Fungal-specific Cyp51 inhibitor VT-1598 demonstrates in vitro activity against Candida and Cryptococcus species, endemic fungi, including Coccidioides species, Aspergillus species and Rhizopus arrhizus.

ABSTRACT

Background: Invasive fungal infections, including those caused by yeasts, moulds and endemic organisms, can be significant causes of morbidity and mortality in immunocompromised hosts, those with multiple comorbidities and occasionally immunocompetent hosts. Current antifungal agents are often limited by drug toxicities, drug interactions or the development of resistance. VT-1598 is a novel tetrazole that has greater specificity for fungal Cyp51 than currently available triazoles and thus the potential for clinically significant drug interactions is reduced. We measured the in vitro activity of VT-1598 against clinical isolates of Candida and Cryptococcus species, endemic fungi, including Coccidioides, Blastomyces and Histoplasma, Aspergillus species and Rhizopus arrhizus. Methods: Antifungal susceptibility testing was performed by broth microdilution or macrodilution methods per CLSI standards. Clinical isolates of each species were used and clinically available antifungal agents were tested against each isolate. Results: VT-1598 demonstrated in vitro activity against yeasts and moulds that was similar to or greater than that of clinically available antifungal agents, including amphotericin B, fluconazole, caspofungin, voriconazole and posaconazole. The in vitro activity of VT-1598 was also maintained against resistant isolates, including fluconazole-resistant Candida isolates. In vitro activity was also observed against endemic fungi, including Blastomyces, Histoplasma and both Coccidioides immitis and Coccidioides posadasii. Conclusions: VT-1598 demonstrated in vitro activity against yeasts, moulds and endemic fungi, which was maintained against isolates that had reduced susceptibility to other antifungals. Further studies are warranted to evaluate the in vivo efficacy of VT-1598 against various fungal pathogens.