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People with a penicillin allergy on their medical record are not given penicillins (or often their relatives, the cephalosporins) when they have infections. Instead, the antibiotics prescribed may be broader-spectrum, less effective, and/or more toxic.

One recent national study from more than 100 U.S. hospitals with almost 11,000 patients demonstrated that if you have a reported penicillin allergy, you are five times more likely to be prescribed clindamycin than if you do not have an allergy.

Clindamycin is an antibiotic that is highly associated with the potentially life-threatening Clostridioides difficile (C. diff) gastrointestinal infection. A study using comprehensive U.K. data recently confirmed that people with a documented penicillin allergy have a 69% increased risk of C. diff.

When patients undergo surgery, a penicillin relative (cefazolin) is often used to prevent an infection at the surgical site. However, according to one study, in patients labeled with a penicillin allergy, cefazolin is routinely avoided in place of a less effective substitute, resulting in a 50% higher risk of surgical site infections for people with a documented penicillin allergy.

Confirming or ruling out a penicillin allergy through penicillin allergy testing could justify the risks of avoiding beta-lactams (the drug class that includes penicillins and cephalosporins), or potentially avert them by allowing doctors to prescribe beta-lactams when they are needed.

Even some patients with severe penicillin allergy histories are able to take penicillins safely again, because penicillin allergy often does not persist for life. In all, about 95% of people tested for penicillin allergy in the U.S. are found not to be allergic.

What allergy testing entails

Penicillin allergy testing often begins with an allergy history. In order to know if testing is appropriate, the clinician needs to know some details about the reaction, such as: When did it happen? What were the symptoms? How were you treated?

If appropriate, the next step may be the penicillin skin test. This test involves pricking the skin and introducing a small amount of allergen. Anyone with a positive skin test to penicillin — there’s usually itching, redness and swelling at the site of the test — is allergic and should avoid penicillin.

People who have no reaction to the skin test can undergo the amoxicillin challenge. In this test, the clinician gives the person amoxicillin (a type of penicillin), and observes for signs and symptoms of an allergic reaction for at least one hour.

Allergists routinely perform penicillin allergy testing. Other types of doctors, nurses, nurse practitioners, and even pharmacists can be trained to perform penicillin allergy skin testing in the US.

The amoxicillin challenge test can also be done by a variety of healthcare providers, as long as they are comfortable diagnosing and treating allergic reactions.

New clinical tools

There are increasing numbers of clinical tools that can help your primary care doctor, or other non-allergist healthcare provider, assess whether you have a true penicillin allergy.

The first tool is a risk stratification scheme, published in JAMA and endorsed by multiple professional associations. The review encourages an amoxicillin challenge be prescribed for low-risk patients.

Patients are classified as low-risk if their reactions occurred more than 10 years ago, and: were isolated and unlikely allergic (gastrointestinal symptoms, headaches); featured itching without rash; and did not include allergic symptoms such as hives, swelling, wheezing, shortness of breath, or chest tightness.

The JAMA review recommends that medium-risk and high-risk patients, including those who did experience one or more allergic symptoms or an anaphylactic reaction, undergo a skin test before completing an amoxicillin challenge.

Another recently developed tool, called PEN-FAST, can be used by all types of medical providers to help decide if it is safe to give you penicillin, and potentially remove your allergy label (“delabel” you). The tool uses your allergy history to determine risk similar to the JAMA expert guideline.

PEN-FAST stands for PENicillin allergy reported by the patient, Five years or less since the reaction (2 points), Anaphylaxis or Angioedema, Severe cutaneous adverse reaction (2 points), Treatment required for the reaction (1 point). You receive a score based on your responses to these four criteria, which reflects the likelihood that you have a true penicillin allergy.

Although you are likely to know the “F” and “T” parts of FAST — when it happened and whether you were treated — the “A” and “S” reaction assessments should be discussed with your doctor.

Anaphylaxis is a bodywide allergic reaction, and angioedema is severe swelling under the skin. Along with the severe skin-related adverse reactions, these are severe and potentially life-threatening reactions.

Patients who are able to answer “no” to the four PEN-FAST criteria (0 points) have a very low risk of true penicillin allergy. A total score of less than 3 indicates a low risk of penicillin allergy. Both of these patient groups would be likely to tolerate an amoxicillin challenge.

Of course, you and your doctor must be prepared for an allergic reaction prior to ingesting any medication to which there is a possible allergy.

Kimberly Blumenthal, M.D., MSc, is a contributor to Harvard Health Publications.

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