Pharmacists Should Be Recommending Penicillin Allergy Testing

When my daughter was about 5 years old, she was taking a course of amoxicillin for a middle ear infection. Around the fifth day of treatment, she broke out into hives all over her body. The pediatrician switched her antibiotic, and from then on, we listed penicillin as an allergy. I had heard about penicillin allergy testing and always thought that one of these days we would have to get around to doing that. Recently, I asked her allergist if we could schedule the penicillin allergy test. During our conversation, her doctor mentioned that out of more than 1000 patients he has tested over many years, only 3 were truly allergic to penicillin—so I expected her to pass the challenge.

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At the appointment, the procedure was to apply 2 types of penicillin to the arm and “scratch” it in, alongside a histamine control—similar to other types of allergy tests. After 15 minutes, the doctor would check it, and if she didn’t react, she would take a dose of oral amoxicillin. Surprisingly, she reacted to both penicillin samples, leading the doctor to confirm that she was allergic to penicillin (and the fourth truly allergic patient he had diagnosed).

After this experience, I thought about how many of our patients may report a penicillin allergy without truly knowing whether they are allergic. As pharmacists, it can be helpful to recommend penicillin allergy testing, especially for those who are uncertain about the specifics of their allergic reaction and/or for those who report that an allergy occurred long ago.

What happened to my daughter is a common scenario. The Allergy & Asthma Network outlines a very similar situation. A young child is prescribed a penicillin antibiotic and soon develops a skin rash. The parent calls the pediatrician, who switches the antibiotic and documents a penicillin allergy on the medical record. The child is now documented as allergic to penicillin but is rarely ever tested to confirm the allergy.¹ Often, this childhood label of a penicillin allergy carries into adulthood. Have you ever asked a patient about their reaction to penicillin, only to hear, “I don’t know; it happened when I was little”?

According to the CDC, approximately 10% of patients in the United States report a penicillin allergy. However, fewer than 1% have a true IgE-mediated allergy. Researchers also note that about 80% of patients who do have this IgE-mediated penicillin allergy will lose the sensitivity after 10 years.² Therefore, the CDC recommends identifying those who are not truly allergic to penicillin in order to decrease unnecessary use of broad-spectrum antibiotics.¹

In addition to avoiding penicillin, many health care providers avoid prescribing cephalosporins to patients labeled with a penicillin allergy, even though a true cross-reactivity between penicillin and cephalosporins is rare. This leads to increased use of other antibiotics like quinolones, macrolides, clindamycin, and vancomycin, which often have more adverse effects. Therefore, penicillin allergy testing is considered an important part of antibiotic stewardship.³

Individuals who have an IgE-mediated (type 1) reaction will typically react right away or within 1 hour. They may have hives; angioedema of the stomach, extremities, genitals, face, mouth, or throat; wheezing; shortness of breath; and/or anaphylaxis.¹

An anaphylactic reaction affects at least two of the following systems:¹

1. Skin: Symptoms may include hives, flushing, itching, angioedema
2. Respiratory: Cough, congestion, dyspnea, chest tightness, wheezing, choking, voice changes, or feeling like the throat is closing
3. Cardiovascular: Hypotension, feeling faint, and tachycardia are more common. Less common symptoms include bradycardia, chest pain, a feeling of impending doom, tunnel vision, and loss of consciousness.
4. Gastrointestinal: Nausea, vomiting, diarrhea, abdominal cramping

The physician will conduct a history and physical exam and order necessary tests. The recommended method typically begins with skin testing. Then, if the skin test is negative, an oral challenge dose of amoxicillin. After taking the oral dose, the patient is usually observed for about an hour in the office for acute reactions and 5 days at home for a delayed reaction.³ The accuracy of skin testing is over 95% and close to 100% when an oral challenge dose is given.¹

Experts recommend that individuals with an unconfirmed penicillin allergy should be evaluated and, if appropriate, tested.³ Not everyone should be tested for a penicillin allergy, though. Individuals with severe hypersensitivity syndromes, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, serum sickness, acute interstitial nephritis, hemolytic anemia, or drug rash with eosinophilia and systemic symptoms, should avoid penicillin. They should not be tested; rather, they should steer clear of penicillins.¹

Tiffany J. Owens, MD, is an allergist/immunologist at The Ohio State University Wexner Medical Center. In her practice, she sees patients every day that list penicillin or amoxicillin as an allergy, often attributing the allergy to childhood. Owens says that allergy symptoms typically appear right away and involve skin and/or respiratory symptoms. She reminds patients that self-reported allergies that involve gastrointestinal symptoms are not actual allergies.

For a patient who does not react to penicillin skin testing or the oral challenge, Owens notes that it “is very reassuring that an individual does not have a risk for anaphylaxis to a penicillin.” Also, regarding the possibility of cephalosporins, Owens recommends that if a patient has previously reacted to a cephalosporin, that particular antibiotic should be tested, too. Owens also noted that she advises patients to notify their pharmacist, dentist, and any other health care provider of any allergy test results.

As accessible health care professionals, pharmacists are in a unique position to assist patients with penicillin allergy concerns. By asking a few simple questions to patients who report a penicillin allergy, pharmacists can identify patients who might benefit from getting tested and can encourage them to consult an allergist about testing. After testing, pharmacists can update the patient’s records and share them with other health care providers.

REFERENCES

1. Fitzgerald G. The truth about penicillin allergy … and why it’s important to get tested. Allergy & Asthma Network. Updated November 23, 2024. Accessed May 18, 2025.https://allergyasthmanetwork.org/news/the-truth-about-penicillin-allergy-and-why-its-important-to-get-tested/

2. Clinical Features of Penicillin Allergy. CDC. April 2, 2024. Accessed May 18, 2025. https://www.cdc.gov/antibiotic-use/hcp/clinical-signs/index.html

3. Macy E, Vyles D. Who needs penicillin allergy testing? Ann Allergy Asthma Immunol. 2018;121(5):523-529. doi:10.1016/j.anai.2018.09.012