Gastric acid drugs linked to increased risk of Clostridium difficile infection

Meta-analysis of studies suggest that patients who receive gastric acid drugs may be at increased risk for recurrent Clostridium difficile infection.

Clostridium difficile micrograph wi 17

People who use gastric acid suppression medications are at a higher risk for recurrent Clostridium difficile infection, a study has found.

US researchers conducted a systematic review and meta-analysis of studies assessing the association between gastric acid suppressant exposure and recurrent C. difficile which were published between 1 January 1995 and 30 September 2015.

A total of 16 observational studies involving 7,703 patients with C. difficile, of which 1,525 (19.8%) developed recurrent C. difficile were identified.

Publishing their findings in JAMA Internal Medicine
(online, 27 March 2017), they found that the rate of recurrent C. difficile in patients with gastric acid suppression was 22.1% (892 of 4,038 patients), compared with 17.3 % (633 of 3,665) in patients without gastric acid suppression, suggesting that acid suppression increased risk of developed recurrent C. difficile (odds ratio, 1.52; 95% confidence interval, 1.20-1.94; P <0 .001).

Senior study author Sahil Khanna, a gastroenterologist at the Mayo Clinic, Rochester, Minnesota, said that while the findings needed to be interpreted with caution because the study had not considered variables, such as the underlying reason why the gastric acid suppressant was needed: “It may be reasonable to re-evaluate the need for these medications in patients with C. difficile.”

Commenting on the study, Mark Wilcox, lead on C. difficile infection for Public Health England, and head of microbiology research and development at Leeds Teaching Hospitals NHS Trust, said: “There is already a body of evidence suggesting that gastric acid suppression could increase the risk of C. difficile infection (CDI). This latest review of published studies shows that there may (also) be an increased risk of recurrent CDI associated with gastric acid suppressant medications.” 

He added that the researchers examined a number of subgroups to try to understand the considerable variability in results across the studies reviewed, but were unable to explain the heterogeneity. 

“Such heterogeneity raises the risk of confounding,” he said. “It is important to caution that the latest findings could be attributable to the way patients were selected for study rather than a true recurrent (CDI) risk caused by gastric acid suppression medications. Nevertheless, if patients with CDI do not have a pressing need to continue gastric acid suppression, it could be prudent to suspend their use in the 1-2 months after a primary episode.” 

David Jenkins, consultant medical microbiologist and deputy director of infection prevention and control at University Hospitals of Leicester, said that, despite a sizeable decrease in rates over the last 10 years – a 75% reduction in England since 2007/2008 – C. difficile infection remains an important challenge, and around one quarter of patients will suffer recurrent infection. 

“While we already knew that proton pump inhibitors (PPIs) are linked to an increased risk of a first episode of CDI, this paper indicates that use of H2-antagonists, as well as PPIs, is associated with a greater chance of recurrent CDI. 

“With the usual caveat that association is not necessarily causation, knowing of this connection may help clinicians identify patients at higher risk of recurrence, and allow them to focus [on] preventative measures on such patients.” 

He added: “This includes the selective use of fidaxomicin, an antibiotic that is licensed for the treatment of first episode CDI and which has been demonstrated to reduce the risk of recurrence relative to vancomycin treatment, but which, in the UK, is around 25 times more expensive than vancomycin.”


[1] Tariq R, Singh S, Gupta A et al. Association of gastric acid suppression with recurrent Clostridium difficile infection: a systematic review and meta-analysis. JAMA Intern Med 2017. doi: 10.1001/jamainternmed.2017.0212

Last updated
The Pharmaceutical Journal, Gastric acid drugs linked to increased risk of Clostridium difficile infection;Online:DOI:10.1211/PJ.2017.20202518

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