title: Daily vancomycin dose requirements as a continuous infusion in obese versus non-obese SICU patients.
abstract: BACKGROUND
  Limited data are available assessing vancomycin concentrations in obese critically ill patients. Currently, there are no studies evaluating dosing requirements in this population who receive vancomycin administered as a continuous infusion (CI). The aim of this study was to assess whether there was a difference in the weight-based maintenance dose required to reach a therapeutic vancomycin concentration at 24 hours when given as a CI in obese versus non-obese critically ill patients.
  
  
  METHODS
  A retrospective cohort study of adult obese patients admitted to the SICU between 2013 and 2015 receiving a vancomycin CI (CIV), and with 24-hour serum measurements were included. Obese patients (body mass index (BMI) ≥35 kg/m(2)) were matched with non-obese patients (BMI <30 kg/m(2)) based on renal function, age and acute physiology and chronic health evaluation (APACHE)-II score at admission. All patients in this study received a loading dose of 25 mg/kg then a maintenance dose based on renal function according to the protocol. The study was approved by the Institutional Review Board. The primary outcome was the weight-based total daily maintenance dose required to achieve a vancomycin level of 20 mg/L. The secondary endpoints included the achievement of a therapeutic level at 24 hours.
  
  
  RESULTS
  Twenty-six matched pairs of patients met the inclusion criteria. Of these, 17 pairs had preserved renal function and 9 pairs required continuous venovenous hemofiltration. Mean BMI was 40.9 kg/m(2) in obese and 24.8 kg/m(2) in non-obese patients. To achieve a vancomycin concentration of 20 mg/L, the weight-based daily maintenance dose in obese patients was 25.6 mg/kg versus 43.8 mg/kg in non-obese patients (p <0.01). Therapeutic 24-hour levels were achieved in 24/26 obese versus 23/26 no-obese patients (p = 0.63). Mean 24-hour vancomycin level was 20.3 ± 3.81 mcg/ml in obese compared to 20.03 ± 3.79 mcg/ml in non-obese patients (p = 0.77). Mean daily maintenance doses required to achieve a level of 20 mcg/ml were 2961 ± 1670 mg in obese compared to 3189 ± 1600.69 mg in non-obese (p = 0.61).
  
  
  CONCLUSIONS
  The results of our study suggest that critically ill obese patients treated with CIV required a significantly lower maintenance dose per unit of body weight than non-obese patients to achieve the same target level.
authors.affiliation: Department of Pharmacy, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA. hlin13@partners.org.
authors.forename: Hsin
authors.initials: H
authors.lastname: Lin
authors.affiliation: Departments of Surgery, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.
authors.forename: Daniel Dante
authors.initials: DD
authors.lastname: Yeh
authors.affiliation: Department of Pharmacy Practice and Administration, University of Saint Joseph School of Pharmacy, 229 Trumbull St, Hartford, CT, USA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Levine
mesh_terms: D018806:APACHE; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001288:Attention; D015992:Body Mass Index; D015331:Cohort Studies; D016638:Critical Illness / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous / Q000379:methods; D007362:Intensive Care Units / Q000458:organization & administration; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000503:physiopathology*; D012189:Retrospective Studies; D014640:Vancomycin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
keywords: Infectious disease; Obesity; Pharmacokinetic and pharmacodynamic; Vancomycin continuous infusion