{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:43:32Z","timestamp":1792122212530,"version":"4.4.0"},"reference-count":123,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Infectious Disease Reports"],"abstract":"<jats:p>Invasive fungal infections (IFIs) represent a growing global health threat, particularly for immunocompromised populations, with mortality exceeding 1.5 million deaths annually. Despite their clinical and economic burden\u2014costing billions in healthcare expenditures\u2014fungal infections remain underprioritized in public health agendas. This review examines the current landscape of antifungal therapy, focusing on advances, challenges, and future directions. Key drug classes (polyenes, azoles, echinocandins, and novel agents) are analyzed for their mechanisms of action, pharmacokinetics, and clinical applications, alongside emerging resistance patterns in pathogens like Candida auris and azole-resistant Aspergillus fumigatus. The rise of resistance, driven by agricultural fungicide use and nosocomial transmission, underscores the need for innovative antifungals, rapid diagnostics, and stewardship programs. Promising developments include next-generation echinocandins (e.g., rezafungin), triterpenoids (ibrexafungerp), and orotomides (olorofim), which target resistant strains and offer improved safety profiles. The review also highlights the critical role of \u201cOne Health\u201d strategies to mitigate environmental and clinical resistance. Future success hinges on multidisciplinary collaboration, enhanced surveillance, and accelerated drug development to address unmet needs in antifungal therapy.<\/jats:p>","DOI":"10.3390\/idr17040091","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T10:07:38Z","timestamp":1754561258000},"page":"91","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Antifungal Agents in the 21st Century: Advances, Challenges, and Future Perspectives"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9485-3877","authenticated-orcid":false,"given":"Francesco","family":"Branda","sequence":"first","affiliation":[{"name":"Unit of Medical Statistics and Molecular Epidemiology, Universit\u00e0 Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2585-7567","authenticated-orcid":false,"given":"Nicola","family":"Petrosillo","sequence":"additional","affiliation":[{"name":"Infection Prevention & Control\/Infectious Disease Service, Fondazione Policlinico Universitario Campus Bio-Medico, 00127 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5921-3180","authenticated-orcid":false,"given":"Giancarlo","family":"Ceccarelli","sequence":"additional","affiliation":[{"name":"Department of Public Health and Infectious Diseases, University of Rome Sapienza, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5849-7326","authenticated-orcid":false,"given":"Marta","family":"Giovanetti","sequence":"additional","affiliation":[{"name":"Department of Science and Technologies for Sustainable Development and One Health, Universit\u00e0 Campus Bio-Medico di Roma, 00128 Rome, Italy"},{"name":"Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8265-5400","authenticated-orcid":false,"given":"Andrea","family":"De Vito","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6099-2273","authenticated-orcid":false,"given":"Giordano","family":"Madeddu","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, Department of Medicine, Surgery and Pharmacy, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3501-714X","authenticated-orcid":false,"given":"Fabio","family":"Scarpa","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3866-9239","authenticated-orcid":false,"given":"Massimo","family":"Ciccozzi","sequence":"additional","affiliation":[{"name":"Unit of Medical Statistics and Molecular Epidemiology, Universit\u00e0 Campus Bio-Medico di Roma, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Bills, G.F., and An, Z. 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