Combination of Amphotericin B and Flucytosine against Neurotropic Species of Melanized Fungi Causing Primary Cerebral Phaeohyphomycosis

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 Delta E 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

Molecular phylogeny and taxonomy of medically important fungi

Some recent advances in study of molecular evolution and taxonomy of human pathogens are discussed. In systemic Onygenales as well as in Chaetothyriales, pathogenic species are phylogenetically intermingled with non-pathogenic taxa. When a teleomorph of Coccidioides immitis is eventually found, it is predicted to resemble Uncinocarpus, a genus otherwise comprising environmental species. In the dermatophytes, Trichophyton and Microsporum are paraphyletic, whereas Epidermophyton is polyphyletic. On the basis of 18S and ITS rDNA sequencing data, Exophiala anamorphs (black yeasts) are confirmed to be closely related to the ascomycete genus Capronia. The related neurotropic species Cladophialophora bantiana is remarkable in consistently having introns in its 18S rDNA gene