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Antifungal therapies in murine infections by Candida kefyr
Marta Sanchis1, Adela Martin-Vicente1, Javier Capilla1
1Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, IISPV, Universitat Rovira i Virgili, Reus, Tarragona, Spain.
Abstract:
Candida kefyr is an emerging pathogen able to cause disseminated infection, especially in immunocompromised patients. Although guidelines for the treatment of invasive candidiasis have been published, no specific recommendations against C. kefyr are available. We determine the in vitro killing activity of amphotericin B (AMB), fluconazole (FLC) and caspofungin (CFG) as well as their efficacy in a murine model of systemic infection by two C. kefyr strains. Time-kill curves of AMB, FLC and CFG were determined in final volumes of 10 ml containing the assayed drugs ranged from 0.03 to 32 μg ml-1 at different time points and efficacy of the drugs was evaluated in a systemic model of candidiasis, conducted in immunosuppressed mice, through survival, (1→3)-β-D-glucan levels in serum and fungal load in kidneys. AMB and CFG showed fungicidal and FLC fungistatic activity against both isolates. The three drugs were able to reduce fungal burden in kidneys and (1→3)-β-D-glucan concentration in serum of infected mice, with CFG showing the highest efficacy, followed by FLC. In conclusion, CFG showed efficacy over AMB and FLC against the systemic candidiasis by C. kefyr. The established epidemiological cut-off for anidulafungin seems the best indicator of outcome for echinocandins.
Insights
Caspofungin (CFG) demonstrates superior efficacy against *Candida kefyr* invasive infections compared to amphotericin B (AMB) and fluconazole (FLC). This study evaluated antifungal drug activity in vitro and in a murine model, highlighting CFG as a promising treatment option.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Pharmacology
Background:
- *Candida kefyr* is an emerging fungal pathogen causing disseminated infections, particularly in immunocompromised individuals.
- Current invasive candidiasis treatment guidelines lack specific recommendations for *C. kefyr*.
Purpose of the Study:
- To determine the in vitro antifungal activity of amphotericin B (AMB), fluconazole (FLC), and caspofungin (CFG) against *C. kefyr*.
- To evaluate the in vivo efficacy of these antifungal agents in a murine model of systemic *C. kefyr* infection.
Main Methods:
- In vitro time-kill curves were generated for AMB, FLC, and CFG against two *C. kefyr* strains.
- In vivo efficacy was assessed in immunosuppressed mice using survival rates, serum (1→3)-β-D-glucan levels, and kidney fungal burden.
Main Results:
- Amphotericin B and caspofungin exhibited fungicidal activity, while fluconazole showed fungistatic activity in vitro.
- All three drugs reduced fungal burden and (1→3)-β-D-glucan levels in infected mice.
- Caspofungin demonstrated the highest efficacy, followed by fluconazole, in the murine model.
Conclusions:
- Caspofungin is more effective than amphotericin B and fluconazole against systemic candidiasis caused by *C. kefyr*.
- The epidemiological cut-off for anidulafungin may serve as a reliable indicator for echinocandin treatment outcomes in *C. kefyr* infections.
