Beta-lactam Antibiotic Allergies

While approximately 10% of US adults and children claim a penicillin allergy, only 1/20 with a reported allergy are truly allergic. Additionally, 80% of patients with IgE mediated penicillin allergy lose sensitivity after 10 years.

It is important to clarify and de-label patients to ensure they receive standard of care, avoid other adverse drug reactions and have a lowered risk of clinical failure. This practice also results in cost savings.

Amol Purandare, MD explains the de-labeling process in place at Children's Mercy and how to gain insight into what to prescribe to a patient with a penicillin allergy.
Beta-lactam Antibiotic Allergies
Featured Speaker:
Amol Purandare, MD
Amol Purandare, MD is an Assistant Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Clinical Assistant Professor of Pediatrics, University of Kansas School of Medicine. 

Learn more about Amol Purandare, MD
Transcription:
Beta-lactam Antibiotic Allergies

Melanie Cole (Host):  While approximately 10% of US adults and children claim a penicillin allergy, only one out of 20 with a reported allergy are truly allergic.  This is Pediatrics in Practice.  I’m Melanie Cole, and with me today, is Dr. Amol Purandare.  He’s a pediatric infectious disease specialist at Children’s Mercy Kansas City.  Dr. Purandare, this is such an interesting topic to me.  Let’s start with a little bit of the historical context behind antibiotic allergy and how this impacts us today.  

Amol Purandare, MD (Guest):  Beta lactam antibiotics include a few different groups including penicillins, cephalosporins, and carbapenems.  For the sake of today, I’ll really focus in on the penicillin class of antibiotics as these should be our go-to antibiotics in kids and that previously thought of 15 to 30% of cross-reactivity among those other groups of beta-lactam antibiotics has really been shown to be much lower than 1-2%.  So, it’s not really a factor when talking about beta-lactam antibiotics as much as we thought.  Focusing on the penicillin group, these really became widely used starting in the 1940’s, and soon after this happened, we really had the immediate reactions of, or reports of drug reactions happening soon after, and as you had mentioned in the intro, one in 10 of the US population has a penicillin label, and what that really means is 5 million children in the US currently are labeled as penicillin allergic, and what I find to be truly shocking about that is that three-fourths of children have this penicillin label placed on them before their third birthday, and what we’re seeing more and more is that one in 20 of people are really, truly allergic, not necessarily that 10% that we were seeing before.  When that happens, when we’re only seeing one in 20, this can be due to penicillin allergy being a side effect.  It can be due to a drug-induced rash, or it can be a drug-viral interaction or just inflammation from the underlying state.  A true hypersensitivity reaction or an IgE-mediated reaction that we think of when it comes to antibiotic allergies are actually quite rare.  We really see this in that small amount, that 1 in 20, and when you have these allergies, 80% of people that have these allergies will tend to lose them after 10 years of the initial allergy being reported. 

Host:  That is just fascinating to me, and as I was doing my research as well, tell us a little bit about the criteria that’s associated with that soft history.  At what point do you actually determine that a child is genuinely allergic?

Dr. Purandare:  This can always be a little tricky for general practice doctors, and even specialists to really come across and how to make this label, and so a big focus is really trying to understand what the allergy is, and so a lot of times when we see a child, and they have this allergy already placed on them from maybe a prior provider or this might have picked up from an emergency room, an ER, or an inpatient stay.  Sometimes, you just see that there’s a reaction—or the family just reports a reaction.  So, we really want to know, what kind of rash was it?  Was it just a –was it flat, morbilliform rash?  Did it itch?  Were there urticaria, and how spread out were they?  Was it just one or two, or was it full body, and then were there signs of angioedema or anaphylaxis?  Because if there’s full body hives; if there’s anaphylaxis, angioedema, that really makes it more concerning for an immediate IgE-mediated or true allergy.  The other thing that we want to know is if they had a severe reaction that might have happened further on.  So, were they inpatient and all of a sudden were described as having skin peeling or a Stevens-Johnson reaction  or something like a dress reaction where they were having a rash and they were showing signs on their bloodwork as well that they were having a delayed reaction.  That would be a severe reaction that would need to be characterized, and we typically don’t see those in day to day practice, but it’s something that we’d see in patients that are on prolonged antibiotics that might be an inpatient stay, and so once we get that clarification, that lets us determine what the next steps are.

Host:  So, do you think then that we need to clarify and de-label?  What are the health implications of that, and if we are, what are the process to follow as far as making sure that this is truly accurate?  
 
