Statins as antifungal agents
Open accessAbstract
Fungal infections are increasing and their treatment is difficult, because the most widely used antifungal drugs are relatively toxic and have serious side effects.Therefore, interest has focused on safely applicable and clinically introduced non-antifungal drugs, which have potent antifungal activity.Statins were originally used as cholesterol lowering agents in human therapy,
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Written from the paper’s full text.
TL;DR
Statins, originally cholesterol-lowering drugs, show in vitro antifungal activity against yeasts and filamentous fungi and can act additively or synergistically with antifungal agents. Because their MICs are much higher (about 1 order of magnitude) than maximum achievable serum concentrations, they are proposed only as combination therapy, with in vivo validation still needed.
Key findings
- Statins exhibit fungicidal or fungistatic effects against yeasts in a dose-dependent manner; SIM displayed the strongest anti-yeast activity, followed by FLV, ATO, ROS, and LOV, while PRA was completely ineffective. Against filamentous fungi, FLV was strongest, followed by ROS, SIM, LOV, and ATO; PRA was also ineffective.
- Statin MICs are much higher (about 1 order of magnitude) than their maximum achievable concentrations in human serum, so statins are not applicable as single antifungal agents for invasive fungal infections.
- Statins interact additively or synergistically with antifungal agents, including azoles, amphotericin B, nystatin, primycin, caspofungin, and voriconazole, against Candida, Cryptococcus, Zygomycetes, and Aspergillus species; terbinafine plus FLV against Pythium insidiosum was antagonistic.
- Clinically, a hypothesis that statins may reduce invasive mould infection in diabetes patients is supported by in vitro data, but a recent retrospective case-control study suggested statins may not decrease risk of invasive mould infection.
Methods
- Narrative review focusing on the antifungal activity of statins alone and in combination with antifungal and non-antifungal drugs, and their possible application in clinical therapy.
- Data summarized include published in vitro studies against yeasts and filamentous fungi, with MIC values presented in Tables 1 and 2 and drug-interaction results in Tables 3 and 4.
- Main analysis is a qualitative synthesis of reported MIC values and interaction classifications (synergy, additive, no interaction, antagonism); no primary experiments or systematic search methodology are described.
Limitations
- The paper states that statin MICs exceed achievable serum levels, so clinical use is possible only in combination with antifungal agents; further in vivo animal model experiments are needed to evaluate practical efficiency and side effects.
- The paper notes that combining statins with antifungals metabolized by the same CYP450 isoenzymes is contraindicated because of potential serious adverse effects.
- Evident from the text: this is a narrative review without stated systematic search or quality assessment, and many table entries are “ND” or formatting-corrupted, limiting quantitative certainty.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 68 cited sources checked · 0 supported · 0 flagged
- Premisecitation
LOV does not cause apoptotic cell death in yeasts compared to filamentous fungi.
“LOV does not cause apoptotic cell death in yeasts compared to filamentous fungi [24,31] .”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation
Supplementation with ergosterol or cholesterol reduced the antifungal effect of statins.
“This assumption is confirmed by the observation that supplementation with ergosterol or cholesterol reduced the antifungal effect of statins [20,25,26] , and that C. albicans transformed from the yeast cell form to the”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [20] Lorenz RT, Parks LW. Effects of lovastatin (mevinolin) on sterol levels and on activity of azoles in Saccharomyces cerevisiae. Antimicrob Agents Chemother 1990;34:1660-1665. source
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- cites [25] source
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- Premisecitation
C. albicans transformed from the yeast cell form to the pseudomycelial form upon exposure to LOV.
“pseudomycelial form upon exposure to LOV [24] .”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [24] source
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- Premisecitation
Statins act as inhibitors of some G-protein actions and Ras or Ras-like signaling, affecting several important bioprocesses.
“Thus, statins act as inhibitors of some G-protein actions and Ras or Ras-like signaling, which affect several important bioprocesses [15] .”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] source
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- Premisecitation
The antifungal activity of FLV is dependent on the pH of the medium.
“The antifungal activity of FLV is dependent on the pH of the medium [27] .”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [27] source
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- Premisecitation
Statins inhibit synthesis of important isoprenoids such as farnesyl pyrophosphate and geranylgeranyl pyrophosphate, which are lipid attachments for the γ subunit of heterotrimeric G-proteins, Ras, and Ras-like proteins.
