Allergic to penicillin? World-first clinical trial explains why this could be false

NASHVILLE, Tenn. — Penicillin allergies are a public health threat, affecting over 25 million Americans and leading to antibiotic resistance and infections in hospitalized patients. The effects of this allergy have been shown to result in poor health outcomes for pregnant women and patients undergoing surgery. Now, the world’s first clinical trial, led by researchers from Vanderbilt University, may help countless people dealing with this critical allergy to medication.

“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,” says study protocol member and Vanderbilt University Medical Center principal investigator Elizabeth Phillips, MD, the John Oates Professor of Clinical Research.

“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,” Phillips continues in a media release.

Those labeled as having an allergy to penicillin may not react as badly to the drug as one may expect. In fact, 75 percent or more penicillin allergy labels emerge by the age of three, often due to confusion with a viral rash. Most of the rashes on toddlers were never even allergy-induced but were labeled as such. Now, there’s lots of adults who ended up still being labeled as allergically reactive to the drug, even if it isn’t really true.

“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,” explains Phillips.

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Most low-risk patients with penicillin allergies have been able to have their allergy label removed with use of a simple procedure known as “direct oral challenge,” as part of the multi-center randomized trial called the Penicillin Allergy Clinical Decision Rule (PALACE) study.

“We would expect more than 95% of these patients to have negative testing and be able to take penicillin in the future,” the study author continues.

The researchers enrolled 382 adults who were assessed using a specialized risk assessment tool called PEN-FAST. They were randomly assigned to receive either a direct oral penicillin challenge or the standard skin test followed by an oral challenge approach. The team wanted to effectively determine if the direct oral penicillin challenge was no worse than the typical approach.

Only one patient reacted positively to the penicillin challenge, showing that the direct oral challenge measures up just as well against the standard method. Additionally, there were no significant differences in adverse events between the two groups and there were no serious adverse events reported, either.

“The evidence provided by the PALACE study will change clinical practice. Many patients in the United States do not have direct access to an allergist to provide specialized testing such as skin testing. Therefore, the ability to go to direct oral challenge with a penicillin in low-risk patients which can be carried out in any observed setting will make it easier for patients in the United States to access health care to safely and effectively remove the label of penicillin allergy,” concludes Phillips.

The findings are published in JAMA Internal Medicine.

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