Selective immediate responders to amoxicillin and clavulanic acid tolerate penicillin derivative administration after confirming the diagnosis

Allergy. 2015 Aug;70(8):1013-9. doi: 10.1111/all.12636. Epub 2015 May 11.


Background: An increasing number of patients show immediate selective hypersensitivity reactions to clavulanic acid (CLV) and amoxicillin (AX), probably due to their increased prescription. The maintenance of this response should be established.

Objective: To assess that the immediate hypersensitivity selective response to AX or to CLV is maintained after repeated administration of penicillin G (PG)/penicillin V (PV) and AX.

Methods: Patients with proven immediate hypersensitivity to AX (Group A) or CLV (Group B) were included. Diagnosis was performed using skin tests with major and minor determinants of PG (PPL/MDM), AX and CLV and by drug provocation test (DPT) if required. Selectivity was established by confirming tolerance to PG/PV (Group A) and to PG/PV and AX (Group B). The maintenance of the selective response was verified by repeating DPT, 15 days after the initial investigation, with the same procedure.

Results: Of 51 patients, 78% belonged to Group A and 22% to Group B. Most had anaphylaxis. In Group A, 72% were skin test positive; 28% required DPT. In Group B, 63% were skin test positive; 37% required DPT. Only two AX-selective cases developed positive responses after re-provocation with PG/PV. No cases selective for CLV developed a positive response to PG, PV or AX.

Discussion: The selective response to AX appears consistent, and a response to penicillin determinants only develops in a minority of cases. For the case of CLV, the selective response appears not to be modified by exposure to penicillin determinants, meaning that patients with CLV allergy can take penicillin derivatives safely.

Keywords: amoxicillin; clavulanic acid; cross-reactivity; immediate response; selective.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Distribution
  • Aged
  • Amoxicillin / adverse effects*
  • Amoxicillin / immunology
  • Chi-Square Distribution
  • Clavulanic Acid / adverse effects*
  • Clavulanic Acid / immunology
  • Cohort Studies
  • Drug Hypersensitivity / diagnosis
  • Drug Hypersensitivity / epidemiology
  • Drug Hypersensitivity / etiology*
  • Female
  • Humans
  • Hypersensitivity, Immediate / diagnosis
  • Hypersensitivity, Immediate / epidemiology*
  • Hypersensitivity, Immediate / etiology
  • Incidence
  • Male
  • Middle Aged
  • Penicillin G / immunology*
  • Prospective Studies
  • Risk Assessment
  • Sex Distribution
  • Skin Tests
  • Young Adult


  • Clavulanic Acid
  • Amoxicillin
  • Penicillin G