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Review
, 11 (6), 781-788

Comparison of the Hospital-Acquired Clostridium difficile Infection Risk of Using Proton Pump Inhibitors Versus Histamine-2 Receptor Antagonists for Prophylaxis and Treatment of Stress Ulcers: A Systematic Review and Meta-Analysis

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Review

Comparison of the Hospital-Acquired Clostridium difficile Infection Risk of Using Proton Pump Inhibitors Versus Histamine-2 Receptor Antagonists for Prophylaxis and Treatment of Stress Ulcers: A Systematic Review and Meta-Analysis

Mohamed Azab et al. Gut Liver.

Abstract

Background/aims: Although proton pump inhibitors (PPIs) have been widely used for the prevention and treatment of stress gastric ulcers in hospital settings, there are concerns that PPIs increase the risk of Clostridium difficile infection (CDI). However, little is known about the risk of CDI following PPI and histamine-2 receptor antagonist (H2RA) use. We evaluated the comparative hospital-acquired CDI occurrence risk associated with the concurrent use of PPIs versus H2RAs.

Methods: A systematic search of PubMed, MEDLINE/Ovid, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and Google Scholar through August 19, 2016, identified 12 studies that reported the hospital-acquired CDI occurrence following H2RA and PPI use for the prevention and treatment of stress gastric ulcers. Random-effects pooled odds ratios and 95% confidence intervals were estimated. Heterogeneity was measured using I², and a meta-regression analysis was conducted. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to assess the overall quality of the evidence.

Results: A total of 74,132 patients from 12 observational studies were analyzed. Compared to H2RAs, PPIs increased the risk of CDI by 38.6% (pooled odds ratio, 1.386; 95% confidence interval, 1.152 to 1.668; p=0.001; I²=42.81%). Subgroup analyses of the purpose of study medication use, study site, and study design confirmed the consistency of a greater CDI risk with PPIs than with H2RAs. The overall quality of evidence was rated as low.

Conclusions: The use of PPIs for both the prevention and treatment of stress ulcers was associated with a 38.6% increased risk of hospital-acquired CDI occurrence compared to H2RA use.

Keywords: Clostridium; Histamine antagonists; Meta-analysis; Proton pump inhibitors; Stomach ulcer.

Conflict of interest statement

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1
Fig. 1
Study selection process. CINAHL, Cumulative Index of Nursing and Allied Health Literature.
Fig. 2
Fig. 2
Meta-analysis results. Comparison of the Clostridium difficile infection (CDI) risk following proton pump inhibitor (PPI) and histamine-2 receptor antagonist (H2RA) use. CI, confidence interval.
Fig. 3
Fig. 3
Publication bias.
Fig. 4
Fig. 4
Subgroup analysis by purpose of medication use; (A) unspecified and (B) prevention. CDI, Clostridium difficile infection; CI, confidence interval; PPI, proton pump inhibitor; H2RA, histamine-2 receptor antagonist.

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