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Poster De Conférence Année : 2018

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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Dates et versions

hal-02528340 , version 1 (01-04-2020)

Identifiants

  • HAL Id : hal-02528340 , version 1

Citer

Pascal Chavanet, Alexia Chauzy, Nadine Defrance, Abdelouaïd Nadji, Jean-Christophe Combes, et al.. Cerebrospinal fluid pharmacokinetics of ceftaroline in neurosurgical patients with external ventricular drain. the 28th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), Apr 2018, Madrid, Spain. ⟨hal-02528340⟩
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