Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: Lessons from the DALI Study

Roberts, J. A., Stove, V., De Waele, J. J., Sipinkoski, B., McWhinney, B., Ungerer, J. P. J., Akova, M., Bassetti, M., Dimopoulos, G., Kaukonen, K.-M., Koulenti, D., Martin, C., Montravers, P., Rello, J., Rhodes, A., Starr, T., Wallis, S. C. and Lipman, J. (2014) Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: Lessons from the DALI Study. International Journal of Antimicrobial Agents, 43 5: 423-430. doi:10.1016/j.ijantimicag.2014.01.023


Author Roberts, J. A.
Stove, V.
De Waele, J. J.
Sipinkoski, B.
McWhinney, B.
Ungerer, J. P. J.
Akova, M.
Bassetti, M.
Dimopoulos, G.
Kaukonen, K.-M.
Koulenti, D.
Martin, C.
Montravers, P.
Rello, J.
Rhodes, A.
Starr, T.
Wallis, S. C.
Lipman, J.
Title Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: Lessons from the DALI Study
Journal name International Journal of Antimicrobial Agents   Check publisher's open access policy
ISSN 0924-8579
1872-7913
Publication date 2014-01-01
Year available 2014
Sub-type Article (original research)
DOI 10.1016/j.ijantimicag.2014.01.023
Open Access Status Not yet assessed
Volume 43
Issue 5
Start page 423
End page 430
Total pages 8
Place of publication Amsterdam, The Netherlands
Publisher Elsevier
Language eng
Abstract The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20 mg/L and the higher range as 10-30 mg/L. Thirteen critically ill patients were available for analysis. The following are the median (interquartile range) total and free concentrations (mg/L): midpoint, total 13.6 (11.2-26.0) and free 1.5 (0.7-2.5); trough, total 11.9 (10.2-22.7) and free 1.8 (0.6-2.6). The percentage free teicoplanin for the mid-dose and trough time points was 6.9% (4.5-15.6%) and 8.2% (5.5-16.4%), respectively. The correlation between total and free antibiotic concentrations was moderate for both the midpoint (ρ = 0.79, P = 0.0021) and trough (ρ = 0.63, P = 0.027). Only 42% and 58% of patients were in the lower and higher therapeutic ranges, respectively. In conclusion, use of standard dosing for teicoplanin leads to inappropriate concentrations in a high proportion of critically ill patients. Variability in teicoplanin protein binding is very high, placing significant doubt on the validity of total concentrations for therapeutic drug monitoring in critically ill patients.
Keyword Antibiotics
Critically ill patients
Glycopeptides
Hypoalbuminaemia
ICU
Pharmacokinetics
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID NHMRC APP1048652
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Medicine Publications
 
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