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 AUCCSF/AUCplasma. 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%). CONCLUSIONS: 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.