Cephalosporin allergy: Did your doctor make a mistake?

Were you told to avoid cephalosporin antibiotics because you have a penicillin allergy… and the two could cross react?

Or perhaps you ‘had an allergy’ because you had a reaction while taking the medication?

If any of these sound like you, you might have fallen victim to one of the biggest mistakes in medicine.

But don’t worry. I’ll show you how to fix it.

Cephalosporin antibiotics aren’t treated fairly when it comes to allergies:

  • Most people avoid cephalosporins due to cross reaction with a penicillin allergy (which, as you’ll see soon, is terrible advice)
  • Or you reacted while taking the medicine and were called allergic (which is usually not an allergy)

The problem: most of you are avoiding one of the most common classes of antibiotics WHEN YOU DON’T HAVE TO!

Hopefully this article will quickly clear up this medical mistake for you and will help you clear yourself of an unnecessary antibiotic allergy!

Who should read this article?

With this article, I’ve targeted a specific group of people.  You should read this article if you:

  • Were told to avoid cephalosporin antibiotics due to cross reactions with penicillins
  • Have a cephalosporin allergy and not a penicillin cross-reaction (you can jump to the cephalosporin allergy section.)
  • Want to find out whether you are allergic to cephalosporin antibiotics (you can jump down to the testing section.)
  • Are a medical provider, read this entire post! (this article is an evidence-based discussion that can guide you to improving your patient care)
  • Have any of your family or friends have penicillin or cephalosporin allergies, please read the summary at the end and then share this article with them.

For everyone else, if you want to stir up a little non-political controversy (although the medical profession has enjoyed the brief break in controversy) then re-post this original content and see what happens (If things get bad, you can always tag me in the article and I’ll show up to your defense!)

What is the medical mistake, exactly?

During medical training, healthcare providers teach penicillin and cephalosporin antibiotics are ‘cousins’ because they share a similar chemical composition (the R chain) and have about 10% chance of being cross-reactive.

This means that if you had a penicillin allergy, taking a cephalosporin had a 1 in 10 chance to cause a potentially life-threatening reaction!

Whew. Close call, right?


With a better understanding of the (10-20 year old!) literature it is closer to think of the penicillin and cephalosporin families as second or third cousins, twice removed (I don’t know anything about family trees, but I know these two medications are less related then Turk and JD.)

Evidence suggests that penicillins and the newer third generation cephalosporins are not 10% cross-reactive but closer to 0% (not a typo: 0%. Zero. Zip. Nada!)

Keep reading and I’ll explain it in more detail

Where did the 10% rule come from?

I… don’t know.

I have been trying to trace the 10% rule back through the literature and haven’t found the source yet. But I know I was taught there is a 7-10% cross rection risk and this number is passed down year to year. (yet another benefit of evidence based medicine and not anecdote-based medicine).

A better guideline is a 2% “general” reaction rate between people with penicillin allergy and cephalosporins.

But if your penicillin reaction was not a severe, life-threatening reaction then the cross-reaction rate is closer to 0.1%.

Recent evidence suggests that the risk of cross reaction between penicillin allergy and cephalosporins is no greather than between penicillins and any other antibiotic.

As a result, second and third generation cephalosporins should be OK if you have a penicillin allergy (the reaction rate is 0.01%)(^1)

It also could have been a contamination issue

It is also possible that the initial cross-reactions between penicillins and the cephalosporin family was more to the first-generation of cephalosporins. The cephalosporins used during these initial studies also had issues leading to contamination with penicillin during manufacturing (oops!)

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What to avoid if you have a penicillin allergy?

Cephalosporin allergy due to penicillin allergy
Avoiding cephalosporins due to penicillin allergy? Maybe you don’t have to worry as much as you used to.

Do you REALLY have a penicillin allergy?

Why would I ask such a thing?

9 out of 10 people who state they have a penicillin allergy actually don’t! And it’s easier than ever to test you and get you an answer.

I’ve written a full article about whether you have a penicillin allergy and I recommend you read it first (maybe I can help you fix multiple issues at once!)

Avoid these cephalosporins in the mean time

I hope I peaked your interest in clearing your penicillin allergy once and for all.

But in the meantime, the drug allergy national practice parameter suggests you avoid certain medications based on if generic penicillin, amoxicillin or ampicillin caused your reaction.

I’ve included your avoidance list in this infographic, but you can also read them in the tables below

Testing for cephalosporin allergies
If you had a reaction to cephalosporins itself, there’s a good chance it’s not really a medicine allergy!

What if you had an allergy to the cephalosporin itself?

Again, I will question whether you had an allergic reaction.


The rate of true cephalosporin allergy is about 0.02% of the patients who take the antibiotic[^3]

This just means that if you experienced hives, swelling or rash with a cephalosporin I would want to make sure that it was really due to the medication and not due to the infection itself (the most common cause of hives is due to infection and most rashes are not true allergic reactions).

I cover how to get tested for a cephalosporin allergy in the next section.

How to test cephalosporin allergy
How do you test for cephalosporin allergy? Just take the antibiotic and see what happens, right? Well, kinda…l

How to get tested for a possible cephalosporin allergy

There is no standardized skin testing available for cephalosporins. As a result, the two steps are to test for penicillin first and then consider an oral mediation challenge.

A board certified allergist should do these steps for you (and not an ENT allergist)

If you are avoiding cephalosporin antibiotics due to penicilin allergy

If you have a history of a penicillin allergy and are avoiding cephalosporins based on a fear of cross-reaction, the advised next step is a penicillin allergy test (which I reviewed in my prior article).

  • A negative penicillin test means you should be OK for cephalosporins and might also be OK for penicillins
  • A positive penicillin test means you should either avoid cephalosporins (and penicillins) OR consider a medication challenge.

