The pharmacokinetics of ampicillin–sulbactam in anuric patients: dosing optimization for prophylaxis during cardiovascular surgery

Background The administration of antibiotic prophylaxis during cardiothoracic surgery can reduce the rate of surgical site infections. Trials of cardiothoracic antibiotic prophylaxis have found it to be beneficial in preventing postoperative wound infections. Objective To determine the more appropriate timing of repeated doses of ampicillin–sulbactam to maintain adequate antibiotic concentrations during cardiovascular surgery in anuric patients. Method Five adult anuric dialysis patients who received ampicillin–sulbactam during cardiovascular surgery at Kagoshima University Hospital, the total plasma concentrations of ampicillin and sulbactam were monitored after ampicillin (1 g)–sulbactam (0.5 g) administration. Pharmacokinetic parameters were estimated and used to predict the free plasma concentrations of ampicillin and sulbactam. Results The mean values for the volume of distribution, total clearance, elimination rate constant and the elimination half-life for ampicillin were 8.9 ± 2.4 L, 1.69 ± 0.93 L/h, 0.180 ± 0.059 h⁻¹ and 4.23 ± 1.48 h, respectively. The pharmacokinetic parameters were similar to those of sulbactam. When ampicillin (1 g)–sulbactam (0.5 g) was intravenously administered at 8, 12 and 24 h intervals, the predicted free trough plasma concentrations of ampicillin were 28.72, 12.06 and 1.25 μg/mL, respectively. Conclusion We suggest that ampicillin (1 g)–sulbactam (0.5 g) should be intravenously administered every 12 h in order to maintain a free ampicillin concentration of more than 12 μg/mL in anuric patients during cardiovascular surgery.