In vitro activity of propyl gallate-azole drug combination against fluconazole- and itraconazole-resistant Candida albicans strains

Aims: The influence of an antioxidant, propyl gallate (PG), on the In vitro antifungal activity of itraconazole and fluconazole, was investigated to determine whether PG could increase the antifungal activity and reduce strain resistance. Methods and Results: Susceptibility tests were performed against azole-resistant isolates of Candida albicans by the microbroth dilution method in the presence of PG at 400 mug ml(-1). PG-triazole combination brought about a marked reduction of inhibitory azole concentration. In particular, the MIC90 for itraconazole and fluconazole dropped from 1 mug ml(-1) to 0.125 mug ml(-1) and from >64 mug ml(-1)-8 mug ml(-1), respectively. Conclusions: It is likely that more than one mechanism is involved in the above synergistic interaction, including effects of PG on ATP synthesis, thus reducing the ABC transporters activity, or an effect on the target of azole, i.e. the P-450 cytochrome. Significance and Impact of the Study: The PG-triazole combination may have a role in future topical antifungal strategies but other studies are warranted