Determinants of ceftazidime clearance by continuous venovenous hemofiltration and continuous venovenous hemodialysis

Although several dosage adjustment regimens have been proposed, there is li ttle quantitative information to guide the initiation of ceftazidime therap y in patients who are receiving continuous renal replacement therapy. To de termine the clearance of ceftazidime by continuous venovenous hemofiltratio n (CVVH) and continuous venovenous hemodialysis (CVVHD), we performed contr olled clearance studies with stable hemodialysis patients with three hemofi lters: a 0.6-m(2) acrylonitrile copolymer (AN69; Hospal) filter, a 2.1-m(2) polymethylmethacrylate filter (PMMA; Toray) filter and a 0.65-m(2) polysul fone (PS; Fresenius) filter. Subjects received 1,000 mg of ceftazidime intr avenously prior to the start of a clearance study. The concentration of cef tazidime in multiple plasma and dialysate or ultrafiltrate samples was dete rmined by high-performance liquid chromatography. The diffusional clearance s (CIdiffusion) and sieving coefficients of ceftazidime were compared by a mixed-model repeated-measures analysis of variance with filter and blood, d ialysate inflow, or ultrafiltration rate as the main effect and the patient as a random effect. The fraction of ceftazidime bound to plasma proteins w as 17% +/- 7% (range, 10 to 25%). The clearances of ceftazidime, urea, and creatinine by CVVHD were essentially constant at blood how rates of 75 to 2 50 ml/min for all three filters. Significant linear relationships (P < 0.00 01) were observed between CIdiffusion of ceftazidime and clearance of urea for all three filters: AN69 (slope = 0.83), PMMA (slope = 0.89), and PS (sl ope = 1.03). Ceftazidime clearance was membrane independent during CVVH and CVVHD. CVVH and CVVHD can significantly augment the clearance of ceftazidi me. Dosing strategies for initiation of ceftazidime therapy in patients rec eiving CVVH and CVVHD are proposed.