Some of the content on this page was created in collaboration with the Antimicrobial Stewardship Program at Sinai Health System, or was developed during our collaboration as a joint program between 2009 and 2024.
The modACCEPT Tool
Beta-lactam Allergy Assessment
Background
Beta-lactam antibiotics (penicillins, cephalosporins, carbapenems) are the most common group of medications to which patients report an allergy. Although 10% of patients report a reaction to beta-lactams, only 0.5-1% of patients would have an allergic reaction upon re-exposure. Additionally, certain types of reactions may decrease over time, making re-challenge a possibility.
This tool was created to help clinicians make antibiotic decisions for patients with self-reported beta-lactam allergies.
Classification of Hypersensitivity Reactions
| Category | IgE Reactions | Non-IgE Reactions |
|---|
| Onset | Within 1 h to up to 6 h | > 6 h to weeks |
|---|
| Severity | Variable | Mild/Intolerance | Severe Systemic/Cutaneous Adverse Reactions (SCAR) |
|---|
| Symptoms | Mucosal: angioedema Dermatologic: urticaria Gastrointestinal: vomiting (with other IgE-related symptoms) Respiratory: bronchospasm Cardiovascular: hypotension, arrhythmia (Note: ≥ 2 organ system involvement is anaphylaxis) | Central nervous system: headache Dermatologic: itching without maculopapular/mobilliform rash Gastrointestinal: isolated nausea/vomiting | Symptoms: desquamation, mucous membrane involvement, vasculitis, arthritis/arthralgia, unexplained fever associated with organ damage unrelated to other causes, generalized pustulosis, lymphadenopathy |
|---|
| Syndromes: Stevens-Johnson Syndrome (SJS), Toxic epidermal necrolysis (TEN), Drug reaction with eosinophilia and systemic symptoms (DRESS), Acute generalized exanthematous pustulosis (AGEP) |
| Prevalence | < 1% of beta-lactam exposures | Common | < 0.1% of beta-lactam exposures |
|---|
| Duration of reaction | < 24 h | Days to weeks |
|---|
| Cross-reactivity | Related to drug molecule structure (see cross-reactivity chart) | Unknown, possible structural relationship |
|---|
| Management | Beta-lactam assessment and management algorithm | Avoid all beta-lactams |
|---|
Beta-lactam Allergy Assessment
Questions to Ask
- What drug was involved in the original reaction?
- How long ago was the reaction?
- Describe what happened during the reaction.
- Examples suggestive of IgE reaction: face/throat swelling, itching with rash, hives, wheezing, dizziness or fainting
- Examples suggestive of mild non-IgE reactions or drug intolerance: isolated nausea and/or vomiting
- Examples suggestive of severe systemic or cutaneous adverse reactions: blistering or peeling skin, mouth or other mucous membrane involvement, drug fever associated with organ damage/dysfunction, increased eosinophils (lab test), severely decreased platelets (lab test) not due to other causes
Algorithm – Based on Responses to Questions Above
Cross-Reactivity Chart
Frequently Asked Questions
The risk of cross-reactivity for IgE reactions is related to the side chain structure of the beta-lactam (see cross reactivity chart). Beta-lactams with dissimilar side chains generally have a risk similar to that of the general population for IgE-mediated allergic reaction (~2%). While possible to have a core beta-lactam ring structure reaction, this is felt to be very uncommon.
There is insufficient evidence to assess cross-reactivity relationships for non-IgE reactions.
If the patient's reaction is sufficiently remote, such as more than 10 years ago, not remembering the reaction likely represents a low-risk history, as long as the patient does not recall needing medical care or that the reaction was life-threatening.
No. There has been no evidence for genetic/familial relationship to beta-lactam allergies.
For patients with IgE reactions, such as hives, angioedema, and anaphylaxis, research shows that 80% of patients no longer have the reaction, even to the same antimicrobial, after 10 years.
For non-IgE reactions, little is known about the durability and longevity of the reaction.
A beta-lactam allergy label has been associated with worse outcomes at both the patient and health system level. Avoidance of beta-lactams leads to use of alternative antimicrobials that may be less effective or have higher risk of adverse effects, such as C. difficile infection.
Depending on the index reaction of beta-lactam allergy, skin testing may not be always needed.
In general, for patients with low-risk penicillin allergy, direct oral challenge can be done without skin testing. However, in patients with more severe index reaction or delayed reaction, skin testing (when available) can help with risk stratification before drug challenge.
Consider referral to allergy/immunology if the antibiotic may be needed again in the future.
Data for the benefit of test doses and oral challenges is limited. Routine monitoring after administration of antimicrobial therapy is sufficient in patients with a history of beta-lactam allergy based on the algorithm below.
References
- Zagursky RJ, Pichichero ME. Cross-reactivity in β-Lactam Allergy. J Allergy Clin Immunol Pract 2018; 6(1):72-81.
- Caruso C, Valluzi RL, Colantuono S, et al. β-Lactam Allergy and Cross-Reactivity: A Clinician's Guide to Selecting an Alternative Antibiotic. Journal of Asthma and Allergy 2021; 11:31-46.
- Blumenthal KG, Peter JG, Trubiano JA, et al. Antibiotic allergy. Lancet 2019; 393:183-98.
- Vardakas KZ, Kalimeris GD, Triarides NA, et al. An update on adverse drug reactions related to β-Lactam antibiotics. Expert opinion on Drug Safety 2018; 17(5): 499-508.
- Lagace-Weins P, Rubinstein E. Adverse reactions to β-Lactam antimicrobials. Expert Opinions on Drug Safety 2012; 11(3):381-99.
- Shenoy ES, Macy E, Rowe T, et al. Evaluation and Management of Penicillin Allergy: A Review. JAMA 2019; 321(2):188-99.
- Macy E, Trautmann A, Chiriac AM, et al. Advances in the Understanding of Drug Hypersensitivity: 2012 Through 2022. J Allergy Clin Immunol Pract 2023; 11(1):80-91.
- Romano A, Gaeta F, valluzzi RL, et al. IgE mediated hypersensitivity to cephalosporins: Cross-Reactivity and tolerability of alternative cephalosporins. J Allergy Clin Immunol 2015; 136:685-91.
- Minaldi E, Phillips EJ, Norton A. Immediate and Delayed Hypersensitivity Reactions to Beta Lactam Antibiotics. Clinical Reviews in Allergy & Immunology 2022; 62:449–462.
- Vyas L, Raja K, Morrison S, et al. Beta-Lactam comprehensive allergy management program in a community medical center. Antimicrob Steward Healthc Epidemiol 2023; 3(1): e189.
- Wrenn RH, Trubiano JA. Penicillin Allergy Impact and Management. Infect Dis Clin N Am 2023; 37:793–822.
- Trubiano JA, Vogrin S, Chua KYL, et al. Development and Validation of a Penicillin Clinical Decision Rule. JAMA Intern Med 2020; 180(5):1-9.
- Copaescu AM, Vogrin S, James F, et al. Efficacy of a Clinical Decision Rule to Enable Direct oral Challenge in Patients with Low-Risk Penicillin Allergy: The PALACE randomized Clinical trial. JAMA Intern Med 2023; 183(9):944-952.
Last Revised: Jun/24/2025
Approvals:
- UHN Antimicrobial Subcommittee: Jul/02/2025
- UHN P&T: Jul/07/2025
