Regular PPI Users at Increased Risk for Cholangitis with MDRB

Regular users of proton pump inhibitors may be at higher risk of cholangitis with multi-drug resistant bacteria after endoscopic retrograde cholangiopancreatography (ERCP), a new study in Japan found.

The retrospective study, published in the Journal of Hepato-Biliary-Pancreatic Sciences, included 2752 patients—1224 (44%) of whom were regular users of proton pump inhibitors (PPI) and 1528 (56%) who were not—who underwent ERCP between January 2010 and August 2019.

“The incidence of cholangitis with MDRB was significantly higher in regular PPI users compared with non-regular PPI users,” the study authors wrote. “After the adjustment of potential confounders using multivariable logistic regression model, this effect of PPI remained consistent. Our analysis also revealed that MDRB were likely to be detected after multiple ERCP sessions in regular PPI users.”

The study was led by Ryunosuke Hakuta, MD, PhD, and colleagues at the University of Tokyo. It excluded patients who underwent ERCP with pancreatic indication, those who underwent endoscopic papillectomy and those under age 20. The primary endpoint was incidence of cholangitis with MDRB.

Patients who took any PPI medication—including omeprazole, lansoprazole, rabeprazole and esomaprazole—were included among the regular PPI users group.

Bile culture was examined in 1791 of 7788 ERCP procedures with 629 samples from regular PPI users and 606 from non-regular PPI users examined after repeated cultures from the same patients were excluded. Regular PPI users were more likely to have malignant biliary obstruction than non-PPI users (42% compared with 26%; P<0.001) and less likely to have bile duct stone (31% compared with 50%; P<0.001).

Regular PPI users were more likely to undergo balloon endoscopy-assisted ERCP (17% vs. 9%; P<0.001).

Cholangitis with MDRB was reported among 54 patients during the study period, with a significantly higher incidence among regular PPI users (3%) than non-regular PPI users (1.1%). The odds ratio was 2.19 (95% confidence interval 1.2-4; P=0.01). Among 254 patients who used H2 receptor antagonist, cholangitis with MDRB was reported among 4 (1.6%).

The risk of cholangitis with MDRB increased with multiple ERCP sessions, with MDRB most frequently detected in the fourth or later session.

MDRB included extended-spectrum β-Lactamase-producing Enterobacteriaceae, methicillin-resistant Staphylococcus aureus (MRSA), multi-drug resistant Pseudomonas aeruginosa, vancomycin-resistant Enterococci (VRE), or carbapenemase-producing Enterobacteriaceae (CRE).

“Considering the fewer incidence of cholangitis with MDRB after multiple ERCP sessions in non-regular PPI users, avoidance of inappropriate long-time PPI use might decrease MDRB induced cholangitis,” the authors wrote. “The precise mechanism is not known, but possible hypothesis is that sustained gastric suppression might increase cholangitis with MDRB in addition to multiple biliary interventions.”

Limitations of the study included that the exposure period of PPI was unknown, previous history of antibiotic agents wasn’t included, it was a single-center study and the number of ERCP sessions prior to the study period was unknown.

More research is needed to determine whether reducing inappropriate longtime use of PPI would decrease the incidence of cholangitis with MDRB.

Previous studies have found an association between PPI exposure and increased risk of infection. A recent study in Denmark found a moderate increase of risk of Clostridium difficile in patients being treated with PPIs. Another study found that patients with gastrointestinal tract problems, including those treated with PPIs, could be at higher risk for severe complications from COVID-19.