title: Vancomycin pharmacokinetic and pharmacodynamic models for critically ill patients with post-sternotomy mediastinitis.
abstract: OBJECTIVE
  Vancomycin is commonly used to treat serious methicillin-resistant staphylococcal infections, especially post-sternotomy mediastinitis (PSM). However, information on pharmacokinetics and pharmacodynamics in intensive care unit (ICU) patients remains scarce. We conducted vancomycin pharmacokinetic-pharmacodynamic modeling for ICU patients with PSM.
  
  
  METHODS
  This cohort study included 30 consecutive patients who received multiple vancomycin doses during primary closed drainage of PSM with Redon catheters, targeting serum drug trough concentrations of 25-35 mg/L, and generating 359 serum vancomycin concentration-time values for analysis. Population pharmacodynamics served to describe the withdrawal of Redon catheters, i.e., the probability of in-ICU cure.
  
  
  RESULTS
  Vancomycin pharmacokinetics corresponded to a two-compartment open model with first-order elimination kinetics. Mean [between-subject variability] population estimates were 1.91 (men)/1.25 (women) [0.28] L/h for vancomycin elimination, with intercompartmental clearance of 5.71 [1.01] L/h, and respective central and peripheral distribution volumes of 21.9 and 68 [0.53] L. Vancomycin clearance increased with body weight and declined with severity at ICU admission and serum creatinine (SCr), thereby allowing the prediction of the vancomycin plateau. Intercompartmental clearance decreased with diabetes mellitus (-70 %). The probability of withdrawing all Redon catheters (patient cured) was dependent only on the area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC) exposures ratio in plasma. Neither preoperative factors, antistaphylococcal co-treatments, nor the initial number of Redon catheters significantly influenced this probability. The AUC/MIC exposures ratio had no significant effect on SCr levels.
  
  
  CONCLUSIONS
  These modeling analysis results identified five clinically relevant covariates that influenced vancomycin pharmacokinetics and might achieve better individualization of vancomycin dosing for methicillin-resistant staphylococcal PSM in ICU patients.
authors.affiliation: Medical Intensive Care Unit, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes Sorbonne Paris Cité, 20 rue Leblanc, 75908, Paris Cedex 15, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Mangin
authors.forename: Saïk
authors.initials: S
authors.lastname: Urien
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Mainardi
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Fagon
authors.forename: Christophe
authors.initials: C
authors.lastname: Faisy
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D016638:Critical Illness; D005260:Female; D006801:Humans; D008297:Male; D008480:Mediastinitis / Q000097:blood* / Q000188:drug therapy; D008875:Middle Aged; D008954:Models, Biological; D011183:Postoperative Complications / Q000097:blood* / Q000188:drug therapy; D056346:Sternotomy; D014640:Vancomycin / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D003404:Creatinine