{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:04:05Z","timestamp":1792785845432,"version":"4.5.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T00:00:00Z","timestamp":1715817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"AVIR Pharma Inc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,19]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Primary antifungal prophylaxis with mold-active azoles is used to prevent invasive fungal infections in patients with high-risk hematological disorders; however, breakthrough infections occur, and the reasons for treatment failure are still not fully understood. To help inform clinical decisions, we sought to define microbiological, clinical, and pharmacological characteristics of proven and probable breakthrough invasive fungal infections (bIFIs) in patients with high-risk hematological disorders receiving voriconazole or posaconazole prophylaxis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search strategy was last conducted on 19 April 2023.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We assessed 5293 studies for eligibility, and 300 were selected for data extraction. These studies described 1076 cases of bIFIs occurring under voriconazole (42.5%) or posaconazole (57.5%). The most commonly found pathogens were Aspergillus (40%), Mucorales (20%), Candida (18%), and Fusarium (9%) species. Mucorales were more frequent among voriconazole-emerging cases, whereas Aspergillus and Fusarium were more prevalent among posaconazole-emerging cases. Definitive, putative, or probable antifungal resistance was found in 31% of cases. Therapeutic drug monitoring showed subtherapeutic azole concentration in 32 of 90 (36%) cases. Infection-related mortality was reported in 117 cases and reached 35%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In our systemic review, the most common bIFIs were aspergillosis, mucormycosis, candidiasis, and fusariosis. Antifungal resistance explains only a minority of cases. Subtherapeutic prophylaxis was frequent but rarely reported. Prospective studies are needed to better understand these infections and to establish optimal management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciae203","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T20:07:34Z","timestamp":1713298054000},"page":"151-160","source":"Crossref","is-referenced-by-count":74,"title":["Breakthrough Invasive Fungal Infections in Patients With High-Risk Hematological Disorders Receiving Voriconazole and Posaconazole Prophylaxis: A Systematic Review"],"prefix":"10.1093","volume":"79","author":[{"given":"Catherine-Audrey","family":"Boutin","sequence":"first","affiliation":[{"name":"Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada"},{"name":"Division of Infectious Diseases, Department of Medicine, Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Durocher","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Beauchemin","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019H\u00f4pital Maisonneuve-Rosemont, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Ziegler","sequence":"additional","affiliation":[{"name":"Direction de l\u2019enseignement et de l\u2019Acad\u00e9mie, Biblioth\u00e8que, Centre hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire Nour","family":"Abou Chakra","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019H\u00f4pital Maisonneuve-Rosemont, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2486-5813","authenticated-orcid":false,"given":"Simon Fr\u00e9d\u00e9ric","family":"Dufresne","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montreal, Quebec, Canada"},{"name":"Centre de Recherche de l\u2019H\u00f4pital Maisonneuve-Rosemont, Montreal, Quebec, Canada"},{"name":"Division of Infectious Diseases and Clinical Microbiology, Department of Medicine, H\u00f4pital Maisonneuve-Rosemont, Centre Int\u00e9gr\u00e9 Universitaire de Sant\u00e9 et de Services Sociaux de l\u2019Est-de-l\u2019\u00cele-de-Montr\u00e9al , Montr\u00e9al, Qu\u00e9bec , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,16]]},"reference":[{"key":"2024071918115715000_ciae203-B1","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1086\/651263","article-title":"Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001\u20132006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) database","volume":"50","author":"Kontoyiannis","year":"2010","journal-title":"Clin Infect Dis"},{"key":"2024071918115715000_ciae203-B2","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.diagmicrobio.2012.06.012","article-title":"The PATH (Prospective Antifungal Therapy) Alliance registry and invasive fungal infections: update 2012","volume":"73","author":"Azie","year":"2012","journal-title":"Diagn Microbiol Infect Dis"},{"key":"2024071918115715000_ciae203-B3","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/ciw326","article-title":"Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America","volume":"63","author":"Patterson","year":"2016","journal-title":"Clin