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Cited by 538Clostridium difficile and Clostridium perfringens researchPharmacovigilance and Adverse Drug ReactionsPharmaceutical Practices and Patient Outcomes

Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis

Janarthanan, Sailajah, Ditah, Ivo, Adler, Douglas G, Ehrinpreis, Murray N·2012·American Journal of Gastroenterology
DOI 10.1038/ajg.2012.179
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Abstract

OBJECTIVES: Clostridium difficile-associated diarrhea (CDAD) is a major cause of morbidity and increasing health-care costs among hospitalized patients. Although exposure to antibiotics remains the most documented risk factor for CDAD, attention has recently been directed toward a plausible link with proton pump inhibitors (PPIs). However, the results of studies on the association between CDAD and PPIs remain controversial. We have conducted a meta-analysis to summarize the association between PPIs and CDAD among hospitalized patients. METHODS: A systematic search of published literature on studies that investigated the association between PPIs and CDAD from 1990 to 2010 was conducted on Medline and PubMed. The identified articles were reviewed for additional references. The most adjusted risk estimates were extracted by two authors and summarized using random effects meta-analysis. We also conducted a subgroup analysis by study design. Publication bias was evaluated using the Begg and Egger tests. A sensitivity analysis using the Duval and Tweedie "trim-and-fill" method has also been performed. RESULTS: Twenty-three studies including close to 300,000 patients met the inclusion criteria. There was a 65% (summary risk estimate 1.69 with a 95% confidence interval (CI) from 1.395 to 1.974; P<0.000) increase in the incidence of CDAD among patients on PPIs. By study design, whether case-control study (17) or cohort study (6), there was still a significant increase in the incidence of CDAD among PPI users. The risk estimates were 2.31 (95% CI from 1.72 to 3.10; P<0.001) and 1.48 (95% CI from 1.25 to 1.75; P<0.001) for cohort and case-control studies, respectively. CONCLUSIONS: There is sufficient evidence to suggest that PPIs increase the incidence of CDAD. Our meta-analysis shows a 65% increase in the incidence of CDAD among PPI users. We recommend that the routine use of PPIs for gastric ulcer prophylaxis should be more prudent. Establishing a guideline for the use of PPI may help in the future with the judicious use of PPIs. Further studies, preferably prospective, are needed to fully explore the association between PPIs and CDAD.

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  • 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 and profound alterations.

    “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 [250]

  • 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.

    “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 [110]

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Authors
Janarthanan, S., Ditah, I., Adler, D. G., & Ehrinpreis, M. N.
Affiliations
  • Wayne State University (US)
  • University of Utah (US)
Corresponding author
Adler, Douglas G
ORCID
Adler, Douglas G
Venue
American Journal of Gastroenterology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2012-07
Volume
107
Issue
7
Pages
1001-1010
ISSN
0002-9270 (ISSN-L)
DOI
10.1038/ajg.2012.179
OpenAlex
W2091320039
Cited by
538
References
56
Citations by year
2026: 24 · 2025: 16 · 2024: 30 · 2023: 31 · 2022: 21 · 2021: 31 · 2020: 31 · 2019: 38 · 2018: 39 · 2017: 63 · 2016: 47 · 2015: 54 · 2014: 53 · 2013: 50 · 2012: 9
FWCI
6.58
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (unspecified)
Locations
  • The American Journal of Gastroenterology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Clostridium difficile and Clostridium perfringens research
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
  • Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
Keywords
Clostridium difficile-associated diarrhea, proton pump inhibitors, risk factors, hospitalized patients, antibiotic exposure, case-control study, cohort studies, publication bias, risk estimates, drug safety, health care costs, Clostridium difficile toxin
MeSH terms
Anti-Bacterial Agents, Enterocolitis, Pseudomembranous, Humans, Risk Factors, Incidence, Clostridioides difficile, Proton Pump Inhibitors

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