Pharmacokinetics of ceftazidime in CAPD-related peritonitis.

Objective: The aim of this study was to measure and evaluate the appropriateness of the actual concentrations of serum and dialysate ceftazidime in Thai continuous ambulatory peritoneal dialysis (CAPD) patients.

Design: Prospective and descriptive study of patients treated following the International Society for Peritoneal Dialysis (ISPD) 2000 recommendation for the empiric therapy of CAPD-related peritonitis.

Setting: Institutional level of clinical care.

Patients: CAPD-related peritonitis patients were diagnosed by dialysate effluent white blood cell count of more than 100/mm3 and polymorphonuclear leukocytes of at least 50%. There were 10 patients, all at least 18 years of age, entered; all completed the study.

Intervention: In accordance with the ISPD 2000 recommendations, the antibiotic regimen comprised continuous intraperitoneal (i.p.) cefazolin and once-daily i.p. ceftazidime. Cefazolin was administered as loading and continuous maintenance doses of 500 and 125 mg/L dialysate respectively. Ceftazidime (20 mg/kg body weight) was given i.p. once daily. Duration of treatment was 96 hours.

Main Outcome Measures: Serum and dialysate effluent samples of the 10 CAPD patients with peritonitis were measured for ceftazidime levels, which were used for the development of pharmacokinetic equations that could predict drug concentrations at any treatment time.

Results: Following ceftazidime administration as in the ISPD 2000 recommendation, serum ceftazidime levels were above 8 microg/mL, the minimum inhibitory concentration (MIC) recommended by NCCLS, throughout 24 hours. Dialysate ceftazidime levels were below the MIC for total periods of 4.19 and 6.26 hours in day 1 and day 4 respectively. The clinical response rate to the empiric regimen was 90%.

Conclusions: Once-daily i.p. administration of ceftazidime according to the ISPD 2000 recommendation could not provide adequately therapeutic levels of ceftazidime in dialysate throughout 24 hours. Despite this finding and the poor post-antibiotic property of ceftazidime, the empiric regimen including once-daily i.p. ceftazidime could yield good clinical outcome.