Limited retrospective data suggest prophylactic oral vancomycin may prevent Clostridioides difficile infection (CDI). We sought to evaluate the effectiveness of oral vancomycin for the prevention of healthcare facility-onset CDI (HCFO-CDI) in targeted patients.

We conducted a randomized, prospective, open-label study at Novant Health Forsyth Medical Center in Winston-Salem, North Carolina, between October 2018 and April 2019. Included patients were randomized 1:1 to either oral vancomycin (dosed at 125 mg once daily while receiving systemic antibiotics and continued for 5 days postcompletion of systemic antibiotics [OVP]) or no prophylaxis. The primary endpoint was incidence of HCFO-CDI. Secondary endpoints included incidence of community-onset healthcare facility-associated CDI (CO-HCFA-CDI), incidence of vancomycin-resistant Enterococci (VRE) colonization after receiving OVP, adverse effects, and cost of OVP.

A total of 100 patients were evaluated, 50 patients in each arm. Baseline and hospitalization characteristics were similar, except antibiotic exposure. No events of HCFO-CDI were noted in the OVP group compared with 6 (12%) in the no-prophylaxis group (P = .03). CO-HCFA-CDI was identified in 2 patients who were previously diagnosed with HCFO-CDI. No patients developed new VRE colonization, with only 1 patient reporting mild gastrointestinal side effects to OVP. A total of 600 doses of OVP were given during the study, with each patient receiving an average of 12 doses. Total acquisition cost of OVP was $1302, $26.04 per patient.

OVP appears to protect against HCFO-CDI during in-patient stay in targeted patients during systemic antibiotic exposure. Further prospective investigation is warranted.