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In the past, flucytosine (5-FC) has been used to treat CBM, but development of resistance is common. Carmofur belongs to the same class as 5-FC and has in vitro inhibitory activity against the main agents of CBM and PHM. The aim of this study was to compare the action of these two pyrimidine analog drugs against CBM and PHM agents. The minimum inhibitory concentration (MIC) and the selectivity index based on cytotoxicity tests of these two drugs against some agents of these mycoses were determined, with carmofur presenting a higher selectivity index than 5-FC. Carmofur demonstrated here synergistic interactions with itraconazole and amphotericin B against Exophiala heteromorpha, Fonsecaea pedrosoi, Fonsecaea monophora, and Fonsecaea nubica strains. Additionally, carmofur plus itraconazole demonstrated here synergism against a Phialophora verrucosa strain. To evaluate the development of carmofur resistance, passages in culture medium containing subinhibitory concentrations of this pyrimidine analog were carried out, followed by in vitro susceptibility tests. Exophiala dermatitidis quickly developed resistance, whereas F. pedrosoi took seven passages in carmofur-supplemented medium to develop resistance. Moreover, resistance was permanent in E. dermatitidis but transient in F. pedrosoi. Hence, carmofur has exhibited certain advantages, albeit accompanied by limitations such as the development of resistance, which was expected as with 5-FC. This underscores its therapeutic potential in combination with other drugs, emphasizing the need for a meticulous evaluation of its application in the fight against dematiaceous fungi.<\/jats:p>","DOI":"10.1093\/mmy\/myae029","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T15:52:37Z","timestamp":1711554757000},"source":"Crossref","is-referenced-by-count":5,"title":["Comparison of the antifungal activity of the pyrimidine analogs flucytosine and carmofur against human-pathogenic dematiaceous fungi"],"prefix":"10.1093","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4255-7486","authenticated-orcid":false,"given":"Rowena Alves","family":"Coelho","sequence":"first","affiliation":[{"name":"Mycology Laboratory, National Institute of Infectious Diseases Evandro Chagas , INI\/Fiocruz, Rio de Janeiro , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7378-1990","authenticated-orcid":false,"given":"Fernando","family":"Almeida-Silva","sequence":"additional","affiliation":[{"name":"Mycology Laboratory, National Institute of Infectious Diseases Evandro Chagas , INI\/Fiocruz, Rio de Janeiro , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Helena Galdino","family":"Figueiredo-Carvalho","sequence":"additional","affiliation":[{"name":"Mycology Laboratory, National Institute of Infectious Diseases Evandro Chagas , INI\/Fiocruz, Rio de Janeiro , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa Brito de Souza","family":"Rabello","sequence":"additional","affiliation":[{"name":"Mycology Laboratory, National Institute of Infectious Diseases Evandro Chagas , INI\/Fiocruz, Rio de Janeiro , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela Rodrigues","family":"de\u00a0Souza","sequence":"additional","affiliation":[{"name":"RPT 11B Bioassay Platform, National Institute of Infectious Diseases Evandro Chagas , INI\/Fiocruz, Rio de Janeiro , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina da Silva","family":"Louren\u00e7o","sequence":"additional","affiliation":[{"name":"RPT 11B Bioassay Platform, National Institute of Infectious Diseases Evandro Chagas , INI\/Fiocruz, Rio de Janeiro , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcio L","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Carlos Chagas Institute , Fiocruz, Paran\u00e1 , Brazil"},{"name":"Institute of Microbiology, Federal University of Rio de Janeiro (UFRJ) , Rio de Janeiro , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6639-6058","authenticated-orcid":false,"given":"Rodrigo","family":"Almeida-Paes","sequence":"additional","affiliation":[{"name":"Mycology Laboratory, National Institute of Infectious Diseases Evandro Chagas , INI\/Fiocruz, Rio de Janeiro , Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,3,26]]},"reference":[{"issue":"1","key":"2024041108560714500_bib1","doi-asserted-by":"crossref","first-page":"14229","DOI":"10.1038\/s41598-020-70915-0","article-title":"Environmental prospecting of black yeast-like agents of human disease using culture-independent methodology","volume":"10","author":"Costa\u00a0F\u00a0de","year":"2020","journal-title":"Sci Rep"},{"issue":"1","key":"2024041108560714500_bib2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1590\/S1517-83822001000100011","article-title":"Isolation of herpotrichiellacious fungi from the environment","volume":"32","author":"Vicente","year":"2001","journal-title":"Braz J Microbiol"},{"issue":"4","key":"2024041108560714500_bib3","doi-asserted-by":"crossref","first-page":"305","DOI":"10.3314\/jjmm.47.305","article-title":"Isolation of Fonsecaea pedrosoi from the shell of the babassu coconut (Orbignya phalerata Martius) in the Amazon region of Maranh\u00e3o Brazil","volume":"47","author":"Marques","year":"2006","journal-title":"Nihon Ishinkin Gakkai Zasshi"},{"key":"2024041108560714500_bib4","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1590\/S0036-46652004000100006","article-title":"Isolation of Fonsecaea pedrosoi from thorns of Mimosa pudica, a probable natural source of chromoblastomycosis","volume":"46","author":"Salgado","year":"2004","journal-title":"Revista do Instituto de Medicina Tropical de S\u00e3o Paulo"},{"issue":"1","key":"2024041108560714500_bib5","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1055\/s-0039-3400957","volume":"41","author":"Arcobello","year":"2020","journal-title":"Phaeohyphomycosis. 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