Disposition of cefepime in the central nervous system of patients with external ventricular drains.
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.


METHODS
Open-label, prospective study.


METHODS
University-affiliated medical center.


METHODS
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.


METHODS
Serial serum and CSF samples were obtained concurrently after the fourth dose during one dosing interval.


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.


CONCLUSIONS
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.
Rhoney
Denise H
DH
Department of Pharmacy Practice, Wayne State University College of Pharmacy and Allied Health Professions, Detroit, Michigan 48201, USA. drhoney@wayne.edu
Tam
Vincent H
VH
Parker
Dennis
D
McKinnon
Peggy S
PS
Coplin
William M
WM
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D000077723:Cefepime; D002490:Central Nervous System / Q000378:metabolism*; D002511:Cephalosporins / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008954:Models, Biological; D011446:Prospective Studies
D002511:Cephalosporins; D000077723:Cefepime