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Cephalosporin-Induced Leukopenia Following Rechallenge with Cefoxitin

Assistant Professor of Clinical Pharmacy, Department of Pharmacy Practice and Pharmacy Administration, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, Philadelphia, PA

Jomy M Joseph, PharmD

Assistant Professor of Clinical Pharmacy, Department of Pharmacy Practice and Pharmacy Administration, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia

Lars O Sjoholm, MD

Attending Trauma Surgeon, Department of Surgery, Cooper University Hospital, Camden, NJ

Reprints: Dr. Whitman, Philadelphia College of Pharmacy, University of the Sciences in Philadelphia, 600 S. 43rd St., Philadelphia, PA 19104, fax 215/596-8586, c.whitman{at}usp.edu

OBJECTIVE: To describe a case of cefazolin-induced leukopenia in a critically ill patient who developed this adverse reaction upon rechallenge with cefoxitin.

CASE SUMMARY: A 22-year-old male was admitted after a motor vehicle crash. β-Lactam therapy was initiated with vancomycin, cefepime, and metronidazole and, upon identification of methicillin-sensitive Staphylococcus aureus bacteremia 4 days later, therapy was narrowed to cefazolin 1 g every 12 hours. The dose was adjusted to 1 g every 12 hours during continuous venovenous hemodialysis. Imipenem was given for 2 days, resulting in a total of 18 days of β-lactam treatment, at which time he developed significant leukopenia (white blood cell [WBC] count 0.9 x 10³/µL). Antimicrobial treatment was changed to tigecycline and continued for suspected pleural space infection. The patient's WBC count recovered within 4 days after the change in therapy. He was taken to surgery 8 days after cefazolin was discontinued and received perioperative prophylaxis with cefoxitin (total dose 3 g). Subsequently, the patient again became severely leukopenic (WBC count 2.4 x 10³/µL). Within a week after surgery, the patient developed septic shock secondary to multidrug-resistant Escherichia coli bacteremia and died.

DISCUSSION: β-Lactam–induced leukopenia is a rare but well-described adverse drug reaction. It is a cumulative dose-dependent phenomenon reported to occur most often after 2 weeks of therapy. The mechanism of leukopenia is thought to be secondary to either an immune-mediated response or direct bone marrow toxicity. Rechallenge with a different β-lactam antibiotic has not been shown to consistently cause recurrent leukopenia. The case described here suggests an immune-related mechanism for the development of leukopenia. Use of the Naranjo probability scale determined the association between cephalosporin use and leukopenia to be probable.

CONCLUSIONS: Cefazolin was a probable cause of this patient's leukopenia. It is important for clinicians to recognize β-lactam–induced leukopenia and maybe recommend use of a drug from a different antibiotic class if continued treatment is indicated.

Key Words: cefazolin, cefoxitin, cephalosporin, β-lactam, leukopenia, neutropenia

Published Online, July 22, 2008. www.theannals.com, DOI 10.1345/aph.1L183