In vitro susceptibility profiles of 16 antifungal drugs against Trichophyton indotineae

Abstract

The worldwide emergence of Trichophyton indotineae has garnered significant attention due to its growing resistance to conventional antifungal therapies, posing significant challenges to the effective management of dermatophytosis. The in vitro activities of 16 antifungals were tested against 37 T. indotineae isolates using the broth microdilution method according to Clinical and Laboratory Standards Institute protocol M38-A3. Luliconazole and amorolfine exhibited low MICs, while itraconazole showed moderately decreased susceptibility, making them preferred treatment options. Echinocandins demonstrated favourable in vitro activity against T. indotineae, but their potential as therapeutic alternatives for recalcitrant dermatophytosis remains uncertain due to pharmacokinetic and pharmacodynamic limitations. In contrast, terbinafine, fluconazole, griseofulvin, oteseconazole, isavuconazole, ravuconazole, and amphotericin B exhibited elevated MICs for many strains, with strong correlations between certain azoles, indicating potential cross-resistance. A difference in the susceptibility to terbinafine and voriconazole between Chinese and Indian isolates was observed. These findings could provide valuable insights into antifungal resistance patterns and help guide treatment strategies for T. indotineae infections.

Importance: Trichophyton indotineae is a novel emerging dermatophyte that has rapidly spread globally in recent years. Its resistance to first-line antifungal agents, particularly terbinafine and fluconazole, has significantly limited treatment options, emphasizing the urgent need for alternative therapies. This study provides comprehensive antifungal susceptibility data for 16 available antifungal agents, offering valuable insights into potential treatment strategies.

Keywords: Trichophyton indotineae; amphotericin B; antifungal susceptibility; azoles; echinocandins.

Fig 1

(A) Heatmap (R version 4.4.1) of Spearman’s rank correlation coefficients for the MICs of six azoles against T. indotineae isolates. Correlation coefficients range from −1 (strong negative correlation) to +1 (strong positive correlation). Color intensity indicates correlation strength, with deeper red representing stronger positive correlations. (B) Scatter plots (GraphPad Prism version 10.1.2) comparing the MICs of nine commonly used antifungals for dermatophytosis between Chinese and Indian T. indotineae isolates. Abbreviations: TBF (terbinafine), FCZ (fluconazole), ITR (itraconazole), VOR (voriconazole), POS (posaconazole), LLCZ (luliconazole), GSF (griseofulvin), AMO (amorolfine), CLC (ciclopirox), PRC (Chinese isolate), IND (Indian isolates). (C) Scatter plots comparing the MICs of seven other antifungals between Chinese and Indian T. indotineae isolates. Abbreviations: RVZ (ravuconazole), OTZ (oteseconazole), ISA (isavuconazole), AmB (amphotericin B), CAS (caspofungin), MCF (micafungin), ANF (anidulafungin), PRC (Chinese isolates), IND (Indian isolates). The x-axis represents the tested drugs, grouped by category, while the y-axis shows MIC (mg/L) plotted on a segmented, non-continuous linear scale to accommodate the wide range of data. Statistical significance was determined using the Kruskal-Wallis test (*P < 0.05, ****P < 0.0001).