USA, 2013.Google Scholar
  2. [2]
    Yang, L.; Liu, Y.; Wu, H.; Song, Z. J.; Hoiby, N.; Molin, S.; Givskov, M. Combating biofilms. FEMS Immunol. Med. Microbiol. 2012, 65, 146–157.CrossRefGoogle Scholar
  3. [3]
    Flemming, H. C.; Wingender, J. The biofilm matrix. Nat. Rev. Microbiol. 2010, 8, 623–633.Google Scholar
  4. [4]
    Donlan, R. M.; Costerton, J. W. Biofilms: Survival mechanisms of clinically relevant microorganisms. Clin. Microbiol. Rev. 2002, 15, 167–193.CrossRefGoogle Scholar
  5. [5]
    Hall-Stoodley, L.; Costerton, J. W.; Stoodley, P. Bacterial biofilms: From the natural environment to infectious diseases. Nat. Rev. Microbiol. 2004, 2, 95–108.CrossRefGoogle Scholar
  6. [6]
    Costerton, J. W.; Stewart, P. S.; Greenberg, E. P. Bacterial biofilms: A common cause of persistent infections. Science 1999, 284, 1318–1322.CrossRefGoogle Scholar
  7. [7]
    Trautner, B. W.; Darouiche, R. O. Role of biofilm in catheter-associated urinary tract infection. Am. J. Infect. Control 2004, 32, 177–183.CrossRefGoogle Scholar
  8. [8]
    Stickler, D. J. Bacterial biofilms in patients with indwelling urinary catheters. Nat. Clin. Pract. Urol. 2008, 5, 598–608.CrossRefGoogle Scholar
  9. [9]
    Schmiemann, G.; Kniehl, E.; Gebhardt, K.; Matejczyk, M. M.; Hummers-Pradier, E. The diagnosis of urinary tract infection: A systematic review. Deut. Arztebl. Int. 2010, 107, 361–367.Google Scholar
  10. [10]
    Darouiche, R. O. Treatment of infections associated with surgical implants. N. Engl. J. Med. 2004, 350, 1422–1429.CrossRefGoogle Scholar
  11. [11]
    Guggenbichler, J. P.; Assadian, O.; Boeswald, M.; Kramer, A. Incidence and clinical implication of nosocomial infections associated with implantable biomaterials–catheters, ventilatorassociated pneumonia, urinary tract infections. GMS Krankenhhyg. Interdiszip. 2011, 6, Doc18.Google Scholar
  12. [12]
    Gould, C. V.; Umscheid, C. A.; Agarwal, R. K.; Kuntz, G.; Pegues, D. A.; Healthcare Infection Control Practices Advisory Committee. Guideline for prevention of catheter-associated urinary tract infections 2009. Infect; Centers for Disease Control and Prevention: Washington D.C., USA, 2009.Google Scholar
  13. [13]
    Purvis, S.; Gion, T.; Kennedy, G.; Rees, S.; Safdar, N.; VanDenBergh, S.; Weber, J. Catheter-associated urinary tract infection: A successful prevention effort employing a multipronged initiative at an academic medical center. J. Nurs. Care Qual. 2014, 29, 141–148.CrossRefGoogle Scholar
  14. [14]
    Meddings, J.; Rogers, M. A. M.; Macy, M.; Saint, S. Systematic review and meta-analysis: Reminder systems to reduce catheter-associated urinary tract infections and urinary catheter use in hospitalized patients. Clin. Infect. Dis. 2010, 51, 550–560.CrossRefGoogle Scholar
  15. [15]
    Malka, E.; Perelshtein, I.; Lipovsky, A.; Shalom, Y.; Naparstek, L.; Perkas, N.; Patick, T.; Lubart, R.; Nitzan, Y.; Banin, E. et al. Eradication of multi-drug resistant bacteria by a novel Zn-doped CuO nanocomposite. Small 2013, 9, 4069–4076.CrossRefGoogle Scholar
  16. [16]
    Alekshun, M. N.; Levy, S. B. Molecular mechanisms of antibacterial multidrug resistance. Cell 2007, 128, 1037–1050.CrossRefGoogle Scholar
  17. [17]
    Andersen, J. L.; He, G. X.; Kakarla, P.; KC, R.; Kumar, S.; Lakra, W. S.; Mukherjee, M. M.; Ranaweera, I.; Shrestha, U.; Tran, T. et al. Multidrug efflux pumps from Enterobacteriaceae, Vibrio cholerae and Staphylococcus aureus bacterial food pathogens. Int. J. Environ. Res. Public Health 2015, 12, 1487–1547.CrossRefGoogle Scholar
