Heartburn drugs tied to higher risk of recurrent C diff


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A new study suggests the use of common heartburn medications may play a role in recurrent Clostridium difficile infection (CDI).

The study, published in JAMA Internal Medicine, is a systematic review and meta-analysis of previous studies assessing the links between exposure to common gastric acid suppressant medications, such as proton-pump inhibitors (PPIs) and H2-receptor blockers (H2Bs), and recurrent cases of CDI, the most common cause of hospital-associated diarrhea.

In the 16 observational studies included in the review, researchers found that nearly 20% of 7,703 patients with primary CDI developed recurrent CDI. The rate of recurrent CDI  in patients using gastric acid suppressants was 22.1%, compared with 17.3% in patients not taking gastric acid suppressant, a finding that suggests acid-suppressing medications are associated with an increased risk of recurrent CDI (odds ratio, 1.52). A sub-analysis that adjusted for age and potential confounding factors, such as comorbidities and concomitant antibiotic use, confirmed the association.

"There is about a 50% increase in risk of recurrent C diff in patients who are taking these gastric acid suppression medications," lead author Sahil Khanna, MBBS, a gastroenterologist at Mayo Clinic, told CIDRAP News.

A problematic pathogen

C difficile, a common environmental bacterium that causes nearly half a million infections and 15,000 deaths a year in the United States, is a problematic pathogen in healthcare settings because of its ability to survive on hospital surfaces.

It mainly affects older patients who are taking antibiotics for other infections. The antibiotics disrupt the normal gut flora, wiping out the good bacteria and allowing C difficile to flourish in the intestinal tract. Reducing unnecessary antibiotic use is considered one of the most effective ways to curb CDI.

Once patients are infected, CDI can be difficult to completely cure, partly because treatment requires more antibiotics. At least 20% of patients who get primary CDI have a recurrent infection within 8 weeks, with the risk being as high as 50% to 60% after three or more infections.

But while CDI is mainly associated with advanced age, healthcare, and antibiotic use, community-associated CDI among patients with low risk factors has also been on the rise, and the use of gastric acid suppressants is one of the factors researchers are exploring.

PPIs like omeprazole (Prilosec) and lansoprazole (Prevacid) and H2Bs like ranitidine (Zantac) and famotidine (Pepcid) are prescribed or sold over the counter for gastric reflux disease, peptic ulcer disease, and functional dyspepsia. They provide temporary relief from symptoms by reducing the secretion of gastric acid in the stomach. But patients often stay on them for much longer than necessary, and they sometimes use them for unnecessary indications.

"Sometimes we see patients who are on these medications for decades," Khanna said.

Khanna, who has been looking at the link between gastric acid suppression and primary cases of CDI for several years, says the evidence suggests an association. But the link between gastric acid suppression and recurrent CDI is less clear. The purpose of the current study was to review the past 20 years' of case-control, cohort, and clinical studies to see if a pattern could be discerned.

One theory is that because stomach acid normally kills C difficile in its vegetative, disease-causing state, suppressing it could help the bacteria proliferate. Another suggestion is that, like antibiotics, gastric acid suppression may contribute to CDI by altering the microbiome in the colon and disrupting the normal gut flora that can keep C difficile in check. So in patients who are already taking antibiotics, gastric acid suppression could exacerbate the problem.

Re-evaluating use of gastric acid suppressants

Even though the exact mechanism is unclear, Khanna said the findings suggest patients with CDI who are taking gastric acid medications should have a discussion about the risks and benefits with their physicians. While some patients truly need to be on these drugs, patients who don't have a true indication may be able to stop taking them.

"If you have a patient who is on these gastric acid suppression medications, we need to re-evaluate that," Khanna said. "Is it really necessary for this patient to be on gastric acid suppression?"

Khanna and his colleagues say that while unnecessary use of gastric acid suppressants should be limited, and that reducing use of the drugs may help reduce primary and recurrent CDI rates, the results should be interpreted with caution.

One of the drawbacks of the review, Khanna said, is that the observational studies they looked at varied in different ways, and their analysis could not account for all confounding factors. One issue is that the type of patients who are already at risk of recurrent CDI—those who are older, sicker, and being treated with antibiotics for other infections—are also more likely to be on gastric acid suppressants.

"That's one potential confounder that we haven't been able to control for," Khanna said.

Finally, Khanna added, the findings of the study indicate an association between gastric acid suppression and recurrent CDI, not cause and effect. The best way to understand better the true relationship between CDI and gastric acid suppression, he explained, is to perform randomized clinical trials in which CDI patients who continue to take the medications are compared with those who stop taking them.

See also:

Mar 27 JAMA Intern Med study

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