ALERT: This system is being upgraded on Tuesday December 12. It will not be available for use for several hours that day while the upgrade is in progress. Deposits to DukeSpace will be disabled on Monday December 11, so no new items are to be added to the repository while the upgrade is in progress. Everything should be back to normal by the end of day, December 12.

Show simple item record

Population Pharmacodynamics of Amphotericin B Deoxycholate for Disseminated Infection Caused by Talaromyces marneffei. Le, Thuy Ly, Vo Trieu Thu, Nguyen Thi Mai Nguyen, Ashley Thanh, Nguyen Tat Chau, Nguyen Van Vinh Thwaites, Guy Perfect, John Kolamunnage-Dona, Ruwanthi Hope, William 2019-05-01T17:34:11Z 2019-05-01T17:34:11Z 2019-02
dc.identifier AAC.01739-18
dc.identifier.issn 0066-4804
dc.identifier.issn 1098-6596
dc.description.abstract 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.).
dc.language eng
dc.publisher American Society for Microbiology
dc.relation.ispartof Antimicrobial Agents and Chemotherapy
dc.relation.isversionof 10.1128/AAC.01739-18
dc.subject PK-PD
dc.subject Penicillium
dc.subject Talaromyces
dc.subject amphotericin
dc.subject antifungal
dc.subject pharmacodynamics
dc.subject population pharmacokinetics
dc.subject talaromycosis
dc.title Population Pharmacodynamics of Amphotericin B Deoxycholate for Disseminated Infection Caused by Talaromyces marneffei.
dc.type Journal article Le, Thuy|0831715 Perfect, John|0113110 2019-05-01T17:34:09Z
pubs.begin-page e01739
pubs.end-page 18
pubs.issue 2
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Medicine, Infectious Diseases
pubs.organisational-group Medicine
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Molecular Genetics and Microbiology
pubs.organisational-group Basic Science Departments
pubs.publication-status Published
pubs.volume 63
duke.contributor.orcid Le, Thuy|0000-0002-3393-6580
duke.contributor.orcid Perfect, John|0000-0002-6606-9460|0000-0003-3465-5518

Files in this item


This item appears in the following Collection(s)

Show simple item record