Factors related to hemodynamic response and vital support measures have a significant influence on the disposition kinetics of amikacin in severely ill patients with sepsis. Consideration of hemodynamic response and vital support measures, in addition to other previously described covariates, can be of great value in the design of initial dosing regimens.

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The new rapid scan method, Flyscan mode, implemented on the DiffAbs beamline at Synchrotron SOLEIL, allows fast micro-X-ray fluorescence data acquisition. It paves the way for applications in the biomedical field where a large amount of data is needed to generate meaningful information for the clinician. This study presents a complete set of data acquired after injection of gold-cluster-enriched mesoporous silica nanospheres, used as potential theranostic vectors, into rats. While classical X-ray fluorescence investigations (using step-by-step acquisitions) are based on a limited number of samples (approximately one per day at the DiffAbs beamline), the Flyscan mode has enabled gathering information on the interaction of nanometer-scale vectors in different organs such as liver, spleen and kidney at the micrometer scale, for five rats, in only a single five-day synchrotron shift. Moreover, numerous X-ray absorption near-edge structure spectra, which are beam-time-consuming taking into account the low concentration of these theranostic vectors, were collected.

This study was designed to determine the population pharmacokinetic parameters of amikacin in two subpopulations of intensive care unit patients with sepsis and cirrhosis and sepsis without cirrhosis. The authors evaluated the usefulness of the obtained parameters to forecast the serum amikacin concentrations in a validation group of patients with sepsis and cirrhosis when used as a priori distribution in a Bayesian forecaster. The population parameters were estimated by a nonparametric expectation maximization algorithm (NPEM), and the accuracy of the predictions were evaluated through a prediction error analysis. Significant differences (p < 0.05) were found in Vd (0.668 versus 0.470 l/kg) and K (0.0701 versus 0.161 h-1) between subpopulations of patients with and without cirrhosis. The model derived for patients with cirrhosis used as a priori distribution, with and without feedback, was superior to the model derived for patients with sepsis in forecasting amikacin serum concentrations. The results show the relevance of using the specific model for the subgroup with cirrhosis as a priori distribution in a Bayesian forecaster to obtain a nonbiased prediction with an acceptable precision.

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