RESUMO Avaliou-se a susceptibilidade de Sporothrix albicans(n = 1), S. brasiliensis(n = 1), S. globosa(n = 1), S. mexicana(n = 1) e S. schenckii(n = 36) frente à terbinafina (TRB) e a TRB em combinação com itraconazol (ITZ), cetoconazol (KTZ) e voriconazol (VRZ) pelo método de microdiluição ( checkerboard); o perfil enzimático destas espécies foi também avaliado, com base no kit API-ZYM. A maioria das interações foram aditivas (27,5%, 32,5% e 5%) ou indiferentes (70%, 50% e 52,5%) para TRB+KTZ, TRB+ITZ e TRB+VRZ, respectivamente. Antagonismo foi observado em 42,5% dos isolados para a combinação TRB+VRZ. Com base nos perfis enzimáticos, as cepas de Sporothrix schenckii evidenciaram 14 biotipos distintos. A atividade da leucina arilamidase (LA) só foi observada em S. albicanse S. mexicana. As espécies S. globosae S. mexicanaforam as únicas que não evidenciaram atividade da enzima β-glucosidase (GS). Estes resultados poderão contribuir para um melhor entendimento da virulência e resistência entre as espécies do gênero Sporothrixem futuros estudos.

SUMMARY Sporothrix schenckiiwas reclassified as a complex encompassing six cryptic species, which calls for the reassessment of clinical and epidemiological data of these new species. We evaluated the susceptibility of Sporothrix albicans (n = 1) , S. brasiliensis (n = 6) , S. globosa (n = 1), S. mexicana(n = 1) and S. schenckii(n = 36) to terbinafine (TRB) alone and in combination with itraconazole (ITZ), ketoconazole (KTZ), and voriconazole (VRZ) by a checkerboard microdilution method and determined the enzymatic profile of these species with the API-ZYM kit. Most interactions were additive (27.5%, 32.5% and 5%) or indifferent (70%, 50% and 52.5%) for TRB+KTZ, TRB+ITZ and TRB+VRZ, respectively. Antagonisms were observed in 42.5% of isolates for the TRB+VRZ combination. Based on enzymatic profiling, the Sporothrix schenckii strains were categorized into 14 biotypes. Leucine arylamidase (LA) activity was observed only for S. albicans and S. mexicana. The species S. globosaand S. mexicanawere the only species without β-glucosidase (GS) activity. Our results may contribute to a better understanding of virulence and resistance among species of the genus Sporothrixin further studies.

In vitro interaction between tacrolimus (FK506) and four azoles (fluconazole, ketoconazole, itraconazole and voriconazole) against thirty clinical isolates of both fluconazole susceptible and -resistant Candida glabrata were evaluated by the checkerboard microdilution method. Synergistic, indifferent or antagonism interactions were found for combinations of the antifungal agents and FK506. A larger synergistic effect was observed for the combinations of FK506 with itraconazole and voriconazole (43%), followed by that of the combination with ketoconazole (37%), against fluconazole-susceptible isolates. For fluconazole-resistant C. glabrata, a higher synergistic effect was obtained from FK506 combined with ketoconazole (77%), itraconazole (73%), voriconazole (63%) and fluconazole (60%). The synergisms that we observed in vitro, notably against fluconazole-resistant C. glabrata isolates, are promising and warrant further analysis of their applications in experimental in vivo studies.

The extensive use of azole antifungal agents has promoted the resistance of Candida spp to these drugs. Candida glabrata is a problematic yeast because it presents a high degree of primary or secondary resistance to fluconazole. In Brazil, C. glabrata has been less studied than other species. In this paper, we compared the activity of three major classes of antifungal agents (azoles, echinocandins and polyenes) against fluconazole-susceptible (FS) and fluconazole-resistant (FR) C. glabrata strains. Cross-resistance between fluconazole and voriconazole was remarkable. Among the antifungal agents, the echinocandins were the most effective against FS and FR C. glabrata and micafungin showed the lowest minimal inhibitory concentrations.

In the present study we used two groups of Candida dubliniensis strains: one containing fluconazole-susceptible clinical isolates and another containing fluconazole-resistant laboratory derivative from the former to examine the changes on susceptibility accompanying the development of resistance to fluconazole. Our findings confirmed the ability of C. dubliniensis isolates to become resistant to fluconazole and indicated that this resistance was crossed with ketoconazole, itraconazole, ravuconazole and terbinafine. We also tested combinations of terbinafine, amphotericin B, itraconazole and voriconazole against both groups of isolates in a checkerboard assay. Surprisingly, most combinations evidenced indifferent interactions, and the best synergism appeared when terbinafine and itraconazole were combined against the fluconazole-resistant group.