Antifungal pharmacodynamic characteristics of amphotericin B against Trichosporon asahii, using time-kill methodology

Abstract

We determined the MIC of amphotericin B against 45 Trichosporon asahii isolates from various clinical and environmental sources, and used in vitro time-kill methods to characterize the relationship between amphotericin B concentrations and MIC for four representative T. asahii isolates. Amphotericin B had concentration-dependent antifungal activity. MICs ranged from 0.5 to 16 μg/ml, and most T. asahii isolates (76%, 34/45) were inhibited at safely achievable amphotericin B serum concentrations (≤ 2 μg/ml). However, 40% (18/45) of isolates were not killed at these concentrations (MFCs from 1.0 to 32 μg/ml). At concentrations ≥2×MIC, amphotericin B exhibited fungicidal activity (<99.9% reduction in CFU) over a 12-hr time-period; the maximal effect was achieved at ≥4×MIC. Susceptibility testing confirmed the resistance of T. asahii to amphotericin B, and in vitro pharmacodynamic results also suggest that amphotericin B is not suitable therapy for T. asahii infection.