Plasma and Cerebrospinal Fluid Population Pharmacokinetics of Vancomycin in Patients with External Ventricular Drain

Chen, Zhendong; Taubert, Max; Chen, Chunli; Dokos, Charalambos; Fuhr, Uwe; Weig, Thomas; Zöller, Michael; Heck, Suzette; Dimitriadis, Konstantinos; Terpolilli, Nicole A.; Kinast, Christina; Scharf, Christina; Lier, Christina J. van; Dorn, Christoph; Liebchen, Uwe

doi:10.1128/aac.00241-23

Cited by 5 publications

(1 citation statement)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The American Thoracic Society Guidelines on Antibiotic Management of Lung Infections recommend IV vancomycin as the first line treatment for pulmonary exacerbations due to MRSA in PwCF (2). Even though, the pharmacokinetics of vancomycin is well studied in other populations (26)(27)(28), there are minimal data on PK of vancomycin in PwCF. Furthermore, the dosing of vancomycin is not consistent across multiple institutions across the United States and is dosed at a wide range between 500 to 2000 mg (6).…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics and Target Attainment Analysis of Vancomycin after Intermittent Dosing in Adults with Cystic Fibrosis

Yellepeddi,

Lindley,

Radetich

et al. 2023

Preprint

View full text Add to dashboard Cite

Vancomycin is the first-line agent to treat pulmonary infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in people with cystic fibrosis (PwCF). However, there is no consensus on vancomycin dosing in this population among health institutions, and there is large variability in dosing regimens across the United States. In this study, we characterized the pharmacokinetics (PK) of vancomycin in PwCF using a population PK approach. The clinical PK data to develop the population PK model was obtained from vancomycin therapeutic monitoring data from PwCF undergoing treatment for infections due to MRSA. The population PK model was then used to perform comprehensive Monte Carlo simulations to evaluate the probability of target attainment (PTA) of 12 different dosing scenarios. The area under the curve to minimum inhibitory concentration ratio (AUC/MIC) ≥ 400 mg*h/L was used as a target for PTA analysis. A total of 181 vancomycin plasma concentrations were included in the analysis. A one-compartment model with first-order elimination best described the data. Weight significantly influenced the vancomycin PK (p < 0.05). In the final model, clearance was estimated as 5.52 L/h/70 kg, and the volume of distribution was 31.5 L/70 kg. The PTA analysis showed that at lower MIC levels (MIC = 1), doses greater than and equal to 1000 mg every 8 hours and 1250 mg every 12 hours resulted in >90% PTA. The PTA results from this study may potentially inform the design of vancomycin dosing regimens to treat pulmonary infections due to MRSA in PwCF.

show abstract

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics and Target Attainment Analysis of Vancomycin after Intermittent Dosing in Adults with Cystic Fibrosis

Yellepeddi,

Lindley,

Radetich

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Vancomycin population pharmacokinetic models: Uncovering pharmacodynamic divergence amid clinicobiological resemblance

Gandia,

Chaiben,

Fabre

et al. 2024

CPT Pharmacom & Syst Pharma

View full text Add to dashboard Cite

Vancomycin is an antibiotic used for severe infections. To ensure microbiological efficacy, a ratio of AUC/MIC ≥400 is recommended. However, there is significant interindividual variability in its pharmacokinetic parameters, necessitating therapeutic drug monitoring to adjust dosing regimens and ensure efficacy while avoiding toxicity. Population pharmacokinetic (PopPK) models enable dose personalization, but the challenge lies in the choice of the model to use among the multitude of models in the literature. We compared 18 PopPK models created from populations with the same sociodemographic and clinicobiological characteristics. Simulations were performed for a 47 years old man, weighing 70 kg, with an albumin level of 35.5 g/L, a creatinine clearance of 100 mL/min, an eGFR of 106 mL/min/1.73 m2, and receiving an intravenous infusion of 1 g × 2/day of VCM over 1 h for 48 h. Simulations of time–concentration profiles revealed differences, leading us to determine the probability of achieving microbiological efficacy (AUC/MIC ≥ 400) with each model. Depending on some models, a dose of 1 g × 2/day is required to ensure microbiological efficacy in over 90% of the population, while with the same dose other models do not exceed 10% of the population. To ensure that 90% of the patients are correctly exposed, a dose of vancomycin ranging from 0.9 g × 2/day to 2.2 g × 2/day is necessary a priori depending on the chosen model. These differences raise an issue in choosing a model for performing therapeutic drug monitoring using a PopPK model with or without Bayesian approach. Thus, it is fundamental to evaluate the impact of these differences on both efficacy/toxicity.

show abstract

A higher area under the concentration-time curve/minimum inhibitory concentration target as a potential prognostic factor for vancomycin treatment of methicillin-resistant Staphylococcus aureus meningitis: A case report

Nakazono,

Saito,

Ohkubo

et al. 2024

IDCases

View full text Add to dashboard Cite

Plasma and Cerebrospinal Fluid Population Pharmacokinetics of Vancomycin in Patients with External Ventricular Drain

Cited by 5 publications

References 51 publications

Population Pharmacokinetics and Target Attainment Analysis of Vancomycin after Intermittent Dosing in Adults with Cystic Fibrosis

Population Pharmacokinetics and Target Attainment Analysis of Vancomycin after Intermittent Dosing in Adults with Cystic Fibrosis

Vancomycin population pharmacokinetic models: Uncovering pharmacodynamic divergence amid clinicobiological resemblance

A higher area under the concentration-time curve/minimum inhibitory concentration target as a potential prognostic factor for vancomycin treatment of methicillin-resistant Staphylococcus aureus meningitis: A case report

Contact Info

Product

Resources

About