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Proton Pump Inhibitors Do Not Increase Risk for Clostridium difficile Infection in the Intensive Care Unit.

ABSTRACT: OBJECTIVES:Patients 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. METHODS:We 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. RESULTS:Of 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. CONCLUSIONS:Exposure 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.

SUBMITTER: Faleck DM

PROVIDER: S-EPMC5096970 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Proton Pump Inhibitors Do Not Increase Risk for Clostridium difficile Infection in the Intensive Care Unit.

Faleck David M DM Salmasian Hojjat H Furuya E Yoko EY Larson Elaine L EL Abrams Julian A JA Freedberg Daniel E DE

The American journal of gastroenterology 20160830 11

<h4>Objectives</h4>Patients 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 th ...[more]

PMID: 27575714

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Project description:BackgroundAntibiotic disruption of the normal intestinal flora is a well-known risk factor for Clostridium difficile-associated diarrhea. Reduced gastric acidity has been suggested as a risk factor, and we hypothesized that proton pump inhibitors, because of their potency, may be an independent risk factor for this problem.MethodsFor the cohort study we identified from a pharmacy database 1187 inpatients at a Montreal teaching hospital who received antibiotics over a 9-month period beginning in August 2002. We compared patients in this group who had also received a proton pump inhibitor or an H(2) blocker with patients who had not received acid suppressive therapy. Hospital laboratory reports of positive assay results for C. difficile toxin were used to ascertain cases in the cohort. To assess the possibility that proton pump inhibitors were prescribed to patients who were sicker and had other risk factors for C. difficile infection, we did a case-control study at a second Montreal teaching hospital. Cases were defined as patients who were positive for C. difficile toxin and who had a history of diarrhea (n = 94). Control subjects were selected from among patients who had received an antibiotic and were matched to cases by ward, age within 5 years and class of antibiotics (n = 94).ResultsIn the cohort study, C. difficile diarrhea developed in 81 (6.8%) of the 1187 patients who received antibiotics while in hospital. In a multivariate analysis, C. difficile diarrhea was significantly associated with use of proton pump inhibitors (adjusted odds ratio [OR] 2.1, 95% confidence interval [CI] 1.2- 3.5), receipt of 3 or more antibiotics (OR 2.1, 95% CI 1.3- 3.4) and admission to a medical ward (OR 4.1, 95% CI 2.3- 7.3). In the case-control study C. difficile diarrhea was associated with female sex (adjusted OR 2.1, 95% CI 1.1-4.0), prior renal failure (adjusted OR 4.3, 95% CI 1.5-11.9), hospital admission in the 3 months before the index admission (adjusted OR 2.6, 95% CI 1.4-5.2) and use of proton pump inhibitors (adjusted OR 2.7, 95% CI 1.4-5.2).InterpretationPatients in hospital who received proton pump inhibitors were at increased risk of C. difficile diarrhea.

Project description:BackgroundAntibiotics and proton pump inhibitors (PPI) are recognized risk factors for acquisition and recurrence of Clostridioides difficile infection (CDI), yet combined effects remain unclear.ObjectivesTo assess the short- and long-term effects of antibiotics and PPIs on CDI risk and recurrence.MethodsPopulation-based study including all 43 152 patients diagnosed with CDI in Sweden (2006-2019), and 355 172 matched population controls without CDI. The impact of antibiotics and PPIs on CDI risk and recurrence was explored for recent (0-30 days) and preceding (31-180 days) use prior to their first CDI diagnosis, using multivariable conditional logistic regression presented as odds ratios (ORs) and 95% confidence interval, adjusted for demographics, comorbidities and other drugs.ResultsCompared to controls, the combined effect of recent PPIs and antibiotics [ORAB+PPI = 17.51 (17.48-17.53)] on CDI risk was stronger than the individual effects [ORAB = 15.37 (14.83-15.93); ORPPI = 2.65 (2.54-2.76)]. Results were less pronounced for exposure during the preceding months. Dose-response analyses showed increasing exposure correlated with CDI risk [recent use: ORAB = 6.32 (6.15-6.49); ORPPI = 1.65 (1.62-1.68) per prescription increase].Compared to individuals without recurrence (rCDI), recent [ORAB = 1.30 (1.23-1.38)] and preceding [ORAB = 1.23 (1.16-1.31); ORPPI = 1.12 (1.03-1.21)] use also affected the risk of recurrence yet without significant interaction between both. Recent macrolides/lincosamides/streptogramins; other antibacterials including nitroimidazole derivates; non-penicillin beta lactams and quinolones showed the strongest association with CDI risk and recurrence, particularly for recent use. PPI use, both recent and preceding, further increased the CDI risk associated with almost all antibiotic classes.ConclusionRecent and less recent use of PPIs and systemic antibiotics was associated with an increased risk of CDI, particularly in combination.

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Proton Pump Inhibitors Do Not Increase Risk for Clostridium difficile Infection in the Intensive Care Unit.

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Proton Pump Inhibitors Do Not Increase Risk for Clostridium difficile Infection in the Intensive Care Unit.

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