Products Cited in Publications Worldwide Enhanced antifungal activity of posaconazole against Candida auris by HIV protease inhibitors, atazanavir and saquinavir

Enhanced antifungal activity of posaconazole against Candida auris by HIV protease inhibitors, atazanavir and saquinavir

Elgammal, Yehia; Salama, Ehab A.; Seleem, Mohamed N.

DOI: PMID:

Abstract

The increasing incidence and dissemination of multidrug-resistant Candida auris represents a serious global threat. The emergence of pan-resistant C. auris exhibiting resistance to all three classes of magnifies the need for novel therapeutic interventions. We identified that two HIV protease inhibitors, and , in combination with exhibited potent activity against C. auris in vitro and in vivo. Both and exhibited a remarkable synergistic activity with against all tested C. auris isolates and other medically important Candida species. In a time-kill assay, both drugs restored the fungistatic activity of , resulting in reduction of 5 and 5.6 log10, resp. Furthermore, in contrast to the individual drugs, the two combinations effectively inhibited the biofilm formation of C. auris by 66.2 and 81.2%, resp. Finally, the efficacy of the two combinations were tested in a mouse model of C. auris infection. The atazanavir/posaconazole and saquinavir/posaconazole combinations significantly reduced the C. auris burden in mice kidneys by 2.04- (99.1%) and 1.44-log10 (96.4%) colony forming unit, resp. Altogether, these results suggest that the combination of with the HIV protease inhibitors warrants further investigation as a new therapeutic regimen for the treatment of C. auris infections.

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Atazanavir

A182779198904-31-398%

Atazanavir

22.0/250mg

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Saquinavir

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Saquinavir

97.0/50mg

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