We present a 76-year-old Japanese male with tinea faciei, tinea corporis, and tinea unguium with dermatophytoma. We performed fungal culture and confirmed the causative fungus to be Trichophyton rubrum. We treated the patient using oral fosravuconazole l-lysine ethanolate (F-RVCZ). More than one year has passed since the end of treatment, but there has been no recurrence. This case suggests that F-RVCZ is effective for tinea other than tinea unguium.
Farnesol is an extracellular quorum-sensing molecule produced by Candida albicans. Farnesol is also a sesquiterpene alcohol existing in many herbal products and has various activity against fungal cells. We aimed to investigate the efficacy of farnesol alone and the contribution of farnesol on the activity of voriconazole and amphotericin B against Aspergillus clinical isolates in vitro. A total of 45 Aspergillus clinical isolates were used in this study. The MIC values of voriconazole, amphotericin B, and farnesol were determined using reference broth microdilution method. The interactions of farnesol with voriconazole and amphotericin B were investigated by the checkerboard method and evaluated based on the fractional inhibitor concentration index (FICI). The MIC ranges of farnesol, voriconazole, and amphotericin B were 1,500-6,000 μM, 0.125-1 μg/mL, and 0.125-0.5 μg/mL against Aspergillus fumigatus isolates, 3,000-12,000 μM, 0.125-0.5 μg/mL, and 0.25-2 μg/mL against Aspergillus flavus isolates, respectively. The most common interaction in combination tests was “no interaction,” and synergistic interaction was not detected. The combinations of farnesol with voriconazole and amphotericin B had antagonistic activity against 38% and 27% of all isolates, respectively. We concluded that the responses of different fungal species against farnesol are variable, and different interactions may be observed when it is combined with different antifungals. Therefore, it should be noted that farnesol may have an adverse effect on some fungi or interact negatively with antifungals used in combination.
Introduction: SO-1105 is an oral mucosal adhesive tablet containing 50 mg of miconazole. It had been shown overseas that a once-daily application of the drug continues antifungal effect in the treatment of oropharyngeal candidiasis. We report the results of the phase 3 clinical study of this drug with miconazole gel as a control in Japan. Methods: The study included patients aged 20 years or older with oropharyngeal candidiasis who had oral lesions characterized by oropharyngeal candidiasis and whose fungi was confirmed by direct microscopic examination. The primary efficacy endpoint was the clinical cure rate on Day15 after 14 days of administration. The population analyzed for efficacy was per protocol set (PPS). Results: 120 subjects were included in PPS. In detail, 59 subjects were in the SO-1105 group (SO-1105 group) and 61 subjects were in the miconazole gel group (Gel group). For efficacy, the clinical cure rate on Day15 was 47.5% in SO-1105 group and 47.5% in Gel group, showing the similar efficacy between both groups. For safety, adverse drug reactions were observed in 29.0% of SO-1105 group and 24.6% of Gel group, showing the similar safety between both groups. Conclusion: The efficacy of SO-1105 was shown to be similar to that of miconazole gel. Meanwhile, SO-1105 is an adhesive tablet and is administered once-daily. For this, SO-1105 is expected to better compliance and useful drug for the elderly. Therefore, SO-1105 is considered to be widely used in clinical practice as one of the therapeutic drugs for oropharyngeal candidiasis.
To clarify the terbinafine (TRF) resistance mechanism in highly TRF-resistant [minimum inhibitory concentration (MIC) >32 μg/mL] strains of Trichophyton indotineae (NUBS19006T and NUBS19007), we investigated the expression of squalene epoxidase (SQLE), pleiotropic drug resistance 1 (PDR1), multidrug resistance 2 (MDR2), and MDR4 genes by real-time quantitative PCR analysis, given the known interaction of the corresponding proteins with antifungals and the efflux blocker tacrolimus (FK506). SQLE, PDR1, MDR2, and MDR4 transcript levels in TRF-resistant strains cultured in SDB were not significantly higher than those of the respective genes in TRF-susceptible strains (1 and 10). By contrast, PDR1, MDR2, and MDR4 transcript levels in TRF-resistant and TRF-susceptible strains cultured in SDB containing 10 μg/mL TRF were 5-100 times higher than those of the respective genes in strains grown in the absence of TRF. However, no differences in PDR1, MDR2, and MDR4 transcript levels were found between TRF-resistant (NUBS19006T and NUBS19007) and TRF-susceptible strains cultured in SDB containing 10 μg/mL TRF. The interaction between TRF and FK506 on antifungal activity was not detected in TRF-resistant strains. These results indicate that ATP-dependent efflux pumps do not confer TRF-resistance mechanisms in TRF-resistant strains.