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Antimicrobial Agents and Chemotherapy, June 2003, p. 1862-1866, Vol. 47, No. 6
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.6.1862-1866.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Clinical Pharmacokinetics of Cefamandole and Ceftazidime Administered by Continuous Intravenous Infusion

J. Berkhout,1,2 L. G. Visser,1* P. J. van den Broek,1 J. A. M. van de Klundert,2 and H. Mattie1

Department of Infectious Diseases,1 Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands2

Received 4 June 2002/ Returned for modification 21 August 2002/ Accepted 18 March 2003

In view of the results of animal studies as well as theoretical considerations, continuous administration of ß-lactam antibiotics should be superior to intermittent administration because of the close relationship between efficacy and the duration of time in which the concentration of unbound antibiotics in plasma remains above the MIC. The aim of the present study was to establish the pharmacokinetic parameters of cefamandole and ceftazidime for patients receiving these cephalosporins by continuous infusion. The interindividual differences in the concentrations in plasma at the steady state were mainly attributable to variations in renal function, as estimated by the rate of creatinine clearance. Using these results, we derived formulas for both cephalosporins that can be used to determine on an individual basis the total daily dose needed to obtain a therapeutic concentration in plasma. These formulas were tested with a group of subsequent patients and proved to be practical and fairly reliable. For some patients, a correction for a possible underestimation of the renal clearance at presentation might be required.

* Corresponding author. Mailing address: Department of Infectious Diseases, Leiden University Medical Center, C5-P-41, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Phone: 31 71 526 2613. Fax: 31 71 526 6758. E-mail: L.G.Visser{at}lumc.nl.

Antimicrobial Agents and Chemotherapy, June 2003, p. 1862-1866, Vol. 47, No. 6
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.6.1862-1866.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.





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