Treatment with proton pump inhibitors increases the risk of secondary infections and ARDS in hospitalized patients with COVID-19: coincidence or underestimated risk factor?
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ABSTRACT:
SUBMITTER: Luxenburger H
PROVIDER: S-EPMC7361636 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
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Treatment with proton pump inhibitors increases the risk of secondary infections and ARDS in hospitalized patients with COVID-19: coincidence or underestimated risk factor?
Luxenburger H H Sturm L L Biever P P Rieg S S Duerschmied D D Schultheiss M M Neumann-Haefelin C C Thimme R R Bettinger D D
Journal of internal medicine 20200701 1
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Project description:Proton pump inhibitors (PPIs) are often used in pediatrics to treat common gastrointestinal disorders, and there are growing concerns for infectious adverse events. Because CYP2C19 inactivates PPIs, genetic variants that increase CYP2C19 function may decrease PPI exposure and infections. We tested the hypothesis that CYP2C19 metabolizer phenotypes are associated with infection event rates in children exposed to PPIs. This retrospective biorepository cohort study included individuals aged 0 to 36 months at the time of PPI exposure. Respiratory tract and gastrointestinal tract infection events were identified by using International Classification of Diseases codes in the year after the first PPI mention. Variants defining CYP2C19 *2, *3, *4, *8, *9, and *17 were genotyped, and all individuals were classified as CYP2C19 poor or intermediate, normal metabolizers (NMs), or rapid or ultrarapid metabolizers (RM/UMs). Infection rates were compared by using univariate and multivariate analyses. In all, 670 individuals were included (median age 7 months; 44% girls). CYP2C19 NMs (n = 267; 40%) had a higher infection rate than RM/UMs (n = 220; 33%; median 2 vs 1 infections per person per year; P = .03). There was no difference between poor or intermediate (n = 183; 27%) and NMs. In multivariable analysis of NMs and RM/UMs adjusting for age, sex, PPI dose, and comorbidities, CYP2C19 metabolizer status remained a significant risk factor for infection events (odds ratio 0.70 [95% confidence interval 0.50-0.97] for RM/UMs versus NMs). PPI therapy is associated with higher infection rates in children with normal CYP2C19 function than in those with increased CYP2C19 function, highlighting this adverse effect of PPI therapy and the relevance of CYP2C19 genotypes to PPI therapeutic decision-making.
| S-EPMC6889971 | biostudies-literature
Project description:Background and aimsProton pump inhibitors (PPIs) are widely prescribed and have effects on gut ion absorption and urinary ion concentrations. PPIs might therefore protect against or contribute to development of kidney stones. We investigated the association between PPI use and kidney stones.MethodsWe performed a retrospective study using data from the Women's Veteran's Cohort Study, which comprised men and women, from October 1, 1999 through September 30, 2017. We collected data from 465,891 patients on PPI usage over time, demographics, laboratory results, comorbidities, and medication usage. Time-varying Cox proportional hazards and propensity matching analyses determined risk of PPI use and incident development of kidney stones. Use of histamine-2 receptor antagonists (H2RAs) was measured and levothyroxine use was a negative control exposure.ResultsPPI use was associated with kidney stones in the unadjusted analysis, with PPI use as a time-varying variable (hazard ratio [HR], 1.74; 95% CI, 1.67-1.82), and persisted in the adjusted analysis (HR, 1.46; CI, 1.38-1.55). The association was maintained in a propensity score-matched subset of PPI users and nonusers (adjusted HR, 1.25; CI 1.19-1.33). Increased dosage of PPI was associated with increased risk of kidney stones (HR, 1.11; CI, 1.09-1.14 for each increase in 30 defined daily doses over a 3-month period). H2RAs were also associated with increased risk (adjusted HR, 1.47; CI 1.31-1.64). We found no association, in adjusted analysis, of levothyroxine use with kidney stones (adjusted HR, 1.06; CI 0.94-1.21).ConclusionsIn a large cohort study of veterans, we found PPI use to be associated with a dose-dependent increase in risk of kidney stones. H2RA use also has an association with risk of kidney stones, so acid suppression might be an involved mechanism. The effect is small and should not change prescribing for most patients.
