Fluconazole plus Cyclosporine: a Fungicidal Combination Effective against Experimental Endocarditis Due to Candida albicans

Marchetti, O.; Entenza, J. M.; Sanglard, D.; Bille, J.; Glauser, M. P.; Moreillon, P.

doi:10.1128/aac.44.11.2932-2938.2000

Cited by 113Antifungal resistance and susceptibilityInfective Endocarditis Diagnosis and ManagementOcular Infections and Treatments

Fluconazole plus Cyclosporine: a Fungicidal Combination Effective against Experimental Endocarditis Due to Candida albicans

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Marchetti, O., Entenza, J. M., Sanglard, D., Bille, J., Glauser, M. P., Moreillon, P.·2000·Antimicrobial Agents and Chemotherapy

DOI 10.1128/aac.44.11.2932-2938.2000PMC PMC101583

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Abstract

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.
“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]
The Abstract describes a rat model of C. albicans endocarditis treated with fluconazole plus cyclosporine, not a mouse model treated with FK506. The Discussion mentions fluconazole–FK506 synergy only for Cryptococcus neoformans, as reported by Del Poeta et al. (Page numbers are unavailable in our copy.) (LLM, conf=0.90)
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Authors: Marchetti, O., Entenza, J. M., Sanglard, D., Bille, J., Glauser, M. P., & Moreillon, P.
Affiliations: Centre Hospitalier Universitaire Vaudois (CH)
Division of Infectious Diseases, Department of Internal Medicine,1 and
Institute of Microbiology,2 Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland
ORCID: Entenza, J. M.
Sanglard, D.
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
DOI: 10.1128/aac.44.11.2932-2938.2000
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
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
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 › Epidemiology › 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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Fluconazole plus Cyclosporine: a Fungicidal Combination Effective against Experimental Endocarditis Due to Candida albicans

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