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Introduction to Antimicrobial Copper Healthcare-Associated Infection (HCAIs) place a significant socioeconomic burden as it effects millions of people from all regions of the world.
In the EU approximately four million people acquire HCAIs each year with approximately 37,000 dying.
The UK reported 300,000 cases of infections in hospitals each year resulting in nearly 5,000 deaths.
In addition to the immeasurable personal costs, the Office for National Statistics (ONS) estimates the direct cost of HCAIs to be £1 billion per year. These infections – such as MRSA and C. difficile – are caused by microbes that thrive on objects we touch every day.
Antibiotic-resistant organisms spread from the healthcare environment to schools, homes and mass transit. Despite aggressive hand washing campaigns and routine cleaning, infection rates remain unacceptably high and more needs to be done to lower the risk of infection and improve patient safety.
Antimicrobial Copper kills the microbes that cause these infections.
Now there is a new weapon in the fight against the microbes that cause these deadly infections: Antimicrobial Copper.
With broad-spectrum and rapid efficacy, Antimicrobial Copper has been shown to kill pathogenic microbes in the laboratory and the clinical environment, significantly and continuously reducing bacteria.
With recent clinical trial data showing key touch surfaces made from Antimicrobial Copper can reduce a patient’s risk of acquiring an HCAI; it has been shown that these antimicrobial products, as part of contemporary hospital architecture and design, can improve infection prevention and control in hospitals.
Antimicrobial Copper is the only solid metal touch surface to have efficacy data independently verified through the US Environmental Protection Agency (EPA) registration, which supports its claim to continuously kill more than 99.9% of the bacteria* that cause HCAIs, within two hours of contact.
e most effective antimicrobial touch surface and has sparked a global campaign advocating the use of these materials to combat infectious microbes in healthcare facilities, mass transit, educational institutions and beyond.
Three main characteristics make Antimicrobial Copper the most effective touch surface material:
Continuously kills microbes
- Efficacy as an antimicrobial is scientifically proven to be far more effective than silver-containing coatings
- Proven to continuously kill the microbes that cause infections
- The only solid metal touch surface approved by the US Environ mental Protection Agency (EPA).
Never wears out
- Continuous and ongoing antimicrobial action
- Remains effective even after repeated wet and dry abrasion and re-contaminationNatural oxidation does not impair efficacy.
Safe to use
- Not harmful to people or the environment
- Inherently antimicrobial, no chemicals added
- Completely recyclable.
Copper and copper alloys are engineering materials that are durable, colourful and recyclable. They 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-called͚ Antimicrobial Copper͛) so 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.
*Laboratory testing shows that, when cleaned regularly, antimicrobial copper surfaces kill greater than 99.9% of the following bacteria within 2 hours of exposure: MRSA, VRE, Staphylococcus aureus, Enterobacter aerogenes, Pseudomonas aeruginosa, and E. coli O157:H7.
Antimicrobial copper surfaces are a supplement to and not a substitute for standard infection control practices and have been shown to reduce microbial contamination, but do not necessarily prevent cross contamination or infections; users must continue to follow all current infection control practices.
Science suggests that Antimicrobial Copper kills bacteria with a rapid multifaceted attack. The mechanisms by which solid copper damages and destroys bacteria and viruses is still being studied but sufficient work has been done to confirm the broad spectrum efficacy of the metal and its alloys such as brass and bronze.
Importantly, even under the dry-touch conditions of a typical indoor environment, copper is able to permanently inactivate pathogens. By interacting with the cell structure, copper initiates a series of cascading events, including rapidly interrupting normal functions and compromising cell membrane integrity. This allows copper to enter the microbe structure and totally overwhelm the metabolism. The final stage is the breaking down of genomic material.
As a whole, these numerous and complex reactions mean that resistance to copper alloys is extremely unlikely to be developed.
