Over the past decade the development of additional disinfecting methods has become increasingly important to prevent hospital acquired infections as antibiotic drug resistance has risen rapidly. One such method involves copper-impregnated self-sanitizing surfaces. Despite the overwhelming evidence that such devices decrease the microbial burden in hospitals, their introduction to clinical settings has been slow.
Copper was used in medicinal preparations in ancient civilizations, long before the concept of microbes arose in the 19th century (1). In past centuries it was known that water stored in copper vessels or transported in copper systems was of superior quality to water stored or transported by other mechanisms. Such knowledge resulted in its use in baths, healthcare facilities, spas, taps, and brewery coppers.
The antimicrobial activities of copper are due to multiple factors. Elevated cellular copper levels cause oxidative damage. Excess copper also results in the loss of membrane integrity, which causes essential nutrients, including potassium and glutamate to leak from cells and cause death. Copper also binds proteins, which either inhibits enzymatic activity or leads to protein degradation (2-4).
The antimicrobial activities of copper against Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Clostridium difficile, vancomycin-resistant enterococci (VRE), and ESBL-producing species, as well as adenoviruses, influenza A, and fungi has been known for decades (5). Nevertheless, medical students routinely cite silver as a primary metal with bacteriostatic or bactericidal activity. This is often in reference to the intra-urethral application of silver for the treatment of gonorrhoea in the pre-antibiotic era (6).
The use of copper materials to reduce environmental contamination on contact surfaces was first postulated over 30 years ago. During a training session to promote hygiene awareness, cleaning staff in a U.S. hospital obtained environmental swabs from multiple locations and assessed the quantities of bacteria that were present on each surface. That assessment revealed that brass doorknobs (an alloy of 67% copper and 33% zinc) contained substantially fewer bacteria than stainless steel doorknobs (7).
Since environmental surfaces are reservoirs for pathogen growth and transmission, and the microbial burden of frequently touched surfaces in healthcare facilities may play a significant role in hospital-acquired infections (HAIs) (8), investigations of environmental surfaces have been increasing.
To standardize the assessment of hospital cleanliness, aerobic colony counts (ACC) on hand-touch sites should not exceed 250 colony forming units (CFU)/cm2 (9). Investigations of terminal room cleaning using a fluorescent indicator showed that sufficient decontamination occurred only 49% of the time following hospital discharge and that less than 30% of toilet handholds, bedpan cleaners, doorknobs, and bathroom light switches were adequately cleaned (10). It is known that the environment may facilitate the transmission of several important healthcare-associated pathogens, including VRE, C. difficile, Acinetobacter spp., MRSA, and norovirus (11-15). Such pathogens are frequently shed by hospital patients, visitors, and staff, and can survive on stainless steel surfaces for days, which increases the risk of transfer to other patients (16). Multiple studies showed that EPA-registered copper surfaces are effective at lowering the microbial burden and augmenting existing infection control strategies (17-26).
In a 2016 study by Schmidt et al., copper surfaces were found to be equally antimicrobial in paediatric settings and adult intensive care units. In that study, the microbial burden on copper bed rails was reduced by 1.996 log (99%). Moreover, the introduction of copper items in eight study rooms was found to reduce the microbial burden recovered from subjects in control rooms by 1.863 log (73%). Thus, it was concluded that copper surfaces warrant consideration for the introduction of no-touch disinfection technologies for reducing HAIs (17).
Schmidt et al. also revealed that the introduction of copper surfaces on objects formerly covered by plastic, wood, stainless steel, or other materials reduced the microbial burden by 83%. Notably, that reduction was maintained over 21 months (18). Similarly, a 2017 study by Coppin et al. showed that copper impregnated tray tables had lower microbial burdens than tray tables made of standard materials. The microbial burden was 81% lower on copper surfaces after 30 hours, compared to levels on non-copper surfaces (19). Copper-impregnated stethoscopes also exhibited up to 91% fewer CFU/cm2, compared to non-copper impregnated stethoscopes (191 vs. >300 CFU/cm2, respectively) (26).
Such findings led to the question of whether the reduced microbial burden observed with copper surfaces could also reduce HAIs. Salgado et al. found that patients cared for in ICU rooms containing copper alloy surfaces had a 58% reduction in the rates of HAIs and/or colonization with MRSA or VRE, compared to patients treated in standard rooms. Based on those data, the authors concluded that additional studies with larger patient populations were warranted to determine the clinical impact of copper alloy surfaces in hospital rooms (27).
A 2015 review by Michaels and Salgado discussed the difficulties with performing large, prospective, longitudinal randomised controlled trials (RCTs) for the use of copper surfaces in hospitals, including the increasing costs of copper (28). Recently, Sentara’s Leigh Hospital in Norfolk tested the use of copper linens. That study revealed an 83% decline in C. difficile infections within 10 months. The rates of MRSA and VRE infections were also reduced by 78%; however, the study failed to implement a control group or well-defined endpoints (29). Conversely, a Chilean study failed to identify any reductions in HAIs, mortality, or antimicrobial costs when copper surfaces were implemented in hospital settings. However, the lack of beneficial effects may have been due to the limited sample size (30).
