• Michael E Pichichero and Janet R Casey.
• Department of Microbiology and Immunology, University of Rochester, Elmwood Pediatric Group, Otolaryngology, University of Rochester Medical Center, Rochester, NY, USA. Michael_pichichero@urmc.rochester.edu
• Otolaryngol Head Neck Surg. 2007 Mar 1; 136 (3): 340-7.

BackgroundRecent analysis of clinical data and a clearer understanding of the role of chemical structure in the development of cross-reactivity indicate that the increased risk of an allergic reaction to a cephalosporin in penicillin-allergic patients is smaller than previously postulated.MethodMedline and EMBASE databases were searched with the keywords: cephalosporin, penicillin, allergy, and cross-sensitivity for the years 1960 through 2005. Among 219 articles retrieved, 9 served as source material for this evidence-based meta-analysis.ResultsA significant increase in allergic reactions to cephalothin (odds ratio [OR] = 2.5; 95% confidence interval [CI] = 1.1 to 5.5), cephaloridine (OR = 8.7; CI = 5.9 to 12.8), and cephalexin (OR = 5.8; CI = 3.6 to 9.2), and all first generation cephalosporins plus cefamandole (OR = 4.8; CI = 3.7 to 6.2) were observed in penicillin allergic patients; no increase was observed with second generation cephalosporins (OR = 1.1; CI, 0.6 to 2.1) or third generation cephalosporins (OR = 0.5; CI = 0.2 to 1.1). Clinical challenges, skin testing, and monoclonal antibody studies point to the paramount importance of similarities in side chain structure to predict cross-allergy between cephalosporins and penicillins.ConclusionFirst-generation cephalosporins have cross-allergy with penicillins, but cross-allergy is negligible with second- and third-generation cephalosporins. Particular emphasis should be placed on the role of chemical structure in determining the risk of cross-reactivity between specific agents.

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