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