Population pharmacokinetics of vancomycin in patients with external ventricular drain‐associated ventriculitis

Jalusic, Kris Oliver; Hempel, Georg; Arnemann, Philip-Helge; Spiekermann, Christina; Kampmeier, Tim-Gerald; Ertmer, Christian; Gastine, Silke; Heßler, Michael

doi:10.1111/bcp.14657

Cited by 16 publications

(20 citation statements)

References 49 publications

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“…A linear three-compartmental model demonstrated that total vancomycin plasma clearance (Cl) depends on creatinine clearance and that CSF lactate concentration correlates with the clearance between the central and the CSF department. Therefore, Jalusic et al recommend the application of TDM and consider the degree of inflammation, measured by CSF lactate, and renal function for vancomycin dosing [ 20 ].…”

Section: Vancomycinmentioning

confidence: 99%

“…Therefore, the type of illness also impacts CSF drug penetration. Moreover, increased renal clearance, as often seen in ICU, affects antibiotic serum concentrations, leading to a different relation between dosing and CSF concentration [ 19 , 20 ]. Therefore, enhanced renal clearance must be considered to prevent underdosing in critically ill patients.…”

Section: Introductionmentioning

confidence: 99%

“…Through statistical modeling, values for VD and Cl are generated to provide the best possible fit of the model and therefore lead to a minimal difference between predicted and measured concentration [ 32 ]. In CNS infections, multiple factors can influence the antibiotics’ PK [ 16 , 20 , 22 ]. Therefore, PK models can deliver valuable information about antibiotic dosing in different types of CNS infections.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, PK models can deliver valuable information about antibiotic dosing in different types of CNS infections. PK models for intravenously administered antibiotic concentrations in CNS infections usually contain a central, a peripheral, and a CSF compartment [ 20 , 35 , 36 , 37 ]. Extensive review about the generation of statistical modeling is out of the scope of this review and can be found elsewhere [ 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of Vancomycin and Meropenem in Central Nervous System Infections in Children and Adults: Current Update

2022

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The current antimicrobial therapy of bacterial infections of the central nervous system (CNS) in adults and pediatric patients is faced with many pitfalls as the drugs have to reach necessary levels in serum and cross the blood-brain barrier. Furthermore, several studies report that different factors such as the structure of the antimicrobial agent, the severity of disease, or the degree of inflammation play a significant role. Despite the available attempts to establish pharmacokinetic (PK) modeling to improve the required dosing regimen for adults and pediatric patients, conclusive recommendations for the best therapeutic strategies are still lacking. For instance, bacterial meningitis, the most common CNS infections, and ventriculitis, a severe complication of meningitis, are still associated with 10% and 30% mortality, respectively. Several studies report on the use of vancomycin and meropenem to manage meningitis and ventriculitis; therefore, this review aims to shed light on the current knowledge about their use in adults and pediatric patients. Consequently, studies published from 2015 until mid-July 2021 are included, and data about the study population, levels of drugs in serum and cerebrospinal fluid (CSF), and measured PK data in serum and CSF are provided. The overall aim is to provide the readers a recent reference that summarizes the pitfalls and success of the current therapy and emphasizes the importance of performing more studies to improve the clinical outcome of the current therapeutical approach.

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Section: Vancomycinmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Efficacy of Vancomycin and Meropenem in Central Nervous System Infections in Children and Adults: Current Update

2022

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“…The drug loss from CSF can be described by the clearance of the CSF compartment (CL CSF ), which was related to the average daily drainage amount (DA) and the elapsed time (ET) after IVT injection. Similarly, a recent PK study for patients with EVD-associated ventriculitis conducted by Jalusic et al (2021) built a three-compartment model with two elimination pathways. They found CSF lactate levels as a substitute for inflammatory processes may be associated with increased CSF vancomycin concentration.…”

Section: Effects Of Patients-specific Factors On Vancomycin Pk/pd For...mentioning

confidence: 99%

Augmented Renal Clearance in Severe Infections—An Important Consideration in Vancomycin Dosing: A Narrative Review

Xiao

Zhang

et al. 2022

Front. Pharmacol.

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Vancomycin is a hydrophilic antibiotic widely used in severe infections, including bacteremia and central nervous system (CNS) infections caused by Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), coagulase-negative staphylococci and enterococci. Appropriate antimicrobial dosage regimens can help achieve the target exposure and improve clinical outcomes. However, vancomycin exposure in serum and cerebrospinal fluid (CSF) is challenging to predict due to rapidly changing pathophysiological processes and patient-specific factors. Vancomycin concentrations may be decreased for peripheral infections due to augmented renal clearance (ARC) and increased distribution caused by systemic inflammatory response syndrome (SIRS), increased capillary permeability, and aggressive fluid resuscitation. Additionally, few studies on vancomycin’s pharmacokinetics (PK) in CSF for CNS infections. The relationship between exposure and clinical response is unclear, challenging for adequate antimicrobial therapy. Accurate prediction of vancomycin pharmacokinetics/pharmacodynamics (PK/PD) in patients with high interindividual variation is critical to increase the likelihood of achieving therapeutic targets. In this review, we describe the interaction between ARC and vancomycin PK/PD, patient-specific factors that influence the achievement of target exposure, and recent advances in optimizing vancomycin dosing schedules for severe infective patients with ARC.

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External validation of population pharmacokinetic models of vancomycin in postoperative neurosurgical patients

Wei

Chen

Zhao

et al. 2023

Eur J Clin Pharmacol

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Population pharmacokinetics of vancomycin in patients with external ventricular drain‐associated ventriculitis

Abstract: Running head: A pharmacokinetic model describing vancomycin in neurocritical care patients with ventriculitis was developed. Based on our analysis, the dosing of vancomycin should be referred to the degree of inflammation and renal function.

Cited by 16 publications

References 49 publications

Efficacy of Vancomycin and Meropenem in Central Nervous System Infections in Children and Adults: Current Update

Efficacy of Vancomycin and Meropenem in Central Nervous System Infections in Children and Adults: Current Update

Augmented Renal Clearance in Severe Infections—An Important Consideration in Vancomycin Dosing: A Narrative Review

External validation of population pharmacokinetic models of vancomycin in postoperative neurosurgical patients

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