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

Publication ,  Journal Article
Le, T; Ly, VT; Thu, NTM; Nguyen, A; Thanh, NT; Chau, NVV; Thwaites, G; Perfect, J; Kolamunnage-Dona, R; Hope, W
Published in: Antimicrob Agents Chemother
February 2019

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 CFU counts in blood also available for analysis. A population pharmacokinetic-pharmacodynamic model was fitted to the data. The relationships between the 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/liter. The maximal rate of drug-induced kill was 0.133 log10 CFU/ml/h, and the plasma concentration of the DAmB that induced the half-maximal rate of kill was 0.02 mg/liter. Fifty percent of patients sterilized their bloodstreams by 83.16 h (range, 13 to 264 h). A higher initial fungal burden was associated with a longer time to sterilization (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.36 to 0.70; P < 0.001). There was a weak relationship between AUC/MIC and the time to sterilization, although this did not reach statistical significance (HR, 1.03; 95% CI, 1.00 to 1.06, P = 0.091). Furthermore, there was no relationship between the AUC/MIC and time to death (HR, 0.97; 95% CI, 0.88 to 1.08; P = 0.607) or early fungicidal activity {slope = log[(0.500 - 0.003·(AUC/MIC)]; P = 0.319} adjusted for the initial fungal burden. The population pharmacokinetics of DAmB are surprisingly consistent. The time to sterilization of the bloodstream may be a useful pharmacodynamic endpoint for future studies. (This study has been registered at the ISRCTN registry under no. ISRCTN59144167.).

Duke Scholars

Published In

Antimicrob Agents Chemother

DOI

EISSN

1098-6596

Publication Date

February 2019

Volume

63

Issue

2

Location

United States

Related Subject Headings

  • Talaromyces
  • Penicillium
  • Microbiology
  • Microbial Sensitivity Tests
  • Male
  • Humans
  • Female
  • Drug Combinations
  • Deoxycholic Acid
  • Area Under Curve
 

Citation

APA
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MLA
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Le, T., Ly, V. T., Thu, N. T. M., Nguyen, A., Thanh, N. T., Chau, N. V. V., … Hope, W. (2019). Population Pharmacodynamics of Amphotericin B Deoxycholate for Disseminated Infection Caused by Talaromyces marneffei. Antimicrob Agents Chemother, 63(2). https://doi.org/10.1128/AAC.01739-18
Le, Thuy, Vo Trieu Ly, Nguyen Thi Mai Thu, Ashley Nguyen, Nguyen Tat Thanh, Nguyen Van Vinh Chau, Guy Thwaites, John Perfect, Ruwanthi Kolamunnage-Dona, and William Hope. “Population Pharmacodynamics of Amphotericin B Deoxycholate for Disseminated Infection Caused by Talaromyces marneffei.Antimicrob Agents Chemother 63, no. 2 (February 2019). https://doi.org/10.1128/AAC.01739-18.
Le T, Ly VT, Thu NTM, Nguyen A, Thanh NT, Chau NVV, et al. Population Pharmacodynamics of Amphotericin B Deoxycholate for Disseminated Infection Caused by Talaromyces marneffei. Antimicrob Agents Chemother. 2019 Feb;63(2).
Le, Thuy, et al. “Population Pharmacodynamics of Amphotericin B Deoxycholate for Disseminated Infection Caused by Talaromyces marneffei.Antimicrob Agents Chemother, vol. 63, no. 2, Feb. 2019. Pubmed, doi:10.1128/AAC.01739-18.
Le T, Ly VT, Thu NTM, Nguyen A, Thanh NT, Chau NVV, Thwaites G, Perfect J, Kolamunnage-Dona R, Hope W. Population Pharmacodynamics of Amphotericin B Deoxycholate for Disseminated Infection Caused by Talaromyces marneffei. Antimicrob Agents Chemother. 2019 Feb;63(2).

Published In

Antimicrob Agents Chemother

DOI

EISSN

1098-6596

Publication Date

February 2019

Volume

63

Issue

2

Location

United States

Related Subject Headings

  • Talaromyces
  • Penicillium
  • Microbiology
  • Microbial Sensitivity Tests
  • Male
  • Humans
  • Female
  • Drug Combinations
  • Deoxycholic Acid
  • Area Under Curve