{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T08:00:09Z","timestamp":1773475209916,"version":"3.50.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T00:00:00Z","timestamp":1661817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Astellas Pharma, Inc"},{"name":"Washington University Institute of Clinical and Translational Sciences"},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000133","name":"Agency for Healthcare Research and Quality","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000133","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Fluconazole is recommended as first-line therapy for candidemia when risk of fluconazole resistance (fluc-R) is low. Lack of methods to estimate resistance risk results in extended use of echinocandins and prolonged hospitalization. This study aimed to develop a clinical predictive model to identify patients at low risk for fluc-R where initial or early step-down fluconazole would be appropriate.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Retrospective analysis of hospitalized adult patients with positive blood culture for Candida spp from 2013 to 2019. Multivariable logistic regression model was performed to identify factors associated with fluc-R. Stepwise regression was performed on bootstrapped samples to test individual variable stability and estimate confidence intervals (CIs). We used receiver operating characteristic curves to assess performance across the probability spectrum.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified 539 adults with candidemia and 72 Candida isolates (13.4%) were fluc-R. Increased risk of fluc-R was associated with older age, prior bacterial bloodstream infection (odds ratio [OR], 2.02 [95% CI, 1.13\u20133.63]), myelodysplastic syndrome (OR, 3.09 [95% CI, 1.13\u20138.44]), receipt of azole therapy (OR, 5.42 [95% CI, 2.90\u201310.1]) within 1 year of index blood culture, and history of bone marrow or stem cell transplant (OR, 2.81 [95% CI, 1.41\u20135.63]). The model had good discrimination (optimism-corrected c-statistic 0.771), and all of the selected variables were stable. The prediction model had a negative predictive value of 95.7% for the selected sensitivity cutoff of 90.3%.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This model is a potential tool for identifying patients at low risk for fluc-R candidemia to receive first-line or early step-down fluconazole.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ofid\/ofac447","type":"journal-article","created":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T14:57:50Z","timestamp":1661871470000},"source":"Crossref","is-referenced-by-count":10,"title":["Creation and Internal Validation of a Clinical Predictive Model for Fluconazole Resistance in Patients With <i>Candida<\/i> Bloodstream Infection"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9555-2550","authenticated-orcid":false,"given":"Adriana M","family":"Rauseo","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine , St Louis, Missouri , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret A","family":"Olsen","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine , St Louis, Missouri , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dustin","family":"Stwalley","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine , St Louis, Missouri , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick B","family":"Mazi","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine , St Louis, Missouri , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsey","family":"Larson","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine , St Louis, Missouri , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William G","family":"Powderly","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine , St Louis, Missouri , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7612-4710","authenticated-orcid":false,"given":"Andrej","family":"Spec","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine , St Louis, Missouri , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,8,30]]},"reference":[{"key":"2022092702275540900_ofac447-B1","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1017\/ice.2016.174","article-title":"Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011\u20132014","volume":"37","author":"Weiner","year":"2016","journal-title":"Infect Control Hosp Epidemiol"},{"key":"2022092702275540900_ofac447-B2","article-title":"Invasive candidiasis statistics","author":"Centers for Disease Control and Prevention","year":"2021"},{"key":"2022092702275540900_ofac447-B3","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/civ933","article-title":"Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America","volume":"62","author":"Pappas","year":"2015","journal-title":"Clin Infect Dis"},{"key":"2022092702275540900_ofac447-B4","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.idc.2015.10.013","article-title":"Invasive candidiasis","volume":"30","author":"McCarty","year":"2016","journal-title":"Infect Dis Clin North