Interação in vitro de itraconazol e anti-inflamatórios não esteroidais frente à Sporothrix schenckii sensu stricto e sporothrix brasiliensis

Abstract

Sporotrichosis is a subcutaneous mycosis caused by dimorphic fungi of the Sporothrix schenckii complex, which is distributed worldwide with endemic areas. The emergence of resistant isolates presented major challenges to the treatment of infections caused by the S. schenckii complex. Therefore, it is necessary to seek new therapeutic strategies. Studies involving Candida spp., Cryptococcus spp. and Trichosporon spp. Demonstrated that the association between NSAIDs and antifungals represents a promising prospect for resistant isolates. The objective of this study was to evaluate the in vitro efficacy of NSAIDs (acetylsalicylic acid, ibuprofen and diclofenac sodium) alone and in combination with antifungal agents (itraconazole and terbinafine) against two clinically relevant species: S. brasiliensis and S. schenckii sensu stricto. The Minimum Inhibitory Concentration (MIC) against the 11 isolates of Sporothrix spp. was determined by the broth microdilution method according to the M38-A2 protocol of the Clinical and Laboratory Standards Institute (2008). Interactions between drugs, as well as the Fractional Inhibitory Concentration Index (FICI) of the selected NSAIDs and antifungal agents were evaluated by the chessboard method. Among the NSAIDs, ibuprofen showed the best inhibitory effect, with nine isolates presenting MIC <1mg / mL, whereas acetylsalicylic acid (ASA) showed activity between 1 and 8mg / mL and diclofenac sodium (DIC) showed no activity to 8mg / mL. In the combination with itraconazole, it was possible to observe synergistic interactions in nine isolates, and two isolates resistant to itraconazole, one S. schenckii sensu stricto and another S. brasiliensis, presented a synergistic reaction reaction with all NSAIDs tested. The combination of terbinafine and NSAIDs was classified as indifferent. Thus, it is possible to observe that the combination of itraconazole and the three NSAIDs tested represents a promising therapeutic alternative for the treatment of sporotrichosis.