Health Estate Journal highlights the contrasting claims made by both “sides”, and reports on two recent studies in particular, one expounding the advantages of copper, and the other painting an equally positive picture for silver. With silver ion and copper alloybased antibacterial materials’ proponents each vigorously promoting their respective technologies, a recent scientific study (Effects of temperature and humidity on the efficacy of methicillin-resistant Staphylococcus aureus challenged antimicrobial materials containing silver and copper) by personnel including a top UK microbiologist compared the effectiveness of silver ion, copper alloy, and stainless steel surfaces in combating bacteria at what the researchers claimed were temperatures in the order of those typically encountered in hospitals. According to the UK-based Copper Development Association (CDA), the study vindicated the copper community’s claims that copper alloy-based surfaces and materials are “more effective” than those incorporating silver ions in combating bacteria in a “real-world hospital” environment. Carried out with support from the International Copper Association and the US-based Copper Development Association Inc, the study was undertaken by three individuals – Harold T Michels, senior vice-president of technology and technology services at the Copper Development Association Inc, Dr Jonathan Noyce, a post-doctoral research fellow in microbiology at the University of Southampton, and Professor C.W (Bill) Keevil, head of the microbiology group and director of the environmental healthcare unit at the same university. The testing was undertaken in the university’s own microbiology laboratories, and the results first appeared in a recent issue of Letters in Applied Microbiology. The CDA, which issued a press release shortly after the study’s publication highlighting the results, and in particular (from its standpoint) the silver technology’s apparent shortcomings in the testing, said the research was especially noteworthy as the first to test the anti-bacterial efficacy of silver ion-containing materials “at the lower temperature and humidity levels typical of indoor environments, such as those found in hospitals”, rather than at the high temperatures (of around 35°C) and high humidity (90% or higher relative humidity) typically used in previous tests. Angela Vessey, Copper Development Association director-general, said the CDA’s view was that many of the tests demonstrating silver’s anti-microbial effectiveness to date had been undertaken “purely in laboratory conditions and not under real-life hospital conditions, generally in a high humidity, high temperature environment”. In contrast this study, the CDA claims, saw the competing metals “tested at similar temperatures and humidities to those encountered in a typical hospital”.
Metal comparisons
Testing of the survival rates of MRSA on two types of silver-ion coated surfaces, five copper alloy surfaces, and a stainless steel surface, the CDA press statement said, showed “only minimal bacterial reduction” at 20°C and 22° humidity with the silver ion tested. Meanwhile the stainless steel, which served as the “experimental control”, showed “no measurable antimicrobial efficacy at any temperature or humidity level”. The CDA said the researchers had used copper alloys as a point of comparison because laboratory testing had shown that they are “effective in reducing over 99% of bacteria within two hours at room temperature (22°C) and normal humidity”. The authors concluded, following the tests, that “the high efficacy levels displayed by the copper alloys, at temperature and humidity levels typical of indoor environments, compared to the low efficacy of the silver ion-containing material under the same conditions, favours the use of copper alloys as antimicrobial materials in indoor environments such as hospitals”. Professor Bill Keevil, who led the research, elaborated: “Much of the testing undertaken so far to try to prove the anti-microbial efficacy of silver ion coatings has been done at relative humidity levels of 90% or even greater, and at temperatures of up to 35°C, as stipulated in the Japanese JIS Z 2801 standard, which was established back in 2000 to test the efficacy of silver incorporated into hydrophobic plastic surfaces.”
