Evaluation of antifungal combination against Cryptococcus spp

Area of Science:

• Medical Mycology
• Antimicrobial Resistance
• Molecular Epidemiology

Background:

• Cryptococcosis is a leading cause of death from systemic mycoses.
• Treatment is complicated by the unavailability of 5-flucytosine in Brazil.
• Understanding antifungal susceptibility across different Cryptococcus genotypes is crucial for effective treatment.

Purpose of the Study:

• To evaluate antifungal agents, alone and in combination, against clinical isolates of Cryptococcus.
• To correlate antifungal susceptibility patterns with specific Cryptococcus genotypes.
• To identify potential alternative treatments for cryptococcosis in the absence of 5-flucytosine.

Main Methods:

• Eighty clinical isolates of Cryptococcus were genotyped using URA5 gene restriction fragment length polymorphism.
• Antifungal susceptibility testing was performed for amphotericin B, 5-flucytosine, fluconazole, voriconazole, itraconazole, and terbinafine.
• Drug interaction assays (chequerboard) evaluated combinations including fluconazole + terbinafine.

Main Results:

• Genotyping identified Cryptococcus deuterogattii (VGII) and Cryptococcus neoformans (VNI, VNII).
• Significant differences in susceptibility were observed between genotypes for amphotericin B, voriconazole, fluconazole, itraconazole, and terbinafine.
• The combination of fluconazole + terbinafine demonstrated high synergistic activity against C. neoformans VNI (95.16%) and VNII (100%).

Conclusions:

• Cryptococcal genotyping is essential as different genotypes exhibit varying antifungal susceptibilities and clinical outcomes.
• Terbinafine and specific antifungal combinations, particularly fluconazole + terbinafine, represent viable alternatives for treating difficult-to-treat cryptococcosis.
• These findings offer valuable insights for managing cryptococcosis in regions with limited antifungal options.