Comparison of the Hospital-Acquired<i>Clostridium difficile</i>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

Azab, Mohamed; Doo, Loomee; Doo, Daniel; Elmofti, Yousif; Ahmed, Muazer; Cadavona, John Jay P.; Liu, Xibei B.; Shafi, Amaan; Joo, Moon Kyung; Yoo, Ji Won

doi:10.5009/gnl16568

Cited by 48 publications

(36 citation statements)

References 35 publications

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“…In contrast, the odds for an increased occurrence of C difficile infection during PPI therapy are relatively low and PPI‐induced hypochlorhydria was shown not to affect C difficile spore integrity or germination . Instead, it has been hypothesized that PPI‐associated alterations in the gut microbiome may create a niche that facilitates the germination and disease initiation of C difficile infection.…”

Section: Discussionmentioning

confidence: 73%

“…In contrast, the odds for an increased occurrence of C difficile infection during PPI therapy are relatively low [8][9][10][11][12] and PPIinduced hypochlorhydria was shown not to affect C difficile spore integrity or germination. 14…”

Section: Enteric Infections and Clostridium Difficile Infectionmentioning

confidence: 85%

“…The association of PPI use and Clostridium difficile infection appears evident. [8][9][10][11][12] However, due to limitations in study designs, low odds ratios (OR) and some uncertainties concerning biological plausibility, the available studies cannot ultimately provide sufficient evidence of causality of this association. 13,14 Then again, PPI use and communityacquired bacterial enteric infection show a strong association with a pooled OR of 4.28 (95% CI 3.01-6.08) for any infection, 4.84 (95% CI 2.75-8.54) for Salmonella infection and 5.09 (95% CI 3-8.64) for Campylobacter jejuni infection, as shown in a recent meta-analysis of nine observational studies 15 (Table 1, Figure 2).…”

Section: Ppis and Enteric Infectionsmentioning

confidence: 99%

“…The association of PPI use and Clostridium difficile infection appears evident . However, due to limitations in study designs, low odds ratios (OR) and some uncertainties concerning biological plausibility, the available studies cannot ultimately provide sufficient evidence of causality of this association .…”

Section: Introduction: Gastric Acid Inhibition and Adverse Effects Ofmentioning

confidence: 99%

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Systematic review: the effects of proton pump inhibitors on the microbiome of the digestive tract—evidence from next‐generation sequencing studies

Macke

Schulz

Koletzko

et al. 2020

Aliment Pharmacol Ther

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Background: Proton pump inhibitors (PPI) are widely used to treat acid-related disorders of the upper gastrointestinal tract. However, large observational studies have raised concerns about PPI-associated adverse events. In recent years, data from next-generation sequencing studies suggested that PPIs affect the composition of the intestinal microbiota, while a balanced gut microbiome is essential for maintaining health.Aim: To review the available evidence from next-generation sequencing studies on the effect of PPIs on the intestinal microbiome and to discuss possible implications of PPI-induced dysbiosis in health and disease.Methods: A systematic review was conducted following the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. A PubMed query yielded 197 results. 19 publications met the prespecified eligibility criteria.Results: Twelve observational study cohorts with 708 PPI users and 11 interventional cohorts with 180 PPI users were included in the review. In most studies, PPI treatment did not affect microbiological richness and diversity, but was associated with distinct taxonomic alterations: In the upper gastrointestinal tract, PPI users showed overgrowth of orally derived bacteria, mostly Streptococcaceae (findings based on six independent cohorts with 126 PPI users). In faecal samples, PPIs increased multiple taxa from the orders Bacillales (eg, Staphylococcaceae), Lactobacillales (eg, Enterococcaceae, Lactobacillaceae, Streptococcaceae) and Actinomycetales (eg, Actinomycetaceae, Micrococcaceae), the families Pasteurellaceae and Enterobacteriaceae and the genus Veillonella. Taxa decreased by PPIs include Bifidobacteriaceae, Ruminococcaceae, Lachnospiraceae and Mollicutes (findings in faecal samples based on 19 independent cohorts with 790 PPI users). Conclusion: PPI use is associated with moderate alterations to upper and distal gut microbiota. The available data suggest that PPI-induced hypochlorhydria facilitates colonization of more distal parts of the digestive tract by upper gastrointestinal microbiota. MACKE Et Al 1 | INTRODUC TI ON: G A S TRI C ACID INHIB ITI ON AND ADVER S E EFFEC TS OF PPIS Gastric acid eliminates microorganisms, promotes the digestive process and facilitates the absorption of iron, calcium and vitamin B12. However, gastric acid also contributes to the development of mild and severe gastroduodenal pathologies. Proton pump inhibitor (PPIs) are the most effective therapy of acid-related diseases and are among the most commonly used drugs. 1 While generally considered a safe therapy, PPIs have been associated with numerous adverse effects in population-based observational studies conducted in recent years. These include cardiovascular and kidney disease, micronutrient deficiencies and osteoporosis, cognitive impairment and death. 2Most studies are retrospective and not hypothesis-driven in design, might be subject to significant confound and thus they cannot establish causality. 2,3 This is also the case for a recent study on ...