“Thus, the effects of statins are connected with the inhibition of the synthesis of important isoprenoids, e.g.farnesyl pyrophosphate and geranylgeranyl pyrophosphate, which are important lipid attachments for the γ subunit of heterotrimeric G-proteins [12] , guanosine triphosphatebinding protein Ras, and Ras-like proteins (Rho, Rab, Rac, Ral, or Rap) [12][13][14] .”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [12] source
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- cites [13] Liao JK. Isoprenoids as mediators of the biological effects of statins. J Clin Invest 2002;110:285-288. source
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- cites [14] Ghittoni R, Patrussi L, Pirozzi K, Pellegrini M, Lazzerini PE, Capecchi PL, Pasini FL, Baldari CT. Simvastatin inhibits T-cell activation by selectively impairing the function of Ras superfamily GTPases. FASEB J 2005;19:605-607. source
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- Premisecitation
Statins exhibit fungicidal or fungistatic effects against yeasts in a dose-dependent manner.
“Statins exhibit fungicidal or fungistatic effects against yeasts in a dose dependent-manner.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] source
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- Premisecitation
The inhibition activity of statins on the growth of filamentous fungi was revealed in several zygomycetous and ascomycetous fungal species.
“The inhibition activity of statins on the growth of filamentous fungi was revealed in the cases of several zygo- [18,19,28,[31][32][33][34][35] and ascomycetous fungal species [18,25,28,29,36,37] .”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [18] source
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- cites [19] source
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- cites [28] Nyilasi I, Kocsubé S, Galgóczy L, Papp T, Pesti M, Vágvölgyi C. Effect of different statins on the antifungal activity of polyene antimycotics. Acta Biol Szeged 2010;54:33-36.
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- Premisecitation
Statins compete with the natural substrate for HMG-CoA reductase's active site, preventing the formation of a functional enzyme structure with reversible binding.
“Statins compete with the natural substrate for the enzyme's active site, preventing the formation of a functional enzyme structure with reversible binding [11] .”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [11] source
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- Premisecitation
Generally, synthetic statins are more effective than natural statins.
“Generally, the synthetic statins are more effective than the natural ones [18,19] .”
Quote in the paperNot a substantial claim0 of 2 sources checked - Interpretationcitation
In clinical practice, administration of statins together with antifungals metabolized by different cytochrome P450 isoenzymes in the liver suggests that drug interactions with the CYP system and serious adverse effects (e.g. myopathy) are avoidable.
“In clinical practice, the administration of statins together with antifungals, which are metabolized by different cytochrome P450 (CYP450) isoenzymes in the liver, suggests that the drug interactions with the CYP system and the serious adverse effects (e.g.myopathy) are avoidable [45] .”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [45] source
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- Rests on an assumption: Statins are safely applicable in humans at doses relevant to antifungal combination therapy.
- Premisecitation
An antifungal peptide secreted by Penicillium chrsyogenum (PAF) and suramin can decrease growth of zygomyceteous fungal species in the presence of different statins.
“An antifungal peptide secreted by Penicillium chrsyogenum (Penicillium chrsyogenum antifungal protein; PAF) and a hexasulfonated naphtylurea, suramin (originally applied as an agent for treatment of parasitic infections) can decrease the growth of zygomyceteous fungal species in the presence of different statins [34,35] .”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Supplementation of sterols to the medium reduces the antifungal activity of statins, as in yeasts.
“Furthermore, supplementation of sterols to the medium reduces the antifungal activity of statins, as in the case of yeasts [25] .”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [25] source
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- Premisecitation
Drug interactions were revealed between statins and nonantifungal drugs that have secondary antifungal activity.
“Drug interactions were revealed between statins and nonantifungal drugs, which have a secondary antifungal activity.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Remarkable antifungal effects were observed on growth of Rhizopus oryze when primycin was combined with statins in concentrations that could not inhibit fungal growth alone.
“Remarkable antifungal effects were observed on the growth of Rhizopus oryze when PN was combined with statins in concentrations that could not inhibit the fungal growth alone [18] .”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] source
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- Premisecitation
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] .”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [29] source
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- Premisecitation
Both synergistic and additive effects were observed on growth reduction of C. albicans and C. glabrata when primycin was combined with FLV, LOV, or SIM.
