The CSF half-lives of lipophilic agents, such as
quinolones, are similar to those in serum and peak concentrations in CSF are achieved relatively quickly. In contrast, the pharmacokinetics of hydrophilic agents (
beta-lactams and
vancomycin) in CSF often differ from those in serum. In particular, the half-lives of these agents in CSF tend to be extended, and the time to achieve peak concentrations in CSF is delayed. Hydrophilic
antibiotics, such as
beta-lactams, penetrate poorly through the BBB, but CSF penetration is significantly increased in the presence of
inflammation. In contrast, lipophilic
antibiotics, such as
quinolones, enter the CSF more efficiently and their penetration is not
inflammation dependent. The pharmacodynamic properties of
antibiotics in CSF are generally similar to those in other body sites;
beta-lactam agents and
vancomycin are time-dependent, whereas the
quinolones and
aminoglycosides are concentration-dependent. However, a notable difference from
infections in other sites is that
quinolones have a short PAE in CSF and need to continually exceed the MBC for maximal effectiveness. Thus, in CSF,
quinolones demonstrate features of both concentration-dependency and time-dependency, evidence that the AUC/MBC is an important predictor of effectiveness. With the exception of
quinolones, many
antibiotics appear to have prolonged sub-MIC effects and longer half-lives in CSF than in serum, suggesting that dosing intervals longer than those used traditionally would be effective in
meningitis. However, this requires clinical verification.