  18. [18]
    Magiorakos, A. P.; Srinivasan, A.; Carey, R. B.; Carmeli, Y.; Falagas, M. E.; Giske, C. G.; Harbarth, S.; Hindler, J. F.; Kahlmeter, G.; Olsson-Liljequist, B. et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance. Clin. Microbiol. Infect. 2012, 18, 268–281.CrossRefGoogle Scholar
  19. [19]
    Palza, H. Antimicrobial polymers with metal nanoparticles. Int. J. Mol. Sci. 2015, 16, 2099–2116.CrossRefGoogle Scholar
  20. [20]
    Perelshtein, I.; Lipovsky, A.; Perkas, N.; Tzanov, T.; Arguirova, M.; Leseva, M.; Gedanken, A. Making the hospital a safer place by sonochemical coating of all its textiles with antibacterial nanoparticles. Ultrason. Sonochem. 2015, 25, 82–88.CrossRefGoogle Scholar
  21. [21]
    Perelshtein, I.; Applerot, G.; Perkas, N.; Wehrschuetz-Sigl, E.; Hasmann, A.; Guebitz, G.; Gedanken, A. CuO–cotton nanocomposite: Formation, morphology, and antibacterial activity. Surf. Coat. Technol. 2009, 204, 54–57.CrossRefGoogle Scholar
  22. [22]
    Uthamanthil, R. K.; Hachem, R. Y.; Gagea, M.; Reitzel, R. A.; Borne, A. T.; Tinkey, P. T. Urinary catheterization of male rabbits: A new technique and a review of urogenital anatomy. J. Am. Assoc. Lab. Anim. Sci. 2013, 52, 180–185.Google Scholar
  23. [23]
    Zak, O.; Sande, M. A. Handbook of Animal Models of Infection: Experimental Models in Antimicrobial Chemotherapy; San Diego: Academic Press, 1999.Google Scholar
  24. [24]
    Eshed, M.; Lellouche, J.; Gedanken, A.; Banin, E. A Zn-doped CuO nanocomposite shows enhanced antibiofilm and antibacterial activities against Streptococcus mutans compared to nanosized CuO. Adv. Funct. Mater. 2014, 24, 1382–1390.CrossRefGoogle Scholar
  25. [25]
    Wu, J.; Wang, L. Y.; He, J.; Zhu, C. H. In vitro cytotoxicity of Cu2+, Zn2+, Ag+ and their mixtures on primary human endometrial epithelial cells. Contraception 2012, 85, 509–518.CrossRefGoogle Scholar
  26. [26]
    Paasche, G.; Ceschi, P.; Löbler, M.; Rösl, C.; Gomes, P.; Hahn, A.; Rohm, H. W.; Sternberg, K.; Lenarz, T.; Schmitz, K. P. et al. Effects of metal ions on fibroblasts and spiral ganglion cells. J. Neurosci. Res. 2011, 89, 611–617.CrossRefGoogle Scholar
  27. [27]
    Perelshtein, I.; Ruderman, Y.; Perkas, N.; Beddow, J.; Singh, G.; Vinatoru, M.; Joyce, E.; Mason, T. J.; Blanes, M.; Mollá, K. et al. The sonochemical coating of cotton withstands 65 washing cycles at hospital washing standards and retains its antibacterial properties. Cellulose 2013, 20, 1215–1221.CrossRefGoogle Scholar
  28. [28]
    Perelshtein, I.; Lipovsky, A.; Perkas, N.; Gedanken, A.; Moschini, E.; Mantecca, P. The influence of the crystalline nature of nano-metal oxides on their antibacterial and toxicity properties. Nano Res. 2015, 8, 695–707.CrossRefGoogle Scholar
  29. [29]
    Pickard, R.; Lam, T.; MacLennan, G.; Starr, K.; Kilonzo, M.; McPherson, G.; Gillies, K.; McDonald, A.; Walton, K.; Buckley, B. et al. Antimicrobial catheters for reduction of symptomatic urinary tract infection in adults requiring short-term catheterisation in hospital: A multicentre randomised controlled trial. Lancet 2012, 380, 1927–1935.CrossRefGoogle Scholar

Copyright information

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.The Mina and Everard Goodman Faculty of Life Sciences and Institute for Advanced Materials and NanotechnologyBar-Ilan UniversityRamat-GanIsrael
  2. 2.The Department of Chemistry and Institute for Advanced Materials and NanotechnologyBar-Ilan UniversityRamat-GanIsrael

Personalised recommendations