{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T14:02:30Z","timestamp":1792245750633,"version":"4.4.0"},"reference-count":15,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T00:00:00Z","timestamp":1733356800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,12,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>Invasive aspergillosis (IA) and mucormycosis (IM) cause significant morbidity and mortality in immunocompromised and\/or hospitalized patients. Isavuconazonium sulfate, a prodrug of the antifungal triazole isavuconazole, has been approved for treatment of IA and IM in adults; and was recently approved in children. This study describes the outcomes, safety, and pharmacokinetics of isavuconazole for the treatment of proven, probable, or possible IA or IM in children. In this phase 2, open-label, non-comparative study, patients aged 1 to &lt;18 years with at least possible invasive mold disease were enrolled across 10 centers in the US, Spain, and Belgium from 2019 to 2022. Patients received 10 mg\/kg isavuconazonium sulfate daily (maximum 372 mg; equivalent to 5.4 mg\/kg or 200 mg isavuconazole) for up to 84 (IA) or 180 days (IM). Outcomes included rates of all-cause case fatality, overall response, treatment-emergent adverse events (TEAEs), and pharmacokinetics. Of 31 patients enrolled, 61.3% were 1\u2013&lt;12 years old; 58.1% had underlying hematologic malignancies. The successful overall response rate at the end of treatment was 54.8%. Day 42 all-cause case fatality was 6.5%; 93.5% experienced TEAEs, and two patients discontinued treatment due to drug-related TEAEs. Dosing at 10 mg\/kg (maximum dose: 372 mg) met the pre-defined exposure threshold of above the 25th percentile for the area under the concentration-time curve (\u226560 mg\u00b7h\/L). Simulated doses of 15 mg\/kg improved drug exposures in patients aged 1\u2013&lt;3 years. Isavuconazole was well tolerated in children, with exposure consistent with adult studies. Successful response was documented in 54.8% of patients.<\/jats:p>\n            <jats:sec>\n              <jats:title>CLINICAL TRIALS<\/jats:title>\n              <jats:p>\n                This study is registered at\n                <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/\" xlink:type=\"simple\">ClinicalTrials.gov<\/jats:ext-link>\n                as\n                <jats:related-object xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" document-id=\"NCT03816176\" source-id=\"10.18810\/clinical-trials-gov\" source-id-type=\"registry-name\" source-type=\"clinical-trials-registry\" xlink:href=\"https:\/\/clinicaltrials.gov\/show\/NCT03816176\">NCT03816176<\/jats:related-object>\n                .\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/aac.00484-24","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T14:02:08Z","timestamp":1731592928000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Safety, outcomes, and pharmacokinetics of isavuconazole as a treatment for invasive fungal diseases in pediatric patients: a non-comparative phase 2 trial"],"prefix":"10.1128","volume":"68","author":[{"given":"Heidi","family":"Segers","sequence":"first","affiliation":[{"name":"Department of Pediatric Hemato-Oncology, University Hospital Leuven","place":["Leuven, Belgium"]},{"name":"Department of Oncology \u2013 Pediatric Oncology, KU Leuven","place":["Leuven, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime G.","family":"Deville","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7690-0695","authenticated-orcid":false,"given":"William J.","family":"Muller","sequence":"additional","affiliation":[{"name":"Ann & Robert H. Lurie Children\u2019s Hospital of Chicago","place":["Chicago, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Manzanares","sequence":"additional","affiliation":[{"name":"Pediatric Infectious Disease Unit, Hospital 12 de Octubre","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7394-3606","authenticated-orcid":false,"given":"Amit","family":"Desai","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc.","place":["Northbrook, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1675-8276","authenticated-orcid":false,"given":"Michael","family":"Neely","sequence":"additional","affiliation":[{"name":"University of Southern California Children's Hospital Los Angeles","place":["Los Angeles, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Bordon","sequence":"additional","affiliation":[{"name":"Ghent University Hospital","place":["Ghent, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Hanisch","sequence":"additional","affiliation":[{"name":"Children's National Hospital","place":["Washington, DC, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Lassaletta","sequence":"additional","affiliation":[{"name":"Hospital Infantil Universitario Ni\u00f1o Jes\u00fas","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian T.","family":"Fisher","sequence":"additional","affiliation":[{"name":"Children's Hospital of Philadelphia and The Perelman School of Medicine at The University of Pennsylvania","place":["Philadelphia, 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