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Current prevention strategies are limited by their failure to account for patients who carry <jats:italic>C. difficile<\/jats:italic> asymptomatically, who may act as hidden reservoirs transmitting infections to other patients. To improve the understanding of asymptomatic carriers\u2019 contribution to <jats:italic>C. difficile<\/jats:italic> spread, we conducted admission and daily longitudinal culture-based screening for <jats:italic>C. difficile<\/jats:italic> in a US-based intensive care unit over nine months and performed whole-genome sequencing on all recovered isolates. Despite a high burden of carriage, with 9.3% of admissions having toxigenic <jats:italic>C. difficile<\/jats:italic> detected in at least one sample, only 1% of patients culturing negative on admission to the unit acquired <jats:italic>C. difficile<\/jats:italic> via cross-transmission. While patients who carried toxigenic <jats:italic>C. difficile<\/jats:italic> on admission posed minimal risk to others, they themselves had a 24-times greater risk for developing a healthcare-onset <jats:italic>C. difficile<\/jats:italic> infection than noncarriers. Together, these findings suggest that current infection prevention practices can be effective in preventing nosocomial cross-transmission of <jats:italic>C. difficile<\/jats:italic>, and that decreasing <jats:italic>C. difficile<\/jats:italic> infections in hospitals further will require interventions targeting the transition from asymptomatic carriage to infection.<\/jats:p>","DOI":"10.1038\/s41591-023-02549-4","type":"journal-article","created":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T16:02:01Z","timestamp":1695052921000},"page":"2526-2534","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Longitudinal genomic surveillance of carriage and transmission of Clostridioides difficile in an intensive care unit"],"prefix":"10.1038","volume":"29","author":[{"given":"Arianna","family":"Miles-Jay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8409-278X","authenticated-orcid":false,"given":"Evan S.","family":"Snitkin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Y.","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teppei","family":"Shimasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3066-708X","authenticated-orcid":false,"given":"Michael","family":"Schoeny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Fukuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thelma","family":"Dangana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9734-8905","authenticated-orcid":false,"given":"Nicholas","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1924-8941","authenticated-orcid":false,"given":"Sarah E.","family":"Sansom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel D.","family":"Yelin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Bell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micah","family":"Keidan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Standke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Bassis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary K.","family":"Hayden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3687-2364","authenticated-orcid":false,"given":"Vincent B.","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,18]]},"reference":[{"key":"2549_CR1","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1056\/NEJMoa1910215","volume":"382","author":"AY Guh","year":"2020","unstructured":"Guh, A. 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