Q&A: National Penicillin Allergy Day spotlights need to re-evaluate patients

National Penicillin Allergy Day is Sept. 28, which acknowledges the day in 1928 when Sir Alexander Fleming, FRS, FRSE, FRCS, discovered that Penicillium mold secretes an antibacterial substance.

Penicillin continues to save lives nearly a century later, but many people incorrectly believe they are allergic to the antibiotic, with potential negative consequences both for themselves and for the health care system.

Healio spoke with Allison C. Ramsey, MD, chair of the American Academy of Allergy, Asthma & Immunology (AAAAI) Adverse Reactions to Drugs, Biologicals and Latex Committee, to find out more.

Healio: What is National Penicillin Allergy Day?

Allison C. Ramsey

Ramsey: It started a few years ago to raise awareness of the importance and significance of the penicillin allergy label. We often associate allergy labels with a way of protecting patients, but this one ultimately can be deleterious for both individual and public health.

National Penicillin Allergy Day is a way of raising awareness that this is the most commonly reported drug allergy. But the vast majority of these people, if they undergo evaluation, won’t be allergic. Such evaluations can improve their future health care and options for antibiotics, and it is important on a public health level as well.

Healio: How common is penicillin allergy?

Ramsey: It’s the most commonly reported drug and antibiotic allergy. It’s reported in about 10% of the U.S. population. In studies on inpatients who are on penicillin-based antibiotics for infections requiring hospitalization, it has been shown to be higher, from 15% to 20%.

Healio: What are some of the risks of penicillin allergy?

Ramsey: People who truly have a penicillin allergy are in the minority. It usually ends up on people’s health records because they have a history of a rash with penicillin exposure. Sometimes swelling or respiratory symptoms like cough, wheezing or trouble breathing. Sometimes a more severe allergic reaction like anaphylaxis can result. Those are the dangers. That’s what people fear. That’s why when patients have any of those symptoms, penicillin goes on their chart as an allergy, and it isn’t revisited.

But only about 1% of the people in that 10% figure are allergic. Or stated another way, 90% to 95% of people who report a penicillin allergy can tolerate penicillin. That’s why it’s important to verify the label. We call it de-labeling.

Having this penicillin allergy label on your allergy list when you would otherwise tolerate penicillin has been shown to contribute to longer and more expensive hospital stays, higher risk for adverse reactions from second-line antibiotics, increased antimicrobial resistance and increased rates of Clostridioides difficile infection, which is an antibiotic-associated diarrheal infection.

When someone can tolerate penicillin but is avoiding it because of some remote reaction, they’re at risk for these adverse personal health outcomes, which are also linked to adverse public health outcomes.

Healio: Where do these misdiagnoses about penicillin allergies come from?

Ramsey: It doesn’t always have to be a misdiagnosis. The most common scenario that we encounter is that someone was on an antibiotic in early childhood for an outpatient infection and developed a rash. Sometimes the rash is linked to the childhood illness itself, not the antibiotic, but there was no way to test or distinguish that at the time. So, it then goes down in the medical history, and it’s left there.

Another thing that comes up is that interplay between the infection and the antibiotic leads to a rash, but subsequent courses of the antibiotic would be tolerated.

The last thing is that people truly may have an allergic reaction to penicillin, but they outgrow it. About 80% of people outgrow penicillin allergy in 10 years. Consider someone who is 80 years old who has been hospitalized for a urinary tract infection, and they’re avoiding penicillin because they got a rash when they were 5 years old. These people are highly likely to tolerate it.

Healio: What other impacts could these inaccurate diagnoses have on patients and on health care?

Ramsey: These patients are at higher risk for adverse effects from second-line antibiotics. Often, penicillin-based antibiotics are used first line for infections. But when patients use alternative antibiotics, their cure rates go down, and their recurrence rates go up. Also, other organs may become involved. Some antibiotic groups will cause acute kidney disease.

From a public health perspective, a lot of these second-line antibiotics raise costs or are more expensive, so that raises individual costs as well as costs to health care systems.

Beyond that, the penicillin allergy label has been linked to higher rates of MRSA, or methicillin-resistant Staphylococcus aureus. Also, some of the families of second-line antibiotics or non-penicillin antibiotics are associated with diarrheal infection and C. difficile, which is a common cause of hospital-acquired infection.

