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