Antimicrobials: Healthcare's Silver Bullet Against HAIs?

By many accounts, antimicrobials are looked to as the silver bullets of the healthcare arsenal against pathogenic microorganisms. Defined broadly, an antibacterial is an agent that interferes with the growth and reproduction of bacteria. Researchers at Tufts University’s Alliance for the Prudent Use of Antibiotics (APUA) emphasize that while antibiotics and antibacterials each attack bacteria, these terms have evolved to mean two different things. Antibacterials are now described as agents used to disinfect surfaces and eliminate bacteria, and are commonly found in consumer-oriented soaps, detergents, health and skincare products, and household cleaners. Antibacterials may be divided into two groups according to their speed of action and residue production. The first group contains those that act rapidly to destroy bacteria, but quickly disappear and leave no active residue behind. Examples of this type are the alcohols, chlorine, peroxides, and aldehydes. The second group consists of compounds that leave long-acting residues on the surface to be disinfected and are residue-producing. Common examples of this group are triclosan, triclocarban, and benzalkonium chloride.

Fighting biofilm formation on medical devices and the growth of pathogenic microorganisms on surfaces are two distinct objectives of today’s modern antimicrobials. From implants to bone cement, antibacterial sutures and catheters to thermometers and everything in between, antimicrobials are being applied, impregnated and are eluting in a wide variety of products and applications in the healthcare environment. Medical devices, such as urological catheters, intravascular catheters, and vascular access devices, have been shown in numerous studies to be reservoirs of pathogenic microorganisms. An increasing number of device manufacturers are using antimicrobials to help fend off growth of opportunistic organisms.

Child (2005) explains that there are two main methods of using antimicrobials — the biocides can be incorporated into the device, or its surface can be coated with a biocide. Examples of fully incorporated biocides would be impregnated materials such as plastics and laminates, while surface coatings could be paints or special applications involving spraying or dipping. Child (2005) emphasizes the importance of the concentration of the biocide within the material: “...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.”

Three technologies have been used for a number of years in medical applications: silver ion technology, organic biocides in coatings or incorporated into objects, and cationic biocide covalently bonded to a reactive silicone compound. Let’s take a closer look at silver ion technology: a coating system is created by binding silver ions to a ceramic powder called a zeolite, which is then dispersed in a carrier. Child (2005) explains, “The ions are then exchanged with sodium, calcium or other ions when the surface comes into contact with water or body fluids ... 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 microorganism. “

There are numerous commercially available antimicrobial compounds that manufacturers use in and on medical devices. Microban Products Company engineers its Microban antimicrobial protection into a product during the manufacturing process so that it becomes an intrinsic part of the item inside and at the surface. When microbes come in contact with the product surface, Microban protection penetrates the cell wall of the microbe and disrupts key cell functions so that the microbe cannot function, grow or reproduce. Agion Technologies, Inc.’s silver-based antimicrobial also is built right into the surfaces of products. Depending on the microorganism, Agion’s antimicrobial technology has been shown to initially reduce microbial populate ions within minutes to hours while maintaining optimal performance for years. A popular antimicrobial for catheter application is AcryMed’s SilvaGard antimicrobial surface treatment, comprised of nanoparticle technology in a liquid form for nano-silver application to any surface of any medical device without changing its intended properties.

Antimicrobial Metals

>>Silver

As noted previously, silver is one of the most popular antimicrobials in the market today for several reasons; it has broad-spectrum antimicrobial action, it is well tolerated by the human body, it is compatible with most materials used in the manufacture of medical devices, and resistance is arguably nonexistent. Gibbins and Warner (2005) note, “Because silver affects so many different functions of the microbial cell, it is nonselective, resulting in antimicrobial activity against a broad spectrum of medically relevant microorganisms including bacteria, fungi, and yeasts. Silver is also more efficient than traditional antibiotics because it is extremely active in small quantities. For certain bacteria, as little as one part per billion of silver may be effective in preventing cell growth.” Gibbins and Warner (2005) explain further, “Nanosilver particles (as small as 1,000th the diameter of a bacterium) constitute the reservoir for the antimicrobial effect. This reservoir effect results when metallic silver, which has no antimicrobial properties, undergoes a chemical change called oxidation, which results in the release of the ionic form. This chemical reaction occurs at the surface of the particle when it is exposed to moisture such as body fluids. Silver metal oxidizes very slowly, however, so it persists on the device to extend its usefulness.”

