Population Pharmacodynamics of Amphotericin B Deoxycholate for Disseminated Infection Caused by Talaromyces marneffei

Amphotericin B deoxycholate (DAmB) is a first-line agent for the initial treatment of talaromycosis. However, little is known about the population pharmacokinetics and pharmacodynamics of DAmB for talaromycosis. Pharmacokinetic data were obtained from 78 patients; among them 55 patients had serial fungal colony forming units counts in blood also available for analysis. A population pharmacokinetics-pharmacodynamics model was fitted to the data. The relationships between area under the concentration time curve (AUC):MIC, and the time to blood culture sterilization and the time to death were investigated. There was only modest pharmacokinetic variability in the average AUC with a mean (standard deviation) of 11.51 (3.39) mg*h/L. The maximal rate of drug induced kill was 0.133 log 10 CFU/mL/h, and the plasma concentration of the DAmB that induced half-maximal rate of kill was 0.02 mg/L. Fifty percent of patients sterilized their bloodstream by 83.16 hours (range 13-264 hours). A higher initial fungal burden was associated with longer time to sterilization (hazard ratio (HR): 0.51, 95% confidence interval (CI): 0.36-0.70, p