Updated meta-analysis of controlled observational studies: proton-pump inhibitors and risk of  Clostridium difficile  infection

Cao, Fei; Chen, Chunxiang; Wang, Min; Liao, Hairong; Wang, Mei‐Xiang; Hua, Shuizhen; Huang, Bin; Xiong, Yan; Zhang, Jieyu; Xu, Yanliang

doi:10.1016/j.jhin.2017.08.017

Cited by 83 publications

(65 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: Discussionmentioning

confidence: 73%

“…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%

“…Weak association between PPI use and Clostridium difficile infection in observational studies (pooled OR 1.26, 95% CI 1.12-1.39). Limited biologic plausibility and probable confounding 11 Non-C difficile enteric infections 2a…”

Section: Clostridium Difficile Infection 2amentioning

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: Ppis and Enteric Infectionsmentioning

confidence: 99%

Section: Clostridium Difficile Infection 2amentioning

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

View full text Add to dashboard Cite

show abstract

“…In fact, studies performed in healthy volunteers showed that after only 4–8 weeks of high-dose PPI, there were increased bacterial taxa associated with C. difficile in stools [10]. A meta-analysis of 50 controlled observational studies showed a significant association between acid suppressant therapy use and risk of developing C. difficile infection (CDI) (odds ratio [OR] 1.26) [11]. Also, a systematic review and meta-analysis of 16 observational studies showed that patients under PPI therapy had an increased risk of recurrent CDI with an OR of 1.52, even after adjustment for age and other potential confounders [12].…”

Section: Proposed Side Effects Of Ppismentioning

confidence: 99%

Proton Pump Inhibitors: Are They a Real Threat to the Patient?

Xavier¹,

Magalhães²,

Cotter³

2018

GE Port J Gastroenterol

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Background: Proton pump inhibitors are among the most frequently prescribed drugs in the world and are generally considered safe. However, there is growing concern regarding their safety. Summary: A nonsystematic review of the current literature was performed regarding proton pump inhibitors and their adverse effects. Proton pump inhibitors seem to be associated with fundic gland polyp development (without clinical relevance) and Clostridium difficile infection. Also, in cirrhotic patients, their prescription should be carefully reviewed. Regarding their association with other enteric infections, micronutrient deficiency, dementia, and chronic kidney disease, current evidence is still of low quality, and further studies are needed. Key Messages: Considering the current evidence, most patients with a clear clinical indication for proton pump inhibitor treatment should probably benefit from the maintenance of their treatment without significant adverse effects. However, higher-quality studies are needed to confirm or dismiss most of the proposed adverse effects.

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Gastroesophageal Reflux Disease

Maret-Ouda

Markar

Lagergren

2020

JAMA

239

195

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astroesophageal reflux disease (GERD) is defined by its cardinal symptoms (recurrent and troublesome heartburn and regurgitation) or by its specific complications (esophagitis, peptic strictures, and Barrett esophagus). 1 Barrett esophagus is a columnar metaplasia replacing parts of the native squamous cell epithelium that can progress to esophageal adenocarcinoma. 2 GERD can be a serious problem and should not be confused with less severe disease such as gastritis or the very common symptoms of dyspepsia or regurgitation that occur in almost all individuals without any underlying gastrointestinal pathology. GERD is caused by gastric contents' reaching the esophagus. Except for causing esophageal symptoms or complications, gastric juices can also reach more proximally (ie, into the pharynx, mouth, larynx, and airways) and cause or worsen various extraesophageal symptoms and conditions such as hoarseness, wheezing, cough, and asthma. 1 Established risk factors for developing GERD include increased body mass index, tobacco smoking, and genetic predisposition, 3 whereas infection with the gastric bacterium Helicobacter pylori can decrease this risk. 4 The prevalence of GERD is high and increasing, with greater rates in high-income countries (15%-25%) than in most low-and middle-income countries (<10%). 2,5 GERD can result in diminished health-related quality of life, and its prevalence and need for longterm treatment can consume substantial health care resources and result in high costs to society. 6,7 This review provides an update of the current evidence regarding GERD, with an emphasis on its clinical management in adults.IMPORTANCE Gastroesophageal reflux disease (GERD) is defined by recurrent and troublesome heartburn and regurgitation or GERD-specific complications and affects approximately 20% of the adult population in high-income countries.OBSERVATIONS GERD can influence patients' health-related quality of life and is associated with an increased risk of esophagitis, esophageal strictures, Barrett esophagus, and esophageal adenocarcinoma. Obesity, tobacco smoking, and genetic predisposition increase the risk of developing GERD. Typical GERD symptoms are often sufficient to determine the diagnosis, but less common symptoms and signs, such as dysphagia and chronic cough, may occur. Patients with typical GERD symptoms can be medicated empirically with a proton pump inhibitor (PPI). Among patients who do not respond to such treatment or if the diagnosis is unclear, endoscopy, esophageal manometry, and esophageal pH monitoring are recommended. Patients with GERD symptoms combined with warning symptoms of malignancy (eg, dysphagia, weight loss, bleeding) and those with other main risk factors for esophageal adenocarcinoma, such as older age, male sex, and obesity, should undergo endoscopy. Lifestyle changes, medication, and surgery are the main treatment options for GERD. Weight loss and smoking cessation are often useful. Medication with a PPI is the most common treatment, and after initial full-dose therapy, w...

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Updated meta-analysis of controlled observational studies: proton-pump inhibitors and risk of Clostridium difficile infection

Cited by 83 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

Proton Pump Inhibitors: Are They a Real Threat to the Patient?

Gastroesophageal Reflux Disease

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