| S-EPMC7483196 | biostudies-literature
Project description:ImportanceProton pump inhibitor (PPI) use may lead to infections through alteration of the microbiota or direct action on the immune system. However, only a few studies were conducted in children, with conflicting results.ObjectiveTo assess the associations between PPI use and serious infections in children, overall and by infection site and pathogen.Design, setting, and participantsThis nationwide cohort study was based on the Mother-Child EPI-MERES Register built from the French Health Data System (SNDS). We included all children born between January 1, 2010, and December 31, 2018, who received a treatment for gastroesophageal reflux disease or other gastric acid-related disorders, namely PPIs, histamine 2 receptor antagonists, or antacids/alginate. The index date was defined as the first date any of these medications was dispensed. Children were followed up until admission to the hospital for serious infection, loss of follow-up, death, or December 31, 2019.ExposurePPI exposure over time.Main outcomes and measuresAssociations between serious infections and PPI use were estimated by adjusted hazard ratios (aHRs) and 95% CIs using Cox models. PPI use was introduced as time-varying. A 30-day lag was applied to minimize reverse causality. Models were adjusted for sociodemographic data, pregnancy characteristics, child comorbidities, and health care utilization.ResultsThe study population comprised 1 262 424 children (median [IQR] follow-up, 3.8 [1.8-6.2] years), including 606 645 who received PPI (323 852 male [53.4%]; median [IQR] age at index date, 88 [44-282] days) and 655 779 who did not receive PPI (342 454 male [52.2%]; median [IQR] age, 82 [44-172] days). PPI exposure was associated with an increased risk of serious infections overall (aHR, 1.34; 95% CI, 1.32-1.36). Increased risks were also observed for infections in the digestive tract (aHR, 1.52; 95% CI, 1.48-1.55); ear, nose, and throat sphere (aHR, 1.47; 95% CI, 1.41-1.52); lower respiratory tract (aHR, 1.22; 95% CI, 1.19-1.25); kidneys or urinary tract (aHR, 1.20; 95% CI, 1.15-1.25); and nervous system (aHR, 1.31; 95% CI, 1.11-1.54) and for both bacterial (aHR, 1.56; 95% CI, 1.50-1.63) and viral infections (aHR, 1.30; 95% CI, 1.28-1.33).Conclusions and relevanceIn this study, PPI use was associated with increased risks of serious infections in young children. Proton pump inhibitors should not be used without a clear indication in this population.
| S-EPMC10425862 | biostudies-literature
Project description:Background/aimsProton pump inhibitors (PPIs) increase gastric pH and alter the gut microbiome. An increased risk for infectious diseases has been reported in PPI users. However, little is known about the association of PPI use with pyogenic liver abscess (PLA) incidence risk.MethodsWe conducted a population-based cohort study using data from a nationwide representative sample of the Korean general population followed up for 10 years (January 1, 2003 to December 31, 2013). We identified PPI prescriptions and considered PPI as a timevarying variable. Proportional hazards regression model was used for incident PLA comparing PPI use versus non-use. Propensity score matching was also conducted.ResultsDuring the 4 209 229 person-years of follow-up, 58 595 participants had at least 1 PPI prescription and 541 patients developed liver abscess. The age-, sex-, residential area-, and income-adjusted hazard ratio for PLA incidence with PPI use was 4.19 (95% CI, 2.54- 6.92). The association was observed in fully adjusted models (hazard ratio 3.88; 95% CI, 2.33-6.44). The positive association between PPI use and PLA was consistent in all subgroups analyzed and in propensity score matching group.ConclusionThe present data indicate that PPI use is associated with an increased PLA risk. Therefore, it is necessary to prescribe PPIs with clear indication and to avoid improper use of PPIs.
