This webinar was recorded on January 29, 2024

In this webinar, Dr. Blumenthal will review why proactive evaluation and delableing of inaccurate antibiotic allergies is a key component of antibiotics stewardship and quality improvement.

Speaker:

  • Kimberly Blumenthal, MD, MSC
    Co-Director, Rheumatology & Allergy Clinical Epidemiology Research Center, Mongan Institute, Massachusetts General Hospital
    Director of Research, Drug and Vaccine Allergy Center, Massachusetts General Hospital
    Associate Professor, Harvard Medical School

Kimberly Blumenthal, MD, MSc is an Allergist/Immunologist and clinical researcher at Massachusetts General Hospital and Associate Professor of Medicine at Harvard Medical School. She is the Co-Director of the Clinical Epidemiology Research Center and Director of Research in the Center for Drug and Vaccine Allergy. Dr. Blumenthal performs drug and vaccine allergy research that uses methods of epidemiology, informatics, economics, decision science, and implementation science. Her research has been funded by the National Institute of Health, Agency for Healthcare Research and Quality, and foundations, including the American Academy of Allergy, Asthma, and Immunology Foundation and CRICO, the risk management foundation of Harvard Medical School. Dr. Blumenthal is internationally recognized for identifying the morbidity and mortality associated with unverified penicillin allergies and creating innovative approaches to the evaluation of penicillin and cephalosporin antibiotic allergies in diverse patient settings. Dr. Blumenthal has authored more than 170 peer-reviewed publications including leading high-impact manuscripts to publication in journals such as NEJM, Lancet, JAMA, and the BMJ. Dr. Blumenthal graduated from Columbia University with a BA in Economics. She studied medicine at Yale University School of Medicine, before training at the Massachusetts General Hospital for Internal Medicine and Allergy and Immunology. She completed a Master of Science in Clinical Epidemiology at the Harvard T.H. Chan School of Public Health in 2017.


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CME is available through ACAAI for this webinar.


Sponsored by the American College of Allergy, Asthma and Immunology

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Transcript: While this transcript is believed to be accurate, errors sometimes occur. It remains your responsibility to evaluate the accuracy and completeness of the information in this transcript. This transcript is not intended to substitute for professional medical advice.

Lynda: Hello, thanks for joining us. I am Lynda Mitchell, CEO of Allergy & Asthma Network. Welcome to this afternoon’s webinar. I am pleased to introduce Dr. Kimberly Blumenthal as a speaker. We have a few housekeeping items to go over before we start. First, all participants will be on mute. We will be recording this webinar and will post it on our website within 24 hours. You can find all recorded webinars on our website, our homepage, allergyasthmanetwork.org and scroll down. You will see recordings listed there. The webinar will be about one hour in length, including time for questions and answers. We will try to get to as many questions as we can, but you can put your questions in at any time. We have people monitoring the questions box and if you have any other technical issues to ask about you can either talk about it in the chat or posted in the Q&A — post it in the Q&A . We do these in partnership with the American College of asthma, allergy and immunology. The ACAAI offer CMA’s for physicians — CME’s for physicians. All attendees will be offered a certificate of attendance. No other continuing education credit is provided. A few days after the webinar you will receive an Email was supplemental information about the topic and a link to download the certificate if you missed the webinar today. We will try to add it in the chat.

Today’s topic is drug allergy, the importance of proactively addressing and delabeling antibiotic allergy. With the rise of drug-resistant organisms, proactive evaluation and delabeling of inaccurate antibiotic allergies is a key component of antibiotic stewardship and quality improvement. Unverified penicillin allergies can have adverse consequences for public and individual health. The goal of proactive penicillin allergy is to remove the label if the allergy is found to be untrue. It is my pleasure to introduce our speaker, Dr. Kimberly Blumenthal, an Allergist/Immunologist and clinical researcher at Mass General Hospital and associate professor at Harvard Medical School. She is the Co-Director of the Clinical Epidemiology Research Center and Director of Research in the Center for Drug and Vaccine Allergy. Dr. Blumenthal performs drug and vaccine allergy research and is internationally recognized for identifying the morbidity and mortality associated with unverified penicillin allergies and creating innovative approaches to the evaluation of penicillin and cephalosporin antibiotic allergies in diverse patient settings. Thank you for being here today, Dr. Blumenthal. I will turn it over to you.

