{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T14:11:25Z","timestamp":1776521485008,"version":"3.51.2"},"reference-count":63,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Sertraline, a selective serotonin reuptake inhibitor (SSRI), has emerged as a candidate for therapeutic repurposing due to its reported antifungal activity. We systematically reviewed in vitro, in vivo, and clinical evidence up to July 2025 (PubMed, Scopus, Web of Science). As a result, 322 records were screened and 63 studies were found to meet the inclusion criteria (PRISMA 2020). We close a critical gap by consolidating relevant evidence on Candida auris, including preclinical in vivo models, which have been under-represented in previous summaries. Outcomes included minimum inhibitory and fungicidal concentrations (MIC\/MFC), biofilm inhibition, fungal burden, survival, and pharmacokinetic\/pharmacodynamic parameters. Preclinical data indicate its activity against clinically relevant fungi\u2014particularly Cryptococcus neoformans and Candida spp., including C. auris\u2014as well as consistent anti-biofilm effects and synergy with amphotericin B, fluconazole, micafungin, or voriconazole. Mechanistic evidence implicates mitochondrial dysfunction, membrane perturbation, impaired protein synthesis, and calcium homeostasis disruption. However, its potential for clinical translation remains uncertain: in cryptococcal meningitis, small phase II studies suggested improved early fungicidal activity, whereas a phase III randomized trial did not demonstrate a benefit regarding survival. Pharmacokinetic constraints at conventional doses, the absence of an intravenous formulation, and safety considerations at higher doses further limit its immediate applicability. Overall, the available evidence supports sertraline as a promising adjuvant candidate, rather than a stand-alone antifungal. Future research should define PK\/PD targets, optimize doses and formulations, and evaluate rational combinations through rigorously designed trials, particularly for multidrug-resistant and biofilm-associated infections.<\/jats:p>","DOI":"10.3390\/microorganisms13102334","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T12:32:47Z","timestamp":1760099567000},"page":"2334","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Therapeutic Repurposing of Sertraline: Evidence for Its Antifungal Activity from In Vitro, In Vivo, and Clinical Studies"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9939-0771","authenticated-orcid":false,"given":"Carmen","family":"Rodr\u00edguez-Cerdeira","sequence":"first","affiliation":[{"name":"Department of University Program for Seniors, University of Vigo, E.E. Industrial R\u00faa Torrecedeira 86, 36201 Vigo, Spain"},{"name":"Fundaci\u00f3n Vithas, Vithas Foundation, 28043 Madrid, Spain"},{"name":"Dermatology Department, Hospital CMQ-Concheiro, Manuel Olivi\u00e9 11, 36203 Vigo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Westley","family":"Eckhardt","sequence":"additional","affiliation":[{"name":"Department of University Program for Seniors, University of Vigo, E.E. Industrial R\u00faa Torrecedeira 86, 36201 Vigo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.2165\/00003088-200241150-00002","article-title":"Clinical pharmacokinetics of sertraline","volume":"41","author":"DeVane","year":"2002","journal-title":"Clin. 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