Population pharmacokinetic parameters of vancomycin in critically ill patients

Llopis-Salvia, P.; Jiménez-Torres, N.V.

doi:10.1111/j.1365-2710.2006.00762.x

Cited by 90 publications

(102 citation statements)

References 27 publications

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“…In this cohort of patients over 80, the best structural model was found to be a two-compartment model, as in most of the studies carried out in adults (9,(18)(19)(20)(21)(22)(23).…”

Section: Discussionmentioning

confidence: 90%

Pharmacokinetics of Vancomycin in Elderly Patients Aged over 80 Years

Bourguignon

Cazaubon

Debeurme

et al. 2016

Antimicrob Agents Chemother

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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 ...

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“…In this cohort of patients over 80, the best structural model was found to be a two-compartment model, as in most of the studies carried out in adults (9,(18)(19)(20)(21)(22)(23).…”

Section: Discussionmentioning

confidence: 90%

Pharmacokinetics of Vancomycin in Elderly Patients Aged over 80 Years

Bourguignon

Cazaubon

Debeurme

et al. 2016

Antimicrob Agents Chemother

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“…Therefore, it cannot be assumed that the outcomes from that study would be applicable to ICU patients undergoing CVVHD, because of the wide variability in the pharmacokinetics of vancomycin in these patients and the differences in types of dialysis. 43,44 However, the results of the current study for initial intermittent dosing of 1.25-1.5 g IV q24h in critically ill patients undergoing CVVHD fall within the range recommended by Joy and others. 16 In the investigation by Davies and others, 17 4 ICU patients were managed with concurrent vancomycin and CVVHD.…”

Section: -41mentioning

confidence: 77%

“…Previous studies have demonstrated that there are significant changes in both clearance and volume of distribution throughout the course of vancomycin therapy in ICU patients. [42][43][44] del Mar Fernández and others 44 observed that the mean volume of distribution of vancomycin among 46 critically ill patients was 1.69 L/kg, nearly double that observed in healthy adult subjects with normal renal function (0.4-1 L/kg). 30,[45][46][47] In a population-based = area under the concentration-time curve over 24 h, MIC = minimum inhibitory concentration.…”

Section: -41mentioning

confidence: 99%

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Initial Vancomycin Dosing Recommendations for Critically Ill Patients Undergoing Continuous Venovenous Hemodialysis

Vijsel

Walker

et al. 2010

CJHP

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“…Due to its nephrotoxic effects, empirical dosing based on creatinine clearance with subsequent TDM of C min plasma concentrations is recommended. 29 …”

Section: Glycopeptidesmentioning

confidence: 99%

Pharmacokinetic considerations and dosing strategies of antibiotics in the critically ill patient

Shah

Barton

Fischer

2015

Journal of the Intensive Care Society

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The treatment of sepsis remains a significant challenge and is the cause of high mortality and morbidity. The pathophysiological alterations that are associated with sepsis can complicate drug dosing. Critical care patients often have capillary leak, increased cardiac output and altered protein levels which can have profound effects on the volume of distribution (Vd) and clearance (Cl) of antibacterial agents, both of which may affect the pharmacokinetics (PK) / pharmacodynamics (PD) of the drug. Along with antibacterial factors such as the hydrophilicity and its kill characteristics and the susceptibility and site of action of the microorganism, different dosing and administration strategies may be needed for the different drug classes. In conclusion, developing dosing and administration regimes of antibacterials that adhere to PK/PD principles increase antibacterial exposure. Tailoring therapy to the individual patient combined with TDM may contribute to improved clinical efficacy and contain the spread of resistance.

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Population pharmacokinetic parameters of vancomycin in critically ill patients

Abstract: The use of population-specific pharmacokinetic parameters and Bayesian forecasting improves dosage-regimen design.

Cited by 90 publications

References 27 publications

Pharmacokinetics of Vancomycin in Elderly Patients Aged over 80 Years

Pharmacokinetics of Vancomycin in Elderly Patients Aged over 80 Years

Initial Vancomycin Dosing Recommendations for Critically Ill Patients Undergoing Continuous Venovenous Hemodialysis

Pharmacokinetic considerations and dosing strategies of antibiotics in the critically ill patient

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