Therapeutic guidelines for Clostridioides difficile infections (CDI) were revised a few years ago, promoting the usage of oral vancomycin even for primary mild infections. Vancomycin-resistant enterococci (VRE) is one of the worldwide most significant pathogens. Our study aim was to explore the independent association between oral vancomycin treatment for CDI, and subsequent VRE acquisitions.

Retrospective cohort study.

Academic 904-bed general hospital (Shamir Medical Center, Israel).

Adult (>18 yr) inpatients with primary CDI and no prior VRE.

Study was conducted for calendar years 2016-2020. Logistic regression was used to model-independent predictors for VRE acquisitions. A propensity score (PS)-matched analysis (logistic regression) of the risk of receiving oral vancomycin was conducted to further eliminate potential confounders.

Overall, 606 patients were included (54% females), with a median age of 75 (IQR = 65–85) years. Independent predictors for VRE acquisition were oral vancomycin as a main therapy (aOR = 4.3, P < 0.001), exposure to systemic vancomycin in the previous 3 months (aOR = 3.2, P < 0.001), dependent functional status (aOR = 2.3, P = 0.006), and diabetes (aOR = 1.8, P = 0.04). After controlling for the PS, the independent association between oral vancomycin and later VRE acquisition remained significant in the regression model (aOR = 3.6, P < 0.01) and per PS matched-pairs analysis (aOR = 4.4, P < 0.01).

Oral vancomycin administered for CDI had a strong independent association with later VRE acquisitions. This finding could promote stewardship interventions in an effort to reduce the usage of oral vancomycin for certain CDI indications, leading to improved CDI management, while curbing the continued emergence of VRE at hospitals.