title: Clinical scoring system for the prediction of target site penetration of antimicrobials in patients with sepsis.
abstract: OBJECTIVE
  The present study investigated the usefulness of routinely employed scoring systems in predicting tissue penetration of antimicrobials. In addition, a novel, easy to use scoring system was designed for the estimation of tissue penetration of antimicrobials in patients with sepsis.
  
  
  METHODS
  Tissue pharmacokinetics were assessed in skeletal muscle and subcutaneous adipose tissue by use of the microdialysis technique in 34 patients with sepsis. Tissue penetration of antimicrobials was retrospectively determined by the ratios of the area under the concentration-time curves (AUC) in soft tissues (AUCtissue) to the AUC in plasma (AUCplasma). Mortality and sepsis scores currently used in intensive care were consecutively calculated and correlated with the AUCtissue:AUCplasma ratio. Single laboratory and clinical parameters showing the highest correlation with tissue penetration were identified and used in the novel Tissue Penetration Prediction Score (TPPS).
  
  
  RESULTS
  The currently used scoring systems Simplified Acute Physiology Scores 3 (r=-0.33, p=0.006), Acute Physiology and Chronic Health Evaluation III (r=-0.27, p=0.03) and Sepsis-Related (or Sequential) Organ Failure Assessment (r=-0.32, p=0.01) showed significant overall correlations with tissue penetration. However, their predictive power for the concentrations of antimicrobials in muscle tissue was not satisfying. The parameters oxygen saturation, serum lactate concentration and the dose per time unit of norepinephrine (noradrenaline) administered showed the best correlation with tissue penetration and were used in the TPPS. Its overall correlation (r=-0.52, p=0.000007) as well as correlations for the concentrations of antimicrobials in muscle (r=-0.46, p=0.006) and adipose tissue (r=-0.59, p=0.0003) were better than the currently used scoring systems.
  
  
  CONCLUSIONS
  The TPPS may prove to be a powerful tool for the estimation of antimicrobial tissue penetration at the bedside in septic patients. This score may allow for adequate individual dose adjustment in septic patients. However, this needs to be verified in subsequent prospective clinical trials.
authors.affiliation: Department of Clinical Pharmacology, Division of Clinical Pharmacokinetics, Medical University of Vienna, Vienna, Austria.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Zeitlinger
authors.forename: Markus
authors.initials: M
authors.lastname: Zeitlinger
authors.forename: Irmgard
authors.initials: I
authors.lastname: Leitner
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
authors.forename: Christian
authors.initials: C
authors.lastname: Joukhadar
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000890:Anti-Infective Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D006801:Humans; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D000890:Anti-Infective Agents