title: A pilot and feasibility study of the plasma and tissue pharmacokinetics of cefazolin in an immature porcine model of pediatric cardiac surgery.
abstract: BACKGROUND
  Surgical site infection (SSI) prevention for children with congenital heart disease is imperative and methods to assess and evaluate the tissue concentrations of prophylactic antibiotics are important to help maximize these efforts.
  
  
  OBJECTIVE
  The purposes of this study were to determine the plasma and tissue concentrations with standard of care, perioperative cefazolin dosing in an immature porcine model of pediatric cardiac surgery, and to determine the feasibility of this model.
  
  
  METHODS
  Piglets (3-5 days old) underwent either median sternotomy (MS) or cardiopulmonary bypass with deep hypothermic circulatory arrest (CPB + DHCA) and received standard of care prophylactic cefazolin for the procedures. Serial plasma and microdialysis sampling of the skeletal muscle and subcutaneous tissue adjacent to the surgical site was performed. Cefazolin concentrations were measured, noncompartmental pharmacokinetic analyses were performed, and tissue penetration of cefazolin was assessed.
  
  
  RESULTS
  Following the first intravenous dose, maximal cefazolin concentrations in the subcutaneous tissue and skeletal muscle were similar between groups with peak tissue concentrations 15-30 min after administration. After the second cefazolin dose given with the initiation of CPB, total plasma cefazolin concentrations remained relatively constant until the end of DHCA and then decreased while muscle- and subcutaneous-unbound cefazolin concentrations showed a second peak during or after rewarming. For the MS group, 60-67% of the intraoperative time showed subcutaneous and skeletal muscle concentrations of cefazolin >16 μg·ml(-1) while this percentage was 78-79% for the CPB + DHCA group. There was less tissue penetration of cefazolin in the group that underwent CBP + DHCA (P = 0.03).
  
  
  CONCLUSIONS
  The cefazolin dosing used in this study achieves plasma and tissue concentrations that should be effective against methicillin-sensitive Staphylococcus aureus but may not be effective against some gram-negative pathogens. The timing of the cefazolin administration prior to incision and a second dose given during cardiopulmonary bypass may be important factors for achieving goal tissue concentrations.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia and The Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Kilbaugh
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia and The Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.|Center for Clinical Pharmacology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Himebauch
authors.affiliation: Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.|Division of Infectious Diseases, The Children's Hospital of Philadelphia and The Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Theoklis
authors.initials: T
authors.lastname: Zaoutis
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia and The Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: David
authors.initials: D
authors.lastname: Jobes
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia and The Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Greeley
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia and The Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Nicolson
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia and The Perelman School of Medicine of the University of Pennsylvania, Philadelphia, PA, USA.|Center for Clinical Pharmacology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Athena F
authors.initials: AF
authors.lastname: Zuppa
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D006348:Cardiac Surgical Procedures; D002437:Cefazolin / Q000097:blood / Q000493:pharmacokinetics*; D002675:Child, Preschool; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D023421:Models, Animal; D010865:Pilot Projects; D013552:Swine
chemical_list: D000900:Anti-Bacterial Agents; D002437:Cefazolin
keywords: cardiac surgery; congenital heart disease; microdialysis; pediatrics; surgical site infection; translational research