Kate Johnson

March 02, 2013

SAN ANTONIO, Texas — Penicillin allergy testing can be done safely and effectively with currently available commercial products, according to a large prospective clinical trial presented here at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2013 Annual Meeting.

"This is an important, real-world study showing that allergists in the United States now have all the tools they need to help undiagnose the 25 million Americans who carry a history of penicillin allergy," senior investigator Eric Macy, MD, from the San Diego Medical Center in California, told Medscape Medical News.

"Only about a third of allergists feel comfortable with penicillin skin testing, which is criminal," Dr. Macy said. "This is something that's safe and effective, but unfortunately, a whole generation of young allergists just never learned how to do it in their training."

The lack of training, he explained, is due to concerns about the reliability of commercially available testing materials. As a result, only about 0.1% of patients with presumed penicillin allergy undergo confirmatory testing each year.

"In the past 30 years, there's been no large clinical trial in the United States that has looked at the commercially available materials penicilloyl-polylysine, penicillin G, and oral amoxicillin to determine whether using only these 3, you can safely determine who is or who is not allergic. This is the first time it's ever been done," Dr. Macy said.

First Large Clinical Trial

The study prospectively tested 500 patients with a reported history of penicillin allergy to confirm the allergy.

The patients, who had a mean age of 41 years, underwent puncture and intradermal skin testing with penicilloyl-polylysine and penicillin G. Patients who tested negative were given a confirmatory oral amoxicillin challenge and were observed for 1 hour.

"The test is a 2-part thing. It's important anytime you do skin testing that you validate it with an oral challenge," Dr. Macy pointed out.

The demographic characteristics of the patients were similar to the other 51,978 penicillin-allergic individuals on the Kaiser Permanente San Diego health plan, he said.

Among the 500 participants, 4 had a positive skin test and were not given an oral challenge. These patients were found to have a bona fide penicillin allergy.

The remaining 496 patients went on to have an oral amoxicillin challenge, after which 4 more patients had a reaction and were also presumed to be truly allergic.

"So we found 1.8% of the 500 appeared to be allergic and the other people were not," said Dr. Macy, emphasizing that the 4 people who reacted after the oral challenge do not represent failures of the skin test.

"The skin test screens out those who will have more flamboyant reactions; we think it's ruling out the seriously bad ones," he said, adding that reactions to the oral amoxicillin challenge were mild. "They had a rash and that was it."

Table. Index Reaction in Patients With Suspected Penicillin Allergy (n = 500)

Symptoms Patients (%)
Rash 40.8
Hives or angioedema 33.8
Unknown 14.4
Other 8.2
Anaphylaxis 2.8
Reaction Time
Unknown 30.4
< 1 hour 10.4
1 to 24 hours 22.6
25 to 72 hours 15.8
> 73 hours 20.8


"We have previously shown that about 98% of individuals who carry a history of penicillin allergy do not have an immunoglobulin E–mediated allergy to penicillin," said Dr. Macy.

"Most adverse reactions are not IgE mediated," he noted. "Only a very small fraction is, but some of them are quite bad. You can get a nasty rash, you can get a bad GI problem, you can get Clostridium difficile, you can grow out a resistant organism — it's not allergic, but they're all called allergies, and that dramatically warps people's perceptions of what the risks are."

Confirmatory testing is essential in patients with a history of penicillin allergy to avoid the unnecessary use of alternative drugs, Dr. Macy said. "The inaccurate diagnosis of penicillin allergy drives more clindamycin use, which is associated with higher rates of Clostridium difficile, and more vancomycin use, which is more toxic to administer than penicillins and is associated with the generation of vancomycin-resistant Staphylococcus aureus."

Asked by Medscape Medical News to comment on the findings, Stuart Abramson, MD, chair of the AAAAI scientific program committee, said, "This is an original, new study that has a very large number of subjects. There have been some other studies that have suggested the Pen G plus Pre-Pen skin testing have a very good sensitivity and specificity for determining those at risk for anaphylaxis from penicillin without additional minor determinant mix testing, which is not commercially available at this time, but the data I am aware of to date have involved very few patients."

Stephen Dreskin, MD, from the University of Colorado School of Medicine in Denver, said during an interview, "This opens up a great opportunity to simplify treatment regimens for patients and to avoid antibiotics with an unnecessarily broad antibacterial spectrum and/or adverse side effects."

The investigators, Dr. Abramson, and Dr. Dreskin report no relevant financial relationships.

American Academy of Allergy, Asthma & Immunology (AAAAI) 2013 Annual Meeting. Abstract 829. Presented February 26, 2013.