{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:55:08Z","timestamp":1790387708873,"version":"4.1.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Voriconazole, isavuconazole, and amphotericin (AmB) formulations are currently recommended to treat invasive pulmonary aspergillosis (IPA). We aimed to estimate the efficacy of different antifungal drugs in the initial treatment of IPA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We included all available randomized controlled trials (RCTs) evaluating first-line treatments for IPA by searching PubMed, Medline, EMBASE, the Cochrane Library, and the <jats:uri>ClinicalTrials.gov<\/jats:uri> database. We performed a network meta-analysis to compare the relative efficacy of different drugs in treating IPA. The primary outcomes were the overall response and all-cause mortality (ACM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eight studies were identified that compared different drugs including voriconazole, isavuconazole, posaconazole, anidulafungin, liposomal AmB (L-AmB) at standard, high and low doses (3-5\u202fmg\/kg\/d; 10\u202fmg\/kg\/d; 1\u202fmg\/kg\/d), AmB deoxycholate (dAmB) and amphotericin B colloidal dispersion (ABCD). We found that second-generation triazole antifungal drugs containing voriconazole, isavuconazole, and posaconazole exhibited significantly superior overall response to dAmB and ABCD. Voriconazole was ranked as the best drug on network rank analysis. We found no difference in efficacy between triazole antifungals and L-AmB. A combination of voriconazole with anidulafungin, isavuconazole and voriconazole showed significantly better safety than dAmB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The efficacy of second-generation triazole antifungal drugs for the first-line treatment of IPA is comparable with L-AmB and is better than both dAmB and ABCD. Isavuconazole may show better safety than voriconazole and posaconazole. Combination therapy with voriconazole and anidulafungin may serve as an alternative option for IPA patients with limited drug tolerance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Systematic review registration<\/jats:title><jats:p><jats:uri>https:\/\/inplasy.com\/<\/jats:uri>.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2024.1504826","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T15:21:08Z","timestamp":1733152868000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Comparison of antifungal drugs in the treatment of invasive pulmonary aspergillosis: a systematic review and network meta-analysis"],"prefix":"10.3389","volume":"15","author":[{"given":"Jing","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hedong","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijin","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tangfeng","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"3398","DOI":"10.1128\/aac.00054-16","article-title":"Drug-drug interaction associated with Mold-active Triazoles among hospitalized patients","volume":"60","author":"Andes","year":"2016","journal-title":"Antimicrob. 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Infect. Dis."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1086\/515033","article-title":"An EORTC international multicenter randomized trial (EORTC number 19923) comparing two dosages of liposomal amphotericin B for treatment of invasive aspergillosis","volume":"27","author":"Ellis","year":"1998","journal-title":"Clin. Infect. Dis."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1086\/322970","article-title":"Counterpoint: invasive aspergillosis and the environment--rethinking our approach to prevention","volume":"33","author":"Hajjeh","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1007\/s40265-013-0069-4","article-title":"Amphotericin B formulations: a comparative review of efficacy and toxicity","volume":"73","author":"Hamill","year":"2013","journal-title":"Drugs"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1056\/NEJMoa020191","article-title":"Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis","volume":"347","author":"Herbrecht","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1080\/03007995.2018.1502659","article-title":"Systematic review and network meta-analysis of clinical outcomes associated with isavuconazole versus relevant comparators for patients with invasive aspergillosis","volume":"34","author":"Herbrecht","year":"2018","journal-title":"Curr. Med. Res. Opin."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1093\/cid\/ciu911","article-title":"Application of the 2008 definitions for invasive fungal diseases to the trial comparing voriconazole versus amphotericin B for therapy of invasive aspergillosis: a collaborative study of the mycoses study group (MSG 05) and the European Organization for Research and Treatment of Cancer infectious diseases group","volume":"60","author":"Herbrecht","year":"2015","journal-title":"Clin. Infect. 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Fungi"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1046\/j.1365-2141.1998.00944.x","article-title":"Liposomal amphotericin B compared with amphotericin B deoxycholate in the treatment of documented and suspected neutropenia-associated invasive fungal infections","volume":"103","author":"Leenders","year":"1998","journal-title":"Br. J. Haematol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1186\/s12879-024-09477-9","article-title":"Compare the efficacy of antifungal agents as primary therapy for invasive aspergillosis: a network meta-analysis","volume":"24","author":"Liu","year":"2024","journal-title":"BMC Infect. Dis."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"3105","DOI":"10.1002\/sim.1875","article-title":"Combination of direct and indirect evidence in mixed treatment comparisons","volume":"23","author":"Lu","year":"2004","journal-title":"Stat. 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Med."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"27","DOI":"10.2147\/dhps.s6321","article-title":"Clinical safety and tolerability issues in use of triazole derivatives in management of fungal infections","volume":"2","author":"Neofytos","year":"2010","journal-title":"Drug Healthc Patient Saf."},{"key":"ref24","doi-asserted-by":"publisher","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":"ref25","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s11739-016-1583-7","article-title":"Network meta-analysis: an introduction for clinicians","volume":"12","author":"Rouse","year":"2017","journal-title":"Intern. Emerg. 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Drug Dev."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"666","DOI":"10.7326\/m15-2521","article-title":"Uncertainty in treatment rankings: reanalysis of network Meta-analyses of randomized trials","volume":"164","author":"Trinquart","year":"2016","journal-title":"Ann. Intern. Med."},{"key":"ref33","doi-asserted-by":"publisher","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":"ref34","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1086\/588475","article-title":"Clinical practice: combination antifungal therapy for mold infections: much ado about nothing?","volume":"46","author":"Vazquez","year":"2008","journal-title":"Clin. Infect. Dis."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1177\/2047487318767199","article-title":"Ranking of the most effective treatments for cardiovascular disease using SUCRA: is it as sweet as it appears?","volume":"25","author":"Wang","year":"2018","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref36","first-page":"635","article-title":"Amphotericin B colloidal dispersion vs. amphotericin B as therapy for invasive aspergillosis","volume":"24","author":"White","year":"1997","journal-title":"Clin. Infect. Dis."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1086\/514672","article-title":"Randomized, double-blind clinical trial of amphotericin B colloidal dispersion vs. amphotericin B in the empirical treatment of fever and neutropenia","volume":"27","author":"White","year":"1998","journal-title":"Clin. Infect. 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