“Silver has been known for its antimicrobial properties for a very long time,” says Mark Rupp, MD, professor in the Department of Internal Medicine, Section of Infectious Diseases at the University of Nebraska Medical Center. “Silver has broad-spectrum activity and I think it is a very good antiseptic. However, there are a few drawbacks; there are mechanisms of resistance that have been described specifically for silver, and there have been outbreaks involving silver-resistant organisms particularly in burn units, where there is widespread use of silver as a topical antiseptic agent. The watchword is judicious use of these antimicrobials. Application of silver to medical devices is an appropriate use in some clinical settings.”

>>Copper

While silver ion technology is most prevalent, other metals are beginning to be respected for their potential to help kill microorganisms. Last year the Environmental Protection Agency (EPA) approved the registration of antimicrobial copper alloys with public health claims that copper, brass and bronze are capable of killing harmful bacteria. Copper is the first solid surface material to receive this type of EPA registration, which is supported by extensive antimicrobial efficacy testing. The EPA registration is based on independent laboratory testing using EPA-prescribed protocols that demonstrate the metals’ ability to kill specific disease-causing bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). Noyce et al. (2004) showed that on copper alloy surfaces, greater than 99.9 percent of MRSA are killed within two hours at room temperature. According to the Copper Development Association (CDA), copper alloys can be used for frequently touched surfaces, including door and furniture hardware, bed rails, intravenous (IV) stands, dispensers, faucets, sinks and workstations. The CDA reports that 275 copper alloys, including brass and bronze, have been registered with the EPA as antimicrobial materials that kill bacteria such as Staphylococcus aureus, Enterobacter aerogenes, Escherichia coli O157:H7, and Pseudomonas aeruginosa.

One study conducted at the University of Southampton’s School of Biological Sciences showed that the concentration of live bacteria (MRSA, E. coli O157:H7 and Listeria monocytogenes) dropped from several orders of magnitude to zero on copper alloys (including high coppers, brasses, bronzes, copper-nickels and copper-nickel-zinc) in a few hours. In contrast, no reduction was seen in the concentration of live organisms on stainless steel during the six-hour test period.

Dresher (2004) points to three areas in which copper has been used to curb healthcare-acquired infections (HAIs): sanitation of the water supply, of air-conditioning systems, and of surfaces. Copper/silver ionizers — championed by the CDC and OSHA — have been used successfully to control L. pneumophila in a number of hospitals in the United States and elsewhere, and that it has displaced hyperchlorination as a long-term disinfection solution. The use of copper plumbing also can be effective in controlling L. pneumophila as well as other Gram-negative bacteria such as E. coli, Pseudomonas aeruginosa, Acinetobacter calcoacticus, Klebsiella pneumonia and Aeromonas hydrophila.

A number of companies have successfully incorporated antimicrobial metals into their commercially available products for the healthcare environment. Michael Triana, CEO and president of Bio Barrier, LLC, observes, “Antimicrobial coatings are an added measure that can minimize a variety of pathogenic organisms for extended periods of time. This is very critical from an environmental services (ES) standpoint, in that anything that can strengthen the interior environment should be considered. ES and infection control professionals cannot be everywhere all the time. Human error, the lack of thorough cleaning protocol, the lack of trained personnel, the overuse of antibiotics, and the lack of handwashing enforcement is a problem in many healthcare settings. As for the emergence of multidrug-resistant organisms, our technology is proven and can reduce the microbial dose on the surfaces themselves. By reducing pathogens one can expect to reduce the infection rates, the overall microbial dose, and help improve operating margins.” According to Triana, Bio Barrier’s ISO-ONE® Pathogen Control System is specially applied to almost all surfaces in a healthcare setting. “Our mPale technology is based on the AEGIS Microbe Shield. Most U.S. hospitals will not go for full-on antimicrobial surface applications with an antimicrobial coating. One reason is that no one has randomized trials backing a coating in a large facility, and the second reason is that patient interruption must be eliminated. We are addressing these two concerns, and are in the process of doing our own clinical trial with an infectious disease expert.”

