Antifungal pharmacodynamic characteristics of amphotericin B against Trichosporon asahii, using time-kill methodology.
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 microg/ml, and most T. asahii isolates (76%, 34/45) were inhibited at safely achievable amphotericin B serum concentrations (< or = 2 microg/ml). However, 40% (18/45) of isolates were not killed at these concentrations (MFCs from 1.0 to 32 microg/ml). At concentrations > or = 2 x MIC, amphotericin B exhibited fungicidal activity (< 99.9% reduction in CFU) over a 12-hr time-period; the maximal effect was achieved at > or =4 x 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.
Toriumi
Yoshimi
Y
Department of Microbiology, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan.
Sugita
Takashi
T
Nakajima
Masamitsu
M
Matsushima
Toshiharu
T
Shinoda
Takako
T
D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D013997:Time Factors; D014250:Trichosporon / Q000187:drug effects*
D000935:Antifungal Agents; D000666:Amphotericin B