Are the Statins promising antifungal agents against invasive candidiasis?
Open accessAbstract
The medical importance of intra-abdominal candidiasis (IAC) contrasts with the limited number of pharmacological treatment options available and the increasing rate of resistance to antifungal drugs. Thus, the repositioning of compounds in clinical use can contribute to the broadening of treatment possibilities for this infection. Statins, a class of drugs used to reduce cardiovascular event risk, have shown antiparasitic, antibacterial, and antiviral activities; however, their antifungal effects remain poorly studied. In this context, the present study aimed to elucidate the antifungal potential of six statins in vitro, as well as to evaluate the therapeutic use of fluvastatin in a mouse model of IAC. The biological effects of statins were evaluated against Candida spp., through the determination of the minimum inhibitory concentration (MIC). For the statins that showed activity, the fungicidal concentration, toxicity/selectivity, synergism with azoles and polyenes, phenotypic effects, and activity against virulence factors were also determined. Atorvastatin, rosuvastatin and fluvastatin were highly active, especially against C. albicans (MIC < 1–128 μg.mL −1 ) and C. glabrata (MIC 32–64 μg.mL −1 ). Fluvastatin and atorvastatin were selective for C. albicans in baby hamster kidney (BHK) cells. Moreover, all active statins in the antifungal assay showed high selectivity for fungal cells over bacteria. The combination of atorvastatin, rosuvastatin, and fluvastatin with azoles was associated with a synergistic effect. Active statins do not act on the fungal membrane or wall, but instead stimulate farnesol-dependent pathogenicity factors such as yeast-to-hyphal transition and biofilm generation. Fluvastatin treatment was evaluated in a mouse model of IAC, showing stimulation of the extra-hepatic dissemination of C. albicans but improvements in renal, splenic, and hepatic histological aspects. In conclusion, statins have potent antifungal activity in vitro, but the therapeutic effect in vivo is restricted to their anti-inflammatory activity.
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Atorvastatin has shown significant antifungal activity against different Candida species, particularly against C. albicans.
“Interestingly, atorvastatin is one of statin drugs has shown significant antifungal activity against different Candida species. particularly against C. albicans (Esfahani et al. 2019; 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 Lima et al. 2019
Section 3.1 and Table 1 show atorvastatin activity against multiple Candida species, including C. albicans. But the paper describes its activity against all C. albicans samples tested as moderate, not significant; it uses “significant” for fluvastatin’s activity against C. albicans. (LLM, conf=0.89)
Experimental — accuracy not yet measuredATV has significant antifungal activity against various Candida species, with notable selectivity for C. albicans, including strains resistant to fluconazole, ketoconazole, itraconazole, and voriconazole, with minimum inhibitory concentrations ranging from 16 to 32 μg/mL.
“ATV also demonstrated significant antifungal activity against various Candida species, with notable selectivity for C. albicans , including strains resistant to fluconazole, ketoconazole, itraconazole, and voriconazole, with minimum inhibitory concentrations ranging from 16 to 32 μg/mL [19].”
From Statins as Antifungal Agents: A Review on Drug Repurposing and Nanotechnology-Driven Delivery Strategies (2025) · cites this paper as [19]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredDrug repurposing or finding new indications for old drugs represents a promising alternative strategy to drug development and bypass antifungal drug resistance.
“Among the different strategies to fight and overcome antifungal resistance, drug repurposing or finding new indications for old drugs represents a promising alternative strategy to drug development and bypass antifungal drug resistance (Vadivoo et al. 2018; Lima et al. 2019; Kim et al. 2020).”
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 Lima et al. 2019
The Introduction presents drug repositioning as a way to reduce the cost and time of developing treatments amid growing antifungal resistance. The Discussion reports that statins reversed fluconazole resistance in one C. albicans strain, but that specific result does not establish that repurposing broadly bypasses antifungal resistance. (LLM, conf=0.83)
Experimental — accuracy not yet measuredDecreasing of inhibition zones of amphotericin B with the presence of ATO is probably due to that ATO reduces the synthesis of the fungal ergosterol, which is the target of amphotericin B, and a decrease in this molecule is one of the mechanisms developed by amphotericin B resistant Candida spp.
“Decreasing of inhibition zones of amphotericin B with the presence of ATO is probably due to that ATO reduces the synthesis of the fungal ergosterol, which is the target of amphotericin B, and a decrease in this molecule is one of the mechanisms developed by amphotericin B resistant Candida spp. (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 Lima et al. 2019
Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredThe same fungicidal effects were associated with combinations of Fluvastatin or pitavastatin with azole drugs against Candida ssp., especially C. albicans.
“The same fungicidal effects were associated the combinations of Fluvastatin (Lima et al. 2019) or pitavastatin (Eldesouky et al. 2020) with azole drugs produced fungicidal effects against Candida ssp., especially C. albicans .”
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 Lima et al. 2019
Section 3.5 reports that fluvastatin combined synergistically with itraconazole, ketoconazole, and fluconazole against C. albicans. But the combination assay measured inhibition, not fungicidal activity; the paper reports fungicidal concentrations for fluvastatin tested alone. The cited results also do not establish the combination effect across Candida species. Pitavastatin is attributed to a different citation and is not judged here. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Recent studies mentioned that combinations of ATO with azole drugs produced synergistic effects against different Candida sp.