Dr. Blumenthal: Thank you so much for having me. I will share my screen. I will start with the disclosure that I have done research for Thermo Fisher Scientific related to penicillin allergy as well as some of the up-to-date sections related to the topic today area our learning objectives are to describe the importance of proactive penicillin allergy evaluation and delabeling, to explain how to perform a penicillin allergy evaluation and identify populations most at risk of an unverified penicillin allergy label. I am excited to talk about this topic which is near and dear to my heart and we will start with the idea of what is a penicillin allergy label and why we care. About 10% of the population reports and allergy to penicillin. This means 32 million U.S. adults. Maybe not as common as in my waiting room, but at least one in 10 patients have a penicillin allergy label. The more our patients are sick or interact with the health care system, this means their frequency of penicillin allergy labels is even higher. Whereas it might be one in 10 and a primary care waiting room, and hospital it is 16% and in a rehab setting, all the way up to 24%. This is — has been the same in cancer patients and other patients frequently accessing health care. What we have known for a while and what we are now challenged to do in this next phase is to verify pencillin allergy labels because we know just because you have a pencillin allergy label on your record does not mean you have a true allergy. This was a meta-analysis from 2017 that looked at all the studies of hospitalized patients, showing 95% of them were not allergic. This is showing those individuals were all skin tested, 1391, and 95% were not accurately labeled. There are penicillin allergy patients labeled correctly, but the majority are in accurate. This is so important for improved patient care and population health, public health because a penicillin allergy label is associated with getting different antibiotics just because of the allergy label, they are more broad spectrum, they can be, have a higher side effect profiles, broader spectrum, so you are at increased risk of MRSA or resistant organisms, and they could have surgery because they are not getting the most effective surgical site infection prophylaxis drugs.

There is an increased risk of C. diff, increased risk of treatment failures, changing frontline therapy and increased risk of adverse events and all cause mortality. We know as allergist that not all these labels are true and we also know they have adverse consequences. Finally we learned in 2017 that when we test patients for penicillin allergy and follow their antibiotic use afterwards, changes. We can as allergists and the allergy community advocate for penicillin allergy assessment to change the antibiotic choice. This is looking at 308 evaluated patients in the Kaiser system versus 1251 not evaluated, a match cohort study. They looked at those who had allergist evaluation and matched those who did not and looked at antibiotic use and follow-up. Penicillin courses were 45% evaluated and only 2.5% not evaluated. First generation cephalosporin courses, prescribed outpatient as well as inpatient went from evaluated as 32 .5% and not evaluated at 20 point 5%. If we test patients, their antibiotic use changes, more penicillin. Because of these data, we have a lot of important — a lot of organization support for what we term penicillin allergy delabeling. I like to say penicillin allergy evaluation with appropriate delabeling. Sometimes we confirm it, sometimes immediate or delayed reactions, but the vast majority are eligible for delabeling or removing of the penicillin allergy label in the electronic record. We can see early on, there is a CDC support. There is a choosing wisely campaign from the Board of internal medicine, do not overuse. Antibiotic stewardship guidelines have encouraged penicillin allergy as part of that. As we talked about in the pregnant population, the American College of abstract tricks and gynecology — obstetrics and gynecology. IDSA supports proactive penicillin allergy evaluation with appropriate delabeling. It is interesting to think about why we would support a certain delabeling and it is because we can improve clinical care and because this intervention is not costly. We did a study in 2017 where we looked at how costly it is to perform a penicillin allergy assessment. You can see different assumptions. We changed the clinician from a medical doctor to nurse practitioner, let’s look at the skin test.

