Copper and its alloys (brasses,
bronzes, cupronickel, copper-nickel-zinc, and others) are natural antimicrobial
materials. Ancient civilizations exploited the antimicrobial properties of
copper long before the concept of microbes became understood in the nineteenth
century. In addition to several copper medicinal preparations, it was also
observed centuries ago that water contained in copper vessels or transported in
copper conveyance systems was of better quality (i.e., no or little visible
slime formation) than water contained or transported in other materials.
The antimicrobial properties of
copper are still under active investigation. Molecular mechanisms responsible
for the antibacterial action of copper have been a subject of intensive research.
Scientists are also actively demonstrating the intrinsic efficacies of copper
alloy "touch surfaces" to destroy a wide range of microorganisms that
threaten public health.
Mechanisms of antibacterial action
of copper
The oligodynamic effect was discovered
in 1893 as a toxic effect of metal ions on living cells, algae, molds, spores,
fungi, viruses, prokaryotic and eukaryotic microorganisms, even in relatively
low concentrations. This antimicrobial effect is shown by ions of copper as
well as mercury, silver, iron, lead, zinc, bismuth, gold, and aluminium.
In 1973, researchers at Battelle
Columbus Laboratories conducted a
comprehensive literature, technology and patent search that traced the history
of understanding the “bacteriostatic and sanitizing properties of copper and
copper alloy surfaces” which demonstrated that copper, in very small
quantities, has the power to control a wide range of molds, fungi, algae and
harmful microbes. Of the 312 citations mentioned in the review across the time period
1892–1973, the observations below are noteworthy:
Copper inhibits Actinomucor elegans, Aspergillus niger, Bacterium
linens, Bacillus megaterium, Bacillus subtilis, Brevibacterium erythrogenes,
Candida utilis, Penicillium chrysogenum, Rhizopus niveus, Saccharomyces
mandshuricus, and Saccharomyces cerevisiae in concentrations above 10 g/L.
Torulopsis utilis is completely inhibited at 0.04 g/L copper
concentrations.
Tubercle bacillus is inhibited by copper as simple cations or complex
anions in concentrations from 0.02 to 0.2 g/L.
Achromobacter fischeri and Photobacterium phosphoreum growth is inhibited
by metallic copper.
Paramecium caudatum cell division is reduced by copper plates placed on
Petri dish covers containing infusoria and nutrient media.
Poliovirus is inactivated within 10 minutes of exposure to copper with
ascorbic acid.
A subsequent paper probed some of copper’s antimicrobial
mechanisms and cited no fewer than 120 investigations into the efficacy of
copper’s action on microbes. The authors noted that the antimicrobial
mechanisms are very complex and take place in many ways, both inside cells and
in the interstitial spaces between cells.
Examples of some of the molecular
mechanisms noted by various researchers include the following:
The 3-dimensional structure of proteins can be altered by copper, so
that the proteins can no longer perform their normal functions. The result is
inactivation of bacteria or viruses
Copper complexes form radicals that inactivate viruses.
Copper may disrupt enzyme structures, and functions by binding to
sulfur- or carboxylate-containing groups and amino groups of proteins.
Copper may interfere with other essential elements, such as zinc and
iron.
Copper facilitates deleterious activity in superoxide radicals. Repeated
redox reactions on site-specific macromolecules generate OH- radicals, thereby
causing “multiple hit 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 microorganisms.
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 copper’s 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 cells’ outer envelope.
Currently, researchers believe
that the most important antimicrobial mechanisms for copper are as follows:
Elevated copper levels inside a cell causes oxidative stress and the
generation of hydrogen peroxide. Under these conditions, copper participates in
the so-called Fenton-type reaction — a chemical reaction causing oxidative
damage to cells.
Excess copper causes a decline in the membrane integrity of microbes,
leading to leakage of specific essential cell nutrients, such as potassium and
glutamate. This leads to desiccation and subsequent cell death.
While copper is needed for many protein functions, in an excess
situation (as on a copper alloy surface), copper binds to proteins that do not
require copper for their function. This “inappropriate” binding leads to
loss-of-function of the protein, and/or breakdown of the protein into
nonfunctional portions.
These potential mechanisms, as
well as others, are the subject of continuing study by academic research
laboratories around the world.
