Dear Editor:

I read with great interest the recent article excerpted from Jain Malkin's book, “The Built Environment as a Risk Factor for Infection” (HEALTHCARE DESIGN, July 2008, pg. 38). Understanding and awareness, of all the factors that can contribute to reducing potentially harmful bacteria in a hospital, are indeed needed, and many designers, architects, infection control professionals, and hospital administrators have committed themselves to becoming educated about new approaches. However, the article makes some generalizations about antimicrobials that can be clarified to provide your readers with a better understanding of the issues.

The position of Ms. Malkin's article is based on a 2006 document authored by the healthcare giant Kaiser Permanente, in which it acknowledged the value of reducing environmental bacteria to break the chain of infection, but concluded that in order to justify the added cost of antimicrobial surfaces, more data are needed to link antimicrobials to infection control. The Kaiser position focused on one type of antimicrobial treatment, stating that “the antimicrobial action of surfaces can only effectively treat the first cell layer of pathogenic material.”

While this is true for certain types of antimicrobials, it is wrong to generalize this mode of action for all. Surface-bound antimicrobials, such as silane quaternary ammonium compounds, require direct contact between the surface-bound molecule and the microorganism,1 and are hampered by a soil load. However, some antimicrobials use a system that provides a controlled amount of the active ingredient to the surface of the treated product, allowing interaction with any bacteria in a residual soil.2 Of course, normal cleaning of a visible soil load remains a requirement for antimicrobial surfaces, as well as use of common spray disinfectants.3 So the Kaiser position on the mechanism of action does not accurately describe the action of embedded antimicrobials that deliver mobile active agents to the surface of the treated material.

An antimicrobial system with release capability, such as Agion, which was mentioned in the article, are able to control bacteria that are not in contact with the treated part and have been independently proven to significantly reduce microbial contamination on surfaces in both laboratory and clinical contexts.4,5,6,7

It is true that the EPA does not allow the same claims for embedded antimicrobials as it does for hard surface disinfectants, however, this is due to the fact that a practical path for such claims does not exist for this category of antimicrobials, not for any performance reasons. For example, if an ICU desired to have all high-touch surfaces treated with an embedded antimicrobial and wanted to present data publicly showing how it reduces various environmental pathogens, 10 to 15 separate studies (one for each material being treated) costing hundreds of thousands to millions of dollars would be required. This is financially impossible for any hospital or supplier of healthcare products to support. In contrast, the EPA does not require that a hard surface disinfectant (usable on any hard surface) complete independent studies on all materials on which it may be used. In fact, disinfectant efficacy has to be shown on only one surface, a glass slide,8 which hardly represents the scope of materials on which the product might be used in a healthcare setting. This regulatory double-standard may limit claims made about the performance of products using embedded antimicrobials, however, the fact that antimicrobials such as Agion can significantly reduce the reservoir of bacteria on important surfaces—the goal of all healthcare hygienic strategies—has been independently proven and is indisputable.4,5,6,7

Another comment by the authors of the Kaiser paper that was repeated by Ms. Malkin was that silver ions are “heavy metals.” The term “heavy metal” is not a scientific term, it is a media phrase without a specific definition. The periodic table is separated into five regions: Alkali Metals, Alkaline Earth Metals, Halogens, Noble Gasses, and Transition Metals. Silver is a Transition Metal, along with elements such as Zn, Fe, Cu, Mn, Co, Mo and Ni, which are essential dietary elements. The phrase “heavy metal” is misleading because it implies that there is some common characterization of metals within a range of density. Generally, when the term “heavy metal” is used to describe Pb, As, Cd or Hg, the first word is left off of the actual meaning: “toxic heavy metal.” The toxicity of those metals has to do with their chemistry and biological activity, not density. Density doesn't correlate to toxicity. So “toxic metal” is a more descriptive and differentiating term for those metals. Silver does not match the chemical or biological profile of the commonly cited “toxic metals.” Silver is regularly used in medical devices to prevent infection and water filters to prevent bacteria propagation and fouling of the filter. The EPA limit for silver in drinking water was actually raised in recent years to 100 ppb because silver poses no negative health effects since silver “does not impair bodily function.”9 This concentration is far higher than the amount typically available on an Agion-treated surface in a healthcare setting.

