Project Summary - Clostridioides difficile is a leading cause of infectious diarrhea and the most common cause of healthcare-associated infection (HAIs) in the US, resulting in >450,000 infections and 29,000 deaths annually. In fact, C. difficile was recently labeled as one of five “urgent threat” organisms by the CDC. Despite its prevalence, C. difficile acquisition and transmission remain poorly understood. Recent changes in testing strategies led to the surprising discovery that patients with C. difficile are more often colonized than infected. Hospitals routinely place patients infected with C. difficile on “contact precautions” to prevent transmission. However, this shifting epidemiology has led to an infection prevention dilemma: should patients with C. difficile colonization be placed on contact precautions? The answer to this question is unknown. Recently published infection prevention guidelines labeled this issue as “unresolved”. As a result, non-standardized practices are being used. In our cohort of hospitals, 50% of hospitals place these patients on contact precautions and 50% do not, suggesting that a substantial number of admitted patients are at potential risk of harm through either a) unnecessary use of contact precautions OR b) through preventable exposure to C. difficile. The overall objective of this proposal is to determine if contact precautions should be used in patients with C. difficile colonization. First, we will determine the frequency, location, and amount of environmental C. difficile contamination among 300 patients with C. difficile colonization (150 with diarrhea and 150 without diarrhea) compared to 150 patients with C. difficile infection (Specific Aim 1). Using these same rooms, we will then determine the frequency, location, and amount of C. difficile contamination of 900 healthcare providers' (HCP) hands, HCP clothes, and 450 pieces of mobile, shared equipment following routine inpatient care of patients with C. difficile colonization (Specific Aim 2). Finally, we will use ~1,500 C. difficile isolates from our unique C. difficile biorepository and study activities in SA 1 and 2 to evaluate potential sources for C. difficile in-hospital transmission using molecular epidemiology and whole genome sequencing (Specific Aim 3). This proposal will capitalize on the strengths of the Duke Center for Antimicrobial Stewardship and Infection Prevention, including our collective expertise in infection prevention and environmental contamination, our proven infrastructure for studies involving environmental sampling, and our validated microbiological, statistical, and molecular epidemiological methods. Our central hypothesis is that patients with C. difficile colonization contaminate their environment (surfaces, HCP, and equipment) as frequently as patients with C. difficile infection and, as a result, are a source of in hospital transmission. The proposed research is innovative because it represents a substantive departure...