dc.contributor.author
Ehmann, Lisa
dc.contributor.author
Zoller, Michael
dc.contributor.author
Minichmayr, Iris K.
dc.contributor.author
Scharf, Christina
dc.contributor.author
Maier, Barbara
dc.contributor.author
Schmitt, Maximilian V.
dc.contributor.author
Hartung, Niklas
dc.contributor.author
Huisinga, Wilhelm
dc.contributor.author
Vogeser, Michael
dc.contributor.author
Frey, Lorenz
dc.contributor.author
Zander, Johannes
dc.contributor.author
Kloft, Charlotte
dc.date.accessioned
2018-06-08T10:21:52Z
dc.date.available
2017-10-26T08:53:01.961Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/20300
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-23604
dc.description.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.
en
dc.format.extent
14 Seiten
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Intensive care
dc.subject
Pharmacokinetics/Pharmacodynamics
dc.subject
Target attainment
dc.subject
Renal function
dc.subject
Risk assessment tool
dc.subject
Continuous renal replacement therapy
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::572 Biochemie
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::615 Pharmakologie, Therapeutik
dc.title
Role of renal function in risk assessment of target non-attainment after
standard dosing of meropenem in critically ill patients
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation
Critical Care (2017) 21:263
dc.title.subtitle
A prospective observational study
dcterms.bibliographicCitation.doi
10.1186/s13054-017-1829-4
dcterms.bibliographicCitation.url
http://doi.org/10.1186/s13054-017-1829-4
refubium.affiliation
Biologie, Chemie, Pharmazie
de
refubium.affiliation.other
Institut für Pharmazie
refubium.mycore.fudocsId
FUDOCS_document_000000028056
refubium.note.author
Gefördert durch die DFG und den Open Access Publikationsfonds der Freien
Universität Berlin.
refubium.resourceType.isindependentpub
no
refubium.mycore.derivateId
FUDOCS_derivate_000000009047
dcterms.accessRights.openaire
open access