A simulation study reveals lack of pharmacokinetic/pharmacodynamic target attainment in de-escalated antibiotic therapy in critically ill patients

Carlier, Mieke, Roberts, Jason A., Stove, Veronique, Verstraete, Alain G., Lipman, Jeffrey and De Waele, Jan J. (2015) A simulation study reveals lack of pharmacokinetic/pharmacodynamic target attainment in de-escalated antibiotic therapy in critically ill patients. Antimicrobial Agents and Chemotherapy, 59 8: 4689-4694. doi:10.1128/AAC.00409-15

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Author Carlier, Mieke
Roberts, Jason A.
Stove, Veronique
Verstraete, Alain G.
Lipman, Jeffrey
De Waele, Jan J.
Title A simulation study reveals lack of pharmacokinetic/pharmacodynamic target attainment in de-escalated antibiotic therapy in critically ill patients
Journal name Antimicrobial Agents and Chemotherapy   Check publisher's open access policy
ISSN 1098-6596
Publication date 2015-08-01
Year available 2015
Sub-type Article (original research)
DOI 10.1128/AAC.00409-15
Open Access Status File (Publisher version)
Volume 59
Issue 8
Start page 4689
End page 4694
Total pages 6
Place of publication Washington, DC United States
Publisher American Society for Microbiology
Collection year 2016
Language eng
Abstract De-escalation of empirical antibiotic therapy is often included in antimicrobial stewardship programs in critically ill patients, but differences in target attainment when antibiotics are switched are rarely considered. The primary objective of this study was to compare the fractional target attainments of contemporary dosing of empirical broad-spectrum β-lactam antibiotics and narrower-spectrum antibiotics for a number pathogens for which de-escalation may be considered. The secondary objective was to determine whether alternative dosing strategies improve target attainment. We performed a simulation study using published population pharmacokinetic (PK) studies in critically ill patients for a number of broad-spectrum β-lactam antibiotics and narrower-spectrum antibiotics. Simulations were undertaken using a data set obtained from critically ill patients with sepsis without absolute renal failure (n = 49). The probability of target attainment of antibiotic therapy for different microorganisms for which de-escalation was applied was analyzed. EUCAST MIC distribution data were used to calculate fractional target attainment. The probability that therapeutic exposure will be achieved was lower for the narrower-spectrum antibiotics with conventional dosing than for the broad-spectrum alternatives and could drastically be improved with higher dosages and different modes of administrations. For a selection of microorganisms, the probability that therapeutic exposure will be achieved was overall lower for the narrower-spectrum antibiotics using conventional dosing than for the broad-spectrum antibiotics.
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Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
School of Pharmacy Publications
 
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