Efficacy and Safety of 5-Day Challenge for the Evaluation of Nonsevere Amoxicillin Allergy in Children

Paul V. Williams

doi:10.1542/peds.2019-2461AA

R Labrosse, L Paradis, J Lacombe-Barrios. J Allergy Clin Immunol Pract. 2018;6(5):1673–1680

Purpose of the Study:

To determine if the use of a 5-day challenge with amoxicillin would not only be safe but also lead to an increase in future amoxicillin use in nonallergic patients compared with a single-dose graded drug provocation.

Study Population:

The population included 130 consecutive children <18 years of age referred to the allergy unit with a history of amoxicillin or amoxicillin and clavulanate. Children with life-threatening reactions or severe non–immunoglobulin E–mediated reactions were excluded. A total of 57.7% presented with a maculopapular rash, 35.4% presented with hives.

Methods:

Initial evaluation included skin testing done in a blinded fashion and a graded drug provocation test (DPT) with 45 mg/kg amoxicillin in 3 steps (1/100, 1/10, and full dose) at 30-minute intervals, independent of skin test results. Patients with negative single-dose DPT results were sent home with a 4-day course of amoxicillin. Phone follow-up was done 2 years later.

Results:

A total of 2.3% had an immediate reaction during the single-dose DPT, and all were mild. Three of the remaining 127 patients had a confirmed nonimmediate reaction during the 4-day challenge (1 on the second day, 1 on the third day, and 1 3 days after completion). All 3 reactions were a mild, isolated maculopapular rash. Three patients had equivocal reactions that were determined to be negative with reassessment. At 2 years, 65.8% had used antibiotics again, and 89.3% had used amoxicillin. Three patients (4.5%) had a mild delayed cutaneous reaction with later use of amoxicillin. In a previous study using a single-dose provocation, 18.3% of patients had refusal to use amoxicillin again compared with 1.3% of the current study.

Conclusions:

Five-day oral challenge with amoxicillin is safe and effective and greatly increases the compliance with future use of penicillin antibiotics.

Reviewer Comments:

It is important to note that the majority of patients in the study presented with a maculopapular rash, which is usually not an immunoglobulin E–mediated reaction. In this largely low-risk population, DPT with a single-dose regimen would be safe without skin testing, and a subsequent 5-day challenge in those that passed the single-dose challenge is safe (with a small number of minor reactions) and does increase the chance that patients would be willing to use this class of antibiotics in the future.