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


METHODS
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.
Division of Nephrology and Hypertension, Department of Internal Medicine, Hannover Medical School, Germany.
Johan M
JM
Lorenzen
Michael
M
Broll
Volkhard
V
Kaever
Heike
H
Burhenne
Carsten
C
Hafer
Christian
C
Clajus
Wolfgang
W
Knitsch
Olaf
O
Burkhardt
Jan T
JT
Kielstein
D058186:Acute Kidney Injury / Q000097:blood / Q000378:metabolism / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000667:Ampicillin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001002:Anuria / Q000378:metabolism / Q000628:therapy; D019540:Area Under Curve; D016638:Critical Illness; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D016903:Drug Monitoring; D004867:Equipment Design; D005260:Female; D005858:Germany; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008567:Membranes, Artificial; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D011108:Polymers; D011446:Prospective Studies; D006435:Renal Dialysis / Q000295:instrumentation; D013407:Sulbactam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D013450:Sulfones; D055815:Young Adult
D000900:Anti-Bacterial Agents; D008567:Membranes, Artificial; D011108:Polymers; D013450:Sulfones; C017662:polysulfone P 1700; C035444:sultamicillin; D000667:Ampicillin; D013407:Sulbactam