title: Empirical models for dosage optimization of four beta-lactams in critically ill septic patients based on therapeutic drug monitoring of amikacin.
abstract: OBJECTIVE
  The study aims to develop empirical models able to predict the pharmacokinetics (PK) of four beta-lactams using the amikacin (AMK) therapeutic drug monitoring (TDM), in order to optimize their dosage regimens.
  
  
  METHODS
  69 critically ill septic patients were included. All received a first dose of AMK combined with piperacillin/tazobactam, ceftazidime, cefepime or meropenem. A multivariate analysis was performed to predict the beta-lactam PK using AMK PK parameters estimated from TDM and using pathophysiological variables.
  
  
  RESULTS
  An optimal prediction model was identified for each PK parameter of each beta-lactam. The best predictor of each model was one of the AMK PK parameters estimated from TDM. Other variables included colloid solution, renal and hepatic biomarkers, age and body weight.
  
  
  CONCLUSIONS
  PK of the four beta-lactams could be easily and rapidly predicted in critically ill septic patients using the AMK TDM. These predictions could improve the beta-lactam dosages in clinical practice.
authors.affiliation: Unit of Clinical Biochemistry, Université Catholique de Louvain, Avenue Hippocrate, 10, B-1200 Brussels, Belgium.
authors.forename: Isabelle K
authors.initials: IK
authors.lastname: Delattre
authors.forename: Flora T
authors.initials: FT
authors.lastname: Musuamba
authors.forename: Roger K
authors.initials: RK
authors.lastname: Verbeeck
authors.forename: Thierry
authors.initials: T
authors.lastname: Dugernier
authors.forename: Herbert
authors.initials: H
authors.lastname: Spapen
authors.forename: Pierre-François
authors.initials: PF
authors.lastname: Laterre
authors.forename: Xavier
authors.initials: X
authors.lastname: Wittebole
authors.forename: Jean
authors.initials: J
authors.lastname: Cumps
authors.forename: Fabio S
authors.initials: FS
authors.lastname: Taccone
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vincent
authors.forename: Frédérique
authors.initials: F
authors.lastname: Jacobs
authors.forename: Pierre E
authors.initials: PE
authors.lastname: Wallemacq
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000583:Amikacin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002138:Calibration; D016638:Critical Illness / Q000628:therapy*; D054796:Drug Dosage Calculations; D016903:Drug Monitoring / Q000379:methods; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D036262:Empirical Research; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D018805:Sepsis / Q000097:blood / Q000188:drug therapy*; D055815:Young Adult; D047090:beta-Lactams / Q000008:administration & dosage*
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D000583:Amikacin