STERILIZATION

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The initiative was announced by the Association of Professionals in Infection Control and Epidemiology (APIC) at its 2007 annual meeting in San Jose, CA. The goal of the initiative is to achieve zero hospital-acquired infections (HAIs) in patients within the next three years. Participating in this effort are the Centers for Disease Control and Prevention (CDC) and the American Society for Healthcare Engineering (ASHE). CDC publishes its efforts on its Web site (www.cdc.gov/ncidod/dhqp/index.html).

The Initiative

An increased use of antimicrobial materials in medical devices and surgical instruments is expected as part of this initiative. These devices could be formulated with antimicrobial chemicals or could be coated so as to provide contact surfaces with antimicrobial characteristics.

In addition to devices that are used at the patient bedside, the initiative is also targeting other products used in hospital environments such as wall coverings, flooring, and climate control systems, as well as touch surfaces such as door handles and bed rails. Antimicrobial surfaces would also be required in public areas such as restaurants, airports, and hotels. Such surfaces are already being used in food-processing facilities. In addition, the initiative would increase emphasis on hand hygiene and skin covering and would promote the greater use of sterilized products and barrier architectures with the idea of making it more difficult for microorganisms to be transmitted from one place to another.

Alternative approaches to reducing surgical site infections include the development of devices and methods that pump warm air and water onto a bandage or blanket so that normal temperature is maintained by the patient. Devices that monitor and maintain normal blood oxygen levels and normal glucose (blood sugar) levels by the administration of insulin also help fight the spread of microorganisms. The initiative will recommend the use of such approaches and devices.

Use of ethanol, isopropanol, and other high-level disinfectants (these are not sterilizing agents) such as phenolics, quaternary ammonium salts, peroxides, and glutaraldehyde would continue. These kill microorganisms almost instantaneously but because of their volatility and chemical reactivity do not provide long-term protection. Other chemicals often used as disinfectants are triclosan and chlorhexidine gluconate. These latter chemicals are now being incorporated into sutures and surgical preparation cloths with the goal of reducing the incidence of surgical site infections. Bleach is also used to disinfect non-patient-contact areas and is especially useful in combating fungi such as Aspergillus niger.

Long-term microorganism-hostile surfaces are now being made with silver. It is hoped that registration with the U.S. Environmental Protection Agency (EPA) will be achieved within the next few months for surfaces made of copper and its alloys. Plastic laminates that incorporate triclosan or other nonvolatile organic disinfectants could also be used. Within the next few years, it is also likely that nanoparticles, especially those of zinc oxide and titanium dioxide, will be components of products with antimicrobial properties.

Use of Copper in Infection Control

A major target for anti-infective surfaces is stainless steel, which has traditionally been the touch surface for sinks, plumbing, bed rails, and other hospital installations. Studies have shown that the viability of microorganisms on different touch surfaces is as follows:

• Stainless steel = days.
• Copper and its alloys = hours.
• Surfaces containing silver = minutes.¹

The copper industry is undertaking a major effort to educate the healthcare community about the antimicrobial properties of this metal. Copper has been used since ancient times by many different civilizations to sterilize water and to treat infections. Egyptians used copper, for example, to sterilize water and wounds. Other civilizations also used copper for similar purposes. Today it is used in antimicrobial medicines and in some hygiene products. For example, copper sulfate is used in preparations for treating skin diseases. Copper organic complexes are used as anti-inflammatory drugs.

Recent studies sponsored by the Copper Development Association (CDA) and the International Copper Association Ltd. have shown that copper and its alloys are effective against methicillin-resistant Staphylococcus aureus (MRSA). The studies were carried out at the University of Southampton (UK). Other studies have shown that copper is also effective against the virulent E. Coli O157:H7 and against influenza A viruses.¹ Copper and its alloys will most likely be used on touch surfaces such as sinks, IV poles, fluid dispensers (e.g., for soaps and alcohol), and work surfaces. Copper and its alloys could also be used on climate-control ducting and other equipment that would use significant quantities of metal.

Medical device manufacturers could also adapt copper and its alloys to achieve greater infection control on their products. The use of a copper-based foil is currently being evaluated for use in a stethoscope diaphragm.

CDA has collected sufficient data to submit a petition to EPA, which is scheduled to rule shortly. If the EPA response is positive, copper will be registered as the first and only metal with health claims under the Federal Insecticide, Fungicide, and Rodenticide Act (FIFRA).

Use of Silver in Infection Control

The effectiveness of silver against many harmful microorganisms has been demonstrated in a number of published research studies. A review has recently been published.² Silver chemistry has been developed commercially in several forms that provide effective and economical options for infection control.

Silver has also been used since ancient times to control infectious organisms. In ancient Egypt and Phoenicia, silver was placed in containers to control contamination of drinking water. The use of silver for wound dressings was first recorded in ancient Rome by Pliny the Elder. These applications are still important today. Silver is used in portable systems to purify drinking water and is occasionally used to purify water in swimming pools and spas when the use of chlorine is impractical.

In the past five years, almost all suppliers of wound-care products have incorporated a noncontact layer containing silver. The silver acts as a barrier to prevent microorganisms from penetrating to the wound surface, and thus minimizes the occurrence of secondary infections. Some FDA-approved products have layers containing silver that can directly contact the wound surface to provide direct antibacterial treatment.

Table I. (click to enlarge) Mechanisms of silver biocide activity.

