Aspergillus species can cause ocular morbidity and
blindness, and thus, appropriate antifungal
therapy is needed. We investigated the in vitro activity of
itraconazole,
voriconazole,
posaconazole,
caspofungin,
anidulafungin, and
amphotericin B against 14 Aspergillus isolates obtained from patients with
ocular mycoses, using the CLSI reference broth microdilution methodology. In addition, time-kill assays were performed, exposing each isolate separately to 1-, 4-, and 16-fold concentrations above the minimum inhibitory concentration (MIC) of each
antifungal agent. A sigmoid maximum-effect (E max) model was used to fit the time-kill curve data. The
drug effect was further evaluated by measuring an increase/decrease in the killing rate of the tested isolates. The MICs of
amphotericin B,
itraconazole,
voriconazole, and
posaconazole were 0.5-1.0, 1.0, 0.5-1.0, and 0.25 µg/ml for A. brasiliensis, A. niger, and A. tubingensis isolates, respectively, and 2.0-4.0, 0.5, 1.0 for A. flavus, and 0.12-0.25 µg/ml for A. nomius isolates, respectively. A. calidoustus had the highest MIC range for the
azoles (4.0-16.0 µg/ml) among all isolates tested. The minimum effective concentrations of
caspofungin and
anidulafungin were ≤0.03-0.5 µg/ml and ≤0.03 µg/ml for all isolates, respectively.
Posaconazole demonstrated maximal killing rates (E(max) = 0.63 h(-1), r(2) = 0.71) against 14 ocular Aspergillus isolates, followed by
amphotericin B (E(max) = 0.39 h(-1), r(2) = 0.87),
voriconazole (E(max) = 0.35 h(-1), r(2) = 0.098), and
itraconazole (E(max) = 0.01 h(-1), r(2) = 0.98). Overall, the antifungal susceptibility of the non-fumigatus Aspergillus isolates tested was species and
antifungal agent dependent. Analysis of the kinetic growth assays, along with consideration of the killing rates, revealed that
posaconazole was the most effective antifungal against all of the isolates.