Antifungal effects of statins

Abstract

Fungal infections are estimated to be responsible for 1.5 million deaths annually. Global anti-microbial resistance is also observed for fungal pathogens, and scientists are looking for new antifungal agents to address this challenge. One potential strategy is to evaluate currently available drugs for their possible antifungal activity. One of the suggested drug classes are statins, which are commonly used to decrease plasma cholesterol and reduce cardiovascular risk associated with low density lipoprotein cholesterol (LDL-c). Statins are postulated to possess pleiotropic effects beyond cholesterol lowering; improving endothelial function, modulating inflammation, and potentially exerting anti-microbial effects. In this study, we reviewed in-vitro and in-vivo studies, as well as clinical reports pertaining to the antifungal efficacy of statins. In addition, we have addressed various modulators of statin anti-fungal activity and the potential mechanisms responsible for their anti-fungal effects. In general, statins do possess anti-fungal activity, targeting a broad spectrum of fungal organisms including human opportunistic pathogens such as Candida spp. and Zygomycetes, Dermatophytes, alimentary toxigenic species such as Aspergillus spp., and fungi found in device implants such as Saccharomyces cerevisiae. Statins have been shown to augment a number of antifungal drug classes, for example, the azoles and polyenes. Synthetic statins are generally considered more potent than the first generation of fungal metabolites. Fluvastatin is considered the most effective statin with the broadest and most potent fungal inhibitory activity, including fungicidal and/or fungistatic properties. This has been demonstrated with plasma concentrations that can easily be achieved in a clinical setting. Additionally, statins can potentiate the efficacy of available antifungal drugs in a synergistic fashion. Although only a limited number of animal and human studies have been reported to date, observational cohort studies have confirmed that patients using statins have a reduced risk of candidemia-related complications. Further studies are warranted to confirm our findings and expand current knowledge of the anti-fungal effects of statins.