Scientific References

Peer-reviewed research papers discussing the antimicrobial properties of copper-based metals

Here is a library of published papers and conference posters covering the laboratory and clinical studies conducted on the antimicrobial characteristics of solid copper and copper alloys over the last 20 years.  Some papers are accessible here as pdfs, others have links to entries in various scientific libraries where full papers can be accessed via a subscription or for a cost.

If you have a paper to suggest we include here, please contact Marleine Williams, Project Co-ordinator, Copper Development Association.

Browse the entire list or use the category filters below.

 

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Effectiveness of copper contact surfaces in reducing the microbial burden (MB) in the intensive care unit (ICU) of Hospital del Cobre, Calama, Chile
V Prado, C Durán, M Crestto, A Gutierrez, P Sapiain, G Flores, H Fabres, C Tardito, M Schmidt. Poster 56.044, presented at the 14th International Conference on Infectious Diseases, Miami, March 11, 2010.

First results from the Calama Hospital copper clinical trial show a significant reduction in bioburden on copper compared to control surfaces.

Survival of Bacteria on Metallic Copper Surfaces in a Hospital Trial
André Mikolay, Susanne Huggett, Ladji Tikana, Gregor Grass, Jörg Braun and Dietrich H Nies. Applied Microbial and Cell Physiology,DOI 10.1007/s00253-010-2640-1. May 2010

Basic chemistry of copper is responsible for its Janus-faced feature: on one hand, copper is an essential trace element required to interact efficiently with molecular oxygen. On the other hand, interaction with reactive oxygen species in undesired Fenton-like reactions leads to the production of hydroxyl radicals, which rapidly damage cellular macromolecules. Moreover, copper cations strongly bind to thiol compounds disturbing redox-homeostasis and may also remove cations of other transition metals from their native binding sites in enzymes. Nature has learned during evolution to deal with the dangerous yet important copper cations. Bacterial cells use different efflux systems to detoxify the metal from the cytoplasm or periplasm. Despite this ability, bacteria are rapidly killed on dry metallic copper surfaces. The mode of killing likely involves copper cations being released from the metallic copper and reactive oxygen species. With all this knowledge about the interaction of copper and its cations with cellular macromolecules in mind, experiments were moved to the next level, and the antimicrobial properties of copper-containing alloys in an "everyday" hospital setting were investigated. The alloys tested decreased the number of colony-forming units on metallic copper-containing surfaces by one third compared to control aluminum or plastic surfaces. Moreover, after disinfection, repopulation of the surfaces was delayed on copper alloys. This study bridges a gap between basic research concerning cellular copper homeostasis and application of this knowledge. It demonstrates that the use of copper-containing alloys may limit the spread of multiple drug-resistant bacteria in hospitals.

Performance of Ultramicrofibre Cleaning Technology with or without Addition of a Novel Copper-Based Biocide
D Hamilton, A Foster, L Ballantyne, P Kingsmore, D Bedwell, T J Hall, S S Hickok, A Jeanes, P G Coen, V A Gant, Journal of Hospital Infection (2010) 74, 62-71. doi:10.1016/j.jhin.2009.08.006.

This study compared the bacterial removal performance of ultromicrofibre cloths and mops (UMF) moistened with water (UMF + water) with those moistened with a novel copper-based biocide (UMF + CuWB50, 300 ppm) in several working hospital environments, specifically Accident and Emergency (A&E) and three other wards.

A total of 13 defined sampling sites (10 sites per ward) were sampled in order to retrieve, culture, and enumerate total viable (bacterial) counts (TVC) for each site.  We sampled 1h before, and 1 and 4h after, cleaning three times per week.  The trial ran for 7 weeks.  Two wards were cleaned with UMF + water for 3 weeks and UMF + CuWB50 for 4 weeks.  The reverse applied to the other two wards in a cross-over design fashion, to eliminate ward- and time-specific bias.  Multivariate statistical analyses were used to establish extent and significance of any perceived differences, and to eliminate the effects of potential confounders.  Cleaning with UMF + water reduced TVC on the test surfaces by 30%, whereas cleaning with TVC + CuWB50 reduced TVC by 56%.  CuWB50 had two separate effects; a direct antibacterial effect (evident shortly after cleaning), and a residual antibacterial effect that lasted approx 2 weeks.  The residual effect requires regular application of CuWB50 if it is to persist.  This 'real life' hospital implementation study demonstrates encouraging microbiological cleaning performance for UMF, which is further enhanced with CuWB50.

