Safety of direct oral provocation testing using the Amoxicillin-2-step-challenge in children with history of non-immediate reactions to amoxicillin

Abstract

Background Previous studies have shown that direct oral provocation tests, without prior skin testing, in children having delayed onset, benign rashes to beta-lactam antibiotic is safe and effective. Although, this test is useful in confirming drug hypersensitivity reactions, there is no standard protocol recommendation of drug provocation tests. This study aimed to evaluate the safety of the direct oral provocation test, using the Amoxicillin-2-step-challenge without prior skin testing, in children with history of non-immediate reactions to amoxicillin. Methods The Amoxicillin-2-step-challenge protocol was performed in children with history of non-immediate reactions to amoxicillin. This protocol is composed of 2 doses of amoxicillin, with a 30-min interval; continued for a total of 5 days. All of the patients had not undergone skin testing before the oral provocation test. Results This study included 54 children, having a median age of 6.6 years, with 70.4% being male. Amoxicillin and amoxicillin-clavulanic acid were reported as the culprit drug in 75.9% and 24.1%, respectively. The index reactions were maculopapular (MP) rash in 79.6% and delayed urticarial rash/angioedema in 20.4%. Five patients (9.3%) had a reaction during the provocation test, all of these patients had delayed urticaria and were treated with oral antihistamine. However, 1 patient developed a fever alongside an MP rash. Laboratory investigation for this patient showed increased atypical lymphocytes and liver enzymes elevation. Conclusions Direct oral provocation tests, using the Amoxicillin-2-step-challenge, without prior skin testing, revealed good, immediate safety for the diagnosis of amoxicillin hypersensitivity in children with history of non-immediate reactions to amoxicillin.

Drug reintroduction testing and beta-lactam hypersensitivity in children: Protocols and results, a 12-year experience

“…Authors challenged amoxicillin with a two-stage therapeutic dose: 10% of the therapeutic dose, then 20 min later, 90% of the therapeutic dose. Koosakulchai et al opted for a 2-dose OPT: 10% followed by 30 min of observation and then 90% residual until the daily therapeutic dose was reached ( Koosakulchai et al, 2021 ). Two-dose protocols have the advantage of being less expensive, less time-consuming, and more applicable to children.…”

Safety of direct oral provocation in children with mild beta‐lactam hypersensitivity reactions

“…Our findings are consistent with recent studies regarding the safety of direct amoxicillin challenges in children with penicillin allergies, in which reaction rates range from 1.5% to 9.3%. 5,6 Regarding the history of drug hypersensitivity, most participants had index reactions since they were young ( the last drug intake and the onset of the symptoms. studies that enrolled patients with adverse drug events that occurred >6 h after medication administration, drug hypersensitivities were generally less prevalent.…”

Safety of direct oral provocation test to delabel reported mild beta-lactam allergy in infants

“…1-3 Around 10% of people report drug allergy and avoid some medication because of the fear of inducing allergic reactions. 4 Many suspicions arise during the early years of life and persist into adulthood with a substantial impact in clinical practice because of prescription constraints. However, only a diagnostic workup confirms whether these reactions are allergic or nonallergic hypersensitivities.…”