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

Denise H. Rhoney, Pharm.D., Vincent H. Tam, Pharm.D., Dennis Parker, Jr., Pharm.D., Peggy S. McKinnon, Pharm.D., William M. Coplin, M.D.


Pharmacotherapy. 2003;23(3) 

In This Article

Abstract and Introduction

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.

Cefepime is a fourth-generation cephalosporin. Its spectrum of activity suggests it should be useful to treat central nervous system (CNS) infections. However, data on cefepime disposition in human CNS are limited. Ceftazidime often is administered because of its CNS penetration (2.7-12.3%).[1,2] In an animal meningitis model, CNS cefepime penetration was 20.2 ± 10.2%. In children with bacterial meningitis, cefepime CNS penetration varied from 9-67%.[3] Cefepime showed good clinical and bacteriologic response as empiric treatment in children with meningitis, when compared with cefotaxime and ceftriaxone.[4]

Cerebrospinal fluid (CSF) antibiotic concentrations should remain above the minimum inhibitory concentration (MIC) for the offending pathogen.[5] -Lactam antibiotics exhibit time-dependent bactericidal activity, so the goal of therapy is to maintain drug concentrations above the MIC over most of the dosing interval.

Assessment of attainable CSF cefepime concentrations is important before consideration of its use for CNS infections in adults. We sought to assess CNS penetration of cefepime (2 g intravenously every 12 hrs) in adults with external ventricular drains and to compare the achieved CSF concentrations with the usual MICs of common pathogens.