“Both synergistic and additive effects were observed on the growth reduction of C. albicans and C. glabrata when primycin (PN), a non-polyene macrolide lactone antibiotic complex, was combined with FLV, LOV, or SIM [18] .”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [18] source
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- Premisecitation
In vitro, FLV and ROS acted synergistically and additively with AMB in inhibiting growth of Zygomycetes over clinically available concentration ranges in human serum.
“In vitro, FLV and ROS acted synergistically and additively with AMB in inhibiting the growth of fungi belonging to Zygomycetes over their clinically available concentration ranges in human serum [19] .”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [19] source
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- Premisecitation
Statins induce apoptosis-like cell death in filamentous fungi.
“Beyond to the harmful effects on membrane fluidity and the synthesis of important isoprenoids for cell signaling and vital processes (such as cell proliferation and differentiation), and protein prenylation [16] , statins induce apoptosis-like cell death in filamentous fungi [15,30,31] .”
Quote in the paperSubstantial claim0 of 3 sources checked - Premisecitation
Synergistic and/or additive interaction of AMB, caspofungin, VCZ, and primycin with FLV on growth reduction of Aspergillus fumigatus was demonstrated.
“Synergistic and/or additive interaction of AMB, caspofungin, VCZ, PN with FLV on the growth reduction of Aspergillus fumigatus was demonstrated [28,37] .”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [28] Nyilasi I, Kocsubé S, Galgóczy L, Papp T, Pesti M, Vágvölgyi C. Effect of different statins on the antifungal activity of polyene antimycotics. Acta Biol Szeged 2010;54:33-36.
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- cites [37] source
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- Premisecitation
Synergistic and additive interactions were revealed between statins and antifungal agents in zygomycetous fungal species.
“Synergistic and additive interactions were revealed between statins and antifungal agents in the case of zygomycetous fungal species [18,19,28,29,33] .”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [18] source
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- cites [19] source
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- cites [28] Nyilasi I, Kocsubé S, Galgóczy L, Papp T, Pesti M, Vágvölgyi C. Effect of different statins on the antifungal activity of polyene antimycotics. Acta Biol Szeged 2010;54:33-36.
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- Premisecitation
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] .”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [29] source
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- Premisecitation
AMB acted additively with ATO and FLV against Aspergillus flavus.
“AMB acted additively with ATO and FLV against Aspergillus flavus [28] .”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [28] Nyilasi I, Kocsubé S, Galgóczy L, Papp T, Pesti M, Vágvölgyi C. Effect of different statins on the antifungal activity of polyene antimycotics. Acta Biol Szeged 2010;54:33-36.
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- Premisecitation
Terbinafine acted antagonistically in combination with FLV against P. insidiosum, with reduced antifungal activity compared to when they were applied alone.
“Terbinafine acted antagonistically in combination with FLV against P. insidiosum.Reduced antifungal activity was observed for their combination compared to when they were applied alone [38] .”
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- Premisecitation
Interaction was not demonstrated between PRA or FLV and fluconazole.
“however, interaction was not demonstrated between PRA or FLV and FCZ [23] .”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [23] Nash JD, Burgess DS, Talbert RL. Effect of fluvastatin and pravastatin, HMG-CoA reductase inhibitors, on fluconazole activity against Candida albicans. J Med Microbiol 2002;51:105-109. source
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- Premisecitation
FLV acted additively with AMB, fluconazole, and itraconazole against C. albicans and C. neoformans.
“FLV acted additively with AMB, FCZ, and ITZ against C. albicans and C. neoformans [21] .”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [21] Chin NX, Weitzman I, Della-Latta P. In vitro activity of fluvastatin, a cholesterol-lowering agent, and synergy with flucanazole and itraconazole against Candida species and Cryptococcus neoformans. Antimicrob Agents Chemother 1997;41:850-852. source
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- Premisecitation
A number of studies detail beneficial effects of statins in transplant or non-transplant recipients with sepsis or infection.
“A number of studies detail the beneficial effects of statins in transplant or non-transplant recipients with sepsis or infection [16] .”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [16] source
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- Interpretationcitation
Statins are not applicable as single antifungal agents for treatment of IFI because their MICs are about one order of magnitude higher than their maximum achievable concentrations in human serum.
