In Vitro Activity of Voriconazole against 71 Clinical Isolates of Dematiaceous Filamentous Fungi.



Background: The spectrum of mycoses incited by dematiaceous filamentous fungi (DFF) includes mycetoma, chromoblastomycosis, sporotrichosis, and various forms of phaeohyphomycosis. As invasive/disseminated disease in compromised hosts has a high mortality rate and limited therapeutic options, isolates received from patients being considered for compassionate therapy were evaluated in vitro. Methods: A total of 39 clinical isolates of DFF (9 S. prolificans [SP], 6 Alternaria spp., 2 each of Curvularia, Cladosporium, Fonsecaea pedrosoi, Phialemonium obovatum, and P. curvatum, and one each of Madurella grisea, Exophiala jeanselmei, Exophiala sp., Phialophora richardsiae, P. verrucosa, Bipolaris hawaiiensis, Rhinocladiella atrovirens, Ramichloridium mackenziei, Wangiella dermatitidis, Sporothrix schenckii, Phoma sp., Pestalotiopsis sp, Epicoccum purpurascens, and a sterile dematiaceous mould) as well as 32 clinical isolates of Scedosporium apiospermum [SA] (thought to be dematiaceous by some) were evaluated for MICs to VORI using a broth macro dilution method following NCCLS guidelines (document M38-P). Results: Geometric mean MICs in µg/ml were as follows: SA, 0.31; SP, 17.2; agents of mycetoma (n=1), 0.5; agents of chromoblastomycosis (n=4), 0.06; and miscellaneous agents of phaeohypomycosis (n=24), 0.64. Conclusions: 1) Potent antifungal activity ( 0.5 µg/ml) was noted for SA, agents of chromoblastomycosis (P. verrucosa, F. pedrosoi, and R. atrovirens), mycetoma (Madurella grisea), and several agents of subcutaneous/cerebral phaeohyphomycosis. 2) Seven isolates in various other genera had MICs between 1-2 µg/ml (GM 1.49), while four isolates in the genera Alternaria, Phialemonium, and Sporothrix displayed MICs between 4-8 µg/ml (GM 5.66). SP appears resistant in vitro. 3) Further studies are needed to correlate in vitro data with clinical outcome.

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42nd Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 42nd