{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:46:43Z","timestamp":1790887603096,"version":"4.1.0"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The natural history of Clostridioides difficile progression in nucleic acid amplification test (NAAT) positive, toxin enzyme immunoassay\u2013negative patients remains poorly described. Better understanding risk for subsequent disease may improve prevention strategies. We aimed to describe the natural history of C. difficile NAAT+\/toxin\u2212 adults.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A cohort of adults (\u226518 years) tested for C. difficile within the Duke University Health System between 15 March 2020 and 31 December 2023 were classified as NAAT\u2212, NAAT+\/toxin\u2212, or NAAT+\/toxin+ and followed up to 90 days. Three time-to-event analyses were conducted. Incidence of toxin+ episodes was assessed by initial test status (analysis 1). Treatment of NAAT+\/toxin\u2212 adults was described using cumulative incidence curves (analysis 2). Rates of toxin+ episodes and severe disease were compared between treated and untreated NAAT+\/toxin\u2212 adults (analysis 3).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The cohort included 24 474 tests and 440 toxin+ episodes among 18 337 unique subjects followed for a median 71 days. NAAT+\/toxin\u2212 status was associated with subsequent toxin positivity (adjusted hazard ratio [aHR], 5.06 [95% confidence interval {CI}, 3.61\u20137.10]), especially after antibiotic receipt (aHR, 15.71 [95% CI, 9.85\u201325.06]). Among 2334 NAAT+\/toxin\u2212 episodes, 33% received presumptive treatment. Just 5% of NAAT+\/toxin\u2212 subjects progressed to toxin positivity. Presumptive treatment was associated with lower hazard of subsequent toxin positivity (aHR, 0.12 [95% CI, .05\u2013.29]) but not fulminant disease (aHR, 1.93 [95% CI, .50\u20137.45]).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Clostridioides difficile NAAT+\/toxin\u2212 status was associated with subsequent toxin positivity, especially after antibiotic receipt, though absolute risk was low overall. Further research is needed to determine whether and for whom presumptive treatment might be beneficial.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciaf020","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T03:38:57Z","timestamp":1737344337000},"page":"975-983","source":"Crossref","is-referenced-by-count":4,"title":["Natural History of <i>Clostridioides difficile<\/i>\u2013Related Disease Progression in the 2-Step Testing Era"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0650-4894","authenticated-orcid":false,"given":"Nicholas A","family":"Turner","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Duke University Medical Center , Durham, North Carolina ,","place":["USA"]},{"name":"Duke Center for Antimicrobial Stewardship and Infection Prevention , Durham, North Carolina ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6037-3253","authenticated-orcid":false,"given":"Steven C","family":"Grambow","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics , Durham, North Carolina ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Polage","sequence":"additional","affiliation":[{"name":"Duke Clinical Microbiology Laboratory, Duke University , Durham, North Carolina ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T","family":"Kuhar","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention , Atlanta, Georgia ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preeta K","family":"Kutty","sequence":"additional","affiliation":[{"name":"Division of Healthcare Quality 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