Antimicrobial Applications to Medical Devices

>>Catheters

“Silver has been used to coat both urinary and intravascular catheters and there are dozens of studies concerning these devices. Recently, a silver-coated endotracheal tube has been developed," Rupp stated. He went on to relate, “However, not all antiseptic-coated catheters are the same. For example, silver sulfadiazine, along with chlorhexidine, appears to be a very effective antiseptic coating for intravascular catheters, but IV catheters coated with silver ions have not demonstrated a beneficial effect in clinical trials. Likewise, silver-alloy coated urinary catheters are effective, particularly in terms of decreasing bacteruria, whereas other urinary catheters, coated with other forms of silver, are not protective.”

Pearson and Abrutyn (1997) note that the use of intravascular catheters, while “integral to the practice of modern medicine,” can invite life-threatening complications and bloodstream infections. They observe, “Antimicrobial or antiseptic coating has been shown to reduce bacterial adherence and biofilm formation on vascular catheters. Initial studies in humans have shown that such coatings can effectively reduce colonization of catheters but have been less conclusive in showing the benefit of such coatings in reducing clinical outcomes, such as ... catheter-related bloodstream infections.”

Studies by Maki and Raad are among the most-cited sources for data on the impact antimicrobial-treated catheters can have on catheter-related bloodstream infections (CRBSIs). The studies evaluated catheter colonization and microbial colonization of the skin at the catheter insertion site, and assessed the overall impact of impregnated catheters in reducing CRBSIs. Maki et al. (1997) showed use of central venous catheters coated with chlorhexidine-silver sulfadiazine was associated with a 44 percent reduction in catheter colonization (13.5 colonized catheters per 100 catheters versus 24.1 colonized catheters per 100 catheters; and a 79 percent reduction in the rate of catheter-related bloodstream infections (1.0 infection per 100 catheters versus 4.6 infections per 100 catheters. Raad et al. (1997) showed use of central venous catheters coated with minocycline and rifampin was also associated with significant reductions in the rates of catheter colonization and CRBSIs (0 bloodstream infections per 1,000 catheter-days versus 7.34 bloodstream infections per 1,000 catheter days).

“An important finding of these two studies was that none of the impregnated catheters was associated with adverse events (such as hypersensitivity reaction or toxicity) or infections caused by resistant pathogens,” observe Pearson and Abrutyn (1997). “However, additional evaluation seems warranted because catheters were in situ for an average of only six days and assessment for rare or uncommon events requires more observations than reported in this study. Emergence of resistant bloodstream pathogens and adverse reactions are two important concerns that still need additional evaluation.”

Pearson and Abrutyn (1997) advise, “In deciding whether to use impregnated central venous catheters in an institution, physicians may be guided by the characteristics of the patient population, the institutional rates of central venous catheter-related infection, and the skill of the personnel at the institution. The studies by Maki and Raad suggest that impregnated catheters, although not a magic bullet, may be an important advance in reducing the rate of central venous catheter-related infections, particularly in critically ill patients with multi-lumen catheters for the short term and in settings in which rates of central venous catheter-related bloodstream infection remain high despite full adherence to proven infection control measures.”

