title: A Larger Dose of Vancomycin Is Required in Adult Neurosurgical Intensive Care Unit Patients Due to Augmented Clearance.
abstract: BACKGROUND
  The objective of this study was to explore the pharmacokinetics of vancomycin and determine an appropriate dosage regimen for vancomycin in adult neurosurgical intensive care unit (ICU) patients.
  
  
  METHODS
  First, a 20-month therapeutic drug monitoring database at a medical center was used to retrospectively analyze the pharmacokinetic parameters of vancomycin in adult neurosurgical patients. Significant covariates were selected through Pearson or Spearman correlation tests and multiple linear regressions. Pharmacokinetic models were built using significant covariates to predict vancomycin clearance. Second, a 12-month prospective cohort of neurosurgical ICU patients was recruited to validate the models. Urine and cerebrospinal fluid samples were collected, and vancomycin concentrations were determined using a high-performance liquid chromatography assay. The relation between the model-predicted and observed pharmacokinetic parameters was assessed by Pearson correlation.
  
  
  RESULTS
  In the retrospective cohort, 98 sets of peak/trough serum concentrations obtained from 73 patients were analyzed. These patients had a mean age of 54 ± 16 years, an estimated creatinine clearance (eClCr) of 83 ± 29 mL/min, a total vancomycin clearance (ClVan) of 101 ± 41 mL/min, and a volume of distribution (Vd) of 0.93 ± 0.27 L/kg. In a subgroup analysis, the ClVan of ICU patients was higher than the ClVan of non-ICU patients (1.57 ± 0.34-fold versus 1.16 ± 0.32-fold of eClCr, P < 0.05). Fifteen patients enrolled in the prospective cohort had an average age of 67 ± 12 years, an eClCr of 108 ± 44 mL/min, a ClVan of 112 ± 29 mL/min, and a Vd of 1.03 ± 0.55 L/kg.
  
  
  CONCLUSIONS
  Adult neurosurgical ICU patients have a significantly elevated ClVan. In this study, 2 dosing equations were derived to achieve optimal serum vancomycin concentrations for this special population.
authors: *Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University; †Department of Pharmacy, National Taiwan University Hospital; ‡School of Pharmacy, College of Medicine, National Taiwan University; and §Department of Surgery, National Taiwan University Hospital, Taipei.
authors: Fe-Lin
authors: FL
authors: Lin Wu
authors: Sheau-Shan
authors: SS
authors: Liu
authors: Ting-Ya
authors: TY
authors: Yang
authors: Ming-Feng
authors: MF
authors: Win
authors: Shu-Wen
authors: SW
authors: Lin
authors: Chih-Fen
authors: CF
authors: Huang
authors: Kuo-Chuan
authors: KC
authors: Wang
authors: Li-Jiuan
authors: LJ
authors: Shen
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D019635:Neurosurgical Procedures; D012189:Retrospective Studies; D014640:Vancomycin / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin