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Prophylaxis for Stress Ulcers With Proton Pump Inhibitors Is Not Associated With Increased Risk of Bloodstream Infections in the Intensive Care Unit.

ABSTRACT: Proton pump inhibitors (PPIs) have been associated with increased risk of infection, likely because of changes in intestinal epithelial permeability and the gastrointestinal microbiome. PPIs are frequently given to patients in the intensive care unit (ICU) to prevent stress ulcers. These patients are at risk for bloodstream infections (BSIs), so we investigated the relationship between PPI use and BSIs among patients in the ICU.We performed a retrospective cohort study of adults (?18 years) admitted to 1 of 14 ICUs within a hospital network of 3 large hospitals from 2008 through 2014. The primary exposure was PPI use for stress ulcer prophylaxis in the ICU. The primary outcome was BSI, confirmed by culture analysis, arising 48 hours or more after admission to the ICU. Subjects were followed for 30 days after ICU admission or until death, discharge, or BSI. Multivariable Cox proportional hazards modeling was used to test the association between PPIs and BSI after controlling for patient comorbidities and other clinical factors.We analyzed data from 24,774 patients in the ICU, including 756 patients (3.1%) who developed BSIs while in the ICU. The cumulative incidence of BSI was 3.7% in patients with PPI exposure compared with 2.2% in patients without PPI exposure (log-rank test, P < .01). After adjusting for potential confounders, PPI exposure was not associated with increased risk of BSI while in the ICU (adjusted hazard ratio, 1.08; 95% confidence interval, 0.91-1.29). Comorbidities, antibiotic use, and mechanical ventilation were all independently associated with increased risk for BSIs.In a retrospective study of patients in the ICU, administration of PPIs to prevent bleeding was not associated with increased risk of BSI. These findings indicate that concern for BSI should not affect decisions regarding use of PPIs in the ICU.

SUBMITTER: Cohen ME

PROVIDER: S-EPMC5474142 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Prophylaxis for Stress Ulcers With Proton Pump Inhibitors Is Not Associated With Increased Risk of Bloodstream Infections in the Intensive Care Unit.

Cohen Margot E ME Hathway Joanne M JM Salmasian Hojjat H Liu Jianfang J Terry Melissa M Abrams Julian A JA Freedberg Daniel E DE

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 20170118 7

<h4>Background & aims</h4>Proton pump inhibitors (PPIs) have been associated with increased risk of infection, likely because of changes in intestinal epithelial permeability and the gastrointestinal microbiome. PPIs are frequently given to patients in the intensive care unit (ICU) to prevent stress ulcers. These patients are at risk for bloodstream infections (BSIs), so we investigated the relationship between PPI use and BSIs among patients in the ICU.<h4>Methods</h4>We performed a retrospecti ...[more]

PMID: 28110095

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Project description:ObjectivesPatients in the intensive care unit (ICU) frequently receive proton pump inhibitors (PPIs) and have high rates of Clostridium difficile infection (CDI). PPIs have been associated with CDI in hospitalized patients, but ICU patients differ fundamentally from non-ICU patients and few studies have focused on PPI use exclusively in the critical care setting. We performed a retrospective cohort study to determine the associations between PPIs and health-care facility-onset CDI in the ICU.MethodsWe analyzed data from all adult ICU patients at three affiliated hospitals (14 ICUs) between 2010 and 2013. Patients were excluded if they had recent CDI or an ICU stay of <3 days. We parsed electronic medical records for ICU exposures, focusing on PPIs and other potentially modifiable exposures that occurred during ICU stays. Health-care facility-onset CDI in the ICU was defined as a newly positive PCR for the C. difficile toxin B gene from an unformed stool, with subsequent receipt of anti-CDI therapy. We analyzed PPIs and other exposures as time-varying covariates and used Cox proportional hazards models to adjust for demographics, comorbidities, and other clinical factors.ResultsOf 18,134 patients who met the criteria for inclusion, 271 (1.5%) developed health-care facility-onset CDI in the ICU. Receipt of antibiotics was the strongest risk factor for CDI (adjusted HR (aHR) 2.79; 95% confidence interval (CI), 1.50-5.19). There was no significant increase in risk for CDI associated with PPIs in those who did not receive antibiotics (aHR 1.56; 95% CI, 0.72-3.35), and PPIs were actually associated with a decreased risk for CDI in those who received antibiotics (aHR 0.64; 95% CI, 0.48-0.83). There was also no evidence of increased risk for CDI in those who received higher doses of PPIs.ConclusionsExposure to antibiotics was the most important risk factor for health-care facility-onset CDI in the ICU. PPIs did not increase risk for CDI in the ICU regardless of use of antibiotics.

