Silver-coated instruments may beat infections


Silver. It's not just for jewelry anymore.

A Colorado company called Nexxion Corp. is hoping a thin film of silver oxide on medical devices will help prevent many of the 2 million infections that patients acquire in hospitals every year.

The revival of silver - an ancient germ-fighter - is an effort to combat "nosocomial" infections, which strike 5 percent to 10 percent of hospital patients, according to the U.S. Centers for Disease Control and Prevention.

The cost of treating them averages $6,000 per patient, or as much as $10 billion a year.

It's been estimated that nosocomial infections contributed to the deaths of 88,000 Americans in 1995, according to the CDC. Most had immune systems weakened by age, underlying disease, or medical or surgical treatment.

If Nexxion wins approval from the Food and Drug Administration, the company says its silver coatings - on such devices as catheters or artificial knees - would kill most of the Staphylococcus aureus, E. coli and other bacteria that the devices frequently carry into a patient's body, preventing infection and allowing wounds to heal normally. The technology would also reduce the use of antibiotics, and help curb the development of dangerous antibiotic resistance among infectious organisms.

"There are no bacteria known to be resistant to silver or silver oxide," said Dan Storey, Nexxion's chief technical officer, who spoke this week in Baltimore at the annual March meeting of the American Physical Society.

Silver isn't new to the war against infection, Storey said. Roman soldiers put silver coins in water to purify it. Silver sutures were developed in the mid-19th century to reduce wound infection. And doctors for generations put silver nitrate drops into the eyes of newborns to prevent blindness caused by gonorrhea contracted from their mothers during childbirth.

The development of antibiotics in the 1940s pushed silver treatments aside, but concerns about the evolution of antibiotic-resistant organisms have revived interest in them.

Not just any silver will do. "In the past, it's been just pure silver," Storey said. "It's somewhat effective, but it's not very strong in its pure form.

"What we're doing new here is we are creating a silver oxide which is inherently an unstable molecule," he said. When these molecules get into the body, they split into a silver ion and an oxygen "free radical," both of which are toxic to microorganisms.

"This is like a one-two punch," Storey said.

A conventional antibiotic typically works by attaching itself to a receptor on the surface of the microbe, and using that route to enter and kill or cripple it. But in time, some of the bacteria will mutate in a way that prevents the drug from working at that receptor anymore. The defensive trait is passed along and a new, antibiotic-resistant strain of bacterium is born.

The silver ion, however, is taken directly into the cell, where it interferes with a variety of cell functions and components, including DNA, killing the organism. "The physical structure of the DNA cannot change such that it rejects this ion," Storey said. "If it were to mutate, it would kill itself, because it wouldn't be able to replicate."

The real challenge for Nexxion was to develop a way to coat medical devices with silver that would preserve its effectiveness without damaging the devices.

The solution was something called "low-temperature ionic plasma deposition." Simply put, the silver is vaporized, passed through an extremely hot oxygen plasma, and deposited on the medical devices in a flexible film a half-micron deep - that's 1/50,000 of an inch.

"We are able to deposit it pretty much on anything," Storey said.

Nexxion says testing shows that its silver coatings reduce bacterial populations by factors of 100,000 to 1 million. "So we are a thousand times better than what is considered `antimicrobial' in the industry," Storey said.

The effects can be extended from a few days to as long as 28 days, if needed, before the body absorbs all the silver and eliminates it, he said.

But silver has its drawbacks. In sufficient concentrations, silver ions are toxic to healthy human cells. Tests of another company's artificial heart valve with a silver component were ended in 2001 after the silver caused adjacent heart cells to die, loosening the valve.

To avoid similar problems with Nexxion's products, Storey said, "we just had to tune it down to find the sweet spot where we're killing bacteria but not killing the human cells."

The silver coating still can cause inflammation, he said. But "that actually seems to speed healing, because when you cause inflammation, it rushes blood and nutrients to that site and helps regrowth."

It's a very promising but problematic field, according to Dr. Dennis G. Maki, a professor of medicine and head of infectious diseases at the University of Wisconsin Medical School. He is not associated with Nexxion.

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