Pharmacokinetics and pharmacodynamics of cephalosporins in cerebrospinal fluid

Largely because of their low lipophilicity, cephalosporins poorly penetrate through the blood-brain barrier, achieving relatively low cerebrospinal fl uid (CSF) concentrations. However, the minimum bactericidal concentrations (MBCs) of the extended spectrum cephalosporins for common meningeal pathoge ns are generally low; thus, therapeutic CSF drug concentrations several-fol d greater than the MBC can be achieved with currently recommended dosage re gimens. However, the effectiveness of cephalosporin therapy is unreliable i n patients with meningitis caused by highly penicillin-resistant pneumococc i. As in other body sites, the bactericidal activity of cephalosporins in CSF predominantly depends on the time their concentrations exceed the MBC of in fecting organisms (t(>MBC)) Experimental studies show that, for maximal eff icacy, t(>MBC)values greater than 90% of the dosage interval are required i n meningitis. Such values are usually achieved in humans with currently rec ommended dosage regimens because the half-lives of cephalosporins are 2- to 3-fold longer in CSF than in serum. Several advanced generation cephalosporins have shown equal efficacy in cli nical trials, but only cefotaxime, ceftriaxone and ceftazidime are currentl y approved for the treatment of patients with bacterial meningitis.