Project description:INTRODUCTION:Proton pump inhibitors, which are widely used as acid-inhibitory agents for the treatment of peptic ulcers, are mainly metabolized by 2C19 isoenzyme of cytochrome P450 (CYP2C19). CYP2C19 has genetic polymorphisms, associated with extensive, poor, intermediate or ultra-rapid metabolism of proton pump inhibitors. Genetic polymorphisms of CYP2C19 could be of clinical concern in the treatment of peptic ulcers with proton pump inhibitors. AIM:To investigate the frequencies of CYP2C19*2, CYP2C19*3, and CYP2C19*17 alleles and genotypes in Russian patients with peptic ulcers. METHODS:We retrospectively reviewed the cases of 971 patients of Caucasian origin with Russian nationality from Moscow region with endoscopically and histologically proven ulcers, 428 males (44%) and 543 females (56%). The mean age was 44.6±11.9 years (range: 15-88 years). DNA was extracted from ethylenediaminetetraacetic acid whole blood samples (10 mL). The polymorphisms CYP2C19 681G.A (CYP2C19*2, rs4244285), CYP2C19 636 G.A (CYP2C19*3, rs4986893) and CYP2C19 -806 C.T (CYP2C19*17, rs12248560) were evaluated using real-time polymerase chain reaction. RESULTS:Regarding CYP2C19 genotype, 317 patients (32.65%) out of 971 were CYP2C19*1/*1 carriers classified as extensive metabolizers. Three hundred and eighty-six (39.75%) with CYP2C19*1/*17 or CYP2C19*17/*17 genotype were ultra-rapid metabolizers. Two hundred and fifty-one people (25.85%) were intermediate metabolizers with CYP2C19*1/*2, CYP2C19*2/*17, CYP2C19*1/*3, CYP2C19*3/*17 genotypes. Seventeen patients (1.75%) with CYP2C19*2/*2, CYP2C19*3/*3, CYP2C19*2/*3 genotypes were poor metabolizers. The allele frequencies were the following: CYP2C19*2 - 0.140, CYP2C19*3 - 0.006, CYP2C19*17 - 0.274. CONCLUSION:There is a high frequency of CYP2C19 genotypes associated with modified response to proton pump inhibitors in Russian patients with peptic ulcers. Genotyping for CYP2C19 polymorphisms is suggested to be a useful tool for personalized dosing of proton pump inhibitors.

Project description:PurposeThis study aims to develop and validate a nomogram for predicting the risk of bloodstream infections (BSI) in critically ill patients based on their admission status to the Intensive Care Unit (ICU).Patients and methodsPatients' data were extracted from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database (training set), the Beijing Friendship Hospital (BFH) database (validation set) and the eICU Collaborative Research Database (eICU-CRD) (validation set). Univariate logistic regression analyses were used to analyze the influencing factors, and lasso regression was used to select the predictive factors. Model performance was assessed using area under receiver operating characteristic curve (AUROC) and Presented as a Nomogram. Various aspects of the established predictive nomogram were evaluated, including discrimination, calibration, and clinical utility.ResultsThe model dataset consisted of 14930 patients (1444 BSI patients) from the MIMIC-IV database, divided into the training and internal validation datasets in a 7:3 ratio. The eICU dataset included 2100 patients (100 with BSI) as the eICU validation dataset, and the BFH dataset included 419 patients (21 with BSI) as the BFH validation dataset. The nomogram was constructed based on Glasgow Coma Scale (GCS), sepsis related organ failure assessment (SOFA) score, temperature, heart rate, respiratory rate, white blood cell (WBC), red width of distribution (RDW), renal replacement therapy and presence of liver disease on their admission status to the ICU. The AUROCs were 0.83 (CI 95%:0.81-0.84) in the training dataset, 0.88 (CI 95%:0.88-0.96) in the BFH validation dataset, and 0.75 (95%CI 0.70-0.79) in the eICU validation dataset. The clinical effect curve and decision curve showed that most areas of the decision curve of this model were greater than 0, indicating that this model has a certain clinical effectiveness.ConclusionThe nomogram developed in this study provides a valuable tool for clinicians and nurses to assess individual risk, enabling them to identify patients at a high risk of bloodstream infections in the ICU.

Dataset Information

Prophylaxis for Stress Ulcers With Proton Pump Inhibitors Is Not Associated With Increased Risk of Bloodstream Infections in the Intensive Care Unit.

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Prophylaxis for Stress Ulcers With Proton Pump Inhibitors Is Not Associated With Increased Risk of Bloodstream Infections in the Intensive Care Unit.

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