Evaluation of the Association Between Gastric Acid Suppression and Risk of Intestinal Colonization With Multidrug-Resistant Microorganisms: A Systematic Review and Meta-analysis

Review of 26 observational studies (n=29,382 of whom 11 439 [38.9%] on acid suppressants) found acid suppression linked to increased odds of multidrug-resistant microorganisms colonization (OR =1.74; 95% CI, 1.40-2.16 based on 12 studies; n=22 305).

SPS commentary:

The researchers suggest that notwithstanding the limitations of observational studies, the association is plausible and is strengthened by controlling for confounders. They add that in view of the global increase in antimicrobial resistance, stewardship to reduce unnecessary use of acid suppressants may help to prevent M multidrug-resistant microorganisms colonization.


A commentary notes that it is well established PPIs are overprescribed, and given their known association with a variety of adverse reactions, the important issue is how to decrease inappropriate use. To begin with, it recommends that prescribers should exercise greater caution when initiating a trial of PPI therapy, especially when used for unexplained dyspepsia or abdominal symptoms, where the evidence of benefit is weaker and symptoms often pass on their own, as the harms of PPI therapy likely outweigh any benefits. In addition, since abrupt discontinuation of PPIs can induce rebound hyperacidity after only a few weeks of daily treatment, initial PPI use can lead to self-perpetuating long-term use where the drug is mistakenly thought to be necessary.


It also discusses deprescribing PPIs in those who are taking them long term, noting there are few guidelines, but one approach that comes from a Canadian guideline that suggests beginning by ascertaining the reason for the original prescription and assessing for ongoing need. It notes a common indication to initiate and maintain PPIs is for the treatment of symptoms related to GORD, and in this case, PPIs should be prescribed at the lowest dose and frequency that is adequate to achieve optimal symptom control. If symptoms have resolved, therapy should be interrupted after an initial 4-week to 8-week trial, and on-demand therapy should be provided in place of continuous therapy. It notes that PPIs are also commonly prescribed to older adults on combinations of blood thinners and anti-inflammatories for primary prevention of upper GI bleeding despite questionable efficacy, with an NNT that approaches 1000.


It suggests that for most patients on PPIs long term, at least an annual reassessment involving the patient in the discussion to deprescribe long-term medications is important for initial success and maintenance over time. It highlights that where possible, lifestyle and dietary modifications for the treatment of reflux-related or heartburn-related symptoms should be emphasized prior to initiating pharmacologic therapy and at the time of deprescribing.


With regards to rebound hyperacidity, it notes this may develop, even after just a few months of therapy, and while there is no clinical trial evidence that tapering over a period of 2 to 4 weeks mitigates this, a systematic review suggests that tapering may be an effective strategy to increase the proportion of patients who remain off PPIs at 1 year. Furthermore, alternatives such as on-demand H2 antagonists, sucralfate, and calcium-based antacids might also be useful but have not been studied in this context. It calls for a trial comparing the long-term success rates between patients randomized to abrupt discontinuation vs taper with and without on-demand adjunctive non-PPI therapies to aid in optimizing PPI deprescribing, and the possibility PPIs are contributing to the emergence of multidrug-resistant infections adds to the motivation to complete such a study.


JAMA Internal Medicine

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