Mechanism of Action of Antimicrobial Copper
Many researchers have studied the mechanism of action related to the contact killing of bacteria when placed on copper alloy surfaces. In order to illustrate the variety of theories and the complexity of copper contact killing mechanism, the following previously published list of examples of modes of action proposed by various researches is reproduced below:
- The 3-dimensional structure can be altered by copper so that the proteins can no longer perform their normal functions. The result is inactivation of bacteria or viruses².
- Copper complexes form radicals that inactivate viruses.
- Copper may disrupt enzyme structures, and functions by binding to sulphur- or carboxylate-containing groups and amino groups of proteins.
- Copper may interfere with other essential element take-up, such as zinc and iron.
- Copper facilitates deleterious activity in superoxide radicals. Repeated redox reactions on site-specific macromolecules generate OH- radicals, thereby causing ‘multiplehit damage’ at target sites.
- Copper can interact with lipids, causing their peroxidation and opening holes in the cell membranes, thereby compromising the integrity of cells. This can cause leakage of essential solutes, which in turn, can have a desiccating effect.
- Copper damages the respiratory chain in Escherichia coli cells and is associated with impaired cellular metabolism.
- Faster corrosion correlates with faster inactivation of micro organisms. This may be due to increased availability of cupric ion, Cu2+, which is believed to be responsible for the antimicrobial action.
- In inactivation experiments on the flu strain, H1N1, which is nearly identical to the H5N1 avian strain and the 2009 H1N1 (swine flu) strain, researchers hypothesized that copper͛s antimicrobial action probably attacks the overall structure of the virus and therefore has a broad-spectrum effect.
- Microbes require copper-containing enzymes to drive certain vital chemical reactions. Excess copper, however, can affect proteins and enzymes in microbes, thereby inhibiting their activities. Researchers believe that excess copper has the potential to disrupt cell function both inside cells and in the interstitial spaces between cells, probably acting on the cells͛ outer envelope.
In addition, a review article, focusing on copper͛s mode of action in bacteria presents an overview of these mechanisms.
However no single mechanism is broadly accepted. The possibilities are complex and multi-faceted. Clearly, studies of these mechanisms should be viewed as ongoing works in progress and to propose a specific mechanism is premature. Copper killing mechanisms need additional investigation and are expected to show different and complex interactions in different organism types.
Let us look at a bacterial cell and explore how copper could act on it.
I) Copper acts on the cell membrane:
Inaddition to a number of types of capsules or walls that lie outside the cell itself, bacterial cells have a cell membrane composed of a lipid matrix embedded with proteins.
The role of the cell membrane is to provide a crucially important barrier between the cell͛s interior and its environment and regulate what enters and leaves the cell. Large numbers and types of proteins are exposed at the outer or inner surface of the membrane and some penetrate across the membrane and are exposed on both surfaces.
Maintenance of this complex structure and its proteins is essential for the life of the cell.
It is suggested that the production of oxidative species, via a Fenton type reaction, causes a loss in cell membrane integrity. Extensive membrane damage is observed within minutes and cells removed from copper surfaces show a loss of cell integrity.
This loss in integrity, in turn, is expected to disrupt energy production via respiration (in bacteria the respiratory enzymes are cell membrane proteins), as well as a loss in control of the movement of water, ions– for example of hydrogen, sodium and potassium – as well as nutrients like sugar and amino acids.
In addition, this damage to membrane integrity causes distortions in the membrane that potentially stimulate stress signals resulting in the activation of enzymes inside the cell that then degrade in tracellular molecules including DNA, RNA and perhaps proteins. Finally, complete and extensive disruption of membrane structure could result in bursting of the cell membrane and the release of cellular contents.
II) Copper also enters the cell:
Cells have multiple mechanisms to protect against harmful intracellular levels of copper. These include pumping copper out of the cell (efflux) and combining it harmlessly (sequestering it) in protein complexes. Most of these mechanisms require energy, which may not be available in a cell with a compromised membrane. In addition, ͞ inappropriate ͟ binding of copper to specific proteins (enzymes) could lead to structural changes, loss-of-function, and/or stimulation of protein destruction. When a lethal dose level is reached, copper seems to interfere with normal cell functions, such as cell metabolism, and causes irreversible and complete destruction to the extent that the cells are non-viable.
