Antimicrobials

The growing use of antimicrobial products is infiltrating healthcare systems across the nation. Are they truly affecting change in the fi ght against infection transmission, or are they simply providing a false sense of security?

There is no argument that infectious organisms can be spread from surfaces to hands to patients. A good example is an outbreak of norovirus reported last year among residents and employees of a 240-bed long-term care facility in Pennsylvania. More than half (52 percent) of the residents and nearly half (46 percent) of surveyed employees reportedly had gastroenteritis symptoms during the reported infectious period.¹ Researchers took environmental surface swabs from resident rooms, a dining room table, and an elevator button in an elevator used only by employees to test the method of transmission in the breakout. All samples tested positive for norovirus and both the environmental and clinical norovirus sequences were found to be identical.

Another study released this summer tested the hypothesis of infection transmission from surfaces to hands.² In this project, researchers inoculated the upholstery, flooring, and wall coverings in a hospital area with vancomycin-resistant enterococci (VRE) and Pseudomonas aeruginosa (P.aeruginosa). To aid in the assessment of potential for transmission, volunteers touched the inoculated surfaces and then palm plates for later review to test for growth.

Twenty-four hours following inoculation, all surfaces had recovery of VRE, and 13 of 14 surfaces had persistent P. aeruginosa. After cleaning (following manufacturers' instructions for each surface), VRE was recovered from seven surfaces, and P. aeruginosa from five surfaces. The plate cultures from the volunteers hands all tested positive for VRE.

Jeffrey A. Trogolo, PhD, chief technology officer at AgION Technologies, Inc., says that AgION is presently working with hospitals and universities to better measure and understand the link between surfaces and infection. With patients moving through a hospital from room to room and to different specialty areas, the specific source of an infection is not always known, he points out. What is known is that bacteria and viruses can survive on surfaces for 24 to 72 hours; that hand contact can transfer bacteria from one surface to another, and that the amount of transfer is dependent on the number of bacteria on the source surface.

Trogolo says that products treated with AgION, an antimicrobial compound, can reduce the number of bacteria on the surface of the product. He says the idea behind the use of the antimicrobial compound is to reduce the size of that source reservoir of bacteria so fewer bacteria are transferred to a susceptible host.

Thomas E. Carr, president and chief executive offi cer (CEO) of CHG, Inc., manufacturer of SANIGUARD antimicrobial treatment, says antimicrobials can play a vital role in preventing healthcare-acquired infections (HAIs). Many common touch points in a healthcare setting can be treated with a permanent antimicrobial when the product is first produced, he asserts. Door hardware, faucet handles, handwash sinks, bed railings, bed pans, and washers are but a few examples of where bacteria and mold grow; and these are also areas that can be treated by manufacturers who have access to credible antimicrobial materials.

He continues, When properly treated, the efficacy of the antimicrobial treatment can outlast the life of the product itself. One of the keys to preventing transmission of disease is to prevent the spread of the bacteria or virus. Powder coating metallic surfaces such as door handles, grab bars, and faucet handles with a permanent treatment of an inorganic antimicrobial material has proven very effective against numerous bacteria and strains of certain viruses including norovirus, severe acute respiratory syndrome (SARS), and methicillin-resistant Staphylococcus aureus (MRSA). Antimicrobials are also effective when impregnated into a plastic surface. There are numerous efficacy tests that have been performed to demonstrate benefits of an antimicrobial.

Carr shares one such efficacy test that found when testing two sets of stainless steel coupons (one set was a control and the other treated with SANIGUARD antimicrobial coating), feline calicivirus was reduced on the set of treated metal coupons.³ Feline calicivirus is a virus in the same family as the human norovirus and is commonly used as a model for evaluating the effectiveness of disinfectants against norovirus. The results indicate that the feline calicivirus loss infectivity faster (more than double the rate) on the SANIGUARD-treated coupons than the control coupons.

