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

Authors:
  • Ministry of Health,Greece

Abstract

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. for their expert
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© TOUCH BRIEFINGS 2011
Healthcare-associated Infections
The Role of Antimicrobial Copper Surfaces in
Reducing Healthcare-associated Infections
Panos A Efstathiou
Orthopedic Surgeon and Secretary General, Hellenic College of Orthopedic Surgeons
Abstract
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.
Keywords
Antimicrobial, copper, environment, HCAI, ICU, infection rate, nosocomial infections, public health
Disclosure: Panos Efstathiou provides consultancy on the antimicrobial properties of copper to the Hellenic Copper Development Institute.
Acknowledgements: The author thanks Evangelia Kouskouni, Katerina Karageorgou, Agapi Vilaeti, Zaharoula Manolidou, Maria Tseroni and Joanna Agrafa for their expert
advice on the Greek studies.
Received: 8 July 2011 Accepted: 1 August 2011 Citation: European Infectious Disease, 2011;5(2):125–8
Correspondence: Panos A Efstathiou, Artis 17, Amarousio PC 15125, Greece. E: panosefstathiou@usa.net
Support: The publication of this article was funded by the Copper Development Association.
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.1More 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 2008.4This 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
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126
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)
copper_development_AC_070811_v1_EU Infectious 08/09/2011 15:29 Page 126
The Role of Antimicrobial Copper Surfaces in Reducing Healthcare-associated Infections
EUROPEAN INFECTIOUS DISEASE 127
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. n
Figure 1: Intensive Care Unit at Sloane Kettering Memorial
Hospital, One of the Three Hospitals in the Multicentre US
Clinical Trial, with Copper Components Installed
Figure 2: Comparative Bacterial Load on Copper and
Standard Key Touch Surfaces in US Trial21 (for all
Rooms, over 197 Weeks’ Sampling)
7,000
6,000
5,000
4,000
3,000
2,000
1,000
0
CFU/100cm2
Bedrail Call button Chair arm Tray table Monitor IV pole
6,517
4,851
374
962 677 305 326 132
2,818
691 955
226
Standard components
(plastic, stainless steel,
wood, chrome, laminate)
Copper components
CFU = colony-forming units, IV = intravenous.
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in respiratory therapy apparatus,
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health care-associated infections and deaths in U.S.
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copper_development_AC_070811_v1_EU Infectious 08/09/2011 15:30 Page 128
... Copper is the only hard surface metal that has received approval by the EPA and this approval has now been given to nearly 300 different copper alloys. This is an important step for the protection of public health and hospital environment issues [4]. According to our results, 63 % copper alloy had compatible results for P. aeruginosa. ...
... Limited hospital trials have demonstrated that significant reductions in nosocomial infections were observed when copper alloys were used in hospital settings [21]. Further to the laboratory and clinical research results, there is now a great interest in producing objectives that will be used by manufacturers in high nosocomial areas like ICUs and medical wards [4]. ...
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... Preliminary assessment of these unpublished data suggests that significant reductions in HCAI were observed when copper alloys were used in an ICU setting. 43 Hospital trials in Japan, South Africa, Greece and Chile are underway and it is possible that results from these trials may provide further evidence in this regard. 22,43 Concerns also arise with regard to the lack of clinical trials assessing the role of copper contact surfaces in eradicating anaerobic spores, especially C. difficile. ...
... 43 Hospital trials in Japan, South Africa, Greece and Chile are underway and it is possible that results from these trials may provide further evidence in this regard. 22,43 Concerns also arise with regard to the lack of clinical trials assessing the role of copper contact surfaces in eradicating anaerobic spores, especially C. difficile. As the decontamination of surfaces exposed to C. difficile spores is challenging for conventional cleaning methods, the beneficial effects of copper contact surfaces may have a significant impact. ...
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The antimicrobial effect of copper has long been recognized and has a potential application in the healthcare setting as a mechanism to reduce environmental contamination and thus prevent healthcare-associated infection (HCAI). To review the rationale for copper use, the mechanism of its antimicrobial effect, and the evidence for its efficacy. A PubMed search of the published literature was performed. Extensive laboratory investigations have been carried out to investigate the biocidal activity of copper incorporated into contact surfaces and when impregnated into textiles and liquids. A limited number of clinical trials have been performed, which, although promising, leave significant questions unanswered. In particular there is a lack of consensus on minimum percentage copper alloys required for effectiveness, the impact of organic soiling on the biocidal effect of copper, and the best approach to routine cleaning of such surfaces. Limited information is available on the ability of copper surfaces to eradicate spores of Clostridium difficile. Additional studies to demonstrate that installing copper surfaces reduces the incidence of HCAI are required and the cost-effectiveness of such intervention needs to be assessed. Further research in a number of key areas is required before the potential benefits of using copper routinely in the clinical setting to prevent and control infection can be confirmed and recommended.
