Cottage Health medical resident, Samantha Mathews, MD, explores the long held belief that patients who are allergic to Penicillin should avoid Cephalosporins and Carbapenems as well.
So this is a common topic that comes up a lot even in our current cpoe system our epic system every time you try and prescribe a patient any cephalosporin or carbapenem there’s always a warning that comes up if they have a penicillin allergy so that kind of prompted me to want to do this topic so why does this matter penicillin cephalosporins and carbapenems
Make up 30% of all the current antibiotics and that’s counting all the antibiotics not even counting the fact that they probably make up 50 or 60% of all the commonly used antibiotics and then for a lot of our infections that we’re treating including things like meningitis pneumonias things like that cephalosporins and carbapenems are often the treatment of choice
First-line treatment and if you’re withholding those because you’re worried about hypersensitivity then that might not be the best for the patient and then also just having to use all these different antibiotics such as like aztreonam or some of the other ones that we have to go to and we’re not allowed to use these other ones that can just promote more resistance
And more superbug infections so how did this all start pharmaceutical companies i hope there’s no pharmacists in the room who are gonna get offended by this but pharmaceutical companies were actually one of the main entities to blame back in 1980 we only had a few sips parnes available to us these were suppose all in cephalexin and safe ellison and then at this
Point the cross-reactivity was estimated to be five to ten percent and there were some estimates just from random like case reports and studies and just like kind of word of mouth that were estimated as high as 40 percent and what the pharmaceutical companies were doing is they were putting these percentages on their little paper that they have inside of all the
Antibiotic and so this was getting just propagated over and over and over again so the facts around penicillin allergies in general 10% of the alicia is going to report a penicillin allergy not necessarily anaphylaxis but it can be anything rash itching things like that and so before 1960 the way antibiotics were made in the lab was very very impure a lot of
The cephalosporins they were making where they were actually using the same fungi that they were using to make penicillin so they were all kind of having traces of different antibiotics in each one and so there were all these theories is it the beta-lactam ring that’s causing the allergy is it the side chains they didn’t quite know which was the culprit and then
There’s also certain patients who just happened to be allergic to multiple antibiotics and these patients were confounding the variables because you can’t they thought it was a cross reaction when it was actually an individual allergy to multiple antibiotics so here’s the example of the beta-lactam ring just as a quick view back to like oh chem as you can see the
Penicillin and the cephalosporin both have this beta-lactam ring and here’s the side chains so these are the similar side chains the two main culprits if you notice for cefalexin and penicillin they have almost an identical side chain with the nh two and then if you look at down below at amoxicillin and cefazolin they also have really similar side chain now if you
Compare this to looking at third and fourth generation cephalosporins to penicillin and amoxicillin there’s no similarities between their side chains completely different so we’ll go back to that in a minute when we talk about some of the studies but here’s just some of the history behind it the first cephalosporin we had was called syphilis in in 1968 and it was
Marketed to be used in penicillin allergic patients the problem was is in the lab where they were making the syphilis in they were using the same fungi as they were making the penicillins with so there were a lot of traces of penicillin contaminating they suffice out sefa thousand so there were all these allergies being reported by patients who are also allergic
To penicillin and this got propagated because of that and so the package insert was changed for syphilis and to reflect that there was a 10% cross-reactivity and that has been continued and continued with multiple cephalosporins now it’s just been continued to be propagated here’s an example of label and this is a current label of that’s actually on ceftriaxone
And this is a current label from 2017 years sorry 2016 they didn’t have a 2017 one on google but as you can see towards the bottom i should have highlighted this but towards the bottom it says serious acute hypersensitivity reactions may occur if you use this to the patient who has demonstrated allergy to penicillin so that is still the current warning that the
Pharmaceutical companies they’re putting out there so now let’s go to the research there’s been a couple more recent articles that i will talk about there was one in 2012 in the journal of emergency medicine and this talked about the use of cephalosporins and penicillin allergic patients and this was a huge literature review they actually reviewed the literature
All the way from 1960 until 2000 and like five and there was hundreds and hundreds of articles that they were looking at and case reports and throughout their entire review they averaged out that the one it was a 1% risk of cross reactivity they did find that there was one article that reported a 27% risk for cepheid rexel but cepheid repsol is a first generation
Cephalosporin that has similar side chain to amoxicillin so that could explain that here’s some more examples of articles there was an article in 1995 and the american academy of allergy asthma and immunology and they concluded there was no risk of cross reaction for the third and fourth generation cephalosporins there was another article in the investigational
Allergy clinical immunology journal in 2015 that showed the skin test and the oral challenges showed no cross reaction to second generation third generation or fourth generation but the important thing to note was the second generation cephalosporins they were looking at were all the ones that had different side chains at uc-davis in 1994 dr. key shyama published