“Statins are not applicable as single antifungal agents for the treatment of IFI because their MICs are much higher (about 1 order of magnitude) than their maximum achievable concentrations in human serum [11,[40][41][42][43][44][45] .”
Quote in the paperSubstantial claim0 of 3 sources checked
- May combine two claims. 16
- Classified as probably not a substantial claim. 2
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PremisecitationErgosterol is a main constituent of the lipid layer of fungal plasma membranes, and the antifungal effect might arise from decreased membrane fluidity in yeast cells.
“Ergosterol is a main constituent of the lipid layer of fungal plasma membranes, and the antifungal effect might arise from decreased membrane fluidity in the yeast cells [24] .”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [24] source
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May combine two claims.
PremisecitationThe various statins exhibit different antifungal effects against yeasts; SIM displays the strongest activity, followed by FLV, ATO, ROS, and LOV, while PRA is completely ineffective.
“These studies demonstrated that the various statins exhibit different antifungal effects against yeasts.SIM displayed the strongest antifungal activity, followed by FLV, ATO, ROS, and LOV.PRA proved to be completely ineffective against them.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [18] source
Not checked in the free run.
- cites [20] Lorenz RT, Parks LW. Effects of lovastatin (mevinolin) on sterol levels and on activity of azoles in Saccharomyces cerevisiae. Antimicrob Agents Chemother 1990;34:1660-1665. source
Not checked in the free run.
- cites [21] Chin NX, Weitzman I, Della-Latta P. In vitro activity of fluvastatin, a cholesterol-lowering agent, and synergy with flucanazole and itraconazole against Candida species and Cryptococcus neoformans. Antimicrob Agents Chemother 1997;41:850-852. source
Not checked in the free run.
May combine two claims.
PremisecitationStatins are competitive inhibitors of HMG-CoA reductase, which catalyses the conversion of HMG-CoA to mevalonate, a rate-limiting step in the isoprenoid biosynthetic pathway involved in cholesterol synthesis in humans and ergosterol synthesis in fungi.
“Statins are competitive inhibitors of HMG-CoA reductase, which catalyses the conversion of HMG-CoA to mevalonate, a rate-limiting step in the isoprenoid biosynthetic pathway, which is involved in the synthesis of cholesterol in humans and ergosterol in fungi [10] .”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [10] source
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May combine two claims.
PremisecitationThe different fungi are not equally sensitive to statins in vitro; SIM exhibits the strongest antifungal activity against yeasts compared to filamentous fungi, whereas the reverse is true for FLV.
“The different fungi are not equally sensitive to statins in vitro, e.g.SIM exhibits the strongest antifungal activity against yeasts compared to filamentous fungi, whereas the reverse is true for FLV [18] .”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [18] source
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PremisecitationNatural statins (e.g. SIM and LOV) mainly exert antifungal activity in their active metabolite forms (hydrolysis of the lactone ring at pH 10) and are less effective as pro-drugs.
“The natural statins (e.g.SIM and LOV) mainly effect their antifungal activity in their active metabolite forms (hydrolysis of the lactone ring at pH 10), and they proved to be less effective as pro-drugs [18,19] .”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationThe growth inhibition effect of statins on yeast cells is related to decreasing ergosterol level, which occurs because of inactivation of HMG-CoA reductase by statins in the isoprenoid biosynthetic pathway.
“The growth inhibition effect of statins on yeast cells is related to the decreasing ergosterol level, which occurs because of the inactivation of HMG-CoA reductase inactivation by statins in the isoprenoid biosynthetic pathway [16] .”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [16] source
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PremisecitationStatins have effective antifungal potential against both yeast and filamentous fungi and can be combined with clinically used antifungal agents.
“Statins are interesting from this respect, as they have effective antifungal potential against both yeast and filamentous fungi; furthermore, they can be combined with clinically used antifungal agents.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] source
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PremisecitationInteractions were not detected between FLV and suramin if the strain was insensitive to both compounds, but synergistic and additive interactions were observed if the fungus was sensitive to FLV and insensitive to suramin; antagonistic interaction was observed if the fungus was sensitive to both drugs.