It is suggested that the primary effects of exposure to copper alloy surfaces are those that occur at the cell membrane and that DNA disintegration is a secondary effect. As evidence that DNA degradation is secondary, researchers demonstrated that, in a 60% Cu alloy, no survivors were found after 45 minutes of exposure, but the genomic DNA was intact. The viewpoint that DNA degradation is a secondary effect, is not universally accepted. Ultimately, this discrepancy, which may vary by organism and the copper content of the alloy it is placed upon, will only be resolved by additional research data. However, all agree that copper kills bacteria and that all of the above cascading events lead to rapid and irreversible cell death in bacteria.
The terms ‘copper resistant’ and ‘copper sensitive’ are used to describe mutant strains exhibiting altered ability to grow in aqueous solutions of different concentrations of copper.
One important question is whether the mechanism of resistance to dissolved copper in aqueous solutions is relevant to the copper killing seen on dry surfaces.
In an investigation of copper-resistance and copper-sensitive mutant stains of E.coli, it was found that the sensitive strain lacking a specific copper detoxification system showed only a slight increase in sensitivity when exposed to two copper alloys surfaces containing either 60% or 65% copper.
In contrast, the copper-resistant strain, which expresses enhanced levels of the copper detoxification system, shows no improvement in survival on these copper alloy surfaces and, in fact, may be slightly more sensitive.
These findings strongly suggest that copper resistance and the copper detoxification systems play a minor role, if any, in the ability of dry copper alloy surfaces to kill bacteria.
To be more specific, the term ‘copper resistance’ is not applicable to the killing observed on dry copper alloy surfaces. It is important to note that copper is an essential nutrient and required for several metabolic functions, but is toxic when internal copper levels become excessive.
Thus, cells must tightly regulate internal copper levels and have evolved several mechanisms for doing this. Copper resistant strains have enhanced these mechanisms and are better able to cope with higher levels of copper within the cell. In contrast, antibiotics play no role in bacterial metabolism or reproduction. Normal bacteria are highly sensitive to even low levels of these metabolic poisons.
Antibiotic resistant strains are able to bypass the toxic effect of antibiotics and reproduce even in the presence of the antibiotic. Thus, copper resistance and antibiotic resistance are not comparable. Copper, however, may have a role in combating the evolution of antibiotic-resistant bacteria by continuously reducing the environmental reservoirs of microbes which otherwise act as breeding grounds for mutant forms.
Viruses are referred to as obligate parasites. Thus, they cannot complete their life cycle without exploiting a suitable host. They consist of a set of reproduction instructions (DNA or RNA) encased in a capsule (capsid) that is capable of gaining entry into the host cell. The host cells͛ metabolic systems are then used for producing more viruses.
However, copper alloys can permanently and irreversibly inactivate viruses and thus may have the potential to significantly decrease their pathobiological consequences, probably by disrupting their ability to invade host cells.
The data suggests that, in murine norovirus, an RNA virus, that capsid integrity is compromised upon contact with copper resulting in irreversible and permanent inactivation of the viral particles. In a subsequent study, a strain of human coronavirus, also an RNA virus, was shown to be inactivated by copper alloy contact. Taken together, these studies suggest that copper alloy surfaces might exhibit antiviral activity against other important RNA viruses for which transmission via touch surfaces is important, including virulent respiratory viruses and Ebola virus. Other types of viruses, including DNA viruses, could also be sensitive to copper alloy surface exposure and continued investigations in this area are essential.
Since prehistoric times copper has been an essential metal, both in is pure state or used in the creation of copper alloys such as brass and bronze, bronze was so popular that one of the major “ages͟” or stage of human history was named after this copper alloy, the Bronze Age.
Copper and its alloys have been very important for many civilisations including, the Ancient Egyptians, the Romans, the Chinese and modern civilisation.
There are many references and artefacts that can be researched, some dating back to 8,000 B.C.
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