No specific standard
The professor explained that the JIS Z 2801 protocols generally involve covering the surface on which the bacteria has been incorprtaed with a polyethylene film, resulting in testing being undertaken with high levels of humidity present. He said: “The trouble to date is that there has been no well-established specific standard for testing the antibacterial efficacy of metal coatings, an anomaly we are looking to address by talking to bodies including the BSI. “Over the past few years many of the tests that have been undertaken have been based on ISO standard ISO 22196:2007 (Plastics – Measurement of antibacterial activity on plastics surfaces), which took as its basis the Japanese JIS test protocols. However the high humidity levels and temperatures at which such testing is undertaken really do not represent a real-world hospital environment, where temperatures might typically be closer to 20-22°C and relative humidity around 50-60%. “Our latest study,” he continued, “involved testing both at the higher humidity and temperature levels, but also at real-world levels, and the conclusions merely reinforced what we already believed – that silver ionbased anti-bacterial technologies only really work well in wet, high humidity environments.” Using standard JIS Z 2801 methodology, the Southampton team’s study showed a >5 log reduction in MRSA viability after 24 hours at >90% relative humidity at 20°C and 35°C for a “silver ion-containing material”, but only a <0.3 log reduction at ~22% RH and 20°C and no reduction at ~22% RH and 35°C. Copper also reportedly demonstrated a >5 log reduction “under all test conditions”. Although the CDA claimed the findings were “pretty conclusive”, Wolverhampton-based antimicrobial technology specialist and anti-bacterial silver ion additive supplier BioCote, which shortly afterwards issued the “extremely positive” results of its own recent trial of silver ion technology in a Leicester nursing home, disagreed.
Complying with protocols
Richard Hastings, a BioCote microbiologist, said: “At BioCote our testing has always complied with ISO 22196, which sets out various protocols, one being that tests should be undertaken at higher humidities and temperatures. In the study the CDA has reported on most recently we would acknowledge that the silver ion did not appear to have shown the level of antibacterial effectiveness it does in a realworld environment. However our own independent laboratory tests paint an altogether different picture, as do several recent studies in hospital environments, such as those at the Heartlands Hospital in Birmingham,1 and at a Leicester nursing home.2 The results of both, published respectively in February and late September last year, and several other studies, prove quite categorically that silver ion-coated products have a strong anti-bacterial effect in healthcare environments. “Laboratory testing is certainly one way to evaluate a technology, but surely evidence that it will perform effectively in a real-world scenario is equally, if not even more, persuasive? All of our laboratory testing to date, as Professor Keevil rightly says, has been undertaken to ISO 22196 standards, but were to test in a lab to different parameters we would not be able to present our evidence in a credible manner. Suffice it to say that not only are there numerous peer-reviewed studies showing BioCote silver ion technology’s ‘real-world’ anti-bacterial credentials, but that the Leicester study was undertaken at around the 22% temperature and 50% RH levels the Copper Development Association advocates.” The nursing home study, on which BioCote issued its own press release in early October, is reportedly the first ever silver antimicrobial product trial carried out in a nursing home environment. The results, which were reported in the British Journal of Community Nursing,1 had, BioCote said, “revealed that levels of potentially deadly bacteria can be dramatically reduced using products treated with silver antimicrobial agents, creating cleaner and safer nursing homes for elderly residents across the UK”. The study took place at the nursing home during its refurbishment by Leicester City Council in 2007. One “residence”, comprising a bedroom and bathroom, was refitted with a range of (BioCote) silver anti-microbial treated products, while another was refurbished with untreated “comparable products” to serve as the control. Both units were occupied by single, long-term residents for the length of the study, and all products in the trial were cleaned according to the same regime; thus any levels of decontamination achieved by the antimicrobial products “was in addition to the effect of normal cleaning”.
Bacterial counts
During a five-month period 42 swabs were collected from each treated and untreated surface in the bedroom and bathroom of each residence and cultured for total counts of bacteria. Results showed that the average difference in bacterial counts between all treated products in the first unit and all untreated products in the control unit ranged from 23% for light switches and electrical sockets to 99% for beds, bins and moulded sheet tiles. The average difference in bacterial counts between all the BioCote-treated products in the test residence and all the untreated products sampled in the control residence was 94.8%. Items used in the research ranged from doors, door handles, architraves and radiator guards, to curtains, safety rails, wardrobes, soap dispensers, and bedding. Richard Hastings said the test results were “another clear signal that BioCote-treated products can be used alongside cleaning practices to help sustain low levels of bacteria on surfaces and in the wider healthcare environment”, adding that, “even more so”, since the introduction of the Health and Social Care Act 2008, and the establishment of new governing body, the Care Quality Commission, there was “a clear need and desire to break the chain of cross-contamination between sources of harmful bacteria and patients”. He said of the nursing home study: “By investing in peer-reviewed and published studies we are committed to leading and informing the debate around infection prevention and ensuring healthcare providers have the information they need to make informed and safe decisions.” Of the CDA’s claims for copper, and its “attempts to discredit silver-ion additives’ antibacterial efficacy”, he added: “There is no doubt that copper is effective as an antimicrobial, as are many other heavy metals. However we have doubts, in particular, over the considerable on-cost of adding it to many products and, of course, the metal will discolour over time. “As for the CDA’s attempts to rubbish silver’s anti-bacterial properties, we have plenty of scientific evidence to back up our claims, and the Association’s aim seems simply to be to undermine us. To be honest we are not overly concerned, although we applaud publication of properly conducted studies which enable people to make up their own minds about the various products and technologies available.”
