The Use of Cephalosporins in Penicillin-allergic Patients: A Literature Review



      The practice of avoiding cephalosporin administration to penicillin-allergic patients persists despite the low rate of cross reactions between both groups of antibiotics.


      The purpose of this literature review is to evaluate the published evidence regarding the commonly held belief that patients with a history of an allergic reaction to penicillin have a significantly increased risk of an allergic reaction to cephalosporins.

      Materials and Methods

      Articles were identified through a computerized search of MEDLINE from 1950 to the present using the search terms “penicillin$,” “cephalosporin$,” “allerg$,” “hypersensitivity,” and “cross-react$.” All articles were reviewed, and additional sources cited in them were added to the literature review.


      Penicillins have a cross allergy with first-generation cephalosporins (odds ratio 4.8; confidence interval 3.7–6.2) and a negligible cross allergy with second-generation cephalosporins (odds ratio 1.1; confidence interval 0.6–2.1). Laboratory and cohort studies confirm that the R1 side chain is responsible for this cross reactivity. Overall cross reactivity between penicillins and cephalosporins is lower than previously reported, though there is a strong association between amoxicillin and ampicillin with first- and second-generation cephalosporins that share a similar R1 side chain.


      Although a myth persists that approximately 10% of patients with a history of penicillin allergy will have an allergic reaction if given a cephalosporin, the overall cross-reactivity rate is approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains. However, a single study reported the prevalence of cross reactivity with cefadroxil as high as 27%. For penicillin-allergic patients, the use of third- or fourth-generation cephalosporins or cephalosporins with dissimilar side chains than the offending penicillin carries a negligible risk of cross allergy.


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