Most people labeled “allergic” to penicillin or other beta-lactam antibiotics are not truly allergic - and a new study helps pinpoint who actually is.
Beta-lactam antibiotics (like penicillins and cephalosporins) are among the most common drugs to receive an anaphylaxis label, which automatically puts patients into a “high-risk” category. The problem: not all of these labels reflect a real, ongoing allergy. This study, done at Mayo Clinic sites in Arizona, Florida, and Rochester between 2019 and 2020, set out to find which clinical features actually predict a confirmed beta-lactam allergy on skin testing.
Researchers reviewed 294 adults who were evaluated for a history of suspected beta-lactam–induced anaphylaxis. The group had a median age of 60, was predominantly female (70%). Penicillin was the most commonly blamed drug, implicated in about 70% of cases.
Yet when these patients underwent formal allergy skin testing, only 43 people - about 15% - had a confirmed beta-lactam allergy. In other words, 85% of patients carrying a serious “anaphylaxis” label did not have their allergy confirmed on testing.
The Key Predictors of True Allergy
The team used multivariable logistic regression to see which aspects of the original reaction (“index reaction”) were associated with a positive skin test.
Two features stood out:
- Recent reactions matter
If the reaction occurred within one year of the allergy evaluation, the odds of a positive skin test were much higher (odds ratio 11.35, 95% CI 3.70–37.98, p = .0001). That suggests that more recent anaphylaxis histories are far more likely to reflect a true, persistent beta-lactam allergy.
- Reactions that led to medical care
Patients who sought medical attention for their reaction had increased odds of a positive skin test (odds ratio 2.41, 95% CI 1.19–5.13, p = .01). Needing urgent or emergency care seems to be a red flag that the event may have been a genuine drug-induced anaphylaxis.
Interestingly, some features that clinicians might assume are strongly predictive did not show a significant link to confirmed allergy:
Presence of urticaria (hives) was not significantly associated with skin test results (p = .50).
Use of epinephrine during the reaction was also not significantly associated (p = .13).
Why This Matters for Patients and Clinicians
For patients, carrying a “beta-lactam anaphylaxis” label can mean avoiding first-line antibiotics for life, getting broader-spectrum alternatives, and facing more side effects, higher costs, and potentially worse outcomes. This study reinforces that only a minority of those labeled as having beta-lactam anaphylaxis actually have a confirmed allergy when tested.
For clinicians, two simple pieces of history can help prioritize who most needs formal allergy evaluation and perhaps more cautious management:
The reaction happened within the last year.
The reaction was severe enough to drive the patient to seek medical care.
Patients whose reactions were remote in time and managed at home may be more likely to tolerate beta-lactams after proper evaluation, including skin testing and, when appropriate, supervised drug challenges.
Take-Home Message
In this Mayo Clinic cohort, only 15% of patients labeled with beta-lactam anaphylaxis had a confirmed allergy on skin testing. Reactions that were recent (within one year) and serious enough to prompt medical attention were the strongest clinical predictors of a true, test-confirmed beta-lactam allergy.
References:
https://www.sciencedirect.com/science/article/pii/S0091674925020500