Synergism between azoles and statins on the growth of opportunistic pathogen yeasts

Abstract

Candida bloodstream infections are an important cause of mortality. A few opportunistic fungemia cases due to Candida utilis have been reported up today. Likewise, numerous cases of infections, particularly in immunocompromised patients, caused by Saccharomyces cerevisiae, a safe regarded microorganism, have been also described. Increased incidence of these opportunist fungal infections, added to the emergence of resistance to several antifungal drugs have focused interest in developing new alternatives for treatment. In this work the synergism between statins, cholesterol-lowering agents, and azoles against S. cerevisiae and C. utilis strains was evaluated by using a diffusion-agar bioassay. Growth inhibition was significantly enhanced, from 11.2 to 77.5%, for azole combinations with lovastatin, simvastatin, rosuvastatin and atorvastatin. Miconazole in combination with simvastatin exhibited the best in vitro activity. Sinergism was confirmed by determining a reduction in cellular sterol levels. Our findings suggested that the combined use of azoles and statins may represent a viable alternative for fastidious mycosis treatment, not only by increasing the fungicidae effects but also by reducing the azole doses to be administrated.