Ceftaroline Diffusion Into Cerebrospinal Fluid of Children With Ventriculitis Due to Ventriculoperitoneal Shunt Infection

Background: Data on ceftaroline cerebrospinal fluid (CSF) levels in children are limited. This study examined ceftaroline diffusion into CSF among children with ventriculoperitoneal shunt (VPS)-related ventriculitis and external ventricular drains. Methods: Patients received a single dose of 15 mg/kg of iv ceftaroline (maximum 600 mg) over 2 hours. Simultaneous plasma and CSF samples were obtained at 3 time points to measure ceftaroline concentration: end of infusion (0 hours), and 2 and 6 hours postinfusion. The areas under the curve (AUCs) for plasma and CSF were calculated using linear interpolation of concentrations at time intervals. The CSF diffusion ratio was measured as AUC CSF /AUC plasma . Clinical and laboratory data were reviewed. Results: Eight children (7 months–16 years; median, 9 years) were included. CSF cultures yielded staphylococcal species in 6 patients. Inflammation was defined by grossly abnormal CSF parameters and/or a C-reactive protein ≥30 mg/L. Among the 5 children meeting these criteria and with complete CSF sampling at 3 time points, the ceftaroline CSF diffusion ratio (0–6 hours) ranged from 1.96% to 35.39%, and the 0–2-hour diffusion ratio ranged from 1.47% to 21.11%. In contrast, the 2 patients with minimal inflammation and concentrations available at 2 time points demonstrated substantially lower 0–2-hour CSF diffusion ratios (0.68% and 0.61%). Conclusion(s): Ceftaroline CSF diffusion in children with VPS-related ventriculitis is variable and correlates with markers of meningeal inflammation. Prospective studies are needed to evaluate the use of ceftaroline in children with VPS infections.