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

Background Owing to its antibacterial properties, ceftaroline could be attractive for prevention or treatment of bacterial post-neurosurgical meningitis/ventriculitis. However, few data are available concerning its meningeal concentrations. Objectives To investigate ceftaroline CSF pharmacokinetics in ICU patients with an external ventricular drain (EVD). Methods Patients received a single 600mg dose of ceftaroline as a 1h intravenous infusion. Blood and CSF samples were collected before and 0.5, 1, 3, 6, 12 and 24h after the end of the infusion. Concentrations were assayed in plasma and CSF by LC-MS/MS. A two-step compartmental pharmacokinetic analysis was conducted. Ceftaroline plasma data were first analysed, and thereafter plasma parameters estimated and corrected for protein binding of 20% were fixed to fit unbound CSF concentrations. In the final model, parameters for both plasma and CSF data were simultaneously estimated. Results Nine patients with an EVD were included. The C-max was 18.293.33mg/L in plasma (total concentrations) and at 0.22 +/- 0.17mg/L in CSF (unbound concentration). The model-estimated CSF input/CSF output clearance ratio was 9.4%, attesting to extensive efflux transport at the blood-CSF barrier. Conclusions Ceftaroline CSF concentrations are too low to ensure prophylactic protection against most pathogens with MICs between 1 and 2mg/L, owing to its limited central distribution.