Ampath Chats

Penicillin Allergy

Ampath Chats
Penicillin Allergy
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PATHCHAT Edition No. 51
October 2018
Please contact your local Ampath pathologist for more information.

Authors:

  • Dr. Louise Murray (Chemical Pathologist, Immunology Department)
  • Dr. Cathy van Rooyen (Clinical Virologist, Immunology Department)

Introduction

βœ… Penicillin Allergy Overview:

  • Most commonly reported antibiotic allergy.
  • Less than 20% of patients with a reported penicillin allergy are truly allergic.
  • Many individuals avoid penicillin unnecessarily, leading to alternative antibiotic use with higher costs and side effects.

πŸ“Œ Penicillin metabolism produces benzyl penicilloyl (major determinant) and multiple minor determinants (e.g., penilloate, penicilloate, benzyl-n-propylamine). Both major and minor determinants contribute to allergic reactions.

Approach to Diagnosing Drug Allergy

βœ… Key Steps:

  1. Obtain a detailed history to determine if the reaction was an immunologically mediated allergy.
  2. Classify the reaction as immediate or delayed.
  3. Identify the underlying immunological mechanism:
    • IgE-mediated reactions (immediate onset).
    • Basophil-mediated reactions (immediate or delayed).
    • Complement-mediated immune complex reactions (delayed).
    • T-cell mediated reactions (delayed).

πŸ”Ή Risk Factors for True Penicillin Allergy:

  • History of hypersensitivity to other drugs.
  • Frequent penicillin administration.
  • Intravenous administration route.
  • History of atopy.

πŸ“Œ Most patients labeled as penicillin-allergic can safely tolerate the drug upon formal testing.

Available In Vitro Tests for Penicillin Allergy

πŸ”Ή Tests for Immediate Reactions:

  • ImmunoCap IgE (Penicilloyl G, Penicilloyl V, Amoxycilloyl, Ampicilloyl).
  • CAST (Cellular Antigen Stimulation Test) for:
    • PPL (Major determinant).
    • MDM (Minor determinants).
    • Penicillin V, Penicillin G, Amoxicillin, Ampicillin, Clavulanic Acid.
  • Minimum diagnostic panel:
    • PPL, MDM, Amoxicillin + Clavulanic Acid.

πŸ”Ή Tests for Delayed Reactions:

  • CAST:
    • PPL, MDM, Clavulanic Acid + Amoxicillin.
  • Lymphocyte Transformation Tests (LTTs) or MELISA:
    • Pen V, Pen G, PPL, MDM, Ampicillin, Clavulanic Acid, Amoxicillin.
  • Minimum diagnostic panel:
    • PPL, MDM, Amoxicillin + Clavulanic Acid.

πŸ“Œ Endorsed by the Immunology Peer Group.

Skin Prick Testing (SPT) & Drug Challenge

βœ… Indications for SPT:

  • For patients with a suspected penicillin allergy who test negative on in vitro assays.
  • Performed using:
    • Penicillin major determinant (PPL).
    • Minor determinant mixture (MDM) (if available).

βœ… Limitations of SPT:

  • PPL and MDM reagents are expensive and unstable, limiting availability in South Africa.
  • Alternative approach:
    • SPT using commercially available penicillin drugs (tablets or vials).
    • Can be performed at Ampath Allergy Clinic (Pretoria) and by other allergy specialists.

βœ… Negative Predictive Value of SPT:

  • 99% when both major and minor determinants test negative.

βœ… Drug Challenge Test (If SPT & In Vitro Tests Are Negative):

πŸ“Œ SPT and drug challenge help confirm tolerance in patients with reported penicillin allergy.

Management of Confirmed Penicillin Allergy

βœ… Key Recommendations:

  • Avoid all penicillins if allergy is confirmed.
  • Educate the patient on alternative antibiotics.
  • Document allergy status in medical records.
  • Desensitization can be done in cases where no alternative exists.

πŸ“Œ Protocols for drug desensitization are available (Chang et al., 2012).

Cross-Reactivity Between Beta-Lactam Antibiotics

βœ… Cephalosporins:

  • Cross-reactivity with penicillins is estimated at ~10%.
  • Lower risk with third-generation cephalosporins (2–5% cross-reactivity).

βœ… Carbapenems (Imipenem, Meropenem, Doripenem, Ertapenem):

  • Share a beta-lactam ring with penicillins.
  • However, 99% of penicillin-allergic patients tolerate carbapenems.

πŸ“Œ Cross-reactivity varies between beta-lactam antibiotics, with newer cephalosporins and carbapenems generally safe for most penicillin-allergic patients.

American Academy of Allergy, Asthma & Immunology (AAAAI) Guidelines

βœ… Approach to Penicillin Allergy Testing:

  • For low-risk patients (unlikely IgE-mediated allergy):
    • Perform direct oral amoxicillin challenge to confirm tolerance.
  • For high-risk patients (likely IgE-mediated allergy):
    • Perform IgE testing or skin prick testing before re-exposure.

βœ… European Approach (Common in South Africa):

  • Basophil activation tests are increasingly used for beta-lactam allergy testing.

πŸ“Œ Penicillin allergy testing is a critical component of antibiotic stewardship, improving patient outcomes by enabling penicillin use when safe.

Key Takeaways for Clinicians

βœ… Most reported penicillin allergies are unconfirmed, leading to unnecessary antibiotic avoidance.
βœ… Skin prick testing (SPT) and drug challenge can safely rule out penicillin allergy in most cases.
βœ… Cross-reactivity between penicillins and third-generation cephalosporins is low (~2–5%).
βœ… Carbapenems (e.g., meropenem) are tolerated by 99% of penicillin-allergic patients.
βœ… Penicillin allergy testing should be considered part of antibiotic stewardship efforts.

πŸ“Œ Accurate penicillin allergy testing can expand treatment options, reduce antibiotic resistance, and improve patient care.

References

  1. Chang C et al. (2012). Overview of penicillin allergy. Clinical Reviews in Allergy and Immunology, 43: 84–97.
  2. American Academy of Allergy, Asthma and Immunology (AAAAI). Penicillin allergy guidelines. Available at: www.aaaai.org/penicillinallergy.
  3. Macy E (2015). Penicillin allergy: optimizing diagnostic protocols. Current Opinion in Allergy and Clinical Immunology, 15: 308–313.
  4. Gonzalez-Estrada A & Radojicic C (2015). Penicillin allergy: A practical guide for clinicians. Cleveland Clinic Journal of Medicine, 82: 295–300.