As mentioned in my recent blog, some metals, especially copper and silver, are being used in touchless disinfecting products in medical environments. In that blog I briefly discussed the multiple non-specific parallel mechanisms by which exposure of microorganisms to high concentrations to these metals result in the microorganisms’ death. In the current blog I would like to concentrate on copper and briefly review what microorganisms have been shown to be killed by this metal, with focus on the studies conducted in relation to hospital acquired infections (HAIs).

The ancient Greeks (400 BC) were the first to discover the sanitizing power of copper. They prescribed copper for pulmonary diseases and for purifying drinking water. Since then copper has been used as a biocide for treating sores and skin diseases and for purifying water by many civilizations, such as the Celts, Phoenicians, Egyptians, Hindus, and Aztecs. Beginning in the early 1950s, a wide range of microorganisms, at least 63 gram negative and gram positive bacteria, yeast, 33 fungi and 22 enveloped and non-enveloped viruses, have been shown to be killed by copper or copper compounds (1). Notably, copper surfaces or copper compounds have also been shown to be efficacious against hard-to-kill spores, including against Clostridium difficile (2,3). Importantly, in March 2008 the U.S. Environmental Protection Agency (EPA) has approved the registration of metallic copper as  a material with antimicrobial properties, thus allowing the Copper Development Association to make public health claims. Similarly, Cupron Enhanced EOS Surface, an engineered solid surface containing copper oxide has also received EPA approval to make public health claims. These public health claims acknowledge that copper, brass and bronze and polymeric substrates containing 16% copper oxide particles weight/weight are capable of killing more than 99.9% of harmful, potentially deadly bacteria, such as Methicillin-resistant S. aureus (MRSA) within two hours, and continue to kill more than 99% of bacteria even after repeated contamination. MRSA is one of the most virulent strains of antibiotic-resistant bacteria and a common cause of HAIs.

Today copper biocides have become indispensable and many thousands of tons are used annually all over the world for i) prevention of roof moss formation;  ii) wood preservation; iii) control of green slime in farm ponds, rice fields, irrigation and drainage canals, rivers, lakes and swimming pools; iv) prevention of downy mildew on grapes; and iv) antifouling paints.

Novel uses of copper or copper-based compounds in health-related applications are being explored and/or implemented. One area is the reduction of transmission of health-associated (nosocomial) pathogens in hospitals, clinics and elderly homes, by producing hospital hard surfaces, such as door knobs, bed rails, and intravenous stands, with metallic copper or polymers containing copper oxide (2,4,5); and by producing hospital soft surfaces, such as sheets, patient robes, patient pajamas, and nurse clothing, from copper-impregnated biocidal textiles (6,7).

The significant contribution of copper surfaces to the reduction of bioburden and HAIs in clinical settings has been demonstrated in several studies. In a study performed in the UK (8) in a busy acute medical ward the median numbers of microorganisms harbored from the copper-containing items were between 90% and 100% lower than in their control equivalents (p values ranging from <0.05 to <0.0001). Similarly, in a study conducted at a busy walk-in primary healthcare clinic in South Africa (9), the mean colony forming units (CFU) isolated from copper surfaces were 71% lower than those isolated from the matched control surfaces (p<0.001). And in a study conducted in an oncological/pneumological and a geriatric ward in Germany (10), the total number of CFU on metallic copper-containing surfaces was 63% of that on the control surfaces (p<0.001). Interestingly, after disinfection of the copper and control surfaces, microbial repopulation of the surfaces was significantly delayed on the copper alloys (p<0.05).

