Antibiotics and proton pump inhibitors may not be the best mix, according to a study published Jan. 24 in the Journal of Antimicrobial Chemotherapy.

People who took an antibiotic when they were taking a PPI had a higher risk for Clostridioides difficile infection, the researchers found.

PPIs belong to a class of drugs used to treat acid reflux. 

Studies already have found an independent association for having a higher risk of CDI in people who took antibiotics and PPIs separately. There’s not much research on the CDI risk when people take the medications together.

A team of researchers at Sweden’s Karolinska Institutet used data from people with CDI infections between 2006 and 2019. The team matched 43,152 people with CDI to 355,172 controls who didn’t have CDI. The scientists assessed the effect of recent (0 to 30 days) and preceding (31 to 180 days) antibiotic and PPI use on CDI and also the recurring risk.

At some point during the study, 63% of people with CDI were exposed to antibiotics before they got CDI; 39% of people with CDI took PPIs before infection. This is compared with 16% and 14% of controls, respectively.

When people took both medications more recently, the odds for being infected with CDI were 17.51 times higher compared with those who didn’t take the medications. The odds were 15.37 times higher if a person took antibiotics and 2.65 times higher if a person only took antibiotics. 

The odds for getting CDI in the preceding time bracket was less pronounced but still existed; the odds were 9.13 in those who took both drugs, 5.42 times higher in those who took antibiotics and 2.08 times higher in those who only took PPIs.

Recent antibiotic use slightly raised a person’s chance for recurrent CDI, whereas recent PPI use wasn’t associated with CDI coming back again.

“Our findings stress the need to reconsider the risk-benefit of both antibiotics and PPIs, which are both still over-prescribed,” the study authors wrote.

“The findings of this study add more weight to the evidence on the role of prescription drugs and the risk of CDI and reveals the even stronger combined effect. This article only investigates one piece of the puzzle regarding drug interactions in relation to CDI risk, especially among this older age group most at risk for CDI, where polypharmacy is rampant,” the authors added.