Is there a role for statins in fungal infections?

Abstract

It has been hypothesized that statins, HMG-CoA reductase inhibitors, may be used to treat fungal infections. Here we review data on antifungal properties of statins, effects on the host inflammatory response as well as available clinical evidence. We conclude that: statins exhibit antifungal properties in vitro although at supraphysiological concentrations; statins appear to have anti-inflammatory effects on host cells in vitro; statins have effects on fungal physiology beyond direct growth inhibition; clinical studies are scarce (n = 5), and their design is retrospective and observational, which is associated with a high risk of bias. Given the limited evidence for a beneficial effect of statins in fungal infection, randomized and controlled trials are highly warranted in this field.

Keywords::

• antifungal agents
• clinical studies
• drug interaction
• fungal infections
• statins

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • It has been hypothesized that statins, HMG-CoA reductase inhibitors, may be used to treat fungal infections.

• • Statins exhibit antifungal properties in vitro, but the concentrations used in these experiments are dramatically higher (100- to 1,000-fold) than could ever be achieved in humans. Statins appear to have anti-inflammatory effects on host cells in vitro.

• • Statins have effects on fungal physiology beyond direct growth inhibition.

• • There are only five clinical studies that evaluate a possible beneficial role of statins in fungal infections. The design is retrospective and observational, which is associated with a high risk of bias. In addition, the results are inconclusive.

• • A possible area to explore is the combination therapy with statins and standard antifungal drugs, in particular for topical use.

• • Systemic combination therapy should focus on pravastatin or pitavastatin, since these drugs are eliminated independently of the cytochrome P450 system, and thus the risk of drug–drug interactions is much lower than for other statins.

• • Given the limited evidence for a beneficial effect of statins in fungal infection, randomized and controlled trials are highly warranted in this field.