On the flip side, not everyone is a believer in the effectiveness of surface antimicrobial usage, as shown in the Utah Department of Health Bureau of Epidemiologys August 2000 report titled Consumer Use of Products Containing Antimicrobial Agents. The report emphasizes that antimicrobial agents that have been added to plastics and other solid materials should not be expected to kill surface microorganisms. It says that water must be present to transport the antimicrobial chemical agents across the cell wall of the microorganisms and that an object with an incorporated antimicrobial agent is not self-sanitizing. Any microbial contamination will require soap and water to wash it off or be killed by adding a liquid germicide, the report reads. The report also goes on to point out that if there is the belief that objects containing an antimicrobial agent are sanitary or self-sanitizing, standard hygiene practices such as washing with soap and water, may not be performed.

Still another lingering argument is the concern over the growing resistance of organisms. According to the Food and Drug Administration (FDA's) Task Force on Antimicrobial Resistance, while antimicrobial-containing devices (e.g. urinary and intravenous catheters, prosthetic heart valves, and joints) have been developed with the intention of preventing infections, clinical safety and effectiveness data for many such devices are lacking. The FDA literature goes on to point out that concerns exist over incorporation of critical drugs into or onto devices, and the potential for the consistent presence of such drugs to foster resistance. There is a need for standardized tests to demonstrate safety and effectiveness, the Task Force writes.

Stuart B. Levy, MD, a Tufts University professor of medicine and of molecular biology and microbiology, director of the Center for Adaptation Genetics and Drug Resistance at Tufts University School of Medicine, a staff physician at the New England Medical Center, and president of the Alliance for the Prudent Use of Antibiotics, say there is no evidence that impregnation of antimicrobials into solid objects has any effect on infection transmission. He points out that this very topic was challenged by the Environmental Protection Agency (EPA), which registers every antimicrobial product as a form of pesticide4, in 1997. The EPA challenged Hasbro, Inc.s health claims that its antimicrobial coverings used on its Playskool toys protect children from infectious diseases caused by bacteria. Hasbro received a fine and was required to take away the health claims from these items, Levy says.

I do not believe that the impregnation of plastics and clothing with these products offers any benefit and is a waste of money and also of potential harm to our environment, he adds. However, Levy says, The most important and beneficial use of antimicrobials is as biocides in handwashing in healthcare centers. These could be both those which incorporate chemicals such as triclosan or alcohol such as the more currently used ones in the hospital setting.

Dawn Sievert, MS, antimicrobial resistance epidemiologist at the Michigan Department of Community Health, states that much of the research concerning the impregnation of various products with antimicrobials and its effect on microbial resistance is still very much up for debate. The antimicrobial triclosan in hand soap has been researched, but there is still continual research being done on it, she offers. I havent seen anything thats overwhelming in either direction. They havent actually shown an increase in resistance, but they have shown different findings. The one argument for that is the chemical structure of triclosan mimics, or looks very close to, some of the antibiotics that are used. Thats the idea and the argument behind doing the research. To say if it does look like it, then it could actually force the changes and create more resistance because of it, but like I said, that debate is still ongoing. There has been no research that shows strongly either way.

Levy adds that there is evidence in the laboratory that antimicrobial biocides those that leave residues (not the alcohols or bleaches or peroxides) can lead to resistance not only to themselves, but also to antibiotics. This finding has not been found in the healthy home studies, he states, but it has not been thoroughly investigated nor in relation to products impregnated with these chemicals.

Several medical devices, primarily catheters and wound care products, containing antimicrobials demonstrate a benefit to the healthcare industry, according to Trogolo. He says Vygon, a European medical device manufacturer that incorporates the AgION material in its Multicath Expert and Lifecath Expert catheters, completed a clinical trial demonstrating that use of the Multicath Expert catheter significantly reduces catheter colonization by bacteria. Trogolo also points out that foley catheters containing silver have been proven to reduce urinary tract infections and have been shown to reduce hospital costs through the prevention of those infections.