“Interactions were not detected between FLV and suramin if the investigated strain proved to be insensitive to both compounds, but synergistic and additive interactions could be observed if the fungus was sensitive to FLV and insensitive to suramin.Antagonistic interaction was observed if the fungus was sensitive to both drugs [35] .”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [35] source
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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationAs a consequence of pleiotropic beneficial effects of statins beyond lipid lowering, there is decreased risk of chronic renal failure and improved endothelial dysfunction.
“As a consequence of the pleiotropic beneficial effects of statins beyond their lipid lowering attributes, there is a decreased risk of chronic renal failure and an improved endothelial dysfunction) [16] .”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [16] source
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May combine two claims.
InterpretationcitationStatins should be promising agents in clinical practice because they can act additively or synergistically with antifungal agents, allowing substantial decreases in therapeutic concentrations and side effects.
“All the same, they should be promising agents in clinical practice because they can act additively or synergistically with antifungal agents, allowing substantial decreases in their therapeutic concentrations and their side effects [45] .”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [45] source
Not checked in the free run.
- Rests on an assumption: In vitro antifungal activity and drug interactions of statins are predictive of clinical efficacy in treating invasive fungal infections.
May combine two claims.
PremisecitationStatins can interact synergistically with azole antifungal agents against yeasts and can reduce their growth significantly.
“Statins can interact synergistically with azole antifungal agents against yeasts and can reduce their growth significantly.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [21] Chin NX, Weitzman I, Della-Latta P. In vitro activity of fluvastatin, a cholesterol-lowering agent, and synergy with flucanazole and itraconazole against Candida species and Cryptococcus neoformans. Antimicrob Agents Chemother 1997;41:850-852. source
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- cites [22] source
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Probably not a substantial claim: may not pass S2 (checkable).
InterpretationreasoningSuch combinations would be advantageous as the basis of a less toxic antifungal therapy.
“Such combinations would be advantageous as the basis of a less toxic antifungal therapy [3] .”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [3] source
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- Rests on an assumption: In vitro antifungal activity and drug interactions of statins are predictive of clinical efficacy in treating invasive fungal infections.
May combine two claims.
PremisecitationThe activities of statin-PAF combinations varied and depended on the activities of the components applied separately; when a strain was resistant to one component, significant interactions could not be detected, and when sensitive to both, synergistic or additive interactions were detected.
“The activities of the statin-PAF combinations on the different strains varied, and depended on the activities of the components applied separately.When a strain was resistant to one of the components, significant interactions could not be detected.On the other hand, when a strain was sensitive to both types of antifungal agents, synergistic or additive interactions were detected [34] .”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [34] source
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May combine two claims.
PremisecitationSynergistic interaction was observed between primycin and FLV, LOV and SIM, and additive interaction between AMB and ATO or SIM in Paecilomyces variotii.
“Synergistic interaction was observed between PN and FLV, LOV and SIM, and an additive interaction was observed between AMB and ATO or SIM in the case of Paecilomyces variotii [18,28] .”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [18] source
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- cites [28] Nyilasi I, Kocsubé S, Galgóczy L, Papp T, Pesti M, Vágvölgyi C. Effect of different statins on the antifungal activity of polyene antimycotics. Acta Biol Szeged 2010;54:33-36.
Not checked in the free run.
May combine two claims.
PremisecitationAdditive interactions were observed between AMB and ATO and ROS, and between nystatin and FLV, LOV, ROS, and SIM in C. albicans and C. glabrata.
“Additive interactions were observed between AMB and ATO and ROS, and between nystatin (NYS) and FLV, LOV, ROS, and SIM in the case of C. albicans and C. glabrata [28] .”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [28] Nyilasi I, Kocsubé S, Galgóczy L, Papp T, Pesti M, Vágvölgyi C. Effect of different statins on the antifungal activity of polyene antimycotics. Acta Biol Szeged 2010;54:33-36.
Not checked in the free run.
May combine two claims.
InterpretationcitationAdministration of statins together with antifungals predominantly metabolized by the same CYP450 isoenzymes in the liver is contraindicated, because such drug interactions may cause serious adverse effects.
“Importantly, the administration of statins together with antifungals that are predominantly metabolized by the same CYP450 isoenzymes in the liver is contraindicated, because such drug interactions with the CYP system may cause serious adverse effects [45] .”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [45] source
Not checked in the free run.
- Rests on an assumption: Statins are safely applicable in humans at doses relevant to antifungal combination therapy.
May combine two claims.
