Assessing the Risk of Hospital-Acquired<i>Clostridium Difficile</i>Infection With Proton Pump Inhibitor Use: A Meta-Analysis

Arriola,; Tischendorf, Jessica S; Musuuza, Jackson; Barker, Anna; Rozelle, Jeffrey W.; Safdar, Nasia

doi:10.1017/ice.2016.194

Cited by 64 publications

(47 citation statements)

References 54 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: Discussionsupporting

confidence: 59%

“…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: Discussionsupporting

confidence: 59%

Section: Ppis and Enteric Infectionsmentioning

confidence: 99%

Section: Introduction: Gastric Acid Inhibition and Adverse Effects Ofmentioning

confidence: 99%

See 1 more Smart Citation

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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“…Age-stratified subgroup analysis revealed that there were significant associations of PPI use with increased initial CDI in both adult (OR 2.30, 95% CI 1.89-2.80) and pediatric (OR 3.00, 95% CI 1.44-6.23) patients. As shown in Table 1, several meta-analyses suggested that PPI use significantly increased the risk of primary/recurrent CDI [21,22] and hospital-acquired CDI [23]. Leonard et al [18] reviewed 6 studies including 11,280 patients with Salmonella , Campylobacter , C. difficile , and other enteric infections, and showed that there was an increased risk of PPI use in those with enteric infections (OR 3.33, 95% CI 1.84-6.02).…”

Section: Infectious and Inflammatory Diseases Possibly Associated Witmentioning

confidence: 99%

Intestinal Dysbiosis Secondary to Proton-Pump Inhibitor Use

Naito

Kashiwagi²,

Takagi³

et al. 2018

Digestion

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Background: Gut dysbiosis associated with the use of proton-pump inhibitors (PPIs) has been found to lead to the occurrence of infectious and inflammatory adverse events. A longitudinal observational cohort study has demonstrated the heightened risk of death associated with PPI use. Summary: We evaluated meta-analyses to determine the association between PPI use and infectious and inflammatory diseases. Meta-analyses showed that PPI use is a potential risk for the development of enteric infections caused by Clostridium difficile, as well as small intestinal bacterial overgrowth, spontaneous bacterial peritonitis, community-acquired pneumonia, hepatic encephalopathy, and adverse outcomes in inflammatory bowel disease. We also examined changes in the composition and function of the gut microbiota with the use of PPIs. PPI use significantly increased the presence of Streptococcaceae and Enterococcaceae, which are risk factors for C. difficile infection, and decreased that of Faecalibacterium, a commensal anti-inflammatory microorganism. Key Message: High-throughput, microbial 16S rRNA gene sequencing has allowed us to investigate the association between the gut microbiome and PPI use. Future prospective comparison studies are necessary to confirm this association, and to develop new strategies to prevent complications of PPI use

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“…Proton pump inhibitors have been associated with an increased risk of C difficile infection 101112. The effect may also be seen with H2 receptor antagonists…”

Section: Who Is At Risk?mentioning

confidence: 99%

Clostridium difficile associated disease

Hassoun

2018

BMJ

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Assessing the Risk of Hospital-AcquiredClostridium DifficileInfection With Proton Pump Inhibitor Use: A Meta-Analysis

Abstract: Introduction-Clostridium difficile is the principal infectious cause of antibiotic associated

Cited by 64 publications

References 54 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

Intestinal Dysbiosis Secondary to Proton-Pump Inhibitor Use

Clostridium difficile associated disease

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