Role of Copper in Reducing Hospital Environment Contamination
A L Casey, D Adams, T J Karpanen, P A Lambert, B D Cookson, P Nightingale, L Miruszenko, R Shillam, P Christian and T S J Elliott, J Hosp Infect (2009), doi:10.1016/j.jhin.2009.08.018.

The environment may act as a reservoir for pathogens that cause healthcare-associated infections (HCAIs). Approaches to reducing environmental microbial contamination in addition to cleaning are thus worthy of consideration. Copper is well recognised as having antimicrobial activity but this property has not been applied to the clinical setting. We explored its use in a novel cross-over study on an acute medical ward. A toilet seat, set of tap handles and a ward entrance door push plate each containing copper were sampled for the presence of micro-organisms and compared to equivalent standard, non-copper-containing items on the same ward. Items were sampled once weekly for 10 weeks at 07:00 and 17:00. After five weeks, the copper-containing and non-copper-containing items were interchanged.

The total aerobic microbial counts per cm2 including the presence of 'indicator micro-organisms' were determined. Median numbers of microorganisms harboured by the copper-containing items were between 90% and 100% lower than their control equivalents at both 07:00 and 17:00. This reached statistical significance for each item with one exception. Based on the median total aerobic cfu counts from the study period, five out of ten control sample points and zero out of ten copper points failed proposed benchmark values of a total aerobic count of <5 cfu/cm2. All indicator micro-organisms were only isolated from control items with the exception of one item during one week. The use of copper-containing materials for surfaces in the hospital environment may therefore be a valuable adjunct for the prevention of HCAIs and requires further evaluation.

Potential for Preventing Spread of Fungi in Air-Conditioning Systems Constructed Using Copper Instead of Aluminium
L Weaver, H T Michels, C W Keevil, Letters in Applied Microbiology ISSN 0266-8254 (2010) 50 (1): 18. doi:10.1111/j.1472-765X.2009.02753.x. PMID 19943884.

Aims:
As copper has been previously suggested as an antimicrobial surface, the effectiveness of copper was investigated as an antifungal surface which could be used in air-conditioning systems as an alternative to aluminium.

Methods and Results:
Coupons of copper (C11000) and aluminium were inoculated with fungal isolates (Aspergillus spp., Fusarium spp., Penicillium chrysogenum and Candida albicans) for various time periods. Culture on potato dextrose agar and an in situ viability assay using the fluorochrome FUN-1 were used to determine whether spores had survived. The results showed increased die off of fungal isolates tested compared to aluminium. In addition, copper also prevented the germination of spores present, thereby reducing the risk of the release of spores.

Conclusions:
Copper offered an antifungal surface and prevented subsequent germination of spores present. FUN-1 demonstrated that fungal spores entered into a viable but not culturable (VBNC) state on copper indicating the importance of using such methods when assessing the effect of an antifungal as culture alone may give false results.

Significance and impact of study:
Copper offers a valuable alternative to aluminium which could be used in air-conditioning systems in buildings, particularly in hospital environments where patients are more susceptible to fungal infections.

Antimicrobial efficacy of copper touch surfaces in reducing environmental bioburden in a South African community healthcare facility
Marais F et al, J Hosp Infect (2009), doi:10.1016/j.jhin.2009.07.010.

A comparative controlled study was conducted at a busy walk-in primary healthcare clinic (PHC) in Grabouw, a rural region of the Western Cape, South Africa, to demonstrate antimicrobial efficacy of copper touch surfaces in reducing bioburden in a community healthcare facility.

Antimicrobial surfaces and their potential in reducing the role of the inanimate environment in the incidence of hospital-acquired infections
Kristopher Page, Michael Wilson and Ivan P Parkin, University College London. January 2009. J. Mater. Chem. 2009 DOI: 10.1039/b818698g

Environmental surfaces and their role in the epidemiology of hospital-acquired infections (HAIs) have become an area of great scientific interest, particularly in light of the much publicised cases of infections due to methicillin-resistant Staphylococcus aureus (MRSA) and Clostridium difficile in UK hospitals. This feature article sets out to examine the role of surfaces and the inanimate environment in the spread of HAIs, and looks at various antimicrobial techniques being researched to reduce microbial contamination of surfaces. Preventative measures such as coatings which reduce initial microbial adhesion to surfaces will be considered alongside actively antimicrobial measures which inactivate microorganisms already adherent to a surface. The principal focus of this feature article will be given to light-activated antimicrobial surfaces such as the photocatalyst TiO2 and surfaces with embedded photosensitisers. Surfaces which release antimicrobial compounds or metal ions such as silver and copper are also examined, alongside materials which kill microbes upon contact. The widespread research and development of these antimicrobial surfaces is of great importance in maintaining acceptable levels of hygiene in hospitals and will help to fight the spread of HAIs via the contamination of inanimate surfaces in the healthcare environment.

