Are you sure you’re allergic to penicillin?

As a pharmacist, when I dispense medication, it’s my responsibility to ensure that the medication is safe and appropriate for the patient. There are numerous checks we go through including verifying the dose, ensuring there are no interactions with other drugs, and verifying the patient has no history of allergy to the product prescribed. Asking about allergies is a mandatory question for every new patient.

Penicillin is one of the oldest antibiotics still in use despite widespread bacterial resistance. Multiple analogs of penicillin have been developed to change its effectiveness, or improve its tolerability. And other classes of antibiotics (e.g., cephalosporins) share some structural features with penicillin. These products are widely used for both routine and serious bacterial infections. Unfortunately, allergies to penicillin are widely reported. Statistically, one in ten of you reading this post will respond that you’re allergic to penicillin. Yet the incidence of anaphylaxis to penicillin is estimated to be only 1 to 5 per 10,000. So why do so many people believe they’re allergic to penicillin? Much of it comes down to how we define “allergy.”

Adverse Events, Reactions, and Allergies

There are a number of confounders when it comes to evaluating allergies. A big one is terminology. While different groups vary in their definitions, the term “adverse drug event” typically means that an undesirable event has occurred, but isn’t causally linked to the consumption of a drug. In contrast, “adverse drug reaction” is usually reserved to where a causal link to the drug has been established, or is fairly certain. Adverse drug reactions can occur under completely normal use of a drug. And they’re not uncommon, as I’ve pointed out before. An allergic reaction to a drug is an adverse drug reaction that is mediated by an immune response. If there is no immune response, it’s not an allergic reaction. So if you take codeine and it makes you drowsy and constipated, that’s not an allergic reaction—that’s an effect of the drug. Erythromycin commonly causes stomach upset, so if you vomit, that’s not an allergy either. So, to sum:

Penicillin Allergies

Within that box of adverse reactions we’re calling “drug allergies” there’s a number of methods of classifying the different immune responses. The most common way is to split events into immunoglobulin E (IgE)–mediated (immediate) reactions, or non–IgE-mediated (delayed) hypersensitivity reactions. The IgE-mediated reactions are the ones we might immediately think of when we hear “penicillin allergy”: flushing, itchy skin, wheezing, vomiting, throat swelling, and even anaphylaxis. These reactions can occur immediately to a few hours after a dose. The non-IgE-mediated reactions are delayed, and can be mild or severe, ranging from serum sickness to the horrific (but fortunately rare) Stevens-Johnson syndrome.

Skin rash (morbilliform eruptions) are non-IgE reactions commonly reported with penicillin therapy, though their relationship to the penicillin itself isn’t clear. Rashes that appears several days after starting therapy (or even after finishing a course of antibiotics) may be due to a poorly-understood relationship between the antibiotic and any concurrent viral infection. These rashes are not itchy. With subsequent exposure to penicillin (or a related drug) the rash can reappear. These types of reactions do not mean that one cannot receive penicillin again, however.

It’s the structure of the penicillin molecule itself that triggers allergic reactions. Both the “parent” drug and any iterations created through metabolism can induce allergic responses. Analogs of penicillin, with different molecular side chains, can trigger selective sensitivity in some. So one could have an allergic reaction to amoxicillin or ampicillin, but be able to tolerate penicillin.

Testing for allergies

Determining if you’re actually allergic to penicillin is important to sort out, as not all reactions mean penicillin cannot be administered again. Skin testing is the standard for testing for IgE-mediated allergies, and needs to be performed under medical supervision, usually by allergy specialists, in settings where access to resuscitation medication is available. Given the unreliability of memory, skin testing is the standard when there’s any doubt all about the type of prior reaction. In cases of the severe non-Ig-E type reactions, there’s no rechallenge attempted, and those patients should never receive penicillins again.

So if you think you’re allergic to penicillin, but are not certain of the type of allergy you have, testing is something worth thinking about. Without it, you’re setting yourself up for a lifetime of risk and consequences of the avoidance of penicillin. Data show that patients considered penicillin-allergic will typically receive more broad-spectrum antibiotics, which may have more side effects, be more expensive, and in some situations, less effective. And given IgE-mediated allergy can wane over time, even significant childhood reactions may not manifest as adult allergies—but only testing can determine this for certain.

Formal evaluations of penicillin allergies support this approach. A recent paper in the Journal of Allergy and Clinical Immunology describes a prospective evaluation of children that presented to an emergency room with a delayed-onset rash from penicillin. Eighty-eight children were enrolled over two years. At the time of enrollment, they were screened for viruses. Each child returned to the hospital two months after their initial visit, where they underwent skin (patch and intradermal) as well as blood evaluations for allergy. They all had an oral challenge with the original antibiotic, too. After evaluation, none had a positive skin test, 11 children (12.5%) had a intradermal reaction, and only six (6.8%) had the rash recur after an oral challenge. Within the group that had a positive oral challenge, two had intradermal-negative, and one was intradermal-positive. Most of the children had tested positive for viral infections, too.

The authors concluded that penicillin allergies are overdiagnosed, and viral infections may be a factor leading to rashes and over-diagnosis. The authors recommended oral challenges, rather than skin, intradermal, or blood tests for all children that develop delayed-onset rashes during treatment with penicillins.


While penicillin allergies can be real, and can be serious, only a small percentage of people that consider themselves allergic actually cannot receive penicillin. Avoiding penicillin can mean using antibiotic alternatives that are less effective, more expensive, and have greater side effects. For this reason, confirming a penicillin allergy with a physician is warranted—before an antibiotic is needed. After all, unless it’s necessary, you don’t want to end up with an infectious disease physician standing over your hospital bed, being asked what their second choice of antibiotic is going to be.


Caubet JC, Kaiser L, Lemaître B, Fellay B, Gervaix A, & Eigenmann PA (2011). The role of penicillin in benign skin rashes in childhood: a prospective study based on drug rechallenge. The Journal of allergy and clinical immunology, 127 (1), 218-22 PMID: 21035175

5 thoughts on “Are you sure you’re allergic to penicillin?

  1. Regarding allergy testing for penicillin: it doesn’t seem to be that simple. My 6 year old, my 3 year old and me have all experienced an almost full-body rash during the course of amoxicillin. In all three cases, it was at the very end, after a week or so on the antibiotic. These reactions were at three different times, for different types of infections.

    I’ve been told different things from different doctors. About my 6 year old “definitely NOT an allergy” then from another doctor “definitely an allergy”. Neither doctor was eager to refer for an allergy test. I also had a conversation about this with the allergy clinic at Sick Kid’s Hospital and Sunnybrook’s drug allergy clinic. They both told me that they only do allergy testing for antibiotics in children if the child is often sick and/or has other heath condition that makes amoxicillin the only good choice as treatment for infections. This is because they do not do the standard skin-testing for drug allergies (I can’t remember why — they gave me a reason which sounded reasonable at the time.) They only do intradermal testing and oral challenges and don’t want to subject kids to this unnecessarily.

    For me, I eventually had my suspected allergy tested at Sunnybrook’s drug allergy clinic. The test was negative, but I waited a few years for this test becuase (a) I was breastfeeding at the time and they didn’t want me to have the test while I was breastfeeding and (b) there was a *very* long wait for an appointment (as I recall, it was longer than 6 months).

    I would like to know these are true allergies in my kids’ case — I suspect they are not but with our strong family history of anaphylacic allergies, it’s not something that we take lightly.

    On a related topic, our oldest (9) has a suspected anaphylactic allergy to Tylenol. (I suspect this one is a true allergy.) I’ve been told that an allergy to Tylenol is very rare and am experiencing the same frustrations that I am with the possible amoxicillin allergy — doctors seem reluctant to test for it.

    All of this to say that I agree, it is important to test suspected allergies but it’s not something that is easy to have done, especially in children.

  2. As a teenager, I had a rash reaction – the reaction occurred immediately after switching from sulfa (which wasn’t helping the uti) to Keflex (cephalexin). For many years, I reported to my doctors the possible allergy to Keflex, and for many years after that, I was refused penicillin drugs – despite having taken them many times throughout childhood with no problem.

    …I finally started leaving off the Keflex when asked about allergies. Since I stopped reporting it, I have received penicillin drugs without issue. How can I convince my doctors that the potential allergy is JUST to keflex or possibly cephalosporins – and NOT penicillin?

  3. Thanks this is helpful.

    Sorting out allergy from toxicity: I recently took ciprofloxacin with flagyl for a gastro infection. I had a rash reaction within a couple days. Physician said …eh? Pharmacist attention to that. So I stopped it. That’s an allergic reaction.

    Over the next few days and weeks, I noticed pain in my ankle. Dismissed it as maybe I bumped it, somewhere? Long story short.

    I have a ruptured achilles tendon. That’s a TOXIC reaction to ciprofloxacin, noted in the product monograph, on wikipedia (good source of unbiased drug info for cipro and others of that class) and on other drugs info websites.

    Pay attention to the allergic reaction. It might be portent to something far more serious.

    With penicillin I get throat constriction, although I haven’t used it for about 20 years now. No idea what I’ll use the next gastro flare up. It sure won’t be cipro.

    And an addendum to this: with all the drug information available to the prescribing doctors, gastro specialists all, why did they not know that drug class is not to be used for what I presented with, not to be used on someone my age, and not to be used concurrently with flagyl?

    There’s the real problem. Pharma has made inroads to our physician’s prescribing habits. Prescribe whatever is the latest, on patent, money maker. Do not even consider the safer, older, cheaper alternative.

    Penicillin you say? I’ll consider it.

  4. I had a reaction to a penecillin once in my 20’s. Broke out in hives. Went back to the doctor and he said I was just likely reacting to a “Cheap” penicillin, and wrote me a prescription for another kind. Never had a reaction since.

  5. After always being able to take penicillin I had to take augmenting for an infection I went into anaphylactic shock and ended up in hospital I am now scared to take antibiotics and being diabetic I need to know what is safe for me

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