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Background Clostridioides difficile - associated disease (CDAD) is the most common cause of healthcare-associated diarrhea with increasing prevalence and mortality rates. Recent reports suggest that prophylactic administration of vancomycin or fidaxomicin might reduce in-hospital CDAD incidence. The aims of this study were to examine whether primary oral vancomycin prophylaxis (OVP) reduces the in-hospital incidence of CDAD in elderly patients treated with systemic antibiotics and its impact on 90-day readmission rate. Methods This single-center, retrospective cohort study included 484 patients ≥ 65 years who received antimicrobial therapy for ≥ 24 hours and were hospitalized for ≥ 72 hours during a 24-month period. Patients diagnosed with CDAD within the first 48 hours of hospitalization were excluded. OVP group received ≥ 1 dose of vancomycin 125 mg once per day. Results Patients within OVP group (122; 25.2%) had higher age adjusted Charlson comorbidity index (CCI) (8; IQR 6–10 vs. 6; 5–8), were more often hospitalized within 3 months (62; 50.8% vs. 121; 33.4%), more commonly received piperacillin/tazobactam (60; 49.2% vs. 81; 22.4%) and carbapenems (27; 22.1% vs. 43; 11.9%) with longer duration of antibiotic therapy (14; 10–20 vs 10; 10–14 days). CDAD was diagnosed in 3 (2.5%) patients in OVP, compared with 45 patients (12.4%, p = 0.0011) in control group. In logistic regression analysis CCI > 6 (OR 3.54; 95% CI 1.79–6.87), OVP (0.19; 0.06–0.57), nursing home residency (4.10; 2.40–7.02), carbapenems (3.14; 1.60–6.15) and piperacillin/tazobactam (5.43; 2.87–10.14) were associated with CDAD. In this cohort, 28 (23.7%) patients from OVP and 69 (21.7%) patients from control group had 90-day readmission. 6 patients in OVP (4 new episodes) and 21 (14 new episodes) in control group were admitted for CDAD. Only CDAD during index hospitalization was associated with 90-day readmission (HR 4.60; 95% CI 1.93–10.96). Conclusion Primary OVP was highly effective in reducing the risk of in-hospital CDAD in elderly patients treated with systemic antimicrobial therapy. Prospective studies with follow-up are needed to define long-term efficacy and potential risks of this strategy. Disclosures All authors: No reported disclosures.

2411. One Dose Vancomycin Prophylaxis for In-Hospital Clostridioides difficile - Associated Disease