Therapy uses viruses as natural antibiotics

FORT WAYNE, Ind. — Stepping barefoot on a nail in April changed the path of Fred Bledsoe's life.

The puncture wound seemed innocuous, but because he's diabetic and wounds are hard to heal, Bledsoe cleaned it carefully.

The Fort Wayne man never imagined that the antibiotic-resistant bacteria that infected his foot would land him in a local hospital for 10 weeks of unsuccessful treatment, then send him halfway around the world in search of a cure.

The treatment that worked, called bacteriophage, is available only in Russia and parts of Eastern Europe and the former Soviet Union. Tbilisi, Georgia, is the world's center for development and use of these naturally occurring viruses that destroy specific bacteria.

It is where Bledsoe, 46, found his miracle cure.

He and his family are spearheading efforts to raise awareness in the United States about phage treatment and help with research to get Food and Drug Administration approval for its use here.

In September, after 2 1/2 months of intravenous antibiotics in a U.S. hospital, doctors told Bledsoe only amputation would stop the spread of staphylococcus. The bacteria was creating oozing wounds on his toes, foot and leg. Dead tissue slowly crept upward.

"They actually had the amputation scheduled," he said. Then he called his sister, Saharra Bledsoe, who was out of town.

"I told him, 'Don't do anything until I get home.' I heard my mother's voice say, 'You didn't come this far to fail.' I knew God had another plan," Saharra Bledsoe said.

Washington connection

When she returned, she happened to see a CBS "48 Hours" show called "Silent Killers." Canadian musician Alfred Gertler told of his yearlong battle with an antibiotic-resistant foot infection that was cleared using phage treatment given in Tbilisi.

From the show, Saharra Bledsoe learned of Betty Kutter, a professor at The Evergreen State College in Olympia, who has done extensive phage research. The professor had connections to Eliava Institute in Georgia, a world-renowned center for developing and manufacturing therapeutic phages.

Saharra Bledsoe contacted Kutter and began making arrangements to take her brother to Tbilisi.

But Fred Bledsoe was skeptical when he heard where he was going and the method of treatment. His brother, Dr. Larry Bledsoe, a Fort Wayne internal medicine specialist, was doubtful, too.

"On the other hand, it was intriguing, the idea of viruses fighting bacteria. So, I went and researched it and found it had been used in the past in this country. There were very few side effects. I felt it was safe," said Larry Bledsoe.

The Bledsoe family chipped in and Fred Bledsoe and his sister were able to buy the $1,200-a-piece round-trip tickets to Tbilisi.

"We were treated like celebrities," Saharra Bledsoe said. They were the first blacks ever to be treated at the Republic of Georgia Regional Hospital, which works closely with the Eliava Institute.

And, "as far as I know, they are the first Americans to be treated there," Kutter said.

Cultures of the bacteria in Fred Bledsoe's foot were taken. A phage solution, containing viruses that work against the three bacteria found in his foot, was injected into the infected areas twice a day for two weeks. Then a phage powder was used for several days. In less than three weeks, tests showed the bacteria were gone. The wounds healed.

Not a new treatment

Scientists have known of the existence of bacteriophages since the early 1900s.

The viruses have the ability to attach to the surface of a specific bacterial cell. After a specific kind of phage finds its bacterial cell "match," the viral DNA is injected into the host cell. In minutes, the virus multiplies until it takes over and kills the cell.

Phage therapy can be used to kill specific pathogens without disturbing beneficial bacteria. They pose no risk to anything other than their specific bacterial host, said Zemphira Alavidze, a phage researcher at the Eliava Institute.

Phages were used in the 1930s in the United States, before penicillin was discovered.

In fact, the American Medical Association did a review of bacteriophage therapy but dismissed its effectiveness at that time because, without the technological ability to see viruses, there was no proof they were living organisms. Besides, pharmaceutical companies were finding more effective antibiotics.

"In Georgia, phages are the meat and potatoes of treatment," said Kutter, who has a Ph.D. in biophysics from the University of Rochester, N.Y. Kutter first traveled to Tbilisi in 1990 to examine bacteriophages of a specific E. coli bacterium. It was then that she learned bacteriophages were widely used there as antibiotics.

"I'm a serious, hard-core scientist. I was very skeptical. It took a while of seeing things happen, talking to people, before I started taking it seriously," she said.

A rush to bring phage to U.S.

Drug-resistant bacteria, such as methicillin-resistant staph aureus (MRSA) has been a growing concern in medical circles in the United States. Staph is one of the three bacteria found in Fred Bledsoe's foot.

There has been a gradual rise in MRSA since 1980, said Dr. William Jarvis of the Centers for Disease Control and Prevention in Atlanta. Some blame overuse or misuse of antibiotics.

The "big gun" used against antibiotic-resistant bacteria has been vancomycin, but cases of vancomycin-resistant staph are cropping up too, according to the CDC.

People should understand that phage treatment will not replace antibiotics, said Dr. Terry Brown, president of Intralytix, a Baltimore-based company researching agricultural and other uses for phage. The company is looking at how phages can keep meat-processing equipment and plants free of potentially deadly bacteria such as listeria.

The company also holds the international license to make, market and distribute PhageBioDerm, a phage patch used to treat burns and other skin wounds. Although PhageBioDerm is used in Georgia, it is not yet available in the United States.

Kutter said for U.S. citizens to access phage, "it will have to be manufactured here. It will not work to import it. (Georgian) standards would not meet FDA approval."

According to the October 2002 issue of Science magazine, there are about two dozen companies worldwide in a frenzy to make phage treatment available in Western markets.

Exponential Biotherapies Inc. of Port Washington, N.Y., has completed FDA State I, or safety, trials of a phage effective against a bacterial strain called vancomycin-resistant enterococci.

The company hopes to launch clinical trials of the phage later this year.