Skeletal muscle and plasma concentrations of cefazolin during cardiac surgery in infants

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 methicillinsensitive S aureus in infants undergoing cardiac surgery.