Open Access Highly Accessed Research

Meropenem and piperacillin/tazobactam prescribing in critically ill patients: does augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used?

Mieke Carlier1, Sofie Carrette2, Jason A Roberts3, Veronique Stove4, Alain Verstraete1, Eric Hoste2, Pieter Depuydt2, Johan Decruyenaere2, Jeffrey Lipman3, Steven C Wallis3 and Jan J De Waele2*

Author Affiliations

1 Department of Clinical Chemistry, Microbiology and Immunology & Department of Critical Care Medicine, Ghent University, De Pintelaan 185, Ghent, 9000, Belgium

2 Department of Critical Care Medicine, Ghent University, De Pintelaan 185, Ghent, 9000, Belgium

3 Burns Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia, Royal Brisbane and Women's Hospital, Herston, QLD 4029, Australia

4 Department of Laboratory Medicine, Ghent University Hospital, De Pintelaan 185, Ghent, 9000, Belgium

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Critical Care 2013, 17:R84  doi:10.1186/cc12705

Published: 3 May 2013

Abstract

Background

Correct antibiotic dosing remains a challenge for the clinician. The aim of this study was to assess the influence of augmented renal clearance on pharmacokinetic/pharmacodynamic target attainment in critically ill patients receiving meropenem or piperacillin/tazobactam, administered as an extended infusion.

Methods

This was a prospective, observational, pharmacokinetic study executed at the medical and surgical intensive care unit at a large academic medical center. Elegible patients were adult patients without renal dysfunction receiving meropenem or piperacillin/tazobactam as an extended infusion. Serial blood samples were collected to describe the antibiotic pharmacokinetics. Urine samples were taken from a 24-hour collection to measure creatinine clearance. Relevant data were drawn from the electronic patient file and the intensive care information system.

Results

We obtained data from 61 patients and observed extensive pharmacokinetic variability. Forty-eight percent of the patients did not achieve the desired pharmacokinetic/pharmacodynamic target (100% fT>MIC), of which almost 80% had a measured creatinine clearance >130 mL/min. Multivariate logistic regression demonstrated that high creatinine clearance was an independent predictor of not achieving the pharmacokinetic/pharmacodynamic target. Seven out of nineteen patients (37%) displaying a creatinine clearance >130 mL/min did not achieve the minimum pharmacokinetic/pharmacodynamic target of 50% fT>MIC.

Conclusions

In this large patient cohort, we observed significant variability in pharmacokinetic/pharmacodynamic target attainment in critically ill patients. A large proportion of the patients without renal dysfunction, most of whom displayed a creatinine clearance >130 mL/min, did not achieve the desired pharmacokinetic/pharmacodynamic target, even with the use of alternative administration methods. Consequently, these patients may be at risk for treatment failure without dose up-titration.

Keywords:
β-lactam antibiotics; hyperfiltration; kidney function; pharmacokinetics; pharmacodynamics; therapeutic drug monitoring