Am"},{"key":"2022092702275540900_ofac447-B5","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.1093\/cid\/cit136","article-title":"Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations","volume":"56","author":"Alexander","year":"2013","journal-title":"Clin Infect Dis"},{"key":"2022092702275540900_ofac447-B6","doi-asserted-by":"crossref","first-page":"e101510","DOI":"10.1371\/journal.pone.0101510","article-title":"Epidemiology and outcomes of invasive candidiasis due to non-albicans species of Candida in 2496 patients: data from the Prospective Antifungal Therapy (PATH) registry 2004\u20132008","volume":"9","author":"Pfaller","year":"2014","journal-title":"PLoS One"},{"key":"2022092702275540900_ofac447-B7","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1128\/AAC.47.10.3149-3154.2003","article-title":"Antifungal susceptibility survey of 2,000 bloodstream Candida isolates in the United States","volume":"47","author":"Ostrosky-Zeichner","year":"2003","journal-title":"Antimicrob Agents Chemother"},{"key":"2022092702275540900_ofac447-B8","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1093\/cid\/cis697","article-title":"Changes in incidence and antifungal drug resistance in candidemia: results from population-based laboratory surveillance in Atlanta and Baltimore, 2008\u20132011","volume":"55","author":"Cleveland","year":"2012","journal-title":"Clin Infect Dis"},{"key":"2022092702275540900_ofac447-B9","first-page":"e449","article-title":"Burden of candidemia in the United States, 2017","volume":"71","author":"Tsay","year":"2020","journal-title":"Clin Infect Dis"},{"key":"2022092702275540900_ofac447-B10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.ss6808a1","article-title":"Population-based active surveillance for culture-confirmed candidemia\u2014four sites, United States, 2012\u20132016","volume":"68","author":"Toda","year":"2019","journal-title":"MMWR Surveill Summ"},{"key":"2022092702275540900_ofac447-B11","doi-asserted-by":"crossref","first-page":"684.e1","DOI":"10.1016\/j.cmi.2015.02.029","article-title":"A simple prediction score for estimating the risk of candidaemia caused by fluconazole non-susceptible strains","volume":"21","author":"Cuervo","year":"2015","journal-title":"Clin Microbiol Infect"},{"key":"2022092702275540900_ofac447-B12","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1007\/BF00199879","article-title":"Influence of concomitant food intake on the oral absorption of two triazole antifungal agents, itraconazole and fluconazole","volume":"46","author":"Zimmermann","year":"1994","journal-title":"Eur J Clin Pharmacol"},{"key":"2022092702275540900_ofac447-B13","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1093\/jac\/dkq136","article-title":"Candidaemia associated with decreased in vitro fluconazole susceptibility: is Candida speciation predictive of the susceptibility pattern?","volume":"65","author":"Oxman","year":"2010","journal-title":"J Antimicrob Chemother"},{"key":"2022092702275540900_ofac447-B14","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofx253","article-title":"Creation and assessment of a clinical predictive calculator and mortality associated with Candida krusei bloodstream infections","volume":"5","author":"Kronen","year":"2018","journal-title":"Open Forum Infect Dis"},{"key":"2022092702275540900_ofac447-B15","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1016\/S1473-3099(19)30405-0","article-title":"Effect of infectious disease consultation on mortality and treatment of patients with Candida bloodstream infections: a retrospective, cohort study","volume":"19","author":"Mejia-Chew","year":"2019","journal-title":"Lancet Infect Dis"},{"key":"2022092702275540900_ofac447-B16","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1111\/myc.12917","article-title":"Creation and assessment of a clinical predictive model for candidaemia in patients with candiduria","volume":"62","author":"Wang","year":"2019","journal-title":"Mycoses"},{"key":"2022092702275540900_ofac447-B17","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1093\/mmy\/myz104","article-title":"Risk factors predicting Candida infective endocarditis in patients with candidemia","volume":"58","author":"Foong","year":"2020","journal-title":"Med Mycol"},{"key":"2022092702275540900_ofac447-B18","article-title":"Pathogen codes 2021","author":"Centers for Disease Control and Prevention","year":"2021"},{"key":"2022092702275540900_ofac447-B19","article-title":"Bloodstream infection event (central line-associated bloodstream infection and non-central line associated bloodstream infection)","author":"Centers for Disease Control and Prevention","year":"2021"},{"key":"2022092702275540900_ofac447-B20","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1097\/00005650-200210000-00010","article-title":"Impact of different measures of comorbid disease on predicted mortality of intensive care unit patients","volume":"40","author":"Johnston","year":"2002","journal-title":"Med Care"},{"key":"2022092702275540900_ofac447-B21","article-title":"National Healthcare Safety Network ICD-10 surgical site infection (SSI) events","author":"Centers for Disease Control and