In vitro synergistic interactions of the effects of various statins and azoles against some clinically important fungi

Abstract

The treatment of opportunistic fungal infections is often difficult as the number of available antifungal agents is limited. Nowadays, there is increasing interest in the investigation of the antifungal activity of nonantifungal drugs, and in the development of efficient antifungal combination therapy. In this study, the in vitro interactions of the effects of various statins (lovastatin, simvastatin, fluvastatin, atorvastatin (ATO), rosuvastatin (ROS) and pravastatin) and various azole antifungals [miconazole, ketoconazole, itraconazole and fluconazole (FLU)] against different opportunistic pathogenic fungi were investigated using a standard chequerboard broth microdilution method. When the investigated strains were sensitive to both compounds of the combination, additive interactions were frequently noticed. Synergistic interactions were observed in many cases when a strain was sensitive only to the azole compound (as in certain combinations with ATO or ROS) or the statin compound (as in certain combinations with FLU). In many combinations with an additive effect, the concentrations of drugs needed for total growth inhibition could be decreased by several dilution steps. Similar interactions were observed when the variability of the within-species sensitivities to some selected drug combinations was investigated.

In vitro synergism of simvastatin and fluconazole against Candida species

“…In a study conducted with strains of C. albicans and C. glabrata, evaluating the synergism between simvastatin and fluconazole, an additive effect was observed 9 . In our study, the results were different; we found a synergistic effect.…”

“…Simvastatin (Sigma-USA) was activated in an ethanol solution of NaOH (15% (vol/vol) and 0.25% (m/vol) NaOH) at 60 °C for one hour 9 . The simvastatin solution was filtered and placed in a desiccator for 72 hours.…”

“…New therapeutic strategies are needed to prevent the spread of resistance. Among these strategies we can highlight the search for new drugs and drug combinations with synergistic purpose 3,9 . Statins are drugs used to treat hypercholesterolemia, but also have antifungal activity 6 .…”

Novel applications of statins for bone regeneration

“…Moreover, several statins, especially simvastatin and fluvastatin, were seen to act synergistically with various antifungals, showing strong fungicidal effects in vitro [67,68]. …”

Is there a role for statins in fungal infections?

“…The MIC determinations vary between different laboratories but are generally in the micromolar range (lowest is 0.4 mg/ml or 0.9 mmol/l). The synergistic effect of statins together with different standard antifungal drugs has also been evaluated [30][31][32][33][34][35][36][37][38][39], and the MIC is then generally lowered, sometimes by as much as with a factor of 10. Two articles report on potent synergistic effects of statins in combination with the atypical drugs primycin [40] and suramin [41] against various moulds.…”