Treatment of disseminated
Trichosporon infections still remains difficult.
Amphotericin B frequently displays inadequate fungicidal activity and
echinocandins have no meaningful antifungal effect against this genus.
Triazoles are currently the drugs of choice for the treatment of
Trichosporon infections. This study evaluates the inhibitory and fungicidal activities of five
triazoles against 90 clinical isolates of Trichosporon asahii. MICs (μg/ml) were determined according to Clinical and Laboratory Standards Institute microdilution method M27-A3 at 24 and 48 h using two endpoints, MIC-2 and MIC-0 (the lowest concentrations that inhibited ∼50 and 100% of growth, respectively). Minimum fungicidal concentrations (MFCs; μg/ml) were determined by seeding 100 μl of
all clear MIC wells (using an inoculum of 10(4) CFU/ml) onto Sabouraud
dextrose agar. Time-kill curves were assayed against four clinical T. asahii isolates and the T. asahii ATCC 201110 strain. The MIC-2 (∼50% reduction in turbidity compared to the growth control well)/MIC-0 (complete inhibition of growth)/MFC values that inhibited 90% of isolates at 48 h were, respectively, 8/32/64 μg/ml for
fluconazole, 1/2/8 μg/ml for
itraconazole, 0.12/0.5/2 μg/ml for
voriconazole, 0.5/2/4 μg/ml for
posaconazole, and 0.25/1/4 μg/ml for
isavuconazole. The MIC-0 endpoints yielded more consistent MIC results, which remained mostly unchanged when extending the incubation to 48 h (98 to 100% agreement with 24-h values) and are easier to interpret. Based on the time-kill experiments, none of the drugs reached the fungicidal endpoint (99.9% killing), killing activity being shown but at concentrations not reached in serum. Statistical analysis revealed that killing rates are dose and antifungal dependent. The lowest concentration at which killing activity begins was for
voriconazole, and the highest was for
fluconazole. These results suggest that
azoles display fungistatic activity and lack fungicidal effect against T. asahii. By rank order, the most active
triazole is
voriconazole, followed by
itraconazole ∼
posaconazole ∼
isavuconazole >
fluconazole.