[Antibiotic Penetration into the Central Nervous System: Decoding the Blood: Brain Barrier and Antibiotics through "Structure" to Inform Therapeutic Strategy].

Clinical outcomes of central nervous system (CNS) infections are determined by not only pathogen coverage but also whether an antibiotic can cross the blood-brain barrier (BBB) to achieve sufficient exposure at the target site. The BBB is a prototypical example of "organ-specific vascular specialization" established by (1) the non-fenestrated nature and tight junctions of cerebral capillary endothelial cells and (2) endothelial cell regulation by pericytes and astrocytes. Therefore, CNS penetration of antibiotics should be understood as an interaction between physicochemical properties of drugs (lipophilicity, molecular weight, ionization state, and polarity) and the BBB state throughout the disease course (from the acute inflammatory phase to post-resolution). To assist readers in estimating passive BBB permeability simply by inspecting structural formulas, we provide a practical workflow-from identifying key functional groups (red-circle annotation) to a three-tier ("likely to pass," "may pass during inflammation," and "unlikely to pass under usual conditions") classification-and demonstrate workflow efficacy using four representative compounds. Reasons why meningeal gadolinium enhancement on magnetic resonance imaging cannot be taken as direct "proof" of antibiotic penetration are summarized, and treatment strategies from acute phase through recovery are discussed.