If you are avoiding cephalosporin antibiotics due to a cephalosporin allergy

If you have a history of a pure cephalosporin allergy, then the recommendation would still be to test for penicillin but probably also to a cephalosporin.

  • A negative skin test would need a drug challenge to the cephalosporin as a second step.
  • A positive skin test means you should either avoid cephalosporins OR consider a very slow, conservative medication challenge (based on your history and your allergist’s plan.)


Cephalosporin allergies are often due to one of two reasons:

  1. You have a penicillin allergy and were told to avoid cephalosporins due to cross reaction
  2. You had a reaction while taking a cephalosporin

Because of these possible mis-diagnosis, you are likely paying more money for a broader spectrum antibiotic which could have increased risk of side effects and also be less effective.

Worse, there are problems with each of these two plans.

  1. If you were avoiding the cephalosporin family due to penicillin cross-reactivity then you now know:
    • The stated 10% cross reaction is NOT TRUE
    • Actual cross reactivity is 2% (although if you didn’t have a life-threatening reaction, it’s closer to 0.1% (only 1 out of every 1000 people have a reaction)[^2]
    • In addition, 9 out of 10 people with penicillin allergies don’t have an allergy any more[^2]
  2. If you were avoiding cephalosporins due to a reaction while taking the medication:
    • The actual rate of true allergic reaction is 0.02% (only 2 out of every 10,000 people have a serious allergic reaction)[^3]
    • The most common cause of hives is due to an infection and not the antibiotic
    • Most rashes are a drug adverse reaction and not a true allergy

To get this figured out once and for all, I recommend making an appointment with an allergist and getting tested using the general protocols I listed above.

And to help you even more, I’ve added a list of the specific medication you will need to avoid at the end of this article below.

Next Steps

If this article sounds interesting to you and you want to clear your antibiotic allergy, scheduling an appointment with an allergist near you (if you want, you can fill out this quiz and I’ll even find one close to you!)

And if you found this article helpful, like me on Facebook.


  1. Anne S, Reisman RE. Risk of administering cephalosporin antibiotics to
    patients with histories of penicillin allergy. Ann Allergy Asthma Immunol
  2. Drug Allergy: An Updated Practice Parameter
  3. Medical Myth: 10% of patients who are allergic to penicillin will have serious reactions if exposed to cephalosporins

Additional Resources

Here is a list of the names of the cephalosporin antibiotics that you need to avoid / that should be OK

If you have a general penicillin allergy or don’t know the exact medicine that caused it

If you’re unsure what medication caused your allergy OR if penicillin itself caused your allergy, it is safest to avoid all first generation penicillin for now.

If you are allergic to penicillin itself, avoid these medications:

Generic name (Trade Name) Generic name (Trade Name)
Cefazolin (cephazolin; Ancef, Kefzol) Cefapirin (cephapirin; Cefadryl)
Cefadroxil (cefadroxyl; Duricef) Cefatrizine
Cephalexin (cefalexin; Keflex) Cefazaflur
Cefaloglycin (cephaloglycin) Cefazedone
Cefalonium (cephalonium) Cefroxadine
Cefaloridine (cephaloradine) Cefradine (cephradine; Velosef)
Cefalotin (cephalothin; Keflin) Cefacetrile (cephacetrile)

If you have an allergy to amoxicillin

If you have an amoxcillin allergy, then avoid these cephalosporins:

Generic name (Trade Name) Generic name (Trade Name)
Cefadroxil (cefadroxyl; Duricef) Cefatrizine
Cefprozil (cefproxil; Cefzil)

if you have an allergy to ampicillin

If you have an ampicillin allergy, then avoid these cephalosporins

Generic name (Trade Name) Generic name (Trade Name)
Cephalexin (cefalexin; Keflex) Cephradine
Cephaclor (Ceclor, Distaclor, Keflor, Raniclor) cephaloglycein

These are the cephalosporins which should be OK to take

Second-generation cephalosporin family

Generic name (Trade Name) Generic name (Trade Name)
Cefaclor (Ceclor, Distaclor, Keflor, Raniclor) Cefonicid (Monocid)
Cefuroxime (Zefu, Zinnat, Zinacef, Ceftin, Biofuroksym, Xorimax) Cefuzonam
Cefmetazole Cefotetan
Cefoxitin Loracarbef (Lorabid)
Cefbuperazone Cefmetazole (Zefazone)
Cefminox Cefotetan (Cefotan)
Cefoxitin (Mefoxin) Cefotiam (Pansporin)

Third-generation cephalosporin family

Generic name (Trade Name) Generic name (Trade Name)
Cefcapene Cefdaloxime
Cefdinir (Sefdin, Zinir, Omnicef, Kefnir) Cefditoren
Cefetamet Cefixime (Fixx, Zifi, Suprax)
Cefmenoxime Cefodizime
Cefotaxime (Claforan) Cefovecin (Convenia)
Cefpimizole Cefpodoxime (Vantin, PECEF, Simplicef)
Cefteram Ceftamere (Enshort)
Ceftibuten (Cedax) Ceftiofur (Naxcel, Excenel)
Ceftiolene Ceftizoxime (Cefizox)
Ceftriaxone (Rocephin) Cefoperazone (Cefobid)
Ceftazidime (Meezat, Fortum, Fortaz) Latamoxef (moxalactam)

Fourth-generation cephalosporin family

Generic name (Trade Name) Generic name (Trade Name)
Cefclidine Cefepime (Maxipime)
Cefluprenam Cefoselis
Cefozopran Cefpirome (Cefrom)
Cefquinome Flomoxe

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