Further Evidence for the Safety of Oral Penicillin Challenges

The vast majority of penicillin allergy–labeled patients are not truly allergic; fewer than 5% have confirmed allergies on testing. In a patient with a low probability of a true allergy based on the PEN-FAST tool (NEJM JW Gen Med Aug 1 2023 and JAMA Intern Med 2023 Jun 20; [e-pub]), direct oral challenge without skin testing is gaining acceptance.

In an international randomized trial, 377 patients with reported penicillin allergies and PEN-FAST scores of <3 (on the 5-point scale^*) were randomized to undergo direct oral challenge or penicillin skin testing followed by oral challenge. One patient in each group developed mild rash within 1 hour; in the 5 days after the challenge, 9 patients in the direct-challenge group and 10 patients in the s…