Proton Pump Inhibitor Use Elevates the Risk of Severe Clostridium Difficile Colitis

Abstract

AIM: Gastric acid suppression is identified as a risk factor for Clostridium difficile infection (CDI). Our objective was to determine if the use of proton pump Inhibitors (PPI) are associated with increased severity of CDI (severe CDI).

 METHODS: Retrospective analysis of hospitalized patients with CDI at Geisinger Medical Center was performed. Hospital admissions with CDI over an 8 year period (Jan 2001 to Oct 2009) were assessed for proton pump inhibitor (PPI)/histamine 2 receptor antagonist (H2RA) use, antibiotic (ABX) use, and features of severe CDI defined as two or more of the following within 5 days of a positive stool test (of index CDI): WBC>15 K or <4 K/μL, bandemia >10%, shock (SBP< 90 mmHg), subtotal/total colectomy after index CDI, organ dysfunction (acute respiratory failure, acute renal failure, altered mental status or serum lactate>2.5 mmol/L). Death (30-day death attributed to CDI) was also analyzed.

RESULTS: 627 patients with CDI were divided into four groups: those on neither PPI nor H2RA, those on purely PPI blockers, those on purely H2RA blockers, and on both PPI and H2RA. Patients on PPI or H2RA were more likely to be on antibiotics (ABX) antibiotics within 90 days of CDI index case or vasopressors. Among all patients, 40% developed severe CDI. Unadjusted odds ratio (OR) of developing severe CDI for PPI was 1.91 (95% CI: 1.36, 2.69, p=0.0002), and for H2RA the OR was 0.66 (95% CI: 0.41, 1.05, p=0.0770). After controlling for confounders the effect of PPI was significantly elevated (OR=1.60, 95% CI: 1.09, 2.351) whereas the effect of H2RA was protective (OR=0.50, 95% CI: 0.31, 0.83).There was no statistically significant difference in 30-day mortality by medication group.

CONCLUSIONS: Results suggest PPI use could lead to an elevated risk of developing severe CDI, while H2RA was found to decrease the risk of severe CDI. This study suggests limiting the indiscriminate use of PPI in hospitalized patients.