Concentrations of cefuroxime in brain tissue of neurointensive care patients [PublishAheadOfPrint]

Introduction Effective concentrations of antibiotics in brain tissue are essential for antimicrobial therapy of brain infections. However, data concerning cerebral penetration properties of antibiotics for treatment or prophylaxis of central nervous system infections are rare.

Methods Six patients suffering subarachnoid hemorrhage and requiring cerebral microdialysis for neurochemical monitoring were included in this study. Free interstitial concentrations of cefuroxime after intravenous application of 1500 mg were measured by microdialysis in brain tissue as well as in plasma at steady-state (n=6) or after single-dose administration (n=1).

Resultsx At steady-state free area under the concentration-time curve from 0 to 24 hours (AUC_0-24) –values of 389.0±210.3 mg/L*h and 131.4±72.8 mg/L*h were achieved for plasma and brain, respectively, resulting in a brain tissue penetration ratio (AUC_{0-24 brain}/AUC_{0-24 freeplasma}) of 0.33±0.1. Plasma and brain tissue concentrations at individual time points correlated well (R=0.59, p=0.001).

At steady-state time over minimal inhibitory concentration (t<MIC) -values of more than 40% of dosing interval were achieved up to an MIC of 16mg/L for plasma and 4mg/L for brain tissue.

Conclusion While MIC₉₀ values could not be achieved in brain tissue for relevant bacteria, current dosing strategies of cefuroxime might be sufficient to treat pathogens with MIC values up to 4mg/L. Activity of cefuroxime in brain tissue might be overestimated when relying exclusively on plasma levels. Although currently insufficient data after single dose administration exist, lower brain-plasma ratios observed after the first dose might warrant a loading dose for treatment and perioperative prophylaxis.

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