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  • Susceptibility of clinically important dermatophytes against statins and different statin-antifungal combinations.

Susceptibility of clinically important dermatophytes against statins and different statin-antifungal combinations.

Medical mycology (2013-09-06)
Ildikó Nyilasi, Sándor Kocsubé, Krisztina Krizsán, László Galgóczy, Tamás Papp, Miklós Pesti, Katalin Nagy, Csaba Vágvölgyi
ABSTRACT

The investigation of the antifungal activities of drugs whose primary activities are not related to their antimicrobial potential is in the current forefront of research. Statin compounds, which are routinely used as cholesterol-lowering drugs, may also exert direct antimicrobial effects. In this study, the in vitro antifungal activities of various statins (lovastatin, simvastatin, fluvastatin, atorvastatin, rosuvastatin and pravastatin) were examined against one isolate each of four dermatophyte species (Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum canis and Microsporum gypseum). Basically, statins were effective in inhibiting all dermatophyte studied, but were particularly active against M. canis and T. mentagrophytes. Fluvastatin and simvastatin were active against all of the tested fungi causing a complete inhibition of their growth at very low concentrations (6.25-12.5 μg/ml). Lovastatin and rosuvastatin had inhibitory effects at higher concentrations (25-128 μg/ml), while atorvastatin and pravastatin proved the less effective. The in vitro interactions between statins and different antifungals (ketoconazole, itraconazole, fluconazole, amphotericin B, nystatin, griseofulvin, terbinafine and primycin) were also investigated using a standard chequerboard broth microdilution method. Synergetic interactions were observed in several cases, most of them were noticed when statins were combined with terbinafine and the different azoles. Some combinations were particularly active (ketoconazole-simvastatin or terbinafine-simvastatin), as they were found to exert synergistic effect against all of the investigated isolates. The other antifungals showed synergistic interactions with statins in only certain cases. These results suggest that statins exert substantial antifungal effects against dermatophyte fungi and they should be promising components in a combination therapy as they can act synergistically with a number of clinically used antifungal agents.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Fluconazole, ≥98% (HPLC), powder
Sigma-Aldrich
Mevinolin from Aspergillus sp., ≥98% (HPLC)
Sigma-Aldrich
Griseofulvin, from Penicillium griseofulvum, 97.0-102.0%
Supelco
Lovastatin, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Fluconazole, United States Pharmacopeia (USP) Reference Standard
USP
Lovastatin, United States Pharmacopeia (USP) Reference Standard
USP
Griseofulvin, United States Pharmacopeia (USP) Reference Standard
Supelco
Griseofulvin, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Fluconazole, Pharmaceutical Secondary Standard; Certified Reference Material
Fluconazole, European Pharmacopoeia (EP) Reference Standard
Lovastatin, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Ketoconazole
Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
Dimethyl sulfoxide, BioUltra, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
Dimethyl sulfoxide, meets EP testing specifications, meets USP testing specifications
Sigma-Aldrich
Dimethyl sulfoxide, for molecular biology
Sigma-Aldrich
Dimethyl sulfoxide, PCR Reagent
Sigma-Aldrich
Dimethyl sulfoxide, Hybri-Max, sterile-filtered, BioReagent, suitable for hybridoma, ≥99.7%
Sigma-Aldrich
Ketoconazole, 99.0-101.0% (EP, titration)
SAFC
L-Glutamine
Sigma-Aldrich
Dimethyl sulfoxide, ≥99.5% (GC), suitable for plant cell culture
Sigma-Aldrich
L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
Sigma-Aldrich
L-Glutamine
Sigma-Aldrich
Dimethyl sulfoxide, anhydrous, ≥99.9%
Sigma-Aldrich
L-Glutamine, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
1-Propanesulfonic acid, technical, ≥99.0% (T)
Sigma-Aldrich
L-Glutamine
Sigma-Aldrich
Dimethyl sulfoxide, suitable for HPLC, ≥99.7%
Sigma-Aldrich
Dimethyl sulfoxide, ACS reagent, ≥99.9%
Sigma-Aldrich
Dimethyl sulfoxide, puriss. p.a., dried, ≤0.02% water