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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Transcript:ย 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:ย Hello, thanks for joining us.ย I am Lynda Mitchell, CEO ofย Allergy & Asthma Network.ย Welcome to this afternoon’sย webinar.ย I am pleased to introduce Dr.ย Kimberly Blumenthal as aย speaker.ย We have a few housekeepingย items to go over before weย start.ย First, all participants will beย on mute.ย We will be recording thisย webinar and will post it on ourย website within 24 hours.ย You can find all recordedย webinars on our website, ourย homepage,ย allergyasthmanetwork.org andย scroll down.ย You will see recordings listedย there.ย The webinar will be about oneย hour in length, including timeย for questions and answers.ย We will try to get to as manyย questions as we can, but youย can put your questions in atย any time.ย We have people monitoring theย questions box and if you haveย any other technical issues toย ask about you can either talkย about it in the chat or postedย in the Q&A — post it in theย Q&A .ย We do these in partnership withย the American College of asthma,ย allergy and immunology.ย The ACAAI offer CMA’s forย physicians — CME’s forย physicians.ย All attendees will be offered aย certificate of attendance.ย No other continuing educationย credit is provided.ย A few days after the webinarย you will receive an Email wasย supplemental information aboutย the topic and a link toย download the certificate if youย missed the webinar today.ย We will try to add it in theย chat.

Today’s topic is drug allergy,ย the importance of proactivelyย addressing and delabelingย antibiotic allergy.ย With the rise of drug-resistantย organisms, proactive evaluationย and delabeling of inaccurateย antibiotic allergies is a keyย component of antibioticย stewardship and qualityย improvement.ย Unverified penicillin allergiesย can have adverse consequencesย for public and individualย health.ย The goal of proactiveย penicillin allergy is to removeย the label if the allergy isย found to be untrue.ย It is my pleasure to introduceย our speaker, Dr. Kimberlyย Blumenthal, anย Allergist/Immunologist andย clinical researcher at Massย General Hospital and associateย professor at Harvard Medicalย School.ย She is the Co-Director of theย Clinical Epidemiology Researchย Center and Director of Researchย in the Center for Drug andย Vaccine Allergy.ย Dr. Blumenthal performs drug andย vaccine allergy research and isย internationally recognized forย identifying the morbidity andย mortality associated withย unverified penicillin allergiesย and creating innovativeย approaches to the evaluation ofย penicillin and cephalosporinย antibiotic allergies in diverseย patient settings.ย Thank you for being here today,ย Dr. Blumenthal. I will turn itย over to you.

Dr. Blumenthal:ย Thank you so much for havingย me.ย I will share my screen.ย I will start with theย disclosure that I have doneย research for Thermo Fisherย Scientific related toย penicillin allergy as well asย some of the up-to-date sectionsย related to the topic today areaย our learning objectives are toย describe the importance ofย proactive penicillin allergyย evaluation and delabeling, toย explain how to perform aย penicillin allergy evaluationย and identify populations mostย at risk of an unverifiedย penicillin allergy label.ย I am excited to talk about thisย topic which is near and dear toย my heart and we will start withย the idea of what is aย penicillin allergy label andย why we care.ย About 10% of the populationย reports and allergy toย penicillin.ย This means 32 million U.S.ย adults.ย Maybe not as common as in myย waiting room, but at least oneย in 10 patients have aย penicillin allergy label.ย The more our patients are sickย or interact with the healthย care system, this means theirย frequency of penicillin allergyย labels is even higher.ย Whereas it might be one in 10ย and a primary care waitingย room, and hospital it is 16%ย and in a rehab setting, all theย way up to 24%.ย This is — has been the same inย cancer patients and otherย patients frequently accessingย health care.ย What we have known for a whileย and what we are now challengedย to do in this next phase is toย verify pencillin allergy labelsย because we know just becauseย you have a pencillin allergyย label on your record does notย mean you have a true allergy.ย This was a meta-analysis fromย 2017 that looked at all theย studies of hospitalizedย patients, showing 95% of themย were not allergic.ย This is showing thoseย individuals were all skinย tested, 1391,ย and 95% were not accuratelyย labeled.ย There are penicillin allergyย patients labeled correctly, butย the majority are in accurate.ย This is so important forย improved patient care andย population health, publicย health because a penicillinย allergy label is associatedย with getting differentย antibiotics just because of theย allergy label, they are moreย broad spectrum, they can be,ย have a higher side effectย profiles, broader spectrum, soย you are at increased risk ofย MRSA or resistant organisms,ย and they could have surgeryย because they are not gettingย the most effective surgicalย site infection prophylaxisย drugs.

