How is a penicillin challenge performed in a patient with a reported penicillin allergy?

Penicillin Challenge Protocol for Patients with Reported Penicillin Allergy

A penicillin challenge in patients with reported penicillin allergy should begin with risk stratification, followed by penicillin skin testing for moderate to high-risk patients and direct oral challenge for low-risk patients, with appropriate monitoring for reactions throughout the process. 1

Risk Stratification

Before performing any testing, patients should be stratified based on their reaction history:

Low-Risk Patients

• History of benign cutaneous reactions (non-urticarial rash)
• Reactions that occurred >10 years ago in adults or >1 year ago in children
• Non-specific symptoms (e.g., headache, nausea, vomiting)
• Family history of penicillin allergy without personal history

High-Risk Patients

• History of anaphylaxis or severe immediate reactions
• Recent reactions (<1 year)
• Reactions involving mucosal or systemic symptoms
• History of severe cutaneous adverse reactions

Testing Protocol

For Low-Risk Patients:

1. Direct Oral Challenge 2, 1
   • Single or two-step oral amoxicillin challenge
   • Two-step approach:
     • First dose: 1/10 of therapeutic dose (40-80 mg amoxicillin)
     • Observation for 30 minutes
     • Second dose: Full therapeutic dose (250-500 mg amoxicillin)
     • Observation for 60 minutes

For Moderate to High-Risk Patients:

1. Penicillin Skin Testing 1

   • Epicutaneous (prick) testing with:
     • Major determinant: Penicilloyl-poly-lysine (Pre-Pen) at 6×10^-5 mol/L
     • Minor determinant: Penicillin G at 10,000 units/mL
     • Positive control: Histamine
     • Negative control: Saline
   • Positive test: Wheal ≥3 mm larger than negative control with ≥5 mm flare
   • If prick tests are negative, proceed to intradermal testing with the same reagents

2. Oral Challenge (if skin testing negative) 1

   • Single therapeutic dose of amoxicillin (250-500 mg)
   • Observation for 60 minutes

Monitoring and Management

• All challenges should be performed under medical supervision with emergency medications available
• Monitor for immediate reactions (within 1-2 hours) and delayed reactions (up to 5 days)
• For any reaction during testing:
  • Mild reactions: Antihistamines may be sufficient
  • Severe reactions: Epinephrine, antihistamines, and/or corticosteroids as needed

Documentation

• Patients who test negative should receive written documentation (wallet card) indicating they are no longer penicillin allergic
• Update all medical records to remove the penicillin allergy label 1

Safety Considerations

• The negative predictive value of penicillin skin testing is >95% 1
• Direct oral challenges in low-risk individuals have shown very low rates of severe reactions 2, 1
• Resensitization after oral treatment with penicillins is rare in both pediatric and adult patients 1

Important Caveats

• Standard testing focuses primarily on immediate IgE-mediated reactions and may not detect delayed hypersensitivity reactions 1
• The presence of trained healthcare professionals during testing is essential to prevent any serious outcomes from reactions 2
• Penicillin allergy testing is cost-effective and improves patient outcomes by allowing appropriate antibiotic use 2