Molecular identification and antifungal susceptibility profiles of clinical strains of <i>Fonsecaea</i> spp. isolated from patients with chromoblastomycosis in Rio de Janeiro, Brazil

<div><p>Background</p><p>Chromoblastomycosis (CBM) is a difficult-to-treat chronic subcutaneous mycosis. In Brazil, the main agent of this disease is <i>Fonsecaea pedrosoi</i>, which is phenotypically very similar to other <i>Fonsecaea</i> species, differing only genetically. The correct species identification is relevant since different species may differ in their epidemiologic aspects, clinical presentation, and treatment response.</p><p>Methodology/Principal findings</p><p>Partial sequencing of the internal transcribed spacer (ITS) was used to identify twenty clinical isolates of <i>Fonsecaea</i> spp. Their <i>in vitro</i> antifungal susceptibility was determined using the broth microdilution method, according to the M38-A2 protocol. Amphotericin B (AMB), flucytosine (5FC), terbinafine (TRB), fluconazole (FLC), itraconazole (ITC), ketoconazole (KTC), posaconazole (POS), voriconazole (VRC), ravuconazole (RVC), caspofungin (CAS), and micafungin (MFG) were tested. The association between ITC/TRB, AMB/5FC, and ITC/CAS was studied by the checkerboard method to check synergism. The available patients’ data were correlated with the obtained laboratory results. <i>Fonsecaea monophora</i> (n = 10), <i>F</i>. <i>pedrosoi</i> (n = 5), and <i>F</i>. <i>nubica</i> (n = 5) were identified as CBM’ agents in the study. TRB and VRC were the drugs with the best <i>in vitro</i> activity with minimal inhibitory concentrations (MIC) lower than 0.25 mg/L. On the other hand, FLC, 5FC, AMB, and MFG showed high MICs. The AMB/5FC combination was synergistic for three <i>F</i>. <i>monophora</i> strains while the others were indifferent. Patients had moderate or severe CBM, and ITC therapy was not sufficient for complete cure in most of the cases, requiring adjuvant surgical approaches.</p><p>Conclusions/Significance</p><p><i>F</i>. <i>monophora</i>, the second most frequent <i>Fonsecaea</i> species in South America, predominated in patients raised and born in Rio de Janeiro, Brazil, without cerebral involvement in these cases. TRB, VRC, and the AMB/5FC combination should be further investigated as a treatment option for CBM.</p>