Defining Optimal Doses of Liposomal Amphotericin B Against Candida auris: Data From an In Vitro Pharmacokinetic/Pharmacodynamic Model.
J Infect Dis
; 229(2): 599-607, 2024 Feb 14.
Article
em En
| MEDLINE
| ID: mdl-38109276
ABSTRACT
BACKGROUND:
Candida auris isolates exhibit elevated amphotericin B (AMB) minimum inhibitory concentrations (MICs). As liposomal AMB (L-AMB) can be safely administered at high doses, we explored L-AMB pharmacodynamics against C. auris isolates in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) dilution model.METHODS:
Four C. auris isolates with Clinical and Laboratory Standards Institute (CLSI) AMB MICs = 0.5-2â mg/L were tested in an in vitro PK/PD model simulating L-AMB pharmacokinetics. The in vitro model was validated using a Candida albicans isolate tested in animals. The peak concentration (Cmax)/MIC versus log10 colony-forming units (CFU)/mL reduction from the initial inoculum was analyzed with the sigmoidal model with variable slope (Emax model). Monte Carlo analysis was performed for the standard (3â mg/kg) and higher (5â mg/kg) L-AMB doses.RESULTS:
The in vitro PK/PD relationship Cmax/MIC versus log10 CFU/mL reduction followed a sigmoidal pattern (R2 = 0.91 for C. albicans, R2 = 0.86 for C. auris). The Cmax/MIC associated with stasis was 2.1 for C. albicans and 9 for C. auris. The probability of target attainment was >95% with 3â mg/kg for wild-type C. albicans isolates with MIC ≤2â mg/L and C. auris isolates with MIC ≤1â mg/L whereas 5â mg/kg L-AMB is needed for C. auris isolates with MIC 2â mg/L.CONCLUSIONS:
L-AMB was 4-fold less active against C. auris than C. albicans. Candida auris isolates with CLSI MIC 2â mg/L would require a higher L-AMB dose.Palavras-chave
Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Limite:
Animals
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article