A penicillin allergy can cause symptoms such as hives, shortness of breath, and areas of swelling. In some cases, it may also lead to anaphylaxis, a life threatening condition that causes low blood pressures, a fast heartbeat, and faintness.

Doctors can use skin prick tests, intradermal tests, and medication to diagnose certain types of penicillin allergies. They may diagnose other types based on a person’s clinical history and physical examination alone. Treatment of mild cases may involve taking an antihistamine, while severe cases may require emergency administration of epinephrine alongside other drugs.

People with penicillin allergies may safely get the COVID-19 vaccine, but someone should observe them for 30 minutes afterward.

Read on to learn more about penicillin allergies, including the symptoms, diagnosis, prevention, and the effects of anaphylaxis and delayed reactions in some people.

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A person may develop an allergy to penicillin if their immune cells produce an antibody called IgE with exposure to penicillin or similar antibiotics.

This IgE antibody resides on mast cells and other allergy cells. Attachment of penicillin to the IgE antibodies on allergy cells can trigger the rapid release of histamine and other substances that cause the symptoms of IgE-mediated allergies, such as hives and itching.

There are also other types of penicillin allergies. Penicillins, which are beta-lactam antibiotics, can lead to the following:

  • a cytotoxic drug allergy, which can lead to serious reactions, such as thrombocytopenia or a low platelet count in the blood
  • immune complex delayed hypersensitivity, which can cause symptoms including fever, a rash, hives, swelling, and joint stiffness
  • immunological nephropathy, which can lead to kidney disorder

The mechanisms differ for each of these types of drug reactions.

According to the American Academy of Allergy, Asthma & Immunology, although 10% of the population report a penicillin allergy, more than 90% have negative allergy testing and can take penicillin and related antibiotics without symptoms. In other words, most individuals with the diagnosis do not have a true allergy.

People usually receive a penicillin allergy diagnosis in childhood. When rashes associated with common childhood infections coincide with a course of amoxicillin- or penicillin-type antibiotics, doctors may stop the antibiotic and recommend avoidance as a precaution. Without further evaluation of a possible antibiotic allergy, people may not question this diagnosis for decades.

Of those with a true allergy, over 90% will lose it over a 10-year period.

Penicillin allergies and the COVID vaccine

If a person has a penicillin allergy, even a severe one, health authorities do not prohibit them from getting the mRNA SARS-CoV-2 vaccine. These include the Pfizer or Moderna vaccine for COVID-19.

However, someone should observe them for 30 minutes afterward to ensure they do not have an adverse reaction.

Alexander Fleming discovered penicillin in 1928.

In 1942, doctors started using it widely to treat streptococcal and staphylococcal bacterial infections. Today, it remains one of the antibiotics doctors most frequently prescribe.

Aside from amoxicillin, medications in the immediate penicillin family include:

Another class of antibiotics, cephalosporins, are structurally similar to penicillin. Because of their close relationship, it is possible for a person with a penicillin allergy to also have an allergy to cephalosporins. This is called cross-reactivity.

However, since the risk of cross-reactivity is less than 5%, someone with a penicillin allergy might be able to take cephalosporins without having a reaction. Examples of antibiotics in this class include cefadroxil (Duricef) and cefazolin (Ancef).

Learn more about amoxicillin allergic reactions here.

A penicillin allergy can stimulate the production of different types of immunoglobulins. If it triggers immunoglobulin E (IgE), the symptoms can appear immediately or within an hour.

These symptoms may include:

  • hives, which are multiple inflamed, itchy, raised areas of skin
  • angioedema, which refers to localized areas of swelling without hives that affect the face, abdomen, genitals, voice box, throat, arms, or legs
  • shortness of breath and wheezing
  • anaphylaxis

Other types of allergy to penicillin are common. These include delayed-type allergies that can cause an itchy rash that may not appear until several days after starting penicillin antibiotics. Doctors refer to one example of this as the maculopapular amoxicillin rash.

There is also a type of penicillin allergy called a serum sickness-like reaction, where a rash can occur with fevers and fatigue, among other symptoms.

Risk factors for an IgE allergic reaction include repeated or frequent penicillin doses.

High doses of parenteral administration may also increase the likelihood of an IgE reaction. Parenteral refers to receiving the medication via injection or intravenous infusion rather than orally, which means by mouth.

