Continuous PPI use associated with recurrent Clostridium difficile infection

1. Patients on continuous proton pump inhibitor (PPI) had an increased risk of recurrence of their Clostridium difficile infection.

2. While PPI use was common, almost half of patients did not have an evidence-based indication for usage.

Evidence Rating Level: 2 (Good)

Study Rundown: Preventing recurrence of Clostridium difficile infection (CDI) is important, as treatment for multiple recurrences can be difficult with limited therapeutic alternatives. It was previously understood that proton pump inhibitor (PPI) use is associated with initial CDI, but it is unclear whether continued PPI use increases risk of CDI recurrence. Given that PPIs are often over-prescribed and patients often remain on them longer than is clinically indicated, this study aimed to determine if PPI use was associated with initial CDI recurrence, what proportion of CDI patients were on PPIs for non-evidence based reason, and finally whether physicians discontinued clinically unnecessary PPIs in the context of CDI.

Patients on continuous PPIs had a 50% increased risk of CDI infection as compared to those not on PPIs. Other variables associated with recurrent CDI were age older than 75, length of stay, and vancomycin treatment during initial episode. Just under half of users did not have an evidence-based indication for PPI use. Strengths of this study include being a large cohort study that controlled for multiple confounders in regression analysis. However, due to being an observational study, one cannot determine causation. Also, the adherence of the PPI use was not analyzed which may have resulted in misclassification bias of the exposure.

Click to read the study, published today in JAMA Internal Medicine

Relevant Reading: Duodenal infusion of donor feces for recurrent Clostridium difficile

In-Depth [retrospective cohort]: This retrospective cohort included 754 patients from two hospitals in Montreal, Canada, who developed an initial episode of nosocomial CDI between January 2010 and January 2013. They were evaluated for a recurrence of CDI (i.e., symptoms with a positive PCR for toxin B) occurring between 15 and 90 days after the initial episode. The exposure of continuous PPI use was defined as use of PPI at initial CDI episode and ongoing exposure in hospital or discharge prescription for PPI lasting longer than 90 days. At CDI recurrence, patients were reevaluated for PPI use to ensure continuous exposure. Clinical indications for PPI use were reviewed through health record examination by two authors. Baseline demographic and comorbid information were gathered from health records, and data was analyzed using Cox proportional hazards model and multivariate regression.

Among the 754 patients, there were 193 recurrences (25.6%) within 90 days. Proton-pump inhibitor users were more likely to experience CDI recurrence (28.8% vs. 20.6%, p = 0.007) or to die within 15-90 days of initial CDI (10.3% vs. 4.7%, p = 0.007). The multivariate analysis hazard ratios for recurrence was 1.5 (95%CI 1.1-2.0) for patients older than 75 years, and 1.5 (95%CI 1.1-2.0) for continuous PPI use. PPI use was common (60.7%), however only 47.1% had an evidence-based indication for use, and PPI use was discontinued in only 3 patients.

Image: PD

©2015 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.