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

J Allergy Clin Immunol Pract. 2018 Sep-Oct;6(5):1673-1680. doi: 10.1016/j.jaip.2018.01.030. Epub 2018 Feb 7.


Background: Penicillin allergy is the most frequent drug allergy, among which aminopenicillins are reputed for causing delayed rashes in children, particularly in the context of viral infections. Despite a negative allergy evaluation, a significant proportion of individuals continue to avoid penicillin antibiotics for fear of an allergic reaction.

Objective: To evaluate the safety and efficacy of a 5-day challenge to amoxicillin and the proportion of subsequent use of amoxicillin.

Methods: Pediatric patients with a history of a reaction to amoxicillin were prospectively recruited in the study. All patients were challenged, and those with negative immediate challenges underwent an ambulatory 5-day challenge to amoxicillin to rule out nonimmediate reactions. Patients were called 2 years after their initial allergy evaluation to assess subsequent amoxicillin use and tolerance.

Results: One hundred thirty children with a history of amoxicillin allergy underwent a graded drug provocation test (DPT) to amoxicillin. Three patients had a positive immediate challenge, 3 had a positive nonimmediate challenge, and 2 were equivocal. Of the 122 patients with a negative challenge, 114 (93.4%) were reached 2 years after their initial allergy evaluation: 75 had used antibiotics since, of which only 1 (1.3%) had refused to reuse amoxicillin because of fear of an allergic reaction. Finally, the 5-day DPT resulted in a 24.1% decrease in future penicillin avoidance compared with classical single-dose graded DPT performed for 1 day in a historical cohort (P < .0001).

Conclusion: The 5-day challenge is a safe and effective way to rule out nonimmediate amoxicillin allergy, and it ensures better compliance with future penicillin use.

Keywords: Allergy; Amoxicillin; Challenge; Hypersensitivity; Pediatric; Prolonged challenge; Resensitization.

Publication types

  • Evaluation Study

MeSH terms

  • Adolescent
  • Allergens / immunology*
  • Amoxicillin / immunology*
  • Child
  • Child, Preschool
  • Drug Hypersensitivity / diagnosis*
  • Female
  • Follow-Up Studies
  • Humans
  • Immunization
  • Infant
  • Male
  • Penicillins / immunology
  • Severity of Illness Index
  • Treatment Outcome


  • Allergens
  • Penicillins
  • Amoxicillin