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While echinocandins and azoles remain the cornerstone of antifungal therapy, their use may be limited by increasing reports of resistance, tolerance, drug-drug interactions, and hepatotoxicity. Liposomal amphotericin B (L-AmB), a broad-spectrum antifungal agent with a more favorable safety profile than conventional amphotericin formulations, may offer a valuable alternative in selected high-risk scenarios. Despite its established role in treating infections such as cryptococcosis, mucormycosis, and leishmaniasis, the potential of L-AmB in other settings remains underutilized and underexplored. We discuss here the hypothetical utility of L-AmB in clinical situations where standard antifungal agents may be inadequate or contraindicated. These include candidemia due to resistant or tolerant strains, biofilm-related infections, infections in patients with hepatic vulnerability, and antifungal prophylaxis or treatment in hematologic patients at high risk for invasive fungal disease. In these contexts, L-AmB\u2019s fungicidal activity, lack of CYP450-mediated interactions, and reduced nephrotoxicity, compared to deoxycholate formulations, may be advantageous. Although definitive clinical evidence is limited, the insights offered here aim to stimulate reflection and support future research. Clinical judgment, guided by expert experience, may justify the selective use of L-AmB in challenging cases where therapeutic alternatives are restricted or risky.\n                  <\/jats:p>","DOI":"10.1128\/cmr.00228-25","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T13:00:15Z","timestamp":1773406815000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Current opinion on the potential role of liposomal amphotericin B in underexplored clinical scenarios"],"prefix":"10.1128","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8433-0394","authenticated-orcid":false,"given":"Jacopo","family":"Angelini","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Institute, University Hospital Friuli Centrale ASUFC","place":["Udine, Italy"]},{"id":[{"id":"https:\/\/ror.org\/05ht0mh31","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine (DMED), University of Udine","place":["Udine, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9326-7659","authenticated-orcid":true,"given":"Sara","family":"Ferin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05ht0mh31","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine (DMED), University of Udine","place":["Udine, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3160-0171","authenticated-orcid":false,"given":"Luca","family":"Martini","sequence":"additional","affiliation":[{"name":"Infectious Diseases Clinic, Azienda Sanitaria Universitaria Friuli Centrale","place":["Udine, Italy."]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Flammini","sequence":"additional","affiliation":[{"name":"Infectious Diseases Clinic, Azienda Sanitaria Universitaria Friuli Centrale","place":["Udine, Italy."]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9625-6024","authenticated-orcid":false,"given":"Carlo","family":"Tascini","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05ht0mh31","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine (DMED), University of Udine","place":["Udine, Italy"]},{"name":"Infectious Diseases Clinic, Azienda Sanitaria Universitaria Friuli Centrale","place":["Udine, Italy."]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2475-8732","authenticated-orcid":false,"given":"Simone","family":"Giuliano","sequence":"additional","affiliation":[{"name":"Infectious Diseases Clinic, Azienda Sanitaria Universitaria Friuli Centrale","place":["Udine, Italy."]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(23)00692-8"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/599039"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/20.6.1526"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2023.08.001"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-5247(24)00039-9"},{"key":"e_1_3_3_7_2","unstructured":"European Centre for Disease Prevention and Control. 2025. 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