Understanding central nervous system efficacy of antimicrobials.

Abstract

The requirements for antimicrobial treatment to reach the central nervous system (CNS) are of maximal importance, for two major reasons: (i) the brain is an immuno-privileged site, with virtually no leukocytes in the brain parenchyma or cerebrospinal fluid (CSF) at baseline; (ii) the blood–brain barrier (BBB) drastically reduces the diffusion of antimicrobials into the CNS [1]. Treatment of CNS infections has been a major area of research since the discovery of the first antimicrobials. Treatment regimens recommended for encephalitis [2, 3], meningitis [4], and brain abscess [5], have to comply with the pharmacokinetic (PK), and pharmacodynamic (PD) characteristics of available antibacterial, antiviral, antifungal, and antiparasitic agents [6]. Due to the numerous constraints created by the BBB, therapeutic options are quite limited, so that current practices for treatment of CNS infections are remarkably similar worldwide, with much less heterogeneity than for other major infectious diseases (e.g. pneumonia, abdominal, or skin and skin structure infections). This paper summarizes the main parameters that must be taken into account to ensure efficacy of antimicrobial agents in the CNS, with an emphasis on antibacterial drugs.