Antifungal susceptibility testing and clinical efficacy observation of methylene blue photodynamic therapy in treating trichophyton indotineae infections

• First clinical evidence that methylene blue photodynamic therapy (MB-PDT) eradicates multidrug-resistant Trichophyton indotineae (squalene epoxidase, SQLE gene-mutated) infections. • MB-PDT achieves mycological cure in 2 weeks (MIC=1 μg/mL) vs. persistent hyphae with terbinafine (MIC=8 μg/mL) in drug-resistant strains. • ROS-mediated multi-target mechanism circumvents traditional antifungal resistance (SQLE/CYP51 mutations), offering a novel therapeutic avenue. • Low cost, minimal adverse reactions, and simple operation make MB-PDT ideal for widespread use in primary care and resource-limited settings. Superficial fungal infections caused by Trichophyton indotineae are spreading globally, with mutations in its SQLE gene (F397L/L393S) increasing resistance to traditional antifungals like terbinafine, creating an urgent need for new therapies [ 1 ]. This study evaluated the clinical efficacy of methylene blue-mediated photodynamic therapy (MB-PDT). In vitro susceptibility testing was performed on a multidrug-resistant T. indotineae strain isolated from a 25-year-old Indian male with extensive skin lesions (confirmed by ITS sequencing). A randomized controlled trial was conducted: the experimental group (forearm lesions) received topical 1% methylene blue plus 630±5nm red light irradiation (100 J/cm², once weekly for 4 weeks), while the control group (other lesions) were treated with topical 1% terbinafine cream twice daily. Results showed the strain was highly sensitive to methylene blue (MIC=1.0 μg/mL) but resistant to terbinafine (MIC=8.0 μg/mL). After 2 weeks, the experimental group achieved scaling resolution and negative fungal microscopy, with sustained efficacy at 4 weeks; the control group retained residual hyphae. Conclusion: MB-PDT rapidly eradicates drug-resistant T. indotineae infections, outperforming traditional topical agents and providing a safe, effective alternative for drug-resistant dermatophytosis.