• 01 May 2018
  • 9 min
  • 01 May 2018
  • 9 min

Dhineli Perera interviews Professor Connie Katelaris about why labelling an individual with a ‘cephalosporin allergy’ is inaccurate. Read the full article in Australian Prescriber.

Transcript

Welcome to the Australian Prescriber Podcast. Australian Prescriber. Independent. Peer-reviewed and free.

I'm Dhineli Perera, your host for this episode, and it's a pleasure to be speaking to Professor Connie Katelaris. Connie writes about the misconceptions around ‘cephalosporin allergy’ labelling. Connie, welcome to the program.

Thank you Dhineli.

So, Connie, can we start with a bigger picture question, I guess. Can you tell us the importance of accurate and detailed allergy labelling? What are the consequences of blanket labelling like a cephalosporin allergy?

Well, there are many consequences, and they are both medical and economic. So when a person carries a label, a blanket label for a whole antibiotic class, it usually precludes them from having any of those prescribed, which necessitates prescription of second- and third-line antibiotics. These are almost always more expensive and often carry greater risk of side effects and certainly of promoting drug resistance eventually. We know now that there is no evidence that a person who is allergic to one cephalosporin must now avoid all cephalosporins. We know that cross reactivity among this class of drugs occurs very rarely in fact. And when it does it's usually due to a similarity between the side chains known as R1 or R2 rather than the central part of the molecule.

Right, OK, so can you tell us a little bit more about these side chains? I guess they're the culprit agents in these allergic reactions.

With the cephalosporins, which are closely related to penicillins, they are part of the family of drugs we call beta-lactam drugs and their central core is a beta-lactam ring. And traditionally with penicillins we've considered that the major moiety to which people develop allergy is the beta-lactam ring. Now with the cephalosporins we know that most people who stimulate an IgE or allergic antibody response to a cephalosporin do so recognising the side chain rather than the beta-lactam ring. So the different cephalosporins vary in the structure of that R1 side chain. So you can use one of the other cephalosporins with impunity because the IgE is directed to a specific side chain and not to the common central core.

OK, so a very common question received and asked by health professionals is what the cross reactivity is between cephalosporins and penicillins?

In reality we believe now that it is less than 1%. Early teaching suggested it was up to about 10% but when you consider that more than 90% of those who are labelled as being penicillin allergic aren't really allergic, or their IgE sensitivity has waned over time, or they were given one of the early-generation cephalosporins years ago where there was similarity in the R1 side chain, or perhaps in the early drugs there was some contamination in the cephalosporin by penicillin. So with all those factors removed the more modern data suggest that that cross reactivity rate is less than 1%.

Right, OK, and interestingly your article suggests that allergic reactions are more common with penicillins than with cephalsporins and this is basically due to their structure.

Yes, penicillins are far more reactive now. All these molecules are small molecules and are not seen by the immune system unless they are linked to a protein carrier. Now with penicillin that occurs when the beta-lactam ring opens up to form what we call penicilloyl and that binds to a lysine residue on various host proteins. So the penicillins are chemically reactive because there's a high degree of tension between the beta-lactam ring and the thiazolidine ring to which it is bound. On the other hand, the cephalosporin beta-lactam ring forms a much more stable structure with its neighbouring ring, which is a dihydrothiazine ring. So when the cephalosporin ring is disrupted it’s unstable and fragments rapidly, so not as available to the immune system to stimulate an allergic response. So that's why the penicillin is more reactive.

OK, so moving on to the tests. Blood tests and skin tests are some of the typical investigations that might be done to elucidate the nature of the allergy. But they come with their own advantages and limitations. Can you describe this a bit more for us?

Yes so, as you alluded to, there are two types of tests. There's the in vitro and the in vivo or skin testing. The in vitro tests are still not as reliable as the skin test. Quite frankly I don't do them. Skin tests are definitely more sensitive. There are some commercial extracts available for the penicillin moieties. They're quite expensive and you need authorisation to import and prescribe but they are available. And then for the cephalosporins we usually use the native molecule and dilute it appropriately

All right, so with challenge testing, what is it and when is it indicated? Is there a time that it shouldn't be undertaken?

OK, so I certainly consider challenge testing to be the current gold standard because there is no test that has a 100% sensitivity and specificity, although skin testing was very reliable. If an individual has negative skin tests, we would then proceed to a challenge with the culprit drug and we do that in a hospital setting. If the risk of the reaction is very low such that the history is very remote, one has the impression that it wasn't a terribly serious reaction, then it could be done in another suitable medical facility. We would never ever challenge a patient where there was strong suspicion that their original drug reaction was a severe cutaneous drug reaction such as Stevens-Johnson syndrome or TEN [toxic epidermal necrolysis]. Remember what we're looking at here are patients who had immediate hypersensitivity. We certainly wouldn't challenge a patient who has had a recent anaphylaxis but if there's a remote history of anaphylaxis that's not a contraindication as sensitivity does wane with time and, providing the skin tests were negative, we would do that. And the reason we would do this is that relabelling is such an important exercise because it allows that patient then to access cheaper and better drugs and, as I said in the beginning, it helps fight against, you know, the development of antibiotic resistance. S for me it's taking a proper history in the beginning. I would then weigh up the risk or the likelihood that we're going to find evidence of a true IgE-mediated hypersensitivity, submit that patient to the appropriate skin tests and then, if they're negative, I would submit them to an oral challenge.

So Connie, for health professionals that are at the coalface and perhaps don't have an expertise in allergy testing, what can we do to improve allergy documentation for patients?

I think the most important person is a person who first delivers the label of an allergy to that patient. We would urge them to take a full history, to document the actual drug, not just the family. Don't just say penicillins. Say whether it was Amoxicil or flucloxacillin. It's good to document what the drug was used for because obviously, if it was used in the context of a viral infection, this may not be an IgE-mediated reaction at all. To document other drugs that were being used simultaneously because there may be another drug that was more likely to have caused the reaction, and then to document whether anything was done to confirm that that drug was the culprit, such as withdrawing the drug and seeing prompt resolution. That careful, accurate, detailed documentation at the point of diagnosis is the most important tool.

Excellent. Well that's unfortunately all we've got time for for this episode. Thank you so much Connie.

My pleasure. Thank you Dhineli.

[Music]

Connie Katelaris’s full article is available online and, like our whole journal, it's free. The views of the hosts and guests on the podcast are their own and may not represent Australia Prescriber or NPS MedicineWise. I'm Dhineli Perera and thanks for joining us on the Australian Prescriber Podcast.