End-of-procedure cefazolin concentrations after administration for prevention of surgical-site infection

Abstract

The adequacy of end-of-procedure free cefazolin concentrations after administration for the prevention of surgical-site infection (SSI) and compliance with national guidelines for antimicrobial prophylaxis for SSI were assessed. Patients undergoing elective surgery and receiving cefazolin for perioperative antimicrobial prophylaxis were prospectively enrolled. Antibiotic administration was controlled by the surgeon and usage was recorded. For each patient, a single blood sample for cefazolin serum free and total concentrations was obtained within 15 minutes of wound closure. A free serum concentration threshold of 4 microg/mL was arbitrarily chosen based on the minimum inhibitory concentration required to inhibit 90% of strains of methicillin-susceptible Staphylococcus aureus and Escherichia coli. Fifty-seven subjects were enrolled, and noncompliance with published guidelines was observed for 26% of patients. Forty-six subjects had serum samples available for assay, 21.7% of whom had end-of-procedure free cefazolin concentrations of <4 microg/mL. Results of multivariate regression and population pharmacokinetic analysis revealed the importance of age and lean body weight in cefazolin clearance. Younger and taller patients had a greater risk of achieving below-threshold end-of-procedure concentrations. Of the patients for whom published guidelines were not followed, 67% had end-of-procedure free cefazolin concentrations below the threshold concentration (4 microg/mL). In contrast, less than 15% of cases where SSI prophylaxis complied with the published guidelines had below-threshold concentrations at the end of surgery. Noncompliance with antimicrobial prophylaxis guidelines was associated with low end-of-procedure antibiotic levels. Compliance with guidelines did not guarantee adequate levels.