Combination of amphotericin B and flucytosine against neurotropic species of melanized fungi causing Primary cerebral phaeohyphomycosis

S. Deng, W. Pan, W. Liao, G. S. De Hoog, A. H G Gerrits Van Den Ende, R. G. Vitale, H. Rafati, M. Ilkit, A. H. Van Der Lee, A. J M M Rijs, P. E. Verweij, S. Seyedmousavi

    Research output: Contribution to journal/periodicalArticleScientificpeer-review

    20 Citations (Scopus)

    Abstract

    Primary central nervous system phaeohyphomycosis is a fatal fungal infection due mainly to the neurotropic melanized fungi Cladophialophora bantiana , Rhinocladiella mackenziei , and Exophiala dermatitidis. Despite the combination of surgery with antifungal treatment, the prognosis continues to be poor, with mortality rates ranging from 50 to 70%. Therefore, a search for a more-appropriate therapeutic approach is urgently needed. Our in vitro studies showed that with the combination of amphotericin B and flucytosine against these species, the median fractional inhibitory concentration (FIC) indices for strains ranged from 0.25 to 0.38, indicating synergy. By use of Bliss independence analysis, a significant degree of synergy was confirmed for all strains, with the sum ΔE ranging from 90.2 to 698.61%. No antagonism was observed. These results indicate that amphotericin B, in combination with flucytosine, may have a role in the treatment of primary cerebral infections caused by melanized fungi belonging to the order Chaetothyriales . Further in vivo studies and clinical investigations to elucidate and confirm these observations are warranted.

    Original languageEnglish
    Pages (from-to)2346-2351
    Number of pages6
    JournalAntimicrobial Agents and Chemotherapy
    Volume60
    Issue number4
    DOIs
    Publication statusPublished - 01 Apr 2016

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