Pharmacokinetics of antibacterial agents in the CSF of children and adolescents

Paediatric Drugs
Amanda K Sullins, Susan M Abdel-Rahman

Abstract

The adequate management of central nervous system (CNS) infections requires that antimicrobial agents penetrate the blood-brain barrier (BBB) and achieve concentrations in the CNS adequate for eradication of the infecting pathogen. This review details the currently available literature on the pharmacokinetics (PK) of antibacterials in the CNS of children. Clinical trials affirm that the physicochemical properties of a drug remain one of the most important factors dictating penetration of antimicrobial agents into the CNS, irrespective of the population being treated (i.e. small, lipophilic drugs with low protein binding exhibit the best translocation across the BBB). These same physicochemical characteristics determine the primary disposition pathways of the drug, and by extension the magnitude and duration of circulating drug concentrations in the plasma, a second major driving force behind achievable CNS drug concentrations. Notably, these disposition pathways can be expected to change during the normal process of growth and development. Finally, CNS drug penetration is influenced by the nature and extent of the infection (i.e. the presence of meningeal inflammation). Aminoglycosides have poor CNS penetration when administere...Continue Reading

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