Use of amplified fragment length polymorphism to identify 42 Cladophialophora strains related to cerebral phaeohyphomycosis with in vitro antifungal susceptibility

Abstract

The amplified fragment length polymorphism technique has been applied to identify neurotropic chaetothyrialean black yeasts and relatives from clinical sources. Cladophialophora bantiana, C. emmonsii, C. arxii, C. devriesii, and C. modesta, previously identified on the basis of sequencing and phenotypic and physiological criteria, were confirmed by cluster analysis, demonstrating the clear separation of C. bantiana as a rather homogeneous group from the other species. C. bantiana is a neurotropic fungus causing cerebral abscesses with a mortality of up to 70%. Successful therapy consists of neurosurgical intervention and optimal antifungal therapy. Since the latter is not clearly defined in a large series, we tested the in vitro activities of eight antifungal drugs against clinical isolates of C. bantiana (n = 37), C. modesta (n = 2), C. arxii (n = 1), C. emmonsii (n = 1), and C. devriesii (n = 1), all of which had caused invasive infections. The resulting MIC(90)s for all neurotropic C. bantiana strains were as follows, in increasing order: posaconazole, 0.125 microg/ml; itraconazole, 0.125 microg/ml; isavuconazole, 0.5 microg/ml; amphotericin B, 1 microg/ml; voriconazole, 2 microg/ml; anidulafungin, 2 microg/ml; caspofungin, 4 microg/ml; and fluconazole, 64 microg/ml. On the basis of these in vitro results and the findings of previous clinical and animal studies, posaconazole seems to be a good alternative to the standard treatment, amphotericin B, for C. bantiana cerebral infections. The new agent isavuconazole, which is also available as an intravenous preparation, has adequate activity against C. bantiana.

FIG. 1.

Dendrogram of AFLP analysis of 42 Cladophialophora isolates (numbers to the right of the figure are CBS strain designations; the scale bar on the left indicates the percent similarity).