That can cost just $42 of real work. This is time driven activity cost, how much work it would be for our clinic to do this. Not much how much we get reimbursed, but how much it would cost our clinic to do penicillin allergy evaluation with no skin evaluation. This $202 was worth — with an MD. We have different assumptions. Will you test also with Ampicillin? Do you have to mix things up, is it more costly to dispose of things? We varied everything up to the highest situation. It was still only $369 for penicillin allergy evaluation, which is not much work for us to put into our clinic. This is what is called a decision analysis that is used for most cost-effectiveness studies. What I set out to do with my colleagues was to look at, is it more cost-effective to do a penicillin allergy evaluation or not? That is what A versus B is. Patient gets a penicillin allergy test or does not. This was full skin testing. Each of these, a decision node, but each of the green circles are where probabilities get put and that is how cost benefit analyses are done. We could not do a cost-effectiveness analysis because it was a cost saving. You cannot study cost-effectiveness, you study cost savings. When we looked at these analyses, this shows many scenarios. The most fun thing to do here is, let’s look the left where we did skin testing and drug challenge. If you can see, the circles and triangles are inpatients and outpatients. On the y axis, the best strategy. The number of simulations were testing saves money. All of them were above 50%. The majority were saving money. In almost every situation you save money. How much money you save is dependent on our health care system, but at least $500 for inpatient and $745 for outpatients. In this one, two step drug challenge and you save even more money because there is not as much cost to work involved as skin testing. Way above 15%. Most of the time you’re at 75%. You save money to do penicillin allergy evaluation in inpatients, outpatients, across Europe and the U.S. This is what I mentioned. If you’re really interested, I wrote my first grant.

On this this is the quadrant where cost-effectiveness analyses are required. When you put in money to get more health, which makes sense — if you look at a new diabetes medicine that is expensive, how they decide to cost it out. How much money will it cost, but how much more health will I get? This is where penicillin allergy is, where you get better at a meiotic — antibiotic choices, less C. diff, less treatment resistance, better health. It mostly is cost saving. We have to figure out how to adopt this. How do we do penicillin allergy evaluations? I want to start with the recent practice parameters published in 2022. These are consensus-based statements. The first is, we recommend against testing in patients with a history inconsistent with penicillin allergy like a history of a headache or family history of penicillin allergy. The one-step amoxicillin challenge can be offered to patients were anxious or request additional reassurance to accept the removal of a penicillin allergy label. This was a strong recommendation with moderate certainty of evidence. A lot of people labeled may not need to see an allergist because they have a headache or family history, but those people should be automatically delabeled. But if we can be helpful, we can offer a one-step amoxicillin challenge for reassurance. The second consensus statement, we recommend penicillin skin testing for patients with a history of anaphylaxis or recent reaction suspected to be IgE mediated. This evidence is not as strong. This is where a lot of our work lies. In someone who recently had a reaction, it sounds like something that is IgE. That is when we need to skin test.

Our colleagues from infectious disease or pharmacy might not be comfortable doing skin test. These are the patients. we absolutely need to see. A couple more penicillin consensus statements. This is recommending against penicillin skin testing before the amoxicillin challenge and pediatric patients with a history of benign cutaneous reactions such as macula popular — maculopapular rashes and urticar ia. It is saying you can go right to the direct challenge. The second, we suggest the direct challenge in adults with histories of maculopapular rashes and urticaria, we can consider skipping skin testing and going straight to a direct amoxicillin challenge. You can see in the pediatrics, the first line, strong and moderate and in adults, conditional and low. Penicillin skin testing has been around for ages. It has enjoyed coming back in America, 2009, when it came out with FDA approval. Internationally, full penicillin allergy kits are available. We do not have that in the U.S.. Some of these studies that show sensitivity and specificity use all reagents available internationally. This was an international diagnostic study, meta-analysis of 27 different studies looking at the sensitivity and specificity of the penicillin skin test. The sensitivity is just about 31% as you can see, but the range, quite long, from 19% to 46%. The specificity is 96.8%. And the range from 94% to 98%. It is a good test, the penicillin allergy skin test, but in the U.S., we do not have access to full testing and, the recent info is that we do not have to do full testing. I want to talk about when we do full testing. This is a study published in 2019 where — it was part of potentially getting us in America the full penicillin allergy skin testing kit. Done at a multi site in the U.S. and there were 63 positive subjects.

