The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Lovastatin Has Significant Activity against Zygomycetes and Interacts Synergistically with Voriconazole
Open accessAbstract
Zygomycetes are emerging opportunistic molds resistant to most conventional antifungals. We evaluated the in vitro activity of lovastatin (LOV), a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, against seven clinical isolates of Zygomycetes by using standard microdilution methods in three different media, disk diffusion testing, and viability dye staining. To further study the in vivo efficacy of LOV against zygomycetes, we developed a Drosophila melanogaster model of zygomycosis. In different experiments, groups of Toll-deficient ( Tl ) flies fed LOV-containing food were subsequently injected with two representative Zygomycetes isolates ( Mucor and Rhizopus spp.). Finally, we examined the effects of LOV on voriconazole (VRC) activity against zygomycetes in vitro by checkerboard dilution, Epsilometer test-based methods, and bis-(1,3-dibutylbarbituric acid) trimethine oxonol staining and in vivo in Tl flies fed food containing LOV plus VRC and infected with zygomycetes. LOV exhibited significant, medium, and strain-independent fungicidal activity against all Zygomycetes isolates in vitro by all testing methods (MIC 50 , 48.0 μg/ml; 50% minimal fungicidal concentration, 56.0 μg/ml; 50% effective concentration, 29.4 μg/ml [6.6 to 38.9 μg/ml]). Tl flies fed LOV-containing food and infected with Mucor had a significantly better 6-day survival rate than did infected Tl flies fed regular food ( P = 0.0005). LOV displayed in vitro synergy with VRC against all Zygomycetes isolates (fractional inhibitory concentration index, 0.104 to 0.290) by all methods used. LOV also displayed synergy with VRC in the Drosophila model of zygomycosis ( P < 0.01). LOV is significantly active against zygomycetes and synergizes with triazoles inherently resistant to them, such as VRC. The clinical significance of these findings needs to be further explored.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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 Chamilos et al. 2006
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“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 Chamilos et al. 2006
Experimental — accuracy not yet measuredIn the citing paper
“In this context, studies on the interaction between azoles and statins have gained renewed attention.10,11,27,32,37”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Amplification and direct sequencing of fungal ribosomal RNA genes for phylogenetics
White, T. J., Bruns, T., Lee, S., & Taylor, J. (1990) · PCR Protocols · doi:10.1016/b978-0-12-372180-8.50042-1 · Cited by 36,648
National Committee for Clinical Laboratory Standards
Bruck, E. (1980) · PEDIATRICS · doi:10.1542/peds.65.1.187 · Cited by 14,736
PCR protocols — A guide to methods and applications
(1990) · Trends in Genetics · doi:10.1016/0168-9525(90)90186-a · Cited by 11,827
Lemaître, B., Nicolas, E., Michaut, L., Reichhart, J., & Hoffmann, J. A. (1996) · Cell · doi:10.1016/s0092-8674(00)80172-5 · Cited by 4,224
Ribes, J. A., Vanover-Sams, C. L., & Baker, D. J. (2000) · Clinical Microbiology Reviews · doi:10.1128/cmr.13.2.236-301.2000 · Cited by 1,702
Kontoyiannis, D. P., Lionakis, M. S., Lewis, R. E., Chamilos, G., Healy, M., Perego, C., Safdar, A., Kantarjian, H. M., Champlin, R. E., Walsh, T. J., et al. (2005) · The Journal of Infectious Diseases · doi:10.1086/428780 · Cited by 674
Self-citationWalsh, T. J., Hiemenz, J. W., Seibel, N. L., Perfect, J. R., Horwith, G., Lee, L., Silber, J. L., DiNubile, M. J., Reboli, A. C., Bow, E. J., et al. (1998) · Clinical Infectious Diseases · doi:10.1086/516353 · Cited by 623
The statins as anticancer agents.
