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Officials Note Outbreaks of Virulent Germ

Diarrhea-causing bacterium seems to be emerging in hospitals and local communities

FRIDAY, Dec. 2, 2005 (HealthDay News) -- A more virulent strain of a diarrhea-causing bacterium is emerging, and seems to be doing so both inside and outside of hospitals, health experts are warning.

The new outbreaks of the organism, Clostridium difficile, appear to be related to the widespread use of a class of antibiotics called fluoroquinolones.

Two studies detailing the phenomenon will be published in the Dec. 8 issue of the New England Journal of Medicine and were released early to coincide with more troubling news.

Usually confined to the hospital setting, recent outbreaks of C. difficile-associated disease (CDAD) seem to be moving into communities, according to a related report in the Dec. 2 issue of the U.S. Center for Disease Control and Prevention's Morbidity and Mortality Weekly Report (MMWR).

"There might be the same thing or a related thing happening out in the community," said Dr. L. Clifford McDonald, lead author of one of the journal studies and co-author of the MMWR report.

"We're not sure yet but we have been hearing reports of people who have never been in hospital, or not recently, and even some who have not had antibiotics -- people we have thought of as low risk are getting CDAD. We're also trying to sound the alarm on that," added McDonald, a medical epidemiologist with the CDC.

C. difficile is the leading cause of hospital-acquired infectious diarrhea. The organism can also cause colitis, resulting in colectomies (removal of part of the colon) and even death.

Unlike other bacteria, which can become resistant to the drugs actually used to treat them, C. difficile can develop a sort of resistance or reaction to antibiotics used to treat other problems, such as pneumonia.

"The major risk factor for getting C. difficile-associated disease is having received an antibiotic for some other reason," McDonald said. "They kill the healthy bacteria in the large bowel and, with that, allow the C. difficile organism that person has in the intestine to overgrow. The antibiotic knocked out the healthy bacteria that are usually keeping C. difficile in check."

Epidemiologists have noted an increase in CDAD from the late 1980s through 2001. More troublesome, however, is a reported increase of 26 percent in the proportion of patients discharged from hospitals with this diagnosis between 2000 and 2001.

The University of Pittsburgh Medical Center, for instance, reported that the incidence of CDAD was nearly twice as high in 2000 and 2001 as it was in 1990 through 1999. During the latter time period, 26 patients required a colectomy and 18 died.

There also seems to have been an increase in the severity of cases. In one nationwide survey, 39 percent of infectious-disease physicians noted a heightening of the intensity of symptoms.

"We had been hearing that cases were more severe," McDonald said. "We hypothesized that part of this could be explained by the mutation or emergence of a strain of the organism that might have special virulence properties and/or by resistance to antibiotics."

To check the hypothesis, McDonald and his colleagues analyzed 187 isolates collected from eight health-care facilities in six states where CDAD had occurred between 2000 and 2003. They compared these samples with isolates collected before 2001.

They found a common strain in all hospitals, a strain that had been found before but only rarely. "It had been a minor player," McDonald said. "Now it was a major outbreak strain. What could have changed?"

Indeed, there was evidence that the strain might be more virulent, as it produced 23-fold more Toxin A and 16-fold more Toxin B than previous strains (Toxins A and B are the main toxins produced by C. difficile). In addition, the scientists found a binary toxin and a gene deletion, both of which might contribute to virulence.

That explained the virulence. It did not, however, explain why this strain had gained more ground in recent years. That could be explained by the increased use of fluoroquinolones in North American hospitals, officials said.

A second study in the journal found parallel developments in Quebec, Canada. A 2004 analysis at 12 Quebec hospitals found a strain of C. difficile associated with more severe disease. It also appeared that resistance to fluoroquinolones spurred the spread of the organisms.

Where do the findings leave the public and public health professionals?

"This leaves us trying to sound the alarm for hospitals to be conducting careful surveillance and prevention," McDonald said.

Another strategy is preventing unnecessary use of antibiotics. "We should be doing that anyway," McDonald said.

With fluoroquinolones, however, this will be a tall order.

"They are a very important class of antibiotics with a low side-effect profile and they're effective," McDonald added. "They have been attractive therapies and maybe they have been used more than they should be."

More information

The CDC has more on C. difficile infection.

SOURCES: L. Clifford McDonald, M.D., medical epidemiologist, U.S. Centers for Disease Control and Prevention, Atlanta; Dec. 8, 2005, New England Journal of Medicine; Dec. 2, 2005, Morbidity and Mortality Weekly Report
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