The Centers for Disease Control and Prevention (CDC) has warned that serious gastrointestinal infections from the bacteria Clostridium difficile (or C. diff) have affected nearly half a million people in 2011, with 29,000 dying within 30 days of the initial diagnosis.

C. diff. has become the most common microbial cause of healthcare-related infections in U.S. hospitals, often occurring in individuals who are on antibiotic regimens. The infection causes difficult symptoms including: diarrhea, abdominal cramping, fever, loss of appetite, and potential complications that can lead to death.

Now, according to a recent study published in the journal Gut and Liver, it seems that proton pump inhibitors (PPIs) like Nexium and Prilosec may increase the risk of this difficult infection. Researchers reported that in critically ill patients treated with PPI, there was a higher risk for C. diff. infections (CDIs).

Critically Ill Patients at Risk for Stress Ulcers

For the study, researchers noted that PPIs and histamine-2 receptor antagonists (H2RAs or H2-blockers) like Zantac and Pepcid are commonly prescribed to treat stress ulcers (stress ulcer prophylaxis or SUP) in critically ill patients. This population is at a higher risk for these types of ulcers than the general population. The ulcers can be particularly dangerous if they cause bleeding, because that increases the length of a patient’s stay in ICU, while also increasing the risk of mortality.

Doctors often prescribe therapy with acid-reducing drugs like PPIs to help prevent complications from stress ulcers. Yet the use of PPIs in critically ill patients has been identified as a potential risk factor for CDI. Researchers decided to look into that risk more carefully by comparing patients taking PPIs with those taking H2-blockers.

Study Links PPIs with Increased Risk of C. Diff. Infection

Scientists analyzed incidences of CDI in patients who were admitted to intensive care units and stayed for more than three days between August 2005 and July 2012. They then traced those patients who were diagnosed with CDI while they were suffering from a stress ulcer.

Out of 1,005 patients—444 were treated with PPIs and 561 with H2-blockers—only 38 or 03.8 percent were diagnosed with stress-ulcer-related CDI. Results showed, however, that patients receiving PPIs were at a considerably higher risk for the infection.

More specifically, a total of 6.7 percent of those taking PPIs developed CDI, compared to only 1.8 percent of those taking H2-blockers.

“PPI therapy,” the researchers reported, “is associated with a higher risk of SUP-related CDI than H2RA therapy in critically ill patients.”

PPIs Intended Only for Short-Term Use

This study is one of many concerning the serious potential side effects of PPIs. Other studies have linked them with an increased risk of chronic kidney disease, bone fractures, low magnesium levels, and dependency.

PPIs were approved for the short-term treatment of gastrointestinal problems like heartburn, gastroesophageal reflux disease (GERD), ulcers, and esophagitis. Because of aggressive advertising by the drug manufactures, however, they are often used for long periods of time, which can increase risk of complications.

A 2014 study, for instance, reported that PPIs were being “abused through overuse,” that there was some evidence that improper use was rising, and that many patients were using them for four years or more.