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In vitro combination between antifungals and diphenyl diselenide against Cryptococcus species

Luana Rossato1, Erico S Loreto1,2, Tarcieli P Venturini1

  • 1Postgraduate Program in Pharmaceutical Sciences, Health Sciences Centre, Federal University of Santa Maria (UFSM), Santa Maria, Rio Grande do Sul, Brazil.

Mycoses
|February 19, 2019
PubMed

Insights

Diphenyl diselenide combined with flucytosine shows 100% synergy against Cryptococcus species, offering a promising new avenue for treating cryptococcal meningitis. This combination therapy warrants further investigation for improved antifungal treatments.

Area of Science:

  • Mycology
  • Infectious Diseases
  • Pharmacology

Background:

  • Cryptococcus species are significant fungal pathogens causing cryptococcal meningitis, a serious infection with limited therapeutic options.
  • Current antifungal treatments like amphotericin B, flucytosine, and fluconazole have documented therapeutic failures and limited effectiveness.
  • Diphenyl diselenide is a synthetic molecule demonstrating known antimicrobial properties.

Purpose of the Study:

  • To evaluate the combined antifungal activity of diphenyl diselenide with established antifungals (fluconazole, amphotericin B, flucytosine) against clinical isolates of Cryptococcus spp.
  • To identify synergistic or indifferent interactions between diphenyl diselenide and standard antifungal agents.

Main Methods:

  • Utilized the CLSI M27-A3 standard method for antifungal susceptibility testing.
  • Employed the checkerboard microdilution technique to assess drug combinations.
  • Tested against 30 clinical isolates of Cryptococcus species.

Main Results:

  • The combination of diphenyl diselenide and flucytosine demonstrated 100% synergism against all tested Cryptococcus isolates.
  • Combinations of diphenyl diselenide with amphotericin B or fluconazole showed approximately 70% indifference.

Conclusions:

  • Diphenyl diselenide exhibits significant synergistic activity when combined with flucytosine against Cryptococcus species.
  • This synergistic interaction suggests that diphenyl diselenide holds potential as a component in novel combination therapies for cryptococcosis.
  • Further research into diphenyl diselenide-based antifungal combinations is recommended for developing alternative treatments.
Keywords:
amphotericin Bcryptococcosisfluconazoleflucytosineselenium

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