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Results

Novexatin® demonstrated dose-dependent fungicidal activity, (median MIC₁₀₀ = 1 mM) and killed Trichophyton spp. via membranolysis within 3 hours of exposure. At sub-MIC concentrations, Novexatin® inhibited germ tube formation, but not germ tube length. Infected nail fragments treated with 10% (w/v) Novexatin® were cleared of accurately quantifiable fungi by 28 days. Light microscopy revealed that treatment with Novexatin® reduced numbers of viable fungal hyphae visible in nail fragments and damage to the nail matrix. Transmission electron microscopy revealed fungicidal effects deep within the nail matrix of Novexatin® treated nail fragments, but not with control antifungals.

Resistance (spontaneous or adaptive) was not evident after >20 passages on exposure of 4 clinical isolates of Trichopyton spp to Novexatin®.

The antifungal susceptibility profile of >80 clinical isolates of dermatophyte and non-dermatophyte fungi. MIC100s range from 0.1 - > 4mM, however the MIC range for dermatophytes was 0.5 - 2 mM.

Following treatment with Novexatin® in a proprietary ex vivo, full thickness human toe nail model for 28 days, fungal growth was eradicated from the nail. Terbinafine (>1000 x MIC₉₀) and all other controls failed to eradicate fungal growth.

Toe nails infected with T. rubrum were treated with Novexatin® or itraconazole for 28 days. Fungi in nails treated with Novexatin® were successfully eradicated, whereas live fungal hyphae could still be detected in nails treated with itraconazole.

No spontaneous or adaptive resistance to Novexatin® developed over 20 successive passages in four clinical isolates of Trichophyton spp. The MIC₁₀₀ range varied less than 4-fold and no increase in MIC₁₀₀ of more than 2-fold was demonstrated.

 

 

 

Methods

Antifungal susceptibilty testing of over 80 dermatophyte and non-dermatopyte fungi from human tinea infections, including onychomycosis, was conducted using in vitro CLSI Approved Standard M38-A2.

An ex vivo nail model system was developed and validated to determine the effectiveness of Novexatin® in eradicating infection versus relevant controls. The ventral face of excised human nail fragments (5 experiments of 3 nail fragments/time point/treatment) were infected with Trichophyton spp. for >2 weeks, by which time the fungal burden reached 10⁵ - 10⁷ cfu/cm². The nails were transferred to an inert support and maintained at 30°C in a humid atmosphere during daily treatment of the dorsal face with Novexatin® and comparators. After 14 and 28 days treatment the fungal burden of the nails was determined by culture-dependent and microscopy methods.