Is your patient really allergic to penicillin? Oral challenge is safe way to find out: study

Patients who report they have a penicillin allergy, but have a low risk of actually having an allergy, can safely have an oral penicillin challenge without having an initial skin test first, new clinical trial results suggest.

The finding may be a first step in reducing the number of people labeled as having an allergy to penicillin.

Penicillin allergies are common, with one in ten people reporting they have one. Physicians prescribe broad-spectrum alternative antibiotics to these patients, but these treatments may be less effective, lead to treatment failure and increase the risk of antibiotic resistance. 

Of the patients labeled with a penicillin allergy, fewer than 5% are truly allergic, according to a review published in JAMA in 2019.

“A penicillin allergy label can appear from multiple sources, such as avoidance as a result of family history or non-allergic mild side effects such as headache or stomach pain, skin rashes associated with viral infections in kids that are subsequently labelled as allergic, fear of the drug, etc.,” said Dr. Ana-Maria Copaescu, associate investigator in the infectious diseases and immunity in global health program at the Research Institute of the McGill University Health Centre (RI-MUHC). “And for various reasons, unverified penicillin allergy labels are not often challenged.”

People who are allergic to penicillin may also be allergic to other beta-lactam antibiotics. “The penicillin family can include many antibiotics that are similar: penicillin, cephalosporins, carbapenems,” Dr. Copaescu told Profession Santé. In her opinion, it’s important to verify a  patients’ allergic status with the utmost certainty, so as not limit other effective therapeutic possibilities.

Currently, testing a suspected penicillin allergy involves a skin test, followed by an oral challenge if the skin test is negative. Access to skin tests is problematic to patients in rural areas or elsewhere around the world. 

“The current procedure to verify or delabel a penicillin allergy requires a specialized skill set and uses costly specialized testing reagents in an allergist’s office. If infectious disease specialists, general internists or general practitioners could delabel low-risk patients through direct oral challenge, this would significantly increase the number of patients who could be safely delabeled and significantly reduce the global burden of penicillin allergy,” Dr. Copaescu said in a press release from MUHC. 

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Researchers from Canada, Australia and the United States tested to see if a direct oral penicillin challenge was a safe way to determine a penicillin allergy in a trial, called PALACE, involving 377 participants. Patients were randomized to have either direct penicillin oral challenge or standard care of a skin test followed by an oral challenge.

The researchers only included patients who were considered at low risk for a positive penicillin allergy test, based on the PEN-FAST point-of-care clinical decision tool, described in a 2020 paper in JAMA Internal Medicine. The tool focuses on four indicators of a positive allergy test. Patients involved in the trial had a PEN-FEST score lower than three, representing a moderate to low risk of a positive penicillin allergy.

There was one immune-mediated reaction within one hour of an oral penicillin challenge in both groups. After five days, there were nine immune-mediated events in the direct oral challenge group and 10 in the usual care group. No serious events were reported.

The researchers concluded that direct oral penicillin challenge is as effective and safe as the current standard.

“The biggest takeaway from the PALACE study is that patients with a low-risk penicillin allergy, like a childhood rash, can safely have a test dose of penicillin to determine if they are still allergic,” said Dr. Copaescu, who was lead author of the study and is also an assistant professor in the Department of Medicine at McGill University. 

“This will change the way doctors test for penicillin allergy in the future. Millions of patients worldwide, including millions of Canadians, will be able to have their penicillin allergy disproved by a safe single oral test dose following a carefully risk-validated risk assessment.” 

Australia recently launched a National Inpatient Penicillin Allergy database, which will collect results of patients’ penicillin allergy testing. The database is one step in a larger penicillin allergy delabelling program. Another step is a survey of clinician’s beliefs on penicillin allergy delabelling.

“The end goal is to broaden the future drug allergy workforce to include pharmacists, who can potentially upskill to offer penicillin allergy testing, perhaps using oral challenge programs in low-risk inpatients,” Dr. Jason Trubiano, senior author of the PALACE study and head of drug and antibiotic allergy and research at Austin Health in Melbourne, Australia, wrote in the University of Melbourne’s news publication Pursuit. Elise Mitri, a PhD candidate, co-wrote the article.

The PALACE trial results were published in JAMA Internal Medicine.

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