Intermittent intraperitoneal ceftazidime dosing in end-stage renal disease

Area of Science:

• Nephrology
• Pharmacokinetics
• Infectious Diseases

Background:

• Infections are a significant concern for patients undergoing dialysis.
• Shortened hospital stays necessitate effective outpatient antibiotic strategies.
• Parenteral antibiotic administration presents logistical and financial challenges, while daily intraperitoneal dosing risks contamination.

Purpose of the Study:

• To investigate the pharmacokinetics of intraperitoneal ceftazidime in chronic peritoneal dialysis patients.
• To evaluate the feasibility of thrice-weekly intraperitoneal dosing of ceftazidime.
• To assess ceftazidime stability and serum/dialysate concentrations.

Main Methods:

• Seven stable chronic peritoneal dialysis patients received a 2g loading dose followed by 1.5g every 48 hours.
• In vitro stability of ceftazidime at 4°C was assessed using high-performance liquid chromatography.
• Serum and dialysate concentrations were measured over 48 hours to determine pharmacokinetic parameters.

Main Results:

• Ceftazidime demonstrated 91% stability in vitro at 120 hours.
• Peak serum concentrations were achieved at 4.9 hours, with significant levels remaining at 24 and 48 hours.
• Median trough dialysate levels at 48 hours were lower than serum levels (2.8 vs 8.5 microg/ml, p=0.0425).
• Key pharmacokinetic parameters included bioavailability (88%), volume of distribution (20 L), and elimination half-life (11.4 hours).

Conclusions:

• Intraperitoneal ceftazidime administered every 48 hours is a viable alternative to parenteral therapy for non-peritoneal infections in dialysis patients.
• The study highlights the practical advantages of this dosing regimen.
• The effectiveness of this regimen in treating peritonitis, considering potential changes in dialysate permeability, requires further investigation.