Pharmacology of Antibacterial Agents in Cerebrospinal Fluid

Abstract

The cerebrospinal fluid (CSF) is produced by the choroidal plexuses of the cerebral ventricles with the role of protecting the central nervous system from mechanical (shock) and infectious (viruses, bacteria, parasites) aggressions and providing essential nutrients for its optimal functioning. It is anatomically at the interface between the blood compartment, interstitial cerebral fluid and the lymphatic compartment. Its composition is strongly influenced by these structures. Two barriers make it possible to regulate the molecular passage in the central nervous system and severely limit access to the latter: the blood-brain barrier and the blood-brain barrier.

The diffusion of antibiotics in the cerebrospinal fluid but also in the cerebral parenchyma depends on several factors: the size of the molecule, its lipophilicity, the binding to plasma proteins and the integrity of the barriers. The phenomena of meningeal inflammation observed in bacterial meningitis increase the permeability of the barriers and facilitate the diffusion of antibiotic agents. The best diffusing molecules in the LCS are fluoroquinolones, linezolid, trimethoprim / sulfamethoxazole, rifampicin and fosfomycin. Beta-lactams have a rather weak diffusion but which increases strongly in case of meningeal inflammation. Very high daily doses make it possible to circumvent the pitfall of diffusion.

Many parameters influence the diffusion of antibiotics into the CSF. The choice of appropriate antibiotic therapy is based on these parameters and the type of infection to be treated in multidisciplinary consultation.