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

PURPOSE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: Noncompliance with antimicrobial prophylaxis guidelines was associated with low end-of-procedure antibiotic levels. Compliance with guidelines did not guarantee adequate levels.