Safety of graded challenges to amoxicillin without penicillin skin testing

Published online: May 23, 2018

Penicillin allergy is reported by approximately 10% of the United States (US) population. Patients with unconfirmed penicillin allergy often receive suboptimal treatment for infectious diseases with second-line, broad-spectrum antibiotics that tend to be less effective, costlier, and associated with an increased risk of antibiotic-resistant infections. The most widely accepted protocol to evaluate penicillin allergy consists of penicillin skin testing followed by an oral amoxicillin challenge in skin test-negative individuals. After a comprehensive evaluation, studies have demonstrated that greater than 94% of patients who report penicillin allergy can tolerate the antibiotic. Recent studies have also found that direct oral challenges to amoxicillin without preceding skin tests are safe in patients who report a low-risk history of penicillin allergy, such as amoxicillin-induced rashes.

In an article recently published in The Journal of Allergy and Clinical Immunology: In Practice, Iammatteo et al. evaluated the safety of a direct oral graded challenge to amoxicillin without prior penicillin skin testing in a broad group of patients ≥ 7 years old who reported a history of penicillin allergy that was non-life-threatening. Patients were excluded if they reported life-threatening reactions involving changes in vital signs (such as low blood pressure or low oxygen levels), reactions requiring intubation or epinephrine, or severe rashes. All patients received placebo prior to a two-step graded challenge to amoxicillin: 80 mg of amoxicillin followed by 30 minutes of observation and subsequent administration of a full therapeutic dose (500 mg) of amoxicillin followed by 60 minutes of observation. Allergic reactions were defined either as objective symptoms confirmed by physicians or subjective symptoms that did not resolve spontaneously.

Of the 155 participants who completed the study, only four patients (2.6%) developed mild reactions that were considered allergic; three patients experienced mild, delayed rashes; and one patient experienced itching that resolved with an antihistamine. Thirty-one patients (20%) experienced non-allergic reactions to either placebo or amoxicillin, which were predominantly characterized by itching and resolved without treatment. The percentage of the study population determined to be allergic is significantly lower than the 8.2% of patients in a prior study performed by the lead investigators at the same clinical site who were determined to be penicillin-allergic based on either a positive skin test or an allergic reaction during a challenge after a negative skin test. The allergic reaction rate in this current study was also significantly less than the estimated 10% US prevalence of penicillin allergy, which suggests that the majority of patients labeled with penicillin allergy would tolerate penicillin. This study demonstrates that placebo-controlled oral graded challenges to amoxicillin without prior penicillin skin testing may be safe for patients ≥ 7 years old with non-life-threatening historical reactions to penicillin. If confirmed by larger studies, skin testing to penicillin prior to an oral amoxicillin challenge could be omitted in this patient population.

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