PremisecitationFluconazole with LOV, and fluconazole or itraconazole with FLV, interact synergistically on the growth of Candida species.
“Fluconazole (FCZ) with LOV, and FCZ or itraconazole (ITZ) with FLV, interact synergistically on the growth of Candida species [21,22] ;”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [21] Chin NX, Weitzman I, Della-Latta P. In vitro activity of fluvastatin, a cholesterol-lowering agent, and synergy with flucanazole and itraconazole against Candida species and Cryptococcus neoformans. Antimicrob Agents Chemother 1997;41:850-852. source
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- cites [22] source
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The paper relies on this without support.
The incidence of invasive fungal infections is increasing.
“The incidence of invasive fungal infections (IFIs) is increasing because of the growing number of immunocompromised hosts and the occurrence of antibiotic resistant strains.”
The paper relies on this without support.
The most widely applied antifungal drugs for invasive fungal infections are relatively toxic and have serious side effects.
“Treatment of IFIs is difficult, because the most widely applied antifungal drugs [e.g.amphotericin B (AMB)] for treatment of such disease are relatively toxic and have serious side effects.”
The authors state this as an assumption.
The different levels of fungal resistance to statins are connected with different copy numbers of the HMG-CoA reductase gene (hmgR) in filamentous species.
“It is hypothesized that the resistance is connected with the different copy numbers of the HMG-CoA reductase gene (hmgR) in the case of filamentous species.This assumption is supported by the observation of Lukács et al [39] .”
The paper relies on this without support.
In vitro antifungal activity and drug interactions of statins are predictive of clinical efficacy in treating invasive fungal infections.
“The observed in vitro antifungal activities of statins and their combinations with clinically antifungal agents would create new therapies for the treatment of IFI, without serious side effects.”
The paper relies on this without support.
Statins are safely applicable in humans at doses relevant to antifungal combination therapy.
“These synergistic combinations establish a basis for a new safely applicable therapy.”
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Mechanisms of Statin-mediated Inhibition of Small G-protein Function
Cordle, A., Koenigsknecht-Talboo, J., Wilkinson, B., Limpert, A., & Landreth, G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505268200 · Cited by 235 · see citing works
Biotechnological production and applications of statins
Barrios-González, J., & Miranda, R. (2009) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-009-2239-6 · Cited by 194 · see citing works
Ghittoni, R., Patrussi, L., Pirozzi, K., Pellegrini, M., Lazzerini, P. E., Capecchi, P. L., Pasini, F. L., & Baldari, C. T. (2005) · The FASEB Journal · doi:10.1096/fj.04-2702fje · Cited by 154 · see citing works
Growth inhibition of<i>Candida</i>species and<i>Aspergillus fumigatus</i>by statins
Macreadie, I. G., Johnson, G., Schlosser, T., & Macreadie, P. I. (2006) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2006.00370.x · Cited by 136 · see citing works
Pitavastatin: Efficacy and Safety Profiles of A Novel Synthetic HMG‐CoA Reductase Inhibitor
Kajinami, K., Takekoshi, N., & Saito, Y. (2003) · Cardiovascular Drug Reviews · doi:10.1111/j.1527-3466.2003.tb00116.x · Cited by 136 · see citing works
Chamilos, G., Lewis, R. E., & Kontoyiannis, D. P. (2006) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.50.1.96-103.2006 · Cited by 121 · see citing works
Lorenz, R. T., & Parks, L. W. (1990) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.34.9.1660 · Cited by 104 · see citing works
