Drug combination linked to Clostridium outbreaks

Canadian researchers have found a connection between C. difficile cases and use of antibiotics with proton pump inhibitors.

By Victoria Stagg Elliott — Posted June 28, 2004

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Montreal hospitals battled outbreaks of Clostridium difficile that sickened hundreds and killed dozens last year, and researchers now are linking this flare-up to the use of antibiotics and proton pump inhibitors, according to a news report and a scientific study published online this month in the Canadian Medical Assn. Journal. The information will appear in the July print issue.

"The activity is higher than usual, and the patients are getting much sicker," said Sandra Dial, MD, the study's lead author and source of case statistics for the news report. She is the director of the ICU at the Montreal Chest Institute. "I sincerely hope that hospitals in America don't have to deal with what we've been dealing with because its been quite tough."

Dr. Dial's research team reviewed the medical records of more than a dozen hospitals in the area, finding more than 1,400 patients who tested positive for the bacteria in 2003. The team also linked 79 deaths to C. difficile. Researchers' analysis found that those who had received antibiotics and used PPIs were more than twice as likely to become sick.

"It's the combination of the two," said Dr. Dial. "If you only take [PPI's] and no antibiotics, your risks are very small."

American infectious disease experts are watching the situation closely. Over the past 20 years C. difficile has grown from being an occasional problem to the most common cause of infectious diarrhea in the hospital setting. Maryland's Greater Baltimore Medical Center announced eight cases in its rehabilitation unit, although that outbreak was small and did not include any fatalities.

"C. diff. is definitely on the rise -- without a doubt," said Scott Woods, MD, MPH, director of epidemiology at Bethesda Hospital in Cincinnati. "It's far more common, and we think of it almost immediately anytime someone has gastrointestinal problems."

Explaining the rise

While everyone agrees that the bug is certainly on the upswing in both numbers and strength, the reason why is more elusive. The link to antibiotic use has been long known. As a result, Dr. Dial is a member of the chorus advocating more judicious antibiotic use.

"Reducing the use of antibiotics will help everything, even the economy," said Sherwood Gorbach, MD, professor of community health and medicine at Tufts University School of Medicine in Boston. "How can you not agree with that?"

Dr. Dial, however, while acknowledging that PPI's are generally good drugs, also urges more judicious use of them.

"God gave you acid in your stomach for a reason, and one of the things your stomach acidity does is kill bacteria for you," she said. "There are clearly people who need to be on these drugs, but not everyone who has heartburn needs them. We need to be careful about all the medications that we use."

Others are skeptical. The PPI link makes a lot of sense, but experts said it was far too soon to start restricting their use because evidence is sketchy.

"We need stronger data," said Dr. Woods. "The problem is that proton pumps have been shown to be so beneficial for so many things that if they were shown to impact the C. diff. risk, it would really have to be pretty destructive to wipe out the beneficial effects."

There is also some disagreement about whether the numbers found by Dr. Dial's team represent a true outbreak. The bacterium has increased in incidence, and many people carry it without becoming ill. Experts suspect that some of the increase could be accounted for by more testing.

"Before you can really get nervous about it, there are so many pieces of information you have to find out," said Dr. Gorbach. "We don't know their background numbers of cases or if they've become more avid about testing."

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External links

"Risk of Clostridium difficile diarrhea in hospitalized in-patients prescribed proton pump inhibitors: cohort and case-control studies," Canadian Medical Assn. Journal, July 6, in pdf (link)

"Hospitals battling outbreaks of C. difficile," Canadian Medical Assn. Journal, July 6, in pdf (link)

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