The Limited Value of Prolonged Drug Challenges in Nonimmediate Amoxicillin (Clavulanic Acid) Hypersensitivity

J Allergy Clin Immunol Pract. 2019 Sep-Oct;7(7):2225-2229.e1. doi: 10.1016/j.jaip.2019.04.021. Epub 2019 Apr 26.


Background: Misdiagnosis of amoxicillin (clavulanic acid) (AX(/CL)) hypersensitivity has serious consequences. A drug challenge (DC) is the final diagnostic to affirm or infirm AX(/CL) hypersensitivity. However, uncertainties remain whether a prolonged drug challenge (pDC) should benefit the diagnosis of a nonimmediate AX(/CL) hypersensitivity.

Objective: To assess the added value of a standardized 7-day pDC in the diagnosis of nonimmediate or unclear penicillin hypersensitivity.

Methods: A total of 132 patients with a history of a nonimmediate hypersensitivity reaction or an unclear reaction to AX(/CL) or an undefined penicillin with a negative diagnostic workup including a single-day DC (DC) with AX(/CL) were selected. In all these patients, an additional pDC with AX(/CL) was planned. Thirteen patients started the pDC immediately after the DC. To ensure that hypersensitivity symptoms manifesting during the pDC course do not result from the DC, in the remaining 119 patients, the pDC was scheduled after a washout of 1 week.

Results: A total of 128 patients (12 without washout, 116 with washout) completed the pDC. Three patients reacted with a mild maculopapular exanthema. However, the value of a pDC was evidenced in only 1 patient who reacted during her pDC after an uneventful washout. In 2 patients pDC was cancelled because they reacted during the washout.

Conclusions: A pDC is of limited added value to the diagnostic algorithms of nonimmediate hypersensitivity reaction or unclear hypersensitivity reactions to AX(/CL). In our hands, the traditionally recommended diagnostic algorithm that offers a 1-day DC as a final diagnostic in patients with negative workup for AX(/CL) is appropriate.

Keywords: Drug challenge; Hypersensitivity; Penicillin.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amoxicillin / administration & dosage
  • Amoxicillin / adverse effects*
  • Amoxicillin-Potassium Clavulanate Combination / adverse effects*
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects*
  • Child
  • Child, Preschool
  • Drug Hypersensitivity / diagnosis*
  • Drug Hypersensitivity / etiology
  • Female
  • Humans
  • Hypersensitivity, Delayed / diagnosis*
  • Hypersensitivity, Delayed / etiology
  • Immunologic Techniques / methods*
  • Male
  • Middle Aged
  • Penicillins / adverse effects
  • Retrospective Studies
  • Time Factors
  • Young Adult


  • Anti-Bacterial Agents
  • Penicillins
  • Amoxicillin-Potassium Clavulanate Combination
  • Amoxicillin