World-first clinical trial to help millions of people with penicillin allergies

The PALACE study, an international research endeavour, has evaluated a safer and simpler approach to penicillin allergy testing.

Montreal, July 17 2023—Penicillin allergy is a widespread public health concern, with one in 10 patients being documented as having a penicillin allergy. Those patients are more likely to be prescribed alternative antibiotics that are often less effective against certain infections. This can lead to treatment failure, increased risks of antibiotic resistance and the development of superbugs. Yet, fewer than 5 per cent of patients labelled with a penicillin allergy are truly allergic.

Conducted by a team of researchers from six specialized centres in Canada, the U.S. and Australia, the PALACE study sought to answer these issues by evaluating a new approach to identifying patients at low risk of penicillin allergy, and determining the best way to test and treat them. The results of this clinical trial, published today in JAMA Internal Medicine, pave the way for the adoption of a simple oral test called “direct oral penicillin challenge” as a safe and effective alternative to traditional skin testing, which is labour-intensive, not easily accessible to all, as well as time-consuming and painful for the patients.

“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. 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,” says Dr. Ana-Maria Copaescu, first author of the study, associate investigator in the Infectious Diseases and Immunity in Global Health Program at the Research Institute of the McGill University Health Centre (RI-MUHC), who was the leading investigator for the North American sites.

“The PALACE study is the first international randomized study to look at reducing the burden of penicillin allergy by seeing if a simple test dose procedure following careful assessment can be used to disprove a patient penicillin allergy, rather than traditional skin or scratch testing,” adds Pr. Jason Trubiano, senior author of the study, director of Infectious Diseases and head of Centre for Antibiotic Allergy and Research at Austin Health in Australia. “With this new procedure, we can give back a lifesaving antibiotic, penicillin, to more than 90 per cent of patients that undergo testing.”

Towards a change of practice

The study enrolled 382 adults who were assessed using a specialized risk assessment tool called PEN-FAST. Participants were randomly assigned to receive either a direct oral penicillin challenge or the standard approach, which involves penicillin skin testing followed by an oral challenge. The primary goal was to determine if the direct oral penicillin challenge was as effective as the standard method for removing the allergy label.

The study found that only one patient (0.5 per cent) in each group experienced a positive reaction to the penicillin challenge. This demonstrates that the direct oral penicillin challenge is just as effective as the standard method. Importantly, there were no significant differences in adverse events between the two groups, and no serious adverse events were reported.

These findings have wide-ranging implications for patient care. By quickly, safely and accurately identifying and testing low-risk penicillin allergy patients, healthcare providers can ensure appropriate antibiotic prescriptions.

A solution to a multifaceted problem

Research has shown that 80 per cent of people who have had a penicillin allergy for over 10 years eventually lose their sensitivity to the medication. Yet many adult patients carry a penicillin allergy label from childhood.

“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.,” says Dr. Copaescu, who is also an assistant professor in the Department of Medicine at McGill University. “And for various reasons, unverified penicillin allergy labels are not often challenged. As a result, many patients receive broad-spectrum alternative antibiotics associated with increased healthcare cost and increased antibiotic resistance, and in some cases, higher rates of treatment failure, medication errors and undesirable side effects or complications”.

The PALACE study represents a major advancement in addressing the global issue of penicillin allergies, with the potential of making penicillin delabeling more universally available.

“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,” adds Dr. Copaescu.

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About the study

Thearticle Efficacy of a clinical decision rule to enable direct oral challenge in a patients with low-risk penicillin allergy – The PALACE Randomized clinical Trial is published in JAMA Internal Medicine

DOI :10.1001/jamainternmed.2023.2986

Dr. Copaescu wishes to thank the Montreal General Hospital Foundation and the RI-MUHC for their support.

About the Research Institute of the McGill University Health Centre

The Research Institute of the McGill University Health Centre (RI-MUHC) is a world-renowned biomedical and healthcare research centre. The institute, which is affiliated with the Faculty of Medicine of McGill University, is the research arm of the McGill University Health Centre (MUHC)—an academic health centre located in Montreal, Canada, that has a mandate to focus on complex care within its community. The RI-MUHC supports over 450 researchers and around 1,200 research trainees devoted to a broad spectrum of fundamental, clinical and health outcomes research at the Glen and the Montreal General Hospital sites of the MUHC. Its research facilities offer a dynamic multidisciplinary environment that fosters collaboration and leverages discovery aimed at improving the health of individual patients across their lifespan. The RI-MUHC is supported in part by the Fonds de recherche du Québec — Santé (FRQS). rimuhc.ca

Media contact

Fabienne Landry
Communications coordinator, Research, MUHC
[email protected]
514 812-7722