There is an increased risk ofย C.ย diff, increased risk ofย treatment failures, changingย frontline therapy and increasedย risk of adverse events and allย cause mortality.ย We know as allergist that notย all these labels are true andย we also know they have adverseย consequences.ย Finally we learned in 2017 thatย when we test patients forย penicillin allergy and followย their antibiotic useย afterwards, changes.ย We can as allergists and theย allergy community advocate forย penicillin allergy assessmentย to change the antibioticย choice.ย This is looking at 308ย evaluated patients in theย Kaiser system versus 1251 notย evaluated, a match cohortย study.ย They looked at those who hadย allergist evaluation andย matched those who did not andย looked at antibiotic use andย follow-up.ย Penicillin courses were 45%ย evaluated and only 2.5% notย evaluated.ย First generation cephalosporinย courses, prescribed outpatientย as well as inpatient went fromย evaluated as 32 .5% and notย evaluated at 20 point 5%.ย If we test patients, theirย antibiotic use changes, moreย penicillin.ย Because of these data, we haveย a lot of important — a lot ofย organization support for whatย we term penicillin allergyย delabeling.ย I like to say penicillinย allergy evaluation withย appropriate delabeling.ย Sometimes we confirm it,ย sometimes immediate or delayedย reactions, but the vastย majority are eligible forย delabeling or removing of theย penicillin allergy label in theย electronic record.ย We can see early on, there is aย CDC support.ย There is a choosing wiselyย campaign from the Board ofย internal medicine, do notย overuse.ย Antibiotic stewardshipย guidelines have encouragedย penicillin allergy as part ofย that.ย As we talked about in theย pregnant population, theย American College of abstractย tricks and gynecology —ย obstetrics and gynecology.ย IDSA supports proactiveย penicillin allergy evaluationย with appropriate delabeling.ย It is interesting to thinkย about why we would support aย certain delabeling and it isย because we can improve clinicalย care and because thisย intervention is not costly.ย We did a study in 2017 where weย looked at how costly it is toย perform a penicillin allergyย assessment.ย You can see differentย assumptions.ย We changed the clinician from aย medical doctor to nurseย practitioner, let’s look at theย skin test.

That can cost justย $42 of real work.ย This is time driven activityย cost, how much work it would beย for our clinic to do this.ย Not much how much we getย reimbursed, but how much itย would cost our clinic to doย penicillin allergy evaluationย with no skin evaluation.ย This $202 was worth — with anย MD.ย We have different assumptions.ย Will you test also withย Ampicillin?ย Do you have to mix things up,ย is it more costly to dispose ofย things?ย We varied everything up to theย highest situation.ย It was still only $369 forย penicillin allergy evaluation,ย which is not much work for usย to put into our clinic.ย This is what is called aย decision analysis that is usedย for most cost-effectivenessย studies.ย What I set out to do with myย colleagues was to look at, isย it more cost-effective to do aย penicillin allergy evaluationย or not?ย That is what A versus B is.ย Patient gets a penicillinย allergy test or does not.ย This was full skin testing.ย Each of these, a decision node,ย but each of the green circlesย are where probabilities get putย and that is how cost benefitย analyses are done.ย We could not do aย cost-effectiveness analysisย because it was a cost saving.ย You cannot studyย cost-effectiveness, you studyย cost savings.ย When we looked at theseย analyses, this shows manyย scenarios.ย The most fun thing to do hereย is, let’s look the left whereย we did skin testing and drugย challenge.ย If you can see, the circles andย triangles are inpatients andย outpatients.ย On the y axis, the bestย strategy.ย The number of simulations wereย testing saves money.ย All of them were above 50%.ย The majority were saving money.ย In almost every situation youย save money.ย How much money you save isย dependent on our health careย system, but at least $500 forย inpatient and $745 forย outpatients.ย In this one, two step drugย challenge and you save evenย more money because there is notย as much cost to work involvedย as skin testing.ย Way above 15%.ย Most of the time you’re at 75%.ย You save money to do penicillinย allergy evaluation inย inpatients, outpatients, acrossย Europe and the U.S.ย This is what I mentioned.ย If you’re really interested, Iย wrote my first grant.

