title: Clinical pharmacokinetics of antibacterials in cerebrospinal fluid.
abstract: In the past 20 years, an increased discrepancy between new available antibacterials and the emergence of multidrug-resistant strains has been observed. This condition concerns physicians involved in the treatment of central nervous system (CNS) infections, for which clinical and microbiological success depends on the rapid achievement of bactericidal concentrations. In order to accomplish this aim, the choice of drugs is based on their disposition toward the cerebrospinal fluid (CSF), which is influenced by the physicochemical characteristics of antibacterials. A reduced distribution into CSF has been documented for beta-lactams, especially cephalosporins and carbapenems, on the basis of their hydrophilic nature. However, they represent a cornerstone of the majority of combined therapeutic schemes for their ability to achieve bactericidal concentrations, especially in the presence of inflamed meninges. The good tolerability of beta-lactams makes possible high daily dose intensities, which may be associated with increased probability of cure. Furthermore, the adoption of continuous infusion seems to be a fruitful option. Fluoroquinolones, namely moxifloxacin, and antituberculosis drugs, together with the agents such as linezolid, reach the highest CSF/plasma concentration ratio, which is greater than 0.8, and for most of these drugs it is near 1. For all drugs that are currently used for the treatment of CNS infections, the evaluation of pharmacokinetic/pharmacodynamic parameters, on the basis of dosing regimens and their time-dependent or concentration-dependent pattern of bacterial killing, remains an important aspect of clinical investigation and medical practice.
authors.affiliation: Division of Pharmacology, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 55, 56126, Pisa, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Di Paolo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gori
authors.forename: Carlo
authors.initials: C
authors.lastname: Tascini
authors.forename: Romano
authors.initials: R
authors.lastname: Danesi
authors.forename: Mario
authors.initials: M
authors.lastname: Del Tacca
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D020806:Central Nervous System Bacterial Infections / Q000134:cerebrospinal fluid* / Q000188:drug therapy; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents