In vitro synergistic interactions of the effects of various statins and azoles against some clinically important fungi: Synergistic interactions between statins and azoles
Open accessAbstract
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.
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Statins exhibit a broad spectrum of biological activities, including antimicrobial, antiparasitic, antibacterial, antiviral, and antifungal potential.
“Moreover, statins exhibit a broad spectrum of biological activities, including antimicrobial, antiparasitic, antibacterial, antiviral, and antifungal potential [110, 111, 112, 113].”
From Statins as Antifungal Agents: A Review on Drug Repurposing and Nanotechnology-Driven Delivery Strategies (2025) · cites this paper as [110]
The Introduction (page unavailable) describes statins’ direct antimicrobial effects and growth inhibition of pathogenic bacteria and fungi, supporting the antimicrobial, antibacterial, and antifungal parts of the claim. Our copy does not describe antiparasitic or antiviral potential, so it does not support the full list. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe synergism between ATO and azole drugs might be attributed to the combined action of these drugs in reducing fungal ergosterol synthesis, which led to increasing cell membrane permeability and increasing the penetration of azoles in the fungal cell.
“The synergism between ATO and azole drugs might be attributed to the combined action of these drugs in reducing fungal ergosterol synthesis, which led to increasing cell membrane permeability and increasing the penetration of azoles in the fungal cell (Chamilos et al. 2006; Nyilasi et al. 2010; Cabral et al. 2013; Lima et al. 2019).”
From In vitro study on the potential fungicidal effects of atorvastatin in combination with some azole drugs against multidrug resistant Candida albicans (2021) · cites this paper as Nyilasi et al. 2010
The Introduction describes azoles as inhibiting a step in ergosterol biosynthesis, and the Interactions between azoles and statins section reports synergy for some ATO–azole combinations. The paper does not attribute that synergy to combined suppression of ergosterol synthesis or report increased membrane permeability and azole penetration. The indexed passages provide section labels but no page numbers. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe obtained results are consistent with previous studies, which mentioned that there were synergistic interactions between statins and azole drugs against Candida spp. Saccharomyces cerevisiae and different filamentous fungi.
“The obtained results are consistent with previous studies, which mentioned that there were synergistic interactions between statins and azole drugs against Candida spp. Saccharomyces cerevisiae and different filamentous fungi (Lorenz and Parks 1990; Chamilos et al. 2006; Nyilasi et al. 2010).”
From In vitro study on the potential fungicidal effects of atorvastatin in combination with some azole drugs against multidrug resistant Candida albicans (2021) · cites this paper as Nyilasi et al. 2010
The ‘Interactions between azoles and statins’ section reports synergistic combinations against Candida albicans and filamentous fungi, including Aspergillus fumigatus and Rhizopus oryzae. The Introduction lists the species studied but does not include Saccharomyces cerevisiae; that part of the citing sentence is not supported by this paper’s findings. (LLM, conf=0.87)
Experimental — accuracy not yet measuredSynergy between simvastatin and azoles has been described for planktonically growing yeast cultures, as for other statin-azole combinations.
“Interestingly, synergy between simvastatin and azoles has been described for planktonically growing yeast cultures46 as is the case for other statin-azole combinations47.”
From Stimulation of superoxide production increases fungicidal action of miconazole against Candida albicans biofilms (2016) · cites this paper as [46]
A recent comprehensive study revealed synergistic and additive interaction between four azole compounds and six statins against C. albicans and C. glabrata.
“A recent comprehensive study, where the interaction was investigated between four different azole compounds (FCZ; ITZ; ketoconazole, KTZ; and miconazole; MCZ) and six different statins (ATO, FLV, LOV, PRA, ROS, and SIM), revealed synergistic and additive interaction between these compounds against C. albicans and C. glabrata [29] .”
From Statins as antifungal agents (2011) · cites this paper as [29]
Additive and synergistic interactions were revealed between statins and azoles against A. flavus, A. fumigatus, and Paecilomyces variotii.
“Additive and synergistic interactions were revealed between statins and azoles against A. flavus, A. fumigatus, and Paecilomyces variotii [29] .”
From Statins as antifungal agents (2011) · cites this paper as [29]
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- Authors
- Nyilasi, I., Kocsubé, S., Krizsán, K., Galgóczy, L., Pesti, M., Papp, T., & Vágvölgyi, C.
- Affiliations
- University of Szeged (HU)
- University of Pecs (HU)
- Corresponding author
- Nyilasi, Ildikó
- Venue
- FEMS Microbiology Letters
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-04-02
- Volume
- 307
- Issue
- 2
- Pages
- 175-184
- ISSN
- 0378-1097 (ISSN-L)
- 1574-6968
- OpenAlex
- W2108358749
- Cited by
- 83
- References
- 36
- Citations by year
- 2025: 6 · 2024: 8 · 2023: 7 · 2022: 10 · 2021: 3 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 4 · 2016: 6 · 2015: 3 · 2014: 4 · 2013: 7 · 2012: 4
- FWCI
- 2.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEMS Microbiology Letters (publishedVersion)
- PubMed (publishedVersion)
- SZTE Publicatio Repozitórium (University of Szeged) (acceptedVersion, other-oa)
- Funders
- Nemzeti Kutatási és Technológiai Hivatal
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Keywords
- statins, azole antifungals, drug synergy, opportunistic fungal infection, combination antifungal therapy, lovastatin, simvastatin, fluvastatin, atorvastatin, rosuvastatin, pravastatin, miconazole, ketoconazole, itraconazole, fluconazole
- MeSH terms
- Antifungal Agents, Aspergillus, Azoles, Candida, Drug Synergism, Microbial Sensitivity Tests, Piperazines, Species Specificity, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Rhizomucor
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