Chin, N. X., Weitzman, I., & Della-Latta, P. (1997) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.41.4.850 · Cited by 101 · see citing works
Cholesterol-independent Effects of Statins and New Therapeutic Targets: Ischemic Stroke and Dementia
Miida, T., Hirayama, S., & Nakamura, Y. (2004) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.11.253 · Cited by 97 · see citing works
Lovastatin Triggers an Apoptosis-like Cell Death Process in the FungusMucor racemosus
Roze, L. V., & Linz, J. E. (1998) · Fungal Genetics and Biology · doi:10.1006/fgbi.1998.1093 · Cited by 96 · see citing works
Nyilasi, I., Kocsubé, S., Krizsán, K., Galgóczy, L., Pesti, M., Papp, T., & Vágvölgyi, C. (2010) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2010.01972.x · Cited by 83 · see citing works
Self-citationWestermeyer, C., & Macreadie, I. G. (2007) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2006.00194.x · Cited by 73 · see citing works
Kontoyiannis, D. P. (2007) · Clinical Infectious Diseases · doi:10.1086/512817 · Cited by 69 · see citing works
Pharmacokinetic Interactions Between Statins and Fibrates
Corsini, A., Bellosta, S., & Davidson, M. H. (2005) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2005.08.007 · Cited by 69 · see citing works
Antifungal activity of statins againstAspergillusspecies
Qiao, J., Kontoyiannis, D. P., Wan, Z., Li, R., & Liu, W. Y. (2007) · Medical Mycology · doi:10.1080/13693780701397673 · Cited by 69 · see citing works
Sun, H., & Singh, N. (2009) · Clinical Infectious Diseases · doi:10.1086/597039 · Cited by 65 · see citing works
Antifungal Activity of Nonantifungal Drugs
Afeltra, J., & Verweij, P. E. (2003) · European Journal of Clinical Microbiology & Infectious Diseases · doi:10.1007/s10096-003-0947-x · Cited by 63 · see citing works
Song, J. L., Lyons, C. N., Holleman, S., Oliver, B. G., & White, T. C. (2003) · Medical Mycology · doi:10.1080/1369378031000137233 · Cited by 62 · see citing works
Gyetvai, Ã., Emri, T., Takács, K., Dergez, T., Fekete, A., Pesti, M., Pócsi, I., & Lenkey, B. (2006) · FEMS Yeast Research · doi:10.1111/j.1567-1364.2006.00097.x · Cited by 53 · see citing works
Current Status and Future of Antifungal Therapy for Systemic Mycoses
Nosanchuk, J. D. (2006) · Recent Patents on Anti-Infective Drug Discovery · doi:10.2174/157489106775244109 · Cited by 50 · see citing works
NASH, J. D., BURGESS, D. S., & TALBERT, R. L. (2002) · Journal of Medical Microbiology · doi:10.1099/0022-1317-51-2-105 · Cited by 44 · see citing works
Cavalheiro, A. S., Zanette, R. A., Spader, T. B., Lovato, L., Azevedo, M. I., Botton, S., Alves, S. H., & Santurio, J. M. (2009) · Veterinary Microbiology · doi:10.1016/j.vetmic.2009.01.036 · Cited by 42 · see citing works
Differentiation of Rhizomucor Species on the Basis of Their Different Sensitivities to Lovastatin
Lukács, G., Papp, T., Nyilasi, I., Nagy, E., & Vágvölgyi, C. (2004) · Journal of Clinical Microbiology · doi:10.1128/jcm.42.11.5400-5402.2004 · Cited by 40 · see citing works
Galgóczy, L., Papp, T., Lukács, G., Leiter, Ã., Pócsi, I., & Vágvölgyi, C. (2007) · FEMS Microbiology Letters · doi:10.1111/j.1574-6968.2007.00661.x · Cited by 37 · see citing works
Self-citationNyilasi, I., Kocsubé, S., Pesti, M., Lukács, G., Papp, T., & Vágvölgyi, C. (2010) · Journal of Medical Microbiology · doi:10.1099/jmm.0.013946-0 · Cited by 35 · see citing works
Fluvastatin potentiates the activity of caspofungin against Aspergillus fumigatus in vitro
Natesan, S. K., Chandrasekar, P. H., Alangaden, G. J., & Manavathu, E. K. (2008) · Diagnostic Microbiology and Infectious Disease · doi:10.1016/j.diagmicrobio.2007.10.015 · Cited by 32 · see citing works
Galgóczy, L., Lukács, G., Nyilasi, I., Papp, T., & Vágvölgyi, C. (2010) · Acta Biologica Hungarica · doi:10.1556/abiol.61.2010.3.11 · Cited by 23 · see citing works
Self-citationAre Statins Applicable for the Prevention and Treatment of Zygomycosis?
