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Antimicrobial Agents and Chemotherapy, November 2001, p. 3148-3155, Vol. 45, No. 11
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.11.3148-3155.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Pharmacokinetics of Cefepime during Continuous Renal Replacement Therapy in Critically Ill Patients

Rebecca S. Malone,1 Douglas N. Fish,2,3,* Edward Abraham,3 and Isaac Teitelbaum4

Department of Pharmacy Practice and Science, University of Arizona Health Sciences Center, Tucson, Arizona,1 and Department of Pharmacy Practice,2 Division of Pulmonary Sciences and Critical Care Medicine,3 and Division of Renal Diseases and Hypertension,4 University of Colorado Health Sciences Center, Denver, Colorado

Received 4 December 2000/Returned for modification 3 June 2001/Accepted 15 August 2001

The pharmacokinetics of cefepime were studied in 12 adult patients in intensive care units during continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodiafiltration (CVVHDF) with a Multiflow60 AN69HF 0.60-m2 polyacrylonitrile hollow-fiber membrane (Hospal Industrie, Meyzieu, France). Patients (mean age, 52.0 ± 13.0 years [standard deviation]; mean weight, 96.7 ± 18.4 kg) received 1 or 2 g of cefepime every 12 or 24 h (total daily doses of 1 to 4 g/day) by intravenous infusion over 15 to 30 min. Pre- and postmembrane blood (serum) samples and corresponding ultrafiltrate or dialysate samples were collected 1, 2, 4, 8, and 12 or 24 h (depending on dosing interval) after completion of the drug infusion. Drug concentrations were measured using validated high-performance liquid chromatography methods. Mean systemic clearance (CLS) and elimination half-life (t1/2) of cefepime were 35.9 ± 6.0 ml/min and 12.9 ± 2.6 h during CVVH versus 46.8 ± 12.4 ml/min and 8.6 ± 1.4 h during CVVHDF, respectively. Cefepime clearance was substantially increased during both CVVH and CVVHDF, with membrane clearance representing 40 and 59% of CLS, respectively. The results of this study confirm that continuous renal replacement therapy contributes substantially to total CLS of cefepime and that CVVHDF appears to remove cefepime more efficiently than CVVH. Cefepime doses of 2 g/day (either 2 g once daily or 1 g twice daily) appear to achieve concentrations adequate to treat most common gram-negative pathogens (MIC <=  8 µg/ml) during CVVH or CVVHDF.

* Corresponding author. Mailing address: University of Colorado Health Sciences Center, Department of Pharmacy Practice, School of Pharmacy, Campus Box C-238, 4200 East Ninth Ave., Denver, CO 80262. Phone: (303) 315-5136. Fax: (303) 315-4630. E-mail: doug.fish{at}uchsc.edu.

Antimicrobial Agents and Chemotherapy, November 2001, p. 3148-3155, Vol. 45, No. 11
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.11.3148-3155.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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