Effect of hemodialysis and peritoneal dialysis on aztreonam pharmacokinetics

Abstract

Aztreonam, a new monobactam, will be widely used because of its broad aerobic gram-negative bacterial coverage and its apparent low risk of allergic phenomena in penicillin/cephalosporin-sensitive patients. We examined aztreonam kinetics in patients during hemodialysis and in the interdialytic period and in patients on continuous ambulatory peritoneal dialysis (CAPD), and related aztreonam to urea clearance (CL). In hemodialysis patients, aztreonam serum half-life was 7.9 hr between and 2.7 hr during dialysis sessions. CL(serum), CL(renal), and CL(other), were 24.4, 0.5, and 23.9 ml/min, respectively, during the interdialytic period. Four hours of dialysis removed 38.2% (range, 27 to 58%) of antibiotic. CL of aztreonam by hemodialysis was 36.6 to 43.2 ml/min, 50 to 77% greater than interdialytic CL. CL of urea by hemodialysis was 112.4 to 155.6 ml/min; CL(aztreonam)/CL(urea) ratio was 0.28 to 0.33 during the hemodialysis sessions. During CAPD, aztreonam serum half-life after intravenous dosing was 7.1 hr; dialysate recovery, 9.7% of the dose; CL(serum), CL(renal), CL(peritoneal dialysis), and CL(other) were 23.8, 0.5, 2.1, and 21.3 ml/min, respectively. CL(urea) by CAPD was 6.5 ml/min. Thus, CL(aztreonam) during CAPD was 32% of CL(urea). Aztreonam was detectable in dialysate at 48 hr (eight exchanges) after peritoneal administration in the first exchange. Hemodialysis and CAPD patients given aztreonam treatment should receive the standard dose of aztreonam as a loading dose, followed by one-fourth the loading dose at standard dose intervals. Hemodialysis patients should receive a supplemental dose equal to half their usual maintenance dose immediately after each dialysis session. For CAPD patients with peritonitis due to susceptible organisms, a 1-g i.v. loading dose followed by a 0.5-g i.p. dose every 6 hr is suggested. In any individual patient undergoing hemodialysis or CAPD, the relationship between CL(urea) and CL(aztreonam) should allow appropriate antibiotic dose adjustment.