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

Author:

Yu Yichao12,Dooley F. Cole3ORCID,Woods Anna3,Gunnett Amy3,Chandasana Hardik14ORCID,Amini Elham15,Garvan Cynthia3,Ihnow Stephanie6,Blakemore Laurel C.7,Sangari Taran8,Seubert Christoph N.3ORCID

Affiliation:

1. Department of Pharmaceutics, University of Florida, Gainesville, FL 32610, USA

2. Drug Development, Clinical Pharmacology, Boehringer Ingelheim, Ridgefield, CT 06810, USA

3. Department of Anesthesiology, University of Florida College of Medicine, Gainesville, FL 32610, USA

4. Clinical Pharmacology, Modeling, and Simulation, Glaxo-Smith-Kline, Collegeville, PA 19426, USA

5. Department of Clinical Pharmacology, Gilead Sciences, Foster City, CA 94404, USA

6. Department of Orthopaedic Surgery & Sports Medicine, University of Florida College of Medicine, Gainesville 32610, FL, USA

7. Pediatric Specialists of Virginia, Fairfax, VA 22031, USA

8. Department of Anesthesiology, University of California at San Francisco, Oakland, CA 94609, USA

Abstract

Background: Cefazolin may 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 for achieved tissue concentrations. Methods: We performed a randomized, controlled, prospective pharmacokinetic pilot study of 12 patients given cefazolin by either intermittent bolus (30 mg/kg every 3 h) or continuous infusion (30 mg/kg bolus followed by 10/mg/kg per hour) during PSF for AIS. Results: Patients were well matched for demographic and perioperative variables. While total drug exposure, measured as area-under-the-curve (AUC), 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 above minimal inhibitory concentration (MIC), both bolus and infusion dosing performed well. However, when targeting a bactericidal concentration of 32 µg/mL, patients in the bolus group spent a median of 1/5 and 1/3 of the typical 6 h operative time below target in subcutaneous and muscle tissue, respectively. Conclusions: We conclude that intraoperative determination of cefazolin tissue concentrations is feasible and both bolus and infusion dosing of cefazolin achieve concentrations in excess of typical MICs. Infusion dosing appears to more consistently achieve bactericidal concentrations in subcutaneous and muscle tissues.

Funder

Department of Pharmaceutics, University of Florida College of Pharmacy

Anesthesiology and Department of Anesthesiology, University of Florida College of Medicine

Publisher

MDPI AG

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