One thing most useful to see come up positive skin test result, the number of subjects in the second column, the percent of those with a positive skin test, and the third column, with a history of penicillin allergy out of the whole group. What we can see is if we only had PRE-PEN, we would not be able to pick up all the true positives. It really only picked up 3% of those with a positive skin test and 0.4% of the allergies in this full cohort. What we need to do if we think someone is allergic and skin test is to skin test as many reagents as possible. This mixture is difficult to make, but the MDM only picks up 38%. Even though it was the minor determinant in this study, it was more than the major determinant. What I want to point out is, we do skin test with ampicillin. Amoxicillin is not sterile, but we can skin test with Ampicillin , hoping we pick up these people, they were positive to both MDM and amoxicillin. 13% of the positive subjects, 21% with a positive skin test result and 3% with allergies. This shows when we are going to skin test we should try with as many reagents as we can get our hands on. And the importance of making a minor determinant mixture or skin testing with an amino penicillin, Ampicillin. I want to point out that right now, our U.S. hospitals largely do not have access to penicillin skin testing. Using methods of direct challenge, test doses, will be a useful way to spread delabeling and best antibiotic use into acute settings like emergency rooms and hospitals.

This is a survey we did in 2020 of 129 sites. You can see these are the ones offering penicillin skin testing. All hospitals, under half of them had penicillin skin testing. They had antibiotic stewardship programs. It does seem even antibiotic stewardship savvy hospitals did not have access to penicillin skin testing. It was even lower at community hospitals, just 32% with access. We are not the only ones who can learn to skin test. Of the places with an insulin skin testing, allergy and immunology did the vast majority, but we have to encourage collaboration given the 32 million labeled patients, so our infectious disease colleagues, pharmacists and nurses can learn to do penicillin skin testing when necessary. 14% was infectious diseases, 12% is pharmacists. Some states do not let pharmacists do skin testing. Nurses do lots of testing in allergy clinics. And pediatrics, special testing is another one. Who needs penicillin allergy testing? Adults should consider going to direct challenge. This is data from 2018 that had 3299 adult and children patients, and immediate onset positives as you can see is just 1.3% and delayed onset positive was just 3.9%. A lot of these were allergist-based studies. If an allergist says you are safe for direct challenge, you are. I also use this 4% because I think everyone should know that we clear immediately in our clinics, to present a 4% of people will have delayed onset positive if not now, in the next 24 to 48 hours. This was a fantastic single site randomized controlled trial published in 2019 where it looked at just penicillin allergy labeled patient and those they identified as low risk, 159. Those 159 were randomized to getting a skin test or graded challenge.

If you choose low-risk people, you will delabel more, 96%, with a graded challenge. If you choose to skin test, 88% were delabeled. If you think somebody is low risk, we should not do the skin testing because it performs worse in low pretest probability patients. In low risk patients, going to direct challenge is the best thing. There was recently also a multinational, randomized controlled trial set up as a non-inferiority study using a clinical decision rule called PEN-FAST. Scores less than 3, they ended up randomizing 382 low risk patients to getting either skin testing followed by a challenge or a direct challenge and they found these groups were so low risk, just 59% of the screen came it, 86% eligible. ONCE they did this direct challenge, just one reaction in each group, zero point — 0.5%. The risk difference is not significant which means it met the threshold for noninferiority. Also total immune mediated adverse events, the direct challenge group had 9 and the skin test had 10 and the risk difference was not significant. In children we should be more aggressive about not skin testing because these are children and the data is better. This is an initial study were 94% of kids passed a direct challenge.

