{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:45:01Z","timestamp":1792100701724,"version":"4.4.0"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1506114N, G057721N, 1SF2224N"],"award-info":[{"award-number":["1506114N, G057721N, 1SF2224N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"Background<\/jats:title>Solid organ transplant recipients on immunosuppressants such as tacrolimus are at increased risk of developing pulmonary aspergillosis, a severe to deadly complication with limited treatment options, especially against azole-resistant strains. This study investigates the antifungal interaction between posaconazole and tacrolimus, prompted by a case where a liver transplant recipient on tacrolimus experienced unexpected eradication of chronic Aspergillus fumigatus<\/jats:italic> colonization following posaconazole prophylaxis.<\/jats:p><\/jats:sec>Methods<\/jats:title>We compared the combined antifungal activity of posaconazole and tacrolimus against azole-sensitive and resistant A. fumigatus in vitro<\/jats:italic> against planktonic isolates and biofilm formation and in vivo<\/jats:italic> in Galleria mellonella<\/jats:italic> larvae, to evaluate the potential benefit over posaconazole monotherapy.<\/jats:p><\/jats:sec>Results<\/jats:title>The posaconazole-tacrolimus combination demonstrated a 4-fold increase in efficacy against azole-resistant isolates and a 30-fold increase against an azole-sensitive strain, in contrast to voriconazole. Moreover, this combination enhanced antifungal activity by 4- to 15-fold against biofilm formation of azole-sensitive strains, though no synergy was observed against azole-resistant biofilms. In vivo<\/jats:italic> studies in Galleria mellonella<\/jats:italic> confirmed a 2- to 7-fold decrease in fungal burden of both azole-sensitive and azole-resistant strains when combining posaconazole with tacrolimus, relative to posaconazole alone.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>In vitro<\/jats:italic> and in vivo<\/jats:italic> findings confirm that posaconazole may offer therapeutic benefits for treating A. fumigatus<\/jats:italic> infections in patients receiving tacrolimus. These results warrant further confirmation in mice and exploration of their clinical implications.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1550457","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T05:26:16Z","timestamp":1745558776000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Combinations of posaconazole and tacrolimus are effective against infections with azole-resistant Aspergillus fumigatus"],"prefix":"10.3389","volume":"15","author":[{"given":"Eliane","family":"Vanhoffelen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tine","family":"Van Win","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Van Braeckel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agustin","family":"Res\u00e9ndiz-Sharpe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno P. 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