The negative predictive value of 5-day drug provocation test in nonimmediate beta-lactam allergy in children

Ann Allergy Asthma Immunol. 2020 May;124(5):494-499. doi: 10.1016/j.anai.2019.12.029. Epub 2020 Jan 7.


Background: Extending the drug provocation test (DPT) period is recommended for patients with suspected nonimmediate beta-lactam antibiotic (BLA) allergy and negative DPT. No consensus has been reached regarding the duration of prolonged provocation.

Objective: We aimed to determine the negative predictive value (NPV) of the 5-day extended DPT.

Methods: Parents of patients with suspected nonimmediate mild cutaneous reactions with BLAs who had been subjected to 5-day DPT with culprit drugs were questioned by telephone interview about reexposure to the tested drug. Patients with reported reaction during reexposure were reevaluated. Skin tests and serum-specific immunoglobulin E (IgE) analysis were not performed before first DPT.

Results: A total of 355 patients had negative results in 5-day DPT. The median age at DPT was 4.2 years, and 52.9% were male. The families of 255 patients (72%) could be contacted. Of these 255 patients, 179 (70%) had used the same drug, and reactions were reported for 6 (3.4%) of those patients, who were subsequently reevaluated. Five of the 6 patients had DPT with amoxicillin-clavulanate and 1 with cefixime. When detailed history was taken, 2 of the 5 patients with amoxicillin-clavulanate reaction were found to have used the drug unintentionally after their reaction to reexposure and did not have any symptoms. One of the patients underwent allergy workup and tested negative, and the other 2 refused the test. The patient with reported cefixime reaction underwent repeated allergy workup and tested negative. Therefore, the NPV of 5-day prolonged DPT was 98.9%.

Conclusion: The 5-day prolonged DPT has high NPV and seems appropriate in duration for children with suspected nonimmediate-BLA allergy.

MeSH terms

  • Administration, Oral
  • Allergens / immunology
  • Amoxicillin-Potassium Clavulanate Combination / adverse effects
  • Amoxicillin-Potassium Clavulanate Combination / immunology
  • Amoxicillin-Potassium Clavulanate Combination / therapeutic use*
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / immunology
  • Anti-Bacterial Agents / therapeutic use*
  • Cefixime / adverse effects
  • Cefixime / therapeutic use*
  • Child
  • Child, Preschool
  • Drug Hypersensitivity / diagnosis*
  • Female
  • Humans
  • Hypersensitivity, Delayed
  • Immunization / methods*
  • Immunoglobulin E / metabolism
  • Infant
  • Male
  • Predictive Value of Tests
  • Time Factors*
  • beta-Lactams / adverse effects
  • beta-Lactams / immunology
  • beta-Lactams / therapeutic use*


  • Allergens
  • Anti-Bacterial Agents
  • beta-Lactams
  • Immunoglobulin E
  • Amoxicillin-Potassium Clavulanate Combination
  • Cefixime