Integration of Population Pharmacokinetics
Integration of Population Pharmacokinetics
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.
Substantial resources are devoted to elucidating the pharmacokinetics and pharmacodynamics of antiinfective agents and to microbiologic surveillance. However, a concerted effort to translate these data into clinically useful information to improve outcome is relatively lacking. Cefepime is a fourth-generation cephalosporin with an extended spectrum of activity. Its pharmacokinetics are well characterized. It is often administered empirically in the critical care setting. We adopted a rational, integrated approach to empiric dosing of cefepime against Pseudomonas aeruginosa as a paradigm for improving treatment outcome.
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.
Substantial resources are devoted to elucidating the pharmacokinetics and pharmacodynamics of antiinfective agents and to microbiologic surveillance. However, a concerted effort to translate these data into clinically useful information to improve outcome is relatively lacking. Cefepime is a fourth-generation cephalosporin with an extended spectrum of activity. Its pharmacokinetics are well characterized. It is often administered empirically in the critical care setting. We adopted a rational, integrated approach to empiric dosing of cefepime against Pseudomonas aeruginosa as a paradigm for improving treatment outcome.
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