Antimicrobial surfaces: much has been written or presented about antimicrobial systems for...

It is a myth that antimicrobial surfaces are the single answer to infection control in hospitals and care homes. Claims that they are the Holy Grail to combat MRSA have damaged the credibility of technologies that are available from reputable companies who are aware of the place for antimicrobial

surfaces within an infection control programme. This paper was written following an in-depth review of technical papers, patents, company literature, trade articles and discussions with manufacturers and infection control nurses. It provides a balanced view of the technologies available, shows their essential differences and indicates where successful applications have been made.

MAJOR CATEGORIES

There are two major categories of antimicrobial surfaces, those resulting from incorporation of the biocide throughout the whole of the article and those with only a surface coating. Examples of totally incorporated biocides would be impregnated materials such as plastics and laminates. Surfaces coatings could in the form of paints, or special applications involving spraying, padding or dipping.

EFFICACY AND DURABILITY

Claims are varied. A disinfective action is claimed by some systems whereas a biostatic action is claimed by most well-established products on the market. None of the claims may be compared directly because there is no internationally recognised performance standard for evaluating antimicrobial surfaces. An internet review of claims for durability shows a vast range, from 7 days to 30 years, depending on the type of product. Paints based on polyurethanes, epoxy materials or styrene acrylics claim, on average, a 10 year lifespan.

APPLICATION AREAS

Paints have been used for coating many areas such as walls, ceilings and floors. Addition of biocide to powder coating treatments has found application in items such as shelving and bed frames. A variety of biocidal treatments has been used for clothing, kitchen utensils, medical devices, bandages, surgical instruments and implants.

TOTALLY EMBEDDED VERSUS SURFACE COATED SYSTEMS

Objects with biocide distributed throughout the body of the material rely on the surface population of biocide to provide the antimicrobial effect. The biocides are tied into the polymer matrix in a manner which is not completely understood and some migration can occur within polymer interstices and in the amorphous parts of the matrix (Watterson and Hanrahan, 2002; Ong and Hanrahan, 2004). The biocides on the surface are fixed and therefore enable food contact approvals and compliance with the Medical Products Directive. In the event of abrasion or wear over a period of time, a degree of self-repair is possible by exposing more biocidal material from beneath the surface. The biocidal action will therefore remain for the lifetime of the product.

The concentration of biocide within the material is an important factor; very high levels will increase rate of kill but may preclude food contact or direct body-fluid contact; levels which are too low may make the surface ineffective, or worse, encourage the growth of resistant strains.

Surface coatings are preferably of the type with the biocide fixed to a thin polymer film thus providing a biostatic action. There is no release of biocide and therefore the surface is non-toxic and non-tainting and the surface activity will be constant unless badly soiled.

Other coating products are available on the market which claim a disinfection action by allowing biocides, or combinations of biocides, to leach out of the polymer film onto the surface. Although this provides a more rapid kill rate, the product will be more toxic to humans and the reservoir of biocide is soon used up, requiring reapplication after a number of days.

PERFORMANCE STANDARDS

There are no internationally recognised standards for evaluating antimicrobial surfaces which makes comparison of data difficult or impossible. This has been recognised in the industry and a standard is being formulated through an OECD funded initiative which will provide a definitive test protocol by the middle of 2005. The test method will be based on a Japanese Industry Standard (JIS Z 2801:2000) and a schematic of the method is indicated below.

The method involves inoculating a test piece and then covering the area with a polyethylene film. The sandwiched cell suspension is incubated for 24 hours, transferred to a neutraliser and TVC determined in the normal way.

The method has been used to make comparative evaluations of several antimicrobial surfaces. In the results shown below, six different antimicrobial surfaces were inoculated with Staphylococcus aureus. Untreated stainless steel and film from a stomacher bag (used in the food industry) were included as standards.

Materials 1 and 2 showed a good disinfection action after 18 hours contact time and materials 3 and 4 showed reasonable log reductions of 3-4. Materials 5 and 6 were not very effective and material 6 showed behaviour similar to the untreated standards. The method, when finalised, will provide a powerful tool in comparing the effectiveness of antimicrobial surfaces. Later stages of the method development will involve introduction of surface soiling.