Table II. (click to enlarge) Harmful microorganisms controllable with silver.

The development of stabilized and controlled-release forms of ionic silver has enabled the increasing use of silver for infection control. Silver salts are photolytically unstable, and silver ion is a highly active and powerful oxidizing agent. Technology using zeolite incarceration or entrapment of ionic silver in titanium dioxide, zinc oxide, or other matrices has enabled the long-term use of ionic silver anti-infective agent properties.

This technology was first developed in Japan in the 1990s and has been licensed and developed globally since then. Although silver is expensive, its effectiveness in controlling bacteria and viruses is in the parts-per-million (ppm) range and is sometimes even lower. Control of fungi usually requires 200–300 ppm by weight of silver. Silver is therefore highly economical as well as effective. When in a controlled-release matrix, silver is also safe, providing long-term protection.

Biocidal silver is now commercially available in the form of sprays and gels. It is also available as an antimicrobial component of coatings, laminates, and textiles. In addition to wound dressings, silver is now found in medical draperies and gowns. Further use is likely to be seen in bedding, notably mattress covers. Textiles containing silver are already used extensively for products such as automotive carpets and sportswear, where odor control is important.

For medical devices, silver as a gel is used in Foley catheters and is being developed for endotracheal tubes. Silver is also used in the construction of stethoscope diaphragms. The integration of silver into medical devices has been slow, because of the need for FDA registration of the product.

Silver has recently been incorporated into portable items with the goal of minimizing the transmission of infectious organisms. Products include clipboards, pens, cell phones, and even paper. Cleanroom furniture also has surface coatings containing silver and other antimicrobial substances. The coatings, most of which are powder form, can be clear or colored. Wall coverings and flooring containing silver already are extensively used in
patient-treatment centers outside North America and are now being marketed here.

Silver can also be used on handrails, light switches, toilet seats, and changing tables. If climate-control system transmission is a concern, as is the case with Legionella and SARS, ducting and condenser elements coated with silver can prevent dispersion of the microorganisms. Plumbing and sink installations are also now available with a powder coating of antimicrobial silver placed on a stainless-steel surface.

Because of its antimicrobial properties, silver has also been proposed for use in the development of respiratory filters and protective clothing for military, emergency, and first-response personnel who may be faced with bioterrorism and perhaps chemical terrorism threats. Research sponsored by the Silver Research Consortium (Durham, NC) is being carried out at North Carolina State University to evaluate methods for depositing silver on textiles to get the requisite barrier properties. Research grants are available through the U.S. Department of Defense and Department of Homeland Security to develop products showing promise.

Silver, because of its reactivity in almost all environments, is generally considered to be environmentally benign. Although silver ion is toxic to fish and to other marine organisms, it reacts rapidly with ambient sulfur and organic chemicals to form innocuous compounds. If ingested, silver causes a bluing of tissue in some segments of the population, but is not otherwise harmful. Those uses of antimicrobial silver not within the jurisdiction of FDA come within the purview of EPA. This latter agency is in the process of revising its Registration Eligibility Document on silver as a pesticide.

Requirements for Success in Reducing HAIs to Zero

A successful initiative for reducing HAIs to zero must include the following:

• Promoting changes in the way research in infective-organism control is communicated to the healthcare community.
• Quick registration at FDA of medical devices and at EPA for generic coatings, laminates, and other products claiming antimicrobial qualities.
• A willingness by hospitals and other patient-treatment centers to build or retrofit areas of their facilities with new materials that prevent the buildup of infectious organisms on surfaces.

Currently, research undertaken by infection control personnel is sponsored in individual facilities by companies trying to determine the effectiveness of proposed
infection control products. Negative results are rarely if ever published, and positive results usually are hampered by the slow regulatory registration process for medical devices and of generic antimicrobial products.

For medical device technologies involving and control of surgical-site infections, insurance companies must often approve such products and procedures. FDA or EPA registration must still be obtained even if products do not directly contact the patient. Coatings for walls and flooring, for example, must be registered. These coatings come under EPA’s jurisdiction and are subject to FIFRA.

EPA is currently undertaking a FIFRA-mandated review and revision of the Registration Eligibility Document for silver. The document was last published in 1993. It is hoped that the copper industry’s initiative to obtain broad application of copper and its alloys as a germicide will make it easier for other products to be registered and marketed.

Whether hospitals will spend money to build or retrofit facilities is unknown. No regulations require compliance, and the program is voluntary. Physician interest in achieving zero HAIs will also be vital in the success of the initiative. Increased regulation, consumer (patient) demand, and the possible adoption of a universal healthcare system may have positive effects. Europe and other industrial nations have already put many of these procedures in place.

Device manufacturers should certainly help as much as they are able to reduce the incidence of HAIs. Input on the kinds of products that are needed can be obtained from nurses and physicians who are in charge of infection control at hospitals and other patient-treatment centers. In the United States, a powerful incentive to move forward in addressing HAIs is that insurance companies and state and federal agencies are considering not paying for the treatment of these infections.

Many technologies are available to reduce the proliferation of infectious organisms. Perhaps deeper analysis of the costs of HAIs may help in justifying expenditure on upgraded facilities.

Jeffrey Ellis provides market research, technology assessment, and commercial development services to companies and trade associations in the chemicals and plastics industries, as well as to government agencies and universities interested in the commercial development of intellectual property. He can be reached at jrellischem@aol.com.