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[The future of antifungal agents. Non azole antifungal agents]
S Maesaki1, M A Hossain, E Sasaki
1Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto Nagasaki 852-8501.
Abstract:
We investigated the efficacy of non-azole antifungal agents. Long circulating immunoliposomal amphotericin B was potent in murine invasive pulmonary aspergillosis. The concentration of AMPH-B was still high in the lung after 6 hours of 34A-PEG-liposomal AMPH-B. Lipid nanosphere amphotericin B (NS-718) showed efficacy against pulmonary aspergillosis in rats and pulmonary cryptococcosis in mice. The renal toxicity of NS-718 was estimated to be lower than that of AMPH-B from the results of the toxicity study in the rat infusion model. FK 463, a novel (1,3)-beta-D-glucan synthase inhibitor, showed efficacy against azole-resistant Candida albicans in murine experimental disseminated candidiasis. FK463 could be a promising drug and the therapy of choice for azole resistant C. albicans infection.
Insights
New antifungal agents, including liposomal amphotericin B and FK463, show promise. These non-azole drugs demonstrated efficacy against serious fungal infections like aspergillosis and candidiasis, with reduced toxicity.
Area of Science:
- Mycology
- Pharmacology
- Infectious Diseases
Background:
- Non-azole antifungal agents are crucial for treating invasive fungal infections.
- Developing novel antifungals with improved efficacy and reduced toxicity is a priority.
- Azole-resistant fungal strains pose a significant therapeutic challenge.
Purpose of the Study:
- To evaluate the efficacy of novel non-azole antifungal agents against invasive fungal infections.
- To assess the pharmacokinetic profile and toxicity of specific amphotericin B formulations.
- To determine the potential of FK463 as a treatment for azole-resistant Candida albicans infections.
Main Methods:
- Murine models of invasive pulmonary aspergillosis were used to test immunoliposomal amphotericin B and lipid nanosphere amphotericin B (NS-718).
- Pharmacokinetic studies tracked the concentration of amphotericin B in lung tissue.
- Rat infusion models assessed the renal toxicity of NS-718 compared to conventional amphotericin B.
- Murine experimental disseminated candidiasis models were employed to evaluate FK463 against azole-resistant strains.
Main Results:
- Long-circulating immunoliposomal amphotericin B was potent against murine invasive pulmonary aspergillosis.
- Lipid nanosphere amphotericin B (NS-718) demonstrated efficacy in rat and mouse models of fungal pneumonia.
- NS-718 exhibited lower estimated renal toxicity compared to conventional amphotericin B.
- FK463 proved effective against azole-resistant Candida albicans in a disseminated candidiasis model.
Conclusions:
- Novel amphotericin B formulations, including liposomal and nanosphere-based systems, offer potent antifungal activity with potentially reduced toxicity.
- FK463 is a promising therapeutic candidate for infections caused by azole-resistant Candida albicans.
- These non-azole agents represent important advancements in managing challenging fungal infections.