title: Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: lessons from the DALI Study.
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.
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia; Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia. Electronic address: j.roberts2@uq.edu.au.
authors.forename: J A
authors.initials: JA
authors.lastname: Roberts
authors.affiliation: Ghent University Hospital, Ghent, Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Stove
authors.affiliation: Ghent University Hospital, Ghent, Belgium.
authors.forename: J J
authors.initials: JJ
authors.lastname: De Waele
authors.affiliation: Queensland Pathology, Brisbane, Queensland, Australia.
authors.forename: B
authors.initials: B
authors.lastname: Sipinkoski
authors.affiliation: Queensland Pathology, Brisbane, Queensland, Australia.
authors.forename: B
authors.initials: B
authors.lastname: McWhinney
authors.affiliation: Queensland Pathology, Brisbane, Queensland, Australia.
authors.forename: J P J
authors.initials: JP
authors.lastname: Ungerer
authors.affiliation: Hacettepe University, School of Medicine, Ankara, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Akova
authors.affiliation: Azienda Ospedaliera-Universitaria 'Santa Maria della Misericordia', Udine, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bassetti
authors.affiliation: 'Attikon' University Hospital, Athens, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Dimopoulos
authors.affiliation: Helsinki University Central Hospital, Helsinki, Finland; Australian and New Zealand Intensive Care Research Centre (ANZIC RC), Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
authors.forename: K-M
authors.initials: KM
authors.lastname: Kaukonen
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia; 'Attikon' University Hospital, Athens, Greece.
authors.forename: D
authors.initials: D
authors.lastname: Koulenti
authors.affiliation: Hôpital Nord, Marseille, France; AzuRea Group, France.
authors.forename: C
authors.initials: C
authors.lastname: Martin
authors.affiliation: Centre Hospitalier Universitaire Bichat-Claude Bernard, AP-HP, Université Paris VII, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Montravers
authors.affiliation: CIBERES, Vall d'Hebron Institute of Research, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Rello
authors.affiliation: St George's Healthcare NHS Trust and St George's University of London, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Rhodes
authors.affiliation: Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Starr
authors.affiliation: Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors.forename: S C
authors.initials: SC
authors.lastname: Wallis
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia; Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Lipman
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics*; D002845:Chromatography; D016638:Critical Illness; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D010949:Plasma / Q000737:chemistry; D011485:Protein Binding; D017334:Teicoplanin / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D017334:Teicoplanin
keywords: Antibiotics; Critically ill patients; Glycopeptides; Hypoalbuminaemia; ICU; Pharmacokinetics