Antimicrobial-impregnated Catheters

Central venous catheters (CVC) have long been associated with bloodstream infections (BSIs), and practitioners have worked long and hard to find an answer in reducing these infections. Guidelines set by the National Institutes of Health (NIH) recommend the use of an antimicrobial- or antiseptic-impregnated CVC in adults whose catheter is expected to remain in place for more than five days.⁵ But does this really make a difference?

Researchers at Creighton University Medical Center say that there is a lack of solid evidence to support the benefit of CVCs impregnated with antimicrobial agents (A-CVCs) for the prevention of catheter-related BSIs.6 However, colleagues at the section of infectious diseases department of medicine at the University of Wisconsin Medical School in Madison, assert that A-CVCs have been the most intensively studied technology for the prevention of CVCrelated bloodstream infections over the past 30 years, adding that there is in fact a large body of evidence that demonstrates a powerful decrease in the risk of infection.⁷

Still another Baylor College of Medicine study says that the A-CVCs were just as likely to be colonized with bacteria as tunneled catheters. However, they did find that BSIs were four times less likely to originate from the ACVCs than from the tunneled catheters (0.36 vs. 1.43, respectively).8 In addition, the researchers note that A-CVCs on average remain in place for a shorter period of time vs. the tunneled catheters (30.2 days vs. 43.8 days) used in the study.

A-CVCs have been found to reduce the risk of CVC-associated BSI by 66 percent in patients receiving total parenteral nutrition,⁹ and in a multicenter, randomized, prospective study, antimicrobial- impregnated ventricular catheters demonstrated a dramatic reduction in the incidence of catheter-related infections.¹⁰ Just how long the antimicrobial lasts varies, but cerebrospinal fluid shunt catheters impregnated with rifampicin and clindamycin have shown antimicrobial activity for up to 127 days.¹¹

Another contributing factor in deciphering efficacy appears to be the use of the particular antimicrobial. For example, while minocycline- and rifampin-impregnated catheters have been associated with a significantly lower rate of bacterial contamination, such as staphylococci colonization, there has also been a proven significant increase in Candida spp. colonization.12 In contrast, the invitro and in-vivo efficacy against Candida albicans and Candida krusei of devices impregnated with chlorhexidine and chloroxylenol was examined in a separate Baylor College of Medicine study and the researchers found that impregnated devices produced large zones of inhibition against both organisms and had significantly lower colony counts than non-impregnated devices.¹³

Bandages, and Dressings, and Ointments Oh My!

John A Dobos, DDS, chief executive officer of MedWrap Corp., and inventor of MedWrap Wound Dressings, says that in his many years of association with professional sports teams in and around Buffalo, N.Y., he realized that it wasnt the initial injury players sustained that kept them off the field for extended periods of time, but the high incidence of secondary infections that were occurring. In response, he initially developed a knee wrap to help lower the incidence of bacterial proliferation to the wound. The whole premise of what our wound cover tries to do is prevent infection before it ever happens, he explains. He says MedWrap uses the premise of an island dressing (an adhesive which wraps all the way around) to set up an optimal healing environment. However, with a moist environment for tissue re-granulation, you also are setting up the perfect environment for bacterial proliferation. So, an island dressing without an added antimicrobial sets the stage for bacterial proliferation, he adds.

After researching the many antimicrobials on the market, Dobos decided upon triclosan to impregnate his dressings. The unique thing with this triclosan is that it is bacterial-static, not bacterial-cidal, he points out. The importance of that is that if you put a wound cover on for a few days, you realize that you are not killing off all of the organisms underneath that environment, but you are limiting them from reproducing. If you limit them from reproducing, then you cant get into the next generation and you cant get the level of bacteria high enough to cause toxicity to the tissue.

Dobos says the dressing is especially effective in protecting against airborne organisms, and the company currently is conducting further studies on the efficacy of the dressing in infection rate reduction. We are trying to prevent infection by putting on an island dressing which will prevent any kind of infection from coming in, any type of infection from seeping out, yet keeping the environment optimal during that period of time, he says.

There have been some questions raised concerning the efficacy of antimicrobial products in the treatment of wounds. Many healthcare professionals send their patients home with instructions to use antimicrobial-impregnated over-the-counter (OTC) products for care of surgical and other wounds.