Rupp et al. (2005) sought to ascertain the effectiveness of a second-generation antiseptic-coated central venous catheter in the prevention of microbial colonization and infection, as well as the safety and tolerability of this device, the microbiology of infected catheters; and the propensity for the development of antiseptic resistance. The study was a multi-center, randomized, double-blind, controlled trial. Patients received either a standard catheter or a catheter coated with chlorhexidine and silver sulfadiazine. Patients with the two types of catheters had similar demographic features, clinical interventions, laboratory values, and risk factors for infection. Antiseptic catheters were less likely to be colonized at the time of removal compared with control catheters (13.3 versus 24.1 colonized catheters per 1,000 catheter-days). The rate of catheter-related bloodstream infection was 1.24 per 1,000 catheter-days for the control group versus 0.42 per 1,000 catheter-days for the antiseptic catheter group. Coagulase-negative staphylococci and other gram-positive organisms were the most frequent microbes to colonize catheters. Rupp et al. concluded, “The second-generation chlorhexidine/silver sulfadiazine catheter is well tolerated. Antiseptic coating appears to reduce microbial colonization of the catheter compared with an uncoated catheter.”

Rupp issues a caveat, however: “Given the right situation, microbes can probably overwhelm any antimicrobial coating on any device,” he says. “In our study we showed that if you changed a catheter over a guide wire and the coated catheter was put into a colonized bed, (the initial catheter was colonized) the coating didn’t protect the patient from colonization of that second catheter. So if you are not using the right precautions in inserting catheters and caring for them, you can overwhelm these protective technologies."

>>Implants

Surgical implants are another category of medical devices being revolutionized through the use of antimicrobial coatings to help prevent surgical site infections. Traditionally, physicians relied upon systemic antibiotic prophylaxis that addressed microorganisms traveling through the bloodstream from a site some distance from the surgical site, as well as from superficial wound infections. More localized applications of antimicrobial agents such as antibiotics or antiseptics can generally offer more concentrated protection in the immediate surgical area or on the surface of the device.

Darouiche (2003) notes, “Compared with the other local antimicrobial approaches, the coating of surgical implants possesses the advantages associated with using an established method of antimicrobial application, knowing the amount of locally available antimicrobial drugs, having a low likelihood of detectable systemic antimicrobial levels, having a relatively persistent local antimicrobial activity lasting from weeks to months, and using a predetermined selection of non-therapeutic drug or drugs of choice. Such potential advantages, coupled with the variable clinical protection afforded by the antimicrobial coating of catheters, have magnified interest in the antimicrobial coating of surgical implants. The objective is to inhibit bacterial colonization of the implant and, it is hoped, to inhibit implant-associated infection. However, the protective efficacy of antimicrobial-coated surgical implants has yet to be demonstrated in a prospective, randomized clinical trial.”

“There has not been much research done in the areas of infections associated with devices other than catheters, such as surgical implants,” says Rabih Darouiche, MD, professor in the Departments of Medicine (Infectious Disease Section) and Physical Medicine and Rehabilitation. He is also founder of the Multidisciplinary Alliance Against Device-Related Infections. “In contrast, there has been much more research done on infections associated with vascular and urinary catheters.” Darouiche adds,”Although infection control measures are the mainstay approach for preventing device-related infection, adherence to such measures is inconsistent. That is why infection control measures need to be complemented with truly protective technology.”

>>Other Devices

Baxter Healthcare Corporation recently introduced its V-Link Luer-activated device (LAD) with VitalShield protective coating, the first needleless intravenous (IV) connector to contain an antimicrobial coating. The device has been shown to kill on average 99.9 percent or more of specific common pathogens known to cause catheter-related bloodstream infections, including MRSA, and testing has demonstrated antimicrobial effectiveness for more than a 96-hour period. V-Link is coated on both inner and outer surfaces with a proprietary silver-based technology called VitalShield, designed to help prevent microbial contamination and growth of pathogens in the device. The interior and exterior surfaces of the device are coated through a process that deposits silver nanoparticles that serve as reservoirs of bactericidal silver ions that are control-released when in contact with solution.

