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Am Fam Physician. 2002;65(6):1196-1201

Cephalosporins are widely prescribed because of their clinical usefulness in a variety of common infections. Physicians often avoid using a cephalosporin because of a patient's history of penicillin allergy, yet the majority of these patients can tolerate a cephalosporin. Kelkar and Li present a review of cephalosporin allergy with suggestions for clinical management.

The most common allergic reactions to cephalosporins are maculopapular or morbilliform rash, drug fever, and a positive Coombs' test. Urticaria, serum-sickness–type reactions (rash plus polyarthritis), and anaphylaxis are less common (see accompanying table).

In earlier studies, the cross-reactivity of cephalosporins and penicillin was overestimated because of trace amounts of penicillin compounds produced by the cephalosporium molds used for extraction of cephalosporin medications. A review of the literature estimated the rate of allergic reactions to cephalosporins to be about 8 percent in patients with a history of penicillin allergy, compared with a baseline rate of about 2 percent in those without penicillin allergy.

Type of reactionFrequency (%)
Rash1.0 to 2.8
Positive Coombs' test1.0 to 2.0
Anaphylaxis0.0001 to 0.1
Fever0.5 to 0.9
Eosinophilia2.7 to 8.2

Patients with a history of penicillin allergy who have negative skin test results have been shown to have less risk for serious reactions to systemic use of penicillin. Unfortunately, the antigenic determinants of cephalosporin allergy have not been similarly elaborated, and neither skin testing nor IgE antibody assays for cephalosporin allergy are clinically available.

Positive reactions to skin testing with penicillin determinants seem to predict a higher rate of allergic reaction to cephalosporins. Small prospective studies of patients with a history of penicillin allergy but negative skin test results showed the rate of allergic reaction to cephalosporin to be unchanged compared with patients who have no history of penicillin allergy (1.3 percent). Positive skin testing for penicillin, however, was associated with a higher rate of cephalosporin allergy (4.4 percent). A history of atopic disease did not correlate with a higher overall rate of allergic reaction but was a risk factor for more serious reactions (e.g., anaphylaxis) in patients with cephalosporin allergy. The majority (80 to 95 percent) of patients with a history of penicillin allergy have negative skin test results.

The authors recommend avoiding the use of cephalosporin antibiotics in patients with a history of penicillin allergy when clinically convenient. If there is a compelling need for cephalosporin use, skin testing may help to identify the majority of patients who will have negative results and, thus, no associated increased risk of allergic reaction to cephalosporins. Desensitization procedures for penicillin allergy are standardized, but procedures for cephalosporin allergy are not.

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