Chan, K., Oza, A. M., & Siu, L. L. (2003) · PubMed · Cited by 607
Sun, Q. N., Fothergill, A. W., McCarthy, D. I., Rinaldi, M. G., & Graybill, J. R. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.46.5.1581-1582.2002 · Cited by 365
In vitro susceptibilities of zygomycetes to conventional and new antifungals
Dannaoui, É. (2002) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkg020 · Cited by 312
Bowman, J. C., Hicks, P. S., Kurtz, M. B., Rosen, H., Schmatz, D. M., Liberator, P. A., & Douglas, C. M. (2002) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.46.9.3001-3012.2002 · Cited by 303
Wilding, E. I., Brown, J. R., Bryant, A. P., Chalker, A. F., Holmes, D. J., Ingraham, K. A., Iordănescu, S., So, C. Y., Rosenberg, M. J., & Gwynn, M. N. (2000) · Journal of Bacteriology · doi:10.1128/jb.182.15.4319-4327.2000 · Cited by 261
Zygomycosis (mucormycosis): emerging clinical importance and new treatments
Greenberg, R. N., Scott, L. J., Vaughn, H. H., & Ribes, J. A. (2004) · Current Opinion in Infectious Diseases · doi:10.1097/00001432-200412000-00003 · Cited by 257
Lovastatin augments apoptosis induced by chemotherapeutic agents in colon cancer cells.
Agarwal, B., Bhendwal, S., Halmos, B., Moss, S. F., Ramey, W. G., & Holt, P. R. (1999) · PubMed · Cited by 251
Analysis of Growth Characteristics of Filamentous Fungi in Different Nutrient Media
Meletiadis, J., Meis, J. F. G. M., Mouton, J. W., & Verweij, P. E. (2001) · Journal of Clinical Microbiology · doi:10.1128/jcm.39.2.478-484.2001 · Cited by 241
Lewis, R. E. (2002) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/49.2.345 · Cited by 226
Self-citationEspinel-Ingroff, A., Fothergill, A., Peter, J., Rinaldi, M. G., & Walsh, T. J. (2002) · Journal of Clinical Microbiology · doi:10.1128/jcm.40.9.3204-3208.2002 · Cited by 203
Colorimetric Assay for Antifungal Susceptibility Testing of Aspergillus Species
Meletiadis, J., Mouton, J. W., Meis, J. F. G. M., Bouman, B. A., Donnelly, J. P., Verweij, P. E., & EUROFUNG Network (2001) · Journal of Clinical Microbiology · doi:10.1128/jcm.39.9.3402-3408.2001 · Cited by 162
Phase II Study of High-Dose Lovastatin in Patients with Advanced Gastric Adenocarcinoma
Kim, W. S., Kim, M. M., Choi, H. J., Yoon, S., Lee, M. H., Park, K., Park, C. H., & Kang, W. K. (2001) · Investigational New Drugs · doi:10.1023/a:1006481423298 · Cited by 137
Antiviral Activity of Lovastatin against Respiratory Syncytial Virus In Vivo and In Vitro
Gower, T. L., & Graham, B. S. (2001) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.45.4.1231-1237.2001 · Cited by 129
Lewis, R. E., Wiederhold, N. P., & Klepser, M. E. (2005) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.49.3.945-951.2005 · Cited by 129
Self-citationRegulation of intracellular actin polymerization by prenylated cellular proteins
Fenton, R. G., Kung, H., Longo, D., & Smith, M. (1992) · The Journal of Cell Biology · doi:10.1083/jcb.117.2.347 · Cited by 116
Urbina, J. A., Lazardi, K., Marchán, E., Visbal, G., Aguirre, T., Piras, M. M., Piras, R., Maldonado, R. A., Payares, G., & de Souza, W. (1993) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.37.3.580 · Cited by 110
Lorenz, R. T., & Parks, L. W. (1990) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.34.9.1660 · Cited by 104
Chin, N. X., Weitzman, I., & Della-Latta, P. (1997) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.41.4.850 · Cited by 101
Espinel‐Ingroff, A., & Rezusta, A. (2002) · Journal of Clinical Microbiology · doi:10.1128/jcm.40.6.2101-2107.2002 · Cited by 100
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
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
Belgacem, Y. H., & Martin, J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.232244199 · Cited by 92
