AMSTERDAM – The long-term safety of proton pump inhibitors has once again come into question, as they may quadruple the chance of carrying a bacterial strain highly resistant to both penicillin and cephalosporin antibiotics, a Dutch study suggested.
The observational study showed only association, not causation, according to Dr. Pepijn Huizinga of the Amphia Ziekenhuis Hospital, Breda, the Netherlands. But, he said, the association of PPIs and extended-spectrum beta-lactamase–producing enterobacteriaceae (ESBL-E) is biologically plausible, and strong enough to warrant deeper investigation. Dr. Huizinga reported the study results at the 2016 European Conference of Clinical Microbiology and Infectious Diseases.
“We are continuously exposed to ESBL-E from many sources – other humans, contaminated foods, and the environment,” Dr. Huizinga said. “The gastric acid barrier is one of the last barriers we have against developing carriage. As long as it is in the normal pH range of 1.5-3, it’s quite efficient at keeping these bacteria from entering our system. But PPIs decrease this to 3 or 4. We already know that this is associated with an increased risk of infections from campylobacteriae, salmonella, and C. [Clostridium] difficile.”
Dr. Pepijn Huizinga
PPI use is exploding in the Netherlands, Dr. Huizinga said, following a worldwide pattern of escalating use. National statistics demonstrate a very sharp upward trend, beginning with the introduction of omeprazole in 1994. By 2013, with five PPIs on the market, there were more than 2.7 million users – 14% of the country’s adult population. About a third of people older than 65 years are using them on a daily basis, according to data from the Dutch Foundation for Pharmaceutical Statistics.
To examine the relationship, Dr. Huizinga mined data from an ESBL-E prevalence survey conducted at Amphia Ziekenhuis Hospital in 2014 and 2015. The study cohort comprised 570 adults who received a rectal culture within a day of admission. Of these, 5.4% (31) were positive for ESBL-E carriage.
He examined correlations between carriage and several patient characteristics. Women were slightly more likely to be carriers than men (6.6% vs. 4%). There was no difference in the incidence of antibiotic use on day of admission, with 6% of the positive patients taking an antibiotic and 5% not taking one. Carriers were younger than noncarriers (64 vs. 65 years). PPI use was significantly more common among those who carried ESBL-E (8.6% vs. 2.9%).
In a multivariate analysis, there were no significant associations with sex, age, or antibiotic use. PPI use conferred the only significant risk, a fourfold increase in the chance of carriage.
Dr. Huizinga noted that the model didn’t consider the length of time taking the drugs, only whether they were in use on the day of admission. Nor did the study account for any medical comorbidity.
“However,” he said, “I think we do need to consider the possibility that the frequent use of PPIs in the general population could be an important driver of the increase we are seeing in ESBL-E carriage.”
Dr. Huizinga had no relevant financial disclosures.
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