Cephalosporin-Induced Leukopenia Following Rechallenge with Cefoxitin

Abstract

To describe a case of cefazolin-induced leukopenia in a critically ill patient who developed this adverse reaction upon rechallenge with cefoxitin. A 22-year-old male was admitted after a motor vehicle crash. beta-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 beta-lactam treatment, at which time he developed significant leukopenia (white blood cell [WBC] count 0.9 x 10(3)/microL). 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 10(3)/microL). Within a week after surgery, the patient developed septic shock secondary to multidrug-resistant Escherichia coli bacteremia and died. beta-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 beta-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. Cefazolin was a probable cause of this patient's leukopenia. It is important for clinicians to recognize beta-lactam-induced leukopenia and maybe recommend use of a drug from a different antibiotic class if continued treatment is indicated.