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Pyrvinium Pamoate Synergizes with Azoles in vitro and in vivo to Exert Antifungal Efficacy Against Candida auris and Other Candida Species

Summary

Researchers tested a combination of an old antiparasitic drug called pyrvinium pamoate with common antifungal medications called azoles against dangerous drug-resistant fungal infections. While pyrvinium pamoate alone was not very effective, when combined with azoles it significantly improved the treatment of Candida auris infections. Tests in insect larvae showed that the combination improved survival rates better than using azoles alone, suggesting a promising new treatment approach for serious fungal infections.

Background

Candida auris is an emerging multidrug-resistant fungal pathogen causing severe invasive infections with high patient mortality rates. Azole-resistant Candida species pose significant clinical challenges requiring novel therapeutic approaches. Pyrvinium pamoate has shown potential to enhance antifungal efficacy of azoles against various fungal pathogens.

Objective

To investigate the antifungal properties of pyrvinium pamoate alone and in combination with azole antifungals against Candida auris and other Candida species both in vitro and in vivo.

Results

Pyrvinium pamoate as single agent showed poor efficacy with MICs ranging from 2-32 μg/mL. Synergistic activity was observed when combining pyrvinium pamoate with azoles, particularly against C. albicans and C. auris isolates. In vivo studies demonstrated significantly improved larval survival rates when pyrvinium pamoate was combined with posaconazole or voriconazole compared to azole monotherapy.

Conclusion

Combining pyrvinium pamoate with azoles represents a promising therapeutic approach for treating azole-resistant C. auris and other Candida species, potentially overcoming resistance mechanisms through mechanisms including aneuploidy targeting and metabolic dysfunction induction.
  • Published in:Infection and Drug Resistance (Infect Drug Resist),
  • Study Type:In vitro and in vivo experimental study,
  • Source: PMID: 39958982, DOI: 10.2147/IDR.S497929
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