Integration of population pharmacokinetics, a pharmacodynamic target, and microbiologic surveillance data to generate a rational empiric dosing strategy for cefepime against Pseudomonas aeruginosa.
OBJECTIVE
To derive steady-state pharmacokinetic profiles of cefepime against Pseudomonas aeruginosa.


METHODS
Retrospective evaluation using a weighted approach based on a minimum inhibitory concentration distribution of cefepime in the United States.


METHODS
Medical and surgical intensive care units.


METHODS
One thousand patients with creatinine clearances of 120, 90, or 60 ml/minute.


METHODS
Administration of a standard dosage of cefepime 2 g every 12 hours, each dose infused over 0.5 hour, and maximum dosage of 2 g every 8 hours, each dose infused over 0.5 hour; and a nonstandard dosage of 2 g every 12 hours, each dose infused over 6 hours, and continuous infusion of 4 g infused over 24 hours.


RESULTS
The standard and maximum dosages achieved pharmacodynamic targets from 4-38% and 21-68%, respectively, for the three groups. With extended infusion of the standard dosage, the probability of achieving the pharmacodynamic target increased to 18-63%. Continuous infusion over 24 hours offered the most promising pharmacodynamic target, attaining 65-81% (p<0.001).


CONCLUSIONS
The recommended dosage of cefepime has a low probability of achieving a pharmacodynamic target predicting a favorable outcome for infections due to P. aeruginosa. The probability of attaining the target could be improved with higher dosages or extended infusion time.
Tam
Vincent H
VH
Division of Clinical Pharmacology, Albany Medical College, and New York State Department of Health, USA.
Louie
Arnold
A
Lomaestro
Ben M
BM
Drusano
George L
GL
D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008826:Microbial Sensitivity Tests; D011159:Population Surveillance; D011552:Pseudomonas Infections / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D012189:Retrospective Studies
D002511:Cephalosporins; D000077723:Cefepime