| S-EPMC8521470 | biostudies-literature
Project description:Peritonitis is a major and the most significant complication of peritoneal dialysis (PD). Although some predictors of peritonitis in PD patients are known, the association between proton pump inhibitor (PPI) use and peritonitis has not been characterized. Here, we examined whether PPI use is a risk factor for the development of peritonitis, based on a single-center retrospective analysis of 230 consecutive Japanese PD patients at Narita Memorial Hospital. We assessed the association between PPI use and subsequent first episode of peritonitis using multivariate Cox proportional hazards models, following adjustment for clinically relevant factors. The median follow-up period was 36 months (interquartile range, 19-57 months). In total, 86 patients (37.4%) developed peritonitis. Analysis with multivariate Cox proportional hazards models revealed the following significant predictors of peritonitis: PPI use (adjusted hazard ratio [HR] = 1.72, 95% confidence interval [CI]: 1.11-2.66; P = 0.016) and low serum albumin level (per g/dl adjusted HR = 0.59, 95% CI: 0.39-0.90; P = 0.014). Thus, PPI use was independently associated with PD-related peritonitis. The results suggest that nephrology physicians should exercise caution when prescribing PPIs for PD patients.
| S-EPMC6837385 | biostudies-literature
Project description: Not available
| S-EPMC4205904 | biostudies-literature
Project description:Background: More and more studies are focusing on the adverse effects and damage caused by PPI abuse, we carried out a systematic review and meta-analysis for assessing whether the proton pump inhibitor (PPI) leads to hepato-biliary-pancreatic cancer. Methods: PubMed, EMBASE and Web of Science were searched until 1 July 2022, 25 studies (17 case-control and 8 cohort studies; 2741853 individuals) included in this study. Pooled Odd Ratios (ORs) were used for random effect models. Sensitivity analysis and dose-response analysis, subgroup analysis were all conducted. Results: The aggregate OR of the meta-analysis was 1.69 (95% confidence interval (CI): 1.42-2.01, p = 0.01) and heterogeneity (I 2 = 98.9%, p < 0.001) was substantial. According to stratified subgroup analyses, the incidence of hepato-biliary-pancreatic cancer was associated, expect for study design, study quality and region. Risk of hepato-biliary-pancreatic cancer is highest when people is treated with normal doses of PPI. The risks decrease and become insignificant when the cumulative defined daily dose (cDDD) increases. Conclusion: The use of PPI may be associated with an increased risk of hepato-biliary-pancreatic cancer. Hence, caution is needed when using PPIs among patients with a high risk of hepato-biliary-pancreatic cancer.
| S-EPMC9515471 | biostudies-literature
Project description:Background and aimThe aim of this study was to assess the impact of proton pump inhibitor (PPI) intake on the development of spontaneous bacterial peritonitis (SBP) or other infections, as well as on mortality, in a thoroughly documented cohort of patients with cirrhosis and ascites.Patients and methodsWe performed a retrospective analysis of follow-up data from 607 consecutive patients with cirrhosis undergoing their first paracentesis at a tertiary center. A binary logistic regression model investigating the association between PPI intake and SBP at the first paracentesis was calculated. Competing risk analyses and Cox models were used to investigate the effect of PPIs on the cumulative incidence of SBP or other infections and transplant-free survival, respectively. Adjustments were made for age, hepatocellular carcinoma, history of variceal bleeding, varices and model of end-stage liver disease score.ResultsEighty-six percent of patients were receiving PPIs. After adjusting for potential confounding factors, PPI intake was neither associated with increased SBP prevalence at the first paracentesis (odds ratio (OR):1.11,95% confidence interval (95%CI):0.6-2.06; P = 0.731) nor cumulative incidence of SBP (subdistribution hazard ratio (SHR): 1.38; 95%CI:0.63-3.01; P = 0.42) and SBP or other infections (SHR:1.71; 95%CI:0.85-3.44; P = 0.13) during follow-up. Moreover, PPI intake had no impact on transplant-free survival in both the overall cohort (hazard ratio (HR):0.973,95%CI:0.719-1.317; P = 0.859) as well as in the subgroups of patients without SBP (HR:1.01,95%CI:0.72-1.42; P = 0.971) and without SBP or other infections at the first paracentesis (HR:0.944,95%CI:0.668-1.334; P = 0.742).ConclusionsThe proportion of cirrhotic patients with PPI intake was higher than in previous reports, suggesting that PPI indications were interpreted liberally. In our cohort with a particularly high prevalence of PPI intake, we observed no association between PPIs and SBP or other infections, as well as mortality. Thus, the severity of liver disease and other factors, rather than PPI treatment per se may predispose for infectious complications.