A similar study involving the use of copper linens in a long-term care facility for patients with brain injuries found a 24% reduction in the HAIs per 1,000 hospitalization days, a 47% reduction in the number of fever days, and a 32% reduction in the total number of antibiotic administrations per 1000 hospitalization days. Thus, a 27% reduction in the costs of antibiotics, X-rays, disposables, labour, and laundry was observed (31).
Overwhelming evidence exists to favour the effects of copper surfaces on reducing the microbial burden for infectious disease control. Despite an the existence of a registered U.S. Environment Protection Agency copper surface system, and subsidies provided by the Canadian Government, the introduction of copper to hospital settings remains difficult (33). The question remains whether copper surfaces should adhere to the FDA criteria for new drug using RCTs in the absence of investments by pharmaceutical companies.
Copper has two key properties that are exploited in consumer products and medical devices. Copper has potent biocidal properties, and is critical for most tissues in the body, including the skin. In the skin, copper is involved in the synthesis and stabilisation of extracellular matrix skin proteins and angiogenesis (32). Thus, those properties were leveraged for the use of copper oxide-impregnated wound dressings, in which wound closure increased due to increased blood vessel formation, and the increased production of pro-angiogenic factors, including placental growth factor and vascular endothelial growth factor (34). A study involving copper oxide containing diapers in elderly patients revealed similar results (35).
In an era of rapidly evolving multidrug resistant bacteria, it is unsurprising that substantial attention has been given to the development of additional disinfecting methods to prevent hospital-acquired infections. One such method is the use of copper-impregnated self- sanitizing surfaces. However, despite the overwhelming evidence that such surfaces significantly decrease the microbial burden, the implementation and introduction of these devices in hospitals has been unacceptably slow. One reason for this is the lack of clinical trials. Additionally, bacterial resistance to metallic copper is known; however, this should be considered a minor concern (36) since copper allergies are rare, particularly in intra-uterine device users (37).
- Dolwett K.H, Sorenson J.R. (1985). Historic uses of copper compounds in medicine. Trace elements in Medicine, 2(2), 80-7.
- Dick R.J, Wray J.A, Johnston H.N. (1973). A Literature and Technology Search on the Bacteriostatic and Sanitizing Properties of Copper and Copper Alloy Surfaces: Phase 1 Final Report, INCRA Project no 212.
- Thurnan R.B, Gerba C.P. (1989). The Molecular Mechanisms of Copper and Silver for Disinfection of Bacteria and Viruses. CRC Crit. Rev. Environ. Control, 18(4), 295-315.
- Manzl C, Enrich J, Ebner H., et al. (2004). Copper induced formation of reactive oxygen species causes cell death and disruption of calcium homeostasis in trout hepatocytes. Toxicology, 196(1-2), 57-64.
- Meyer T.J, Ranfall J, Thu P., et al. (2015). Antimicrobial Properties of Copper in Gram-Negative and Gram-Positive Bacteria. Int. J. Biol. Biomol. Agric. Food and Biotechnol. Engineering, 9(3).
- Corgas W.C. (1918). Venereal Diseases and the War. Am. J. Public Health, 8(2).
- Kuhn P.J. (1983). Doorknobs: a source of nosocomial infections. Diagnost. Med. 62-3.
- Boyce J.M. (2007). Environmental contamination makes an important contribution to hospital infection. J. Hosp. Inf., 65, 50-54.
- Dancer S.J. (2004). How do we assess hospital cleaning? A proposal for microbiological standards for surface hygiene in hospitals. J. Hosp. Infect., 56, 10-15.
- Carling P. C, Parry M. F, von Beheren S.M., et al. (2008). Identifying opportunities to enhance hospital cleaning in 23 acute care hospitals. Infect. Control. Hosp. Epidemiol., 29, 1-7.11. Dancer S.J. (2008). Importance of the environment in methicillin resistant Staphylococcus aureus acquisition: the case for hospital cleaning. Lancet Infect. Dis., 8, 101-13.
- Martinez J.A., Ruthazer R, Hanjosten K., et al. (2003). Role of environmental contamination as a risk factor for acquisition of vancomycin resistant enterococci in patients treated in a medical intensive care unit. Arch. Int. Med., 163, 1905-12.
- Tankovic J, Legrand P, de Gatines G., et al. (1994). Characterisation of a hospital outbreak of imipenem-resistant Acinetobacter baumannii by phenotype and genotype typing methods. J. Clin. Microbiol., 32, 2677-81.
- Green J, Wright P.A, Gallimore C.I., et al. (1998). The role of environmental contamination with small rounded viruses in a hospital investigated by reverse-transcriptase polymerase chain reaction assay. J. Hosp. Inf., 39, 39-45.