In my practice, I use advanced silver dressings for both treatment and prevention even in wounds that are being treated with systemic antibiotics, says Cynthia A. Fleck, MBA, BSN, RN, ET/WOCN, CWS, DNC, DAPWCA, FCCWS, a certified wound specialist and an advanced practice nurse in dermatology. Fleck is the vice president of clinical marketing for Medline Industries, Inc.s advanced skin and wound care division and serves on the boards of the American Academy of Wound Management (AAWM), the Association for the Advancement of Wound Care (AAWC), and the American Professional Wound Care Association (APWCA). The literature states that even deeply infected wounds that are being managed with oral and intravenous antibiotics should also be cared for simultaneously with broad-spectrum antimicrobials, such as silver, topically. This is because wounds are often not well vascularized and blood flow cannot adequately carry the antibiotics to this tissue.

Fleck says silver is broad spectrum, killing both gram-positive and gram-negative bacteria, including resistant forms of MRSA and VRE, fungus, viruses, and yeast. It is more universally effective than antibiotics and more broadly effective than chlorine, she adds. She says silver is effective because it attacks the cell wall, membrane transport, RNA function, DNA synthesis, and protein function all at once.

The antibacterial activities of five commercially available silver-coated/impregnated dressings were compared against nine common burn and wound pathogens including MRSA, Enterococcus faecalis, P. aeruginosa, Escherichia coli, Enterobacter cloacae, Proteus vulgaris, Acinetobacter baumannii (A. baumannii), and a multi-drug-effl ux-positive A. baumannii.¹⁴

After testing under in vitro conditions, all five silver-impregnated dressings investigated exerted bactericidal activity particularly against gram-negative bacteria. Two of the bandages were found to have a broad spectrum of bactericidal activities against both gram-positive and gram-negative bacteria, while other dressings demonstrated a narrower range of bactericidal activities. The spectrum and rapidity of action range widely for different dressings, and a thorough understanding of the characteristics of these bandages may enable providers to specifi cally target their use for prophylaxis in skin grafting or for MRSA wounds, the researchers note.

The University of Miami School of Medicine tested the effi cacy of four OTC antimicrobialcontaining bandages as compared to two OTC ointments against Staphylococcus aureus (S.aureus).¹⁵ Only one of the antibiotic bandages and one of the topical ointments were found effective in reducing S. aureus proliferation in partial thickness wounds. Both of those products contained neomycin. Although many OTC bandages and ointments contain antimicrobials, they may not be effective at reducing bacteria in wounds, the study points out.

Barrier protection is also important, especially when dealing with a highly contagious, highly resistant MRSA infection. Nanocrystalline silver dressings, for example, have been found to provide a complete, or almost complete, barrier to the penetration or spread of MRSA in 95 percent of readings, according to one Austrian study.16 Of further mention in this study, the researchers note that 67 percent of the 10 MRSAcolonized wounds studied showed a decrease in the MRSA load with an eradication rate of 11 percent when using the nanocrystalline silver dressing.

Sievert, who works with community-acquired MRSA, says she has seen a significant increase of MRSA incidence over the past three years. Through her role at the Michigan Department of Community Health, she continuously tries to educate people on the manner in which infection transmission occurs. When we talk about spread or whether we should use special products or buy things that are impregnated with stuff, it comes down to something more basic than that, and that is general hand washing and hygiene. So if people are worried about sharing a keyboard vs. trying to keep that piece of equipment sterile which I think is going to be very difficult to do no matter what you put in it the idea is if you use something and youre going to do something else, wash your hands. Its not about trying to sterilize the environment; its about the very simple procedure of trying to keep our hands clean. That would make a huge difference if people would just start doing that everywhere.

Fleck adds that if a wound is progressing well, a biocide or antimicrobial simply is not necessary. These are usually wounds that progress along the normal healing cascade. Many of these wounds are acute in nature and if the host or person is not sick and doesnt have other major diseases such as vascular problems, diabetes, or other co-morbid states, their wounds tend to heal without problems. Weve all heard the old saying, If its not broken, dont fix it, and that goes for wounds too. If an overgrowth of bio-burden isnt part of the problem, we dont need to utilize these advanced technologies, she says.

