title: Skeletal muscle and plasma concentrations of cefazolin during cardiac surgery in infants.
abstract: OBJECTIVE
  To describe the pharmacokinetics and tissue disposition of prophylactic cefazolin into skeletal muscle in a pediatric population undergoing cardiac surgery.
  
  
  METHODS
  The subjects included 12 children, with a median age of 146 days (interquartile range, 136-174) and median weight of 5.5 kg (interquartile range, 5.2-7.3) undergoing cardiac surgery and requiring cardiopulmonary bypass with or without deep hypothermic circulatory arrest. Institutional cefazolin at standard doses of 25 mg/kg before incision and 25 mg/kg in the bypass prime solution were administered. Serial plasma and skeletal muscle microdialysis samples were obtained intraoperatively and the unbound cefazolin concentrations measured. Noncompartmental pharmacokinetic analyses were performed and the tissue disposition evaluated.
  
  
  RESULTS
  After the first dose of cefazolin, the skeletal muscle concentrations peaked at a median microdialysis collection interval of 30 to 38.5 minutes. After the second dose, the peak concentrations were delayed a median of 94 minutes in subjects undergoing deep hypothermic circulatory arrest. Skeletal muscle exposure to cefazolin measured by the area under concentration time curve 0-last measurement was less in the subjects who underwent deep hypothermic circulatory arrest than in those who received cardiopulmonary bypass alone (P = .04). The skeletal muscle concentrations of cefazolin exceeded the goal concentrations for methicillin-sensitive Staphylococcus aureus prophylaxis; however, the goal concentrations for gram-negative pathogens associated with surgical site infections were achieved only 42.1% to 84.2% and 0% to 11.2% of the intraoperative time in subjects undergoing cardiopulmonary bypass alone or deep hypothermic circulatory arrest, respectively.
  
  
  CONCLUSIONS
  This cefazolin dosing strategy resulted in skeletal muscle concentrations that are likely not effective for surgical prophylaxis against gram-negative pathogens but are effective against methicillin-sensitive S aureus in infants undergoing cardiac surgery.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Pennsylvania Perelman School of Medicine and The Children's Hospital of Philadelphia, Philadelphia, Pa; Center for Clinical Pharmacology, University of Pennsylvania Perelman School of Medicine and The Children's Hospital of Philadelphia, Philadelphia, Pa.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Himebauch
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Pennsylvania Perelman School of Medicine and The Children's Hospital of Philadelphia, Philadelphia, Pa.
authors.forename: Susan C
authors.initials: SC
authors.lastname: Nicolson
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Pennsylvania Perelman School of Medicine and The Children's Hospital of Philadelphia, Philadelphia, Pa.
authors.forename: Martha
authors.initials: M
authors.lastname: Sisko
authors.affiliation: Center for Clinical Pharmacology, University of Pennsylvania Perelman School of Medicine and The Children's Hospital of Philadelphia, Philadelphia, Pa.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Moorthy
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, University of Pennsylvania Perelman School of Medicine and The Children's Hospital of Philadelphia, Philadelphia, Pa.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Fuller
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, University of Pennsylvania Perelman School of Medicine and The Children's Hospital of Philadelphia, Philadelphia, Pa.
authors.forename: J William
authors.initials: JW
authors.lastname: Gaynor
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Pennsylvania Perelman School of Medicine and The Children's Hospital of Philadelphia, Philadelphia, Pa; Center for Clinical Pharmacology, University of Pennsylvania Perelman School of Medicine and The Children's Hospital of Philadelphia, Philadelphia, Pa.
authors.forename: Athena F
authors.initials: AF
authors.lastname: Zuppa
authors.affiliation: Center for Clinical Pharmacology, University of Pennsylvania Perelman School of Medicine and The Children's Hospital of Philadelphia, Philadelphia, Pa; Division of Oncology, Department of Pediatrics, University of Pennsylvania Perelman School of Medicine and The Children's Hospital of Philadelphia, Philadelphia, Pa.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fox
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, University of Pennsylvania Perelman School of Medicine and The Children's Hospital of Philadelphia, Philadelphia, Pa. Electronic address: kilbaugh@email.chop.edu.
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Kilbaugh
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019072:Antibiotic Prophylaxis; D006348:Cardiac Surgical Procedures / Q000009:adverse effects; D002315:Cardiopulmonary Bypass; D002437:Cefazolin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D050792:Circulatory Arrest, Deep Hypothermia Induced; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D017551:Microdialysis; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000378:metabolism*; D013530:Surgical Wound Infection / Q000382:microbiology / Q000517:prevention & control*
chemical_list: D000900:Anti-Bacterial Agents; D002437:Cefazolin