The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Systematic Review of the Risk of Enteric Infection in Patients Taking Acid Suppression
Abstract
CONTEXT: Proton pump inhibitors (PPIs) and H(2) receptor antagonists (H(2)RAs) have become the mainstay of therapy in acid-related upper gastrointestinal disorders. There have been concerns raised about the possible association of PPIs with enteric infections. OBJECTIVE: We conducted a systematic review to evaluate any association between acid suppression and enteric infection. We also assessed differences between types of enteric infections and the type of acid suppression. DATA SOURCES: Electronic searches of MEDLINE (1966-2005), EMBASE (1988-2005), and CINAHL (1982-2005) were undertaken using a combination of subject headings and text words related to PPI therapy, H(2)RAs, and enteric infections. STUDY SELECTION: All observational studies were eligible, including cross-sectional, case control, and cohort studies that evaluated risk of enteric infection associated with antisecretory therapy. Eligibility assessment was made by two independent researchers. DATA EXTRACTION: Information on study design, patient population, type of acid suppression, type of infection, and outcomes was collected. The odds ratio (OR) of taking acid suppression therapy in cases and controls was calculated and results were synthesized using a random effects model (DerSimonian and Laird, Stats direct version 2.4.4). DATA SYNTHESIS: A total of 12 papers evaluating 2,948 patients with Clostridium difficile were included in the review. There was an increased risk of taking antisecretory therapy in those infected with C. difficile (pooled OR 1.94, 95% CI 1.37-2.75). There was significant heterogeneity between the studies (P= 0.0006) that was not explained by planned subgroup analysis. The association was greater for PPI use (OR 1.96, 95% CI 1.28-3.00) compared with H(2)RA use (OR 1.40, 95% CI 0.85-2.29). A total of six studies evaluated Salmonella, Campylobacter, and other enteric infections in 11,280 patients. There was an increased risk of taking acid suppression in those with enteric infections (OR 2.55, 95% CI 1.53-4.26). There was significant heterogeneity between the studies (P < 0.0001) that was not explained by subgroup analysis. The association was greater for PPI use (OR 3.33, 95% CI 1.84-6.02) compared with H(2)RA use (OR 2.03, 95% CI 1.05-3.92). CONCLUSION: There is an association between acid suppression and an increased risk of enteric infection. Further prospective studies on patients taking long-term acid suppression are needed to establish whether this association is causal.
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In the citing paper
“Supporting the importance of such mechanisms, a growing body of evidence has linked acid-reducing medications such as proton pump inhibitors and histamine H2 antagonists, with increased risk of enteric infections such as clostridium difficile[248–250] and profound alterations”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [249]
In the citing paper
“PPIs can influence the onset of enteric infections, resulting in an increased risk of Clostridium difficile infection (CDI), as well as Salmonella, Campylobacter and diarrheagenic Escherichia coli (E. coli)[110-113].”
From Proton pump inhibitors and dysbiosis: current knowledge and aspects to be clarified (2019) · cites this paper as [112]
Citations
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Dellinger, R. P., Levy, M. M., Rhodes, A., Annane, D., Gerlach, H., Opal, S. M., Sevransky, J., Sprung, C. L., Douglas, I. S., Jaeschke, R., et al. (2013) · Intensive Care Medicine · doi:10.1007/s00134-012-2769-8 · Cited by 7,371
Alhazzani, W. A., Møller, M. H., Arabi, Y. M., Loeb, M. B., Gong, M. N., Fan, E., Oczkowski, S. J. W., Levy, M. M., Derde, L. P. G., Dzierba, A. L., et al. (2020) · Critical Care Medicine · doi:10.1097/ccm.0000000000004363 · Cited by 1,578
Proton pump inhibitors affect the gut microbiome
Imhann, F., Bonder, M. J., Vich Vila, A., Fu, J., Mujagic, Z., Vork, L., Tigchelaar, E. F., Jankipersadsing, S. A., Cenit, M. C., Harmsen, H. J. M., et al. (2016) · Gut · doi:10.1136/gutjnl-2015-310376 · Cited by 1,371
Interaction between drugs and the gut microbiome
Weersma, R. K., Zhernakova, A., & Fu, J. (2020) · Gut · doi:10.1136/gutjnl-2019-320204 · Cited by 1,028
Proton pump inhibitors alter the composition of the gut microbiota
Jackson, M. A., Goodrich, J. K., Maxan, M.-E., Freedberg, D. E., Abrams, J. A., Poole, A. C., Sutter, J. L., Welter, D., Ley, R. E., Bell, J. T., et al. (2016) · Gut · doi:10.1136/gutjnl-2015-310861 · Cited by 895
Metadata
- Authors
- Leonard, J., Marshall, J. K., & Moayyedi, P.
- Affiliations
- McMaster University (CA)
- Venue
- The American Journal of Gastroenterology
- Published
- 2007-09
- Volume
- 102
- Issue
- 9
- Pages
- 2047-2056
- ISSN
- 0002-9270 (ISSN-L)
- 1572-0241
- OpenAlex
- W2114271048
- Cited by
- 633
- References
- 46
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 22 · 2023: 24 · 2022: 32 · 2021: 35 · 2020: 39 · 2019: 29 · 2018: 35 · 2017: 41 · 2016: 30 · 2015: 28 · 2014: 30 · 2013: 63 · 2012: 55
- FWCI
- 3.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
- Health Sciences › Medicine › Gastroenterology › Gastroesophageal reflux and treatments
- Health Sciences › Medicine › Gastroenterology › Helicobacter pylori-related gastroenterology studies
- Keywords
- acid suppression, proton pump inhibitors, H2 receptor antagonists, gastrointestinal infections, Clostridium difficile infection, Salmonella, Campylobacter, Clostridium difficile-associated diarrhea, antisecretory therapy, infection risk, drug safety, Helicobacter pylori, Helicobacter heilmannii
- MeSH terms
- Bacterial Infections, Gastric Acid, Gastrointestinal Diseases, Histamine H2 Antagonists, Humans, Risk Factors, Proton Pump Inhibitors
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