Sievert tends to agree, adding that the use of simple measures and simply getting people to understand the variables of infection is what is of the most importance. The transmission and the spread; if people understood how it spreads, then they could understand how easy it is to prevent it. If you stop that train of transmission, then you can solve that problem. Its soap and water. It doesnt have to be fancy, she concludes. 

References

1. Wu HM, et. al. A norovirus outbreak at a long-term-care facility: the role of environmental surface contamination. Infect Control Hosp Epidemiol. 2005 Oct;26(10):802-10.

2. Lankford MG, et. al. Assessment of materials commonly utilized in health care: Implications for bacterial survival and transmission. Am J Infect Control. 2006 Jun;34(5):258-63.

3. Charles P. Gerba, Charles P and Naranjo, Jaime E. Feline Calicivirus Reduction by Component Hardware Group Treated Coupons. Department of Soil, Water and Environmental Science. University of Arizona, Tucson. May 23, 2005.

4. National Coalition Against the Misuse of Pesticides. Pesticides and You. Beyond Pesticides. Vol. 24, No. 3, 2004.

5. OGrady NP. Et. Al. Guidelines for the prevention of intravascular catheter-related infections [published erratum appears in MMWR Weekly 2002 Aug 16;51(32):71]. MMWR Recomm Rep 2002 Aug 9;51 (RR-10):1-29. [293 references] PubMed.

6. McConnell SA, Gubbins PO, Anaissie EJ. Are antimicrobial-impregnated catheters effective? Replace the water and grab your washcloth, because we have a baby to wash. Clin Infect Dis. 2004 Dec 15;39(12):1829-33. Epub 2004 Nov 19.

7. Crnich CJ, Maki DG. Are antimicrobialimpregnated catheters effective? Dont throw out the baby with the bathwater. Clin Infect Dis. 2004 May 1;38(9):1287-92. Epub 2004 Apr 15.

8. Darouiche RO, et. Al. Comparison of antimicrobial impregnation with tunneling of long-term central venous catheters: a randomized controlled trial. Ann Surg. 2005 Aug;242(2):193-200.

9. Alonso-Echanove J, et. al. Effect of nurse staffing and antimicrobial-impregnated central venous catheters on the risk for bloodstream infections in intensive care units. Infect Control Hosp Epidemiol. 2003 Dec;24(12):916-25.

10. Sloffer CA, et. Al. Antimicrobial-impregnated external ventricular catheters: does the very low infection rate observed in clinical trials apply to daily clinical practice? Neurosurgery. 2005 May;56(5):1041-4; discussion 1041-4.

11. Pattavilakom A, et. al. Duration of in vivo antimicrobial activity of antibiotic-impregnated cerebrospinal fluid catheters. Neurosurgery. 2006 May;58(5):930-5; discussion 930-5.

12. Leon C, et. Al. Benefits of minocycline and rifampin-impregnated central venous catheters. A prospective, randomized, double-blind, controlled, multi-center trial. Intensive Care Med. 2004 Oct;30(10):1891-9. Epub 2004 Jul 20.

13. Darouiche RO, Mansouri MD, Kojic EM. Antifungal activity of antimicrobialimpregnated devices. Clin Microbiol Infect. 2006 Apr;12(4):397-9.

14. Ip M, et. al. Antimicrobial activities of silver dressings: an in vitro comparison. J Med Microbiol. 2006 Jan;55(Pt 1):59-63.

15. Davis SC, et. al. Over-the-counter topical antimicrobials: effective treatments? Arch Dermatol Res. 2005 Nov;297(5):190-5. Epub 2005 Nov 11.

16. Strohal R, et. al. Nanocrystalline silver dressings as an efficient anti-MRSA barrier: a new solution to an increasing problem. J Hosp Infect. 2005 Jul;60(3):226-30.