>>Wound Dressings

While not technically a medical device, wound dressings are an important front in which to showcase the advancements of antimicrobials. A range of silver-coated or antimicrobial-impregnated dressings are now commercially available for use but comparative data on their antimicrobial efficacies are limited. Silver-containing dressings are widely used to assist with management of infected wounds and those at risk of infection. However, such dressings have varied responses in clinical use due to technological differences in the nature of their silver content and release and in properties of the dressings themselves.

Parsons et al. (2005) note, “Critical colonization and infection of wounds present a dual problem for clinicians. First, there is the possibility of delayed wound healing, particularly in the presence of a compromised immune system or where the wound is grossly contaminated or poorly perfused. Second, colonized and infected wounds are a potential source for cross-infection — a particular concern as the spread of antibiotic-resistant species continues. For patients, an infected wound can have additional consequences including increased pain and discomfort, a delay in return to normal activities, and the possibility of a life-threatening illness. For healthcare providers, there are increases in treatment costs and nursing time to consider. Until recently, local wound infection has been a challenge with few management options. However, the advent of advanced wound dressings containing topical antimicrobial agents, such as silver, has provided a new approach to the control of wound pathogens.”

Smith & Nephew has introduced a number of antimicrobial barrier dressings used in wound care to help prevent infection. Acticoat dressings are designed to rapidly kill a broad spectrum of bacteria in as little as 30 minutes (in-vitro) and are effective for at least three days. The Acticoat dressing consists of three layers: an absorbent inner core sandwiched between outer layers of silver coated, low adherent polyethylene net. Nanocrystalline silver protects the wound site from bacterial contamination while the inner core helps maintain the moist environment optimal for wound healing. The Acticoat 7 with Silcryst™ Nanocrystals dressing product features a nanocrystalline coating of silver and consists of five layers: two layers of an absorbent inner core sandwiched between three layers of silver coated, low adherent polyethylene net.

Several researchers have attempted to compare the antibacterial activities of commercially available silver-coated/impregnated dressings against common pathogens (Ip et al., 2006; Thomas and McCubbin, 2003; and Parsons et al., 2005). Thomas and McCubbin (2003) noted, “Although caution must always be exercised when extrapolating the results of laboratory-based studies to the clinical situation, potentially important differences were detected in the antimicrobial activity of the products examined. It is also possible that the silver ions released by the dressings may have effects on wound healing that are unrelated to their antimicrobial activity. Further work is needed to address this issue.” Parsons (2005) advised, “... dressing selection should be based on the overall properties of the dressing as clinically relevant to the wound type and condition.”

“I’m not aware of any well-done studies indicating a decrease in wound infections by using silver dressings,” says Rupp. “There are some data looking microscopically at colonization and other surrogate markers for their biologic activity, and those show a benefical effect, but I haven’t seen data from an adequately-powered, prospective, randomized study. I don’t think those studies have been done and they probably should be before clinicians widely adopt these as a standard for post-operative dressings.”

Rupp says this is a problem for infection control in general. “There are very significant clinical questions in infection control, and we need the resources to allow us to answer these questions. In the past, for the most part, we have not had the resources to conduct adequately-sized, multi-center studies to answer the real questions of the day. Instead, it has been up to individual investigators working on a shoestring budget to try to pull off a study that is inadequately supported. Folks who have power of the purse strings must be made aware of this and rededicate some resources to address the problem of HAIs.”

Rupp continues, “Its been estimated that there are 100,000 deaths per year in this country linked to HAIs, but how much money is earmarked and how many resources are dedicated at the federal or local levels to address these issues? Unfortunately, very little! For the most part, until very recently, this has been a quiet issue. We have lacked a grass-roots advocacy effort. I mean, you don’t see people wearing colored ribbons or wristbands to draw attention to the problem of HAIs. Folks aren’t going on “fun runs” to generate money to fight HAIs. That is starting to change, but unfortunately the new interest has, in some cases, been diverted into draconian mandates and unwieldy legislation. Rupp relates, “In recent months SHEA and other organizations have been in front of congressional committees in order to educate our elected officials about the importance of this issue and suggest ways to constructively address the problem of HAIs. SHEA and the Infectious Diseases Society of America (IDSA) have partnered with a variety of other organizations including APIC to draft guidelines on how best to introduce and maintain infection preventive measures in healthcare institutions. These guidelines should be out in the Fall of 2008 and we hope they will help mobilize institutions to improve. We fully appreciate that many HAIs can be prevented using current methods and technology.” Rupp continues, “Although we know a lot about preventing HAIs, we have a lot more to learn. We need to set research priorities and then have resources set aside to address these issues.”

