Dosing Cefazolin for Surgical Site Infection Prophylaxis in Adolescent Idiopathic Scoliosis Surgery: Intermittent Bolus or Continuous Infusion?

Abstract

Background: Cefazolin is typically used to minimize the risk of surgical site infection (SSI) following posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). Cefazolin dosing recommendations vary and there is limited evidence of the tissue concentrations achieved throughout surgery. Methods: We performed a randomized, controlled, prospective pharmacokinetic pilot study of 12 patients given cefazolin by either intermittent bolus (30mg/kg every 3 hours) or continuous infusion (30 mg/kg bolus followed by 10/mg/kg per hour throughout the surgery) during PSF for AIS. We measured plasma cefazolin concentrations and used a clinical microdialysis technique to measure skeletal muscle and subcutaneous adipose tissue concentrations. Results: Patients were well matched for demographic and perioperative variables. As expected, patients in the infusion group received more cefazolin. While global drug exposure measured as area under the curve was similar in plasma for bolus and infusion dosing, infusion dosing achieved greater cefazolin exposure in subcutaneous and muscle tissue. Using the pharmacodynamic metric of time spent below minimal inhibitory concentration both bolus and infusion dosing performed well. However, when targeting a bactericidal concentration of 32 µg/mL for the typical 6 hour operative time, patients in the bolus group spent a median of 1/5 and 1/3 of below that target in subcutaneous and muscle tissue, respectively. Conclusions: Intraoperative determination of cefazolin tissue concentrations is feasible in PSF for AIS. Both, bolus and infusion dosing of cefazolin achieve concentrations in excess of typical minimal inhibitory concentrations. Infusion dosing appears to more consistently achieve bactericidal concentrations in subcutaneous and muscle tissues.