Patients Taking Amoxicillin-Clavulanic Can Become Simultaneously Sensitized to Both Drugs

J Allergy Clin Immunol Pract. 2017 May-Jun;5(3):694-702.e3. doi: 10.1016/j.jaip.2017.02.007. Epub 2017 Mar 22.


Background: Patients can react to amoxicillin (AX) and clavulanic acid (CLV) taken in combination because of selective reactions to either drug. However, scant information exists concerning patients who react simultaneously to both compounds.

Objective: To analyze the mechanisms involved in 4 patients who developed allergic reactions to AX-CLV administration (3 with immediate IgE-mediated reaction and 1 with nonimmediate T-cell-mediated reaction) and who responded specifically to both AX and CLV.

Methods: Skin tests with benzylpenicillin (BP), AX, and CLV were done and, if necessary, drug provocation tests with BP/penicillin V, AX, and AX-CLV were carried out. In immediate reactors, serum specific IgE to benzylpenicilloyl and amoxicilloyl was determined by using the CAP-FEIA system (Pharmacia Diagnostics, Uppsala, Sweden), and basophil activation test to BP, AX, CLV, and AX-CLV was done. In nonimmediate reactors, immunohistochemistry of skin biopsy and analysis of dendritic cell maturation and T-cell-specific response to BP, AX, CLV, and AX-CLV at both acute and resolution phases of the reaction were conducted.

Results: All patients with immediate reactions (N = 3) had good tolerance to BP and penicillin V. Two cases also had specific IgE to AX and all had a basophil activation test positive to AX, CLV, and AX-CLV. The patient with a nonimmediate reaction exhibited dendritic cell and T-lymphocyte responses specific to both AX and CLV. Finally, the analysis of the cells infiltrating the skin and peripheral blood during the acute phase indicated a TH1 pattern response.

Conclusions: Our study provides evidence that reactions to both AX and CLV can appear in the same patient.

Keywords: Allergy; Amoxicillin; Clavulanic acid; IgE; T cells.

Publication types

  • Case Reports

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Allergens / immunology*
  • Amoxicillin / immunology*
  • Amoxicillin / therapeutic use
  • Biopsy
  • Cells, Cultured
  • Clavulanic Acid / immunology*
  • Clavulanic Acid / therapeutic use
  • Drug Hypersensitivity / complications
  • Drug Hypersensitivity / diagnosis*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hypersensitivity, Delayed / etiology
  • Hypersensitivity, Delayed / prevention & control*
  • Hypersensitivity, Immediate / etiology
  • Hypersensitivity, Immediate / prevention & control*
  • Immunization
  • Immunoglobulin E / blood
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Skin Tests
  • Th1 Cells / immunology*


  • Allergens
  • Clavulanic Acid
  • Immunoglobulin E
  • Amoxicillin