Low Serum Vitamin D is Associated With Increased Risk of Community-Acquired Clostridium difficile Infection

Abstract

Introduction:Clostridium difficile infection (CDI) is increasingly recognized as an important community-acquired pathogen causing disease in patients with no recent healthcare contact (CA-CDI). Vitamin D [25(OH)D] has immune modulatory effects and plays an important role in intestinal immunity. The role of vitamin D in CA-CDI has not been examined previously, but may offer insights into pathogenesis and prevention. Methods: This was a single center case-control study. Cases comprised of patients with a positive C. difficile toxin assay who had a serum 25(OH)D measured within 12 months prior or within 14 days of CDI diagnosis. The analysis was restricted to community-acquired cases diagnosed as an outpatient or within 48 hours of inpatient status and no recent hospitalization or long-term care facility stay within 30 days prior to diagnosis. Controls were drawn from patients who had 25(OH)D checked and matched based on age, gender, race, and health status. Serum 25(OH)D was stratified as <15 ng/mL, 15-30 ng/mL or > 30 ng/mL. Regression models adjusting for potential confounders including comorbidity, season, and antibiotic use were used to define independent effect of serum 25(OH)D on risk of CA-CDI. Results: We identified 58 matched case-control pairs. Two-thirds were women and a majority was Caucasian with a mean age of 62 years. The mean serum 25(OH)D level was significantly lower in CA-CDI cases compared to controls (28.5 ng/mL vs. 33.8 ng/mL, p=0.046) (Figure 1). Cases had significantly higher rate of antibiotic exposure (odds ratio [OR] 10.8; 95% confidence interval [CI] 4.6-25.8), lower serum albumin (mean 3.2 vs. 4.3), and significantly more comorbiditty. Serum 25(OH)D below 15 ng/mL was associated with a significantly increased risk of CA-CDI on univariate (OR 3.9; 95% CI 1.1-13.4) and multivariate analysis adjusting for comorbidity and season of measurement (OR 3.84; 95% CI 1.10-13.42). Serum 25(OH)D levels between 15-30 ng/mL did not modify disease risk. Additional adjustment for antibiotic use only weakly attenuated the effect (p=0.066).Figure 1: Serum 25(OH)D levels in Clostridium difficile cases and controls.Conclusion: Low serum 25(OH)D < 15ng/mL was associated with increased risk of CA-CDI. This suggests vitamin D may have a role in determining susceptibility to CA-CDI, and offers intriguing insights into pathogenesis and potential for disease prevention. Disclosure - Dr. Ananthakrishnan - Scientific advisory board, Cubist pharmaceuticals.