{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:22:32Z","timestamp":1760059352437,"version":"build-2065373602"},"reference-count":18,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T00:00:00Z","timestamp":1749254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institute of Medical Sciences of the Opole University","award":["P-2023-010"],"award-info":[{"award-number":["P-2023-010"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Previous studies have demonstrated that Candida spp. isolates exposed in vitro to the folic acid antagonist methotrexate may develop multidrug cross-resistance to azole antifungals. The aim of this study was to determine whether systemic therapy with antineoplastic antifolates\u2014pemetrexed or methotrexate\u2014constitutes a risk factor for colonization or infection with fluconazole-resistant yeasts. The study group comprised 44 cancer patients who received high-dose systemic antifolate therapy, while the control group consisted of 48 patients without prior exposure to either methotrexate or pemetrexed. Oral swabs and relevant clinical data were collected from all participants. In total, 109 fungal strains representing 13 species were isolated, identified, and subsequently tested for fluconazole susceptibility. Fluconazole-resistant isolates were identified in 4 out of 44 (9.1%) antifolate-treated patients and in 3 out of 48 (6.3%) control patients. Our findings suggest that, although this phenomenon occurs in vitro, systemic antineoplastic antifolate therapy does not induce azole resistance among endogenous yeast species in vivo.<\/jats:p>","DOI":"10.3390\/pathogens14060574","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T06:46:01Z","timestamp":1749451561000},"page":"574","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Systemic Antifolate Chemotherapy Does Not Select for Fluconazole-Resistant Candida: A Multicenter Clinical Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9921-0811","authenticated-orcid":false,"given":"Dawid","family":"\u017byrek","sequence":"first","affiliation":[{"name":"Department of Histology, Institute of Medical Sciences, University of Opole, 45-052 Opole, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4001-4189","authenticated-orcid":false,"given":"Joanna","family":"Nowicka","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9881-8294","authenticated-orcid":false,"given":"Magdalena","family":"Paj\u0105czkowska","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2603-4634","authenticated-orcid":false,"given":"Mariola","family":"Pa\u015bciak","sequence":"additional","affiliation":[{"name":"Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Machnik","sequence":"additional","affiliation":[{"name":"Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Werner","sequence":"additional","affiliation":[{"name":"Clinical Department of Pulmonology, Institute of Medical Sciences, University of Opole, 45-052 Opole, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zygmunt","family":"Konieczny","sequence":"additional","affiliation":[{"name":"Department of Pulmonology with a Chemotherapy Subunit, Hospital in Glucholazy, Lompy 3, 48-340 Glucholazy, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"J\u0119drzejczak","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Lower Silesian Center of Oncology, Pulmonology and Hematology, Grabiszy\u0144ska 105, 53-439 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominika","family":"Ra\u017aniewska","sequence":"additional","affiliation":[{"name":"Department of Oncology, Institute of Medical Sciences, University of Opole, 45-040 Opole, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"Fija\u0142kowska","sequence":"additional","affiliation":[{"name":"Clinical Department of Pulmonology, Institute of Medical Sciences, University of Opole, 45-052 Opole, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Micha\u0142","family":"Pi\u0105tek","sequence":"additional","affiliation":[{"name":"Department of Oncology, Institute of Medical Sciences, University of Opole, 45-040 Opole, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Radecka","sequence":"additional","affiliation":[{"name":"Department of Oncology, Institute of Medical Sciences, University of Opole, 45-040 Opole, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kinga","family":"\u017byrek","sequence":"additional","affiliation":[{"name":"Division of Physiotherapy, Faculty of Health Sciences, Wroclaw Medical University, 50-367 Wroclaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3240-1939","authenticated-orcid":false,"given":"El\u017cbieta","family":"Wo\u017aniak-Grygiel","sequence":"additional","affiliation":[{"name":"Department of Histology, Institute of Medical Sciences, University of Opole, 45-052 Opole, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5800-7817","authenticated-orcid":false,"given":"Iwona","family":"Dzie\u0144dziora-Urbi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Histology, Institute of Medical Sciences, University of Opole, 45-052 Opole, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ko\u017ami\u0144ski, P., Halik, P.K., Chesori, R., and Gniazdowska, E. 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