The antimicrobial properties of copper surfaces against a range of important nosocomial pathogens
S W J Gould, M D Fielder, A F Kelly, M Morgan, J Kenny, D P Naughton,Annals of Microbiology, 59 (1) 151-156 (2009)

Hospital-acquired infections (HAI) are a major problem worldwide and controlling the spread of these infections within a hospital is a constant challenge.  Recent studies have highlighted the antimicrobial properties of copper and its alloys against a range of different bacteria.

The objective of this study was to evaluate the antimicrobial properties of copper compared to stainless steel against a range of clinically important pathogens.  These pathogens consisted of five isolates of each of the following organisms; meticillin resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Escherichia coli, vancomycin-resistant Enterococci (VRE) and Panton-Valentine Leukocidin positive community acquired-MSSA (PVL positive CA-MSSA, MRSA, P. aeruginosa, E.coli and CA-MSSA isolates were not detectable after a median time of 60 minutes.  No detectable levels for all VRE iosolates were determined after a median time of 40 minutes.  However, for all isolates tested the stainless steel had no effect on the survival of the bacteria and levels remained similar to the time zero count.

The results of this study demonstrate that copper has a strong antimicrobial effect against a range of clinically important pathogens compared to stainless steel and potentially could be employed to aid the control HAI.

Copper for Preventing Microbial Environmental Contamination
A L Casey, P A Lambert, L Miruszenko, T S J Elliott. October 2008

Poster presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), October 2008.

Microbial Burden (MB) of Objects (obs) in ICU Rooms (rms)
C D Salgado, K A Sepkowitz, T Plaskett, J F John, J R Cantey, H H Attaway, L L Steed, H T Michels, M G Schmidt. October 2008.

This study sought to determine the microbial burden (MB) on frequently touched inanimate objects in the ICU rooms of patients at three different US hospitals.The findings showed that Staphylococci were the predominant organism isolated within this MB.

Objects found in ICU rooms can serve as a reservoir for the spread of bacteria, particularly staphylococci, to patients, healthcare workers, and visitors.  Objects in close proximity to patients pose the greatest risk, particularly bed rails.

Patient acquisition of organisms that were recovered from ICU rooms may lead to healthcare-acquired infections resulting in substantial morbidity and mortality.  Future studies should focus on strategies to reduce high level bacterial contamination of common objects in patient rooms and potential spread of these bacteria in order to potentially reduce healthcare-acquired infections.

Antimicrobial Properties of Copper Alloy Surfaces, with a Focus on Hospital-Acquired Infections
H Michels, W Moran and J Michel, International Journal of Metalcasting, Summer 2008, pp 47-56

Discusses the antimicrobial properties of copper alloys and their potential to reduce the amount of certain bacteria on frequently touched surfaces. Efficacy data address other materials and the effects of tarnishing, bacteria concentration and repeated contamination. EPA testing, results and registration are highlighted.

Antimicrobial Efficacy of Copper Surfaces Against Spores and Vegetative Cells of Clostridium Difficile: The Germination Theory
L. J. Wheeldon, T. Worthington, P. A. Lambert, A. C. Hilton, C. J. Lowden and T. S. J. Elliott, Journal of Antimicrobial Chemotherapy 2008 62(3):522-525; doi:10.1093/jac/dkn219.

Methods: Antimicrobial efficacy was assessed using a carrier test method against dormant spores, germinating spores and vegetative cells of C. difficile (NCTC 11204 and ribotype 027) over a 3h period in the presence and absence of organic matter.

Results: Copper metal eliminated all vegetative cells of C. difficile within 30 min, compared with stainless steel which demonstrated no antimicrobial activity (P < 0.05).  Copper significantly reduced the viability of spores of C. difficile exposed to the germinant (sodium taurocholate) in aerobic conditions within 60 min (P < 0.05) while achieving a ≥2.5 log reduction (99.8% reduction) at 3 h. Organic material did not reduce the antimicrobial efficacy of the copper surface (P > 0.05).

