Integration of population pharmacokinetics, a pharmacodynamic target, and microbiologic surveillance data to generate a rational empiric dosing strategy for cefepime against Pseudomonas aeruginosa.

Study Objective: To derive steady-state pharmacokinetic profiles of cefepime against Pseudomonas aeruginosa.

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

Setting: Medical and surgical intensive care units.

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

Intervention: 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.

Measurements And Main 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).

Conclusion: 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.