WELL-ESTABLISHED TECHNOLOGIES

In selecting technologies for more detailed description, it is important to consider those with a well-established history of application in the health care sector. These will have undergone extensive safety testing and several new applications will have been developed over the years. Three technologies have been used for a minimum of 20 years in medical applications and each is different in principle although with some overlap:

* Silver ion technology

* Organic biocides in coatings or incorporated into objects

* Cationic biocide covalently bonded to a reactive silicone compound

SILVER ION TECHNOLOGY

In its simplest form, a coating system is formed by binding silver ions to a fine ceramic powder (zeolite), dispersed in a carrier. The ions are then exchanged with sodium, calcium or other ions when the surface comes into contact with water or body fluids. Further developments, particularly in the area of nanotechnology, have enabled the use of silver technology in plastics, fabrics and coatings without the use of zeolite (Wagener et al, 2004). Uptake of silver ions by a cell can occur by several mechanisms, including passive diffusion and active transport by systems that normally transport essential ions. While the silver ions may bind non-specifically to cell surfaces and cause disruptions in cellular membrane function, it is widely believed that the antimicrobial properties of silver depend on silver binding within the cell. Once inside the cell, silver ions begin to interrupt critical functions of the micro-organism.

Silver ions are highly reactive and readily bind to electron donor groups containing sulphur, oxygen and nitrogen, as well as negatively charged groups such as phosphates and chlorides. A prime molecular target for the silver ions resides in cellular thiol (-SH) groups commonly found in enzymes. The resultant denaturation of the enzymes incapacitates the energy source of the cell and the microbe will die.

APPLICATIONS OF SILVER ION TECHNOLOGY

A review of applications shows that this technology has been used in the following health care areas: treatment of steel ducting and components in HVAC systems (Steele, 2001), building materials (Myers, 2004), laminates, floors, walls(in paints), carpets, cubicle curtains, lockers, safety cabinets, bedpans, sack holders, soap dispensers, keypads, medical devices (Duran, 1999; Lin et al, 2001; Finelli et al, 2002), wound dressings and implants (Duran et al, 1994; Carrel, 1998).

Antimicrobial paint containing silver ions was used during the phase 4 development at St. James' Hospital, Leeds. A high performance coating was applied to all operating theatre walls, covering 3,000m2, in order to provide long-term protection against the growth of bacteria, mould and other micro-organisms.

ORGANIC BIOCIDES

Organic biocides may be incorporated into plastic and fabrics during the manufacturing stage. For plastics, the biocide is added into the manufacturer's virgin resin, blended, melted, then moulded or extruded into the final article. For fabrics, the biocide may be incorporated in several different ways according to the method of manufacture. Usually the biocide is applied by foaming, padding or spraying. The innovative aspect of this technology is the nature of the interaction of the biocide with the polymer or fibre matrix. In plastics, this should provide a fixed population of the active ingredient on the surface of the article, without causing colour changes or, in the case of fabrics, where the antimicrobial agent is often added with a latex binder (Payne, 2003), without affecting 'feel' of the fabric. The biocide must remain durable and not be washed out during normal laundering.

The concentration of biocide is optimised to provide adequate protection, without the dangers of under or overdosing. Many different organic biocides are now in use, some specially selected for specific applications. Some of the earliest applications involved combating the growth of odourcausing bacteria on medical devices.

APPLICATIONS OF ORGANIC BIOCIDES

There are many applications in the building industry, for example in producing wall laminates for high risk areas in food processing and clean rooms. In the hospital environment, applications include: bedding, bed frames; carts for transport of medication, linens, equipment and other supplies; hand rails, pulls, trims and door handles; slings and hoists; window blinds; dental trays; incise drapes; wound dressings; keyboards and mouse.