Rupp continues, “You have 100,000 deaths per year linked to HAIs, but how much money is earmarked and how many resources are dedicated at the federal or local levels that are aimed at these issues? When you talk to people at the NIH they say the CDC is supposed to take care of that and the CDC has never had an investigator-initiated research program. We are left in the middle of not having an adequate resource pool to help answer our questions. If you talk about the number of lives impacted by nosocomial infections, you don’t see people wearing colored ribbons or wristbands to draw attention to the problem of HAIs. People aren’t going on fun runs to generate money to fight HAIs. Instead, it’s this silent epidemic that we have not had the resources to address.”

Rupp says the fundamentals of infection prevention and control can get lost amidst the rush to adopt new technologies such as antimicrobials. “Many times what you see in the literature are studies related to gizmos because gizmos have financial resources behind them,” Rupp says. “That’s because a company is manufacturing them and they are willing to sponsor a small trial to gain credibility; the trials are often not designed to show a statistically significant impact on a meaningful infection. Instead surrogate markers for infection are sometimes targeted and extrapolations are made. We’re caught in the middle trying to judge what’s best for our patients. Furthermore, many of the most pressing issues don’t have anything to do with new devices – instead, they relate to influencing human behavior, education, and performance improvement – topics that have not received a lot of research support.”

Antimicrobial Hardware

Hardware is one of the high-touch surfaces in a hospital, and is another category in which antimicrobials are making a big appearance in the marketplace. Component Hardware Group, a manufacturer of hardware components for the healthcare arena and other industries, offers its products with Saniguard, a built-in antimicrobial treatment for metal and plastic products and coatings. When microbes, such as bacteria, yeasts, molds, and fungi, come into contact with a treated product surface, Saniguard’s inorganic, silver ion technology actively inhibits their growth by hindering cell wall transmissions, disrupting cell metabolism, and interfering with cellular reproduction. MicroShield is a hardware finish coating designed to permanently suppress the growth of bacteria, algae, fungus, mold and mildew for the lifetime of the hardware components under normal wear-and-tear conditions. The AgION antimicrobial compound is a silver-based antimicrobial agent that is incorporated into the MicroShield coating. Sargent, a hardware manufacturer, offers its product lines coated with MicroShield.

“Architectural hardware products with our MicroShield coating are a perfect compliment to the hand hygiene and environmental services protocols currently applied by hospitals across the country,” says Robert R. Tibbling, director of business development for healthcare and public facilities at ASSA ABLOY. “We know that compliance to protocols is relatively low. A silver-based antimicrobial coating continuously inhibits the growth of bacteria and viruses and can be applied in high-touch areas of a hospital where the potential for cross-contamination is high. The antimicrobial technology is another tool in the fight against HAIs.”

While the antimicrobial properties of treated hardware may be enticing to hospital administrators, costs may be a concern. “A realistic way to think about the cost-benefit equation is this — compare the cost of a single HAI to the additional price of the coating (about 5 percent or less of the total price of the architectural hardware item),” Tibbling says. “In addition, a clinician should consider the changes in reimbursement for HAI-related procedures, specifically the Centers for Medicare and Medicaid Services’ ruling on “never events” and the non-reimbursement for HAIs starting in October, as well as the potential harm to a hospital’s reputation over HAIs.”