On thisย this is the quadrant whereย cost-effectiveness analyses areย required.ย When you put in money to getย more health, which makes senseย — if you look at a newย diabetes medicine that isย expensive, how they decide toย cost it out.ย How much money will it cost,ย but how much more health will Iย get?ย This is where penicillinย allergy is, where you getย better at a meiotic —ย antibiotic choices, less C.ย diff, less treatmentย resistance, better health.ย It mostly is cost saving.ย We have to figure out how toย adopt this.ย How do we do penicillin allergyย evaluations?ย I want to start with the recentย practice parameters publishedย in 2022.ย These are consensus-basedย statements.ย The first is, we recommendย against testing in patientsย with a history inconsistentย with penicillin allergy like aย history of a headache or familyย history of penicillin allergy.ย The one-step amoxicillinย challenge can be offered toย patients were anxious orย request additional reassuranceย to accept the removal of aย penicillin allergy label.ย This was a strongย recommendation with moderateย certainty of evidence.ย A lot of people labeled may notย need to see an allergistย because they have a headache orย family history, but thoseย people should be automaticallyย delabeled.ย But if we can be helpful, weย can offer a one-stepย amoxicillin challenge forย reassurance.ย The second consensus statement,ย we recommend penicillin skinย testing for patients with aย history of anaphylaxis orย recent reaction suspected to beย IgE mediated.ย This evidence is not as strong.ย This is where a lot of our workย lies.ย In someone who recently had aย reaction, it sounds likeย something that is IgE.ย That is when we need to skinย test.

Our colleagues fromย infectious disease or pharmacyย might not be comfortable doingย skin test. These are theย patients.ย we absolutely need to see.ย A couple more penicillinย consensus statements.ย This is recommending againstย penicillin skin testing beforeย the amoxicillin challenge andย pediatric patients with aย history of benign cutaneousย reactions such as maculaย popular — maculopapular rashesย and urticarย ia.ย It is saying you can go rightย to the direct challenge.ย The second, we suggest theย direct challenge in adults withย histories of maculopapularย rashes and urticaria, we canย consider skipping skin testingย and going straight to a directย amoxicillin challenge.ย You can see in the pediatrics,ย the first line, strong andย moderate and in adults,ย conditional and low.ย Penicillin skin testing hasย been around for ages.ย It has enjoyed coming back inย America, 2009, when it came outย with FDA approval.ย Internationally, fullย penicillin allergy kits areย available.ย We do not have that in theย U.S..ย Some of these studies that showย sensitivity and specificity useย all reagents availableย internationally.ย This was an internationalย diagnostic study, meta-analysisย of 27 different studies lookingย at the sensitivity andย specificity of the penicillinย skin test. The sensitivity isย just about 31% as you can see,ย but the range, quite long, fromย 19% to 46%.ย The specificity is 96.8%.ย And the range from 94% to 98%.ย It is a good test, theย penicillin allergy skin test,ย but in the U.S., we do not haveย access to full testing and, theย recent info is that we do notย have to do full testing.ย I want to talk about when we doย full testing.ย This is a study published inย 2019 where — it was part ofย potentially getting us inย America the full penicillinย allergy skin testing kit.ย Done at a multi site in theย U.S.ย and there were 63 positiveย subjects.

