
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
β 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.
π 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
β Key Steps:
- Obtain a detailed history to determine if the reaction was an immunologically mediated allergy.
- Classify the reaction as immediate or delayed.
- 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).
πΉ Risk Factors for True Penicillin Allergy:
- History of hypersensitivity to other drugs.
- Frequent penicillin administration.
- Intravenous administration route.
- History of atopy.
π Most patients labeled as penicillin-allergic can safely tolerate the drug upon formal testing.
Available In Vitro Tests for Penicillin Allergy
πΉ 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.
πΉ 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.
π Endorsed by the Immunology Peer Group.
Skin Prick Testing (SPT) & Drug Challenge
β 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).
β 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.
β Negative Predictive Value of SPT:
- 99% when both major and minor determinants test negative.
β Drug Challenge Test (If SPT & In Vitro Tests Are Negative):
- Protocols available at www.aaaai.org/penicillinallergy.
- Not indicated for Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN) cases.
π SPT and drug challenge help confirm tolerance in patients with reported penicillin allergy.
Management of Confirmed Penicillin Allergy
β 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.
π Protocols for drug desensitization are available (Chang et al., 2012).
Cross-Reactivity Between Beta-Lactam Antibiotics
β Cephalosporins:
- Cross-reactivity with penicillins is estimated at ~10%.
- Lower risk with third-generation cephalosporins (2β5% cross-reactivity).
β Carbapenems (Imipenem, Meropenem, Doripenem, Ertapenem):
- Share a beta-lactam ring with penicillins.
- However, 99% of penicillin-allergic patients tolerate carbapenems.
π 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
β 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.
β European Approach (Common in South Africa):
- Basophil activation tests are increasingly used for beta-lactam allergy testing.
π Penicillin allergy testing is a critical component of antibiotic stewardship, improving patient outcomes by enabling penicillin use when safe.
Key Takeaways for Clinicians
β
Most reported penicillin allergies are unconfirmed, leading to unnecessary antibiotic avoidance.
β
Skin prick testing (SPT) and drug challenge can safely rule out penicillin allergy in most cases.
β
Cross-reactivity between penicillins and third-generation cephalosporins is low (~2β5%).
β
Carbapenems (e.g., meropenem) are tolerated by 99% of penicillin-allergic patients.
β
Penicillin allergy testing should be considered part of antibiotic stewardship efforts.
π Accurate penicillin allergy testing can expand treatment options, reduce antibiotic resistance, and improve patient care.
References
- Chang C et al. (2012). Overview of penicillin allergy. Clinical Reviews in Allergy and Immunology, 43: 84β97.
- American Academy of Allergy, Asthma and Immunology (AAAAI). Penicillin allergy guidelines. Available at: www.aaaai.org/penicillinallergy.
- Macy E (2015). Penicillin allergy: optimizing diagnostic protocols. Current Opinion in Allergy and Clinical Immunology, 15: 308β313.
- Gonzalez-Estrada A & Radojicic C (2015). Penicillin allergy: A practical guide for clinicians. Cleveland Clinic Journal of Medicine, 82: 295β300.