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Section: Discussionmentioning

confidence: 73%

Section: Enteric Infections and Clostridium Difficile Infectionmentioning

confidence: 85%

Section: Ppis and Enteric Infectionsmentioning

confidence: 99%

Section: Introduction: Gastric Acid Inhibition and Adverse Effects Ofmentioning

confidence: 99%

See 2 more Smart Citations

Systematic review: the effects of proton pump inhibitors on the microbiome of the digestive tract—evidence from next‐generation sequencing studies

Macke

Schulz

Koletzko

et al. 2020

Aliment Pharmacol Ther

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“…87 Because of the acid-reducing mechanism of PPIs, histamine H2 receptor antagonists (H2-blockers) have been studied as well, with a lower risk of CDI in H2-blockers as compared with PPIs. 16,65,88 Based on the observational nature of the studies and significant heterogeneity, it is unclear whether the association between PPI use and CDI derives from proposed downstream effects of the medication or confounding by the indications for therapy among patients receiving PPIs.…”

Section: Proton Pump Inhibitorsmentioning

confidence: 99%

Clostridium difficile Infection: An Epidemiology Update

Roo

Regenbogen

2020

Clinics in Colon and Rectal Surgery

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Clostridium (reclassified as “Clostridioides”) difficile infection (CDI) is a healthcare-associated infection and significant source of potentially preventable morbidity, recurrence, and death, particularly among hospitalized older adults. Additional risk factors include antibiotic use and severe underlying illness. The increasing prevalence of community-associated CDI is gaining recognition as a novel source of morbidity in previously healthy patients. Even after recovery from initial infection, patients remain at risk for recurrence or reinfection with a new strain. Some pharmaco-epidemiologic studies have suggested an increased risk associated with proton pump inhibitors and protective effect from statins, but these findings have not been uniformly reproduced in all studies. Certain ribotypes of C. difficile, including the BI/NAP1/027, 106, and 018, are associated with increased antibiotic resistance and potential for higher morbidity and mortality. CDI remains a high-morbidity healthcare-associated infection, and better understanding of ribotypes and medication risk factors could help to target treatment, particularly for patients with high recurrence risk.

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Effectiveness and Safety of Histamine H2 Receptor Antagonists: An Umbrella Review of Meta‐Analyses

Meng

Chen

Zhang

et al. 2022

The Journal of Clinical Pharma

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Histamine H2 receptor antagonists (H2RAs) were widely used to inhibit gastric acid secretion, but its association with adverse events remains controversial and unclear. We conducted an umbrella review of meta-analyses to systematically assess the quality and credibility of the correlations between H2RA use with the risk of adverse outcomes through searching 4 major databases from inception to April 30, 2022. Forty-six individual metaanalyses were identified, including 29 meta-analyses of observation studies with 32 unique outcomes and 19 meta-analyses of randomized controlled trials with 3 unique outcomes for comparing the H2RA versus non-H2RA group. A Measurement Tool to Assess Systematic Reviews 2 rating for the included meta-analyses showed that 4 of 46 meta-analyses were assigned as high scores, 3 were assigned as "moderate," and 25 were assigned as low scores. Grading of Recommendations Assessment, Development and Evaluation assessment for combined results demonstrated that 6 outcomes were rated as "moderate," 9 outcomes were rated as "low," and 17 outcomes were rated as "very low." We confirmed significant associations of H2RA use with pneumonia, peritonitis, necrotizing enterocolitis, Clostridium difficile infection, liver cancer, gastric cancer, and hip fracture diseases. No associations for colorectal cancer, melanoma, kidney cancer, lung cancer, or common reproductive system cancer or renal, neurological, and cardiovascular system diseases were observed. We found a variety of evidence for the associations between H2RAs and adverse outcomes, which would give clinicians more positive guidance on prescription of H2RAs in clinical practice.

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Comparison of the Hospital-AcquiredClostridium difficileInfection Risk of Using Proton Pump Inhibitors versus Histamine-2 Receptor Antagonists for Prophylaxis and Treatment of Stress Ulcers: A Systematic Review and Meta-Analysis

Cited by 48 publications

References 35 publications

Systematic review: the effects of proton pump inhibitors on the microbiome of the digestive tract—evidence from next‐generation sequencing studies

Systematic review: the effects of proton pump inhibitors on the microbiome of the digestive tract—evidence from next‐generation sequencing studies

Clostridium difficile Infection: An Epidemiology Update

Effectiveness and Safety of Histamine H2 Receptor Antagonists: An Umbrella Review of Meta‐Analyses

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