Researchers Identify Link Between Gastric Acid Suppressants and Recurrent C. Diff Infection

Patients with Clostridium difficile infection (CDI) who take medications to suppress their gastric acid levels are significantly more likely to experience a recurrence of the infection, according to researchers from the Mayo Clinic.

The study published in JAMA Internal Medicine notes that CDI, also called C-diff, is the most common cause of hospital-acquired diarrhea and can lead to potentially fatal inflammation. Some of the existing literature has found that patients taking gastric acid suppressant medications, including proton pump inhibitors (PPIs) and H₂ receptor blockers (H2Bs), have a higher risk of primary CDI, but studies on the risk of recurrent CDI have been conclusive.

To clarify the risk of recurrent CDI associated with gastric acid suppressant medications, the Mayo Clinic researchers conducted a meta-analysis of 16 relevant studies. They also performed subgroup analyses to control for potential confounders, like age or comorbid conditions.

Of the 7703 patients in the studies, 1525 went on to develop recurrent CDI. Those taking the gastric acid suppressant drugs had a recurrence rate of 22.1%, while only 17.3% of those not taking the medications experienced CDI recurrence. Even after controlling for potential confounders through subgroup analysis, the use of gastric acid suppressants was still associated with an increased risk of CDI.

The researchers also determined that the studies on PPI use alone demonstrated an increased risk of CDI recurrence, while the studies on the use of PPIs and/or H2Bs did not. There was only 1 study that looked solely H2B use.

According to a press release from the Mayo Clinic, gastric acid suppression drugs like omeprazole, which is a PPI, and ranitidine, an H2b, are commonly used medications sold without a prescription to help treat gastroesophageal reflux disease, peptic ulcer disease, or dyspepsia.

In the study, the authors suggested that changes in the gut microbiome brought on by gastric acid suppressants could be a mechanism contributing to the increased risk of CDI. They recommended that further studies explore this connection while controlling for confounding variables.

There were limitations in the study, like the inability to determine why the gastric acid suppressants were needed, Sahil Khanna, MBBS, senior author, said in the press release. Still, the finding that these drugs could potentially put patients at risk of CDI and its dangerous complications should not be ignored.

"It may be reasonable to re-evaluate the need for these medications in patients with C-diff," said Khanna.

The researchers called for further prospective studies on the association between gastric acid suppression and recurrent CDI, particularly those that focus on the dosage and duration of the suppressant use or the simultaneous use of antibiotics.

“A randomized clinical trial evaluating the effect of continuing the use of gastric acid suppressants vs stopping them in patients with no serious indication might be helpful in assessing the true association between gastric acid suppressants and the risk of recurrent CDI,” the study authors concluded.