Recent work investigating the antimicrobial characteristics of copper has led to a re-evaluation of the role of this essential metal in healthcare.
While ancient civilisations used copper for its health benefits it seems its usefulness has been forgotten. The requirement for evidence-based
interventions for infection control has been the driver behind recent scientific assessments of the benefits of copper. Ten years of laboratory
research has led to clinical trials confirming a very significant and continuous reduction in environmental bioburden in a number of healthcare settings globally. The newest and most comprehensive clinical research has now reported an impressive 40 % reduction in healthcare-associated infections in intensive care units (ICUs) where copper was incorporated in key touch surfaces. The deployment of copper touch surfaces should be considered as an additional infection control measure to reduce care costs and improve bed availability and patient outcomes.

Historical Context
That copper has beneficial effects for humans has been known for at
least 4,000 years. The use of copper for drinking water containers to ensure potability and the application of the powdered metal to wounds for disinfection, are reported in ancient Egypt. The Aztecs used copper to treat various skin diseases. Hippocrates, the father of medicine (460–380 BCE), recommended the use of copper for leg ulcers related to varicose veins. In France, during the three cholera epidemics around 1850, it was observed that workers in copper foundries were not affected by the disease.

More recently, in 1970, the American College of Chest Physicians
published on the ‘antibacterial action of copper’. They showed that the use of copper in large reservoir nebulisers for respiratory therapy
resulted in the contents remaining sterile.1 More pertinently, in 1983, a hospital study in Pennsylvania showed copper’s effectiveness in lowering the Escherichia Coli count on brass door knobs.2

The Healthcare-associated Infection Problem
During the subsequent decades, the major concern within the medical
community has been healthcare-associated infections (HCAIs), or
‘nosocomial’ infections. This year’s report from the World Health
Organization (WHO) notes how difficult it is to gather reliable and
comparable HCAI evidence globally, or even nationally. But they are able to conclude that hundreds of millions of patients are affected by them around the world.3

Only receiving public attention when a family member suffers or when there are outbreaks, HCAIs are a very real endemic, ongoing problem and one that no institution or country can claim to have solved, despite many efforts. The statistics are harrowing. The European Centre for Disease Prevention and Control (ECDC) indicated HCAI levels in Europe as 7.1 % in 2008.4 This equates to over four million patients being affected each year. The estimated incidence rate in the US was 4.5 % in 2002, corresponding to 1.7 million affected patients.5

Infections in intensive care units (ICUs) can be as high as 51 %, most of these being healthcare associated. Furthermore, the longer patients stay in an ICU, the more at risk they become of acquiring an infection.3

The measures taken towards reducing microbe transportation through frequently touched surfaces started in the last decade with the WHO ‘Clean Care is Safer Care’ campaign. In many national healthcare systems, specific guidelines were given to healthcare professionals in order to raise awareness and help combat nosocomial infections.

In 2001 in the UK, the ‘EPIC Project: Developing National Evidence-based Guidelines for Preventing Healthcare associated Infections’ among other good practices, points out touch surfaces as one of the major components of microbial concentration and transfer.6

Copper in Laboratory Studies
In 2000, the early laboratory studies from the University of Southampton indicated that copper cast alloys (e.g. brass and bronze) were able to reduce E.Coli O157 cross-contamination during food-handling procedures. The research showed that although stainless steel may appear clean, bacteria can survive on these surfaces for considerable periods of time. In comparison, survival on many copper alloys is limited to just a few hours or even minutes. Due to the intrinsic characteristics of copper alloys, i.e. being homogenous and solid, wear resistant and durable, complete lifetime antimicrobial efficacy could be expected. These may then be utilised in facilities where bacterial contamination cannot be tolerated.7

One fundamental consideration in the early laboratory studies was
which test of efficacy to employ. The only existing test for a solid material had been developed in Japan (JIS Z 2801) but stipulated conditions wholly different to a typical indoor environment, i.e. 35 ºC and in a relative humidity of 100 %. Copper alloys were shown to easily ‘pass’ this test, which required contact for 24 hours. More appropriate standards were those based upon liquid disinfectants, like the current EN 1276, which used a more typical 20 ºC and allowed the inoculum to dry in sterile air. The Southampton team developed a modified version of this and was able to measure efficacy at specified times in order to obtain a kill rate curve.

