TY - JOUR
T1 - Combination of amphotericin B and flucytosine against neurotropic species of melanized fungi causing Primary cerebral phaeohyphomycosis
AU - Deng, S.
AU - Pan, W.
AU - Liao, W.
AU - De Hoog, G. S.
AU - Van Den Ende, A. H G Gerrits
AU - Vitale, R. G.
AU - Rafati, H.
AU - Ilkit, M.
AU - Van Der Lee, A. H.
AU - Rijs, A. J M M
AU - Verweij, P. E.
AU - Seyedmousavi, S.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
U2 - 10.1128/AAC.02526-15
DO - 10.1128/AAC.02526-15
M3 - Article
C2 - 26833164
SN - 0066-4804
VL - 60
SP - 2346
EP - 2351
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 4
ER -