The logic behind coating such medical devices as indwelling catheters, invasive lines and implants with antimicrobials is simple: By adding inhibitory or cidal agents to items that enter or penetrate a normally intact area, it's possible to prevent, or at least decrease, the chance of a bacterial infection occurring in that space or organ. But does the clinical evidence bear this logic out? Take the true-or-false quiz on the next page and then read on for an exploration of the potential benefits of products treated with antimicrobials.

Battling biofilms
If a bacterial cell attaches to a surface, be it a blood vessel, heart valve or the surface of an orthopedic implant, it can then multiply by simple cell division. The cells remain attached to each other, and as they continue to multiply they may begin to form a biofilm, composed of a layer of polysaccharide, that surrounds the bacterial colony, making it difficult for white cells to engulf the cells or for antibiotics to penetrate and have any effect on them. "A significant proportion of medical implants become(s) the focus of a device-related infection, difficult to eradicate because bacteria that cause these infections live in well-developed biofilms," researchers from the University of Southern California's Center for Biofilms wrote in a 2005 study.[1]

We already take many precautionary measures to prevent biofilms from developing at the surgical site or on surfaces that come into contact with the surgical site. Hand hygiene, antibiotic prophylaxis, skin preparation, gloving, gowning and draping are all part of this sterile technique. But when you're inserting or implanting a foreign device for a prolonged period, these strategies may not be enough to prevent harmful biofilms from developing. One or more bacteria can enter any area where an intact surface is compromised, with an indwelling catheter, an invasive line or an implantable device acting as a potential point of entry. In these instances, antimicrobial agents — typically used to treat device-related infections — can be very effective weapons in your SSI prevention arsenal. By coating materials that will enter the body superficially or deeply with antimicrobial agents, you can kill or at least inhibit any microorganisms on the surface of the device and prevent bacteria from entering the incision site.

Know your antimicrobials
The term "antimicrobial agent" encompasses both the molecules synthesized by microorganisms and the substances made in a laboratory. All such agents work by blocking some function needed for bacterial growth. Antibiotics such as rifampin, heavy metals such as silver and copper and chemical agents such as chlorhexidine have all been used to coat or otherwise treat products and devices used in surgery, including catheters, implants, wound dressings and hand scrubs. Antimicrobials can either be completely embedded in the material of the device or applied as surface coatings. Let's look at the 3 types of antimicrobial coatings.

• Antibiotics. Different types of organic biocides are effective against different types of bacteria, so in many cases you'll see a combination of antibiotics used to coat devices. For example, we know that the antibiotic rifampin can penetrate some biofilms; that's why it's used as part of an antibiotic coating on catheters. But because bacteria become resistant to this drug very quickly, it's often paired with a second antibiotic, such as minocycline. A 1999 study showed "vascular catheters impregnated with minocycline and rifampin (M/R) were found to be highly efficacious in preventing catheter-related infections,"[2] and a 2008 study concluded that central venous catheters impregnated with minocycline and rifampin "demonstrated superior anti-adherence activity and more prolonged antimicrobial durability when compared with other approved anti-infective catheters against" multidrug-resistant bacteria.[3]

In another example, the combination of rifampin, the antiseptic triclosan (which targets bacteria by inhibiting fatty acid synthesis) and trimethoprim (a sulfa that interferes with folic acid synthesis), was shown to be effective in vitro when used to coat a modified silicon peritoneal catheter. Antibacterial activity lasted for at least 280 days with a greater than 99.9% reduction in attachment of bacteria to the CAPD catheter, with no colonization.[4] If this proves to be effective in vivo, it could have a significant impact on reducing peritonitis in dialysis patients.

There is, however, a downside to coating devices with antibiotics. Microorganisms that survive this exposure may develop resistance to the drug and cause infections that are difficult to treat. The 1999 study on M/R-coated intravascular catheters found no existing evidence of resistance to either agent caused by the antimicrobial coatings, but concluded that "further studies are required to determine whether the risk of resistance outweighs the benefits derived from their use."[2]

• Heavy metals. Heavy metals such as silver have been used for many years as a way to prevent, or at least slow down, invasive bacterial infections. (Think of silver nitrate eye drops in neonates and silver sulfadiazine for burns.) Ionic silver has several antimicrobial effects, including the inhibition of DNA replication and enzymes essential to the production of adenosine triphosphate, a primary transporter of energy in the cell. It's also been hypothesized that silver ions affect the function of membrane-bound enzymes, such as those in the respiratory chain. In addition to its broad-spectrum effect on microorganisms, silver is favored for its compatibility both with human tissue and with medical device materials.[5]
• Antiseptic and antibacterial chemicals. We're all aware of the use of chlorhexidine gluconate (CHG) as a surgical scrub and a surgical skin prep. This antiseptic, which can kill both gram-positive and gram-negative microbes, has also been impregnated into dressings that serve as a barrier for bacterial entry at a catheter site and as a coating on some materials that enter sterile body areas. However, keep in mind that the possibility of a hypersensitivity reaction, such as anaphylaxis, is possible when chlorhexidine is used as a coating — just as is the case when used as an agent in surgery.[6, 7]

Do they work?
We know that indwelling medical devices pose a significant infection risk, and we know that antimicrobial agents can help reduce that risk by killing or inhibiting microorganisms that can colonize these devices. But do we know for sure that these products can play a significant role in preventing device-related infections — enough to justify their often higher cost? Well, it depends on which application of antimicrobials you're talking about.

The bulk of the available research on devices treated with antimicrobials focuses on catheters, both urinary catheters and intravascular catheters, as they are two of the most common culprits in device-related infections. Most of the studies show some level of improvement in preventing infections with antimicrobial-treated catheters. A 1999 study conducted at the University of Texas MD Anderson Cancer Center concluded that antimicrobial intravascular catheters "have been shown to be highly cost effective in decreasing the risk of catheter-related bloodstream infection."[2] A 2008 systematic review of the literature on antimicrobial urinary catheters "found consistent but variable evidence that antimicrobial-coated catheters prevent catheter-associated bacteriuria/funguria during short-term catheterization; however, no study demonstrated a clinical benefit."8 Antimicrobial coatings on urinary catheters have proven to be of little or no value if catheterization goes past a few days. In fact, continued catheterization beyond 3 to 4 days significantly increases the incidence of catheter-associated urinary tract infections, which is why CMS' Surgical Care Improvement Project recently added removal of these catheters within 24 hours as a compliance measure.9

There are fewer available studies on the efficacy of antimicrobial-treated devices other than catheters, but depending on the type of product you're considering and how long it's been on the market, you should be able to get your hands on some research that can help you determine whether its potential infection prevention benefits are worth the extra expense. Be sure to review the literature carefully and be wary of any product for which there is scant clinical evidence; a single article validating its efficacy may prove to be premature and not reproducible. Finally, remember that products treated with antimicrobials are just 1 element in your infection prevention protocol and shouldn't overshadow such basic best practices as proper hand hygiene and skin preparation.

Answers
1. True [10]; 2. False; 3. True [8]; 4. False; 5. True [2]; 6. False; 7. True [3]