Increased Adverse Drug Reactions to Cephalosporins in Penicillin Allergy Patients with Positive Penicillin Skin Test

Abstract

Background: Cephalosporin administration in patients with a history of penicillin allergy is controversial. Studies looking at the safety of cephalosporin in patients with a history of penicillin allergy lacked a control group, had a small number of patients, and/or lacked confirmation of penicillin allergy by penicillin skin testing. The purpose of this study was to determine whether patients with penicillin allergy were at increased risk of adverse drug reactions when administered cephalosporin. Methods: A cohort study of patients with a history of penicillin allergy and a positive or negative penicillin skin test when administered cephalosporin was conducted. Charts were reviewed for adverse drug reactions to cephalosporin after penicillin skin testing. Results: Eighty-five patients with a history of penicillin allergy and positive penicillin skin test and 726 patients with a history of penicillin allergy and negative penicillin skin test were administered cephalosporin. Five (6%) of 85 cases had an adverse drug reaction to cephalosporin as compared to 5 (0.7%) of 726 of the referent population (p = 0.0019). The rate of presumed IgE-mediated adverse drug reactions to the cephalosporins amongst the cases was 2 (2%) of 85 compared to 1 (0.1%) of 726 amongst the referent population (p = 0.0304). Conclusion: A greater risk of an adverse drug reaction to cephalosporin exists in patients with penicillin allergy. We recommend penicillin skin testing if cephalosporin, especially a first-generation cephalosporin, is to be administered to patients with a history of penicillin allergy.

Clinical Outcome in the Use of Cephalosporins in Pediatric Patients with a History of Penicillin Allergy

“…In the current study, 0.7% (1 of 152 patients) had an adverse drug reaction to a cephalosporin in patients with a history of penicillin allergy and negative penicillin skin test compared to none in penicillin skin test-positive patients with a history of penicillin allergy. The low rate of adverse drug reaction to a cephalosporin in patients with a history of penicillin allergy and a negative penicillin skin test is consistent with our recent study in adults that showed an adverse drug reaction rate of 0.7% when challenged with a cephalosporin in patients with a history of penicillin allergy and a negative penicillin skin test [8]. Our study is also consistent with the literature review by Kelkar and Li [17] who found an adverse drug reaction of 0.6% in patients challenged with a cephalosporin with a history of penicillin allergy and a negative penicillin skin test.…”

“…The lack of any adverse drug reaction to a cephalosporin in patients with a history of penicillin allergy and a positive penicillin skin test contrasts with our recent study in adults that showed a 6% adverse drug reaction rate to cephalosporins in patients with a history of penicillin allergy and positive penicillin skin test [8]. Moreover, Atanaskovic-Markovic et al [18], in a pediatric population, showed that patients with a history of penicillin allergy and a positive penicillin skin test were also more likely to be skin test positive to cephalexin (23.9%), cefaclor (23.8%), ceftriaxone (0.7%) and cefotaxime (0.3%).…”

“…In vitro testing has shown moderate cross-reactivity between these two drugs [1,2,3], and clinical cross-reactivity has been reported among patients with a history of penicillin allergy challenged with a cephalosporin [1,3,4,5,6,7]. However, cross-reactivity between penicillins and cephalosporins may occur more likely with first-generation cephalosporins [8,9] or when similarity exists between the side chains of a penicillin and a cephalosporin antibiotic [4,10,11,12,13]. …”

Clinical Practice Guideline for the Diagnosis and Management of Acute Bacterial Sinusitis in Children Aged 1 to 18 Years

“…[65][66][67] Thus, patients allergic to amoxicillin with a non-type 1 (late or delayed, >72 hours) hypersensitivity reaction can safely be treated with cefdinir, cefuroxime, or cefpodoxime. [66][67][68] Patients with a history of a serious type 1 immediate or accelerated (anaphylactoid) reaction to amoxicillin can also safely be treated with cefdinir, cefuroxime, or cefpodoxime.…”

“…[66][67][68] The susceptibility of S pneumoniae to cefdinir, cefpodoxime, and cefuroxime varies from 60% to 75%, [56][57][58][59] and the susceptibility of H influenzae to these agents varies from 85% to 100%. 56,58 In young children (<2 years) with a serious type 1 hypersensitivity to penicillin and moderate or more severe sinusitis, it may be prudent to use a combination of clindamycin (or linezolid) and cefixime to achieve the most comprehensive coverage against both resistant S pneumoniae and H influenzae.…”