Antibiotic pharmacodynamics in cerebrospinal fluid

Irja Lutsar, George H. McCracken, Ian R. Friedland

Research output: Contribution to journalArticle

168 Citations (Scopus)

Abstract

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 (β-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 β-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; β-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, quinolines 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.

Original languageEnglish (US)
Pages (from-to)1117-1129
Number of pages13
JournalClinical Infectious Diseases
Volume27
Issue number5
StatePublished - Nov 1998

Fingerprint

Quinolones
Cerebrospinal Fluid
Lactams
Anti-Bacterial Agents
Vancomycin
Serum
Quinolines
Inflammation
Aminoglycosides
Meningitis
Area Under Curve
Pharmacokinetics
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Antibiotic pharmacodynamics in cerebrospinal fluid. / Lutsar, Irja; McCracken, George H.; Friedland, Ian R.

In: Clinical Infectious Diseases, Vol. 27, No. 5, 11.1998, p. 1117-1129.

Research output: Contribution to journalArticle

Lutsar, I, McCracken, GH & Friedland, IR 1998, 'Antibiotic pharmacodynamics in cerebrospinal fluid', Clinical Infectious Diseases, vol. 27, no. 5, pp. 1117-1129.
Lutsar, Irja ; McCracken, George H. ; Friedland, Ian R. / Antibiotic pharmacodynamics in cerebrospinal fluid. In: Clinical Infectious Diseases. 1998 ; Vol. 27, No. 5. pp. 1117-1129.
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