Diagnosis and Treatment of Mold Onychomycosis: Challenges and Combination Therapies

Conclusions

• Non-dermatophyte mold onychomycosis should be suspected when nail disease is unusually aggressive, combined in pattern, or accompanied by periungual inflammation and pus discharge.
• Because mold can be a contaminant in culture, diagnosis should rely on clinical suspicion plus repeat mycological testing rather than a single positive culture alone.
• Treatment is difficult because these infections recur, drug penetration into the nail plate is poor, and biofilm formation may reduce response.
• A combination approach is preferred, typically pairing systemic antifungals with topical agents and regular mechanical or chemical nail debridement.
• Itraconazole and terbinafine are the main systemic options, while ciclopirox and amorolfine are commonly used topical agents where available.
• Response to therapy varies by organism, with Scopulariopsis, Fusarium, and Acremonium tending to respond more poorly than Aspergillus and Penicillium.
• Longer treatment courses and ongoing debridement are often needed for resistant mold species.
• Laser therapy and other emerging approaches may help in selected cases, but current evidence for non-dermatophyte mold infections remains limited.
• Future strategies such as microneedles, iontophoresis, and photodynamic therapy aim to improve transungual drug delivery and outcomes.
• Overall, the main conclusion is that non-dermatophyte mold onychomycosis requires individualized, multimodal, and often prolonged therapy, with newer adjunctive techniques still investigational.