Galgóczy, L., Nyilasi, I., Papp, T., & Vágvölgyi, C. (2009) · Clinical Infectious Diseases · doi:10.1086/600825 · Cited by 22 · see citing works
Self-citationTaxonomy of actinomycetes capable of hydroxylation of ML-236B (compactin)
OKAZAKI, T., Serizawa, N., Enokita, R., et al. (1983) · The Journal of Antibiotics · doi:10.7164/antibiotics.36.1176 · Cited by 20 · see citing works
Lukács, G., Papp, T., Somogyvári, F., Csernetics, Á., Nyilasi, I., & Vágvölgyi, C. (2009) · Antonie van Leeuwenhoek · doi:10.1007/s10482-008-9287-2 · Cited by 19 · see citing works
<i>In vitro</i> interaction between suramin and fluvastatin against clinically important Zygomycetes
Galgóczy, L., Papp, T., & Vágvölgyi, C. (2009) · Mycoses · doi:10.1111/j.1439-0507.2008.01634.x · Cited by 14 · see citing works
Self-citationCase–control study of statin prevention of mould infections
Thompson, J. N., Huycke, M. M., Greenfield, R. A., Kurdgelashvili, G., & Gentry, C. A. (2011) · Mycoses · doi:10.1111/j.1439-0507.2010.01957.x · Cited by 14 · see citing works
L’activité antifongique des statines
Lefebvre, M., ALshawa, K., & Dupont, B. (2010) · Journal de Mycologie Médicale · doi:10.1016/j.mycmed.2010.05.007 · Cited by 12 · see citing works
Lyons, K., & Harbinson, M. (2009) · The Journal of the Royal College of Physicians of Edinburgh · doi:10.4997/jrcpe.2009.425 · Cited by 11 · see citing works
Effect of different statins on the antifungal activity of polyene antimycotics
Nyilasi, I., Kocsubé́, S., Galgóczy, L., Papp, T., Pesti, M., & Vágvölgyi, C. (2010) · Acta Biologica Szegediensis · Cited by 10 · see citing works
Self-citationInhibition of<i>Candida albicans</i>by Fluvastatin Is Dependent on pH
Schmidt, M., Dzogbeta, S., & Boyer, M. P. (2009) · Research Letters in Biochemistry · doi:10.1155/2009/151424 · Cited by 7 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Buemi M, Floccari F, Nostro L, Campo S, Caccamo C, Sturiale A, Aloisi C, Giacobbe MS, Frisina N. Statins in the prevention of cardiovascular events in patients with renal failure. Cardiovasc Hematol Disord Drug Targets 2007;7:7-13.
Cited by
Sorted by citations
Assessment of the in vitro and in vivo activity of atorvastatin against Candida albicans.
Ajdidi, A., Sheehan, G., Abu Elteen, K., & Kavanagh, K. (2019) · Journal of medical microbiology · doi:10.1099/jmm.0.001065 · Cited by 18 · see citing works
Topical statins as antifungals: a review
Khoury, D. M., Ghaoui, N., El Tayar, E., Dagher, R., El Hawa, M., Rubeiz, N., Abbas, O., & Kurban, M. (2024) · International Journal of Dermatology · doi:10.1111/ijd.17068 · Cited by 3 · see citing works
Multifunctionality of statins as antimicrobials
Plotkin, B. J., Borrelli, A., Erbst, M., Zheng, V., Konaklieva, M. I., Schileru, N., & Sigar, I. M. (2022) · World Journal of Biology Pharmacy and Health Sciences · doi:10.30574/wjbphs.2022.11.3.0114 · Cited by 1 · see citing works
- Authors
- Galgóczy, L.
- Affiliations
- Ben-Gurion University of the Negev (IL)
- Corresponding author
- Galgóczy, László
- ORCID
- Galgóczy, László
- Venue
- World Journal of Clinical Infectious Diseases
- Publisher
- Baishideng Publishing Group Inc.
- Published
- 2011
- Volume
- 1
- Issue
- 1
- Pages
- 4
- ISSN
- 2220-3176 (ISSN-L)
- OpenAlex
- W2329049973
- Semantic Scholar
- 636be1f938e569164ce008a558408cb70c5f2eab
- Cited by
- 21
- References
- 45
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 2 · 2015: 3 · 2014: 2 · 2013: 2
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- World Journal of Clinical Infectious Diseases (publishedVersion, cc-by-nc)
- SZTE Publicatio Repozitórium (University of Szeged) (acceptedVersion, other-oa)
- Funders
- Hungarian Scientific Research Fund
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- statins, antifungal activity, fungal infection, drug repurposing, antifungal toxicity
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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