Silver: The Once and Future Antimicrobial

A few years ago, a friend of mine named Randy received a nasty gash on his leg while helping with a rescue on Tennessee’s Ocoee River, a favorite play spot for whitewater enthusiasts. Randy was immediately taken to a local emergency room where his leg was stitched up and he was given a prescription for antibiotics. That should have been the end of the story.

A few weeks later Randy's fiancé received a message that Randy (who lived in another state) had been hospitalized. Concerned, she phoned his doctor, who said, “We’re pretty sure now that he’s going to make it, but we’re not sure we can save the leg.” Randy’s wound had become infected with a multiple drug resistant (MDR) bacteria. It is pretty certain that this bacteria came not from the less-than-pristine waters of the Ocoee, but from the hospital where he was treated. The wonder of modern medicine in the 21st century is that every routine visit to a hospital is a lottery in which you might become infected with a life-threatening pathogen. Infections like Randy’s cause 90,000 deaths in the U.S. per year, more than twice the number of AIDS deaths, according to the CDC. In this case, although Randy had a rough time of it, the story had a happy ending; the leg was saved and the happy couple got married.

MDR bacteria are a real time example of evolution in action. The minute the FDA approves a new antibiotic, the bacteria start evolving a way around it. With a doubling time of 20 minutes to an hour, bacteria can evolve faster than the pharmaceutical company’s product cycle, which is realistically about 12 years between innovation and FDA approval. MDR bacteria tend to hang around hospitals, where the use of antibiotics is the highest, although episodes of community-acquired infection are increasing.

In the last week, the FDA approved an old drug, an antibacterial called silver, the same precious metallic stuff that earrings and bracelets are made of. The FDA approval consisted of Silver Soaker catheters from I-Flow, which use AcryMed’s “silver nanotechnology that can render existing medical devices impervious to infection-causing bacteria”. The catheters are coated with silver nanoparticles that kill most bacteria, even those that are resistant to the most advanced antibiotics.

Silver helps heal wounds; this little sliver of information has been common knowledge in the medical profession since the ancient Greeks, long before the germ theory was formulated. Bulk silver, however, doesn’t dissolve well, so its efficacy as an antimicrobial has been marginal at best. Thus it has largely been displaced by modern antibiotics.

Antibiotics are cleverly designed molecules that interfere with a microbe’s biochemistry, usually at a single site. Silver, by contrast, is a blunt instrument that interferes in several different ways with a bug’s life style. As a result, it is difficult for a bacterium to develop resistance. Silver is able to kill vancomycin and methicillin resistant pathogens, which have spilled out from hospitals into the community in recent years to become a major problem.

Nanocrystalline silver is a textbook example of the difference in behavior between nanophase material and bulk material. The antimicrobial action of highly disordered nanocrystalline silver occurs more rapidly (in as little as 30 minutes) and lasts longer than bulk silver particles.

Nucryst Pharmaceutical produces Acticoat, a dressing for serious burns that is impregnated with nanocrystalline silver. The product replaces a generic silver-containing cream that was only active for a few hours, after which it had to be scraped off (at considerable cost in agony to the burn patient) and reapplied. Acticoat, on the other hand, is good for a week and can be lifted off in one piece. Acticoat is now also FDA approved for use with serious wounds, including diabetic ulcers. These wounds, which usually form on the feet or limbs, can require amputation if the wounds do not heal. Acticoat was named one of the top ten nanotech products for 2004 (even though it was introduced in 1998) by the Forbes Wolf/Nanotech report. Though manufactured entirely by Nucryst, Acticoat is marketed by health science giant Smith and Nephew. The product has allowed Nucryst to score modest profits in 2003 and 2004.

The success of Acticoat in healing recalcitrant wounds led researchers to speculate that an antimicrobial action was not the whole story. Sure enough, it turns out that nanocrystalline silver has an anti-inflammatory action as well—specifically, it suppresses the activity of two inflammatory cytokines, interleukin 12B, and tumor necrosis factor alpha. Therefore Nucryst is exploring use its use in inflammatory conditions, including atopic dermatitis and certain respiratory conditions.

Nucryst is a subsidiary of Westaim Corporation [NASDAQ—WEDX; TSX—WED].