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

Carlier, Mieke, Carrette, Sofie, Roberts, Jason A., Stove, Veronique, Verstraete, Alain, Hoste, Eric, Depuydt, Pieter, Decruyenaere, Johan, Lipman, Jeffrey, Wallis, Steven C. and De Waele, Jan J. (2013) Meropenem and piperacillin/tazobactam prescribing in critically ill patients: Does augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used?. Critical Care, 17 3: R84.1-R84.9. doi:10.1186/cc12705


Author Carlier, Mieke
Carrette, Sofie
Roberts, Jason A.
Stove, Veronique
Verstraete, Alain
Hoste, Eric
Depuydt, Pieter
Decruyenaere, Johan
Lipman, Jeffrey
Wallis, Steven C.
De Waele, Jan J.
Title Meropenem and piperacillin/tazobactam prescribing in critically ill patients: Does augmented renal clearance affect pharmacokinetic/pharmacodynamic target attainment when extended infusions are used?
Journal name Critical Care   Check publisher's open access policy
ISSN 1364-8535
1466-609X
Publication date 2013-05-03
Year available 2013
Sub-type Article (original research)
DOI 10.1186/cc12705
Open Access Status DOI
Volume 17
Issue 3
Start page R84.1
End page R84.9
Total pages 9
Place of publication London, United Kingdom
Publisher BioMed Central Ltd.
Language eng
Subject 2706 Critical Care and Intensive Care Medicine
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.
Keyword β-lactam antibiotics
hyperfiltration
kidney function
pharmacodynamics
pharmacokinetics
therapeutic drug monitoring
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID APP1048652
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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