Gentamicin inactivation by piperacillin or carbenicillin in patients with end-stage renal disease

Abstract

Possible antibiotic inactivation was studied in 12 subjects with end-stage renal disease who were undergoing thrice-weekly hemodialysis. The study was a randomized three-way crossover. Subjects received (i) gentamicin as a single intravenous dose of 2 mg/kg, (ii) 4 g of piperacillin intravenously every 12 h for four doses or 2 g of carbenicillin intravenously every 8 h for six doses, and (iii) gentamicin as described in (i) plus piperacillin or carbenicillin as described in (ii). Subjects were studied on their off-dialysis days, and each treatment phase was separated by a 3-week wash-out period. Gentamicin was inactivated to a greater extent by carbenicillin than by piperacillin (P less than 0.05). In the six subjects in the carbenicillin group, the terminal elimination-phase half-life (t 1/2 beta) of gentamicin was 61.6 h when gentamicin was administered alone, and it was 19.4 h when gentamicin was administered with carbenicillin. In six subjects in the piperacillin group, the mean t 1/2 beta of gentamicin when gentamicin was given alone was 53.9 h, and it was 37.7 h when gentamicin was given with piperacillin. The inactivation rate constant (ki) of gentamicin was 0.0251/h for the carbenicillin group and 0.0064/h for the piperacillin group, demonstrating that carbenicillin inactivated gentamicin for time faster than did piperacillin. No inactivation of either beta-lactam could be measured. Control samples verified that no in vitro inactivation occurred.