One thing most useful to seeย come up positive skin testย result, the number of subjectsย in the second column, theย percent of those with aย positive skin test, and theย third column, with a history ofย penicillin allergy out of theย whole group.ย What we can see is if we onlyย had PRE-PEN, we would not beย able to pick up all the trueย positives.ย It really only picked up 3% ofย those with a positive skin testย and 0.4% of the allergies inย this full cohort.ย What we need to do if we thinkย someone is allergic and skinย test is to skin test as manyย reagents as possible.ย This mixture is difficult toย make, but the MDM only picks upย 38%.ย Even though it was the minorย determinant in this study, itย was more than the majorย determinant.ย What I want to point out is, weย do skin test with ampicillin.ย Amoxicillin is not sterile, butย we can skin test withย Ampicillin , hoping we pick upย these people, they wereย positive to both MDM andย amoxicillin.ย 13% of the positive subjects,ย 21% with a positive skin testย result and 3% with allergies.ย This shows when we are going toย skin test we should try with asย many reagents as we can get ourย hands on.ย And the importance of making aย minor determinant mixture orย skin testing with an aminoย penicillin, Ampicillin.ย I want to point out that rightย now, our U.S.ย hospitals largely do not haveย access to penicillin skinย testing.ย Using methods of directย challenge, test doses, will beย a useful way to spreadย delabeling and best antibioticย use into acute settings likeย emergency rooms and hospitals.

This is a survey we did in 2020ย of 129 sites.ย You can see these are the onesย offering penicillin skinย testing.ย All hospitals, under half ofย them had penicillin skinย testing.ย They had antibiotic stewardshipย programs. It does seem evenย antibiotic stewardship savvyย hospitals did not have accessย to penicillin skin testing.ย It was even lower at communityย hospitals, just 32% withย access.ย We are not the only ones whoย can learn to skin test. Of theย places with an insulin skinย testing, allergy and immunologyย did the vast majority, but weย have to encourage collaborationย given the 32 million labeledย patients, so our infectiousย disease colleagues, pharmacistsย and nurses can learn to doย penicillin skin testing whenย necessary.ย 14% was infectious diseases,ย 12% is pharmacists.ย Some states do not letย pharmacists do skin testing.ย Nurses do lots of testing inย allergy clinics.ย And pediatrics, special testingย is another one.ย Who needs penicillin allergyย testing?ย Adults should consider going toย direct challenge.ย This is data from 2018 that hadย 3299 adult and childrenย patients, and immediate onsetย positives as you can see isย just 1.3% and delayed onsetย positive was just 3.9%.ย A lot of these wereย allergist-based studies.ย If an allergist says you areย safe for direct challenge, youย are.ย I also use this 4% because Iย think everyone should know thatย we clear immediately in ourย clinics, to present a 4% ofย people will have delayed onsetย positive if not now, in theย next 24 to 48 hours.ย This was a fantastic singleย site randomized controlledย trial published in 2019 whereย it looked at just penicillinย allergy labeled patient andย those they identified as lowย risk, 159.ย Those 159 were randomized toย getting a skin test or gradedย challenge.

If you choose low-risk people,ย you will delabel more, 96%,ย with a graded challenge.ย If you choose to skin test, 88%ย were delabeled.ย If you think somebody is lowย risk, we should not do the skinย testing because it performsย worse in low pretestย probability patients.ย In low risk patients, going toย direct challenge is the bestย thing.ย There was recently also aย multinational, randomizedย controlled trial set up as aย non-inferiority study using aย clinical decision rule calledย PEN-FAST. Scores less than 3,ย they ended up randomizing 382ย low risk patients to gettingย either skin testing followed byย a challenge or a directย challenge and they found theseย groups were so low risk, justย 59% of the screen came it, 86%ย eligible.ย ONCE they did this directย challenge, just one reaction inย each group, zero point — 0.5%.ย The risk difference is notย significant which means it metย the threshold forย noninferiority.ย Also total immune mediatedย adverse events, the directย challenge group had 9 and theย skin test had 10 and the riskย difference was not significant.ย In children we should be moreย aggressive about not skinย testing because these areย children and the data isย better.ย This is an initial study wereย 94% of kids passed a directย challenge.

