Pharmacokinetics of intraperitoneal cefazolin and gentamicin in empiric therapy of peritonitis in continuous ambulatory peritoneal dialysis patients

Abstract

◆ Objective: The aim of this study was to measure and evaluate the appropriateness of the actual concentrations of serum and dialysate cefazolin and gentamicin in Thai continuous ambulatory peritoneal dialysis (CAPD) patients treated following the International Society for Peritoneal Dialysis (ISPD) 1996 recommendations for the empiric therapy of CAPD-related peritonitis. ◆ Design: Prospective and descriptive study. ◆ Setting: Institutional level of clinical care. ◆ Patients: CAPD-related peritonitis patients were diagnosed by dialysate effluent white cell count of more than 100/mm3 and polymorphonuclear leukocytes of at least 50%. There were 18 patients, all at least 15 years of age, entered; all completed the study. ◆ Intervention: In accordance with the ISPD 1996 recommendations, the antibiotic regimen included continuous intraperitoneal (IP) cefazolin and once-daily IP aminoglycoside. Cefazolin was administered as loading and continuous maintenance doses of 500 and 125 mg/L dialysate, respectively. Gentamicin, 0.6 mg/kg body weight, was given IP once daily. Duration of treatment was 120 hours. ◆ Main Outcome Measures: Serum and dialysate effluent samples of the 18 CAPD patients with peritonitis were measured and used for the synthesis of pharmacokinetic equations that could predict drug concentrations at any treatment time. ◆ Results: Following administration according to the ISPD 1996 treatment recommendations, serum cefazolin reached levels higher than the recommended levels (8 μg/mL) at 3.3 minutes after drug administration, and persisted through the 5-day duration of the study. Dialysate cefazolin levels during the studied period also were persistently higher than the recommended values. The peak serum gentamicin levels were lower than the suggested values of 4 μg/mL, whereas the trough serum gentamicin levels were higher than the minimal toxic concentrations (2 μg/mL). Dialysate gentamicin levels were higher than therapeutic concentrations for only 4.75 hours in each day. It was difficult, using pharmacokinetic studies, to adjust the dosage regimen of gentamicin to achieve appropriately therapeutic levels in both serum and dialysate. ◆ Conclusions: The ISPD 1996 recommended dosage of continuous IP cefazolin could be appropriate for the treatment of CAPD-related peritonitis. Once-daily IP gentamicin administration, however, has less therapeutic benefit and should be re-evaluated.