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Terbinafine-resistant onychomycosis is increasing, with newer antifungals like fosravuconazole and efinaconazole showing high efficacy against resistant and non-dermatophyte strains.
A 9-year retrospective study has revealed crucial trends in the causative organisms and drug resistance patterns of onychomycosis, underscoring emerging challenges in its treatment. Researchers analyzed 477 culture-positive cases of nail fungal infections between July 2015 and June 2024.
Among the 422 cases of toenail onychomycosis, the majority were caused by Trichophyton rubrum (T. rubrum, 78.0%), followed by T. interdigitale (19.0%), non-dermatophyte molds (2.8%), and Candida species (0.2%). In contrast, fingernail infections (n = 69) were primarily due to Candida species (46.4%) and T. rubrum (43.5%), with smaller contributions from T. interdigitale (2.9%), non-dermatophyte molds (4.3%), and Trichosporon species (2.9%). Of particular concern is the heightened prevalence of terbinafine-resistant dermatophyte onychomycosis.
Since 2020, 17 such cases have been recorded, representing 6.0% of all cases—markedly higher than the 2.3% reported in earlier Japanese surveys. These resistant infections were predominantly elicited by T. rubrum (94.1%), with 1 case involving T. interdigitale (5.9%). Notably, 58.8% of these strains also exhibited minimized susceptibility to itraconazole (0.125–0.5 mg/L), though they remained highly sensitive to newer antifungals like ravuconazole, efinaconazole, and luliconazole. Treatment with oral fosravuconazole (n = 13) and topical efinaconazole (n = 4) proved effective in achieving clinical cure.
Non-dermatophyte mold onychomycosis (n = 15) was mainly attributed to Aspergillus (40.0%) and Fusarium (33.3%) species, with rare isolates including Penicillium citrinum, Talaromyces muroii, Botryosphaeria dothidea, and Scopulariopsis brevicaulis. These strains frequently illustrated resistance to terbinafine (71.4%) and itraconazole (92.9%) when tested against a breakpoint of 0.5 mg/L. Nonetheless, efinaconazole (n = 7) and fosravuconazole (n = 5) were promising therapeutic options for these patients.
Yeast onychomycosis (n = 35) predominantly affected fingernails (97.1%) and was mostly aroused by Candida albicans (88.6%). Notably, 2 cases were attributed to non-albicans Candida species—C. guilliermondii and C. parapsilosis—which exhibited low sensitivity to fluconazole and itraconazole. Additionally, Trichosporon species were isolated in 2 cases of fingernail infections. This study highlights the shifting landscape of onychomycosis in Japan, emphasizing the growing issue of antifungal resistance and the emerging role of newer agents like ravuconazole, efinaconazole, and fosravuconazole for optimal disease management.
Medical Mycology
Emerging Antifungal-Resistant Onychomycosis in a Dermatology Clinic in Kumamoto, Japan
Sayaka Ohara et al.
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