The bacteriostatic properties of copper and brass were discovered two decades ago by Kuhn (1983) who discovered that older, tarnished brass hardware was actually more hygienic than newly installed stainless steel doorknobs and push plates. Kuhn used E. coli, Staphylococcus aureus, Streptococcus Group D and pseudomonas species to innoculate strips of metal, air-dried them for 24 hours at room temperature, inoculated them onto blood agar plates and incubated for 24 hours at 98.6 degrees F. The broths contained approximately 10 million bacteria/ml, a significant inoculum. Kuhn found that the copper and brass showed little or no microbial growth, while the aluminum and stainless steel produced a heavy microbial growth of all species. The test was repeated using several drying intervals, from 15 minutes to 24 hours. Kuhn noted that copper rid itself of some microbes within 15 minutes, while brass disinfected itself in seven hours or less, and newly scoured brass disinfected itself in one hour. Kuhn observed significant of all isolates on the aluminum and stainless steel strips as long as eight days after exposure. After three weeks, there was growth of all species except for Pseudomonas; scanning electron microscopy demonstrated that E. coli remained on the stainless steel but was eliminated on the brass.

Kuhn (1983) writes, “Culturing a stainless steel knob on a door between a burn unit and an intensive care unit, I found a multiply resistant Staphylococcus epidermidis with a susceptibility pattern identical to that found in the blood of a septic patient in the intensive-care unit. Cultures of wounds of several other patients yielded similar organisms. None of these observations prove cause, of course, but they ought to impress us with the need to take precautions, particularly in the presence of multiply resistant microbes ...We have known for years that certain metals are toxic to bacteria. It is the application of this knowledge to better infection control that warrants further attention.”

Antimicrobial Agents and Resistance Issues

American consumers’ love affair with antimicrobial products doesn’t seem to be fading. According to data from Tufts University’s APUA, within the last 20 years, residue-producing antibacterials — once used almost exclusively in healthcare institutions — have been added to increasing numbers of household products and cleaning agents. A recent survey reported that 76 percent of liquid soaps contained triclosan and approximately 30 percent of bar soaps contained triclocarban. Triclosan is a popular antimicrobial that has been bonded to the surfaces of everything from kitchen cutting boards to toys, and is an active ingredient in shampoos, facial cleansers, mouth rinses and toothpastes.

“There is a significant overuse of antiseptics in consumer goods,” Rupp observes. “I think triclosan is overused; it is found in toothpaste, soap, mouthwash, even cutting boards and mattress covers — you name a product and it seems triclosan has been incorporated into it these days. I think this practice is not doing any good in people’s households. “Having said that, however, it makes good sense to use antiseptics in medical/surgical applications within healthcare facilities. I think the concern over the development of antiseptic resistance and whether that co-develops with antimicrobial and antibiotic resistance is theoretical to some degree, but also is a justified concern. There are some data that indicate that there are specific genes and mechanisms of action for some antiseptics and specific mutations in those genes that are linked to resistance. We know that triclosan can serve as a substrate for the antibiotic multi efflux pumps, so I think there is some concern that if we use certain antiseptics they may actually co-promote antibiotic resistance. The judicious application of some antiseptics, chlorhexidine in particular, or those that don’t leave a residuum, like alcohol, make a lot of sense in hospital settings. Likewise, I think the use of alcohols in hand gels that consumers use as a convenient way to achieve good hand hygiene, is great. When they evaporate they don’t leave any residuum behind, so there is no risk of development of resistance.”

Tufts University’s APUA explains, “Because of their rapid killing effect, the non-residue producing antibacterial agents are not believed to create resistant bacteria. Resistance results from long-term use at low-level concentrations, a condition that occurs when consumer use residue-producing agents such as triclosan and triclocarban. Until recently, it was accepted that these agents did not affect a specific process in bacteria, and because of this, it was unlikely that resistant bacteria could emerge. However, recent laboratory evidence indicates that triclosan inhibits a specific step in the formation of bacterial lipids involved in the cell wall structure. Additional experiments found that some bacteria can combat triclosan and other biocides with export systems that could also pump out antibiotics. It was demonstrated that these triclosan-resistant mutants were also resistant to several antibiotics, specifically chloramphenicol, ampicillin, tetracycline and ciprofloxacin. Resistance to antibacterials has been found where these agents are used continuously (as in the hospital and food industry); however, at the present time, this modest increase in resistance has not yet created a clinical problem.”

