Protein binding of β-lactam antibiotics in critically Ill patients: can we successfully predict unbound concentrations?

Wong, Gloria, Briscoe, Scott, Adnan, Syamhanin, McWhinney, Brett, Ungerer, Jacobus, Lipman, Jeffrey and Roberts, Jason A. (2013) Protein binding of β-lactam antibiotics in critically Ill patients: can we successfully predict unbound concentrations?. Antimicrobial Agents and Chemotherapy, 57 12: 6165-6170. doi:10.1128/AAC.00951-13

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Author Wong, Gloria
Briscoe, Scott
Adnan, Syamhanin
McWhinney, Brett
Ungerer, Jacobus
Lipman, Jeffrey
Roberts, Jason A.
Title Protein binding of β-lactam antibiotics in critically Ill patients: can we successfully predict unbound concentrations?
Journal name Antimicrobial Agents and Chemotherapy   Check publisher's open access policy
ISSN 0066-4804
1098-6596
Publication date 2013-01-01
Sub-type Article (original research)
DOI 10.1128/AAC.00951-13
Open Access Status File (Publisher version)
Volume 57
Issue 12
Start page 6165
End page 6170
Total pages 6
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Subject 2736 Pharmacology (medical)
3004 Pharmacology
2725 Infectious Diseases
Abstract The use of therapeutic drug monitoring (TDM) to optimize beta-lactam dosing in critically ill patients is growing in popularity, although there are limited data describing the potential impact of altered protein binding on achievement of target concentrations. The aim of this study was to compare the measured unbound concentration to the unbound concentration predicted from published protein binding values for seven beta-lactams using data from blood samples obtained from critically ill patients. From 161 eligible patients, we obtained 228 and 220 plasma samples at the midpoint of the dosing interval and trough, respectively, for ceftriaxone, cefazolin, meropenem, piperacillin, ampicillin, benzylpenicillin, and flucloxacillin. The total and unbound beta-lactam concentrations were measured using validated methods. Variabilities in both unbound and total concentrations were marked for all antibiotics, with significant differences being present between measured and predicted unbound concentrations for ceftriaxone and for flucloxacillin at the mid-dosing interval (P<0.05). The predictive performance for calculating unbound concentrations using published protein binding values was poor, with bias for overprediction of unbound concentrations for ceftriaxone (83.3%), flucloxacillin (56.8%), and benzylpenicillin (25%) and underprediction for meropenem (12.1%). Linear correlations between the measured total and unbound concentrations were observed for all beta-lactams (R2= 0.81 to 1.00; P<0.05) except ceftriaxone and flucloxacillin. The percent protein binding of flucloxacillin and the plasma albumin concentration were also found to be linearly correlated (R2=0.776; P<0.01). In conclusion, significant differences between measured and predicted unbound drug concentrations were found only for the highly protein-bound beta-lactams ceftriaxone and flucloxacillin. However, direct measurement of unbound drug in research and clinical practice is suggested for selected beta-lactams.
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Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
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