This test protocol has subsequently been verified in a number of other laboratories worldwide. The test is versatile and sensitive enough to allow comparison of different inoculum levels: from the disinfectant-based standard of 10 million colony-forming units (CFU) down to more typical hospital contamination levels such as 1,000 CFU or less. It has also been used to show efficacy at refrigeration temperatures. Comparative work
using this test protocol (under typical indoor conditions) shows that
silver-containing composites, like the stainless steel control, showed
no efficacy.8

Subsequently, many papers have been published from numerous
researchers expanding the understanding of the antimicrobial activity of
copper alloys.9,10,11 As a simple comparison, against an antibiotic,
co-workers compared a copper alloy (CuZn37) with Aminoglycocide in a
zone of inhibition test, showing comparable efficacy.12

In 2008, the US Environmental Protection Agency (EPA), following
rigorous independent testing based upon the Southampton-developed
protocol, permitted the registration of nearly 300 copper alloys.13 This
allows public health claims to be made for the alloys under the terms of
the registration, a first for solid materials.

Most recently, further developments of the laboratory test protocols
have led to published work showing that efficacy on a dry surface can
be as short as two minutes.14 The Southampton team also published
work showing that even high inoculum levels of MRSA and VRE in
droplet-like contamination events were eradicated in less than 10
minutes.15,16 These have both been driven by attempts to make the
laboratory tests similar to real life conditions.

Broad Spectrum Efficacy
In general, antimicrobial copper alloys are effective against bacteria,
viruses, fungi and moulds, including these significant pathogens (see Table 1).

Mechanisms
Work is ongoing on the mechanism14–16 by which copper exerts its
effect, but it is clear that the attack is a complex interaction rather than
just one process interrupter. The speed at which the reactions occur
complicates the research and a number of modes of action have been identified. Theories include membrane puncture and leakage,
disturbance of osmotic balance and generation of free radicals causing oxidative stress. At some stage the cell DNA is completely destroyed, indicating that transfer of antimicrobial resistance should not be a factor of concern.

Clinical Trials
The first qualitative clinical trial was performed at Kitasato University
Hospital in Japan in 2005.17 However, a fully quantitative trial was
initiated in 2007 on a 20-bed medical ward at Selly Oak Hospital in
Birmingham, UK.

‘Hot spot’ touch surfaces were identified by a team of clinicians and
microbiologists. The components included dressings trolleys, light
switches, taps, door and equipment handles, push plates, grab rails and
over-bed tables. These were upgraded to copper or copper alloy and placed on the ward over the course of six months. Once installed, the clinical assessment ran for three months and was able to report 90–100 % reductions in contamination on copper surfaces compared with controls. Standard cleaning procedures and products were used throughout the trial.18

Subsequently, a clinical trial in ICU rooms at Calama Hospital in Chile
reported similar reductions. Notably, this region has regular daytime
humidity levels of just 6 %.19

In a recent out-patient study, not only was the reduction in microbial burden confirmed but a ‘halo’ effect was observed: reduced
contamination in the immediate vicinity of the copper surfaces. The
copper surfaces were calculated to reduce the risk of exposure to
environmental microbes by a factor of 17.20

Infection Rates
In a three-centre clinical trial (see Figure 1) completed in June 2011, the first proof of improved patient outcomes was reported. The trial initially carried out an observational assessment of key touch surfaces and contamination levels in an ICU environment, identifying which room components to upgrade to copper alloys.

