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

J. A. Roberts, V. Stove, J. J. De Waele, B. Sipinkoski, B. McWhinney, J. P.J. Ungerer, M. Akova, M. Bassetti, G. Dimopoulos, K. M. Kaukonen, D. Koulenti, C. Martin, P. Montravers, J. Rello, A. Rhodes, T. Starr, S. C. Wallis, J. Lipman, S. Paul, A. M. RibasL. DeCrop, H. Spapen, J. Wauters, T. Dugernier, P. Jorens, I. Dapper, D. De Backer, F. S. Taccone, L. Ruano, E. Afonso, F. Alvarez-Lerma, M. P. Gracia-Arnillas, F. Fernández, N. Feijoo, N. Bardolet, A. Rovira, P. Garro, D. Colon, C. Castillo, J. Fernado, M. J. Lopez, J. L. Fernandez, A. M. Arribas, J. L. Teja, E. Ots, J. C. Montejo, M. Catalan, I. Prieto, G. Gonzalo, B. Galvan, M. A. Blasco, E. Meyer, F. D. Nogal, L. Vidaur, R. Sebastian, P. M. Garde, M. Velasco Mdel, R. Z. Crespo, M. Esperatti, A. Torres, O. Baldesi, H. Dupont, Y. Mahjoub, S. Lasocki, J. M. Constantin, J. F. Payen, J. Albanese, Y. Malledant, J. Pottecher, J. Y. Lefrant, S. Jaber, O. Joannes-Boyau, C. Orban, M. Ostermann, C. McKenzie, W. Berry, J. Smith, K. Lei, Francesca Rubulotta, A. Gordon, S. Brett, M. Stotz, M. Templeton, C. Ebm, C. Moran, V. Pettilä, A. Xristodoulou, V. Theodorou, G. Kouliatsis, E. Sertaridou, G. Anthopoulos, G. Choutas, T. Rantis, S. Karatzas, M. Balla, M. Papanikolaou, P. Myrianthefs, A. Gavala, G. Fildisis, A. Koutsoukou

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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. © 2014 Elsevier B.V. and the International Society of Chemotherapy.
Original languageEnglish
Pages (from-to)423-430
JournalInternational Journal of Antimicrobial Agents
Volume43
Issue number5
DOIs
Publication statusPublished - 1 May 2014

Keywords

  • Antibiotics
  • Critically ill patients
  • Glycopeptides
  • Hypoalbuminaemia
  • ICU
  • Pharmacokinetics

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