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Critical Care
Published in: Critical Care 1/2015

Open Access 01-12-2015 | Research

Are standard doses of piperacillin sufficient for critically ill patients with augmented creatinine clearance?

Authors: Andrew A Udy, Jeffrey Lipman, Paul Jarrett, Kerenaftali Klein, Steven C Wallis, Kashyap Patel, Carl MJ Kirkpatrick, Peter S Kruger, David L Paterson, Michael S Roberts, Jason A Roberts

Published in: Critical Care | Issue 1/2015

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Abstract

Introduction

The aim of this study was to explore the impact of augmented creatinine clearance and differing minimum inhibitory concentrations (MIC) on piperacillin pharmacokinetic/pharmacodynamic (PK/PD) target attainment (time above MIC (fT>MIC)) in critically ill patients with sepsis receiving intermittent dosing.

Methods

To be eligible for enrolment, critically ill patients with sepsis had to be receiving piperacillin-tazobactam 4.5 g intravenously (IV) by intermittent infusion every 6 hours for presumed or confirmed nosocomial infection without significant renal impairment (defined by a plasma creatinine concentration greater than 171 μmol/L or the need for renal replacement therapy). Over a single dosing interval, blood samples were drawn to determine unbound plasma piperacillin concentrations. Renal function was assessed by measuring creatinine clearance (CLCR). A population PK model was constructed, and the probability of target attainment (PTA) for 50% and 100% fT>MIC was calculated for varying MIC and CLCR values.

Results

In total, 48 patients provided data. Increasing CLCR values were associated with lower trough plasma piperacillin concentrations (P < 0.01), such that with an MIC of 16 mg/L, 100% fT>MIC would be achieved in only one-third (n = 16) of patients. Mean piperacillin clearance was approximately 1.5-fold higher than in healthy volunteers and correlated with CLCR (r = 0.58, P < 0.01). A reduced PTA for all MIC values, when targeting either 50% or 100% fT>MIC, was noted with increasing CLCR measures.

Conclusions

Standard intermittent piperacillin-tazobactam dosing is unlikely to achieve optimal piperacillin exposures in a significant proportion of critically ill patients with sepsis, owing to elevated drug clearance. These data suggest that CLCR can be employed as a useful tool to determine whether piperacillin PK/PD target attainment is likely with a range of MIC values.
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Metadata
Title
Are standard doses of piperacillin sufficient for critically ill patients with augmented creatinine clearance?
Authors
Andrew A Udy
Jeffrey Lipman
Paul Jarrett
Kerenaftali Klein
Steven C Wallis
Kashyap Patel
Carl MJ Kirkpatrick
Peter S Kruger
David L Paterson
Michael S Roberts
Jason A Roberts
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2015
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-015-0750-y

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