Table 1: Antimicrobial Copper Alloys are Effective
Against These Pathogens
Acinetobacter baumannii Klebsiella pneumoniae
Adenovirus Legionella pneumophila
Aspergillus niger Listeria monocytogenes
Candida albicans Methicillin-resistant Staphylococcus
aureus (MRSA, including E-MRSA
and methicillin-sensitive
S. aureus [MSSA])
Campylobacter jejuni Poliovirus
Clostridium difficile (including spores) Pseudomonas aeruginosa
Enterobacter aerogenes Salmonella enteritidis
Escherichia coli O157:H7 S. aureus
Helicobacter pylori Tubercle bacillus
Influenza A (H1N1) Vancomycin-resistant
enterococcus (VRE)

The Role of Antimicrobial Copper Surfaces in Reducing Healthcare-associated Infections

Just six key components were selected and re-engineered to take a copper or copper alloy surface. This included the bed rails, visitor chair arms and nurse call-buttons. After upgrade, reduction in contamination levels on these items was verified to be 97 % (see Figure 2) – confirming the results from Selly Oak. Finally, after three and a half years, the interim result reported at the 1st WHO International Conference on Prevention and Infection Control (ICPIC) indicated a reduction in HCAIs of 40 % for patients in the copper rooms compared with those in the non-copper rooms. For patients in a copper room with all six copper items present throughout their stay, the reduction was nearly 70 %.21

Future Activities
Up until now, all research and applications appear to show great
potential regarding the effectiveness of antimicrobial copper alloys
against bacteria and other pathogenic organisms.

Further to the scientific and clinical research results, manufacturers
have also shown great interest in producing objects that are used
frequently in high nosocomial potential areas (e.g. ICU, medical wards, etc.). However, implementation outside hospital areas, where microbial flora are at high levels, also worries public health planners.

In Laval, France, the brand new Center Inter-Generational Multi Accueil (CIGMA)22 – a nursery for 35 infants and a 60-bed care home for dependent elderly people – has deployed copper alloys on all handrails and door handles. In Tokyo, Japan, the Mejiro Daycare Center for Children fitted copper sinks and handrails, as well as other touch surfaces.23

In Athens, Greece, a large private elementary school with 2,500 students
changed all the handrails, door handles and push plates to those made
from copper alloy (Cu 64 %, Zn 36 %). The first results showed 90–100 %
less contamination than on standard, non-copper surfaces.24

In another application area, transport, the Santiago Metro system in Chile has installed copper alloy handrails at one new station.25
Subsequently, the Metro has signed contracts to fit brass handrails on two new lines under construction – some 30 stations.

Economics
The total cost of copper or copper alloy objects is a combination of raw
material and manufacturing time. Many copper alloys are still used
widely in industry because they can be fabricated into complex parts
easily and quickly (e.g. taps and lock mechanisms). This means that
copper alloy components will become cost-effective when product
volumes are economic even if prototypes carry a premium.

Furthermore, because these components are generally straightforward
to install, they will be more cost-effective than many high-tech
propositions. Installing during a typical refurbishment project, when
such common equipment would be refitted anyway, requires few special skills and is therefore broadly cost neutral. These items will also likely have a 30-year minimum lifetime.

Due to the antimicrobial efficacy, the cost of replacing and installing copper alloy components cannot be compared to the cost of objects made from other types of material (stainless steel, plastic, etc.). Rather, it is the value of the benefit of copper that should be assessed. Targeted installation of copper clearly results in a decrease in environmental bioburden. Now the link has been established between this and infection rates: Dr Schmidt’s conservative assessment indicates a 40 % reduction in ICU-acquired infections, with the potential for a 70 % reduction. This should lead to a reduction in care costs, better bed availability and an
improvement in patient outcomes. When, as should result, we are able to decrease antibiotics usage, we have a further a benefit of incalculable value. In times when multi-resistant bacteria are increasing and antibiotics could have run their course, the antimicrobial copper era may have dawned.

