{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T21:34:09Z","timestamp":1773956049707,"version":"3.50.1"},"reference-count":16,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:00:00Z","timestamp":1760659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>This retrospective case series evaluated off-label voriconazole for distal lateral subungual onychomycosis (DLSO) unresponsive to standard therapy. Twenty-nine culture-confirmed patients who had failed terbinafine (250 mg daily \u00d7 12 weeks) and itraconazole pulses (200 mg twice daily for 1 week\/month \u00d7 3) received voriconazole (200 mg twice on day 1, then 200 mg daily for 3\u20134 months). Assessments occurred at 2, 4, 6\u20139, and 12 months; the primary endpoint was combined clinical cure (\u226590% nail clearance) plus mycological cure (negative KOH and culture) at 12 months. Intention-to-treat included 29 patients; per-protocol included 27 (two did not complete follow-up). In the per-protocol cohort, combined cure was 55.6% (15\/27) and mycological cure 74.1% (20\/27). Complete clinical cure occurred in 66.7% (18\/27); 25.9% (7\/27) improved markedly, 3.7% (1\/27) mildly, and 3.7% (1\/27) showed no improvement. Voriconazole was well tolerated and may be considered for DLSO refractory to terbinafine \u00b1 itraconazole. Antifungal stewardship remains essential.<\/jats:p>","DOI":"10.3390\/pathogens14101049","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:07:22Z","timestamp":1760706442000},"page":"1049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and Safety of Voriconazole for Difficult-to-Treat Distal Lateral Subungual Onychomycosis (DLSO)"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8664-7723","authenticated-orcid":false,"given":"Aditya K.","family":"Gupta","sequence":"first","affiliation":[{"name":"Division of Dermatology, Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mesbah","family":"Talukder","sequence":"additional","affiliation":[{"name":"School of Pharmacy, BRAC University, Dhaka 1212, Bangladesh"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1121-5619","authenticated-orcid":false,"given":"Elizabeth A.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, University of Western Ontario, London, ON N6A 5C1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lee","family":"Magal","sequence":"additional","affiliation":[{"name":"Shemer Clinic, Netanya 4250602, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Avner","family":"Shemer","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Sheba Medical Center, Tel-Hashomer, Ramat-Gan 52621, Israel"},{"name":"Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3390\/jof1010030","article-title":"Onychomycosis: A Review","volume":"1","author":"Piraccini","year":"2015","journal-title":"J. Fungi"},{"key":"ref_2","first-page":"39","article-title":"Impact of onychomycosis on the quality of life of patients","volume":"9","author":"Debbagh","year":"2023","journal-title":"Curr. Med. Mycol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1080\/14787210.2024.2362911","article-title":"Safety and efficacy of new generation azole antifungals in the management of recalcitrant superficial fungal infections and onychomycosis","volume":"22","author":"Gupta","year":"2024","journal-title":"Expert Rev. Anti Infect. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Christenson, J.K., Peterson, G.M., Naunton, M., Bushell, M., Kosari, S., Baby, K.E., and Thomas, J. (2018). Challenges and Opportunities in the Management of Onychomycosis. J. Fungi, 4.","DOI":"10.3390\/jof4030087"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1592\/phco.30.8.842","article-title":"Management of drug and food interactions with azole antifungal agents in transplant recipients","volume":"30","year":"2010","journal-title":"Pharmacotherapy"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.jaad.2012.10.013","article-title":"Efinaconazole 10% solution in the treatment of toenail onychomycosis: Two phase III multicenter, randomized, double-blind studies","volume":"68","author":"Elewski","year":"2013","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_7","first-page":"734","article-title":"Topical antifungals for treatment of onychomycosis","volume":"94","author":"Krasaeath","year":"2016","journal-title":"Am. Fam. Physician"},{"key":"ref_8","first-page":"6185","article-title":"Spotlight on tavaborole for the treatment of onychomycosis","volume":"9","author":"Jinna","year":"2015","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Mahmood, H.R., Shams-Ghahfarokhi, M., and Razzaghi-Abyaneh, M. (2025). Computational analysis of missense mutations in squalene epoxidase associated with terbinafine resistance in clinically reported dermatophytes. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-03300-4"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e13768","DOI":"10.1111\/myc.13768","article-title":"Potential emergence of terbinafine resistance by squalene epoxidase gene mutations: An 18-month cohort study of onychomycosis patients in the United States","volume":"67","author":"Gupta","year":"2024","journal-title":"Mycoses"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1358\/dot.2001.37.2.614849","article-title":"Voriconazole: A second-generation triazole","volume":"37","author":"Chandrasekar","year":"2001","journal-title":"Drugs Today"},{"key":"ref_12","unstructured":"(2025, August 11). Highlights of Prescribing Information, VFEND\u00ae (Voriconazole), Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/021266s057,021267s067,021630s047lbl.pdf."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e14014","DOI":"10.1111\/dth.14014","article-title":"Successful treatment of resistant onychomycosis with voriconazole in a liver transplant patient","volume":"33","author":"Nofal","year":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1684\/ejd.2011.1616","article-title":"Successful eradication of Scytalidium dimidiatum-induced ungual and cutaneous infection with voriconazole","volume":"22","author":"Spriet","year":"2012","journal-title":"Eur. J. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1007\/s40257-021-00660-1","article-title":"Efinaconazole in Onychomycosis","volume":"23","author":"Gupta","year":"2022","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/s40266-021-00917-8","article-title":"Onychomycosis in Older Adults: Prevalence, Diagnosis, and Management","volume":"39","author":"Gupta","year":"2022","journal-title":"Drugs Aging"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/10\/1049\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:44:10Z","timestamp":1760708650000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/10\/1049"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,17]]},"references-count":16,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["pathogens14101049"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14101049","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,17]]}}}