This was 818 patients out ofย Canada.ย One thing really novel aboutย this, it took all comers fromย the kids of allergies toย amoxicillin and they all gotย drug challenged without skinย testing and 94% were notย allergic.ย Since then, there have been 28ย different studies, probablyย more.ย This was published in 2023 as aย meta-analysis of 28 studies.ย I want to show the immediate orย non-immediate and immediate.ย This sums risk of reactionsย across different studies.ย The studies are never the same,ย but it provides information Iย use clinically.ย When I think about your risk asย a kid of having any reactionย with direct challenge I like toย use this number, 5.2%.ย Something like, across 28ย studies, we can see there is aย risk of 5.2% if there was aย wreck — reaction eitherย immediately or in the next 48ย hours.ย And this is your risk ofย reaction in front of your face,ย less than 1%.ย Many studies and childrenย across the world have shownย there is safety in directย challenge.ย This is what we do, which Iย included because we do notย update it with every paper outย there, but we updated it inย 2019 to bifurcate riskย categories.ย Thinking about who was low andย who was high so across ourย whole group everyone is doingย the same thing and there isย consistency in what is our skinย test and what is our gradedย challenge.ย Our high risk group, patientsย with recent IgE reactions lessย than five years ago, cutaneousย or systemic, those people willย get skin testing to everythingย we have.ย We do not have MDM, but we doย PRE-PEN, penicillin.ย The people on the left, we billย for skin testing because weย cannot do the one stepย challenge of 60 minutes.ย On the right, the lower riskย category, cutaneous reactions,ย non-IgE, unknown reactions, andย these patients we do two step,ย 30 minute challenges and theyย get, we bill for just theย challenge only.ย There is a note here.ย Just the allergy risk is aboutย the reaction, but also aboutย the host. I think about thisย all the time because we are aย major referral center.

Patients come to us before aย long transplant, a valve, orย they are pregnant.ย I consider these high-riskย patients and I skin test them.ย It gives us and the patientย reassurance because they areย higher risk.ย There have been predictionย models used to distinguish highย versus low risk.ย Instead of just saying this isย my clinical experience, to sayย it is high or low, there haveย been large studies that useย data to say this is high riskย and this is not this is from aย review article in 2021 that Iย put together.ย I was trying to list out theย common different predictionย models published.ย Trubiano is the one we justย reviewed.ย What are the consistent risksย of high-risk?ย A history of anaphylaxis isย consistent across all studies.ย You have to ask aboutย anaphylaxis.ย The other is elapsed time sinceย reaction before evaluation.ย I use these in many ways.ย I consider that my colleaguesย should ask about anaphylaxis inย the time since reaction forย risk stratification.ย Those are the two mostย important factors.ย We should also use them in ourย own internal riskย stratification.ย Patient withs anaphylaxis orย recent reactions are the onesย we should be skin testing.ย Whereas the others we may notย need to skin test. I want toย review more about the PEN-FASTย role.ย We might be asked to lead itย for different groups,ย collaborative hospitals.ย It is catchy and easy to use.ย Part of me loves it, so I doย want to tell you about it.ย Fast stands for five yearsย since reaction or less,ย anaphylaxis or angioedema,ย severe cutaneous adverseย reaction, and treatmentย required for reaction.ย In PEN-FAST, you get numbers ofย different points for theseย things, you add them and canย decide what to use as your cutย off.ย The authors propose to cut offย of less than three should beย low risk.ย I think it depends who we areย working with.ย I recently worked with dentistsย and they would like to useย PEN-FASTs, if you have anyย points for PEN-FASTs, youย should go to analogy is but ifย lower, the dentist can dealย with it.ย Five Points is five years orย lessons reaction.ย It is really the time sinceย reaction has been theย predictor.