Conclusions: The use of copper surfaces within the clinical environment and application of a germination solution in infection control procedures may offer a novel way forward in eliminating C. difficile from contaminated surfaces and reducing CDAD.

Antimicrobial regulatory efficacy testing of solid copper alloy surfaces in the USA
H T Michels and D G Anderson, pp 185-190, Metal Ions in Biology and Medicine: Vol 10, Eds Ph Collery, I Maymard, T Theophanides, L Khassanova, T Collery. John Libbey Eurotext, Paris © 2008

Discusses potential impact of antimicrobial copper alloys on amount of certain bacteria on frequently touched surfaces in healthcare settings.  Describes the steps required to make public health claims and summarises EPA test protocols and results.

Survival of Clostridium difficile on copper and steel: futuristic options for hospital hygiene
L Weaver, H T Michels, and C W Keevil, Journal of Hospital Infection, Vol 68, Issue 2, pp 145-151, February 2008

Compares the viability of Clostridium difficile on copper and stainless steel. Reports a significant reduction of Clostridium difficile was observed on alloys with >70% copper content while no reduction is observed on steel. Suggests use of copper alloys in hospitals may reduce the levels of Clostridium difficile on frequently touched surfaces.

The antimicrobial activity of copper and copper alloys against nosocomial pathogens and Mycobacterium tuberculosis isolated from healthcare facilities in the Western Cape: an in-vitro study
S Mehtar, I Wiid, and S D TodorovJournal of Hospital Infection, Vol. 68, Issue 1, pp 45-51, January 2008

Compares the viability of MRSA, Klebsiella pneumonia, Pseudomonas aeruginosa, Acinetobacter baumannii, Candida albicans and Mycobacterium tuberculosis on copper alloys, stainless steel and PVC.  Results illustrate copper's ability to kill pathogens most commonly associated with hospital-acquired infections.  No effect was observed on PVC and stainless steel.

Inactivation of Influenza A Virus on Copper versus Stainless Steel Surfaces
J O Noyce, H Michels and C W Keevil, Applied and Environmental Microbiology, pp 2748 - 2750, Vol 73, No 8, April 2007

Uses fluorescent microscopy to compare viability of Influenza A on copper and stainless steel. Copper showed a 4-log reduction after 6 hours while steel only showed a 1-log reduction after 24 hours.

The Antimicrobial Properties of Copper Alloys and their Potential Applications
H T Michels, D G Anderson, J O Noyce, S A Wilks and C W Keevil, Proceedings of the Sixth International Copper-Cobre Conference, pp 121-133, Vol I, August 2007

Describes potential healthcare applications and barriers for antimicrobial copper alloys. Authors review efficacy data against various organisms and EPA testing.

Survival of Listeria monocytogenes Scott A on metal surfaces: implications for cross-contamination
S A Wilks, H T Michels and C W Keevil, International Journal of Food Microbiology, 111, September (2006), pp 93-98.

Compares the viability of Listeria monocytogenes on various copper alloys and stainless steel. Copper-based alloys produced a significant reduction in viability compared to stainless steel. Suggests materials selection could impact bioload in various environments.

Antimicrobial Characteristics of Copper
H T Michels, ASTM Standardization News, October 2006.

Article provides an overview on the antimicrobial characteristic of copper. Describes the research performed to date and the potential applications of antimicrobial copper products. Includes a letter from the editor which highlights the article.

Potential use of copper surfaces to reduce survival of epidemic methicillin-resistant Staphylococcus aureus in the healthcare environment
J O Noyce, H Michels and C W Keevil, Journal of Hospital Infection, Vol 63, Issue 3, pp 289-297, July 2006

Demonstrates copper's ability to kill epidemic Methicillin-resistant Staphylococcus aureus under different conditions in comparison to stainless steel. Illustrates effects of bacteria concentration, temperature and copper content on antimicrobial efficacy.

Use of Copper Cast Alloys to Control Escherichia coli O157 Cross Contamination during Food Processing
J O Noyce, H Michels, and C W Keevil, Applied and Environmental Microbiology, pp 4239-4244, June 2006.

