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Ongoing use of proton pump inhibitors (PPIs) appears to increase the risk of acute viral gastroenteritis (AGE) during high-circulation periods of enteric viruses, a large French cohort study suggested.

Ana-Maria Vilcu, MSMSc, of Sorbonne University in Paris, and colleagues, writing in , found an all-ages adjusted relative risk (aRR) of acute gastroenteritis that was 1.81 times higher (95% CI 1.72-1.90) in the 233,596 patients receiving continuous PPI therapy than in the 626,887 patients who were not.

This risk was highest among adults ages 65-74 (aRR 2.19, 95% CI 1.98-2.2), though the authors noted that no association between continuous PPI use and AGE occurrence emerged in patients younger than age 45.

In an , Mina Tadrous, PharmD, MS, PhD, of Women's College Hospital in Toronto, and colleagues wrote that it is imperative to ask patients about all medication use, including over-the-counter drugs, and understand why a patient is using a PPI -- all key to "identifying deprescribing needs and reducing adverse drug effects."

They wrote that clinicians should ensure that the expected benefits of prescribed PPIs are balanced against the risks that the lowest effective dose is used for the shortest recommended duration. Tadrous and co-authors noted that unnecessary off-label long-term use of PPIs is prevalent, with finding that up to 65% of hospitalized patients in the U.S. had no documented ongoing indication for these acid suppressants, raising concerns about the risks of .

They added that the research provides "important takeaway points related to the large number of higher-risk patients using PPIs and whether long-term therapy is indicated," and that the results "add to a growing body of literature supporting the importance of deprescribing of PPIs to reduce potential adverse effects."

Vilcu and co-authors wrote that considerable previous research has reported an association between PPIs and bacterial enteric infections, such as isolated and recurrent . By reducing hydrochloric acid secretion in the stomach, these agents may promote the growth of the gastrointestinal microflora, increase bacterial translocation, alter the and weaken the immune system, the team explained.

Study Details

For the analysis, using a main outcome of at least one AGE episode during an acute gastroenteritis epidemic during winter 2015-2016 in France, the team identified episodes using a previously validated algorithm based on a drug-dispensing database of ambulatory-care prescriptions from 7,000 community pharmacies.

Median age of patients in each group was about 70, and about 56% were women. At least one epidemic episode was identified in 3,131 patients (1.3%) receiving PPI therapy and in 4,327 patients (0.7%) not receiving PPI therapy. The highest AGE incidence occurred in week 3 of 2016, with the epidemic period lasting from week 1 of 2016 to week 5 (January 4 to February 7). The pre-epidemic period lasted from September 26, 2015, to January 3, 2016; and the post-epidemic period lasted from February 8, 2016, to May 17, 2016.

The aRR of acute gastroenteritis was highest among adults ages 65-74, followed by adults age 75 and older (aRR 1.98, 95% CI 1.81-2.15), and adults ages 45-64 (aRR 1.66, 95% CI 1.54-1.80).

The analysis also found a significant overall association between continuous histamine 2 receptor antagonists such as ranitidine (Zantac) and AGE occurrence in 1,681 exposed patients versus 4,739 unexposed patients (aRR 2.08, 95% CI 1.27-3.39).

Vilcu and colleagues stressed the need for further research to confirm the PPI-AGE association and examine the pathophysiological mechanisms behind it.

Study limitations, the researchers said, included the lack of availability of diagnoses, so that AGE status relied solely on drug-dispensing data even though AGE drugs are not disease-specific; that since the actual doses were not known, it was not possible to assess any dose-response relationship; and that the risk of incomplete patient follow-up may have resulted in misclassification of outcome or exposure status.

In addition, the study's "strict exposure definition" may have resulted in the exclusion of some individuals on continuous PPIs, and no information was available on potential confounders such as sociodemographic characteristics, food consumption, potentially contagious contacts, body mass index, smoking, and alcohol consumption. Finally, although patients who had antibiotics prescribed along with AGE drugs were not counted as AGE cases, other antibiotic-dispensing events were not taken into account, they wrote.