Clostridioides difficile Infection (CDI) is a persistent healthcare issue. In the US, CDI is the most common infectious cause of hospital-onset (HO) diarrhea. Assess the impact of admission testing for toxigenic C. difficile colonization on the incidence of HO-CDI. Pragmatic stepped-wedge Infection Control initiative. NorthShore University HealthSystem is a four-hospital system near Chicago, IL. All patients admitted to the four hospitals during the initiative. From September 2017 through August 2018 we conducted a quality improvement program where admitted patients had a peri-rectal swab tested for toxigenic C. difficile. All colonized patients were placed into contact precautions. We tested admissions who: i) had been hospitalized within two months, ii) had a past C. difficile positive test, and/or iii) were in a long-term care facility within six months. We measured compliance with all other practices to reduce the incidence of HO-CDI. 30% of admissions were tested and 8.3% were positive. In the year prior to the initiative (Period 1) there were 63,057 admitted patients when HO-CDI incidence was 5.96 cases/10,000 patient days. During the 12-month initiative (Period 2) there were 62,760 admissions and the HO-CDI incidence was 4.23 cases/10,000 patient days (p = 0.02). There were no other practice or antibiotic use changes. Continuing admission surveillance provided a HO-CDI incidence of 2.9 cases/10,000 patient days during the final 9 months of 2018 (p<0.0001 compared to Period 1), equaling <1 case/1,000 admissions. This was not a randomized controlled trial, and multiple prevention practices were in place at the time of the admission surveillance initiative. Admission C. difficile surveillance testing is an important tool for preventing hospital-onset C. difficile infection. This quality improvement initiative is registered at ClinicalTrials.gov. The unique registration identifier number is NCT04014608.

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