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American Journal of Health-System Pharmacy, Vol. 64, Issue 18, 1927-1934
Copyright © 2007 by American Society of Health-System Pharmacists
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American Journal of Health-System Pharmacy, Vol. 64, Issue 18, 1927-1934
Copyright © 2007. American Society of Health-System Pharmacists, Inc. All rights reserved. 1079-2082/04/0602-1242$06.00


Clinical Report

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

Erin Koopman, David E. Nix, Brian L. Erstad, Michael J. Demeure, Melinda M. Hayes, John T. Ruth and Kathryn R. Matthias

ERIN KOOPMAN, PHARM.D., BCNSP, is Clinical Specialist in Nutrition Support, Saint Mary’s Hospital, Mayo Clinic, Rochester, MN; at the time of the study she was Critical Care Resident, University of Arizona, Tucson. DAVID E. NIX, PHARM.D., BCPS, FASHP, is Associate Professor, College of Pharmacy; BRIAN L. ERSTAD, PHARM.D., BCPS, FASHP, is Professor, College of Pharmacy; MICHAEL J. DEMEURE, M.D., is Professor of Surgery, College of Medicine; MELINDAM. HAYES, M.D., is Clinical Instructor, Department of Anesthesiology, College of Medicine; JOHN T. RUTH, M.D., is Professor of Clinical Orthopedic Surgery, College of Medicine; and KATHRYN R. MATTHIAS,PHARM.D., BCPS, is Critical Care Pharmacy Resident, College of Pharmacy, University of Arizona.

Address correspondence to Dr. Nix at the College of Pharmacy, University of Arizona, 1703 East Mabel Street, P.O. Box 210207, Tucson, AZ 85721-0202 (nix{at}pharmacy.arizona.edu).


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 µg/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 µg/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 µg/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.

Index terms: Age; Bacterial infections; Blood levels; Cefazolin; Cephalosporins; Compliance; Excretion; Minimum inhibitory concentration; Pharmacokinetics; Protocols; Surgery; Weight

 






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