A safe, ‘flexible’ material
BioCote says it works with a growing number of manufacturers of healthcare equipment and furniture to incorporate antimicrobial silver ion-based technology into its products, adding: “Silver is a safe, natural antimicrobial, commonly used in wound dressings and surface-coated catheters, and can be incorporated into a variety of materials, including plastics, fabrics, paints, powder coatings, and papers.” Richard Hastings explained that, on hearing the “basic description” of the latest copper study, the head of the independent microbiology laboratory BioCote uses for efficacy validation said he believed that, to achieve the low relative humidifies reported, both the sample and test bacteria must have been dried out. This, he, said, would result in loss of antimicrobial activity in both the silver and the copper. He was “surprised”, under these circumstances, at the level of copper “activity”. Southampton University’s Professor Keevil said he had not heard about the latest BioCote study, but believed that, for silver ion coatings to gain wider acceptance and similar credibility to copper alloys as an effective antibacterial tool in healthcare, the coatings would need to secure the same “high-level approval” from the US’s Environmental Protection Agency as had some 275 different copper alloys to date following the EPA’s rigorous testing. This was an achievement he said the proponents of silver coatings had so far sought to emulate, “but so far unsuccessfully”. Richard Hastings disagreed: “Registration with the EPA is, to my understanding, undertaken via submission of a company’s own data set, and merely allows a company or organisation to make certain healthrelated claims in its marketing about its products’ efficacy. Due to stipulations in the European Biocidal Products Directive, and because we wish to be able to continue selling our anti-bacterial coatings into the US, we will be seeking EPA registration, having so far, in fact, been somewhat put off by the rather convoluted registration process. In the meantime we are more than happy for potential BioCote customers to judge the anti-bacterial effectiveness of our coatings based on the wealth of evidence we already have.” A strong BioCote riposte then to the Copper Development Association’s recent reported research. However the CDA maintains that copper’s antimicrobial efficacy at room temperature and humidity against bacteria including MRSA, Clostridium difficile, Aspergillus niger fungi, and viruses (including Influenza A) has been demonstrated not just in the research reported in Letters in Applied Microbiology, but also in several other laboratory studies, with the material’s “exceptional” antimicrobial performance in the laboratory-based testing “under typical indoor conditions” leading, for example, to a series of ongoing clinical trials initiated in early 2007 at Birmingham’s Selly Oak Hospital. The first results, unveiled in October 2008, showed a 90-100% reduction in bioburden on copper alloy surfaces such as door handles, push plates, and toilet seats, compared with non-copper surfaces.
