{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T12:47:22Z","timestamp":1786970842589,"version":"build-2736575974"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,12,15]],"date-time":"2019-12-15T00:00:00Z","timestamp":1576368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mycoses"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Oral follow\u2010up therapy is problematic in moulds with reduced azole\u2010susceptibility, such as azole\u2010resistant <jats:italic>Aspergillus fumigatus<\/jats:italic> infection. Currently, only intravenous liposomal amphotericin B (L\u2010AmB) is advocated by guidelines for the treatment of azole\u2010resistant aspergillosis infections. Preclinical research indicates that high\u2010dose posaconazole (HD\u2010POS) might be a feasible option provided that high drug exposure (ie POS serum through levels &gt;3\u00a0mg\/L) can be achieved and is safe.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To describe our experience with the use of oral HD\u2010POS as treatment strategies for patients infected with pathogens with a POS MIC close to the clinical breakpoint.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients\/Methods<\/jats:title><jats:p>We review evidence supporting the use of HD\u2010POS and describe our experience on safety and efficacy in 16 patients. In addition, we describe the adverse events (AE) observed in 25 patients with POS concentrations at the higher end of the population distribution during treatment with the licensed dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sixteen patients were treated intentionally with HD\u2010POS for voriconazole\u2010resistant invasive aspergillosis (7\/16), mucormycosis (4\/16), salvage therapy for IA (4\/16) and IA at a sanctuary site (spondylodiscitis) in 1. Grade 3\u20104 AEs were observed in 6, and all of them were considered at least possibly related. Grade 3\u20104 AEs were observed in 5 of the 25 patients with spontaneous high POS serum through levels considered at least possibly related using Naranjo scale.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>High\u2010dose posaconazole is a treatment option if strict monitoring for both exposure and for AE is possible.<\/jats:p><\/jats:sec>","DOI":"10.1111\/myc.13028","type":"journal-article","created":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T10:17:14Z","timestamp":1572344234000},"page":"122-130","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["High\u2010dose posaconazole for azole\u2010resistant aspergillosis and other difficult\u2010to\u2010treat mould infections"],"prefix":"10.1111","volume":"63","author":[{"given":"Alexander F. A. 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M.","family":"Br\u00fcggemann","sequence":"additional","affiliation":[{"name":"Center of Expertise in Mycology Radboudumc\/CWZ Nijmegen The Netherlands"},{"name":"Department of Pharmacy Radboud University Medical Centre Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01159-9"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/591531"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30316-X"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw323"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid1710.110226"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2015.08.001"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw326"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa061094"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa061098"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks268"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/1078155217722405"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2010.64"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12281-016-0255-4"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx029"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt508"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1981.154"},{"key":"e_1_2_9_18_1","unstructured":"European Medicines Agency Committee for Medicinal Products for Human Use.Assessment report Noxafil Procedure No. EMEA\/H\/C\/000610\/X\/0028.http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/EPAR_-_Assessment_Report_-_Variation\/human\/000610\/WC500168187.pdf. 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