The Importance of Amoxicillin and Amoxicillin-Clavulanate Determinants in the Diagnosis of Immediate Allergic Reactions to β-Lactams

Int Arch Allergy Immunol. 2016;170(1):62-6. doi: 10.1159/000446961. Epub 2016 Jul 8.


Background: Immediate allergic reactions to β-lactam antibiotics are considered to be one of the most important drug hypersensitivities. A positive skin test (ST) with a combination of major and minor penicillin determinants is usually sufficient to recommend avoidance of the culprit drug, whereas a negative ST is usually followed by an oral challenge test (OCT). Recently, concern has been raised regarding the role of amoxicillin (AMX) ST in the diagnosis of AMX allergy.

Objective: The aim of this study was to examine the additive value of AMX determinants in STs of patients with immediate hypersensitivity reactions to AMX or AMX-clavulanate (AMX-C).

Methods: Patients with a history of immediate AMX or AMX-C allergy underwent an ST using a combination of penicilloyl-polylysine (PPL) and minor determinants as well as AMX. An ST with AMX-C was added when appropriate.

Results: Thirty-one patients were evaluated. Eight patients, all of them with a history of AMX allergy, had positive reactions only to the AMX component. Two patients with AMX-C allergy had a positive ST reaction only to the AMX-C component. Moreover, only 14 patients (13 with AMX and 1 with AMX-C allergy) had a positive reaction to PPL, whereas most patients (54.8%) had positive reactions to other determinants. One patient, who was positive for AMX, developed several urticarial lesions after the test.

Conclusions: Skin testing with AMX and AMX-C is mandatory in patients with immediate allergy to these drugs. Failure to perform it may result in a false-negative ST jeopardizing these patients with anaphylactic reactions during a hazardous OCT.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amoxicillin / immunology*
  • Amoxicillin-Potassium Clavulanate Combination / immunology*
  • Child
  • Child, Preschool
  • Drug Hypersensitivity / diagnosis*
  • Drug Hypersensitivity / immunology*
  • Epitopes / immunology*
  • Female
  • Humans
  • Hypersensitivity, Immediate / diagnosis*
  • Hypersensitivity, Immediate / immunology*
  • Infant
  • Male
  • Middle Aged
  • Skin Tests
  • Young Adult
  • beta-Lactams / adverse effects*


  • Epitopes
  • beta-Lactams
  • Amoxicillin-Potassium Clavulanate Combination
  • Amoxicillin