| S-EPMC4219684 | biostudies-literature
Project description:IntroductionLimited studies have evaluated the association between Clostridium difficile infection (CDI) and the duration of proton pump inhibitor (PPI) or histamine H2-receptor blocker (H2RA) use and provided a cutoff duration for PPI or H2RA use to mitigate a substantially increased risk of CDI. We aimed to evaluate these associations in hospitalized patients using a nationwide insurance claims database.MethodsWe conducted a nested case-control study to identify cases with a first ever record of CDI in a study cohort undergoing PPI or H2RA therapy from the National Health Insurance Database from 2012 to 2018. Each case was matched with one control by age, sex, and calendar year. We used conditional logistic regression to estimate the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC ROC). Youden's J statistic was used to identify the optimal cutoff duration in days for PPI or H2RA use.ResultsIn the main analysis, the AUC ROC was 0.64 (95% CI 0.63-0.66) and optimal cutoff duration was 15 days for PPI users. The AUC ROC was 0.63 (95% CI 0.62-0.64) and optimal cutoff duration was 16 days for H2RA users. In the sensitivity analyses, the results were similar to those of the main analysis, and the optimal cutoff duration was in the range of 14-15 days.ConclusionsThe optimal cutoff duration for PPI and H2RA use was about 2 weeks. It is necessary to be cautious regarding the risk of CDI in patients taking PPIs or H2RAs for longer than 2 weeks.
| S-EPMC10904693 | biostudies-literature
Project description:BackgroundRecent evidence suggests that proton pump inhibitors (PPIs) might be linked with adverse cardiac events, but a causal relationship is unproven.MethodsWe applied the self-matched case series method to two studies using population-based health care data from Ontario, Canada between 1996 and 2008. The first included subjects aged 66 years or older hospitalized for acute myocardial infarction within 12 weeks following initiation of PPI, while the second included subjects hospitalized for heart failure. In both studies we designated the primary risk interval as the initial 4 weeks of therapy and the control interval as the final 4 weeks. To test the specificity of our findings we examined use of histamine H2 receptor antagonists and benzodiazepines, drugs with no plausible causal link to adverse cardiac events.ResultsDuring the 13-year study period, we identified 5550 hospital admissions for acute myocardial infarction and 6003 admissions for heart failure within 12 weeks of commencing PPI therapy. In the main analyses, we found that initiation of a PPI was associated with a higher risk of acute myocardial infarction (odds ratio 1.8; 95% confidence interval 1.7 to 1.9) and heart failure (odds ratio 1.8; 95% confidence interval 1.7 to 1.9). However, secondary analyses revealed similar risk estimates histamine H2 receptor antagonists and benzodiazepines, drugs with no known or suspected association with adverse cardiac events.ConclusionPPIs are associated with a short-term risk of adverse cardiac events, but similar associations are seen with other drugs exhibiting no known cardiac toxicity. Collectively these observations suggest that the association between PPIs and adverse cardiac events does not represent reflect cause-and-effect.
| S-EPMC3873988 | biostudies-literature