Antimicrobial efficacy of copper
alloy touch surfaces
Copper alloy surfaces have
intrinsic properties to destroy a wide range of microorganisms. In the interest
of protecting public health, especially in healthcare environments with their
susceptible patient populations, an abundance of peer-reviewed antimicrobial
efficacy studies have been conducted in the past 10 years regarding copper’s
efficacy to destroy E. coli O157:H7, methicillin-resistant Staphylococcus
aureus (MRSA), Staphylococcus, Clostridium difficile, influenza A virus,
adenovirus, and fungi. Stainless steel was also investigated since it is such
an important surface material in today’s healthcare environments. The studies
cited here, plus others directed by the United States Environmental Protection
Agency, resulted in the 2008 registration of 274 different copper alloys as
certified antimicrobial materials that have public health benefits.
E. coli
E. coli O157:H7 is a potent,
highly infectious, ACDP (Advisory Committee on Dangerous Pathogens, UK) Hazard
Group 3 foodborne and waterborne pathogen. The bacterium produces potent toxins
that cause diarrhea, severe aches and nausea in infected persons. Symptoms of
severe infections include hemolytic colitis (bloody diarrhea), hemolytic uremic
syndrome (kidney disease), and death. E. coli O157:H7 has become a serious
public health threat because of its increased incidence and because children up
to 14 years of age, the elderly, and immunocompromised individuals are at risk
of incurring the most severe symptoms.
Efficacy on copper surfaces
Recent studies have shown that
copper alloy surfaces kill E. coli O157:H7. Over 99.9% of E. coli microbes are
killed after just 1–2 hours on copper. On stainless steel surfaces, the
microbes can survive for weeks.
Results of E. coli O157:H7
destruction on an alloy containing 99.9% copper (C11000) demonstrate that this
pathogen is rapidly and almost completely killed (over 99.9% kill rate) within
ninety minutes at room temperature (20 °C). At chill temperatures (4 °C), over
99.9% of E. coli O157:H7 are killed within 270 minutes. E. coli O157:H7
destruction on several copper alloys containing 99%–100% copper (including
C10200, C11000, C18080, and C19700) at room temperature begins within minutes.
At chilled temperatures, the inactivation process takes about an hour longer.
No significant reduction in the amount of viable E. coli O157:H7 occurs on
stainless steel after 270 minutes.
Studies have been conducted to
examine the E. coli O157:H7 bactericidal efficacies on 25 different copper
alloys to identify those alloys that provide the best combination of
antimicrobial activity, corrosion/oxidation resistance, and fabrication
properties. Copper’s antibacterial effect was found to be intrinsic in all of
the copper alloys tested. As in previous studies, no antibacterial properties
were observed on stainless steel (UNS S30400). Also, in confirmation with
earlier studies the rate of drop-off of
E. coli O157:H7 on the copper alloys is faster at room temperature than at
chill temperature.
For the most part, the bacterial
kill rate of copper alloys increased with increasing copper content of the
alloy.This is further evidence of copper’s intrinsic antibacterial properties.
Efficacy on brass, bronze,
copper-nickel alloys
Brasses, which were frequently
used for doorknobs and push plates in decades past, also demonstrate
bactericidal efficacies, but within a somewhat longer time frame than pure
copper. All nine brasses tested were almost completely bactericidal (over 99.9%
kill rate) at 20 °C within 60–270 minutes. Many brasses were almost completely
bactericidal at 4 °C within 180–360 minutes.
The rate of total microbial death
on four bronzes varied from within 50–270 minutes at 20 °C, and from 180 to 270
minutes at 4 °C.
The kill rate of E. coli O157 on
copper-nickel alloys increased with increasing copper content. Zero bacterial
counts at room temperature were achieved after 105–360 minutes for five of the
six alloys. Despite not achieving a complete kill, alloy C71500 achieved a
4-log drop within the six-hour test, representing a 99.99% reduction in the
number of live organisms.
Efficacy on stainless steel
Unlike copper alloys, stainless
steel (S30400) does not exhibit any degree of bactericidal properties. This
material, which is one of the most common touch surface materials in the
healthcare industry, allows toxic E. coli O157:H7 to remain viable for weeks.
Near-zero bacterial counts are not observed even after 28 days of
investigation. Epifluorescence photographs have demonstrated that E. coli
O157:H7 is almost completely killed on copper alloy C10200 after just 90
minutes at 20 °C; whereas a substantial number of pathogens remain on stainless
steel S30400.