Investigates ability of copper to kill Escherichia coli O157:H7 which is responsible for diseases caused by food contamination. Incorporates beef juice with bacteria to simulate food cross contamination scenario. High copper containing alloys greatly reduced the amount of E. coli O157:H7 at room (22C) and low temperatures (4C). Stainless steel, the control, had no effect.

The survival of Escherichia coli O157 on a range of metal surfaces
S A Wilks, H Michels and C W Keevil, International Journal of Food Microbiology, 105 (2005), pp 445-454.

Compares the survivability of an infectious strain of Escherichia coli on copper alloys and stainless steel. Copper alloys exhibited a large reduction within several hours while stainless steel did not.  Addresses the advantages of alloying and suggests using antimicrobial surfaces in environments where bacterial contamination is a concern.

Copper Alloys for Human Infectious Disease Control
H T Michels, J P Noyce, S A Wilks and C W Keevil. Copper for the 21st Century, Materials Science & Technology 2005 (MS&T’05) Conference, Pittsburgh, PA, September 25-28, 2005, ASM, ACerS, AIST, AWS, TMS, ISSN: 1546-2498

Illustrates the ability of copper alloys to kill several food borne pathogens known to cause infection. Also demonstrates efficacy against Methicillin-resistant Staphylococcus aureus which is largely responsible for hospital acquired infections. Stainless steel, the control, had no effect on any of the pathogens. Results suggest copper alloys may reduce the levels of infectious pathogens on surfaces in contact with food and touched by humans.

Inactivation of Escherichia coli and coliform bacteria in traditional brass and earthenware water storage vessels
P Tandon, S Chhibber and R Reed, Antonie van Leeuwenhoek (2005) 88:35-4, 14pp

The detection and enumeration of indicator bacteria such as Escherichia coli is used to assess the extent of faecal contamination of drinking water. On the basis of this approach, the effectiveness of storing water contaminated with faecal indicator bacteria in brass or earthen vessels (mutkas) of the type used in rural India have been investigated.

Suspensions of bacteria in sterile distilled water were maintained for up to 48 h in each vessel and enumerated by surface plate counts on nutrient agar (non-selective) and several selective coliform media at 37 °C either under standard aerobic conditions, or under conditions designed to neutralise reactive oxygen species (ROS), e.g. using an anaerobic cabinet to prepare plates of pre-reduced growth medium or by inclusion of sodium pyruvate in the growth medium, with incubation of aerobically-prepared plates in an anaerobic jar.

The counts obtained for E. coli decreased on short-term storage in a brass mutka; counts for selective media were lower than for equivalent counts for non-selective medium, with ROS-neutralised conditions giving consistently higher counts than aerobic incubation. However, after 48 h, no bacteria were cultivable under any conditions. Similar results were obtained using water from environmental sources in the Panjab, and from rural households where brass and earthern mutkas are used for storage of drinking water, with enumeration on selective coliform media (presumptive total coliforms). In all cases results indicated that, while storage of water in a brass mutka can inactivate E. coli and coliforms over a 48 h period, standard aerobic plate counting using selective media may not be fully effective in enumerating sub-lethally damaged bacteria.

The Effects of Copper Alloy Surfaces on the Viability of Bacterium, E. coli 0157:H7
H T Michels, S A Wilks and C W Keevil. The Second Global Congress Dedicated to Hygienic Coatings & Surfaces, Orlando, Florida, USA, 26-28 January, 2004, Paper 16, Published by Paint Research Association, Middlesex, UK, ISBN 0-9543164-5-2, 2004.

Tests the viability of E. coli O157:H7 on a variety of copper alloy surfaces. All tested copper alloys rendered the bacteria non viable after several hours. E. coli O157:H7 has been responsible for a number of food recalls and can survive on stainless steel for days. Results suggest copper alloys will be useful beyond food processing applications.

Copper and copper alloys are engineering materials that are durable, colourful and recyclable and are widely available in various product forms suitable for a range of manufacturing purposes. Copper and its alloys offer a suite of materials for designers of functional, sustainable and cost-effective products.

Copper and certain copper alloys have intrinsic antimicrobial properties (so-called ‘Antimicrobial Copper’) and products made from these materials have an additional, secondary benefit of contributing to hygienic design. Products made from Antimicrobial Copper are a supplement to, not a substitute for standard infection control practices. It is essential that current hygiene practices are continued, including those related to the cleaning and disinfection of environmental surfaces.

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