Penicillin Allergy: Can Testing Improve Antibiotic

Why does penicillin allergy matter after COVID-19?

CDC reports that resistant infections beginning in hospitals and associated deaths both increased by at least 15% between 2019 and 2020 across seven pathogens. Overstretched hospitals, disrupted infection prevention and antibiotic exposure contributed to the broader setback. These are historical findings, not measurements of resistance in October 2026. They establish why protecting effective treatment options remains a priority. [CDC pandemic resistance assessment](https://www.cdc.gov/antimicrobial-resistance/data-research/threats/covid-19.html).

One potentially correctable obstacle is an unverified penicillin allergy. CDC estimates that approximately 10% of U.S. patients report this allergy, while fewer than 1% of the population are truly allergic. Those percentages have different denominators from the proportion testing positive among referred patients. An inaccurate label can lead clinicians to choose broader-spectrum alternatives with additional risks. [CDC allergy estimates](https://www.cdc.gov/antibiotic-use/communication-resources/is-it-really-penicillin-allergy.html), [CDC clinical guidance](https://www.cdc.gov/antibiotic-use/hcp/clinical-signs/index.html).

What did the PALACE trial show about oral allergy testing?

The PALACE randomized trial, published in JAMA Internal Medicine in 2023, assigned 382 adults to direct oral penicillin challenge or skin testing followed by oral challenge; 377 were analyzed. Participants had low-risk histories assessed using the validated PEN-FAST clinical rule. An immediate immune-mediated reaction occurred in one person in each group, approximately 0.5%. Both reactions were mild and treated with antihistamines. [PALACE trial](https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2806976).

The findings support a simpler evaluation pathway for eligible adults, potentially reducing dependence on specialist skin-testing resources. However, delayed reactions also occurred, and the study's predominantly White outpatient population limits generalization. PALACE evaluated allergy assessment; it did not demonstrate a reduction in resistant infections or deaths. Its practical contribution is evidence that selected patients can have an inaccurate allergy label removed through a supervised process. [Trial results and limitations](https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2806976).

Who can have a penicillin allergy label reassessed?

Assessment starts with the original drug, symptoms, timing and treatment required. A childhood viral rash or diarrhea may have been mistaken for allergy. Depending on the history, clinicians may recommend supervised oral challenge or skin testing followed by challenge. Testing requires observation and access to medicines for treating reactions. [CDC assessment guidance](https://www.cdc.gov/antibiotic-use/hcp/clinical-signs/index.html).

Previous anaphylaxis requires specialist assessment. Severe delayed reactions, including Stevens-Johnson syndrome, DRESS or drug-related organ injury, exclude routine skin testing and oral challenge with the culprit drug. Patients should never test themselves using leftover antibiotics. Removing an inaccurate label expands prescribing options; it does not make penicillin effective against bacteria already resistant to it. [CDC safety guidance](https://www.cdc.gov/antibiotic-use/hcp/clinical-signs/index.html).