This was 818 patients out of Canada. One thing really novel about this, it took all comers from the kids of allergies to amoxicillin and they all got drug challenged without skin testing and 94% were not allergic. Since then, there have been 28 different studies, probably more. This was published in 2023 as a meta-analysis of 28 studies. I want to show the immediate or non-immediate and immediate. This sums risk of reactions across different studies. The studies are never the same, but it provides information I use clinically. When I think about your risk as a kid of having any reaction with direct challenge I like to use this number, 5.2%. Something like, across 28 studies, we can see there is a risk of 5.2% if there was a wreck — reaction either immediately or in the next 48 hours. And this is your risk of reaction in front of your face, less than 1%. Many studies and children across the world have shown there is safety in direct challenge. This is what we do, which I included because we do not update it with every paper out there, but we updated it in 2019 to bifurcate risk categories. Thinking about who was low and who was high so across our whole group everyone is doing the same thing and there is consistency in what is our skin test and what is our graded challenge. Our high risk group, patients with recent IgE reactions less than five years ago, cutaneous or systemic, those people will get skin testing to everything we have. We do not have MDM, but we do PRE-PEN, penicillin. The people on the left, we bill for skin testing because we cannot do the one step challenge of 60 minutes. On the right, the lower risk category, cutaneous reactions, non-IgE, unknown reactions, and these patients we do two step, 30 minute challenges and they get, we bill for just the challenge only. There is a note here. Just the allergy risk is about the reaction, but also about the host. I think about this all the time because we are a major referral center.

Patients come to us before a long transplant, a valve, or they are pregnant. I consider these high-risk patients and I skin test them. It gives us and the patient reassurance because they are higher risk. There have been prediction models used to distinguish high versus low risk. Instead of just saying this is my clinical experience, to say it is high or low, there have been large studies that use data to say this is high risk and this is not this is from a review article in 2021 that I put together. I was trying to list out the common different prediction models published. Trubiano is the one we just reviewed. What are the consistent risks of high-risk? A history of anaphylaxis is consistent across all studies. You have to ask about anaphylaxis. The other is elapsed time since reaction before evaluation. I use these in many ways. I consider that my colleagues should ask about anaphylaxis in the time since reaction for risk stratification. Those are the two most important factors. We should also use them in our own internal risk stratification. Patient withs anaphylaxis or recent reactions are the ones we should be skin testing. Whereas the others we may not need to skin test. I want to review more about the PEN-FAST role. We might be asked to lead it for different groups, collaborative hospitals. It is catchy and easy to use. Part of me loves it, so I do want to tell you about it. Fast stands for five years since reaction or less, anaphylaxis or angioedema, severe cutaneous adverse reaction, and treatment required for reaction. In PEN-FAST, you get numbers of different points for these things, you add them and can decide what to use as your cut off. The authors propose to cut off of less than three should be low risk. I think it depends who we are working with. I recently worked with dentists and they would like to use PEN-FASTs, if you have any points for PEN-FASTs, you should go to analogy is but if lower, the dentist can deal with it. Five Points is five years or lessons reaction. It is really the time since reaction has been the predictor.

