Synergistic effect of Punica granatum derived antifungals on strains with clinical failure to terbinafine and azoles drugs

Dermatomycosis is a commonly occurring widespread superficial fungal infection. The infection is mostly caused by the dermatophytes (e.g., Trichophyton spp.), and yeasts (e.g., Candida spp.). Due to their persistent, recalcitrant nature and treatment failure it has become a worldwide concern. In our study, we have used multidrug-resistant Trichophyton mentagrophytes var. interdigitale clinical isolates for evaluation of the synergistic effect of the plant-based extract with existing drugs. Here, Punica granatum peel (PGP) extracts alone and their combination with existing antifungal drugs (e.g., Ciclopirox olamine, Zinc pyrithione, Ketoconazole, and Fluconazole) were evaluated as an alternative synergistic combination against Trichophyton and Candida species. Synergy had been determined for PGP extract with other antifungals against Candida and Trichophyton species by checkerboard, ZOI (zone of inhibition), and E-test methods respectively. The isolates exhibited resistance towards some azoles and allylamines. PGP extract alone and in combination with other antifungals had shown, FIC Index from 0.133 to 0.2 against C. albicans strains, 0.2 to 0.5, FIC against T. rubrum strains respectively. E-test also showed 512±0.0 and 341.3±0.0-fold decrease of MIC (minimum inhibitory concentration), against azole-resistant C. albicans MTCC 227 respectively. The study reveals that PGP extract alone and in combination with other antifungals is a promising source of alternative antifungal therapy to minimize the resistance profile.