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Potential Inhibitory Effect of Miltefosine against Terbinafine-Resistant Trichophyton indotineae

Iman Haghani1,2, Javad Akhtari3, Zahra Yahyazadeh2

  • 1Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari 48157-33971, Iran.

Pathogens (Basel, Switzerland)
|April 28, 2023
PubMed

Insights

Miltefosine shows promising in vitro activity against terbinafine-resistant dermatophytes like Trichophyton indotineae. This suggests potential for treating difficult-to-treat fungal infections when standard antifungals fail.

Area of Science:

  • Medical Mycology
  • Antimicrobial Susceptibility Testing
  • Dermatophytosis Treatment

Background:

  • Emerging outbreaks of terbinafine-resistant dermatophytosis caused by Trichophyton indotineae are a growing global health concern.
  • Standard antifungal treatments are becoming less effective against these resistant strains.
  • Miltefosine, an established treatment for leishmaniasis, has shown limited in vitro activity against some terbinafine-resistant fungi.

Purpose of the Study:

  • To evaluate the in vitro antifungal activity of miltefosine against terbinafine-resistant Trichophyton indotineae.
  • To compare miltefosine's efficacy with other common antifungal agents against resistant and susceptible dermatophyte isolates.
  • To determine the minimum inhibitory concentration (MIC) ranges for miltefosine against clinical isolates.

Main Methods:

  • Broth microdilution method (CLSI M38-A3) was employed for susceptibility testing.
  • Tested isolates included 40 terbinafine-resistant T. indotineae and 40 terbinafine-susceptible T. mentagrophytes/T. interdigitale.
  • Antifungal agents tested were miltefosine, terbinafine, butenafine, tolnaftate, and itraconazole.

Main Results:

  • Miltefosine demonstrated notable in vitro activity against both terbinafine-resistant and susceptible isolates, with MIC ranges of 0.063-0.5 µg/mL.
  • MIC50 and MIC90 values for miltefosine against resistant isolates were 0.125 µg/mL and 0.25 µg/mL, respectively.
  • Miltefosine showed statistically significant differences in MIC results compared to other antifungals against terbinafine-resistant strains (p-value < 0.05).

Conclusions:

  • Miltefosine exhibits potential as a therapeutic agent for infections caused by terbinafine-resistant Trichophyton indotineae.
  • The in vitro findings warrant further investigation into miltefosine's in vivo efficacy for treating resistant dermatophytosis.
  • This study highlights a potential alternative treatment option for challenging fungal skin infections.
Keywords:
T. indotineaeT. interdigitaleT. mentagrophytesmiltefosineterbinafine

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