Mahipal G Sinnollareddy1,2, Michael S Roberts1,2, Jeffrey Lipman3,4, Sandra L Peake5, Jason A Roberts3,4,6,7. 1. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia. 2. Therapeutics Research Centre, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, Australia. 3. University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia. 4. Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia. 5. Department of Intensive Care Medicine, The Queen Elizabeth Hospital, Adelaide, Australia. 6. Pharmacy Department, Royal Brisbane and Women's Hospital, Brisbane, Australia. 7. Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia.
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.
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 illpatients 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.