eprintid: 23673
rev_number: 12
eprint_status: archive
userid: 1589
dir: disk0/00/02/36/73
datestamp: 2017-11-03 13:17:12
lastmod: 2024-05-04 17:39:16
status_changed: 2017-11-03 13:17:12
type: article
metadata_visibility: show
creators_name: Ehmann, Lisa
creators_name: Zoller, Michael
creators_name: Minichmayr, Iris K.
creators_name: Scharf, Christina
creators_name: Maier, Barbara
creators_name: Schmitt, Maximilian V.
creators_name: Hartung, Niklas
creators_name: Huisinga, Wilhelm
creators_name: Vogeser, Michael
creators_name: Frey, Lorenz
creators_name: Zander, Johannes
creators_name: Kloft, Charlotte
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
subjects: ddc-570
divisions: i-160100
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.
date: 2017
publisher: BioMed Central; Springer
id_scheme: DOI
ppn_swb: 1657064840
own_urn: urn:nbn:de:bsz:16-heidok-236737
language: eng
bibsort: EHMANNLISAROLEOFRENA2017
full_text_status: public
publication: Critical care
volume: 21
number: 263
place_of_pub: London; Berlin, Heidelberg
pagerange: 1-14
issn: 1466-609X
citation:   Ehmann, Lisa ; Zoller, Michael ; Minichmayr, Iris K. ; Scharf, Christina ; Maier, Barbara ; Schmitt, Maximilian V. ; Hartung, Niklas ; Huisinga, Wilhelm ; Vogeser, Michael ; Frey, Lorenz ; Zander, Johannes ; Kloft, Charlotte  (2017) Role of renal function in risk assessment of target non-attainment after standard dosing of meropenem in critically ill patients: a prospective observational study.  Critical care, 21 (263).  pp. 1-14.  ISSN 1466-609X     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/23673/1/13054_2017_Article_1829.pdf