As part of the world-first multicenter randomized control trial known as the Penicillin Allergy Clinical Decision Rule (PALACE) project, many low-risk individuals with penicillin allergies were able to have their penicillin allergy label removed using a simple method known as ‘direct oral challenge’.
Penicillin allergy affects about 25 million people in the United States (up to one in every ten Americans), and it has been linked to particularly bad health outcomes in pregnant women and surgical patients. It also poses a public health risk by causing antibiotic resistance and potentially fatal infections in hospitalized patients.
By the age of three, seventy-five percent or more penicillin allergy labels appear, possibly due to confusion with a viral rash. The majority of these rashes were not allergic, but the labels ‘stick’ throughout adulthood and have numerous negative implications.”
As part of a world-first multicenter randomized control trial known as the Penicillin Allergy Clinical Decision Rule (PALACE) project, many low-risk penicillin allergy patients were able to have their penicillin allergy label removed using a simple method known as “direct oral challenge”.
The majority of patients labeled as penicillin allergic, more than 90%, have low-risk histories, meaning they did not have a history to suggest a severe or more recent reaction to a penicillin.
Elizabeth Phillips
In the PALACE study, investigators randomized low-risk penicillin-allergic patients to two different approaches to remove their allergy label. They either underwent the current standard of care to have skin testing followed if negative by oral challenge with a penicillin or they went straight to oral challenge (“direct oral challenge”) without preceding skin testing.
“The majority of patients labeled as penicillin allergic, more than 90%, have low-risk histories, meaning they did not have a history to suggest a severe or more recent reaction to a penicillin,” said PALACE study protocol member and Vanderbilt University Medical Center principal investigator Elizabeth Phillips, MD, the John Oates Professor of Clinical Research. “We would expect more than 95% of these patients to have negative testing and be able to take penicillin in the future.”
A team of researchers from specialist institutes in North America and Australia conducted the study, which included 382 adults who were examined using PEN-FAST, a specific risk assessment instrument. Participants were randomly randomized to either a straight oral penicillin challenge or the conventional protocol (penicillin skin testing followed by an oral challenge). The major purpose was to see if the direct oral penicillin challenge was any worse than the traditional approach of skin testing followed by oral challenge, which must be done in an allergist’s clinic.
Only one patient (0.5%) in each group had a positive reaction to the penicillin challenge, indicating that the direct oral penicillin challenge is as effective as the usual technique. Importantly, there were no significant differences in adverse events between the two groups, and no severe adverse events were identified.
The findings have broad ramifications for patients. Health care practitioners can assure adequate antibiotic prescriptions by correctly identifying patients with low-risk penicillin allergies. Patients with a confirmed penicillin allergy are more likely to be offered other antibiotics, sometimes known as second-line antibiotics, which are frequently less efficient against certain illnesses and may have greater adverse effects.
“Patients with penicillin allergy are more likely to get second-line or broader spectrum antibiotics that lead to risk of antibiotic resistance and serious infections such as antibiotic-associated diarrhea due to Clostridioides difficile, which can spread through hospitals and become a major public health problem.” Phillips said. “In the U.S. increasingly we also have a major problem with other antibiotic-resistant ‘superbugs’ such as multi-resistant gram-negative infections, Candida auris and even a resurgence of syphilis for which penicillin is the best treatment and the only treatment that should be used in pregnancy to prevent transmission to an unborn child.
“The evidence given by the PALACE trial will influence clinical practice. Many patients in the United States may not have direct access to an allergist who can perform specialist tests such as skin testing. As a result, the ability to perform a direct oral challenge with a penicillin in low-risk patients in any observed context will make it easier for people in the United States to obtain health care and safely and efficiently remove the label of penicillin allergy,” she stated.