Dr. Purandare:  I really do think we need to clarify because as I’d indicated before, a true penicillin allergy is rare and likely far rarer than we even give credit to right now, and while there are other antibiotic options that we have, the penicillin antibiotics are still overall are safest from a side effect profile and are [the] most effective antibiotics in treating infections, and the reasons to clarify are really that we have risks geared towards our patients.  So, the risks to our patients are that you see over 35% of patients that have a label will get care that’s deviating from the standard of care.  They will also have three times higher risk of adverse drug reactions.  There’s an increased risk of clinical failure with other antibiotic classes, and you have an increased risk of resistant pathogens and infections of surgical sites and so on, and on top of that, all the health risks—there’s also the cost to the patient.  So, you’ll have prescriptions that can be up to 40% more expensive to families, and you can have inpatient stays if they have this label that can be 4000, 5000 dollars more expensive to families just because of that antibiotic label, and so, trying to make sure that we really clarify these for our families, is going to be a big help for their health and from a cost-saving endpoint to them.  

The process is—the first part is going to be clarifying the allergy, describing it, as I mentioned, and then figuring out was it a rash or was it something that might be more of a side effect that may—that they may tolerate the antibiotic if needed, and things like that can be diarrhea, vomiting, if they have any kind of nausea with it, or sometimes a lot what we see often is a family will say there’s a family history of drug allergy, and a lot of times those are things that—there really hasn’t been a true correlation ever made from a family history or not, and so after clarifying that allergy, you also want to know what was the time frame of this?  Was it the first time the child was given the antibiotic, or have they been on this antibiotic before?  Was it something that happened immediately where if it happened within the first 30 minutes or within a few hours, it’s probably a true allergy or an IgE-mediated allergy?  That would need to be looked at by a specialist or if it happened maybe day three or four, that could be a either an IgE-mediated or likely a drug-viral or late drug rash, and then if it happened later on, like day seven or you know, beyond, then that might be a delayed reaction, which may be safe for them to take the medication unless there is one of those severe T-cell findings that we had mentioned before, and so once you’ve gotten the time frame down, too, then the next steps would be figuring out do I need to refer this patient to be de-labeled or is it something I can do in the office?  So, as I mentioned, if it’s something like a side effect, like the diarrhea, abdominal pains, spitting up, vomiting or something like a family history, then, in your office you can take that label out, and it’s a lot of just talking with the family, letting them know that these are not true allergies, and they’re more side effects or intolerances—that the medicine is actually safe to give.  Then, the other thing that we would say from a delayed length standpoint is—what we often see is someone will come to us where they’ve been on an antibiotic—they have the label and then they went to a different place.  They went to—out of state.  They went to an urgent care, an ER, and they were given a penicillin antibiotic because it wasn’t in their chart, and they tolerated it just fine.  So, if that’s the case, in the office, you can remove that label right away, and then, if it’s something else, then I think at that time, referring them to a specialist that can de-label.  So, at Children’s Mercy, here, through infectious disease, we can do de-labeling or treat the allergy group then you can as well have them de-label.

Host:  Such a good point you make about parents, doctor, as you give us some of those guidelines for de-labeling very briefly, do you find that it’s difficult to convince parents whose children have soft histories to begin using penicillin again?  What would you like other providers to know about what to prescribe for patients with a true penicillin allergy and how to deal with the parents that say, “Oh no no, in my history, in my family history”—which you’ve already told us is not generally the case—how do they deal with the parents in that case? 

Dr. Purandare:  Sometimes it can be very difficult to talk to families about this, especially if the parent themselves has had a history of a severe IgE-mediated reaction, or they saw severe hives or this kind of head-to-toe urticaria that came about, and so it takes a lot of sitting down and really building rapport with the families and going through the steps.  When families are really hesitant, even though there’s this—maybe a history of a side effect or this family history, then I think it really helps you there kind of in the office or referring them to a specialist where they can do in office—by doing an oral challenge—observing, making sure the family knows there will be medications there too, if in case there was a severe reaction, they’d be able to reverse the severe reaction, and that way, it gives that peace of mind, I think, once you explain that there are risks, but the other medications out there can have equally just as many risks or can actually do more harm.  I find that families are pretty receptive to that and then if they are absolutely hesitant or in the meantime while we’re waiting to do testing with a specialist in your clinic, you might often wonder what do I give?  Through Children’s Mercy, we have a handy book that we’ve done through our antimicrobial search that can be accessed at childrensmercy.org, and it’s under our acute otitis media section where you can find our outpatient stewardship guide, and we have a lot of helpful recommendations for if you have a penicillin allergy, what to give instead.  

The other thing to kind of keep in mind is if there are any reactions or allergies in the past, try to see if a cephalosporin can be given in place.  While, again, cephalosporins for many of the infections are second line, if there’s a true allergy, those could be potentially considered in place as well, and then if there really is a concern, your friendly, neighborhood ID doc is always around to kind of field questions and will be happy to give recommendations in regard to what the next option would be.

Host:  Thank you so much, doctor, for joining us today.  It’s such an interesting topic and thank you for sharing your expertise.  This has been Pediatrics in Practice with Children’s Mercy Kansas City.  To refer your patient or for more information please visit childrensmercy.org to get connected with one of our providers.  Please remember to subscribe, rate, and review this podcast and all the other Children’s Mercy podcasts.  I’m Melanie Cole.