Infect Dis"},{"key":"2024071918115715000_ciae203-B4","author":"Baden"},{"key":"2024071918115715000_ciae203-B5","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.cmi.2018.01.002","article-title":"Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline","volume":"24","author":"Ullmann","year":"2018","journal-title":"Clin Microbiol Infect"},{"key":"2024071918115715000_ciae203-B6","doi-asserted-by":"crossref","first-page":"ofab502","DOI":"10.1093\/ofid\/ofab502","article-title":"SUBA-itraconazole for primary antifungal prophylaxis after allogeneic hematopoietic cell transplantation","volume":"8","author":"Lindsay","year":"2021","journal-title":"Open Forum Infect Dis"},{"key":"2024071918115715000_ciae203-B7","doi-asserted-by":"crossref","first-page":"ofad424","DOI":"10.1093\/ofid\/ofad424","article-title":"Real-world use of mold-active triazole prophylaxis in the prevention of invasive fungal diseases: results from a subgroup analysis of a multicenter national registry","volume":"10","author":"Nguyen","year":"2023","journal-title":"Open Forum Infect Dis"},{"key":"2024071918115715000_ciae203-B8","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1111\/myc.12960","article-title":"Defining breakthrough invasive fungal infection\u2014position paper of the Mycoses Study Group Education and Research Consortium and the European Confederation of Medical Mycology","volume":"62","author":"Cornely","year":"2019","journal-title":"Mycoses"},{"key":"2024071918115715000_ciae203-B9","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1111\/myc.13148","article-title":"Breakthrough invasive fungal infections: who is at risk?","volume":"63","author":"Jenks","year":"2020","journal-title":"Mycoses"},{"key":"2024071918115715000_ciae203-B10","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1111\/myc.12213","article-title":"Our 2014 approach to breakthrough invasive fungal infections","volume":"57","author":"Maschmeyer","year":"2014","journal-title":"Mycoses"},{"key":"2024071918115715000_ciae203-B11","doi-asserted-by":"crossref","first-page":"2634","DOI":"10.1093\/jac\/dkw199","article-title":"A cohort study on breakthrough invasive fungal infections in high-risk patients receiving antifungal prophylaxis","volume":"71","author":"Biehl","year":"2016","journal-title":"J Antimicrob Chemother"},{"key":"2024071918115715000_ciae203-B12","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.1093\/cid\/cix130","article-title":"Changing epidemiology of invasive mold infections in patients receiving azole prophylaxis","volume":"64","author":"Lamoth","year":"2017","journal-title":"Clin Infect Dis"},{"key":"2024071918115715000_ciae203-B13","doi-asserted-by":"crossref","first-page":"S127","DOI":"10.1093\/mmy\/myy091","article-title":"Breakthrough invasive fungal diseases in acute myeloid leukemia patients receiving mould active triazole primary prophylaxis after intensive chemotherapy: an Italian consensus agreement on definitions and management","volume":"57","author":"Girmenia","year":"2019","journal-title":"Med Mycol"},{"key":"2024071918115715000_ciae203-B14","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"2024071918115715000_ciae203-B15","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1093\/cid\/ciz1008","article-title":"Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium","volume":"71","author":"Donnelly","year":"2020","journal-title":"Clin Infect Dis"},{"key":"2024071918115715000_ciae203-B16","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1002\/phar.2850","article-title":"Utility of triazole antifungal therapeutic drug monitoring: insights from the Society of Infectious Diseases Pharmacists: endorsed by the Mycoses Study Group Education and Research Consortium","volume":"43","author":"McCreary","year":"2023","journal-title":"Pharmacotherapy"},{"key":"2024071918115715000_ciae203-B17","doi-asserted-by":"crossref","first-page":"e375","DOI":"10.1016\/S1473-3099(21)00203-6","article-title":"Global guideline for the diagnosis and management of rare yeast infections: an initiative of the ECMM in cooperation with ISHAM and ASM","volume":"21","author":"Chen","year":"2021","journal-title":"Lancet Infect Dis"},{"key":"2024071918115715000_ciae203-B18","first-page":"1068","article-title":"The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study","volume":"91","author":"Pagano","year":"2006","journal-title":"Haematologica"},{"key":"2024071918115715000_ciae203-B19","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1056\/NEJM200402263500923","article-title":"Breakthrough zygomycosis after voriconazole treatment in recipients of hematopoietic stem-cell transplants","volume":"350","author":"Marty","year":"2004","journal-title":"N Engl J Med"},{"key":"2024071918115715000_ciae203-B20","doi-asserted-by":"crossref","first-page":"592","DOI":"10.3390\/jof9050592","article-title":"Clinical features and treatment progress of invasive mucormycosis in