Anaphylaxis or angioedema. If we are asking patients this, they need to know how to discuss this with patients. Anaphylaxis is a technical term. Our patients do not necessarily know it. Did you have hives and wheezing? That is anaphylaxis. Severe cutaneous adverse reaction, this is a contraindication to challenge. Though it is nicer to have this S listed here, it might be harmful in our discussions with our colleagues because we want them to identify severe cutaneous adverse reactions, but do not want them to think about challenging it and you only get 2 points so I like to think of it as an exclusion to challenge and someone who needs to see allergy immunology or dermatology. Finally, treatment required. Something like antihistamines or epinephrine required. We found in studies in the U.S., it is more seeking medical attention, the emergency room might be a better factor than receiving medicines. A few caveats. It performs well at the extremes. We can tell somebody who is really high-risk and somebody really low risk. Somebody in the middle is challenging. We should think about what we recommend our colleagues use for PEN-FAST, if they are going to use it, what they should use as a cut off. We do need a higher sensitivity tool in that it picks up just 20% of positives. Like I mentioned, SCAR is only a 2, but is a contraindication. So far it does not work with children. There have been no studies in diverse patients. I will present this study in 2024, with Mayo Clinic and Mass General data, a production model. I present this as a warning about adoption of PEN-FAST before it is ready for our patients. PEN-FAST performed along this line. This line is when a test is just as good as flipping a coin, so not so good. We were able to make a better prediction model, this one in the yellow-orange. This one was using machine learning. It is useful to recognize maybe data-driven prediction models are going to outperform our own clinical judgment which can sometimes be random, but not ready for prime time. I wanted to show you, our best model, the orange one, we were able to see new factors requiring medical attention less than one year since the reaction and hives were drivers of having a confirmed allergy. The way you could see there were drivers, I look at hives. You can see the blues and pinks here, shows you it is a driver and requires medical attention. It is really split. Those are factors we found important in our own data. I would like to draw your attention to this 1:1:1 criteria which was a European criteria for hives. Hives have been underpowered in these prediction model studies. We do not know necessarily high-risk hives versus low risk hives. One study said if your hives appear to follow this 1:1:1 criteria, they might be higher risk. Moving on to key populations, these are key populations I would love to introduce to you as the idea we need to spread penicillin allergy DeLillo billing — delabeling. This blue shows places we do not do delabeling. There are different colors by how much we are doing them. We have outpatient allergy clinics, doing the most penicillin allergy delabeling. We have a lot of work to do. Like I mentioned before, surgery is an area of performance — importance.

If you have a penicillin allergy and they want to use cefazolin, one of the best reasons to use it is to get rid of the penicillin allergy label. All of these others are recommended often as well. It is not complicated as much anymore because this study showed a lower risk of cross-reactivity. The risk was less than 1%, which is often considered largely noise. There is a difference if you self-report a penicillin allergy, 0.6%. But if confirmed, it is 3%. That could be cross-reactivity or dual allergy, like multiple drug allergy. I want to move to the consensus-based statement that is useful for thinking about cefazolin. We suggest for patients with an unverified non-anaphylactic penicillin allergy, a cephalosporin can be administered without testing or additional percussions. The strength of the recommendation is conditional and the certainty of evidence is moderate. For patients with a history of anaphylaxis to penicillin, a nonprofit cephalosporin can be administered. Cefazolin is different than penicillin, you do not need testing even with a history of anaphylaxis. It is amazing new news for anesthesia colleagues. It will take a while to get the speed to have confidence in this conditional recommendation. I still prefer a drug challenge if there is time to do it preoperatively. We have done a number of studies where we found if you remove the penicillin allergy label before surgery, 100% almost of the patients get cefazolin. But if you tell them it is OK to use cefazolin they might not use it. That was this group. You can improve cefazolin use 27 fold if you remove the penicillin allergy label before. But if you tell them they can use it, we did a study where it was just two-fold. It requires work to get up to speed to encourage cefazolin use in penicillin allergy. I want to show you this best practice alert, another way to encourage referrals of penicillin allergy patients before surgery. This was used by University Iowa before orthopedic surgery.

To move to immunosuppressed populations it is clear these people will use antibiotics and 40% of days had antibiotic exposure, neutropenic fever. Studies have shown we should be proactively assessing immunosuppressed patients. This is one study of just 59 cancer patients and looking after antibiotic testing and showing we can prove the change in antibiotics if we do testing versus not. This is a pretesting period, a narrow spectrum. It increases from 13.9%, 14 point 8% before, to 33.3 percent after and looking at restricted antibiotics, the ones we want to decrease if you test immunosuppressed cancer patients, from 60.5% — A few more populations, older adults. My parents would be offended by the little man with the cane. Older adults we think of as patients accessing health care more often, more likely to have immunosuppression and multiple medicines. The drug allergy labels increase with age. Also a higher prevalence of infections. Adverse reactions can have more complications for patients when older. We did a study looking at older adults and drug allergy evaluations and were able to delabel 96% of drug allergies. This is the total evaluations, 486. 281 were penicillin, the remainder were not. This bar were all the people delabeled. And these are immediate or delayed reactions. The big picture is we should be delabeling our older adults. Finally I would like to move to how we improve effectiveness of delabeling. There are many things we can do to improve the effectiveness of penicillin allergy evaluation delabeling.

