Pharmacokinetics of piperacillin in critically ill patients with acute kidney injury receiving sustained low-efficiency diafiltration. (1st March 2018)

• Record Type: Journal Article
• Authors: Sinnollareddy, Mahipal G; Roberts, Michael S; Lipman, Jeffrey; Peake, Sandra L; Roberts, Jason A
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 73:Number 6(2018)
• Page Start: 1647
• Page End: 1650
• Publication Date: 2018-03-01
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dky057
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Background: Piperacillin is a β-lactam penicillin antibiotic commonly used for the empirical therapy of sepsis and other hospital-acquired infections. However, knowledge regarding the effect of sustained low-efficiency diafiltration (SLED- f ), a technique increasingly being used in ICUs, on piperacillin pharmacokinetics (PK) and dosing in critically ill patients is lacking. Objectives: To describe the PK of piperacillin during SLED- f and compare the results with those reported for other forms of renal replacement therapies. Methods: Serial blood samples were collected at pre- and post-filter ports within the SLED- f circuit during SLED- f in one session and from an arterial catheter during sampling without SLED- f . Piperacillin concentrations were measured using a validated chromatography method. Non-compartmental PK analysis of the data was performed. Results: The median clearance and area under the concentration–time curve during SLED- f were 6 L/h and 532 mg·h/L, respectively. Fifty-eight percent of piperacillin was cleared by a single SLED- f session (6 h) compared with previous reports of 30%–45% clearance by a 3.5 h intermittent haemodialysis session. Clearance, half-life and area under the concentration–time curve during SLED- f obtained from this study were comparable with those reported in the post-dilution mode of continuous veno-venous haemodiafiltration studies. Conclusions: As it can be challenging to accurately predict when SLED- f will be initiated in the critically ill, a maintenance dose of at least 4 g every 12 h with at least a 2 g replacement dose post-SLED- f would be a practical approach to piperacillin dosing in ICU patients with anuria receiving SLED- f with a duration similar to the current study.