patients with hematological malignancies","volume":"9","author":"Yang","year":"2023","journal-title":"J Fungi (Basel)"},{"key":"2024071918115715000_ciae203-B21","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.cmi.2020.12.035","article-title":"Has the mortality from pulmonary mucormycosis changed over time? A systematic review and meta-analysis","volume":"27","author":"Muthu","year":"2021","journal-title":"Clin Microbiol Infect"},{"key":"2024071918115715000_ciae203-B22","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.jinf.2023.05.005","article-title":"Breakthrough invasive fungal infection among patients with haematologic malignancies: a national, prospective, and multicentre study","volume":"87","author":"Puerta-Alcalde","year":"2023","journal-title":"J Infect"},{"key":"2024071918115715000_ciae203-B23","doi-asserted-by":"crossref","first-page":"217","DOI":"10.3390\/jof7030217","article-title":"Breakthrough mucormycosis developing on mucorales-active antifungals portrays a poor prognosis in patients with hematologic cancer","volume":"7","author":"Axell-House","year":"2021","journal-title":"J Fungi (Basel)"},{"key":"2024071918115715000_ciae203-B24","doi-asserted-by":"crossref","first-page":"e405","DOI":"10.1016\/S1473-3099(19)30312-3","article-title":"Global guideline for the diagnosis and management of mucormycosis: an initiative of the European Confederation of Medical Mycology in cooperation with the Mycoses Study Group Education and Research Consortium","volume":"19","author":"Cornely","year":"2019","journal-title":"Lancet Infect Dis"},{"key":"2024071918115715000_ciae203-B25","doi-asserted-by":"crossref","first-page":"e470","DOI":"10.1016\/S2666-5247(23)00067-8","article-title":"Worldwide emergence of fluconazole-resistant Candida parapsilosis: current framework and future research roadmap","volume":"4","author":"Daneshnia","year":"2023","journal-title":"Lancet Microbe"},{"key":"2024071918115715000_ciae203-B26","doi-asserted-by":"crossref","first-page":"798","DOI":"10.3390\/jof9080798","article-title":"Candida parapsilosis sensu stricto antifungal resistance mechanisms and associated epidemiology","volume":"9","author":"Franconi","year":"2023","journal-title":"J Fungi (Basel)"},{"key":"2024071918115715000_ciae203-B27","doi-asserted-by":"crossref","first-page":"e02615-20","DOI":"10.1128\/AAC.02615-20","article-title":"Azole susceptibility profiles of more than 9,000 clinical yeast isolates belonging to 40 common and rare species","volume":"65","author":"Desnos-Ollivier","year":"2021","journal-title":"Antimicrob Agents Chemother"},{"key":"2024071918115715000_ciae203-B28","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1111\/j.1567-1364.2009.00508.x","article-title":"Dynamics of in vitro acquisition of resistance by Candida parapsilosis to different azoles","volume":"9","author":"Pinto e Silva","year":"2009","journal-title":"FEMS Yeast Res"},{"key":"2024071918115715000_ciae203-B29"},{"key":"2024071918115715000_ciae203-B30","doi-asserted-by":"crossref","first-page":"922","DOI":"10.3390\/pathogens9110922","article-title":"Invasive Saprochaete infections: an emerging threat to immunocompromised patients","volume":"9","author":"El Zein","year":"2020","journal-title":"Pathogens"},{"key":"2024071918115715000_ciae203-B31","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.cmi.2018.07.011","article-title":"The epidemiology and clinical manifestations of mucormycosis: a systematic review and meta-analysis of case reports","volume":"25","author":"Jeong","year":"2019","journal-title":"Clin Microbiol Infect"},{"key":"2024071918115715000_ciae203-B32","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1086\/432579","article-title":"Epidemiology and outcome of zygomycosis: a review of 929 reported cases","volume":"41","author":"Roden","year":"2005","journal-title":"Clin Infect Dis"},{"key":"2024071918115715000_ciae203-B33","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofad500.2320","article-title":"Breakthrough fungal infection after isavuconazole primary prophylaxis in patients with hematologic malignancy and hematopoietic stem cell transplant: systematic review","volume":"10","author":"Ishida","year":"2023","journal-title":"Open Forum Infect Dis"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciae203\/57673010\/ciae203.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/79\/1\/151\/58599968\/ciae203.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/79\/1\/151\/58599968\/ciae203.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T14:13:13Z","timestamp":1721398393000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/79\/1\/151\/7673806"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,16]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,5,16]]},"published-print":{"date-parts":[[2024,7,19]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciae203","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,7,15]]},"published":{"date-parts":[[2024,5,16]]}}}