Comparative Effectiveness of Vancomycin vs. Metronidazole in Mild Clostridium difficile Infections, and Potential Impact on Subsequent Vancomycin-Resistant Enterococcus (VRE) Isolation

BACKGROUND: The epidemiology and clinical characteristics of Clostridium difficile infections (CDI) have evolved dramatically in the past decade. Vancomycin is the treatment of choice for moderate to severe CDI, with superior cure rates observed in comparative trials. However, controlled comparative efficacy data pertaining to mild CDI is lacking. Furthermore, the potential impact of vancomycin treatment on subsequent Vancomycin-Resistant Enterococcus (VRE) isolation rates remains unknown at the individual patient level. METHODS: A Retrospective cohort analysis was executed at the Assaf Harofeh Medical Center, Israel, from 2010 to 2015. Adult patients (>18 years) with a first episode of acute CDI, determined per pre-established criteria, were enrolled. The efficacy of vancomycin vs..metronidazole was evaluated in the subset of patients with mild CDI. The outcomes of patients, who received vancomycin or metronidazole (but not both), were compared by Cox regression. A prediction score was used to control for possible confounders associated with being treated with vancomycin. The independent association of oral vancomycin treatment during the acute CDI and later (up to 18 months) VRE isolation was analyzed using Cox regression. RESULTS: A total of 413 patients with CDI were included in the study. The majority were elderly (median age 75 years, range 19–120), and had extensive comorbidities (mean Charlson’s combined condition score 6.7 ± 3.4) and significant acute illness indices (35% with severe to fulminant Horn index). Among 126 patients with mild disease, no differences were observed in terms of clinical outcomes between vancomycin or metronidazole treatment. Metronidazole remained non-inferior even after incorporating a prediction score to control for confounders associated with being a “vancomycin case”. Ten patients had new post-CDI VRE isolation. In multivariable analysis, oral vancomycin treatment during the acute CDI was the strongest independent predictor for later isolation of VRE (aOR=6.7, P = 0.04). CONCLUSION: Our study suggests that metronidazole should remain the recommended treatment of choice for mild CDI, due to clinical non-inferiority and an apparent association between vancomycin therapy and subsequent VRE isolation on an individual patient level analysis. DISCLOSURES: All authors: No reported disclosures.