The Importance of Putting Penicillin Allergy Labels to the Test

Rates of patient reactions to direct penicillin challenges are infrequent and comparable to indirect challenges after allergy testing, according to a meta-analysis in JAMA Internal Medicine.

In this exclusive video interview, study author Kimberly Blumenthal, MD, MSC, of Harvard Medical School and Massachusetts General Hospital in Boston, discusses the research and the importance of incorporating routine delabeling efforts into practice.

The following is a transcript of her remarks:

My name is Kim Blumenthal, and I’m an allergist, immunologist, and researcher at Massachusetts General Hospital and an associate professor of medicine at Harvard Medical School.

The objective of this study is to evaluate the safety of something called a direct penicillin challenge, which is the giving or the administration of penicillin to patients or individuals who have a history of allergy to penicillin.

Traditionally, most of our evaluation for penicillin allergy was much more cumbersome, including penicillin skin tests and sometimes blood tests. Recently, a lot of studies have come out that really show that the giving of penicillin under observation, typically we use amoxicillin for this, is actually quite safe in low-risk individuals.

In this study, which was a systematic review and meta-analysis, we meta-analyzed 56 included studies that had 9,225 participants. Across all of these participants, we only identified 438 reactions and only five were severe reactions. None of those reactions were fatal. So what we did was we identified a reaction risk of 3.5% across all direct penicillin challenges.

We also noted that this reaction rate of 3.5% is actually really similar to the prior background studies that show the reaction rate after using the penicillin skin test. So the patients that used to be all penicillin skin-tested and then get a penicillin challenge after a negative skin test, that reaction rate is quite similar, about 3.5% as well.

What this study’s findings mean is that patients who have a history of low-risk penicillin allergy as defined by these included studies — sometimes they define low-risk as non-anaphylactic reactions, sometimes they define low-risk as just a skin-only reaction — and across all these types of low-risk patients, we found a very, very low risk of having a reaction at all. So most of the time — a 100 minus 3.5% of the time — there was no reaction at all. And actually there were only five reactions altogether.

So what this study shows is that it’s really safe to think about direct penicillin challenges, or the use of direct amoxicillin challenge, which is what we do most often in America, in individuals who have a low-risk history of penicillin allergy.

This study really is the largest study, with a huge group of patients because it’s all of the included studies that have happened in the last decade, and it has over 9,000 people. So it really provides a lot of evidence, safety, security about this idea that we can just give the amoxicillin back, give the penicillin back, in low-risk patients without a concern for severe reactions, or even that the reaction rate is low overall.

Penicillin allergy is incredibly morbid. If you have a penicillin allergy label, you’re more likely to receive these alternative antibiotics that are less effective, that are more toxic, that contribute to antibiotic resistance. You’re more likely to have a surgical infection if you have a penicillin allergy label and go into surgery. So because of all of these adverse consequences of having a penicillin allergy label, the idea of removing a penicillin allergy label or testing for penicillin allergy is now globally recommended as part of antibiotic stewardship; as part of improving quality of care.

And this specific study helps us do that because we don’t need to know how to do penicillin skin tests to do that. There are a lot of individuals who have these low-risk penicillin allergy histories, and in those patients, we can just give amoxicillin back in a few steps — one or two steps.

My global recommendation moving forward is that penicillin allergy labels should be noted by all the healthcare team members as potentially not being confirmed; that individuals should receive penicillin allergy evaluation. Low-risk patients, we should consider de-labeling or removal of the penicillin allergy label with these direct penicillin challenges whenever patients present with things that might be low-risk, that aren’t anaphylactic reactions, that are skin-only reactions or intolerance-type reactions, and that we should do this across ages and geographies to improve clinical care and combat antibiotic resistance.

I think that the next steps for where this specific research will head relates to understanding what is the best definition of low-risk is better. So what we learned through this process was that all of those 56 studies defined low-risk in different ways. We tried to come up with the best definition of low-risk, because not leaving that to interpretation is the best way to implement direct penicillin challenges, but we didn’t find that there was any uniformity or consistency across definitions, so I’m hopeful that investigators and public health individuals will come up with a good definition or guideline for what we should all consider low-risk and come up with that recommendation next.