New research shows that individuals taking proton pump inhibitors have a moderately higher risk of community-associated Clostridioides difficile infection (CDI). The research also shows that the higher risk lasts for up to one year after receiving the treatment.
The study was conducted in Denmark as scientists are examining the dangers of community-associated CDI versus the hospital-associated cases that are more common. The report noted that in the United States and Europe, approximately 20% to 30% of CDI cases are community-associated rather than hospital-associated.
Health care professionals have believed that proton pump inhibitors make an individual more susceptible to CDI for many years. That belief has been somewhat controversial because of a lack of randomized controlled trials.
The researchers conducted a nationwide cohort study to examine any connections. They used databases of patients who received care for CDI in Denmark between 2010 and 2013.
They compiled patient characteristics, C diff testing data, and filled prescription data, and they used the Danish National Microbiological Database to find cases of community-associated CDI. Then the scientists used self-controlled case series analyses to estimate incidence rate ratios for community-associated CDI based on whether the individual has used proton pump inhibitors. The investigators also took into account when the prescription had been filled relative to when the infection began. In addition, they accounted for several confounding factors like socioeconomic status and chronic disease.
The research found 3583 cases of community-associated CDI. More than a quarter of the cases (964) occurred while patients were taking proton pump inhibitors, 324 occurred in the 6 months following treatment, and 123 happened within 6 and 12 months of taking proton pump inhibitors. The remaining 2172 cases occurred when patients were not, or had not recently, used the drugs.
Those data translated into an adjusted incidence rate ratio (IRR) of 2.03 (95% CI, 1.74-2.36) of community-associated CDI among patients taking proton pump inhibitors compared with those not using the therapy. For 0 to 6 months and 6 to 12 months, the IRRs were 1.54 (95% CI, 1.31-1.80) and 1.24 (95% CI, 1.00-1.53), respectively.
The authors noted that the study did not determine why proton pump inhibitors appear to heighten the risk of CDI. One possibility is that the proton pump inhibitors instigate alterations in intestinal microbiota that either induce proliferation of C diff or inhibit the normal microbiome’s ability to suppress pathogen growth. However, such a connection has yet to be proven, they said.
“It is also possible that the use of [proton pump inhibitors] may increase the risk of infection with gastrointestinal pathogenic bacteria,” they wrote. “Because such infections cause diarrhea, diagnostic activity may increase and, hence, C diff might be demonstrated as a pure bystander rather than the actual cause of gastrointestinal illness.”
One key limitation of the study was the lack of information regarding the use of the therapy. While the individuals filled their prescriptions, the researchers had no way to know if they actually took the drugs as prescribed. Denmark’s national prescription registry does not include prescriptions administered to inpatients.
Even so, the investigators said, misclassification of drug exposure would tend to bias the results “towards the null and, if present, would not change the conclusion of the study.”