title: Variability of linezolid concentrations after standard dosing in critically ill patients: a prospective observational study.
abstract: BACKGROUND
  Severe infections in intensive care patients show high morbidity and mortality rates. Linezolid is an antimicrobial drug frequently used in critically ill patients. Recent data indicates that there might be high variability of linezolid serum concentrations in intensive care patients receiving standard doses. This study was aimed to evaluate whether standard dosing of linezolid leads to therapeutic serum concentrations in critically ill patients.
  
  
  METHODS
  In this prospective observational study, 30 critically ill adult patients with suspected infections received standard dosing of 600 mg linezolid intravenously twice a day. Over 4 days, multiple serum samples were obtained from each patient, in order to determine the linezolid concentrations by liquid chromatography tandem mass spectrometry.
  
  
  RESULTS
  A high variability of serum linezolid concentrations was observed (range of area under the linezolid concentration time curve over 24 hours (AUC24) 50.1 to 453.9 mg/L, median 143.3 mg*h/L; range of trough concentrations (Cmin) < 0.13 to 14.49 mg/L, median 2.06 mg/L). Furthermore, potentially subtherapeutic linezolid concentrations over 24 hours and at single time points (defined according to the literature as AUC24 < 200 mg*h/L and Cmin < 2 mg/L) were observed for 63% and 50% of the patients, respectively. Finally, potentially toxic levels (defined as AUC24 > 400 mg*h/L and Cmin > 10 mg/L) were observed for 7 of the patients.
  
  
  CONCLUSIONS
  A high variability of linezolid serum concentrations with a substantial percentage of potentially subtherapeutic levels was observed in intensive care patients. The findings suggest that therapeutic drug monitoring of linezolid might be helpful for adequate dosing of linezolid in critically ill patients.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT01793012. Registered 24 January 2013.
authors.forename: Michael
authors.initials: M
authors.lastname: Zoller
authors.forename: Barbara
authors.initials: B
authors.lastname: Maier
authors.forename: Cyrill
authors.initials: C
authors.lastname: Hornuss
authors.forename: Christina
authors.initials: C
authors.lastname: Neugebauer
authors.forename: Gundula
authors.initials: G
authors.lastname: Döbbeler
authors.forename: Dorothea
authors.initials: D
authors.lastname: Nagel
authors.forename: Lesca Miriam
authors.initials: LM
authors.lastname: Holdt
authors.forename: Mathias
authors.initials: M
authors.lastname: Bruegel
authors.forename: Thomas
authors.initials: T
authors.lastname: Weig
authors.forename: Béatrice
authors.initials: B
authors.lastname: Grabein
authors.forename: Lorenz
authors.initials: L
authors.lastname: Frey
authors.forename: Daniel
authors.initials: D
authors.lastname: Teupser
authors.forename: Michael
authors.initials: M
authors.lastname: Vogeser
authors.forename: Johannes
authors.initials: J
authors.lastname: Zander
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000081:Acetamides / Q000008:administration & dosage / Q000097:blood; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood; D016638:Critical Illness / Q000453:epidemiology / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D007362:Intensive Care Units / Q000639:trends; D000069349:Linezolid; D023303:Oxazolidinones / Q000008:administration & dosage / Q000097:blood; D011446:Prospective Studies
chemical_list: D000081:Acetamides; D000890:Anti-Infective Agents; D000069349:Linezolid; D023303:Oxazolidinones