When you use alternative antibiotics that aren’t tailored to a specific infection, you’re allowing the bacteria you’re targeting to see a broader antibiotic. Therefore, they develop more resistance mechanisms. That comes up with S. aureus in particular. The penicillin allergy label has also been associated with higher rates of vancomycin-resistant Enterococcus. Essentially, the more bacteria see these other antibiotics, the more they’re able to change their own defenses and evade the antibiotics’ efficacy.

You want to use the most tailored antibiotic you can. In a lot of cases, that’s penicillin-based antibiotics.

Healio: What are some of the broader consequences of antibiotic resistance?

Ramsey: If bacteria evolve and mutate to where you don’t have effective antibiotics against them, that’s a big public health problem. The more that we can use appropriate antibiotics to target infections, the more we can keep that under control, because antibiotic development isn’t keeping pace with the risk of antibiotic and antimicrobial resistance. You don’t want to end up with any bacteria species that you don’t have a good antibiotic to target them with.

Healio: What can health care providers do to improve penicillin allergy diagnoses?

Ramsey: We’ve been promoting proactive penicillin allergy evaluation. There’s good evidence that younger kids who have a history of a cutaneous-only reaction will tolerate a challenge to penicillin where you don’t even need to have skin testing or the poke or prick typically associated with an allergy immunology visit. We try to let pediatricians know that this is something they can bring up at well visits.

We’re also targeting other specific groups of patients such as hospitalized patients. A lot of hospitals have penicillin allergy evaluations as part of their antimicrobial stewardship teams, which hospitals are required to have. We need to make sure that patients who are already in the hospital are evaluated so they can be on the best antibiotic.

Anybody who has an unverified penicillin allergy label should be evaluated. Right now, that’s usually by an allergist as an outpatient. There are a few infectious disease physician-run programs, mostly on an inpatient basis. More and more studies coming out are about risk-stratifying patients by their penicillin allergy reaction history. We’re hoping it won’t all end up under allergy and immunology purview, because there are fewer allergists than there are penicillin-allergic patients. There’s not enough of us to go around.

Healio: What is AAAAI doing to lead this charge?

Ramsey: The AAAAI website has patient information materials. We retooled the website, so there are videos and information for patients to learn about how they could access testing. We have a compilation of resources for allergy and immunology physicians who may not be providing these evaluations in their office, because they’re easy to implement. We have research links to all the data and studies supporting the need for evaluations. We just finished a letter for allergists to send to their local media. We’re also working on presentation and information materials that we can use to educate our colleagues in other specialties about the benefits of penicillin allergy evaluation. Also, penicillin allergy is going to be a major initiative of our incoming president, David A. Khan, MD.

We really need to raise awareness among our colleagues and among the public. Patients end up in our offices by word of mouth among each other and based on their doctors’ recommendations, and the AAAAI is going at that from both angles.

Healio: Is there anything else about penicillin allergies that you would like to add?

Ramsey: In allergy and immunology, we used to skin test everybody for penicillin allergy. We used skin prick testing, which people are familiar with if they’ve ever been tested for environmental allergies, and intradermal testing, which is an injection under the skin. But studies in penicillin allergy have really evolved. It’s becoming accepted now that patients with a remote history of just skin reactions can forgo that skin testing.

Instead, they can receive what is called a test dose, also known as a graded challenge. The patient gets a small dose of amoxicillin, waits 30 minutes, receives a full dose and then is monitored in the allergy and immunology office. Needle phobia is often why patients avoid this evaluation. But if they have the appropriate reaction history, which is usually just the skin reaction, they can forgo the poking. That’s a big win, especially in the pediatric population.

Our knowledge has evolved. We know that this is safe, so we’ve skipped the skin testing in appropriate patients. That’s a win all around. It’s less expensive. It’s maybe a little bit easier for allergy and immunology offices to handle. It’s certainly easier than testing in the hospital setting. Patients appreciate it as well.

Healio: Where else can providers go for more information?

Ramsey: The AAAAI website has many updated resources. The CDC website has information about antimicrobial stewardship, and it is also a good resource. The Individual health care systems also often have information about their programs and penicillin allergy.

For more information:

Allison C. Ramsey, MD, can be reached at allison.ramsey@rochesterregional.org.