1. Deane RS, Mills EL, Hamel AJ, Antimicrobial action of copper in respiratory therapy apparatus, Chest, 1970;58(4):373–7
2. Kuhn PJ, Doorknobs: a source of nosocomial infection?, Diagnostic Medicine, 1983;62–3.
3. WHO, Report on the Burden of Endemic Healthcare-Associated Infection Worldwide, 2011.
4. European Centre for Disease Prevention and Control (ECDC), Annual Epidemiological Report, 2008.
5. Klevens RM, Edwards JR, Richards CL Jr, et al., Estimating health care-associated infections and deaths in U.S. hospitals, 2002, Public Health Rep, 2007;122:160–6.
6. EPIC, Guidelines for preventing healthcare-associated infections, J Hosp Infect, 2001;47(Suppl.):S1.
7. Noyce JO, Michels H, Keevil CW, Use of copper cast alloys to control Escherichia coli O157 cross-contamination during food processing, Appl Environ Microbiol, 2006:72;4239–44.
8. Michels HT, Noyce JO, Keevil CW, Effects of temperature and humidity on the efficacy of methicillin-resistant Staphylococcus aureus challenged antimicrobial materials containing silver and copper, Lett Appl Microbiol,
2009;49(2):191–5.
9. Noyce JO, Michels H, Keevil CW, Inactivation of influenza A virus on copper versus stainless steel surfaces, Appl Environ Microbiol, 2007;73(8):2748–50.
10. 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.
11. Wheeldon LJ, Worthington T, Lambert PA, et al., Antimicrobial
efficacy of copper surfaces against spores and vegetative cells of Clostridium difficile: the germination theory, J Antimicrob Chemother, 2008;62:522–5.
12. Kouskouni E, Tsouma I, Patikas I, et al., Antimicrobial activity of copper alloys compared to aminoglycosides against multidrug resistant bacteria, Abstract 3597, Presented at: the ECCMID-ICC, 7–10 May 2011.
13. Michels HT, Anderson DG, Antimicrobial regulatory efficacy testing of solid copper alloy surfaces in the USA, Metal Ions Biol Med, 2008;10:185–90.
14. Santo CE, Ee WL, Elowsky CG, et al., Bacterial killing by dry metallic copper surfaces, Appl Environ Microbiol, 2011;77(3):794–802.
15. Keevil CW, Warnes SL, New insights into the antimicrobial
mechanisms of copper touch surfaces, BMC Proceedings, 2011;5(Suppl. 6):P39.
16. Warnes SL, Keevil CW, Mechanism of copper surface toxicity in vancomycin-resistant enterococci following ‘wet’ or ‘dry’ contact, Appl Environ Microbiol, 2011;[Epub ahead of print].
17. Sasahara T, Niiyama N, Ueno M, Use of copper and its alloys to reduce bacterial contamination in hospitals (invited lecture), J JRICu, 2007;46(1);12–6.
18. Casey A, Adams D, Karpanen TJ, et al., Role of copper in reducing hospital environment contamination, J Hosp Infect, 2010;74:72–7.
19. Prado V, Duran C, Crestto M, et al., Effectiveness of copper contact surfaces in reducing the microbial burden (MB) in the intensive care unit (ICU) of Hospital del Cobre, Calama, Chile, Presented at: the 14th International Conference on Infectious Diseases, Poster 56.044, Miami, 11 March 2011.
20. Hirsch BE, Attaway H, Nadan R, et al., Copper Surfaces Reduce the Microbial Burden in an Out-Patient Infectious Disease Practice, Poster 458, Presented at: the 50th Interscience Conference on Antimicrobial Agents in Chemotherapy (ICAAC), Boston, MA, 12–15 September 2010.
21. Schmidt MG, Copper Touch Surface Initiative Microbiology and Immunology, Medical University of South Carolina, Charleston, USA, BMC Proceedings, 2011;5(Suppl. 6):O53
22. Copper Development Association, Pioneering eco care home specifies antimicrobial copper – Laval, France, PR 799, 2011.
23. Copper Development Association, Antimicrobial Copper to Protect Children against Infections – Tokyo, Japan, PR 797, 2011.
24. Efstathiou P, Koustoni E, Tseroni M, et al., Elementary schools in Athens – application of antimicrobial copper, Presented at: XVI Congreso Nacional y V Internacional de la Sociedad Española de Medicina Preventiva alud Publica e Higiene, (SEMPSPH), 25–27 May 2011.
25. Financial Report, Codelco, January – March 2011.