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  • Title: Penetration of doripenem in human brain: an observational microdialysis study in patients with acute brain injury.
    Author: Poeppl W, Zeitlinger M, Donath O, Wurm G, Müller M, Botha F, Illievich UM, Burgmann H.
    Journal: Int J Antimicrob Agents; 2012 Apr; 39(4):343-5. PubMed ID: 22325119.
    Abstract:
    Concentration-time profiles of unbound doripenem were determined by microdialysis in the cerebral interstitium of five patients with acute brain injury. The ratio of the area under the concentration-time curve in brain to that in plasma (AUC(brain)/AUC(plasma)) was 0.17 in one patient and 0.01 in the remaining four patients. Based on the percentage of the dosing interval during which the doripenem concentration exceeded a certain minimum inhibitory concentration (T>MIC), a value of ≥35% of the dosing interval was reached for pathogens with MICs up to 0.05 mg/L. The present data indicate that breakpoints based on concentrations of doripenem in plasma may overestimate antimicrobial activity in brain parenchyma.
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