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... All these cited studies and others (Efstathiou 2011;Gould et al., 2009;Rai et al., 2012) highlight the fact that copper used in hospital furniture and accessories could be an interesting antimicrobial agent for the reduction of environmental bioburdens, nevertheless, the impact on HAI incidence needs to be confirmed by welldesigned epidemiological intervention studies. ...
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Aim Aim of this study was to evaluate the reduction on Intensive Care Unit (ICU) microbial flora after the antimicrobial copper alloy (Cu+) implementation as well as the effect on financial – epidemiological operation parameters. Methods Medical, epidemiological and financial data into two time periods, before and after the implementation of copper (Cu 63 % – Zn 37 %, Low Lead) were recorded and analyzed in a General ICU. The evaluated parameters were: the importance of patients’ admission (Acute Physiology and Chronic Health Evaluation – APACHE II and Simplified Acute Physiology Score – SAPS), microbial flora’s record in the ICU before and after the implementation of Cu+ as well as the impact on epidemiological and ICU’s operation financial parameters. Results During December 2010 and March 2011 and respectively during December 2011 and March 2012 comparative results showed statistically significant reduction on the microbial flora (CFU/ml) by 95 % and the use of antimicrobial medicine (per day per patient) by 30 % (p = 0.014) as well as patients hospitalization time and cost. Conclusions The innovative implementation of antimicrobial copper in ICUs contributed to their microbial flora significant reduction and antimicrobial drugs use reduction with the apparent positive effect (decrease) in both patients’ hospitalization time and cost. Under the present circumstances of economic crisis, survey results are of highest importance and value.
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Survival of pathogens on touch surfaces contributes to increasing incidence and spread of antibiotic resistance and infection in hospitals. One way to address this could be to use biocidal surfaces in conjunction with improved cleaning regimes. Exposure to moist copper alloy surfaces, to simulate fomite contamination, resulted in a rapid kill of significant bacterial, viral and fungal pathogens. We now report studies on dry surfaces with a range of pathogens to elucidate the antimicrobial mechanism.
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Contaminated touch surfaces have been implicated in the spread of hospital-acquired infections, and the use of biocidal surfaces could help to reduce this cross-contamination. In a previous study we reported the death of aqueous inocula of pathogenic Enterococcus faecalis or Enterococcus faecium isolates, simulating fomite surface contamination, in 1 h on copper alloys, compared to survival for months on stainless steel. In our current study we observed an even faster kill of over a 6-log reduction of viable enterococci in less than 10 min on copper alloys with a "dry" inoculum equivalent to touch contamination. We investigated the effect of copper(I) and copper(II) chelation and the quenching of reactive oxygen species on cell viability assessed by culture and their effects on genomic DNA, membrane potential, and respiration in situ on metal surfaces. We propose that copper surface toxicity for enterococci involves the direct or indirect action of released copper ionic species and the generation of superoxide, resulting in arrested respiration and DNA breakdown as the first stages of cell death. The generation of hydroxyl radicals by the Fenton reaction does not appear to be the dominant instrument of DNA damage. The bacterial membrane potential is unaffected in the early stages of wet and dry surface contact, suggesting that the membrane is not compromised until after cell death. These results also highlight the importance of correct surface cleaning protocols to perpetuate copper ion release and prevent the chelation of ions by contaminants, which could reduce the efficacy of the surface.
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The oligodynamic effects of introducing copper into large reservoir nebulizers used in respiratory therapy has resulted in the nebulizer contents remaining in a sterile state. A closed filling system of this type apparatus is required so that no contamination takes place by unsterile hands. Blood copper levels carried out on patients receiving IPPB revealed essentially normal levels. The addition of a copper bactericidal trap on the exhaled side of the circuit results in a significant reduction in the contamination of air and the patient's environment with patient pathogenic organisms, and reduces the chances of cross infection. The apparent incidence of pulmonary infection in patients in our intensive care unit is also reduced.