title: Therapeutic drug monitoring of vancomycin in severe sepsis and septic shock.
abstract: BACKGROUND
  The sudden changes (increase in capillary permeability, edema formation, vasodilation and hypotension) observed in septic patients and the measurements taken in order to revert this situation make vancomycin concentrations difficult to interpret. Therapeutic drug monitoring (TDM) of vancomycin is routinely performed at steady state, target concentrations are peaks between 20 and 40 mg/l and troughs of 5-10 mg/l. Lately, continuous infusion of vancomycin (CIV) has been used as an alternative mode of administration mainly in critically ill patients with sepsis or septic shock. Despite this novel mode of administration, the need of drug monitoring in this population is under discussion.
  
  
  OBJECTIVE
  The aim of our study was to test the usefulness of a multi-compartment model in order to understand the rapid changes that occur in critically ill patients.
  
  
  METHODS
  A prospective, cohort study was carried out in the intensive care unit of the University Hospital. 25 intensive care unit adults patients with severe sepsis or septic shock receiving vancomycin in CIV modality for documented gram-positive infections were included in the study. Once the infusion was started, blood samples were drawn periodically and analyzed by fluorescence polarisation immunoassay (FPIA, TDx, Abbott Laboratories, Chicago, IL, USA). A multi-compartment model was used to predict vancomycin level evolution throughout the treatment of patients with sepsis.
  
  
  RESULTS
  High doses of vancomycin were administered in order to rescue patients from septic shock. Plasma drug concentration dropped while clinical condition of patients worsened. Conversely, drug levels increased spontaneously once the infection was reverted. The theoretical model provided greater insight into pharmacokinetic features related with the use of vancomycin in septic patients.
  
  
  CONCLUSIONS
  There was consistency between the model based prediction and the experimental data so dose adjustment was performed in order to reach target concentrations above 20 mg/l and an initial dose of 3 grams of vancomycin per day was recommended to reach these levels.
authors.affiliation: Pharmaceutical Sciences Department, Therapeutic Drug Monitoring Service, Faculty of Chemistry, Montevideo, Uruguay. mvazquez@fq.edu.uy
authors.forename: M
authors.initials: M
authors.lastname: Vázquez
authors.forename: P
authors.initials: P
authors.lastname: Fagiolino
authors.forename: A
authors.initials: A
authors.lastname: Boronat
authors.forename: M
authors.initials: M
authors.lastname: Buroni
authors.forename: C
authors.initials: C
authors.lastname: Maldonado
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016903:Drug Monitoring / Q000379:methods*; D016231:Fluorescence Polarization Immunoassay; D006801:Humans; D007262:Infusions, Intravenous; D007362:Intensive Care Units; D008954:Models, Biological; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood* / Q000188:drug therapy; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000097:blood / Q000188:drug therapy; D013997:Time Factors; D014640:Vancomycin / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin