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Critical Care
Published in: Critical Care 1/2017

Open Access 01-12-2017 | Research

Role of renal function in risk assessment of target non-attainment after standard dosing of meropenem in critically ill patients: a prospective observational study

Authors: Lisa Ehmann, Michael Zoller, Iris K. Minichmayr, Christina Scharf, Barbara Maier, Maximilian V. Schmitt, Niklas Hartung, Wilhelm Huisinga, Michael Vogeser, Lorenz Frey, Johannes Zander, Charlotte Kloft

Published in: Critical Care | Issue 1/2017

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Abstract

Background

Severe bacterial infections remain a major challenge in intensive care units because of their high prevalence and mortality. Adequate antibiotic exposure has been associated with clinical success in critically ill patients. The objective of this study was to investigate the target attainment of standard meropenem dosing in a heterogeneous critically ill population, to quantify the impact of the full renal function spectrum on meropenem exposure and target attainment, and ultimately to translate the findings into a tool for practical application.

Methods

A prospective observational single-centre study was performed with critically ill patients with severe infections receiving standard dosing of meropenem. Serial blood samples were drawn over 4 study days to determine meropenem serum concentrations. Renal function was assessed by creatinine clearance according to the Cockcroft and Gault equation (CLCRCG). Variability in meropenem serum concentrations was quantified at the middle and end of each monitored dosing interval. The attainment of two pharmacokinetic/pharmacodynamic targets (100%T>MIC, 50%T>4×MIC) was evaluated for minimum inhibitory concentration (MIC) values of 2 mg/L and 8 mg/L and standard meropenem dosing (1000 mg, 30-minute infusion, every 8 h). Furthermore, we assessed the impact of CLCRCG on meropenem concentrations and target attainment and developed a tool for risk assessment of target non-attainment.

Results

Large inter- and intra-patient variability in meropenem concentrations was observed in the critically ill population (n = 48). Attainment of the target 100%T>MIC was merely 48.4% and 20.6%, given MIC values of 2 mg/L and 8 mg/L, respectively, and similar for the target 50%T>4×MIC. A hyperbolic relationship between CLCRCG (25–255 ml/minute) and meropenem serum concentrations at the end of the dosing interval (C8h) was derived. For infections with pathogens of MIC 2 mg/L, mild renal impairment up to augmented renal function was identified as a risk factor for target non-attainment (for MIC 8 mg/L, additionally, moderate renal impairment).

Conclusions

The investigated standard meropenem dosing regimen appeared to result in insufficient meropenem exposure in a considerable fraction of critically ill patients. An easy- and free-to-use tool (the MeroRisk Calculator) for assessing the risk of target non-attainment for a given renal function and MIC value was developed.

Trial registration

Clinicaltrials.gov, NCT01793012. Registered on 24 January 2013.
Appendix
Available only for authorised users
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Metadata
Title
Role of renal function in risk assessment of target non-attainment after standard dosing of meropenem in critically ill patients: a prospective observational study
Authors
Lisa Ehmann
Michael Zoller
Iris K. Minichmayr
Christina Scharf
Barbara Maier
Maximilian V. Schmitt
Niklas Hartung
Wilhelm Huisinga
Michael Vogeser
Lorenz Frey
Johannes Zander
Charlotte Kloft
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2017
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-017-1829-4

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