Wise Use of Antibiotics: The Importance of Penicillin Allergy Evaluation and Delabeling

Penicillin Allergy Prevalence and Mislabeling

Around 10% of Americans report a penicillin allergy, yet only about 1% has a true allergy when tested. Mislabeling often occurs due to confusion between side effects, viral rashes, and allergic reactions, and sometimes caregivers mistakenly believe that a family history of penicillin allergy means the child is penicillin allergic. Importantly, even true IgE-mediated allergies wane over time—50% resolve within five years and 80% within 10 years.¹

Impact of Penicillin Allergy Labels

Patients labeled as penicillin allergic are frequently prescribed broad-spectrum antibiotics, which are less effective, more expensive, and carry higher risks of side effects and antibiotic resistance.² These patients experience worse health outcomes compared with those without the allergy label.³ Many children are labeled before age 3 and retain this label throughout adulthood, compounding risks over time.⁴

National Recommendations/Guidelines

In December 2022, the American Academy of Allergy, Asthma, and Immunology (AAAAI) and the American College of Allergy, Asthma, and Immunology (ACAAI) jointly published a Drug Allergy Practice Parameter Update that recommends proactive efforts to delabel patients with reported penicillin allergies when appropriate.⁵ Direct oral challenges without prior skin testing are recommended for pediatric patients at low risk of IgE-mediated immediate reactions⁵ and have been shown to be safe and effective, even for children with history of hives.^6-9 Penicillin skin testing is more commonly reserved for patients at high risk of IgE-mediated reactions, particularly anaphylaxis.

Children’s Mercy Initiatives

To address high rates of inaccurate penicillin allergy labels (PALs) and to improve antibiotic stewardship, the Children’s Mercy Kansas City (CMKC) Urgent Care launched a quality improvement project, in collaboration with CMKC Infectious Diseases and Allergy divisions, to improve adverse drug reaction (ADR) documentation and reduce PALs. To date, 625 patients have had their penicillin allergies delabeled, 78% by detailed ADR history taking alone and 22% by antibiotic challenge testing. The percentage of Urgent Care patients with PALs seen each month has decreased from 7.1% to 6.4%. In addition, a multidisciplinary CMKC team developed a clinical pathway to guide clinicians in evaluating PAL-labeled patients’ risks of serious penicillin allergy and determining next steps.

Clinical Pathway

Penicillin Adverse Drug Reaction (HISTORICAL) Risk Stratification

This clinical pathway helps stratify patients’ risks of serious penicillin allergy based on their prior ADRs and gives guidance on future allergy testing and antibiotic prescribing.

• Patients with PALs at no increased risk for IgE-mediated reactions (e.g., mislabeled due to side effects or family history, and those who have subsequently tolerated the antibiotic) can have their allergy labels removed after discussion with caregivers and explanatory documentation in the electronic health record, and can be prescribed penicillin antibiotics.
• Patients at low risk of immediate IgE-mediated reactions (e.g., experienced rash six or more hours after first dose) may receive any cephalosporin or carbapenem without challenge testing, even those with the same or similar side chains. For allergy evaluation, these patients may be referred for antibiotic challenge testing or may receive a single monitored dose of amoxicillin in a setting equipped to manage any reaction. (Exclusion Criteria for Observed Oral Amoxicillin Dose)
• Patients at high risk of immediate IgE-mediated reactions (e.g., experienced prior reactions less than six hours after first dose, such as hives, angioedema or anaphylaxis) require treatment with alternative antibiotics without the same or similar side chains. These patients should be referred for possible antibiotic challenge testing. Patients with prior anaphylaxis can be referred and tested five years or more after their initial ADR.
• Patients with prior severe delayed reactions (e.g., severe cutaneous adverse reactions [SCARs] such as blistering or mucosal rashes, fever and joint swelling, or organ damage) should avoid all beta-lactam antibiotics in the future and retain their allergy labels. Although testing is not recommended, referral to the Allergy Clinic could be considered for further delineation of the allergy.

Alternative Antibiotic Guidance

Cross-reactivity among beta-lactam antibiotics depends more on shared or similar R-group side chains than on their core beta-lactam ring. The clinical pathway includes an Alternative Antibiotic Table to guide safe antibiotic prescribing for patients with PALs who require treatment before their allergy can be evaluated and for patients who should not receive penicillin antibiotics.

Where to Refer?

Patients with prior ADRs to any antibiotic may be referred to CMKC’s Allergy Clinic, whereas the Infectious Diseases Clinic evaluates patients with prior reactions to penicillin or to amoxicillin only (not to Augmentin). See Patient Referral Information for Antibiotic Allergy Evaluation.

A Call to Action

Accurate ADR documentation and penicillin allergy delabeling improve patient care and safety, reduce unnecessary broad-spectrum antibiotic use, and support antibiotic stewardship. Together we can reduce inaccurate PALs by placing allergy labels judiciously after ADRs, using the risk stratification clinical pathway, and referring eligible patients for penicillin allergy evaluation.

References:

1. Trubiano J, Adkinson N, Phillips E. Penicillin allergy is not necessarily forever. JAMA. 2017;318(1):82-83.
2. Joerger T, Taylor MG, Li Y, Palazzi DL, Gerber JS. Impact of penicillin allergy labels on children treated for outpatient respiratory infections. J Pediatric Infect Dis Soc. 2023;12(2):92-98.
3. Kaminsky LW, Al-Obaydi S, Hussein RH, Horwitz AA, Al-Shaikhly T. Impact of penicillin allergy label on clinical outcomes of pneumonia in children. J Allergy Clin Immunol Pract. 2023;11:1899-906.e2.
4. Norton A, Konvinse K, Phillips EJ, Broyles AD. Antibiotic allergy in pediatrics. 2018;141(5):e20172497.
5. Khan D, Banerji A, Blumenthal K, et al. Drug allergy: a 2022 practice parameter update. J Allergy Clin Immunol. 2022;150:1333-1393.
6. Mill C, Primeau M, Medoff E, et al. Assessing the diagnostic properties of a graded oral provocation challenge for the diagnosis of immediate and non-immediate reactions to amoxicillin in children. JAMA Pediatr. 2016;170(6):e160033.
7. Vyles D, Adams J, Chiu A, et al. Allergy testing in children with low-risk penicillin allergy symptoms. 2017;140(2):e20170471.
8. Shenoy E, Macy E, Rowe T, Blumenthal K. Evaluation and management of penicillin allergy: a review. 2019;321(2):188-199.
9. Vyles D, Chiu A, Routes J, et al. Oral amoxicillin challenges in low-risk children during a pediatric emergency department visit. J Allergy Clin Immunol Pract. 2020; 8(3);1126-1128.e1.