Disposition of Cefepime in the Central Nervous System of Patients with External Ventricular Drains

Study Objective. To assess central nervous system (CNS) penetration of cefepime in adults with external ventricular drains and to compare the achieved cerebrospinal fluid (CSF) concentrations with the usual minimum inhibitory concentrations (MICs) of common pathogens. Design. Open‐label, prospective study. Setting. University‐affiliated medical center. Patients. Seven patients with external ventricular drains and normal renal function (documented creatinine clearance > 60 ml/min) who received cefepime 2 g intravenously every 12 hours for treatment of nosocomial pneumonia. Intervention. Serial serum and CSF samples were obtained concurrently after the fourth dose during one dosing interval. Measurements and Main Results. The concentration‐time profiles in serum and CSF were comodeled by using a two‐compartment model with zero‐order infusion to the central compartment. The CSF concentration‐time profiles of the individual patients were compared with published MIC90 of common pathogens isolated in nosocomial meningitis. Our model reasonably characterized the disposition of cefepime in serum and CSF. Penetration into the CNS was 4–34% based on area under the curve and was 5–58% based on minimum concentration. Conclusion. Penetration of cefepime into the CNS was variable among the patients (4–34%) but appeared similar to that reported for other cephalosporins given to treat meningitis. The concentrations attained by most patients in this study were above the MIC90 of many common nosocomial organisms.