ObjectivesPatients with Clostridioides difficile infection (CDI) who receive treatment at outpatient infusion centers (OICs) pose a risk for spore transmission. We investigated C. difficile contamination in the environment of CDI and non-CDI patients and evaluated the effectiveness of standard cleaning. MethodsThis is a multicenter, non-conventional study including 8 OICs between October 2019 and December 2020. Samples were collected at baseline, after infusion, and after cleaning CDI and non-CDI areas. Cleaning was performed using hypochlorite and non-hypochlorite products for CDI and non-CDI, respectively. Samples were cultured for toxigenic C. difficile and strain-typed via fluorescent PCR ribotyping and whole-genome sequencing. ResultsThe overall C. difficile contamination rate was 7.9% (156/1969) with 8.1% in patient and 5.6% in non-patient care areas, respectively. For CDI areas, contamination rates were 5.9% at baseline, 15.0% after infusion, and significantly reduced to 6.2% after cleaning (P = 0.004). For non-CDI areas, contamination was similar at baseline (9.5%), after infusion (7.6%), and after cleaning (4.3%). The difference in C. difficile-positive samples after infusion was significant for CDI vs. non-CDI (15.0% vs. 7.6%, P = 0.004). Overall contamination was 11.5% for floors, 7.9% for infusion chairs, and 3.8% for equipment (P = 0.001). The most frequent ribotypes were F014-020 (42.6%), F106 (15.6%), F255 (6.1%), F001 (5.2%) and F027 (3.5%). Cleaning resulted in elimination of F106, F255, F001, F027 and partial reduction of F014-020. ConclusionsEnvironmental C. difficile contamination was increased after CDI infusions and significantly reduced after cleaning with a hypochlorite solution, reducing the potential risk of spore transmission to others.