What is the protocol for a patient presenting for a Penicillin (PCN) challenge?

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Last updated: July 31, 2025View editorial policy

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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:

  1. 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
  2. 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:

  1. Epicutaneous (prick) testing first:

    • Major determinant: Benzylpenicilloyl poly-L-lysine
    • Minor determinant: Penicillin G (10,000 U/mL)
    • Positive control: Histamine
    • Negative control: Saline
  2. 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
  3. 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:

  1. 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
  2. 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:

  1. 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"
  2. 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.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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