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| Jeff Trogolo, CTO, Sciessent |
The recent MPMN cover story, "Antimicrobials: Beyond Silver," discusses next-generation antimicrobial technologies that are diverging from the silver trend. To some, research in these areas may imply an underlying notion that silver-based technologies have run their course or have certain limitations. However, there is ample evidence pointing to the strength of silver as it continues to dominate the market for antimicrobial devices with multiple new silver-based devices receiving FDA approval within the past six months. And while some of these technologies have new chemistry--which demonstrates the adaptability of silver--the general principles have been around for decades. Medical device manufacturers using the correct silver-based antimicrobial technology for a specific application have found that silver is quite versatile and tunable for most clinical uses. The same cannot be said for all rival, silver-alternative technologies, however.
One specific example is a category of nonsilver antimicrobial technologies that are referred to as 'contact-kill' technologies. They generally consist of long-chain molecules with cationic ends. The cationic end pierces components of the bacterial cell wall causing it to rupture and die. Advantages claimed by manufacturers of these technologies are that they are nonleaching and do not lead to the development of resistance in microorganisms. These claims sound impressive on the surface, but if you dig a little deeper into the technology and how it works, it becomes clear that these contact-kill technologies cannot be effective for any meaningful duration in a clinical environment. These long-chain compounds need to have direct contact with the microorganisms in order to penetrate their cell walls. It is well known that artificial surfaces introduced into the body immediately (within minutes) become covered in a conditioning layer of adsorbed proteins. This conditioning layer masks these long chains and effectively neutralizes the functional ends of the molecules, rendering the surface identical to a nonantimicrobial standard device and allowing microorganisms to adhere to this layer of adsorbed proteins.
In contrast to these long-chain molecules that are bound to the surface, silver-based technologies elute silver ions. The short-range mobility of ionic species circumvents the fouling characteristics of protein buildup. Therefore, provided the device is sufficiently loaded to overcome the effect of adsorbed proteins, an effective concentration of silver ions will be present at the surface to prevent bacterial colonization. Silver-based devices on the market today have shown efficacy in this challenging protein environment for up to 30 days.
One reason that medical device manufacturers increasingly choose silver as their embedded antimicrobial of choice is its ability to overcome the harsh environment of the body while maintaining biocompatibility. A naturally occurring element whose antimicrobial properties have been recognized for hundreds of years, silver has proven to be an outstanding fit for the medical device market, providing an effective piece in the infection control tool kit and an ideal differentiator for manufacturers.
Read the cover story, "Antimicrobials: Beyond Silver," to learn more about the silver-alternative technologies that Trogolo references. Plus, check out MPMN's gallery highlighting five novel antimicrobial technologies in development.
The opinions expressed in this article solely represent the views of the author and do not necessarily represent the opinions of MPMN, Qmed, or their parent company UBM.
Comments
Long-Chain Cationic Antimicrobials Provide Versatility and Efficacy Well Beyond Silver
By: Jerry Olderman, Ph.D.; VP, Research & Development; Quick-Med Technologies, Inc.
A recent opinion published by MPMN entitled “Silver-Alternative Antimicrobial Technologies Lack Versatility, Efficacy” attributes certain key limitations to long chain molecules with cationic ends. While the shortcomings the author cites may apply to mono-quat antimicrobials such as benzalkonium chloride and siloxane quats, long-chain cationic polyquats perform quite differently, and the distinctions are worth considering.
Long chain cationic polyquats are polymers with a high molecular weight and are now available in several medical devices. They can exceed more than 200,000 daltons with more than 2,000 covalently-bonded quat groups along its backbone. They are very different to the long chain molecules with cationic ends mentioned and this comment is offered as a clarification. A polycation has a very high charge density as a consequence of its numerous cationic charge sites. Simply stated, the mechanism of microbicidal action is a disruption of the cell wall and cell membrane, resulting in collapse of the bacterial cell and loss of its cytoplasm
The most advanced polyquats not only have very high charge density but also are bonded to the substrate of the medical device. Importantly, when a polyquat is bonded to a substrate, none of the bonded polyquat is released into the human body. A demonstrated lack of cytotoxicity and biocidal activity substantiate this important attribute. On the other hand, silver must elute (leach) in order to work.
