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.

The First Isolation of Ustilaginomycetous Anamorphic Yeasts, Pseudozyma Species, from Patients' Blood and a Description of Two New Species: P. parantarctica and P. thailandica

“…While the susceptibility of unusual yeasts to antifungal agents varies, drug-resistant yeasts have been identified. Candida haemulonii, C. lusitaniae, Pichia farinosa, and Trichosporon asahii are resistant to amphotericin B (5,10,13,18). C. inconspicua, C. norvegensis, and some species of Rhodotorula are resistant to fluconazole (1,5).…”

Fungemia due to Trichosporon asahii in a Neutropenic Child Refractory to Amphotericin B

“…1 Trichosporon asahii is now the species most often implicated in disseminated infections in neutropenic patients. 1,4 Treatment of systemic Trichosporon infection with conventional antifungal agents, such as amphotericin B and fluconazole, has generally been unrewarding, resulting in a crude mortality rate approximating 80%. 1,4 Recent studies have shown that voriconazole, a second-generation triazole, is highly active against T. asahii isolates in vitro.…”

“…in immunocompromised patients, especially those with hematologic malignancies, are frequently associated with poor prognosis. [1][2][3][4] Since the taxonomic revision of the genus Trichosporon in 1992, it has been recognized that the formerly used designation Trichosporon beigelii includes several genetically distinct species. 1 Trichosporon asahii is now the species most often implicated in disseminated infections in neutropenic patients.…”

Candida pseudohaemulonii Sp. Nov., an Amphotericin B‐ and Azole‐Resistant Yeast Species, Isolated from the Blood of a Patient from Thailand

“…Despite more than 40 years of clinical use, resistance to amphotericin B is very rare. Only C. lusitaniae, C. haemulonii, and Trichosporon asahii have reduced sensitivity to this drug (2,9,11,16). Although C. pseudohaemulonii and the two types of C. haemulonii are resistant to both amphotericin B and azole agents, they are very susceptible to 5-FC and micafungin.…”