title: Decreasing the time to achieve therapeutic vancomycin concentrations in critically ill patients: developing and testing of a dosing nomogram.
abstract: BACKGROUND
  Achievement of optimal vancomycin exposure is crucial to improve the management of patients with life-threatening infections caused by susceptible Gram-positive bacteria and is of particular concern in patients with augmented renal clearance (ARC). The aim of this study was to develop a dosing nomogram for the administration of vancomycin by continuous infusion for the first 24 hours of therapy based on the measured urinary creatinine clearance (8 h CLCR).
  
  
  METHODS
  This single-center study included all critically ill patients treated with vancomycin over a 13-month period (group 1), in which we retrospectively assessed the correlation between vancomycin clearance and 8 h CLCR. This data was used to develop a formula for optimised drug dosing. The efficiency of this formula was prospectively evaluated in a second cohort of 25 consecutive critically ill patients (group 2). Vancomycin serum concentrations between 20 to 30 mg/L were considered adequate. ARC was defined as 8 h CLCR more than 130 ml/min/1.73 m(2).
  
  
  RESULTS
  The incidence of ARC was 36% (n = 29/79) and 40% (10/25) in group 1 (n = 79) and 2 (n = 25), respectively. The mean serum vancomycin concentration on day 1 was 21.5 (6.4) and 24.5 (5.2) mg/L, for both groups respectively. On the treatment day, vancomycin plasma clearance was 5.12 (1.9) L/h in group 1 and correlated significantly with the 8 h CLCR (r(2) = 0.66; P < 0.001). The achievement of adequate vancomycin serum concentrations in group 2 was 84% (n = 21/25) versus 51% (n = 40/79) - P < 0.005.
  
  
  CONCLUSIONS
  This new vancomycin nomogram enabled the achievement of adequate serum concentrations in 84% of the patients on the first day of treatment.
authors.affiliation: Serviço de Medicina Intensiva, Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal. joaopedrobaptista@gmail.com.
authors.forename: João Pedro
authors.initials: JP
authors.lastname: Baptista
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Queensland, Australia. j.roberts2@uq.edu.au.|Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK. j.roberts2@uq.edu.au.|Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia. j.roberts2@uq.edu.au.|Pharmacy Department, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia. j.roberts2@uq.edu.au.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.affiliation: Serviço de Medicina Intensiva, Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal. j.eduardo.sousa@gmail.com.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Sousa
authors.affiliation: Serviço de Medicina Intensiva, Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal. rfreitas@netcabo.pt.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Freitas
authors.affiliation: Serviço de Medicina Intensiva, Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal. nmdeveza@gmail.com.
authors.forename: Nuno
authors.initials: N
authors.lastname: Deveza
authors.affiliation: Serviço de Medicina Intensiva, Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal. jmppimentel@gmail.com.
authors.forename: Jorge
authors.initials: J
authors.lastname: Pimentel
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood; D016638:Critical Illness / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D049451:Nomograms; D012189:Retrospective Studies; D013997:Time Factors; D014640:Vancomycin / Q000008:administration & dosage* / Q000097:blood
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin