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Fluconazole plus Cyclosporine: a Fungicidal Combination Effective against Experimental Endocarditis Due to Candida albicans
Open accessAbstract
Recent observations demonstrated that fluconazole plus cyclosporine (Cy) synergistically killed Candida albicans in vitro. This combination was tested in rats with C. albicans experimental endocarditis. The MICs of fluconazole and Cy for the test organism were 0.25 and >10 mg/liter, respectively. Rats were treated for 5 days with either Cy, amphotericin B, fluconazole, or fluconazole-Cy. Although used at high doses, the peak concentrations of fluconazole in the serum of rats (up to 4.5 mg/liter) were compatible with high-dose fluconazole therapy in humans. On the other hand, Cy concentrations in serum (up to 4.5 mg/liter) were greater than recommended therapeutic levels. Untreated rats demonstrated massive pseudohyphal growth in both the vegetations and the kidneys. However, only the kidneys displayed concomitant polymorphonuclear infiltration. The therapeutic results reflected this dissociation. In the vegetations, only the fungicidal fluconazole-Cy combination significantly decreased fungal densities compared to all groups, including amphotericin B ( P < 0.0001). In the kidneys, all regimens except the Cy regimen were effective, but fluconazole-Cy remained superior to amphotericin B and fluconazole alone in sterilizing the organs ( P < 0.0001). While the mechanism responsible for the fluconazole-Cy interaction is hypothetical, this observation opens new perspectives for fungicidal combinations between azoles and other drugs.
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“In a mouse model of invasive candidiasis by C. albicans, the efficacy of fluconazole was increased by co-administration of FK506 (56).”
From Echinocandin tolerance and persistence in vitro are regulated by calcineurin signaling in Candida glabrata (2026) · cites this paper as [56]
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Self-citation
Metadata
- Authors
- Marchetti, O., Entenza, J. M., Sanglard, D., Bille, J., Glauser, M. P., & Moreillon, P.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- <!--label omitted: 1-->Division of Infectious Diseases, Department of Internal Medicine,1 and
- <!--label omitted: 2-->Institute of Microbiology,2 Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2000-11
- Volume
- 44
- Issue
- 11
- Pages
- 2932-2938
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- PMC
- PMC101583
- OpenAlex
- W2080315399
- Cited by
- 113
- References
- 43
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 6 · 2020: 4 · 2019: 5 · 2018: 2 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 7 · 2013: 3 · 2012: 4
- FWCI
- 5.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Antimicrobial Agents and Chemotherapy (publishedVersion)
- PubMed Central (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Infective Endocarditis Diagnosis and Management
- Health Sciences › Medicine › Ophthalmology › Ocular Infections and Treatments
- Keywords
- fluconazole, cyclosporine, Candida albicans, fungal endocarditis, combination antifungal therapy, amphotericin B, drug interactions, pseudohyphal growth, vegetation, serum drug concentration
- MeSH terms
- Animals, Antifungal Agents, Candida albicans, Candidiasis, Disease Models, Animal, Drug Resistance, Microbial, Drug Therapy, Combination, Endocarditis, Female, Kidney, Microbial Sensitivity Tests, Fluconazole, Cyclosporine, Treatment Outcome, Rats, Wistar, Rats
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