Commentary: Celebrate National Penicillin Allergy Day by de-labeling your patients

After patients experience potential allergic reactions to a medicine, they can suffer several long-term adverse consequences that people do not often think about.

For example, during childhood, up to 10% of children will experience symptoms while being treated with amoxicillin. Although most of these reactions are benign rashes related to a virus, parents are told that their children are allergic to penicillin and given a warning for lifelong avoidance. Rarely are they tested to confirm this advice.

By the time a child is an adult, only 1% to 5% of penicillin allergies are confirmed true when tested. An untested avoidance thus becomes a lifelong “label” of allergy that adversely influences the care that the individual receives.

A label of penicillin allergy applied at age 3 years may cause a child’s doctor to avoid first-line treatments for a skin infection when the patient is a teenager, or affect her pregnancies as an adult when a penicillin-susceptible organism needs to be treated to protect her baby.

The label may also cause this patient’s surgeon to avoid first-line antibiotic prophylaxis for her knee operation at age 30 years or delay an emergency treatment for pneumonia at age 50 years as doctors try to pick the next best option.

Unnecessary avoidance of a key, first-line antibiotic agent then causes further harm during all these episodes when it leads to increased use of less effective, more toxic second-line drugs, which put the patient at risk for increased antibiotic failures, multidrug-resistant bacterial infections, antibiotic side effects and, under certain circumstances, death.

Above and beyond the adverse health consequences to an individual, there are also significant societal and public health consequences such as development of antibiotic resistance due to use of unnecessarily broad-spectrum and second-line antibiotics, as well as increased costs of treatment.

De-labeling is necessary, therefore, because it allows a patient to get rid of an untrue penicillin allergy. This then protects that patient from adverse consequences by giving their doctor more choices and making it more likely that they get “the right antibiotic at the right time,” which is a key goal of antimicrobial stewardship.

Expanding de-labeling services

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

But the medical community also uses the day to promote the need to de-label patients who may mistakenly believe that they have a penicillin allergy, so they can experience the benefits of this historic antibiotic.

In fact, the British Society for Allergy and Clinical Immunology (BSACI) recently issued guidelines so clinicians who are not trained in allergy and immunology can provide de-labeling services to their patients. I really think this is a good idea.

Our own research supports the idea that between 60% and 70% of all patients who report penicillin allergies experienced symptoms that are so low risk that they can safely take a dose under observation in a health care setting and have their penicillin allergy disproved that way. That is what is called a direct provocation challenge or a direct challenge.

We have an ongoing program in our hospital that we began in 2019, which is run by our pharmacists, that de-labels patients with low-risk penicillin allergies at the point of care every single day, using direct provocation challenges.

Our pharmacists ask patients about the story of their penicillin allergy, assess the riskiness of that story, and then go after the ones who are low risk, especially when the reported allergy is interfering with us giving the best antibiotic for an infection.

The safety we have observed within our program and that others have observed with similar programs suggest that we should really be getting ready to offer penicillin allergy de-labeling in even more settings.

The CDC has already put out some really great information on penicillin allergies, and they already advise that patients should get their penicillin allergies evaluated. I would really welcome the idea we could also go one step further in our policymaking toward ensuring that de-labeling an unnecessary penicillin allergy is recognized as a routine preventative care service and is made available to every patient in the US.

However, the key issue is that in the US, there are only about 7,000 allergy doctors, and between 10% and 15% (tens of millions!) of the US population report that they are allergic to penicillin.

Given the size of the problem, I am therefore a firm believer that to scale up penicillin allergy de-labeling, we are going to need to, first, make the ability to evaluate and de-label someone’s penicillin allergy readily available to all kinds of health care providers and, second, have our insurers and government incentivize de-labeling as a crucial preventative health effort in our guidelines and reimbursement.

We should offer de-labelling to as many patients as we can, in as many settings as we can, wherever the patients need us to do it. If we safely got rid of the millions of unnecessary penicillin allergy labels that are affecting our antibiotic decision making, we should potentially see reductions in all kinds of adverse outcomes and health care costs, because more patients would be able to get “the right treatments at the right time.”

BSACI guidelines

As for the recommendations from the BSACI, I think the authors did a great job in making guidance that should fit into the practices of care in the United Kingdom. Their guidelines are a step in the right direction. They are also very close to how we are trying to change our practices at Vanderbilt, based on the available evidence. I only see two nuanced differences between the BSACI’s recommendations and our own efforts.

One is that we do not use a lot of multidose challenges before de-labeling a patient’s penicillin allergy, but that is a stylistic point that is still being actively researched. Namely, how often do we actually need to use multiple doses to disprove that a patient is at risk for a low-severity rash or not? This is still an area for debate among allergists.

Between two and five out of every 100 patients that you treat with any antibiotic will have a mild rash, and these are essentially random and not reproducible. Most of them can be readily treated with antihistamines and topical treatments.

So far, having done hundreds of low-risk penicillin challenges with a single dose, we have a rate of about 0.5% that we have observed who will have a rash and who will need to keep their penicillin allergy in the chart.

The other difference between our approaches and the BSACI guidelines is that we will still offer penicillin de-labeling to even our sickest patients (severe heart disease, severe lung disease, immune compromised) who are either in our drug allergy clinic or who have already been admitted to the hospital or ICU and stabilized from their acute episode. These patients are often the ones who benefit the most from de-labeling, as 30% of them will immediately go on to treatment with a penicillin.

In our experience with hundreds of sick patients who report low-risk penicillin allergies, even those with COVID-19, it has been safe to test for de-labeling. Patients with low-risk allergies areonly at risk of rashes like everyone else, although a setting where patients feel safe and can be safely monitored is really important for de-labeling, too.

In conclusion, I welcome what I consider to be an excellent policy move by the BSACI. Further, I think that on Penicillin Allergy Day, it is wise to take a moment to consider how the lowly penicillin allergy is insidiously affecting our personal and societal antibiotic use, and how we might be able to do something about it.

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For more information:

Cosby A. Stone Jr., MD, MPH, is assistant professor of medicine in the division of allergy, pulmonology, and critical care medicine within the department of medicine at Vanderbilt University Medical Center and VUMC Drug Allergy Research. He can be reached at cosby.a.stone@vumc.org.