Reversal of itraconazole resistance in Sporothrix brasiliensis and Sporothrix schenckii by nonsteroidal anti-inflammatory drugs

Background The emergence of resistant isolates has brought challenges to the treatment of sporotrichosis, prompting the search for new therapeutic strategies. Previous studies reported that nonsteroidal anti-inflammatory drugs (NSAIDs) show in vitro activity against several pathogenic fungi, including species of Candida, Cryptococcus, and Trichosporon. Aims This study aimed to investigate the in vitro efficacy of three NSAIDs (acetylsalicylic acid, diclofenac sodium, and ibuprofen), alone and in combination with itraconazole, against eleven clinical isolates of Sporothrix brasiliensis and Sporothrix schenckii. Methods Minimal inhibitory concentrations were determined by the broth microdilution method. Drug interactions and the fractional inhibitory concentration index of NSAIDs and itraconazole were assessed by the checkerboard method. Results When used alone, ibuprofen was the most active NSAID, followed by acetylsalicylic acid. Combinations of NSAIDs with itraconazole showed synergistic antifungal activity against nine isolates. It was also found that itraconazole combined with acetylsalicylic acid, diclofenac sodium, or ibuprofen, led to resistance reversal in two, three, and five of the six drug-resistant isolates, respectively. Conclusions The results indicate that the combination of itraconazole and the evaluated NSAIDs are a promising strategy for the treatment of sporotrichosis.