Evidence Supporting the Use of Cephalosporin Antibiotics in Penicillin-Allergic Patients

The objective was to review the frequency of allergic cross-reactivity between penicillins and cephalosporin antibiotics. MEDLINE and EMBASE databases were searched for all English language articles relevant to penicillin and cephalosporin cross-sensitivity. Among 219 retrieved articles, 103 were included in the review. Based on 38 studies, the evidence suggests that the crossreactive, immunoglobulin E (IgE)-mediated immune responses between penicillins and cephalosporins are based on molecular side chain similarities of the antibiotics rather than similarities in β lactam rings. Twenty-eight studies examined 5420 patients with a history of penicillin allergy compared to 47,976 without such a history who received cephalosporins; possible allergic reactions were noted in 138 (2.55%) and 654 (1.36%) patients respectively (p < 0.0001). However, the risk of a cross-allergic reaction occurred predominantly among patients receiving first-generation cephalosporins with related chemical side chains to penicillin or amoxicillin. The proportion of patients with a cross-allergy to a first generation cephalosporin was increased by 6.1% (95% confidence interval [CI] for difference between penicillin allergic and nonallergic = 5.4%–6.9% p < 0.0001) while to second- and third-generation cephalosporins with unrelated chemical side chains, the proportion was decreased by 0.45% (95% CI = –1.2%–0.3%; p = 0.25). Cephalosporin skin testing, described in 21 articles, predicts hypersensitivity to the specific cephalosporin skin test reagents or those with similar side chains and based on 3 studies a positive skin test is 10%–38% predictive of a clinical reaction. Experimental and clinical studies suggest that side-chain–specific antibodies predominate in the allergic immune response to cephalosporins thereby explaining the lack of cross-sensitivity between second- and third-generation cephalosporins and penicillins. (Pediatr Asthma Allergy Immunol 2005; 18[4]:230–246.)