Relationship Between Remote History of Cholecystectomy and Risk for Incident Clostridium difficile Infection

Abstract

Introduction:Clostridium difficile infection (CDI) is the leading cause of healthcare-associated diarrhea and gastroenteritis-associated death. Secondary bile acids inhibit C. difficile germination in vitro and confer resistance to CDI in animals. Cholecystectomy (CCY) alters gut bile acid composition, with increased fecal levels of secondary bile acids. This study tested the hypothesis that remote CCY confers protection against CDI by increasing gut levels of secondary bile acids. Methods: This was a retrospective case control study. The study population included all adult inpatients tested for the C. difficile toxin B gene by stool PCR between 1 January 2010 and 30 June 2017 at our institution, excluding those with a previous positive test for CDI within 90 days. For patients with multiple stool tests for C. difficile, the first test was selected. Remote CCY was defined as a history of CCY at least 6 months prior to the index test. Cases of CDI were defined as a positive stool PCR followed by anti-CDI treatment and were matched 1:1 with non-CDI controls by gender, age, BMI, and recent antibiotics exposure. Additional clinical factors including demographics, baseline comorbidities, medication exposures, and laboratory values were retrieved using automated queries. Conditional logistic regression modeling was used to estimate the relationship between remote CCY and risk for CDI, after adjusting for other factors. Results: The final study population was 4,918, including 2,459 CDI cases and 2,459 controls. Cases and controls did not differ based on gender, age, BMI, or recent antibiotics exposure. Patients with CDI had higher serum creatinine, more baseline comorbidities, and longer hospital stays. They were more likely to have an abnormal white blood cell count, to be in an intensive care unit, and to have recently received proton pump inhibitors. More patients with remote CCY were obese compared to patients without history of CCY (31% vs 25%, p<0.05) and were female (69% vs 50%, p<0.01). Rates of remote CCY did not differ based on CDI status (8.1% vs 7.9%, p=0.83). This result was unchanged after adjusting for additional clinical factors (adjusted OR 1.05, 95% CI 0.85-1.29, see Table) and also unchanged after adjusting for the matching variables. Conclusion: There was no association between remote CCY and risk for CDI in this large retrospective cohort study. Either gut bile acid content is not a major driver of CDI in humans or CCY impacts gut bile acids less than previously believed.168 Figure 1 No Caption available.