{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:08:01Z","timestamp":1785305281245,"version":"3.55.0"},"reference-count":10,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T00:00:00Z","timestamp":1674604800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pericles.pericles-gcp.literatumonline.com"],"crossmark-restriction":true},"short-container-title":["Mycoses"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Itraconazole is the recommended first\u2010line treatment for mild\u2010to\u2010moderate blastomycosis and consolidation treatment of moderate\u2010to\u2010severe disease. Itraconazole is metabolised into three metabolites, including an active metabolite hydroxy\u2010itraconazole. Literature provides little evidence indicating whether therapeutic drug monitoring targets should be based on itraconazole parent compound alone or a sum of itraconazole and hydroxy\u2010itraconazole serum concentrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>This study aims to compare clinical outcomes and adverse drug events (ADEs) of combined itraconazole and hydroxy\u2010itraconazole concentrations versus itraconazole parent compound alone in patients with blastomycosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients\/Methods<\/jats:title><jats:p>This study was a retrospective cohort review of patients \u226518\u2009years with probable or proven <jats:italic>Blastomyces<\/jats:italic> infection who received itraconazole with at least one documented serum itraconazole concentration. The primary outcome was rate of partial or complete treatment response across three patient groups: (1) Itraconazole parent compound &gt;1.0\u00a0mcg\/ml (parent), (2) parent compound &lt;1.0\u00a0mcg\/ml, but a combined itraconazole and hydroxy\u2010itraconazole &gt;1.0\u00a0mcg\/ml (combined) and (3) failure to achieve a combined or parent concentration\u2009&gt;1.0\u00a0mcg\/ml (subtherapeutic) for &gt;75% of the duration of itraconazole therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 80 patients were included (parent\u00a0=\u00a032, combined\u00a0=\u00a036, subtherapeutic\u00a0=\u00a012). No statistically significant difference was observed for rate of partial or complete treatment response (97% parent vs 94% combined, <jats:italic>p<\/jats:italic>\u00a0=\u2009.99). Significantly higher mortality due to blastomycosis was observed in patients in the subtherapeutic group (0% parent vs 3% combined vs 25% subtherapeutic, <jats:italic>p<\/jats:italic>\u00a0=\u2009.01).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study supports an itraconazole therapeutic target combining itraconazole and hydroxy\u2010itraconazole &gt;1.0\u00a0mcg\/ml for blastomycosis treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/myc.13565","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T14:57:53Z","timestamp":1673967473000},"page":"412-419","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Does metabolite matter? Defining target itraconazole and hydroxy\u2010itraconazole serum concentrations for blastomycosis"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6033-5142","authenticated-orcid":false,"given":"Danielle","family":"Firkus","sequence":"first","affiliation":[{"name":"Department of Pharmacy Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar M.","family":"Abu\u00a0Saleh","sequence":"additional","affiliation":[{"name":"Division of Public Health Infectious Diseases and Occupational Medicine Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Enzler","sequence":"additional","affiliation":[{"name":"Division of Public Health Infectious Diseases and Occupational Medicine Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5629-439X","authenticated-orcid":false,"given":"Paul J.","family":"Jannetto","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine &amp; Pathology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8783-0191","authenticated-orcid":false,"given":"Kristin","family":"Mara","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6581-3956","authenticated-orcid":false,"given":"Paschalis","family":"Vergidis","sequence":"additional","affiliation":[{"name":"Division of Public Health Infectious Diseases and Occupational Medicine Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8308-3264","authenticated-orcid":false,"given":"Christina G.","family":"Rivera","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5050-6689","authenticated-orcid":false,"given":"Ryan W.","family":"Stevens","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,25]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1086\/521259"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/588300"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/45.3.371"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2019.1671971"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00199879"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12281-022-00430-4"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000438"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2016-0418"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02353-20"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1086\/605499"}],"container-title":["Mycoses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/myc.13565","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/myc.13565","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/myc.13565","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T12:41:47Z","timestamp":1693917707000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/myc.13565"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,25]]},"references-count":10,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["10.1111\/myc.13565"],"URL":"https:\/\/doi.org\/10.1111\/myc.13565","archive":["Portico"],"relation":{},"ISSN":["0933-7407","1439-0507"],"issn-type":[{"value":"0933-7407","type":"print"},{"value":"1439-0507","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,25]]},"assertion":[{"value":"2022-10-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}