Diagnosis of Penicillin, Amoxicillin, and Cephalosporin Allergy:Reliability of Examination Assessed by Skin Testing and Oral Challenge

Abstract

Pichichero ME, Pichichero DMJ Pediatr.1321998137143The major aims were to 1) assess the reliability of pediatrician-diagnosed allergic reactions to commonly used β-lactam antibiotics based on the examination at the time of reaction followed by elective skin testing and oral challenge, and 2) monitor prospectively the predictive value of negative skin testing for subsequent reactions to antibiotics administered.Children and adolescents (n = 247) experiencing an adverse reaction to penicillin, amoxicillin, and/or an oral cephalosporin sufficient to lead to the recommendation to avoid further use of the drug.Skin testing with penicillin G, commercial benzylpenicilloyl phosphate (Pre-pen), penicillin minor determinant mixture (MDM), ampicillin, cefazolin, cefuroxime, and/or ceftriaxone was performed according to the suspected cause of the reaction. This was followed by an oral challenge, repeat testing, and prospective follow-up if no reactions were observed.Overall, 84 (34%) of 247 patients had an immunoglobulin E (IgE)-type reaction on skin testing or oral challenge. Twenty-seven (32%) of 85 suspected penicillin reactions, 53 (34%) of 156 suspected amoxicillin reactions, and 13 (50%) of 26 suspected cephalosporin reactions were felt to be IgE-mediated. Positive skin tests were observed in 20 patients with non-IgE-type adverse reactions, including 15 patients with only a pruritic polymorphous rash. No reactions to oral challenge were severe after negative skin testing. One hundred sixty-three patients received multiple treatment courses with β-lactam antibiotics after a negative skin test and oral challenge and 3 (1.8%) had adverse IgE-type reactions, all of which were mild.Physician-diagnosed allergic reactions to β-lactam antibiotics based on the examination at the time of the reaction is more accurate than patient history alone, but still overestimates the rate of true allergy in 66% of patients. Elective penicillin, amoxicillin, and cephalosporin skin testing and oral challenge protocols are necessary to identify patients at risk.How often (ie, monthly, weekly, or even daily) do you encounter a patient with a history of a β-lactam allergy? In our current era of emerging antibiotic resistance, this clinical issue has reached an even greater degree of importance. This article addressing the diagnosis of β-lactam allergy should strike a cord with both pediatricians and allergy/immunology specialists. There are several useful “take home” messages. First, examination of the patient at the time of the adverse antibiotic reaction accurately diagnosed an IgE-mediated reaction only 30% of the time. Second, young and middle-aged adults (ages 20–49) seemed to have the greatest risk of acute allergic reactions to antibiotics. Third, this investigation confirms the safety of testing for penicillin allergy with penicillin G, Pre-pen, and MDM, as well as with cephalosporin skin testing reagents. Fourth, after negative skin testing, use of an oral challenge is the safest method of confirming the negative result. Fifth, while a potential for increased hypersensitivity to first-generation cephalosporins exists in those patients who have histories of penicillin, second- and third-generation cephalosporins have a lower incidence of allergic reactions. Finally, patients observed during subsequent, multiple treatment courses with β-lactams after negative testing and oral challenge rarely had mild IgE-mediated reactions.