Anaphylaxis or angioedema.ย If we are asking patients this,ย they need to know how toย discuss this with patients.ย Anaphylaxis is a technicalย term.ย Our patients do not necessarilyย know it.ย Did you have hives andย wheezing?ย That is anaphylaxis.ย Severe cutaneous adverseย reaction, this is aย contraindication to challenge.ย Though it is nicer to have thisย S listed here, it might beย harmful in our discussions withย our colleagues because we wantย them to identify severeย cutaneous adverse reactions,ย but do not want them to thinkย about challenging it and youย only get 2 points so I like toย think of it as an exclusion toย challenge and someone who needsย to see allergy immunology orย dermatology.ย Finally, treatment required.ย Something like antihistaminesย or epinephrine required.ย We found in studies in theย U.S., it is more seekingย medical attention, theย emergency room might be aย better factor than receivingย medicines.ย A few caveats.ย It performs well at theย extremes.ย We can tell somebody who isย really high-risk and somebodyย really low risk.ย Somebody in the middle isย challenging.ย We should think about what weย recommend our colleagues useย for PEN-FAST, if they are goingย to use it, what they should useย as a cut off.ย We do need a higher sensitivityย tool in that it picks up justย 20% of positives.ย Like I mentioned, SCAR is onlyย a 2, but is a contraindication.ย So far it does not work withย children.ย There have been no studies inย diverse patients.ย I will present this study inย 2024, with Mayo Clinic and Massย General data, a productionย model.ย I present this as a warningย about adoption of PEN-FASTย before it is ready for ourย patients.ย PEN-FAST performed along thisย line.ย This line is when a test isย just as good as flipping aย coin, so not so good.ย We were able to make a betterย prediction model, this one inย the yellow-orange.ย This one was using machineย learning.ย It is useful to recognize maybeย data-driven prediction modelsย are going to outperform our ownย clinical judgment which canย sometimes be random, but notย ready for prime time.ย I wanted to show you, our bestย model, the orange one, we wereย able to see new factorsย requiring medical attentionย less than one year since theย reaction and hives were driversย of having a confirmed allergy.ย The way you could see thereย were drivers, I look at hives.ย You can see the blues and pinksย here, shows you it is a driverย and requires medical attention.ย It is really split.ย Those are factors we foundย important in our own data.ย I would like to draw yourย attention to this 1:1:1ย criteria which was a Europeanย criteria for hives.ย Hives have been underpowered inย these prediction model studies.ย We do not know necessarilyย high-risk hives versus low riskย hives.ย One study said if your hivesย appear to follow this 1:1:1ย criteria, they might be higherย risk.ย Moving on to key populations,ย these are key populations Iย would love to introduce to youย as the idea we need to spreadย penicillin allergy DeLilloย billing — delabeling.ย This blue shows places we doย not do delabeling.ย There are different colors byย how much we are doing them.ย We have outpatient allergyย clinics, doing the mostย penicillin allergy delabeling.ย We have a lot of work to do.ย Like I mentioned before,ย surgery is an area ofย performance — importance.

If you have a penicillinย allergy and they want to useย cefazolin, one of the bestย reasons to use it is to get ridย of the penicillin allergyย label.ย All of these others areย recommended often as well.ย It is not complicated as muchย anymore because this studyย showed a lower risk ofย cross-reactivity.ย The risk was less than 1%,ย which is often consideredย largely noise.ย There is a difference if youย self-report a penicillinย allergy, 0.6%.ย But if confirmed, it is 3%.ย That could be cross-reactivityย or dual allergy, like multipleย drug allergy.ย I want to move to theย consensus-based statement thatย is useful for thinking aboutย cefazolin.ย We suggest for patients with anย unverified non-anaphylacticย penicillin allergy, aย cephalosporin can beย administered without testing orย additional percussions.ย The strength of theย recommendation is conditionalย and the certainty of evidenceย is moderate.ย For patients with a history ofย anaphylaxis to penicillin, aย nonprofit cephalosporin can beย administered.ย Cefazolin is different thanย penicillin, you do not needย testing even with a history ofย anaphylaxis.ย It is amazing new news forย anesthesia colleagues.ย It will take a while to get theย speed to have confidence inย this conditionalย recommendation.ย I still prefer a drug challengeย if there is time to do itย preoperatively.ย We have done a number ofย studies where we found if youย remove the penicillin allergyย label before surgery, 100%ย almost of the patients getย cefazolin.ย But if you tell them it is OKย to use cefazolin they might notย use it.ย That was this group.ย You can improve cefazolin useย 27 fold if you remove theย penicillin allergy labelย before.ย But if you tell them they canย use it, we did a study where itย was just two-fold.ย It requires work to get up toย speed to encourage cefazolinย use in penicillin allergy.ย I want to show you this bestย practice alert, another way toย encourage referrals ofย penicillin allergy patientsย before surgery.ย This was used by Universityย Iowa before orthopedic surgery.

