Abstract
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.
Highlights
Bacterial infections of the central nervous system (CNS) are a significant health concern affecting adults and pediatric patients [1,2]
This review presents PK data on the use of meropenem and vancomycin in pediatric and adult patients with ventriculitis and meningitis
Intraventricular administration of vancomycin was only practiced in two studies, both of them in infant ventriculitis, while in the vast majority of studies, meropenem and vancomycin were administered intravenously as an intermittent or continuous infusion in adult meningitis and ventriculitis patients
Summary
Bacterial infections of the central nervous system (CNS) are a significant health concern affecting adults and pediatric patients [1,2]. Essential factors to consider in antibiotic dosage are meningeal inflammation, increased renal clearance, and drainage volume. Increased renal clearance, as often seen in ICU, affects antibiotic serum concentrations, leading to a different relation between dosing and CSF concentration [19,20]. Important model parameters are the clearance (Cl) and the volume of distribution (VD) [32] This latter one is calculated by dividing the amount of drug in the body by the drug’s plasma concentration. PK models for intravenously administered antibiotic concentrations in CNS infections usually contain a central, a peripheral, and a CSF compartment [20,35,36,37]. The overall aim is to provide the readers with a recent reference that summarizes the pitfalls and success of the current therapy and improves the clinical outcome of the antibiotic therapy of patients affected by meningitis and ventriculitis
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