A study that showed in vitro study actually showed reaction so i got my hands on this article and i looked to see what they were testing cuz it was just an in vitro study they weren’t actually using oral trials or anything like that and it turns out they were doing a skin test that was just showing some like that the patient was reacting to the beta-lactam ring
And they weren’t actually having a reaction to the cephalosporin they were just picking up some antibodies that were to the beta-lactam ring that was the same in the cephalosporins and the penicillins and then the medical letter 2012 showed there was a point 1 percent risk of reaction to first and second generations but they did not include identical sidechain
Cephalosporins dr. romano presented an article just recently in 2016 in current allergy and asthma report and this was a huge meta-analysis from 1966 to 2005 and they showed that there was a significant increase to first generation cephalosporins including stefan and cephalexin and these are both ones that had similar side chains but there was no increase to
The second generation or third generation for the ones that didn’t have similar side chains cephalosporin facts there’s no documented cases actually in the literature or in any study that show that there’s been cross reaction in patients two third or fourth generation however if you look at a rocephin label it still shows that there’s an increased risk of severe
Allergic reaction in these penicillin allergic patients same for the cept aerelon package it reports clear cross reactivity risk even though there’s never been a documented case ever in the literature so what is the truth about cephalosporins maybe the incidence is 1 to 3 percent for people just having baseline cephalosporin allergy for non penicillin allergic
Patients that’s just an individual allergy to cephalosporins on its own the incidence of anaphylaxis is very low in these less than 0.02 percent and i think the bottom line should be if people are allergic to amoxicillin you should avoid first and second generation cephalosporins that have the similar side chains such as cefalexin because we don’t actually know
What the incidence is and some studies reported at 10% some have reported it at 27% so that should be the only ones that should be avoided now let’s talk about carbapenems before we go to the overall conclusions there have been some studies because if you if you click on ordering meropenem or imipenem in the cpu i mean sorry in epic the same warning pops up as
It does for the cephalosporins and i just ordered one the other day and this morning definitely pops up i should have taken a screenshot okay but in 2006 romano looked at 112 patients and they did skin tests first and out of out of the all these patients only one patient had a reaction to the skin test then he tested all of these patients with a trial dose and
All of them including the person who had the reaction to the skin test tolerated the 500 milligram dose without any reaction he also did another study in 2007 with a separate population of 104 patients and again only one patient had the reaction to meropenem skin test and all the patients again also tolerated the trial dose here’s a couple more recent studies
That showed pretty similar outcomes one of them was clinical infectious diseases in 2015 patients who had a confirmed skin allergy test for penicillin because they didn’t want to just take all the patients that just report having a rash so they confirmed that they were actually allergic to penicillin and then they gave them carbapenems they started with the skin
Test as well in this study and then went to trial dose and all of them were fine except for a 1% reaction they had a rash dr. romano published another article in 2016 in current allergy and asthma report and he tested 211 patients who had a confirmed positive skin test to penicillin and none of them reacted to getting a trial dose of imipenem so what is the truth
About carbapenems the cross-reactivity to the skin test was 1% but if the patient’s tolerated the skin test there have been no reports of any allergic reactions when they’d be given full doses so the bottom line for this is if you can do a skin to great doing just to be safe especially in the nf lactic patients but if you can’t do a skin test start with the trial
Dose and see what happens research key findings we kind of already went through all this but the moral the story just looked from looking at all the research though overall cross-reactivity seems to be around 1% for both cephalosporins and carbapenems and it might not even be that high overall cross-reactivity rate with patients who definitely had confirmed skin
Test to penicillin was 2.5 percent overall in the literature if you average out all the different reports cross reactivity between penicillin and all third and fourth generations is negligible there was pretty much no reports of this and then if a patient has an allergy to amoxicillin or ampicillin you should avoid first then checking second generation cephalosporins
With dissimilar side chains because that was more seen in case reports and analyst i really like this slide this is actually one of the current us emily study books and i feel like it’s pretty accurate so they’re basically giving you a little cheat sheet and saying if the patient has an effective reaction to penicillin and you’re trying to figure out if you want
To give them a first generation cephalosporin it’s kind of plus or minus this is the plus would be if it’s if you’re gonna give them something that doesn’t have a similar side chain you probably can without any problems you want to avoid things like cefazolin cephalexin if they have a similar side chain same type of thing for the first and second generation it’s
Better just to avoid those medications there’s plenty of other cephalosporins you can give and then for all the other groups it’s perfectly fine to use cephalosporins so the bottom line you should be able to feel comfortable giving any of your patients any of the third or fourth generation cephalosporins and carbapenems even if they have documented penicillin
Allergy it would be safer to avoid the cephalosporins with identical side chains as i was saying and then if a patient does have a reaction it’s more likely that they just have allergy individual allergy to both penicillin and cephalosporin not across
Transcribed from video
Medical Mythbusters – Penicillin Allergy Cross-Reactivity By Cottage Health