To move to immunosuppressedย populations it is clear theseย people will use antibiotics andย 40% of days had antibioticย exposure, neutropenic fever.ย Studies have shown we should beย proactively assessingย immunosuppressed patients.ย This is one study of just 59ย cancer patients and lookingย after antibiotic testing andย showing we can prove the changeย in antibiotics if we do testingย versus not.ย This is a pretesting period, aย narrow spectrum.ย It increases from 13.9%, 14ย point 8% before, to 33.3ย percent after and looking atย restricted antibiotics, theย ones we want to decrease if youย test immunosuppressed cancerย patients, from 60.5% — A fewย more populations, older adults.ย My parents would be offended byย the little man with the cane.ย Older adults we think of asย patients accessing health careย more often, more likely to haveย immunosuppression and multipleย medicines.ย The drug allergy labelsย increase with age.ย Also a higher prevalence ofย infections.ย Adverse reactions can have moreย complications for patients whenย older.ย We did a study looking at olderย adults and drug allergyย evaluations and were able toย delabel 96% of drug allergies.ย This is the total evaluations,ย 486.ย 281 were penicillin, theย remainder were not.ย This bar were all the peopleย delabeled.ย And these are immediate orย delayed reactions.ย The big picture is we should beย delabeling our older adults.ย Finally I would like to move toย how we improve effectiveness ofย delabeling.ย There are many things we can doย to improve the effectiveness ofย penicillin allergy evaluationย delabeling.

We have to think globally andย locally as far as hospitals areย concerned.ย We have to increase uptake.ย Sometimes we go to the hospitalย and the patient is notย interested in evaluation.ย We have to increase knowledgeย and uptake.ย We have to correctย documentation.ย We have the tools to correctย our documentation, but we haveย to spread that.ย Even those with family historyย of allergy, or sometimes I goย to evaluate someone and theyย say, I am not sure if it is meย or my twin sister.ย We have to encourage others soย we can do testing.ย After testing, we have to useย beta-lactams. Maybe after aย delabeling the patient orย clinicians are still nervousย about using beta-lactam s.ย We have to understand theย barriers to encourageย beta-lactam use.ย Once we delabel, unfortunatelyย the pesky label comes back.ย We have to figure out how toย prevent relabeling.ย This is an interestingย prevention of a best practiceย alert from University of Texasย set — southwestern.ย To make sure we do not reenterย a penicillin allergy after itย was purposefully removed.ย They had to create a system toย catch it.ย This says an amoxicillinย challenge with no reaction wasย previously documented andย penicillin allergy was added.ย Please review.ย It catches you and you say, oh,ย this is not an allergy I shouldย add back without talking to theย patient.ย Sometimes we are adding backย allergies because of epic care.ย These are things important whenย thinking about the patient inย front of us and ourย communities.

Many barriers exist toย penicillin allergy delabeling.ย They found reluctance toย discuss, an abundance of otherย antibiotics, racially andย ethnically minority eyes —ย minoritized people deterred byย past treatment, cliniciansย concerned about harm, andย clinician concerned aboutย clinic operational barriers.ย And there were facilitators,ย patients were interested andย clinicians wanted to use safeย and effective antibiotics andย improve their ability to doย delabeling discussions.ย This is what we learned inย primary cares in Boston.ย These are quotes I findย interesting.ย A clinician saying, why don’tย we make this approachable,ย something we consider normal?ย We discuss safe sex withย adolescents.ย It is something you should justย do.ย If someone has a penicillinย allergy label we should alsoย address this because we will beย encouraging colleagues to alsoย address it.ย Finally, inpatient qualitativeย study about clinicians andย their barriers shown in thisย dark red arrow.ย The little arrow, allย clinicians in the hospitalย think it is important.ย But they do not have confidenceย in their skills, or worriedย about hurting patients, thereย is no ownership, competingย demands.ย We are up against a lot toย spread penicillin — penicillinย allergy delabeling.ย Here are all the concerns.ย We have to think globally aboutย how to set up our colleaguesย and ourselves for success,ย thinking about training andย education, the electronicย health record, our healthย systems, innovations andย research policy changes andย resources to do testing.ย Thank you so much for yourย attention today.ย I am happy to take questionsย with our remaining time.

Lynda:ย Thank you, Dr. Blumenthal.ย Really appreciate this thoroughย presentation.ย I have questions from theย audience.ย Can a history of a skin rash beย — when can a history of a skinย rash be considered benignย versus something more severe orย at risk for anaphylaxis?