Prevention","year":"2022"},{"key":"2022092702275540900_ofac447-B22","article-title":"Clinical Classifications Software Refined (CCSR)","author":"Healthcare Cost and Utilization Project","year":"2022"},{"key":"2022092702275540900_ofac447-B23","article-title":"Performance standards for antifungal susceptibility testing of yeasts. Wayne, PA; CLSI;","author":"Clinical and Laboratory Standards Institute","year":"2017"},{"key":"2022092702275540900_ofac447-B24","volume-title":"Clinical prediction models: a practical approach to development, validation and updating","author":"Steyerberg","year":"2010"},{"key":"2022092702275540900_ofac447-B25","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1128\/AAC.00479-10","article-title":"Risk factors for fluconazole-resistant candidemia","volume":"54","author":"Garnacho-Montero","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"key":"2022092702275540900_ofac447-B26","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1093\/jac\/dkq053","article-title":"Candidaemia in adult cancer patients: risks for fluconazole-resistant isolates and death","volume":"65","author":"Slavin","year":"2010","journal-title":"J Antimicrob Chemother"},{"key":"2022092702275540900_ofac447-B27","first-page":"e02091","article-title":"A risk score for fluconazole failure among patients with candidemia","volume":"6","author":"Ostrosky-Zeichner","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"2022092702275540900_ofac447-B28","doi-asserted-by":"crossref","first-page":"3239","DOI":"10.1128\/AAC.00019-12","article-title":"Impact of prior inappropriate fluconazole dosing on isolation of fluconazole-nonsusceptible Candida species in hospitalized patients with candidemia","volume":"56","author":"Shah","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"key":"2022092702275540900_ofac447-B29","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1086\/502016","article-title":"Risk factors for vancomycin-resistant Enterococcus (VRE) infection in colonized patients with cancer","volume":"23","author":"Husni","year":"2002","journal-title":"Infect Control Hosp Epidemiol"},{"key":"2022092702275540900_ofac447-B30","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.3201\/eid1308.070071","article-title":"Risk factors for colonization with extended-spectrum beta-lactamase-producing bacteria and intensive care unit admission","volume":"13","author":"Harris","year":"2007","journal-title":"Emerg Infect Dis"},{"key":"2022092702275540900_ofac447-B31","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1093\/clinids\/23.4.767","article-title":"Risk factors associated with vancomycin-resistant Enterococcus faecium infection or colonization in 145 matched case patients and control patients","volume":"23","author":"Tornieporth","year":"1996","journal-title":"Clin Infect Dis"},{"key":"2022092702275540900_ofac447-B32","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1128\/AAC.05947-11","article-title":"Antibiotic exposure as a risk factor for fluconazole-resistant Candida bloodstream infection","volume":"56","author":"Ben-Ami","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"key":"2022092702275540900_ofac447-B33","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1086\/315193","article-title":"Candidemia in allogeneic blood and marrow transplant recipients: evolution of risk factors after the adoption of prophylactic fluconazole","volume":"181","author":"Marr","year":"2000","journal-title":"J Infect Dis"},{"key":"2022092702275540900_ofac447-B34","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1111\/1469-0691.12312","article-title":"A prospective, cohort, multicentre study of candidaemia in hospitalized adult patients with haematological malignancies","volume":"20","author":"Gamaletsou","year":"2014","journal-title":"Clin Microbiol Infect"},{"key":"2022092702275540900_ofac447-B35","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1007\/s10096-004-1128-2","article-title":"Clinical factors associated with fluconazole resistance and short-term survival in patients with Candida bloodstream infection","volume":"23","author":"Fujihara","year":"2004","journal-title":"Eur J Clin Microbiol Infect Dis"}],"container-title":["Open Forum Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ofid\/advance-article-pdf\/doi\/10.1093\/ofid\/ofac447\/45616428\/ofac447.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/9\/9\/ofac447\/46041805\/ofac447.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ofid\/article-pdf\/9\/9\/ofac447\/46041805\/ofac447.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T02:29:20Z","timestamp":1664245760000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ofid\/article\/doi\/10.1093\/ofid\/ofac447\/6678811"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,30]]},"references-count":35,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,9,2]]}},"URL":"https:\/\/doi.org\/10.1093\/ofid\/ofac447","relation":{},"ISSN":["2328-8957"],"issn-type":[{"value":"2328-8957","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,9,1]]},"published":{"date-parts":[[2022,8,30]]},"article-number":"ofac447"}}