Protocol for Penicillin (PCN) Challenge
The standard protocol for a penicillin challenge involves skin testing followed by oral challenge in patients with negative skin tests, with direct oral challenge appropriate for low-risk patients with non-severe reaction histories. 1
Patient Risk Stratification
Before conducting a penicillin challenge, stratify patients based on their reaction history:
Low-risk patients (appropriate for direct oral challenge):
- History inconsistent with true allergy (headache, isolated GI symptoms, family history only)
- Benign rash occurring >1 year ago without anaphylaxis/angioedema
- No history of severe cutaneous reactions
High-risk patients (require skin testing before challenge):
- History of anaphylaxis or recent suspected IgE-mediated reaction
- Severe cutaneous reactions
- Reactions requiring treatment
- Reactions occurring within the past year
Penicillin Skin Testing Protocol
For high-risk patients, perform skin testing with:
Epicutaneous (prick) testing first:
- Major determinant: Benzylpenicilloyl poly-L-lysine
- Minor determinant: Penicillin G (10,000 U/mL)
- Positive control: Histamine
- Negative control: Saline
If prick tests are negative, proceed to intradermal testing with the same reagents
- Positive result: Wheal diameter ≥2mm larger than negative control after 15 minutes
- Negative result: Proceed to oral challenge
Special precautions:
- For patients with history of anaphylaxis or asthma, use 100-fold dilutions first
- Ensure no recent antihistamine use (varies by medication: 24 hours to 3 weeks)
- Test in a monitored setting with anaphylaxis treatment available
Oral Challenge Protocol
For patients with negative skin tests or low-risk histories:
Two-step challenge approach:
- First dose: 1/10 of therapeutic dose (typically 40-80mg amoxicillin for adults)
- Observation period: 30 minutes
- Second dose: Full therapeutic dose (typically 250-500mg)
- Final observation: 60 minutes after last dose
Single-step challenge (for very low-risk patients):
- Full therapeutic dose of amoxicillin
- Observation for 60 minutes
Documentation and Follow-up
After completing the challenge:
If negative challenge:
- Remove penicillin allergy label from all medical records
- Provide patient with written documentation (wallet card)
- Educate patient about the significance of being "de-labeled"
If positive challenge or skin test:
- Document specific reaction
- Consider desensitization if penicillin is essential
- Evaluate cross-reactivity risk with cephalosporins
Common Pitfalls to Avoid
- False negative results: Ensure patients haven't taken antihistamines before testing
- Inadequate monitoring: Always observe patients for at least 60 minutes after final dose
- Incomplete documentation: Failure to remove allergy label from all medical records
- Inappropriate patient selection: Direct challenge should not be performed in patients with history of severe reactions without prior skin testing
- Reacquisition of allergy label: Ensure all healthcare providers are informed about the negative challenge results
Penicillin challenges should only be performed by healthcare providers trained in recognizing and treating anaphylaxis, with appropriate emergency medications and equipment immediately available.