MRSA
Methicillin-resistant
Staphylococcus aureus (MRSA) is a dangerous bacteria strain because it is
resistant to beta-lactam antibiotics. Recent strains of the bacteria, EMRSA-15
and EMRSA-16, are highly transmissible and durable. This is of extreme
importance to those concerned with reducing the incidence of hospital-acquired
MRSA infections.
In 2008, after evaluating a wide
body of research mandated specifically by the United States Environmental
Protection Agency (EPA), registration approvals were granted by EPA in 2008
granting that copper alloys kill more than 99.9% of MRSA within two hours.
Subsequent research conducted at
the University of Southampton (UK) compared the antimicrobial efficacies of
copper and several non-copper proprietary coating products to kill MRSA. At 20
°C, the drop-off in MRSA organisms on copper alloy C11000 is dramatic and
almost complete (over 99.9% kill rate) within 75 minutes. However, neither a
triclosan-based product nor two silver-containing based antimicrobial
treatments (Ag-A and Ag-B) exhibited any meaningful efficacy against MRSA.
Stainless steel S30400 did not exhibit any antimicrobial efficacy.
In 2004, the University of
Southampton research team was the first to clearly demonstrate that copper
inhibits MRSA.[35] On copper alloys — C19700 (99% copper), C24000 (80% copper),
and C77000 (55% copper) — significant reductions in viability were achieved at
room temperatures after 1.5 hours, 3.0 hours and 4.5 hours, respectively.
Faster antimicrobial efficacies were associated with higher copper alloy
content. Stainless steel did not exhibit any bactericidal benefits.
Clostridium difficile
Clostridium difficile, an
anaerobic bacterium, is a major cause of potentially life-threatening disease,
including nosocomial diarrheal infections, especially in developed countries.
C. difficile endospores can survive for up to five months on surfaces. The
pathogen is frequently transmitted by the hands of healthcare workers in
hospital environments. C. difficile is currently a leading hospital-acquired
infection in the UK, and rivals MRSA as the most common organism to cause
hospital acquired infections in the US It is responsible for a series of
intestinal health complications, often referred to collectively as Clostridium
difficile Associated Disease (CDAD).
The antimicrobial efficacy of
various copper alloys against Clostridium difficile was recently evaluated.[40]
The viability of C. difficile spores and vegetative cells were studied on
copper alloys C11000 (99.9% copper), C51000 (95% copper), C70600 (90% copper),
C26000 (70% copper), and C75200 (65% copper). Stainless steel (S30400) was used
as the experimental control. The copper alloys significantly reduced the
viability of both C. difficile spores and vegetative cells. On C75200, near
total kill was observed after one hour. On C11000, near total kill was observed
after 3 hours. On C70600, near total kill was observed after 5 hours. On
C26000, near total kill was achieved after 48 hours. On stainless steel, no
reductions in viable organisms were observed after 72 hours (3 days) of
exposure and no significant reduction was observed within 168 hours (1 week).
Influenza A
Influenza, commonly known as flu,
is an infectious disease from a viral pathogen different from the one that
produces the common cold. Symptoms of influenza, which are much more severe
than the common cold, include fever, sore throat, muscle pains, severe
headache, coughing, weakness and general discomfort. Influenza can cause
pneumonia, which can be fatal, particularly in young children and the elderly.
After incubation for one hour on
copper, active influenza A virus particles were reduced by 75%. After six
hours, the particles were reduced on copper by 99.999%. Influenza A virus was
found to survive in large numbers on stainless steel.
Once surfaces are contaminated
with virus particles, fingers can transfer particles to up to seven other clean
surfaces. Because of copper’s ability to destroy influenza A virus particles,
copper can help to prevent cross-contamination of this viral pathogen.
Adenovirus
Adenovirus is a group of viruses
that infect the tissue lining membranes of the respiratory and urinary tracts,
eyes, and intestines. Adenoviruses account for about 10% of acute respiratory
infections in children. These viruses are a frequent cause of diarrhea.
In a recent study, 75% of
adenovirus particles were inactivated on copper (C11000) within 1 hour. Within
six hours, 99.999% of the adenovirus particles were inactivated. Within six
hours, 50% of the infectious adenovirus particles survived on stainless steel.
Fungi
The antifungal efficacy of copper
was compared to aluminium on the following organisms that can cause human
infections: Aspergillus spp., Fusarium spp., Penicillium chrysogenum,
Aspergillus niger and Candida albicans. An increased die-off of fungal spores
was found on copper surfaces compared with aluminium. Aspergillus niger growth
occurred on the aluminium coupons; growth was inhibited on and around copper
coupons.
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