We have to think globally and locally as far as hospitals are concerned. We have to increase uptake. Sometimes we go to the hospital and the patient is not interested in evaluation. We have to increase knowledge and uptake. We have to correct documentation. We have the tools to correct our documentation, but we have to spread that. Even those with family history of allergy, or sometimes I go to evaluate someone and they say, I am not sure if it is me or my twin sister. We have to encourage others so we can do testing. After testing, we have to use beta-lactams. Maybe after a delabeling the patient or clinicians are still nervous about using beta-lactam s. We have to understand the barriers to encourage beta-lactam use. Once we delabel, unfortunately the pesky label comes back. We have to figure out how to prevent relabeling. This is an interesting prevention of a best practice alert from University of Texas set — southwestern. To make sure we do not reenter a penicillin allergy after it was purposefully removed. They had to create a system to catch it. This says an amoxicillin challenge with no reaction was previously documented and penicillin allergy was added. Please review. It catches you and you say, oh, this is not an allergy I should add back without talking to the patient. Sometimes we are adding back allergies because of epic care. These are things important when thinking about the patient in front of us and our communities.

Many barriers exist to penicillin allergy delabeling. They found reluctance to discuss, an abundance of other antibiotics, racially and ethnically minority eyes — minoritized people deterred by past treatment, clinicians concerned about harm, and clinician concerned about clinic operational barriers. And there were facilitators, patients were interested and clinicians wanted to use safe and effective antibiotics and improve their ability to do delabeling discussions. This is what we learned in primary cares in Boston. These are quotes I find interesting. A clinician saying, why don’t we make this approachable, something we consider normal? We discuss safe sex with adolescents. It is something you should just do. If someone has a penicillin allergy label we should also address this because we will be encouraging colleagues to also address it. Finally, inpatient qualitative study about clinicians and their barriers shown in this dark red arrow. The little arrow, all clinicians in the hospital think it is important. But they do not have confidence in their skills, or worried about hurting patients, there is no ownership, competing demands. We are up against a lot to spread penicillin — penicillin allergy delabeling. Here are all the concerns. We have to think globally about how to set up our colleagues and ourselves for success, thinking about training and education, the electronic health record, our health systems, innovations and research policy changes and resources to do testing. Thank you so much for your attention today. I am happy to take questions with our remaining time.

Lynda: Thank you, Dr. Blumenthal. Really appreciate this thorough presentation. I have questions from the audience. Can a history of a skin rash be — when can a history of a skin rash be considered benign versus something more severe or at risk for anaphylaxis?

Dr. Blumenthal: Great question. We should consider it almost by default. Was it hives or non-hives, and an adverse reaction or not? If it is a rash that did not involve the mucosal space or organs, skin did not peel off, not a severe cutaneous reaction probably. Hives versus not I use the same definition of hives. I ask if it is racy, — if it is itchy, raised, disappear in a few hours, or slow-moving. If it is slow-moving, I would consider benign. If it is robust urticaria, this 1:1:1 criterion is that the rash comes on within an hour, it receives — recedes quickly, it appears after a dose. Those are higher risk hives.

Lynda: The same person — I cannot read my own handwriting. Does the classification — are teenagers considered adults or children for the purposes of dealing with this?

Dr. Blumenthal: Good question. You can consider them probably with children because they were labeled as very young children and are still pretty close to the. — that. If the reaction was more recent, within a few years, I would test them more along adult guidance. I would consider them children. Three in four children are labeled before age three with a penicillin allergy. Most of this is early on, probably misdiagnosis for a viral rash.

Lynda: are patients with urticaria more likely to react to antibiotics resulting in say a rash? Many PCPs will label this as an allergy.

