Amoxicillin non-immediate reactions - a prolonged challenge increases the sensitivity of the allergy work-up!


Published Online: November 6, 2014

Hypersensitivity to amoxicillin is very common, with an estimated incidence of 1-10%. The non-immediate reactions occur after more than 1 hour of the administration of the antibiotic, and are the most common reactions to beta-lactams, especially in children. A prolonged drug provocation test seems to improve the sensitivity of the allergy work-up in cases of non-immediate drug reactions in children, but a standardized protocol is lacking.

In an article recently published in The Journal of Allergy and Clinical Immunology: In Practice, Mori F. et al. explored the sensitivity and specificity of an allergy work-up that included a five day drug provocation test in children with histories of non-immediate reactions to amoxicillin through focusing on a pediatric population with histories of immediate and non-immediate reactions to amoxicillin.

Charts from all consecutive patients referred to the Allergy Unit of Anna Meyer Children’s Hospital for suspected drug allergy from 2008-2011 were reviewed and data (clinical evaluation, allergy testing and drug provocation test outcomes) of children referred for amoxicillin allergy were analyzed. Most of those children, regardless of the skin test results, were challenged with amoxicillin for a total of five days.

In 4 years, 200 patients were evaluated for a history of drug hypersensitivity to amoxicillin. The majority of patients (76%) had a history of mild non-immediate reactions. All 200 patients underwent skin tests, and 9 out of 200 tested positive. A total of 177 drug provocation tests were performed with amoxicillin for five days in each child. Diagnosis of amoxicillin allergy was confirmed by drug provocation test in 17 patients (9.6%); 14/17 had history of non-immediate reactions; 4/14 (26.6%) reacted on day 5.

According to this study, a 5-day drug provocation test protocol increases the sensitivity of the allergy work-up, leading physicians to reach a diagnosis in 9.6% of cases. The authors think that picking up four more reactors out of 17 by using the 5-day challenge (versus the shorter challenge) would be important. Moreover, this protocol is not time consuming because patients complete the drug provocation test at home. This protocol also appears to be safe in that reactions after the drug provocation test—in both skin test positive and negative patients—were rare and very mild, never requiring hospital admission and never being severe.


The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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