title: Therapeutic Drug Monitoring of Daptomycin: A Retrospective Monocentric Analysis.
abstract: BACKGROUND
  Daptomycin dose is adjusted to body weight and renal function and is usually not guided by therapeutic drug monitoring. Daptomycin plasma concentration measurement was established at our institution in January 2009 and is now increasingly being used. The aim of this study was to describe and characterize variability in daptomycin exposure during routine clinical therapy.
  
  
  METHODS
  We collected daptomycin plasma concentrations that were measured at our institution during the period January 2009-July 2012. Additional clinical and demographic data and their association with daptomycin exposure were tested by a multilevel linear regression analysis.
  
  
  RESULTS
  A total of 332 daptomycin plasma concentrations were determined in 86 patients. Sixty-six percent (n = 218) of all determinations were trough concentrations (Cmin), and 34% (n = 114) were peak concentrations (Cmax). Cmin ranged 2-68 mg/L (median, 16.7 mg/L), and Cmax 20-236 mg/L (median, 66.2 mg/L). A significant positive association of total dose, albumin, creatinine and a significant negative association of dose interval and intermittent hemodialysis with Cmin were found in the regression analysis. Total dose and intensive care unit (ICU) stay were significantly associated with Cmax (P < 0.05). However, only 28% (P < 0.005) of Cmin variability and 8% (P = 0.08) of Cmax variability were explained by the factors included in the analysis.
  
  
  CONCLUSIONS
  Daptomycin plasma concentrations are often unpredictable as shown by highly variable drug exposure that is only partially explained by dose administered and underlying renal function.
authors.affiliation: *Department of Clinical Pharmacology and Toxicology, University Hospital Zurich; †Institute of General Practice and Health Services Research, University of Zurich; and ‡Institute of Clinical Chemistry, University Hospital Zurich, Zürich, Switzerland.
authors.forename: Claudine
authors.initials: C
authors.lastname: Reiber
authors.forename: Oliver
authors.initials: O
authors.lastname: Senn
authors.forename: Daniel
authors.initials: D
authors.lastname: Müller
authors.forename: Gerd A
authors.initials: GA
authors.lastname: Kullak-Ublick
authors.forename: Natascia
authors.initials: N
authors.lastname: Corti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000097:blood*; D003404:Creatinine / Q000097:blood; D017576:Daptomycin / Q000097:blood*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D017582:Renal Replacement Therapy; D012189:Retrospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D003404:Creatinine; D017576:Daptomycin