“Similarly, the recent studies mentioned that combinations of ATO with azole drugs produced synergistic effects against different Candida sp. (Lima et al. 2019; Eldesouky et al. 2020).”
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 Lima et al. 2019
Section 3.5 reports that atorvastatin (ATO) was synergistic with itraconazole, ketoconazole and fluconazole against C. albicans. The paper’s combination results are limited to C. albicans, so this source does not establish the claimed effect across different Candida species. (LLM, conf=0.88)
Experimental — accuracy not yet measuredStatins inhibit HMG-CoA reductase, and their antimicrobial activity is thought to stem from inhibition of isoprenoid biosynthesis, disrupting ergosterol biosynthesis, G-protein signaling, and Ras-dependent pathways.
“Statins act as inhibitors of hydroxymethylglutaryl‐CoA (HMG‐CoA) reductase, and their antimicrobial activity is thought to stem from the inhibition of isoprenoid biosynthesis, thereby disrupting key processes in fungal physiology, including ergosterol biosynthesis, modulation of G‐protein signaling, and activation of Ras‐dependent pathways [18, 19].”
From Statins as Antifungal Agents: A Review on Drug Repurposing and Nanotechnology-Driven Delivery Strategies (2025) · cites this paper as [19]
Other studies mentioned that the antifungal activities of ATO and other statin drugs can be attributed to the inhibition of ergosterol and isoprenoid-biosynthesis.
“Other studies mentioned that the antifungal activates of ATO and other statin drugs can be attributed to the inhibition of ergosterol and isoprenoid-biosynthesis are thought to result in these antifungal properties (Rahal et al. 2015; Rodrigues 2018; 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 Lima et al. 2019
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Linolenic Acid-Modified MPEG-PEI Micelles for Encapsulation of Amphotericin B
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“A In the case of rosuvastatin and FLC, the combination is effective against C. albicans [73]. species.”
BackgroundLima, W. G., Brito, J. C. M., Nizer, W. S. D. C., & de Assis, D. C. S. (2022) · Biocatalysis and Agricultural Biotechnology · doi:10.1016/j.bcab.2022.102335 · Cited by 12 · see citing works
Self-citationAraújo, S. G., Lima, W. G., Pinto, M. E. A., Morais, M. Í., de Sá, N. P., Johann, S., Rosa, C. A., & Lima, L. A. R. D. S. (2019) · Biocatalysis and Agricultural Biotechnology · doi:10.1016/j.bcab.2019.101345 · Cited by 12 · see citing works
Self-citationLima, W. G., Araújo, M. G. D. F., Brito, J. C. M., Castilho, R. O., Cardoso, V. N., & Fernandes, S. O. A. (2022) · Journal de Mycologie Médicale · doi:10.1016/j.mycmed.2022.101255 · Cited by 11 · see citing works
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Spectrum of activity and mechanisms of azole–bisphosphonate synergy in pathogenic Candida
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Cardoso, B. G., Lima, W. G., Fernandes, S. O. A., de Lima, M. E., & Cardoso, V. N. (2022) · Natural Product Research · doi:10.1080/14786419.2022.2079122 · Cited by 8 · see citing works
Self-citationAbsence of farnesol salvage in Candida albicans and probably in other fungi
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Antifungal Evaluation of Benzoxazole and Benzothiazole Derivatives: An In Vitro and In Silico Study
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Topical statins as antifungals: a review
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Effect of statin therapy on oral Candida carriage in hyperlipidemia patients: A pioneer study
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Self-citation
- Authors
- Lima, W. G., Alves-Nascimento, L. A., Andrade, J. T., Vieira, L., de Azambuja Ribeiro, R. I. M., Thomé, R. G., dos Santos, H. B., Ferreira, J. M. S., & Soares, A. C.
- Affiliations
- Federal University of São João del-Rei (BR)
- Corresponding author
- Lima, William Gustavo
- ORCID
- Venue
- Biomedicine & Pharmacotherapy
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 111
- Pages
- 270-281
- ISSN
- 0753-3322 (ISSN-L)
- OpenAlex
- W2906561227
- Cited by
- 65
- References
- 49
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 13 · 2023: 3 · 2022: 12 · 2021: 7 · 2020: 13 · 2019: 5
- FWCI
- 4.72
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biomedicine & Pharmacotherapy (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fundação de Amparo à Pesquisa do Estado de Minas Gerais
- Universidade Federal de Minas Gerais
- Universidade Federal de São João del-Rei
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Keywords
- statins, antifungal activity, invasive candidiasis, intra-abdominal candidiasis, Candida albicans, Candida glabrata, fluvastatin, atorvastatin, rosuvastatin, drug repurposing, antifungal resistance, farnesol, yeast-to-hypha transition, biofilm, mouse model
- MeSH terms
- Animals, Antifungal Agents, Candida albicans, Dose-Response Relationship, Drug, Female, Cricetinae, Mesocricetus, Microbial Sensitivity Tests, Random Allocation, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Mice, Candidiasis, Invasive
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