Recurrent Clostridium difficile Infection Is Associated With Vitamin A Deficiency

Abstract

Introduction:Clostridium difficile infection (CDI) is associated with significant morbidity and mortality and often recurs. Vitamin D and zinc deficiencies have been shown to correlate with severity and recurrence of CDI. Vitamin A is an essential fat-soluble vitamin that plays a role in epithelial cell barrier function and immunity. Vitamin A deficiency (VAD) has been associated with diarrheal disease, weight loss, and malnutrition, but is prevalent in only 1% of the national population. VAD has not previously been studied in patients with recurrent Clostridium difficile infection (rCDI). We aim to establish whether rCDI is associated with VAD and to identify characteristics of rCDI patients that are associated with VAD. Methods: Patients with rCDI who underwent fecal microbiota transplant at a tertiary care center from 2013 through 2016 were retrospectively reviewed. Inclusion criteria were 1) at least two documented episodes of CDI and 2) vitamin A levels drawn within 90 days of a CDI episode. Age, gender, hospitalization, chronic liver disease, inflammatory bowel disease (IBD), and severity of CDI were documented. Results: 82 patients (74% women, 26% men) met criteria;18 (22%) were found to have low vitamin A levels based on the institutional cut-off of 32.5 mcg/dL. VAD was more prevalent among rCDI patients than the national population (P<0.0001, 95% CI 13.6-32.5%, one proportion test). Half of vitamin A deficient versus 23% of vitamin A replete patients were hospitalized for CDI (P=0.04, Fischer's exact). Using logistic regression with adjustment for age, sex and IBD status, VAD correlated with severity (P=0.04, OR=6.1) but not hospitalization (P=0.12 OR=2.6). One third of vitamin A deficient patients had chronic liver disease compared to 9.7% of those with normal vitamin A (P=0.02). Conclusion: Our data suggests a significant association between rCDI and VAD. After adjustment for group characteristics, severe CDI was associated with a greater rate of VAD. VAD was also significantly associated with liver disease, consistent with known mechanisms of absorption and storage. No data currently exists on VAD in patients with rCDI. Oral vitamin A supplementation has been found to decrease the duration of general diarrheal episodes in children. On a cellular level, retinol helps restore epithelial cell function following exposure to Clostridium difficile Toxin A. Further research is warranted to determine whether deficient patients with rCDI should be supplemented with vitamin A.Table: Table. Patient DemographicsTable: Table. Clinical characteristics of patients with rCDI