In Vitro Activities of Five Antifungal Drugs Against Conidia and Sclerotic Cells of Chromoblastomycosis Agent Fonsecaea spp.

Chromoblastomycosis (CBM) is a chronic skin and subcutaneous infection mainly caused by Fonsecaea pedrosoi, a dematiaceous fungus with various morphotypes. Characteristic sclerotic cells-globe-shaped, multiseptated and pigmented-are found in lesions of infected individuals, though their differentiation in the host remains poorly understood. To evaluate in vitro activity of five antifungal drugs-itraconazole (ITZ), posaconazole (PCZ), voriconazole (VCZ), fluconazole (FCZ), and caspofungin (CAS)-against Fonsecaea spp. conidia or sclerotic cells, assessing their minimum inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) and correlated the ITZ MIC with patients' clinical evolution. Forty-three clinical isolates of Fonsecaea spp. and the F. pedrosoi strain ATCC 46428 were assessed for susceptibility to ITZ, PCZ, VCZ, FCZ, and CAS following Clinical Laboratory Standard Institute guidelines (CLSI) (document M38-A2). MIC values were determined after 5 days of incubation at 30°C, followed by MFC determination, with geometric mean MIC (GMMIC) and MFC (GMMFC) used for comparison. PCZ was the most effective antifungal drug, with geometric mean MICs of 0.3 µg/mL (conidia) and 1 µg/mL (sclerotic), and MFCs of 2.98 and 6.72 µg/mL, respectively. Clinical follow-up revealed that higher ITZ MIC values (0.9 µg/mL) correlated with poor patient outcomes compared to lower values in improved or cured patients. These findings highlight PCZ and VCZ as promising options for CBM treatment, especially for patients not responding to ITZ.