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In vitro antifungal activity of CAN-296: a naturally occurring complex carbohydrate
A M Ben-Josef1, E K Manavathu, D Platt
1Department of Medicine, School of Medicine, Wayne State University, Detroit, MI, USA.
Abstract:
The in vitro activity of a naturally occurring complex carbohydrate, CAN-296, was evaluated by testing 132 clinical and ATCC isolates of yeast and Aspergillus fumigatus, many of which were azole-resistant. The in vitro susceptibility tests were performed by standardized broth micro- and macrodilution methods and results were compared with those obtained for amphotericin B, fluconazole, ketoconazole, flucytosine and the pneumocandin L-733,560. All tested Candida species showed highly uniform susceptibility to CAN-296 at concentrations of 0.078 to 0.312 microgram/ml; non-albicans Candida were as susceptible to CAN-296 as the Candida albicans strains. Multi-azole-resistant Candida species were highly sensitive to CAN-296. Minimum inhibitory concentration measurements did not differ from minimum lethal concentrations by more than two-fold for all tested Candida species. Aspergillus fumigatus, on the other hand, showed only moderate susceptibility to CAN-296. The kinetics of the anti-Candida activity of CAN-296 was investigated by kill-curve experiments using C. albicans and C. glabrata and the results were compared with those obtain for amphotericin B. CAN-296 was found to be rapidly fungicidal in concentrations ranging from 4-16 fold the mean MIC value. The broad spectrum of anti-Candida activity together with the rapid fungicidal effect make this complex carbohydrate a promising agent for clinical use.
Insights
A novel carbohydrate, CAN-296, shows potent in vitro activity against diverse Candida species, including azole-resistant strains. This complex carbohydrate demonstrates rapid fungicidal effects, positioning it as a promising antifungal agent.
Area of Science:
- Mycology
- Pharmacology
- Biochemistry
Background:
- Antifungal resistance is a growing global health concern, particularly among Candida species.
- Existing antifungal therapies face challenges with resistance and toxicity.
- Novel therapeutic agents with broad-spectrum activity are urgently needed.
Purpose of the Study:
- To evaluate the in vitro antifungal activity of CAN-296, a complex carbohydrate.
- To assess CAN-296's efficacy against a panel of clinical and ATCC yeast isolates, including azole-resistant strains.
- To compare CAN-296's activity with established antifungal drugs.
Main Methods:
- Standardized broth micro- and macrodilution methods were employed for susceptibility testing.
- 132 clinical and ATCC isolates of Candida species and Aspergillus fumigatus were tested.
- Kill-curve experiments were conducted to determine the kinetics of antifungal activity.
Main Results:
- CAN-296 exhibited high and uniform in vitro activity against all tested Candida species at low concentrations (0.078–0.312 µg/ml).
- Multi-azole-resistant Candida strains were highly sensitive to CAN-296.
- CAN-296 demonstrated rapid fungicidal activity against Candida albicans and Candida glabrata.
- Aspergillus fumigatus showed moderate susceptibility to CAN-296.
Conclusions:
- CAN-296 possesses broad-spectrum anti-Candida activity, including against azole-resistant isolates.
- The compound exhibits rapid fungicidal kinetics, comparable to amphotericin B.
- CAN-296 represents a promising candidate for clinical development as a novel antifungal therapeutic.