Some may wonder if the continued widespread use of antibacterial agents could lead to more resistant bacteria. According to the APUA, “Many scientists feel that this is a potential danger, but others argue that the laboratory conditions used in the research studies do not represent the real world. So far, studies of antibacterial use in home products such as soap, deodorant and toothpaste have not shown any detectable development of resistance. However, such products have only been in use for a relatively short period of time and studies of their effects are still extremely limited.”

Child (2005) emphasizes that antimicrobial products and treatments “must not undermine the success of traditional hygiene methods and neither must conventional cleaning and hygiene operations be relaxed if antimicrobial coatings are employed.” 

References:

APUA. Tufts University’s Alliance for the Prudent Use of Antibiotics. http://www.tufts.edu/med/apua/Practitioners/healthcare.html and http://www.tufts.edu/med/apua/Q&A/Q&A_antibacterials.html

Child T. Antimicrobial surfaces. 2005. Accessed at http://www.allbusiness.com/asia/484476-1.html

Gibbins B and Warner L. Surface treatments: The role of antimicrobial silver nanotechnology. Medical Device & Diagnostic Industry. August 2005.

Dresher WH. Copper Applications in Health & Environment Area. August 2004. Accessed at: http://www.copper.org/publications/newsletters/innovations/2004/08/copper_helps_control_infection_in_healthcare_facilities.html

Noyce J, Michels H and Keevil C. Potential use of copper surfaces to reduce survival of epidemic meticillin-resistant Staphylococcus aureus in the healthcare environment. J Hosp Infection. Vol. 63, No. 3, Pp 289-297.

Noyce, JO and CW Keevil. The antimicrobial effects of copper and copper alloys on methicillin-resistant Staphylococcus aureus. Presented at the American Society of Microbiology, May 2004.

Pearson ML and Abrutyn E. Reducing the risk for catheter-related infections: A new strategy. Ann Intern Med. August 15, 1997. Vol. 127, No. 4. Pp. 304-306.

Maki DG, Stolz SM, Wheeler S, Mermel LA. Prevention of central venous catheter-related bloodstream infection by use of an antiseptic-impregnated catheter. A randomized, controlled trial. Ann Intern Med. 1997;127:257-66.

Raad I, Darouiche R, Dupuis J, Abi-Said D, Gabrielli A, Hachem R, et al. Central venous catheters coated with minocycline and rifampin for the orevention of catheter-related colonization and bloodstream infections. A randomized, double-blind trial. Ann Intern Med. 1997;127:267-74.

Rupp ME, Lisco SJ, Lipsett PA, Perl TM, Keating K, Civetta JM, Mermel LA, Lee D, Dellinger EP, Donahoe M, Giles D, Pfaller MA, Maki DG, and Sherertz R. Effect of a second-generation venous catheter impregnated with chlorhexidine and silver sulfadiazine on central catheter-related infections. Ann Intern Med. 2005;143:570-580.

Darouiche RO. Antimicrobial approaches for preventing infections associated with surgical implants. Clin Infect Diseases. May 15, 2003:36.

Ip M, Lui SL, Poon VK, Lung I, Burd A. Antimicrobial activities of silver dressings: an in vitro comparison. J Med Microbiol 55 (2006), 59-63.

Thomas S and McCubbin P. A comparison of the antimicrobial effects of four silver-containing dressings on three organisms. 1: J Wound Care. 2003 Mar;12(3):101-7.

Parsons D, Bowler PG, Myles V, Jones S. Silver antimicrobial dressings in wound management: A comparison of antibacterial, physical, and chemical characteristics. Medscape.com. Oct. 4, 2005.

Kuhn PJ. Doorknobs: A source of nosocomial infection? Diag. Med. Nov/Dec. 1983. Accessed at: http://www.copper.org/health/papers/doorknob.html

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