Do the types and routes of proton pump inhibitor treatments affect clostridium difficile in ICU patients? A retrospective cohort study

ABSTRACT

Background: : Proton pump inhibitors (PPI) are associated with Clostridium difficile infection (CDI). Impact of the route of administration is unknown.

Research Design and Methods: Patients in Multiparameter Intelligent Monitoring in Intensive Care II database (MIMIC-II) from 2001 to 2008, >18 years old, admitted to medical, surgical, or cardiac ICUs were included. PPI exposures were omeprazole, esomeprazole, lansoprazole, and pantoprazole. PPI administration routes were oral or intravenous. Patients who received histamine receptor antagonists (H2RA) were the control arm. CDI was identified using ICD-9 diagnostic code 008.45. Multiple logistic regression analysis was performed to calculate odds ratios (OR).

Results: The study included 16,820 patients (57% male) with a mean age of 63 (SD±17) years and hospitalization duration of 10.2 days (SD±11). Pantoprazole was the most common PPI (94%). CDI occurred in 2.4% and more in patients receiving PPIs than H2RAs (3.0% vs. 0.8%, p < 0.001). CDI prevalence increased with intravenous (95%CI = 1.69–3.39, OR 2.4) and oral (95%CI = 1.59–3.27, OR 2.3) PPI use compared to H2RAs. CDI prevalence was not associated with PPI route in the multivariable model (OR 1.07, 95%CI 0.86–1.34).

Conclusions: Both intravenous and oral PPI use in the ICU were independently associated with CDI.

KEYWORDS:

• Clostridium difficile
• proton pump inhibition
• histamine receptor antagonists
• pantoprazole
• cdi
• ppi
• intravenous
• oral
• route

Article Highlights

• Proton pump inhibitor (PPI) exposure has been associated with Clostridium difficile infection (CDI) in patients in the intensive care unit (ICU).

• The impact of the route of administration of PPI on CDI has not been assessed

• We conducted an observational cohort study of 16,820 ICU patients

• Pantoprazole was the most common PPI (94%) prescribed

• PPI exposure was associated with CDI in ICU patients when compared to histamine-2 receptor antagonists.

The route of PPI administration did not have any impact on CDI

Declaration of interest

C. Alvarez receives funding from National Health Institute (NIH) and Merck. R. Hall receives funding from Merck and Medical Titan Group. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

P. Lee, R. Hall, and C. Alvarez contributed to the design and conception of the work presented. D. Fike and H. Yang extracted, analyzed, and interpreted the data for this manuscript. All authors contributed to drafting and critically editing the submitted manuscript. All authors gave final approval to the submitted manuscript. All authors are in agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.