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RESEARCH PRODUCT

Cerebrospinal fluid pharmacokinetics of ceftaroline in neurosurgical patients with external ventricular drain

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International audience; Background: Due to its antibacterial properties ceftaroline could be attractive for the treatment of bacterial postneurosurgicalmeningitis. However only few data are available concerning its meningeal concentrations. The aim of this studywas to investigate ceftaroline cerebrospinal fluid (CSF) pharmacokinetics (PK) in intensive care unit (ICU) patients with anexternal ventricular drain (EVD).Materials/methods: Patients received a single 600 mg dose of ceftaroline as a one-hour intravenous infusion . Blood and CSFsamples were collected before and 0.5, 1, 3, 6, 12 and 24 hours after the end of the infusion. Concentrations were assayed inplasma and CSF by LC-MS/MS. A two steps compartmental pharmacokinetic (PK) analysis was conducted; plasma parameterswere estimated and corrected for protein binding of 20%. In the final model, parameters for both plasma and CSF data weresimultaneously estimated.Results: Nine patients with suspected post neurosurgical meningitis were included. Peak concentrations (Cmax) weremeasured at 13.73 ± 2.25 mg/L in plasma (total concentrations) and at 0.25 ± 0.19 mg/L in CSF (unbound concentration). Themodel estimated unbound CSF/plasma area under the curves (AUC) ratio was equal to 6.7% attesting for extensive effluxtransport at the blood-CSF barrier.Conclusions: The PK model well described ceftaroline concentration-time profiles both in plasma and CSF, and shows thatafter intravenous administration of ceftaroline at a dose of 600mg, CSF concentrations are too low for ensuring prophylacticprotection against most pathogens with MICs between 1 and 2 mg/L, due to its limited central diffusion.