cSince the 1950s, vancomycin has remained a reference treatment for severe infections caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Vancomycin is a nephrotoxic and ototoxic drug mainly eliminated through the kidneys. It has a large interindividual pharmacokinetic variability, which justifies monitoring its plasma concentrations in patients. This is especially important in patients aged over 80 years, who frequently have renal impairment. However, the pharmacokinetics of vancomycin in this population is very poorly described in the literature. The objective of this work was to propose a model able to predict the pharmacokinetics of vancomycin in very elderly people. First, a population pharmacokinetic model was carried out using the algorithm NPAG (nonparametric adaptive grid) on a database of 70 hospitalized patients aged over 80 years and treated with vancomycin. An external validation then was performed on 41 patients, and the predictive capabilities of the model were assessed. The model had two compartments and six parameters. Body weight and creatinine clearance significantly influenced vancomycin volume of distribution and body clearance, respectively. The means (؎ standard deviations) of vancomycin volume of distribution and clearance were 36.3 ؎ 15.2 liter and 2.0 ؎ 0.9 liter/h, respectively. In the validation group, the bias and precision were ؊0.75 mg/liter and 8.76 mg/liter for population predictions and ؊0.39 mg/liter and 2.68 mg/ liter for individual predictions. In conclusion, a pharmacokinetic model of vancomycin in a very elderly population has been created and validated for predicting plasma concentrations of vancomycin. Vancomycin is a glycopeptide antibacterial that is widely used for the treatment of serious Gram-positive infections, notably those caused by methicillin-resistant Staphylococcus aureus (MRSA) (1). With the widespread appearance of resistant pathogens such as MRSA, the use of vancomycin has dramatically increased since the early 1980s. The activity of vancomycin is related to an inhibition of the biosynthesis of the bacterial cell wall. The molecule diffuses into the cell wall and binds to the disaccharide pentapeptides, preventing their polymerization and leading to discontinuation of the synthesis of peptidoglycan of the bacterial cell wall.The concentration-effect relationship of vancomycin has been characterized, and the pharmacokinetic (PK)-pharmacodynamic parameter that best describes the efficacy is the ratio of the area under the serum drug concentration-time curve to the MIC (AUC/MIC) (2, 3). Regarding toxicity, it has been shown that vancomycin nephrotoxicity is dose dependent and linked to vancomycin trough concentration (4). As vancomycin elimination is mainly renal, patients with renal impairment are at risk of overexposure and toxicity. As a consequence, a careful monitoring of vancomycin serum concentrations is recommended (5, 6) to optimize efficacy and prevent toxicity.Several methods can be used to individualize dosage ...

Objective: To construct and validate a network to predict the first dose of amikacin. Methods: Anthropometric and therapeutic data were recorded for 120 patients. Bayesian network (BN) was built to predict the dose to achieve a fixed target peak concentration of 64 mg/l. In 40 subjects, doses predicted with the BN (BND) and based on body weight (BWD) were compared with adjusted doses calculated using a pharmacokinetic software (MM-USCPACK; BID). Results: The calculated dose differed by <20% from the ideal dose in 62.5% of the patients with the BN and in 43.8% of the patients with the BW. Conclusion: BN is a promising approach to optimize the prediction of the first dose.

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