Gastric Acid Suppression Increases Odds of Gut Colonization With Resistant Organisms

By Will Boggs MD

February 25, 2020

NEW YORK (Reuters Health) - The use of gastric acid suppressants is associated with increased odds of intestinal colonization with multidrug-resistant microorganisms (MDROs), according to a systematic review and meta-analysis.

"In view of the global problem of antimicrobial resistance and the facilitating effect that proton pump inhibitors (PPIs) appear to have on colonization with these multidrug-resistant microorganisms, we hope that physicians will realize that by being critical when prescribing PPIs, they help in preventing the spread of resistant strains," Dr. Roel P. J. Willems from Amsterdam UMC, Vrije Universiteit Amsterdam told Reuters Health by email.

Some observational studies have reported an increased risk of MDRO colonization with acid suppression, whereas others have shown no such association.

Dr. Willems and colleagues investigated whether acid suppression therapy is associated with colonization by MDROs in their systematic review and meta-analysis of 26 studies, including 19 that measured intestinal carriage of MDROs of the Enterobacterales order (MDR-E) and 7 that measured carriage of vancomycin-resistant enterococci (VRE).

In the primary analysis, acid suppression was associated with 74% higher odds of MDRO colonization, compared with no acid suppression, according to the online report in JAMA Internal Medicine.

In subgroup analysis, acid suppression was associated with 60% higher odds of MDR-E carriage and 97% higher odds of VRE carriage.

The increased odds of MDRO carriage appeared to be limited to PPI users (80% increased odds), with no apparent association between histamine 2 receptor antagonists and MDRO colonization.

Acid suppression was associated with MDRO colonization both at hospital admission and during hospital stay.

"We advocate that acid suppressants should be used when necessary but that unnecessary use should be avoided," the authors conclude.

"Reducing unnecessary use would require simultaneous efforts from physicians and their patients," Dr. Willems said. "Increased awareness among physicians should encourage them to critically evaluate at all times the necessity of the treatment together with their patients. Also, it is important to evaluate the impact of over-the-counter use, because of the lack of medical surveillance for medications that can be bought at drugstores."

"Our study summarizes the evidence gathered from observational studies only," he added. "Although we firmly believe that the effect we observe is correct, because the effect is consistent, independently of the type of analysis we performed, we realize that controlled trials are more convincing to the medical community. Unfortunately, a controlled trial would be very difficult, because it would not be ethically possible to randomize patients either to PPIs or to placebo."

Dr. Todd C. Lee from McGill University Health Center, Montreal, Quebec, Canada, who co-authored an invited commentary related to this report, told Reuters Health by email, "Medications should either help patients live better or longer. We should, as a profession, reevaluate the medications we prescribe on a regular basis to understand whether the treatments we are providing are achieving these goals."

"While PPIs are, in general, very safe medications, rare and important adverse events and side effects do occur and become relevant when millions of people are taking these drugs," he said. " Like benzodiazepines, antipsychotics, gabapentinoids, and narcotics, the PPIs require ongoing reevaluation."

"Ongoing efforts to improve the use of proton pump inhibitors are underway in many countries worldwide," Dr. Lee said. "They have shown mixed results because rebound hyperacidity is a major problem. Nonetheless, many long-term users of PPIs can either move to intermittent pulse therapy or discontinue therapy if that is appropriate."

He added, "Antibiotic resistance is a major international problem. Anything we can do to reduce its burden and improve treatment will have a major effect. If the judicious use of PPIs can help prevent colonization and therefore infection, it is incumbent on all of us to try to achieve that aim."

Dr. Rishi Chanderraj from the University of Michigan in Ann Arbor, who recently described an association between PPI use and VRE colonization, told Reuters Health by email, "Despite widespread implementation of antibiotic stewardship programs, antibiotic resistance continues to grow. It's clear that we need new strategies, and this article suggests that broadening the scope of antimicrobial stewardship to other medications not traditionally thought of as antibiotics might be effective."

"I think it's actually more important to educate clinicians than it is to educate patients - these medications aren't without side effects!" he said. "I think that it's usually we clinicians that are prescribing PPIs indiscriminately with the thought that they don't do much harm."

He added, "The main message is, the gut microbiome is a key player in the spread of antibiotic resistance, and that medications other than antibiotics can change the structure of the gut microbiome and influence health in ways we weren't aware of before the current explosion in microbiome science."

SOURCE: JAMA Internal Medicine, online February 24, 2020.