Three items replaced
The 10-week trial, reported in a paper in the Journal of Hospital Infection (2009), 1-6 [Casey A.L. et al, Role of copper in reducing hospital environment contamination, J Hosp Infect (2009), doi:10.1016/j.jhin.2009.08.018], was undertaken in a general ward at the hospital, and saw, initially, three specific items subject to frequent touching by patients and staff – tap handles, ward entrance door push plates, and toilet seats – measured twice a day for bacteria, with the items a combination of stainless steel and plastic components and copper replacements. Five weeks into the trial the copper-containing and non-copper-containing items were swapped over to “exclude the possibility of preferential use of particular items based on location”. Each item was sampled in duplicate at each time point, selecting adjacent areas so that no area was sampled twice in any one day. For each toilet seat and door push plate sample a sterile nasopharyngeal swab moistened in a sterile 0.9% (w/V) saline was firmly applied 15 times horizontally and 15 times vertically over a 5 cm x 5 cm area using a sterile plastic template. The same methodology was applied to the tap handles over a 5 cm x 2 cm area. The study found that the median number of micro-organisms harboured by the copper-containing items was between 90% and 100% lower than their control equivalents at both the 7.00 am and 5.00 pm testing points. Based on the median total aerobic colony-forming unit counts from the study period, five out of 10 control sample points, and zero out of 10 copper points, failed proposed “benchmark” values of a total aerobic count of <5 cfu/cm2. The trial was led by Professor Tom Elliott, the consultant medical microbiologist and deputy medical director at the University Hospitals Birmingham NHS Foundation Trust, and followed earlier laboratory work by Southampton University led by Professor Bill Keevil, which showed “exceptionally high levels” of MRSA bacteria were eliminated within 90 minutes on copper surfaces. Further research by the same Southampton team showed copper’s effectiveness in destroying C. difficile “within one or two days”.
Ongoing research
Last year, as part of the ongoing research at Selly Oak Hospital, two further trials, this time each three months long, were initiated, under which a wide range of items, such as over-bed tables, grab rails, light switches, door handles, and push plates incorporating both copper and silver ion surfaces, are being tested to gauge the materials’ anti-bacterial efficacy. After the first three-month testing, completed recently, copper surfaced items were replaced with items with silver ion coating and vice versa to ensure a thorough evaluation. The results of the latest trials are not expected until some time this year. Professor Tom Elliott told HEJ the latest trials will “provide data on which are the most heavily contaminated surfaces and therefore the highest priority for substituting with copper”. He says: “The longer time period gives a greater possibility of copper being challenged with a broader range of organisms”. Speaking at the recent Healthcare Estates conference and exhibition in Harrogate, Mark Tur, a technical consultant to the CDA, gave a little more detail on the Selly Oak trial, having first put the recent work in context by explaining that the University of Southampton study of copper and copper alloys’ anti-bacterial effectiveness had actually begun in 1994. He also cited several studies, including one undertaken in 1983 at Hamot Hospital, Pennsylvania (brass versus stainless steel doorknobs); another both in rural Punjab in India and at the University of Northumbria in 2005 (which showed that E. coli was eliminated in drinking water when stored in large brass “pots”), and another ongoing project study in Wandsbek in Germany, whose findings were still in draft, to back the CDA’s claims. He added that another study, by Professor Keevil’s Southampton team, comparing MRSA’s “viability” on a range of surfaces, including those made of copper, S30400, AgB, Agar and TS, showed the number of colony-forming units fell from around 100 million to close to zero in around 70 minutes on the copper surface, and remained at that level for the six-hour test. In contrast, levels of MRSA on the other surfaces “hardly fell”. (The test was conducted at a temperature of around 20°C with an ambient humidity of 40-50°C). Moving on to discuss the Selly Oak trial specifically, Mark Tur said that among the “hot spot” touch surface items where copper had replaced stainless steel or other materials in a 20-bed unit at Selly Oak (a number of items, such as sanitiser and call buttons, and soap and towel dispensers, were requested by staff to be replaced with copper variants but sourcing copper versions had so far proved problematical) were: door handles, push plates, thumb turns, cubicle locks, grab rails, hot and cold taps, toilet seats, switches, sockets, bed table tops, light pulls, cistern flush levers, dressings trolleys, commodes, and sink traps and wastes.
