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Drug resistance { November 12 2002 }

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   http://www.freep.com/news/health/nstaph12_20021112.htm

http://www.freep.com/news/health/nstaph12_20021112.htm

Germs develop a deadly defense

Drug-resistant bacteria discovered in Detroit
November 12, 2002

BY EMILIA ASKARI
FREE PRESS STAFF WRITER

A 40-year-old Detroit area woman had endured painfully infected foot sores for more than a year.

Doctors gave her numerous antibiotics, but nothing worked. Finally, last April, they amputated one of her toes -- and made a frightening discovery.

Her sores were infected with a virulent new strain of the bacterium staphylococcus aureus, or staph aureus. By stealing genetic material from another bug, the new strain became totally resistant to vancomycin, the longtime drug of last defense against it. Health officials would not identify the metro Detroit woman or what hospital treated her.

The infection was the first of its kind in the world and a landmark defeat for doctors and public health officials in the fight against growing antibiotic resistance. It also was evidence that the Detroit area has become an incubator for resistant strains.

"From a scientific point of view, it's probably one of the most remarkable and significant events in my lifetime," said Dr. Steve Lerner, vice chief of infectious diseases at Detroit Medical Center.

Added Dr. Fred Tenover of the federal Centers for Disease Control and Prevention in Atlanta: "This is an organism that could cause very serious disease if it was in the community."

Staph aureus is a common pathogen that infects about 400,000 U.S. hospital patients a year. About one-quarter of them die. For decades, scientists have been dreading -- but expecting -- a staph aureus strain to emerge that is resistant to vancomycin.

Some experts postulate that eventually, so many bacteria will develop resistance that antibiotics won't work and hospitals will be filled with people dying from infections, as they were in the 1920s.

Staph aureus can live innocuously in the nose of a healthy person. About 5 to 10 percent of Michiganders have it and don't know it, said William Brown, a Wayne State University pathology professor. If it infects the blood, however, it can quickly become fatal, particularly if the person has another medical condition.

In the 1920s, British scientist Alexander Fleming discovered penicillin, the first antibiotic developed from mold. By the mid-1950s, about a decade after penicillin came into wide use, most staph aureus strains in this country were resistant to it. So the pharmaceutical industry came up with methicillin and a series of related drugs.

Also developed in the late 1950s, vancomycin had a lot of side effects and was not widely used. Methicillin and its kin were much more popular -- and the bacteria soon began growing resistant to them.

That was especially true in the Detroit area, where many intravenous drug users in the 1970s began mixing antibiotics, including methicillin, with heroin. It was a misguided attempt to avoid infection from dirty needles, said Dr. Marcus Zervos, an infectious disease physician at Beaumont Hospital in Royal Oak.

The primary effect: a rapidly increasing methicillin resistance in the metro area. Subsequently, the resistant bacteria infected hospital patients and others who didn't use illicit drugs.

"Since our part of the country overused vancomycin compared to other areas, that's why we saw this problem with staph aureus," Zervos said.

For years, some physicians held out hope that vancomycin was a super drug, one that would never be outsmarted by bugs. The first indication that staph aureus was becoming resistant to vancomycin came in 1997 in Japan, a country known in medical circles for its liberal use of antibiotics. Vancomycin still could kill the strain discovered there -- but only at a much larger dosage. Later that year, the world's second case of staph aureus with partial resistance to vancomycin was found at Oakwood Hospital in Dearborn.

"We're the capital of staph aureus resistance," Lerner, with the Detroit Medical Center, said.

The bacteria causing the Detroit area woman's infection this year was even more virulent. The emergence of a vancomycin-resistant strain has medical experts concerned that the number of U.S. patients who die from infections may soon exceed 100,000 a year.

"In the scheme of public health threats, this has to rank close to the top," David Ropeik, director of risk communication at the Harvard Center for Risk Analysis, said of antibiotic resistance. "It's a serious threat now, and it's getting worse fast. It's dramatically more of a public health threat than pesticides on food."

To combat resistance and ensure drugs work when needed, health officials want people to do without antibiotics when infections are not life-threatening, said Matt Boulton, Michigan's state epidemiologist.

"We have to change consumer attitudes," he said. "There should not always be an expectation that you'll leave the doctor's office with antibiotics."

Aggressively keeping patients with resistant infections in isolation has helped several Scandinavian countries slow antibiotic resistance dramatically. Doctors there also prescribe the drugs only in extreme circumstances.

Many health professionals hope that following this summer's discovery of vancomycin-resistant staph aureus in the metro woman's foot, Americans will be scared enough to accept limited use of antibiotics.

So far, however, the public remains largely unaware of the discovery that shook doctors around the world.

Brown, the WSU professor who also directs the microbiology lab at the Detroit Medical Center, vividly remembers the June morning a technologist informed him of the strange test results. A doctor caring for a woman at an outpatient dialysis clinic had sent in a swab with a sample of pus from a sore where a catheter punctured the woman's skin. It looked like staph aureus, but it was showing strong resistance to vancomycin.

"I figured it was a mistake," Brown recalled. So he took the suspect bacteria to a special room used for handling the most dangerous microbes. There, he tested the bacteria for vancomycin resistance and again got an off-the-chart reading.

That's when Brown got on the phone -- fast. He knew that he had to work quickly to keep the bacteria from spreading. "I thought, 'Oh my God. This is it,' " he recalled.

Within two weeks, a team from the CDC in Atlanta had flown in and identified 400 people in the Detroit area who needed to be tested for signs of the rogue bacteria: hospital workers and patients, members of the woman's choir and women who had gone to the same nail salon as the woman.

So far, 300 more Michiganders have been tested, and no one else has been found to have the vancomycin-resistant staph aureus, which doctors call VRSA (pronounced VER-sa). Even though the bacteria causing the woman's infection were not killed by vancomycin, they did respond in the laboratory to three other drugs. Two are antibiotics introduced within the past two years. The other, an older drug, was given to the woman for three weeks.

Since then, the woman's infections have mostly healed and tests show no sign of VRSA in her body. Doctors expect to continue to test her for months.

The antibiotics that worked against the woman's staph aureus infection have several downsides, including a cost of more than $100 a day. And they're not a silver bullet either: Other strains of staph aureus already have become resistant to them.

In September, a second case of vancomycin-resistant staph aureus was discovered in a Pennsylvania patient who appears to be recovering.

But with two such incidents in three months, the medical profession is on high alert. Around the world, experts are watching for the next VRSA and fervently hoping they will be able to stop it.

From the Kalamazoo labs of drugmaker Pharmacia, Vice President Ferdinand Massari said it's harder to find new drugs. It takes at least a decade and $100 million to try, he said.

"For every one drug that you see in the store, there are probably 10,000 that were tested and didn't make it," he said.




Contact EMILIA ASKARI at 313-223-4461 or askari@freepress.com.




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