Lionakis, M. S., Lewis, R. E., May, G. S., Wiederhold, N. P., Albert, N. D., Halder, G. A., & Kontoyiannis, D. P. (2005) · The Journal of Infectious Diseases · doi:10.1086/428587 · Cited by 90
Self-citationKatano, H., Pesnicak, L., & Cohen, J. I. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0305149101 · Cited by 87
Itraconazole-Amphotericin B Antagonism in Aspergillus fumigatus : an E-Test-Based Strategy
Kontoyiannis, D. P., Lewis, R. E., Sagar, N., May, G. S., Prince, R. A., & Rolston, K. V. I. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.10.2915-2918.2000 · Cited by 69
Self-citationGrellier, P., Valentin, A., Millerioux, V., Schrével, J., & Rigomier, D. (1994) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.38.5.1144 · Cited by 59
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
Pentamidine Is Active In Vitro against Fusarium Species
Lionakis, M. S., Lewis, R. E., Samonis, G., & Kontoyiannis, D. P. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.10.3252-3259.2003 · Cited by 25
Self-citationMonma, M., Nakamura, Y., Okamura, T., & Sugai, J. (1977) · The Journal of Japan Atherosclerosis Society · doi:10.5551/jat1973.5.3_253 · Cited by 2
Research works printed but not linked: 1
- 10.1128/CMR.13.2.236 · DOI
Cited by
Sorted by citations
Epidemiology and Clinical Manifestations of Mucormycosis
Petrikkos, G. L., Skiada, A., Lortholary, O., Roilides, E., Walsh, T. J., & Kontoyiannis, D. P. (2012) · Clinical Infectious Diseases · doi:10.1093/cid/cir866 · Cited by 1,461
“Type 1, type 2, and secondary diabetes mellitus are all reportedly risk factors for mucormycosis [73].”
BackgroundSelf-citationESCMID† and ECMM‡ joint clinical guidelines for the diagnosis and management of mucormycosis 2013
Cornely, O. A., Arıkan-Akdağlı, S., Dannaoui, É., Groll, A. H., Lagrou, K., Chakrabarti, A., Lanternier, F., Pagano, L., Skiada, A., Akova, M., et al. (2014) · Clinical Microbiology and Infection · doi:10.1111/1469-0691.12371 · Cited by 864
Translating biosynthetic gene clusters into fungal armor and weaponry
Keller, N. P. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1897 · Cited by 277
Farmakiotis, D., & Kontoyiannis, D. P. (2016) · Infectious Disease Clinics of North America · doi:10.1016/j.idc.2015.10.011 · Cited by 215
Self-citationSipsas, N. V., Gamaletsou, M. N., Anastasopoulou, A. N., & Kontoyiannis, D. P. (2018) · Journal of Fungi · doi:10.3390/jof4030090 · Cited by 203
“, but reliable clinical data are lacking [111,112].”
BackgroundSelf-citation
Metadata
- Authors
- Chamilos, G., Lewis, R. E., & Kontoyiannis, D. P.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Kontoyiannis, Dimitrios P.
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2006-01
- Volume
- 50
- Issue
- 1
- Pages
- 96-103
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC1346800
- OpenAlex
- W2121543756
- Cited by
- 121
- References
- 36
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 8 · 2021: 6 · 2020: 8 · 2019: 11 · 2018: 6 · 2017: 2 · 2016: 5 · 2015: 9 · 2014: 4 · 2013: 6 · 2012: 8
- FWCI
- 2.77
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Infectious Diseases › Fungal Infections and Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- lovastatin, mucormycosis, Zygomycetes, voriconazole, drug synergy, statins, Mucor, Rhizopus, Drosophila model, antifungal activity, triazole resistance
- MeSH terms
- Animals, Antifungal Agents, Drug Synergism, Fungi, Lovastatin, Microbial Sensitivity Tests, Mycoses, Pyrimidines, Triazoles, Voriconazole
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.
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.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
