Penicillin Allergy Evaluation: A Prospective, Multicenter, Open-Label Evaluation of a Comprehensive Penicillin Skin Test Kit

Background: Ten percent of the population claims an allergy to penicillin, but 90% of these individuals are not allergic. Patients labeled as penicillin-allergic have higher medical costs, longer hospital stays, are more likely to be treated with broad-spectrum antibiotics, and develop drug-resistant bacterial infections. Most penicillin skin test reagents are not approved by the Food and drug Administration or readily available to evaluate patients labeled penicillin-allergic. Objective: To determine the negative predictive value (NPV) of the Penicillin Skin Test Kit containing the major allergenic determinant (penicilloyl polylysine), a minor determinant mixture (penicillin G, penicilloate, penilloate), and amoxicillin, produced according to Food and Drug Administration standards. Methods: This was a prospective, multicenter, open-label investigation of penicillin skin testing using the Penicillin Skin Test Kit. Skin test–negative subjects were challenged with 250 mg amoxicillin, whereas skin test–positive patients were not challenged. The primary end point was NPV of the Penicillin Skin Test Kit, defined as the percentage of subjects with negative skin test results who did not experience an IgE-dependent reaction within 72 hours of amoxicillin challenge. Results: In total, 455 patients with a history of penicillin allergy underwent skin testing and 63 (13.8%) had 1 or more positive test results; 65% of the positive test results were to the minor determinant mixture and/or amoxicillin alone. In the per protocol group of 373 skin test–negative subjects, 8 developed potential IgE-dependent reactions following oral amoxicillin challenge, translating to an NPV of 97.9% (95% CI, 95.8-99.1; P < .0001). All but 1 of the reactions was mild or moderate, and most subjects who required treatment received only antihistamines. Conclusions: The Penicillin Skin Test Kit, containing all relevant penicillin allergenic determinants, demonstrated very high NPV. Removal of a penicillin allergy label in a large majority of currently mislabeled patients has substantial personal and public health implications.