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

Lynda:ย The same person — I cannotย read my own handwriting.ย Does the classification — areย teenagers considered adults orย children for the purposes ofย dealing with this?

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

Lynda:ย are patients with urticariaย more likely to react toย antibiotics resulting in say aย rash?ย Many PCPs will label this as anย allergy.

Dr. Blumenthal:ย If the patient has underlyingย urticaria, it is important toย test all the medicines.ย Potentially these are added toย their allergy list when theyย had chronic urticaria that hadย nothing to do with theย medicines.ย Chronic urticaria patients withย infections are likely to flareย with chronic urticaria, notย that the drug is causing aย problem.ย We often will get patients intoย remission with chronic hives.ย When stable we would challengeย to delabel different drugย allergies at that time.

Lynda:ย Somebody asked, the firstย question I asked you aboutย history of skin rash, would itย make any difference if it wasย amoxicillin versus penicillin?

Dr. Blumenthal:ย No.ย The reason why sometimes we areย really interested in theย difference between, was yourย reaction to amoxicillin versusย penicillin, is actually becauseย some people are allergic toย amino penicillins, likeย Ampicillin and amoxicillinย which share a cross chain andย has cross-reactivity toย cephalosporin, those four.ย Sometimes it is important toย know what penicillin it was forย that purpose.ย Also, you could be crossย allergic to Piperacillin.ย You want to rule out a severeย cutaneous reaction andย distinguish between hives andย benign cutaneous eruptions.

Lynda:ย Is there testing for otherย types of antibiotics?

Dr. Blumenthal:ย Our skin testing is not greatย in that we can do skin testingย for immediate reactions fromย many drugs using theย nonirritating concentration,ย when you put it on the skin itย does not cause a flayer the wayย of food allergy would.ย What we know is, if just theย penicillin is validated andย some of the others are prettyย goodย like cephalosporin but it isย often a drug challenge we needย to do area we need to knowย whether they tolerate it.ย And the skin test cannot doย that without clear propertiesย every we do not have that forย any other drug.

Lynda:ย Somebody asked, what isย considered a severe cutaneousย adverse reaction?ย I was wondering because my son,ย when he was little, he hadย ampicillin or amoxicillin andย had a hive on his back that wasย the size of his back.ย When you are explaining that Iย was thinking, I wonder whatย that was.

Dr. Blumenthal:ย A severe cutaneous adverseย reaction, it is the acronymย SCAR.ย The biggest is Stevens Johnsonย syndrome, a rash that involvesย new membranes, inside the mouthย and eyes, or another, when theyย heal, the skin almost fallsย off, not just fine peeling, itย falls off and dress syndromeย where there is organย involvement like the liver orย kidney are involved and thoseย are the common ones we have toย think about.ย Sometimes these benign rashesย can be pretty ugly for theย patient and severe, impactful.ย That can impact delabeling,ย too.ย I have patients thatย technically had a benign rash,ย but they had to take steroids,ย antibiotics, antihistamines,ย they missed work.ย We have to meet our patientsย halfway because some people,ย regardless how benign it is, doย not want to do it again.ย We have to talk about risks andย benefits.ย Maybe there is an antibioticย need, you are using things moreย likely to cause C.ย diff or not treat the infectionย well.ย Risk,, maybe try to delabelย again on a Friday when you doย not have something important onย the weekend.

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

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

Lynda:ย We have a lot of school nursesย in the audience traditionallyย for these webinars.ย What if they have a student whoย has a penicillin allergy orย amoxicillin allergy, and thenย they are older, go intoย adulthood, like my son.ย I would have to ask him if heย ever got delabeled.ย Would you recommend if someoneย was labeled with one of theseย allergies as a child toย consider getting tested forย delabeling?

Dr. Blumenthal:ย Yes if I were a school nurseย and had to give a kid anย antibiotic that was notย amoxicillin or cap flex keflex,ย I would pass along theย information that once you haveย an allergy, it does not alwaysย stay.ย And there are adverseย circumstances to not.ย If they are using sulfa orย other antibiotics, maybe theyย are doing it because of theย allergy label.ย May be the family andย pediatrician have no idea thatย we can evaluate penicillinย allergy and try it againย because those are the bestย medicines for most pediatricย infections.

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