Study of C. difficile outside hospitals suggests bacteria may be changing
 
Helen Branswell, Canadian Press, Wednesday, December 21, 2005

TORONTO -- A new study by Montreal researchers suggests rates of C. difficile in non-hospitalized people may be rising, even among people who haven't been taking antibiotic drugs - something previously thought to be a virtual prerequisite to infection.

Use of commonly prescribed medications - antacids known as proton pump inhibitors and prescription painkillers known as non-steroidal anti-inflammatory drugs or NSAIDs - appeared to increase the risk of contracting the disease outside of health-care institutions.

But experts said those previously suspected (proton pump inhibitors) and surprising (NSAID) risk factors couldn't fully explain the rise of C. difficile rates in the community.

They suggested the findings seem to point to genetic changes in Clostridium difficile that may be making the bug easier to pick up outside of hospitals.

"That is really a remarkably high increase in cases," Dr. Dale Gerding, a leading U.S. expert in the field, said of the findings of the study led by Dr. Sandra Dial of McGill University.

Gerding, who was not involved in the work, said it is "imperative" that researchers look at another outpatient database to see if the findings are true elsewhere.

"I think this needs verification in another database," he said from Chicago, where he is associate chief of staff for research at the Hines Veterans Affairs Hospital.

"It's very tantalizing that there is something else going on and something probably new, because of the increased rate of disease."

C. difficile is a bacterium that can be carried in the colon without causing disease. But when it does, it causes severe and recurrent diarrhea that can be difficult to treat. In the worst cases, it can lead to inflammation or deterioration of the colon that can be fatal.

It has typically been viewed as a hospital disease, with the overwhelming majority of cases occurring within health-care facilities.

The difficulty of eradicating C. difficile spores once an environment has been contaminated by an infected patient makes the bug easier to contract in hospitals. And high rates of antibiotic use in institutions leave patients susceptible to the bacterium. (Antibiotics alter the natural flora of the bowel, allowing C. difficile to take hold.)

Dial and her co-authors searched a large British outpatient database for cases of C. difficile diagnosed among people who had not been hospitalized in the year prior to developing infection. Their study was published Wednesday in the Journal of the American Medical Association.

They found that from 1994 to 2004, the rate of cases in the community rose steadily, from about one case per 100,000 at the start to 22 per 100,000 at the end of the period.

Gerding said the increase was "very alarming."

More startling still was the fact that only 37 per cent of the people infected had been prescribed antibiotics in the 90 days prior to their infection.

"That floors me a little bit," said Dr. Clifford McDonald, a C. difficile expert at the U.S. Centers for Disease Control in Atlanta who was not involved in the research.

The study found that people taking proton pump inhibitors - Nexium is one - were three times more likely to develop C. difficile than people who weren't taking the drugs. People taking NSAIDs were also at a modestly elevated risk of developing C. difficile.

Dial admitted her team wasn't expecting that latter finding.

"We actually stumbled upon that," she said, adding she could only offer a theory about why painkiller would increase the risk of infection.

"We know they damage the lining of the upper gastrointestinal tract.... And we also found that they can damage the lower intestinal tract. We just wondered if an injured intestinal tract might be more susceptible to the organism."

The three researchers all agreed the changing pattern of infection suggests the bacterium may have undergone subtle changes that hitherto have gone unnoticed.

That may be because recent research efforts, led by Gerding and by McDonald and colleagues at the CDC, have focused on the emergence of an epidemic strain of C. difficile that has been plaguing hospitals in parts of the U.S. and in Quebec.

That strain produces massively elevated toxin levels and leads to significantly more serious disease and higher rates of death than traditional strains.

"The epidemic strain is . . . the latest permutation in this organism. But there might have been some permutations going on below the radar screen before this," McDonald said.

"And they might be what's more responsible for some of the early increase both in this country" - the United States - "(and) this community stuff in Great Britain.

"Maybe there are some other genetic changes. I think we need to keep our mind open. Think beyond the epidemic strain."

The findings suggest the potential link between the bacterium and drugs like NSAIDs and proton pump inhibitors needs to be explored further - and doctors and patients alike should think twice before the drugs are used, Dial said.

"The message I've tried to give with this is that every drug potentially can have side-effects," she said.

"And that whenever patients are prescribed or are taking drugs, they have to really discuss with their physician the risks and benefits about the drugs that they're taking."

The Canadian Press 2005