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

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.

Gentamicin and ticarcillin in subjects with end-stage renal disease. Comparison of two assay methods and evaluation of inactivation rate.

Eight subjects with end-stage renal disease were given gentamicin alone (single dose) and in combination with ticarcillin (multiple doses) to determine to what extent ticarcillin inactivates gentamicin in vivo and when this inactivation becomes significant. Gentamicin serum concentrations were performed by both a rapid radioimmunoassay (1 1/2 hours) and a conventional bioassay (8 hours) to determine whether the bioassay results would be falsely lowered by ticarcillin. The results of the study showed that ticarcillin inactivates gentamicin in vivo with an inactivation rate of 0.01 hours(-1). This was demonstrated by a decrease in serum gentamicin levels which became significant at 12 hours after gentamicin was given, and a decrease in gentamicin half-life from 46 to 28 hours during ticarcillin administration. Ticarcillin did not interfere with the bioassay method of measuring gentamicin levels. Although ticarcillin inactivates gentamicin in subjects with end-stage renal disease, the serum level data of gentamicin suggest that supplemental doses of the aminoglycoside are not necessary for 48 hours after a single loading dose of gentamicin. Widely used microbiological assay procedures are reliable in determining gentamicin levels and do not appear to be falsely lowered by concurrent ticarcillin administration.

Piperacillin pharmacokinetics in subjects with chronic renal failure.

The pharmacokinetic parameters of piperacillin sodium were studied in eight volunteer subjects with chronic renal failure. Subjects were given a single 30-min intravenous infusion of 70 mg/kg (lean body weight) on their off-dialysis day. Blood was drawn from the contralateral arm at 15 and 30 min and 1, 3, 6, 9, and 12 h from the start of the infusion. Kinetic parameters were determined during the elimination phase with a one-compartment open model for linear kinetics. The following pharmacokinetic parameters (mean +/- standard deviation) were determined for the eight subjects: elimination half-life = 3.33 +/- 0.99 h, elimination rate constant = 0.22 +/- 0.06 h-1, apparent volume of distribution = 0.18 +/- 0.05 liters per kg, and total body clearance = 0.041 +/- 0.019 liters per kg/h. The mean peak serum concentration was 372 +/- 125 microgram/ml, and mean trough at 12 h was 39 +/- 27 microgram/ml. A dose of 70 mg/kg (lean body weight) or a dose of 4 g appears to provide adequate serum concentrations against susceptible organisms for a 12-h interval. No adverse reactions were noted in any subject throughout the study.

Hypogeusia and zinc depletion in chronic dialysis patients.

Dialysis patients generally have a poor appetite, do not enjoy eating, and complain of food, particularly protein, as being disagreeable. Twenty dialysis patients with the above symptoms were tested for taste acuity, serum zinc (Zn), Zn concentrations in hair samples (intracellular Zn), and daily caloric intake. A double-blind, cross-over study was instituted using a Zn supplement and a placebo. After supplementation with Zn, taste acuity markedly improved in 95% of patients and Zn concentrations in hair increased in 85% of patients. The patients' appetites were improved; the average caloric intake increased by 675 kcal/day, and intolerance to protein diminished. In addition 10 normal control subjects were studied pre- and post-Zn supplementation for fasting blood glucose, serum Zn levels, and hair Zn concentration. Side effects were noted, and these usually correlated with elevated serum Zn levels and were minimized or disappeared with decrease in dosage or cessation of therapy.

Portable/wearable artificial kidney (WAK) - initial evaluation.

This report discusses the modus operandi and results achieved using this new mode of haemodialysis. An insulated 20 L dialysate bath acts as a carrying case for the system. When empty the case is large enough to hold the wearable module and complete supplies for one week's operation. The total weight is 17 kg. The wearable unit consists of a combined blood and dialysate pump (1.2 kg), rechargeable batteries, tubing, Dow dialyser and charcoal regeneration module with a total weight of 3.5kg. Ideally the patient dialyses using a single needle some 3 hours/day, 6 days/week. It is necessary for the wearable module to be connected to the 20 L dialysate bath for an average of 90 minutes to achieve adequate urea and 5+ removal. One patient was dialysed on 35 consecutive days and 4 others were dialysed intermittently. Routine laboratory tests and mass balance studies were performed on all patients. Ultrafiltration rates reached 700 ml/hour, routine serum chemistries remained stable and mass balance studies demonstrated a daily removal of urea 14-20 G, creatinine 1500-2000 mg, uric acid 500-900 mg and K+ 30-55 mEq. It is concluded that dialy dialysis with WAK is biochemically adequate and also permits the patient a much less restricted esistence.