Absorption and Clearance of Ceftazidime During CAPD

Continuous ambulatory peritoneal dialysis (CAPD) peritonitis causes substantial morbidity and consumes scarce healthcare resources. The costs oftreating peritonitis extend beyond the cost of antibiotics alone. Outpatient care is less costly for patients not requiring admission on clinical grounds. Complex multicomponent regimes consume more patient, medical, nursing, and pharmacy time. Repeated injections into dialysate bags are generally undesirable. An optimal outpatient regime should maximize patient convenience, confidence, and compliance by incorporating the least possible number of drugs and doses that do not compromise therapeutic efficacy. Current therapeutic practice (1-3) favors an initial combination regime ofintraperitoneal (IP) antibiotics with activity against both gram-positive and gramnegative pathogens. The combination of vancomycin and ceftazidime produces good cure rates (4,5). Vancomycin has been successfully used (primarily for gram-positive infections) in an intermittent IP dose regime. The pharmacokinetics of a single IP bolus have been studied in noninfected (6,7) and infected (8,9) CAPD patients. Therapeutic efficacy has been established in a prospective randomized trial (10). Ceftazidime is normally removed almost exclusively by renal excretion, with little metabolism or biliary excretion (11). Its properties in patients with impaired renal function (12,13) suggest that it, too, could potentially be used in an intermittent IP dose regime. We have studied the absorption and clearance of a single IP dose in noninfected CAPD patients over 48 hours, with particular focus on the maintenance of bactericidal drug concentrations in effluent dialysate and plasma throughout this period