{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:46:07Z","timestamp":1790934367412,"version":"4.1.0"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":27,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100031288","name":"F2G","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100031288","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Olorofim is an antifungal agent with a novel mechanism of action against Aspergillus spp., rare moulds and dimorphic fungi. Preclinical studies reported unidirectional antagonism between olorofim and mould-active azoles (e.g. azoles other than fluconazole) against Aspergillus fumigatus in which the azole reduces the antifungal effect of olorofim.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To assess the potential clinical impact of this preclinical finding, we compared outcomes of olorofim with and without concomitant azoles from a Phase 2b salvage study in patients with invasive fungal diseases with few or no treatment options.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Analyses are limited by the study size but outcomes were similar for olorofim with and without an azole in combination (whether mould-active or not) at Days 42 (the primary study endpoint) and 84 for both Mycoses Study Group\u2013European Organization for Research and Treatment of Cancer (MSG-EORTC) responses and for all-cause mortality in patients with aspergillosis (77 not receiving an azole, 24 receiving an azole in combination), in patients with coccidioidomycosis (11 not receiving an azole, 30 receiving an azole in combination) and in patients with other fungal infections (50 not receiving an azole, 10 receiving an azole in combination). In addition, the rate of drug-induced liver injury was not increased in patients receiving combination with an azole.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although limited by small numbers of patients for individual fungi, this analysis did not demonstrate a pattern of reduced clinical efficacy or tolerability of olorofim when given in combination with either the mould-active azoles or with fluconazole.<\/jats:p>\n                    <jats:p>Trial registration number. NCT03583164.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag118","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T10:28:35Z","timestamp":1774952915000},"source":"Crossref","is-referenced-by-count":5,"title":["Olorofim in combination with azole antifungals: results from the Phase 2 salvage therapy study"],"prefix":"10.1093","volume":"81","author":[{"given":"Johan","family":"Maertens","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Transplantation, KU Leuven , Leuven ,","place":["Belgium"]},{"name":"Department of Haematology, University Hospitals Leuven , Leuven ,","place":["Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9983-6603","authenticated-orcid":false,"given":"Sharon C A","family":"Chen","sequence":"additional","affiliation":[{"name":"Centre for Infectious Diseases and Microbiology Laboratory Services, Institute for Clinical Pathology and Medical Research, New South Wales Health Pathology , Sydney ,","place":["Australia"]},{"name":"Department of Infectious Diseases, Westmead Hospital, The University of Sydney , Sydney ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"George R","family":"Thompson","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine, University of California Davis Medical Center , Sacramento, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6203-5693","authenticated-orcid":false,"given":"Fariba","family":"Donovan","sequence":"additional","affiliation":[{"name":"Valley Fever Center for Excellence, Division of Infectious Diseases, Department of Medicine, University of Arizona , Tucson, AZ ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Dane","sequence":"additional","affiliation":[{"name":"DaneStat Consulting , Macclesfield ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Birch","sequence":"additional","affiliation":[{"name":"F2G Ltd. , Nether Alderley, Macclesfield ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7294-3054","authenticated-orcid":false,"given":"Corinne","family":"Pinder","sequence":"additional","affiliation":[{"name":"F2G Ltd. , Nether Alderley, Macclesfield ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill","family":"Bennett","sequence":"additional","affiliation":[{"name":"F2G Ltd. , Nether Alderley, Macclesfield ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Ravenna","sequence":"additional","affiliation":[{"name":"F2G Ltd. , Nether Alderley, Macclesfield ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Marin Fernandez","sequence":"additional","affiliation":[{"name":"F2G Ltd. , Nether Alderley, Macclesfield ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoff","family":"Ross","sequence":"additional","affiliation":[{"name":"F2G Ltd. , Nether Alderley, Macclesfield ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Zinzi","sequence":"additional","affiliation":[{"name":"F2G Ltd. , Nether Alderley, Macclesfield ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H","family":"Rex","sequence":"additional","affiliation":[{"name":"F2G Ltd. , Nether Alderley, Macclesfield ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Phase 2b Olorofim Salvage Therapy Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Maria","family":"Aguado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara D","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mickael","family":"Aoun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Bazaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger J","family":"Br\u00fcggemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke H W","family":"Bruns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Methee","family":"Chayakulkeeree","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Cornelissen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver A","family":"Cornely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley","family":"Fitton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus","family":"Fort\u00fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aspasia","family":"Georgala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah P","family":"Hammond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher H","family":"Heath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hoenigl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M","family":"Holland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Royce","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Koehler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Varun","family":"Mehra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Mehta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa H","family":"Miceli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine Orla","family":"Morrissey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Moussa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Hong","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Ostrosky-Zeichner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L","family":"Paterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas F","family":"Patterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Plate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galia","family":"Rahav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riina","family":"Rautemaa-Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Rijnders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Schaenman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shmuel","family":"Shoham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica K","family":"Sikka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica A","family":"Slavin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amparo","family":"Sol\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrej","family":"Spec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank L","family":"Van de Veerdonk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose A","family":"Vazquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul E","family":"Verweij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J","family":"Walsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen R","family":"Walsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,31]]},"reference":[{"key":"2026033106282623700_dkag118-B1","doi-asserted-by":"publisher","first-page":"122","DOI":"10.3390\/jof6030122","article-title":"Review of the novel investigational antifungal olorofim","volume":"6","author":"Wiederhold","year":"2020","journal-title":"J Fungi (Basel)"},{"key":"2026033106282623700_dkag118-B2","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3390\/jof6020047","article-title":"The dynamic influence of olorofim (F901318) on the cell morphology and organization of living cells of Aspergillus fumigatus","volume":"6","author":"du Pr\u00e9","year":"2020","journal-title":"J Fungi (Basel)"},{"key":"2026033106282623700_dkag118-B3","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1016\/S1473-3099(25)00224-5","article-title":"Olorofim for the treatment of invasive fungal diseases in patients with few or no therapeutic options: a single-arm, open-label, phase 2b study","volume":"25","author":"Maertens","year":"2025","journal-title":"Lancet Infect Dis"},{"key":"2026033106282623700_dkag118-B4","doi-asserted-by":"publisher","first-page":"149S","DOI":"10.1592\/phco.21.12.149S.34505","article-title":"Rationale for combination antifungal therapy","volume":"21","author":"Lewis","year":"2001","journal-title":"Pharmacotherapy"},{"key":"2026033106282623700_dkag118-B5","doi-asserted-by":"publisher","first-page":"81","DOI":"10.7326\/M13-2508","article-title":"Combination antifungal therapy for invasive aspergillosis: a randomized trial","volume":"162","author":"Marr","year":"2015","journal-title":"Ann Intern Med"},{"key":"2026033106282623700_dkag118-B6","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1093\/jac\/dkz529","article-title":"Madurella mycetomatis, the main causative agent of eumycetoma, is highly susceptible to olorofim","volume":"75","author":"Lim","year":"2020","journal-title":"J Antimicrob Chemother"},{"key":"2026033106282623700_dkag118-B7","doi-asserted-by":"publisher","first-page":"e0221522","DOI":"10.1128\/mbio.02215-22","article-title":"Antagonism of the azoles to olorofim and cross-resistance are governed by linked transcriptional networks in Aspergillus fumigatus","volume":"13","author":"van Rhijn","year":"2022","journal-title":"mBio"},{"key":"2026033106282623700_dkag118-B8","doi-asserted-by":"publisher","first-page":"3452","DOI":"10.1093\/jac\/dkaf393","article-title":"Antagonistic in vitro interaction between olorofim and voriconazole against Aspergillus fumigatus","volume":"80","author":"Laloum","year":"2025","journal-title":"J Antimicrob Chemother"},{"key":"2026033106282623700_dkag118-B9","doi-asserted-by":"publisher","first-page":"3139","DOI":"10.1093\/jac\/dkaf354","article-title":"In vitro evaluation of olorofim and antifungal combinations against Aspergillus and Candida species","volume":"80","author":"Pinder","year":"2025","journal-title":"J Antimicrob Chemother"},{"key":"2026033106282623700_dkag118-B10","doi-asserted-by":"publisher","first-page":"3150","DOI":"10.1093\/jac\/dkaf355","article-title":"Antagonistic interaction between posaconazole and olorofim in a murine model of invasive pulmonary aspergillosis","volume":"80","author":"Darlow","year":"2025","journal-title":"J Antimicrob Chemother"},{"key":"2026033106282623700_dkag118-B11","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1086\/588660","article-title":"Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer\/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC\/MSG) Consensus Group","volume":"46","author":"De Pauw","year":"2008","journal-title":"Clin Infect Dis"},{"key":"2026033106282623700_dkag118-B12","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1086\/590566","article-title":"Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria","volume":"47","author":"Segal","year":"2008","journal-title":"Clin Infect Dis"},{"key":"2026033106282623700_dkag118-B13","doi-asserted-by":"publisher","first-page":"e01318-18","DOI":"10.1128\/JCM.01318-18","article-title":"Coccidioidomycosis complement fixation titer trends in the age of antifungals","volume":"56","author":"McHardy","year":"2018","journal-title":"J Clin Microbiol"},{"key":"2026033106282623700_dkag118-B14","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.amjmed.2015.10.029","article-title":"Oral azole antifungal medications and risk of acute liver injury, overall and by chronic liver disease status","volume":"129","author":"Lo Re","year":"2016","journal-title":"Am J Med"},{"key":"2026033106282623700_dkag118-B15","doi-asserted-by":"publisher","first-page":"107","DOI":"10.3109\/03602532.2011.645579","article-title":"Role of immune reactions in drug-induced liver injury (DILI)","volume":"44","author":"Ju","year":"2012","journal-title":"Drug Metab Rev"},{"key":"2026033106282623700_dkag118-B16","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1128\/AAC.48.3.693-715.2004","article-title":"Combination antifungal therapy","volume":"48","author":"Johnson","year":"2004","journal-title":"Antimicrob Agents Chemother"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/81\/4\/dkag118\/67688828\/dkag118.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/81\/4\/dkag118\/67688828\/dkag118.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T10:28:36Z","timestamp":1774952916000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/doi\/10.1093\/jac\/dkag118\/8566115"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":16,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,3,4]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkag118","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2026,3,4]]},"article-number":"dkag118"}}