- Kaatz G.W, Gitlin S.D, Schaberg D.R et al. (1988). Acquisition of Clostridium difficile from the hospital environment. Am. J. Epidemiol., 127, 1289-94.
- Kramer A, Schwebke I, Kampf G., et al. (2006). How long do nosocomial pathogens persist on inanimate surfaces? A systematic review. BMC Inf. Dis., 6(130), 2334-6.
- Schmidt M.G, von Dessauer B, Benavente C., et al. (2016). Copper surfaces are associated with significantly lower concentrations of bacteria on selected surfaces within a pediatric intensive care unit. Am. J. Inf. Control., 44(2), 203-9.
- Schmidt M.G, Attaway H, Sharpe P.A. (2012). Sustained Reduction of Microbial Burden on Common Hospital Surfaces through Introduction of Copper. J. Clin. Microbiol., 50(7), 2217-23.
- Coppin J.D, Villamoria F.C, Williams M.D. (2017). Self-sanitizing copper impregnated surfaces for bioburden reduction in patient rooms. Am. J. Infect. Control., 45(6), 692-4.
- Humphreys H. (2014). Self-disinfecting and Microbiocide Impregnated Surfaces and Fabrics: What Potential in Interrupting the Spread of Healthcare-Associated Infection? Clin. Infect. Dis., 58(6), 848-53.
- Grass G, Rensing C, Solioz M., et al. (2011). Metallic Copper as an Antimicrobial Surface. Appl. Environm. Microbiol., 77(5), 1541-47.
- Monk A.B, Kanmukhla V, Trinder K. (2014). Potent bactericidal efficacy of copper oxide impregnated non-porous solid surfaces. BMC Microbiol., 14, 57).
- Karpanen T.J, Casey A.L, Lambert P.A., et al. (2012). The antimicrobial efficacy of copper alloy furnishing in the clinical environment: a cross over study. Inf. Control Hosp. Epidemiol., 33(1), 3-9.
- Villapun V.M, Dover L.G, Cross A., et al. (2016). Antibacterial Metallic Touch Surfaces. Materials, 9, 736.
- Zhitnitsky D, Rose J, Lewinson O. (2017). The highly synergistic broad-spectrum antibacterial activity of organic acids and transition metals. Scientific Reports, 7, 44554.
- Schmidt M.G, Tuuri R.E, Dharsee A., et al. (2017). Antimicrobial copper alloys decreased bacteria on stethoscope surfaces. Am. J. Inf. Control, 45(6), 642-7.
- Salgado C.D, Sekowitz K.A, Cantey J.F., et al. (2013). Copper surfaces reduce the rate of healthcare acquired infections in the intensive care unit. Inf. Control Hosp. Epidemiol., 34(5), 479-88.
- Michaels T, Keevil mC.W, Salgado C.D., et al. (2015). From Laboratory Research to a Clinical Trial. HERD, 9(1), 64-79.
- Cifri C.D, Burke G.H, Enfield K,B. (2016). Reduced healthcare associated infections in an acute care community hospital using a combination of self-disinfecting copper impregnated composite hard surfaces and linens. Am. J. Inf. Control, 44(12), 1565 71.
- Rivero P., Brenner P, Nerceilles R. (2014). Impact of copper in the reduction of hospital acquired infections, mortality and antimicrobial costs in the Adult Intensive Care Unit. Rev Chilena Infectol., 3, 274-9.
- Lazary A, Weinberg J, Vatine J., et al. (2014). Reduction of healthcare associated infections in a long-term care brain injury ward by replacing regular linens with biocidal copper oxide impregnated linens. Int. J. Inf. Dis., 24, 23-9.
- Borkow G. (2014). Using Copper to Improve the Well-Being of the Skin. Curr. Chem. Biol., 8(2), 89-102.
- ECRI Institute (2016) Antimicrobial Copper Surfaces for Reducing Hospital-acquired Infection Risk. ECRI Institute 2016; February. Accessed August 1, 2017. https://www.ecri.org/Resources/AHCJ/2016_Resources/Antimicrobial_Copper_Surfaces_for_Reducing_Hospital-acquired_Infection_Risk.pdf
- Borkow G, Okon-Levy N, Gabbay J. (2010). Copper Oxide Impregnated Wound Dressing: Biocidal and Safety Studies. Wounds, 22(12), 301-10.
- Weinberg I, Lazary A, Jefidoff A., et al. (2013). Safety of using diapers containing Copper Oxide in Chronic Care Elderly Patients. Open Biology Journal, (6), 1-7.
- Santo C.E, Vasconcelos Morais P, Grass G. (2010). Isolation and Characterization of Bacteria Resistant to Metallic Copper Surfaces. Appl. Environ. Microbiol., 78(5), 1341 -48.
- Dry J. Leganedier F, Bennani A. (1978). Intrauterine copper contraceptive devices and allergy to copper and nickel. Ann. Allergy, 41(3), 194.