Intermittent Intraperitoneal Ceftazidime Dosing in End-Stage Renal Disease

Abstract

Infections are a common problem in dialysis patients. As hospital stay shortens, many require outpatient antibiotic therapy. Parenteral administration may pose considerable logistic and financial burdens, whereas daily intraperitoneal dosing increases the risk of contamination. Ceftazidime, with its long half-life, may provide adequate dosing when administered intraperitoneally thrice weekly. The authors therefore studied the kinetics of a 2 g loading dose followed by a 1.5 g dose every 48 hr in seven stable chronic peritoneal dialysis patients. In vitro stability at 4°C (measured by high performance liquid chromatography) was 91% at 120 hr. Peak serum concentration (60 ± 22 µg/ml) was reached at 4.9 ± 2.2 hr. Serum values were 25 ± 9 and 8 ± 3 µg/ml at 24 and 48 hr, respectively. However, median trough levels at 48 hr in dialysate were significantly lower than in serum (2.8 vs 8.5 µg/ml, respectively; p=0.0425). Pharmacokinetic parameters were as follows: bioavailabilhy (F), 88% ± 8%; volume of distribution at steady state (VD_ss, 20 ± 8 L; absorption half-life (T_½(abs)), 1.8 ± 1.3 hr; elimination half-life (T_½(el)), 11.4 ± 4.5 hr; and clearance (CL), 22 ± 10 ml/min. Intraperitoneal ceftazidime every 48 hr is a practical alternative to parenteral therapy of nonperitoneal infections. In peritonitis, whether increased permeability results in improved dialysate levels remains to be defined.