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Antimicrobial Agents and Chemotherapy, June 2005, p. 2421-2428, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2421-2428.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Pharmacokinetics and Pharmacodynamics of Imipenem during Continuous Renal Replacement Therapy in Critically Ill Patients

Douglas N. Fish,1,3* Isaac Teitelbaum,2 and Edward Abraham3

Department of Clinical Pharmacy,1 Division of Renal Diseases and Hypertension,2 Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado 802623

Received 16 August 2004/ Returned for modification 29 November 2004/ Accepted 15 February 2005

The pharmacokinetics of imipenem were studied in adult intensive care unit (ICU) patients during continuous venovenous hemofiltration (CVVH; n = 6 patients) or hemodiafiltration (CVVHDF; n = 6 patients). Patients (mean ± standard deviation age, 50.9 ± 15.9 years; weight, 98.5 ± 15.9 kg) received imipenem at 0.5 g every 8 to 12 h (total daily doses of 1 to 1.5 g/day) by intravenous infusion over 30 min. Pre- and postmembrane blood (plasma) and corresponding ultrafiltrate or dialysate samples were collected 1, 2, 4, and 8 or 12 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 imipenem were 145 ± 18 ml/min and 2.7 ± 1.3 h during CVVH versus 178 ± 18 ml/min and 2.6 ± 1.6 h during CVVHDF, respectively. Imipenem clearance was substantially increased during both CVVH and CVVHDF, with membrane clearance representing 25% and 32% of CLS, respectively. The results of this study indicate that CVVH and CVVHDF contribute to imipenem clearance to a greater degree than previously reported. Imipenem doses of 1.0 g/day appear to achieve concentrations adequate to treat most common gram-negative pathogens (MIC up to 2 µg/ml) during CVVH or CVVHDF, but doses of 2.0 g/day or more may be required to adequately treat and prevent resistance in pathogens with higher MICs (MIC = 4 to 8 µg/ml). Higher doses should only be used after consideration of potential central nervous system toxicities or other risks of therapy in these severely ill patients.

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

Antimicrobial Agents and Chemotherapy, June 2005, p. 2421-2428, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2421-2428.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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