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Antimicrobial Agents and Chemotherapy, June 2000, p. 1639-1644, Vol. 44, No. 6
School of Medicine1
and School of Pharmacy, Center for Clinical
Pharmacology,2 University of
Pittsburgh, and Renal Section, VA Pittsburgh Health Care
System,4 Pittsburgh, Pennsylvania, and
Division of Nephrology and Hypertension, School of
Medicine, University of North Carolina, Chapel Hill, North
Carolina3
Received 8 November 1999/Returned for modification 4 March
2000/Accepted 26 March 2000
Although several dosage adjustment regimens have been proposed,
there is little quantitative information to guide the initiation of
ceftazidime therapy in patients who are receiving continuous renal
replacement therapy. To determine the clearance of ceftazidime by
continuous venovenous hemofiltration (CVVH) and continuous venovenous
hemodialysis (CVVHD), we performed controlled clearance studies with
stable hemodialysis patients with three hemofilters: a
0.6-m2 acrylonitrile copolymer (AN69; Hospal)
filter, a 2.1-m2 polymethylmethacrylate filter
(PMMA; Toray) filter and a 0.65-m2 polysulfone
(PS; Fresenius) filter. Subjects received 1,000 mg of ceftazidime
intravenously prior to the start of a clearance study. The
concentration of ceftazidime in multiple plasma and dialysate or
ultrafiltrate samples was determined by high-performance liquid
chromatography. The diffusional clearances (CIdiffusion) and sieving coefficients of ceftazidime were compared by a mixed-model repeated-measures analysis of variance with filter and blood, dialysate
inflow, or ultrafiltration rate as the main effect and the patient as a
random effect. The fraction of ceftazidime bound to plasma proteins was
17% ± 7% (range, 10 to 25%). The clearances of ceftazidime, urea,
and creatinine by CVVHD were essentially constant at blood flow rates
of 75 to 250 ml/min for all three filters. Significant linear
relationships (P < 0.0001) were observed between
CIdiffusion of ceftazidime and clearance of urea for all three filters: AN69 (slope = 0.83), PMMA (slope = 0.89), and
PS (slope = 1.03). Ceftazidime clearance was membrane independent during CVVH and CVVHD. CVVH and CVVHD can significantly augment the
clearance of ceftazidime. Dosing strategies for initiation of
ceftazidime therapy in patients receiving CVVH and CVVHD are proposed.
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Determinants of Ceftazidime Clearance by Continuous Venovenous
Hemofiltration and Continuous Venovenous Hemodialysis
*
Corresponding author. Mailing address: University of
Pittsburgh, School of Pharmacy, 724 Salk Hall, Pittsburgh, PA 15261. Phone: (412) 624-8153. Fax: (412) 648-8088. E-mail:
matzke{at}pitt.edu.
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