In vitro effects of the new antifungal compound manogepix (APX001) against the three most clinically relevant species of Sporothrix.

Sporotrichosis is an endemic mycosis that pose significant public health challenges, particularly in Brazil, where zoonotic transmission has increased the number of cases in several regions of the country. The disease is caused by Sporothrix genus, with S. brasiliensis, S. schenckii, and S. globosa as the major agents. The currently available therapies may face limitations such as varying cure rates, long and expensive treatment, and adverse effects. Fosmanogepix, a prodrug converted into manogepix within the host, has demonstrated broad-spectrum antifungal activity, including other thermodimorphic fungal species. Thus, this study aimed to evaluate the in vitro antifungal efficacy of manogepix against three clinically relevant Sporothrix species. Minimal inhibitory and fungicidal concentrations were determined against 24 Sporothrix spp. isolates, as well as potential synergism with antifungal drugs, induction of resistance and growth kinetics of the fungus in the presence of the new antifungal drug. Manogepix exhibited fungicidal activity against the three Sporothrix species tested, with minimum inhibitory concentrations (MIC) ranging from 0.06 to 1 µg/ml. Furthermore, manogepix demonstrated a lower geometric mean of MIC values compared to the antifungal drugs and indifferent interactions with itraconazole, terbinafine and amphotericin B. Prolonged exposure to subinhibitory manogepix concentrations did not induce resistance in the tested strains. These findings indicate manogepix as a promising candidate for the treatment of sporotrichosis, offering a potential alternative in cases of resistance or treatment failure with current antifungals. Further studies are needed to confirm this activity in clinical settings, particularly in diverse geographic regions and against a broader range of Sporothrix strains.