Minimal disruption
Aside from the initial trials’ indications that copper can significantly reduce bioburden, Mark Tur said another “major positive” was that the various copper fittings had all been installed by tradespeople – plumbers, electricians, fitters and porters – with no special training, and with “minimal disruption”. Speed of replacement had also been impressive; for example handles, locks, push plates and kick plates for a 20-bed unit had typically taken just 30 minutes each to fit; “electricals” 20 minutes each, and taps, traps, and wastes, around 2.5 hours each. Based on a 20-bed Nightingale ward with three siderooms and ancillary facilities, Mark Tur said the CDA’s calculations suggested that replacing all the fittings would cost around £15,000, with the copper items having an anticipated lifetime of over 30 years. In the case of “big cost” items, the current cost of replacing those made of “conventional materials” with copper alternatives showed “there remained work to do”; for example the difference between the cost of a “traditional” toilet seat and a copper replacement would be around £100, while a copper bed table would currently cost twice as much as a more conventional table. “However,” he added, “these are all prototypes, and if you consider that the cost of replacing the fittings at Selly Oak was only £6,000 extra based on a 20-bed unit, you have probably eliminated, in one hit, the cost of a single infection with this one investment.” Sharing the platform was BioCote’s Richard Hastings, who countered on behalf of silver’s proponents with his own references to scientific studies, for instance a study reported in Ural Nurs, 2008, April; 28 (2): 07-9, which described how a small rehabilitation hospital in Arkansas in the USA that had experienced problems with catheterassociated urinary tract infections found that using an ionic silver Foley catheter “dramatically reduced” the incidence of such infections among its patients. He also cited a study by Inoue Y. et al in Chem. Pharm. Bull 56 (5) 692-694 (2008), which revealed that “almost all cells lost their ability to form colonies after only five minutes of contact” when exposed to BioCote.
Lasting ‘for a lifetime’
The microbiologist reiterated the “proven anti-bacterial benefits” of inorganic silver, which he said would last for a product’s lifetime, and explained that silver and silver alloys’ anti-bacterial effectiveness had been proven in both in vitro testing, and in “real-world” trials such as that at the nursing home in Leicester. He re-affirmed that the Leicester and Heartlands Hospital, Birmingham (see panel above, “Getting to the heart of the matter” regarding the latter) trials undertaken on BioCote’s behalf had shown “very substantial” reductions in bacteria counts “on both products and in environments” when silver and silver alloy-coated products were substituted for “standard” items. One especially interesting finding from both was that untreated items in a treated environment appear to be less contaminated, suggesting reduced contamination also culminates in lower cross-contamination. A number of the conclusions are now being further analysed by the Centre for the Application of Advanced Materials in Infection Control, part of the Heartlands Research & Innovation Unit at Birmingham Heartlands Hospital. The team there is also considering such questions as what products appear to best reduce cross-contamination; is a surgical ward environment comparable to a an outpatient’s clinic, and how can the information gleaned best be harnessed to enhance cleaning and infection control strategies?
Historical legacy
In both copper and silver’s case, of course, any seasoned observer will know that each material’s anti-bacterial properties have been well-documented for many years. Given this historical legacy, and the extremely high priority placed on infection control in the NHS today, one might ask why only now are these properties really being harnessed, and their potential impact on combating a range of bacteria being recognised? With the NHS expected to face significant short-to-medium term financial pressure, the costs of deploying any new technology will inevitably determine whether, and how widely and quickly, it is taken up. However the proponents of both silver ion and copper alloy-based items point out that, not only is it hard to put a value on an individual’s health, but that, additionally, while today, for instance, some copper healthcare items might cost around twice as much as their “traditional” counterparts, such “on-costs” could fall significantly given wider-take up and the resulting economies of scale. The recent studies described in this article certainly offer convincing arguments for both copper alloy and silver as potent anti-bacterials, to the extent that hospitals and other healthcare facilities would surely do well to fully explore the advantages of each. Further study and research evidence in coming months, such as the results of the latest Selly Oak Hospital trials, should provide further food for thought, and, although more “futuristic” technologies like nanotechnology are increasingly emerging as potent rival “weapons” in the fight against HAIs, it would seem foolish to ignore the apparently considerable anti-bacterial potential of two metals whose destructive impact on bacteria has been recognised, and seized upon, around the world for centuries. If such anti-bacterial properties can indeed be harnessed and incorporated into a wide range of common hospital items, fixtures, and fittings, at a cost that keeps the accountants happy, patients, the ultimate “consumer”, can surely only benefit, while the health service could be on the verge of a major breakthrough in the tough ongoing battle against healthcare-acquired infection.
References
1 Journal of Infection Prevention, 2009. Vol.10, pp 6-12. 2 British Journal of Community Nursing, 2009. Vol.14, No.6, S25-29