Exploring synergy between azole antifungal drugs and statins for Candida auris
Open accessAbstract
Background: Global emergence of rapidly developing resistance to multiple antifungal drugs and high mortality pose challenges to the treatment of invasive Candida auris infections. New therapeutic approaches are needed, such as repurposing drugs including combination with antifungals. Statins have been reported to exert antifungal effects against various Candida species. Objectives: Our study investigated potential synergy between the statins (rosuvastatin and fluvastatin) and azoles (voriconazole, posaconazole and isavuconazole) on clinical isolates of C. auris. Methods: Twenty-one clinical isolates of C. auris were obtained. Chequerboard assays based on the CLSI broth microdilution method were used to assess synergy based on FIC index (FICI) calculations of MICs of individual drugs and in combinations. Results: Single drug geometric mean (GM) MICs of fluvastatin and rosuvastatin were ≥128 mg/L in all 21 isolates. GM (range) MICs of posaconazole, voriconazole and isavuconazole were 0.259 (0.016–1 mg/L), 0.469 (0.016–2 mg/L) and 0.085 (0.004–1 mg/L), respectively. Combination of azoles with fluvastatin showed synergy in 70%–90% of C. auris isolates. In particular, voriconazole/fluvastatin resulted in 16-fold reduction in voriconazole MIC and synergy in 14/21 (67%) isolates. Posaconazole/fluvastatin resulted in 8-fold reduction in posaconazole MIC and synergy in 19/21 (90%) isolates. Combining rosuvastatin with the azoles also showed synergy against C. auris in 40%–60% of the isolates and additive effect in 40%–50%. None of the combinations was antagonistic. Conclusions: Our results provide a rationale for pursuing in vivo synergy tests as well as clinical studies to explore tolerability, treatment outcomes, optimal dose and exposure targets.
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
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?
Itraconazole and rosuvastatin combinations produce marked synergy against clinical isolates of C. albicans.
“For instance, itraconazole and rosuvastatin combinations have produced marked synergy against 11 clinical isolates of C. albicans [125].”
From Statins as Antifungal Agents: A Review on Drug Repurposing and Nanotechnology-Driven Delivery Strategies (2025) · cites this paper as [125]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
PCR protocols — A guide to methods and applications
(1990) · Trends in Genetics · doi:10.1016/0168-9525(90)90186-a · Cited by 11,826 · see citing works
Chowdhary, A., Prakash, A., Sharma, C., Kordalewska, M., Kumar, A., Sarma, S., Tarai, B., Singh, A., Upadhyaya, G., Upadhyay, S., et al. (2018) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkx480 · Cited by 577 · see citing works
Brüggemann, R. J. M., Alffenaar, J. C., Blijlevens, N. M. A., Billaud, E. M., Kosterink, J. G. W., Verweij, P. E., & Burger, D. M. (2009) · Clinical Infectious Diseases · doi:10.1086/598327 · Cited by 458 · see citing works
Self-citationAn updated review of pharmacokinetic drug interactions and pharmacogenetics of statins
Hirota, T., Fujita, Y., & Ieiri, I. (2020) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2020.1801634 · Cited by 190 · see citing works
Candida auris Pan-Drug-Resistant to Four Classes of Antifungal Agents
Jacobs, S. E., Jacobs, J. L., Dennis, E. K., Taimur, S., Rana, M., Patel, D., Gitman, M., Patel, G., Schaefer, S., Iyer, K., et al. (2022) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00053-22 · Cited by 190 · see citing works
Ademe, M. (2020) · doi:10.2147/idr.s249864 · Cited by 182 · see citing works
Zhu, Y., O’Brien, B., Leach, L., Clark, A., Bates, M., Adams, E. H., Ostrowsky, B. E., Quinn, M., Dufort, E. M., Southwick, K. L., et al. (2019) · Journal of Clinical Microbiology · doi:10.1128/jcm.01503-19 · Cited by 166 · see citing works
Confirmation of fifth <i>Candida auris</i> clade by whole genome sequencing
Spruijtenburg, B., Badali, H., Abastabar, M., Mirhendi, H., Khodavaisy, S., Sharifisooraki, J., Taghizadeh Armaki, M., de Groot, T., & Meis, J. F. (2022) · Emerging Microbes & Infections · doi:10.1080/22221751.2022.2125349 · Cited by 164 · 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
Tavakkoli, A., Johnston, T. P., & Sahebkar, A. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107483 · Cited by 73 · see citing works
Biswas, C., Sorrell, T. C., Djordjevic, J. T., et al. (2013) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkt282 · Cited by 70 · see citing works
Ong, C. W., Chen, S. C. ‐., Clark, J. E., Halliday, C. L., Kidd, S. E., Marriott, D. J. E., Marshall, C. L., Morris, A. J., Morrissey, C. O., Roy, R., et al. (2019) · Internal Medicine Journal · doi:10.1111/imj.14612 · Cited by 60 · see citing works
Self-citationEldesouky, H. E., Salama, E. A., Li, X., Hazbun, T. R., Mayhoub, A. S., & Seleem, M. N. (2020) · Scientific Reports · doi:10.1038/s41598-020-64571-7 · Cited by 55 · see citing works
Nyilasi, I., Kocsubé́, S., Krizsán, K., Galgóczy, L., Papp, T., Pesti, M., Nagy, K., & Vágvölgyi, C. (2013) · Medical Mycology · doi:10.3109/13693786.2013.828160 · Cited by 44 · see citing works
Pfaller, M. A., Messer, S. A., Deshpande, L. M., Rhomberg, P. R., UTT, E. A., & Castanheira, M. (2021) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02031-20 · Cited by 38 · see citing works
Salama, E. A., Eldesouky, H. E., Elgammal, Y., Abutaleb, N. S., & Seleem, M. N. (2023) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2023.106906 · Cited by 23 · see citing works
Effect of Statin Use on Outcomes of Adults with Candidemia
Cuervo, G., Garcia-Vidal, C., Nucci, M., Puchades, F., Fernández-Ruiz, M., Mykietiuk, A., Manzur, A., Gudiol, C., Pemán, J., Viasus, D., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077317 · Cited by 20 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [11]CLSI. Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts—Fourth Edition: M27. 2017.
- [13]CLSI. Epidemiological Cutoff Values for Antifungal Susceptibility Testing—Fourth Edition: M57S. 2022.
Cited by
Sorted by citations
e Silva, D. M., de Souza Lacerda, L., de Souza Andrioli, A., Braz, W. R., Campos, L. M., de Paiva, M. R. B., Pittella, F., Fabri, R. L., & Tavares, G. D. (2025) · Fundamental & Clinical Pharmacology · doi:10.1111/fcp.70046 · Cited by 7 · see citing works
- Authors
- Halliday, C., Kim, H. Y., Tay, E., Chen, S. C. A., & Alffenaar, J.-W.
- Affiliations
- Westmead Hospital (AU)
- The University of Sydney (AU)
- Corresponding author
- Kim, Hannah Yejin
- Venue
- Journal of Antimicrobial Chemotherapy
- Publisher
- Oxford University Press (OUP)
- Published
- 2023-10-12
- Volume
- 78
- Issue
- 12
- Pages
- 2824-2829
- ISSN
- 0305-7453 (ISSN-L)
- 1460-2091
- PMC
- PMC10689908
- OpenAlex
- W4387563909
- Cited by
- 14
- References
- 17
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 2
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Antimicrobial Chemotherapy (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- RUNE (Research UNE) (submittedVersion, cc-by-nc)
- Funders
- The University of Sydney Infectious Diseases Institute
- 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
- Candida auris, statins, azole antifungals, drug repurposing, drug synergy, voriconazole, posaconazole, isavuconazole, fluvastatin, rosuvastatin, antifungal resistance, combination antifungal therapy, clinical isolates
- MeSH terms
- Rosuvastatin Calcium, Fluvastatin, Candida auris, Antifungal Agents, Azoles, Candidiasis, Microbial Sensitivity Tests, Nitriles, Pyridines, Triazoles, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Drug Resistance, Fungal, 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
