TY - JOUR

T1 - Photodynamic therapy

T2 - A treatment option for terbinafine resistant Trichophyton species

AU - Shen, Julia J.

AU - Arendrup, Maiken C.

AU - Jemec, Gregor B.E.

AU - Saunte, Ditte Marie L.

PY - 2021

Y1 - 2021

N2 - Background: Terbinafine is a first-line agent against Trichophyton-infections. However, treatment failure and resistance due to squalene epoxidase (SQLE) alterations are increasingly being reported. Photodynamic therapy (PDT) is based on combining a photosensitizer, light and oxygen to create photo-activated reactive oxygen species. It has demonstrated in vitro and in vivo activity against various microorganisms including dermatophytes. We investigated if PDT is equally effective against terbinafine resistant and susceptible strains. Methods: Minimum inhibitory concentrations (MIC) of methylene blue (MB)-PDT against wildtype and resistant Trichophyton rubrum and Trichophyton interdigitale were determined in duplicate in microtitre plates following EUCAST E.Def 11.0 reference methodology. Included mutants harboured F397L, L393F, L393S, F415S or F397I SQLE-alterations. Illumination with red diode light was performed after <3 min, 30 min and 3 h of incubation, respectively, and plates were cultured at 25 °C for 5 days. Geometric mean MICs and MIC ranges were calculated for each isolate. Results: MB-PDT led to complete inhibition of all isolates at geometric mean concentrations of 1−16 mg/L. Efficacy was independent of incubation time prior to illumination, terbinafine susceptibility (MICs ≤0.004–4 mg/L) and presence of SQLE mutations. However, the MB-PDT MIC was slightly elevated (MB: 2−8 mg/L and 8−16 mg/L) in isolates from two pigmented cultures of Trichophyton interdigitale (one wildtype and one harbouring L393F) with a darker color when compared to unpigmented cultures (MB: 0.5−4 mg/L). Conclusion: Terbinafine resistant and susceptible strains are equally susceptible to MB-PDT. Lower efficacy was observed against dark coloured isolates which we speculate may be due to melanisation interfering with photo-activation due to preferential light absorption.

AB - Background: Terbinafine is a first-line agent against Trichophyton-infections. However, treatment failure and resistance due to squalene epoxidase (SQLE) alterations are increasingly being reported. Photodynamic therapy (PDT) is based on combining a photosensitizer, light and oxygen to create photo-activated reactive oxygen species. It has demonstrated in vitro and in vivo activity against various microorganisms including dermatophytes. We investigated if PDT is equally effective against terbinafine resistant and susceptible strains. Methods: Minimum inhibitory concentrations (MIC) of methylene blue (MB)-PDT against wildtype and resistant Trichophyton rubrum and Trichophyton interdigitale were determined in duplicate in microtitre plates following EUCAST E.Def 11.0 reference methodology. Included mutants harboured F397L, L393F, L393S, F415S or F397I SQLE-alterations. Illumination with red diode light was performed after <3 min, 30 min and 3 h of incubation, respectively, and plates were cultured at 25 °C for 5 days. Geometric mean MICs and MIC ranges were calculated for each isolate. Results: MB-PDT led to complete inhibition of all isolates at geometric mean concentrations of 1−16 mg/L. Efficacy was independent of incubation time prior to illumination, terbinafine susceptibility (MICs ≤0.004–4 mg/L) and presence of SQLE mutations. However, the MB-PDT MIC was slightly elevated (MB: 2−8 mg/L and 8−16 mg/L) in isolates from two pigmented cultures of Trichophyton interdigitale (one wildtype and one harbouring L393F) with a darker color when compared to unpigmented cultures (MB: 0.5−4 mg/L). Conclusion: Terbinafine resistant and susceptible strains are equally susceptible to MB-PDT. Lower efficacy was observed against dark coloured isolates which we speculate may be due to melanisation interfering with photo-activation due to preferential light absorption.

KW - Antifungal resistance

KW - Dermatophyte

KW - Methylene blue

KW - PDT

KW - Photodynamic therapy

KW - Trichophyton

U2 - 10.1016/j.pdpdt.2020.102169

DO - 10.1016/j.pdpdt.2020.102169

M3 - Journal article

C2 - 33497815

AN - SCOPUS:85099941688

VL - 33

JO - Photodiagnosis and Photodynamic Therapy

JF - Photodiagnosis and Photodynamic Therapy

SN - 1572-1000

M1 - 102169

ER -