A further distinction is that polyquats are very effective for “meaningful durations in a clinical environment.” A particular strength of high-charge density polyquats is their ability to maintain efficacy in the presence of blood and other proteinaceous challenges. Unlike silver, which can be “blinded” in the presence of proteinaceous challenges, polyquats function well in the heavy exudate of the clinical burn environment and in in vitro tests of up to 90% defibrinated blood. In a recent clinical evaluation conducted in the burn center at Shands at University of Florida, control dressings on heavy exudating wounds become green in color and highly malodorous due to Pseudomonas aeruginosa contamination while polyquat dressings on similar wounds remained white and with no odor. Notably, both dressings were applied over a silver primary dressing that is against the wound and under the secondary dressings involved in this particular study. The odor in burn wards is unmistakable and pungent. The same wards dress the wounds with silver products that have yet to achieve this level of performance in heavy exudate environments. The difference is a function of the ability of each type of antimicrobial to perform in the presence of proteinaceous challenges.
Silver antimicrobials are widely used in medical device applications. However, a new breed of polyquat antimicrobials overcomes certain key limitations of silver ions. As a result, they are being introduced in a growing range of applications including foams, films, gauze, and are being actively developed for catheters.
In contrast to the subject opinion, it is evident that there are alternative antimicrobial technologies that are quite versatile and perform aggressively even in high concentrations of proteinaceous challenges. Their features deserve consideration in next-generation medical devices.
The author of this article, Jeffrey A. Trogolo, could hardly be called an unbiased outside party. He is Chief Technology Officer of Sciessent Corp., who recently acquired Agion, a manufacturer of silver ion antimicrobial products.
In the article, Mr. Trogolo denounces contact-kill technologies, which he correctly states "generally consist of long-chain molecules with cationic ends. The cationic end pierces components of the bacterial cell wall causing it to rupture and die. Advantages claimed by manufacturers of these technologies are that they are nonleaching and do not lead to the development of resistance in microorganisms."
These are all true statements. However, the author follows them by stating that contact-kill technologies "cannot be effective for any meaningful duration in a clinical environment." However, his entire premise is based on an old debate tactic, which is to make a broad UNCONDITIONAL statement, and then attempt to back it up using a very narrow, VERY CONDITIONAL example as evidence.
His stated rationale behind his disparagement of contact kill technologies is based on "artificial surfaces INTRODUCED INTO THE BODY" being covered with adsorbed proteins, which he states will mask the functional ends of the molecules.
However, most germ-killing products used in a clinical environment are applied to inanimate surfaces within the facility, not internally within the patient. They are applied to floors, walls, fixtures, equipment, carpet, drapes, beds, etc. They are not swallowed by the patient.
He is broadly stating that silver ion antimicrobial products are better overall, yet he does not address the fact that most antimicrobial agents, particularly those that use contact-kill technologies, are used on the "other 99%" of surfaces in the hospital other than the patient's internal system.
In fact, to the best of my knowledge there has never been any head-to-head comparison between silver ion technologies and the silane quats that are typically found in contact-kill products. Silver ion products are, of course, based on the price of silver, so their costs can fluctuate rapidly. Also, they operate (function) on a much different principle than most silane-quat lysis based technology. The silver-based technology functions only in the presence of water. A water molecule contacts the silver particle (usually nano particles) and displaces a silver ion. This silver ion then has to migrate through the water solution to find a bacteria, where it enters through the cell wall and "poisons" the cell. Hence, these silver ions are very mobile and can migrate into the body on contact with an open wound. They can migrate anywhere, and they can be wiped off and allowed to leach into the environment.
Silane quat products, such as the one that my company markets, will not do that due its reactive nature. If applied to a bandage, the silane quat product remains fixed on the bandage, does not enter the body, and testing has shown it will kill 6 log of the bacteria coming into contact with it. Our silane quat product has a broad spectrum antimicrobial killing power, and is also effective against fungi and viruses. Can the silver ion technology make this same claim?
Also, bear in mind that the EPA is currently working on banning some applications of the silver ion technology for surface applications, due to it leaching into the environment. They did stop the use of silver ion technology for clothes laundering applications, as the runoff ends up in streams and lakes from the waste water discharge.
The author disparages contact-kill technologies, and alludes to high protein loads coating the polymer chains and preventing the product from working effectively. I have not seen evidence of this, only the dead carcasses preventing live bacteria from contacting the treated surfaces.
Also, this is not what has been reported in the open literature. Tsao et. al. reported that silane coated glass beads effectively killed viruses (Herpes Simplex, etc.) even in extremely high protein loadings. White, et. al. reported that fabrics treated with the silane quat used in hospital settings effectively killed bacteria (i.e. Klebsiella, etc.) that were inoculated into whole blood - and there are very high protein loadings in whole blood.
Like the author, I am not an unbiased outside party. Our website, www.GermFreeLife.com, promotes Vitacide Z-71, an anti-microbial treatment based on silane quat technology. However, I will not disparage silver ion technology, which certainly has its place in the medical community. I only wish to set the record straight on the merits of silane quat technology as an effective, poison-free antimicrobial process.