In vitro synergistic antifungal activity of hypocholesterolemic statins with azoles as witnessed by Saccharomyces cerevisiae- and Candida utilis bioassays

CABRAL, MARÍA E.; FIGUEROA, LUCÍA I. C.; FARIÑA, JULIA I.

JOURNAL OF GENERAL AND APPLIED MICROBIOLOGY

MICROBIOL RES FOUNDATION

Lugar: Tokyo, Japon; Año: 2010

0022-1260

Summary Frequent opportunist fungal infections and the resistance to available antifungal drugs promoted the development of new alternatives for treatment, like antifungal drug combinations. This work aimed to detect the antifungal synergism between statins and azoles by means of an agar-well diffusion bioassay with Saccharomyces cerevisiae ATCC 32051 and Candida utilis Pr1-2 as test strains. Growth inhibition was significantly increased when clotrimazole, fluconazole, itraconazole, ketoconazole and miconazole were combined with atorvastatin, lovastatin, rosuvastatin and simvastatin. Highest growth inhibition increments on S. cerevisiae (77.5%) or C. utilis (43.2%) were observed with a sub-inhibitory concentration of simvastatin plus a minimal inhibitory concentration of miconazole, i.e. 4 +2.4 ìg ml-1 or 20 + 4.8 ìg ml-1, respectively. Pravastatin had almost no significant effects (0-7.6% inhibition increment). Highest interaction ratios between antifungal agents (2.2-3)corresponded to simvastatin miconazole combinations and were indicative of synergism. Synergism was also confirmed by the increased reduction in cellular sterols levels (ca. 20%).Statin-induced ergosterol synthesis blockage was corroborated by means of ergosterol rescue bioassays, being pravastatin the easiest inhibition to be abolished whilst rosuvastatin, the most ergosterol-refractory. Selected statin-azole combinations might be viable alternatives for the therapeutic management of mycosis at lower administration doses or with higher efficiency.