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

AIM: Gastric acid suppression is identified as a risk factor forClostridium difficile infection (CDI). Our objective was to determineif the use of proton pump Inhibitors (PPI) are associated withincreased severity of CDI (severe CDI).METHODS: Retrospective analysis of hospitalized patientswith CDI at Geisinger Medical Center was performed. Hospitaladmissions with CDI over an 8 year period (Jan 2001 to Oct 2009)were assessed for proton pump inhibitor (PPI)/histamine 2 receptorantagonist (H2RA) use, antibiotic (ABX) use, and features of severeCDI defined as two or more of the following within 5 days of apositive stool test (of index CDI): WBC>15 K or <4 K/μL, bandemia>10%, shock (SBP< 90 mmHg), subtotal/total colectomy after indexCDI, organ dysfunction (acute respiratory failure, acute renal failure,altered mental status or serum lactate>2.5 mmol/L). Death (30-daydeath 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, thoseon purely H2RA blockers, and on both PPI and H2RA. Patients onPPI or H2RA were more likely to be on antibiotics (ABX) antibioticswithin 90 days of CDI index case or vasopressors. Among allpatients, 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 wassignificantly elevated (OR=1.60, 95% CI: 1.09, 2.351) whereas theeffect of H2RA was protective (OR=0.50, 95% CI: 0.31, 0.83).Therewas no statistically significant difference in 30-day mortality bymedication group.CONCLUSIONS: Results suggest PPI use could lead to anelevated risk of developing severe CDI, while H2RA was found todecrease the risk of severe CDI. This study suggests limiting theindiscriminate use of PPI in hospitalized patients.