Dr. Blumenthal: If the patient has underlying urticaria, it is important to test all the medicines. Potentially these are added to their allergy list when they had chronic urticaria that had nothing to do with the medicines. Chronic urticaria patients with infections are likely to flare with chronic urticaria, not that the drug is causing a problem. We often will get patients into remission with chronic hives. When stable we would challenge to delabel different drug allergies at that time.

Lynda: Somebody asked, the first question I asked you about history of skin rash, would it make any difference if it was amoxicillin versus penicillin?

Dr. Blumenthal: No. The reason why sometimes we are really interested in the difference between, was your reaction to amoxicillin versus penicillin, is actually because some people are allergic to amino penicillins, like Ampicillin and amoxicillin which share a cross chain and has cross-reactivity to cephalosporin, those four. Sometimes it is important to know what penicillin it was for that purpose. Also, you could be cross allergic to Piperacillin. You want to rule out a severe cutaneous reaction and distinguish between hives and benign cutaneous eruptions.

Lynda: Is there testing for other types of antibiotics?

Dr. Blumenthal: Our skin testing is not great in that we can do skin testing for immediate reactions from many drugs using the nonirritating concentration, when you put it on the skin it does not cause a flayer the way of food allergy would. What we know is, if just the penicillin is validated and some of the others are pretty good like cephalosporin but it is often a drug challenge we need to do area we need to know whether they tolerate it. And the skin test cannot do that without clear properties every we do not have that for any other drug.

Lynda: Somebody asked, what is considered a severe cutaneous adverse reaction? I was wondering because my son, when he was little, he had ampicillin or amoxicillin and had a hive on his back that was the size of his back. When you are explaining that I was thinking, I wonder what that was.

Dr. Blumenthal: A severe cutaneous adverse reaction, it is the acronym SCAR. The biggest is Stevens Johnson syndrome, a rash that involves new membranes, inside the mouth and eyes, or another, when they heal, the skin almost falls off, not just fine peeling, it falls off and dress syndrome where there is organ involvement like the liver or kidney are involved and those are the common ones we have to think about. Sometimes these benign rashes can be pretty ugly for the patient and severe, impactful. That can impact delabeling, too. I have patients that technically had a benign rash, but they had to take steroids, antibiotics, antihistamines, they missed work. We have to meet our patients halfway because some people, regardless how benign it is, do not want to do it again. We have to talk about risks and benefits. Maybe there is an antibiotic need, you are using things more likely to cause C. diff or not treat the infection well. Risk,, maybe try to delabel again on a Friday when you do not have something important on the weekend.

Lynda: When referring to older adults, do you have an age in mind?

Dr. Blumenthal: 65 and up, the welcome to Medicare population. High level of delabeling. I would love to have something that the welcome to Medicare physical exam says, you have these three allergy labels, let’s get that evaluated.

Lynda: We have a lot of school nurses in the audience traditionally for these webinars. What if they have a student who has a penicillin allergy or amoxicillin allergy, and then they are older, go into adulthood, like my son. I would have to ask him if he ever got delabeled. Would you recommend if someone was labeled with one of these allergies as a child to consider getting tested for delabeling?

Dr. Blumenthal: Yes if I were a school nurse and had to give a kid an antibiotic that was not amoxicillin or cap flex keflex, I would pass along the information that once you have an allergy, it does not always stay. And there are adverse circumstances to not. If they are using sulfa or other antibiotics, maybe they are doing it because of the allergy label. May be the family and pediatrician have no idea that we can evaluate penicillin allergy and try it again because those are the best medicines for most pediatric infections.

Lynda: it is4:59. — 4:59. Thank you for being here. We really learned a lot today. Our next webinar, atopic dermatitis on skin of color, with Dr. Kelly Maples. I hope you can join us for that. You will be receiving an Email in a few days with supplemental information about medicine, allergy and delabeling of penicillin allergy. Thank you for being here today and joining us Allergy & Asthma Network at Allergy & Asthma Network. Hope you will be back. Thank you, everybody.