Researchers at McGill University say re-analysis of data from a large British database supports their controversial argument that widely prescribed antacid drugs may be predisposing some users to develop C. difficile outside of hospital settings.

Led by Dr. Sandra Dial, the study suggests people who were taking the drugs — called proton pump inhibitors — were 3½ times more likely to develop Clostridium difficile- associated disease than non-hospitalized people who didn't take the popular medications. The study was published Monday by the Canadian Medical Association Journal.

Evidence has been conflicting, with some teams finding a link and others discounting it. More studies are likely to emerge in the next few weeks as infectious disease researchers converge on two major conferences for their field, one in San Francisco later this week and one in Toronto in mid-October.

If Dial's work proves to be true, it would suggest research on C. difficile has been focused too narrowly to date, looking mainly at the incidence and causes of cases found in hospitals.

"The more I've looked into Clostridium difficile, I think there's a whole lot more we need to learn about this disease," Dial said from Montreal.

Antibiotics blamed unfairly

Concern over the increasing incidence and severity of C. difficile hit the scientific community several years ago. In the flurry of research papers that has followed, the nasty and recurrent diarrhea has been largely described as a hospital-based problem, where rampant antibiotic use has made patients vulnerable to the sometimes fatal bacterium.

But Dial and others are suggesting antibiotics alone can't account for the entire increase, particularly in C. difficile infections in people who haven't recently been hospitalized.

"It's almost like they got an unfair head start in the blame game," Dial said.

"They definitely play an important role. But the message we'd maybe like to get out is: if your patient in the community hasn't gotten an antibiotic but they're having diarrhea, and if they're elderly and they're sick and have some of the other things [risks] we've found, consider checking them for C. diff.

"Don't just assume they don't have it because they didn't get an antibiotic."

Proton pump inhibitors are used to treat acid reflux and peptic ulcers and to prevent peptic ulcers in people taking daily doses of Aspirin or other painkillers that are hard on the stomach. Popular brands include Nexium, Losec and Pariet.

Study design critiqued

Dial and several of the same co-authors suggested the drugs might be playing a role in C. difficile disease in an article published last December in the Journal of the American Medical Association. Their argument, based on analysis of cases from this same British database, met with skepticism in some quarters, in part because of the way their study was designed.

In an effort to make the argument more airtight, they went back to the database, focusing only on people who received an oral form of the antibiotic vancomycin. As the only accepted use for the expensive drug is to treat C. difficile, anyone who was prescribed the drug probably had the disease, they argued.

But some experts not involved in the study, including a field leader, Dr. Dale Gerding, acknowledge being "a little skeptical about the study design."

Gerding, a researcher at Hines Veterans Affairs Hospital in Chicago, said it would be useful to test the PPI theory in the animal model used to study the disease, hamsters.

It's important to find out if the drugs are playing a role in development of C. difficile since PPIs are so widely used, agreed Dr. Clifford McDonald, a C. difficile expert at the U.S. Centers for Disease Control in Atlanta.

As the study of C. difficile expands, it's becoming apparent what happens in hospitals is only part of the story, he suggested, noting there is other emerging evidence to support the idea PPIs may be playing a role.

"I think we can say the fact that people can have C. diff without antibiotic exposure is becoming more clear," McDonald said.

"Whether that's a new phenomenon or people are testing more, we don't know."

Some antacids have mild antibiotic effect

Gerding suggested if PPIs are linked to a rise in C. difficile cases, it may be because proton pump inhibitors have a mild antibiotic effect — not because, as others argue, they lower the acidity of the stomach and make it easier for C. difficile spores to survive and thrive.

To boost his argument, he noted that Dial's study found that people taking another type of antacid drug were not at greater risk of developing C. difficile.

Dr. Andrew Simor, an infectious disease specialist at Toronto's Sunnybrook Health Sciences Centre, said while he's open to the argument Dial is making, the jury is still out on whether PPIs are fostering an increase in C. difficile cases, but something more is at play than over-use of antibiotics.

"This disease occurred before antibiotics. So while in today's environment there is little doubt antibiotics are the major player, they are obviously not the only one. And there has to be multiple risk factors involved in many of these patients."