COVALENT BONDING OF BIOCIDE TO A REACTIVE SILICONE COMPOUND

This technology utilises the properties of reactive silanols and their ability to form covalent bonds with a target surface. The silanols are modified with biocidal adjuncts, so that when the silanols fix onto a surface, the active biocidal sites become fixed too. The films created are extremely thin, between 15nm and 180nm, and therefore the original physical properties of the surface are little affected. The mode of action is illustrated in the diagram below.

Bacteria arriving on the surface encounter the hydrocarbon portion of the biocidal adjunct which may be assimilated into the cell without any disruption. However, contact with the positively charged nitrogen atom will unbalance the electrical equilibrium within the porin channels and on the outer protein layers such that the cells can no longer function correctly and the microbes will die (Speir and Malek, 1982; Tiller et al, 2001). This effect is indicated in the two images below showing the fate of E. coil on a treated surface.

The reactive silanol will form a covalent bond with any surface containing oxygen, nitrogen or carbon in any form. For example hydroxides or oxides on the surfaces of metals (including stainless steel) will form a durable bond. The application is therefore very versatile and many types of surface may be treated, such as plastic, metal, fabric and painted surfaces.

APPLICATIONS OF BIOCIDAL REACTIVE SILANOLS

The fixed nature of the biocide is important where toxicity, taint and other organoleptic aspects are of concern. This is a bacteriostatic surface treatment, not removed by normal cleaning procedures. In fact, it is important to maintain the normal cleaning regime in order to 'refresh' the biocidal surface. The thinness of the film enables application in areas where optical properties are important such as treatment of contact lenses. The technology has been used for treatment of bedsheets, hospital garments (Murray et al, 1988), curtains, floor and wall materials, air filtration systems, medical devices, bandages, surgical instruments and implants (Gottenbos et al, 2002). The technique has been used to prevent biofilm growth on catheters, stents, contact lenses and endotracheal tubes.

An actual case study in USA involved treatment of the entire building of the A. G. James Cancer Hospital/Ohio State University to reduce the incidence of allergies with mould sensitive individuals after a disastrous flood in the hospital. Prior to treatment 2,800 CFUs per cubic metre of air were recovered. Following application, a sharp reduction in the aeromicrobial level was observed. Significantly, even after two years, the average microbial count was less than 1 CFU (Gettings et al, 1990; Kruger and White, 1999).

CONCLUSION

It is important to state that antimicrobial coatings must not undermine the success of traditional hygiene methods and neither must conventional cleaning and hygiene operations be relaxed if antimicrobial coatings are employed. Indeed, this could become a downside of employing the technology should this occur. However, this study has highlighted that there could be a useful place for antimicrobial coatings as a complementary part of infection control programmes. Apart from specialised applications, such as treatment of medical devices or incorporation into fabrics for hospital garments, the treatment of large surface areas within hospitals and care homes, such as walls and floors, will reduce the risk of contaminated surfaces acting as a reservoir for organism transfer to humans. The choice of system will be determined by the method of application intended and the type of location to be treated and professional advice should be sought. Finally, performance claims should be backed up by an appropriate internationally recognised standard.

ACKNOWLEDGEMENTS

1. Figure 1 is reproduced by kind permission of Peter Askew from Industrial Microbiological Services Ltd

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2. Figure 2 is from data provided by John Holah and reproduced with permission of Campden & Chorleywood Food Research Association, UK. www.campden.co.uk

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3. Figures 3 and 4 are reproduced by kind permission of KCM Biogreen 2000 Ltd

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Dr Terrence Child would like to acknowledge valuable input from Microban Europe in preparing this article (Tel: +44 1908 556100). Thanks go to KCM Biogreen 2000 Ltd for additional information related to reactive silanol biocides (Tel: +44 8256 5030).

REFERENCES

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Duran I.W. (1999) Antimicrobial Surface technologies: Novel Approaches to Prevent Medical Device-Related Infections. Eleventh International Biodeterioration and Biodegradation Symposium, Arlington, VA.

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AUTHOR

Dr Terence Child CSci CChem FRSC Hygiene Consultant Food Hygiene Technologies Windermere House 27 Firwood Drive Camberley Surrey GU15 3QD Email: tchild@foodhygienetech.com Telephone/Fax: +44 (0)1276 503057