The article also raises a question about the environmental impact of silver used in antimicrobial-treated articles. In the context of antimicrobials, the question is warranted since, by definition, any antimicrobial or biocide is toxic to some level because it is used to kill a living organism. Silver is no more of an environmental toxin than other common antimicrobials used in healthcare (quats, phenols, chlorine, peroxide, iodine, aldehyde), which are all somewhat toxic to aquatic species. Whether a potential toxin is a particular concern or not depends on how it is used, where it goes, and in what form it reaches the environment. The typical active ingredient content for these products is 0.01 to 10% of the formulation. The amount of active ingredient released to the surface of a product treated with the silver-based antimicrobial Agion (mentioned in the article) is ≈50 ppb. This concentration is 2 thousand to 2 million times lower than the active ingredient content in the surface disinfectants. Due to the high efficiency at low concentrations, very little silver is actually used.

For example, the amount of silver in a single sterling silver flatware place setting is enough to produce over 400,000 chairs using with Agion-containing upholstery. If only the armrests, and not the seat, are treated, over 2,000,000 chairs can be manufactured with the silver from that single place setting.

Furthermore, the form in which the active ingredient reaches the environment is a critical factor in the impact on an ecosystem. Silver ions, the active ingredient employed by Agion-treated products, bond quickly to proteins, chlorides, and sulfides—compounds that are ubiquitous in the environment. When these insoluble compounds form, silver is no longer in the ionic biologically active form.10,11,12,13,14 Therefore, it is important to note that the form of the active ingredient, not merely the presence alone, correlates to environmental impact.

The same technology used in upholstery has been evaluated in a patient care environment, but in a much more challenging application. Catheters using the same technology have been evaluated in clinical studies and the conclusion was that Agion-protected catheters resulted in significantly reduced bacterial colonization.6,7 The environment is different though the objective is the same—reduce the colonization and propagation of bacteria on the surface.

The conclusion from a scientific review of the literature is that cross-contamination does happen via fomites—surfaces that can harbor pathogens—and that fewer bacteria on the source surface results in fewer bacteria being transferred to another surface.15 Studies also clearly show that reducing the number of pathogens on surfaces in a particular environment results in reduced illness in people frequenting those environments.16,17,18 Bacteria and viruses can survive on fomites for up to a week.19,20 Common practice, experience, and simple logic support the idea that if there are fewer locations where pathogens can survive for days, it's less likely that those pathogens will reach a susceptible host and result in an infection.

Not all disinfectants have been proven to show that their use reduces infections, but hospitals around the world use a daily regimen of disinfectants for just that purpose. Should they stop using a phenol, or chlorine, because the studies were done with quats? No one would suggest such a thing, because it's understood that the benefit—reduced pathogen concentration on surfaces—is the objective, not the use of a particular chemical. Embedded antimicrobials are another means to the same end, and possess the advantage of being passive, working 24/7, without human interaction. The performance of disinfectants depends on how it is used and requires the user to understand where problematic pathogens are most likely to reside. Many disinfectants require that the surface be saturated for 10, 20, or even 30 seconds to be effective, however, most users spray and wipe within only a few seconds. Hand washing and sanitizers are another component of healthcare hygiene, but many studies have shown that compliance is limited.21,22 Agion maintains that, since the active, manual strategies promoted for decades in the healthcare environment have not eliminated HAIs, it is prudent to look at other strategies, especially those that do not depend on the human variable.

Jeffrey A. Trogolo, PhD

Chief Technology Officer

Agion Technologies, Inc.

Wakefield, Mass.

Jain Malkin responds:

I am delighted that my article prompted such a thoughtful response. This is just the type of dialogue we need on a topic as important as infection control. I am not qualified to agree or disagree with the science Dr. Trogolo refers to in supporting his claims, but my sense, as an educated reader, is that he is not just backing his product from a marketing standpoint. He seems to be explaining what may be unreasonable levels of certainty that are being imposed when assessing the benefits of the Agion component of various products. He makes a very convincing case about the silver ion issue and whether they could leach into the water supply and be considered “heavy metals.” I hope that other vendors will weigh in with scientific support for their infection control additives. To date, much of what has been available is marketing hype. Typically when I ask for the science behind a product or additive, I am sent something that even I can evaluate as biased and lacking in rigor.


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