Importantly, in a multi-center trial in which patients were randomly placed in available rooms with or without copper alloy surfaces, there was a 58% reduction in the rate of HAI (p<0.05). MRSA/Vancomycin-resistant enterococci (VRE) patient’s colonization was also reduced by 42% in the copper arm of the study as compared to the control arm (p<0.05) (11). The use of copper oxide impregnated hard and soft surfaces, such as bed rails, bed tables, countertops and linens, was found also to reduce HAI rates in an acute care hospital (12). Specifically, there were 78% and 83% fewer HAIs due to Multi Drug Resistant Organisms or Clostridium difficile, respectively (p<0.05). Two clinical trials have examined so far the effect on HAIs of using copper-oxide impregnated medical textiles only. Both studies found statistically significant reductions (23 to 55%) in HAI and HAI related events per 1000 hospitalization days (13,14).

In conclusion, the wide biocidal spectrum of copper and other metals, who can endure the harsh cleaning and environmental stresses present in the medical environment, make them attractive candidates for use in the fight against nosocomial pathogens and HAIs.

References:

  1. Borkow, G. Using copper to fight microorganisms. Current Chemical Biology 2012; 6: 93-103.
  2. Weaver L, Michels HT, Keevil CW. Survival of Clostridium difficile on copper and steel: futuristic options for hospital hygiene. J Hosp Infect 2008; 68: 145-51.
  3. Wheeldon LJ, Worthington T, Lambert PA, Hilton AC, Lowden CJ, Elliott TS. Antimicrobial efficacy of copper surfaces against spores and vegetative cells of Clostridium difficile: the germination theory. J Antimicrob Chemother 2008; 62: 522-5.
  4. Noyce JO, Michels H, Keevil CW. Potential use of copper surfaces to reduce survival of epidemic meticillin-resistant Staphylococcus aureus in the healthcare environment. J Hosp Infect 2006; 63: 289-97.
  5. Monk, A.B., Kanmukhla, K., Trinder, K., and Borkow, G. Potent bactericidal efficacy of copper oxide impregnated non-porous solid surfaces. BMC Microbiology 2014; 14:57.
  6. Borkow G, Gabbay J. Putting copper into action: copper-impregnated products with potent biocidal activities. FASEB J 2004; 18: 1728-30.
  7. Gabbay J, Mishal J, Magen E, Zatcoff RC, Shemer-Avni Y, Borkow G. Copper oxide impregnated textiles with potent biocidal activities. Journal of Industrial Textiles 2006; 35: 323-35.
  8. Casey AL, Adams D, Karpanen TJ et al. Role of copper in reducing hospital environment contamination. J Hosp Infect 2010; 74: 72-7.
  9. Marais F, Mehtar S, Chalkley L. Antimicrobial efficacy of copper touch surfaces in reducing environmental bioburden in a South African community healthcare facility. J Hosp Infect 2010; 74: 80-2.
  10. Mikolay A, Huggett S, Tikana L, Grass G, Braun J, Nies DH. Survival of bacteria on metallic copper surfaces in a hospital trial. Appl Microbiol Biotechnol 2010; 87: 1875-9.
  11. Salgado CD, Sepkowitz KA, John JF et al. Copper surfaces reduce the rate of healthcare-acquired infections in the intensive care unit. Infect Control Hosp Epidemiol 2013; 34:479-486.
  12. Sifri CD, Burke GH, Enfield KB. Reduced health care-associated infections in an acute care community hospital using a combination of self-disinfecting copper-impregnated composite hard surfaces and linens. Am J Infect Control. 2016; 44(12):1565-1571.
  13. Lazary, A., Weinberg, I., Vatine, J-J., Jefidoff, A., Bardenstein, R., Borkow, G., and Ohana, N. Reduction of healthcare-associated infections in a long-term care brain injury ward by replacing regular linens with biocidal copper oxide impregnated linens. International Journal of Infectious Diseases 2014; 24:e23–e29.
  14. Marcus, E.L., Yosef, H., Borkow, G., Caine, Y., Sasson, A., and Moses, A. E. Reduction of healthcare-associated infection indicators by copper oxide impregnated textiles: crossover, double-blind controlled study in chronic ventilator-dependent patients. Am J Infect Control. 2016; S0196-6553(16)31085-9.