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Combination antifungal therapy against resistant C. albicans: efficacy and immune response in mice
Ali Taghizadeh-Maleki1, Farahnaz Hatami1, Sima-Sadat Seyedjavadi1
1Department of Mycology, Pasteur Institute of Iran, No.69, Pasteur Ave, Tehran, 1316943551, Iran.
Abstract:
This study demonstrates the therapeutic effects of combination therapies against Candida albicans in mouse models, as opposed to mono-therapeutic treatments, while also comparing the pathogenicity of both sensitive and resistant strains. Fluconazole-resistant strain of Candida albicans was isolated from an infected patient, and its infectivity potential was compared with a susceptible strain by injecting a fungal cell suspension into the mice model. Additionally, the level of secretory interleukin 17 in the mice was examined. Furthermore, the efficacy of combination therapy was assessed using Fluconazole-Caspofungin (Flu-Cas) and Fluconazole-Amphotericin B (Flu-AmB) in comparison to monotherapy. The results indicate that the resistant strain exhibits higher pathogenicity compared to the susceptible strain in inducing systemic infection within the mouse model, as significant differences between the resistant and susceptible groups were observed at day 5 (p = 0.0401) and day 7 (p = 0.0182). The concentrations of IL-17 (pg/ml) on days 1 to 7 were 43.66 to 259 pg/ml, and 39.66 to 210 pg/ml in resistant and susceptible groups, respectively, which were only significant on days 5 (p = 0.0356) and 7 (p = 0.0280). Combination therapies using Flu-Cas and Flu-AmB demonstrated an effective reduction in fungal colonization after 17 days. This study demonstrates that Fluconazole-resistant Candida albicans strains are more pathogenic than susceptible ones in mice. Combination therapies with Fluconazole-Amphotericin B were most effective in reducing fungal colonization, outperforming monotherapy. These results support combination treatment for resistant Candida infections.
Insights
Fluconazole-resistant Candida albicans strains are more pathogenic in mice than susceptible strains. Combination therapies, particularly Fluconazole-Amphotericin B, effectively reduce fungal colonization, supporting their use against resistant Candida infections.
Area of Science:
- Mycology
- Infectious Diseases
- Immunology
Background:
- Candida albicans is a common human pathogen, with increasing resistance to antifungal drugs like fluconazole posing a significant clinical challenge.
- Understanding the pathogenicity of drug-resistant strains and identifying effective therapeutic strategies are crucial for managing invasive candidiasis.
Purpose of the Study:
- To compare the pathogenicity of fluconazole-resistant and susceptible Candida albicans strains in a mouse model.
- To evaluate the efficacy of combination antifungal therapies against Candida albicans infections.
- To assess the role of interleukin-17 (IL-17) in the host response to Candida albicans.
Main Methods:
- Isolation of a fluconazole-resistant Candida albicans strain from a patient and comparison of its infectivity with a susceptible strain in a mouse model.
- Administration of monotherapy and combination therapies (Fluconazole-Caspofungin and Fluconazole-Amphotericin B) to infected mice.
- Measurement of secretory interleukin-17 levels in mice serum and assessment of fungal colonization.
Main Results:
- The fluconazole-resistant Candida albicans strain exhibited significantly higher pathogenicity and induced a stronger IL-17 response compared to the susceptible strain in the mouse model.
- Combination therapies, specifically Fluconazole-Amphotericin B, demonstrated superior efficacy in reducing fungal colonization compared to monotherapy.
- Significant differences in pathogenicity and IL-17 levels were observed between resistant and susceptible groups at later time points (day 5 and 7).
Conclusions:
- Fluconazole-resistant Candida albicans strains demonstrate increased pathogenicity in vivo.
- Combination antifungal therapies, particularly Fluconazole-Amphotericin B, are effective in controlling Candida albicans infections, especially those caused by resistant strains.
- These findings support the clinical use of combination therapies for treating fluconazole-resistant Candida infections.
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