Pharmacokinetics of ampicillin/sulbactam in critically ill patients with acute kidney injury undergoing extended dialysis

Abstract

Background and objectives: The fixed antibacterial combination of ampicillin and sulbactam is frequently used for various infections. Intact kidneys eliminate approximately 71% of ampicillin and 78% of sulbactam. Patients on thrice-weekly low-flux hemodialysis exhibit an ampicillin t(1/2) of 2.3 hours on and 17.4 hours off dialysis. Despite its frequent use in intensive care units, there are no available dosing recommendations for patients with AKI undergoing renal replacement therapy. The aims of this study were to evaluate the pharmacokinetics of ampicillin/sulbactam in critically ill patients with AKI undergoing extended dialysis (ED) and to establish a dosing recommendation for this treatment method.

Design, setting, participants, & measurements: Twelve critically ill patients with anuric AKI being treated with ED were enrolled in a prospective, open-label, observational pharmacokinetic study. Pharmacokinetics after a single dose of ampicillin/sulbactam (2 g/1 g) was obtained in 12 patients. Multiple-dose pharmacokinetics after 4 days of twice-daily ampicillin/sulbactam (2 g/1 g) was obtained in three patients.

Results: The mean dialyzer clearance for ampicillin/sulbactam was 80.1 ± 7.7/83.3 ± 12.1 ml/min. The t(1/2) of ampicillin and sulbactam in patients with AKI undergoing ED were 2.8 ± 0.8 hours and 3.5 ± 1.5 hours, respectively. There was no significant accumulation using a twice-daily dosage of 2 g/1 g ampicillin/sulbactam.

Conclusions: Our data suggest that in patients treated with ED using a high-flux dialyzer (polysulphone, 1.3 m(2); blood and dialysate flow, 160 ml/min; treatment time, 480 minutes), a twice-daily dosing schedule of at least 2 g/1 g ampicillin/sulbactam, with one dose given after ED, should be used to avoid underdosing.

Figure 1.

Mean plasma concentrations of ampicillin/sulbactam in plasma of critically ill patients with AKI undergoing extended dialysis (duration depicted by box size) after a single intravenous dose of 2.0 g/1.0 g ampicillin/sulbactam. Infusion period was 30 minutes. Extended dialysis started about 3 hours after the end of the ampicillin/sulbactam infusion. Values are arithmetic means ± SEM, n=12.

Figure 2.

Dialyzer clearance of ampicillin/sulbactam in plasma of critically ill patients with AKI undergoing extended dialysis. Predialyzer and postdialyzer blood samples were drawn 15 minutes after start of treatment with no net ultrafiltration. Data are visualized as box and whisker plots. Horizontal bars indicate median values.

Figure 3.

Median concentrations of ampicillin/sulbactam in plasma of critically ill patients (n=3) with AKI undergoing extended dialysis (duration depicted by box size) after the first intravenous dose of 2.0 g/1.0 g ampicillin/sulbactam, as well as on day 4 of treatment at a dosing schedule of 2.0 g/1.0g ampicillin/sulbactam twice daily. Data are presented as median values, n=3. SD, single dose; MD, multiple dose.