Diagnosis starts with a history and physical exam, during which the doctor will ask about prior abnormal responses to penicillin and note a person’s symptoms.

If symptoms suggest a penicillin allergy, the next diagnostic step involves a skin prick test with penicillin. This is called a penicillin skin test.

A positive result occurs when a raised, inflamed area at least 3 millimeters (mm) wide is visible on the skin. This positive reaction might occur within 15 minutes.

If the skin prick test is negative, doctors may conduct further exams, such as the intradermal test. This involves injecting a small amount of penicillin a little deeper so it may reach the area between layers of skin. As with the skin prick test, a raised, inflamed area at least 3 mm wide is a positive result. Medical staff observe the results at 15 minutes for an immediate response and 48 and 72 hours later for a delayed response.

The skin prick and intradermal tests are only useful in evaluating an IgE-mediated penicillin allergy. These tests will not help diagnose or exclude the possibility that a person has any other type of penicillin allergy.

Anaphylaxis is a life threatening condition that can occur immediately or within an hour of taking penicillin. Symptoms can affect two or more of the following organ systems:

Delayed reactions may occur days to weeks after a person takes penicillin and may involve:

  • toxic epidermal necrolysis, a life threatening skin reaction
  • hemolytic anemia, a blood condition where the body destroys red blood cells faster than it can replace them
  • Stevens-Johnson Syndrome, a serious reaction to medication that affects the skin and mucous membranes
  • interstitial nephritis, a kidney disorder that can lead to kidney failure
  • vasculitis, inflammation of the blood vessels
  • serum sickness, a hypersensitivity disorder that is similar to an allergy
  • neutropenia, a condition where the body has too few of a type of white blood cells called neutrophils
  • thrombocytopenia, a condition that manifests in bleeding, bruising, or slow blood clotting following an injury

Treatment depends on the severity of the allergic reaction.

Antihistamines are a class of medications doctors may prescribe in the first instance for mild rashes and itching. Examples include diphenhydramine (Benadryl) or cetirizine (Zyrtec). Topical steroid ointments, such as hydrocortisone, may also provide relief for non-hive rashes.

In contrast, an anaphylaxis reaction is a life threatening event that necessitates immediate treatment. This involves someone having an epinephrine injection every 5–15 minutes until symptoms subside. Additionally, a person may need one of the following medications:

  • Antihistamines: They may require an injection of an H1 antihistamine, such as diphenhydramine (Benadryl), or an H2 antihistamine, such as ranitidine (Zantac).
  • Glucocorticoids: These are drugs that reduce inflammation. One example is methylprednisone (Medrol).
  • Bronchodilators: This medication dilates the airways. Doctors use it to treat airway spasms. An example of this type of drug is Albuterol (Accuneb).

Aside from treatment to relieve symptoms, doctors will discontinue the penicillin and prescribe a different one.

Other severe symptoms besides anaphylaxis may also warrant medical attention, such as blistering or peeling of the skin, accompanying fevers or fatigue, and other less common manifestations of a drug allergy.

The following classes of antibiotics are alternatives to penicillins:

  • tetracyclines, such as doxycycline (Doryx)
  • macrolides, such as clarithromycin (Biaxin)
  • glycopeptides, such as vancomycin (Vancocin)
  • quinolones, such as ciprofloxacin (Ciproxin)
  • aminoglycosides, such as gentamicin (Garamycin)
  • cephalosporins, such as cefuroxime (Ceftin)


Sometimes there is no other antibiotic besides penicillin that is effective for treating a person’s infection.

If their allergic response indicates an IgE-mediated reaction, desensitization might be an option. This process involves the person receiving incrementally higher doses of penicillin until they can tolerate the entire usual dose.

Desensitization involves dosage in any of the following forms:

  • oral
  • injection into a vein
  • injection under the skin

Doctors would not recommend desensitization for any allergy that is not IgE mediated, regardless of severity, as desensitization is only known to work in IgE-mediated allergies.

A penicillin allergy happens when a person’s body recognizes the medication as an allergen. An allergen is something that stimulates an immune response specific to it that is reproducible on reexposure to the allergen. One of the many types of possible immune response is an IgE-mediated response.

The immune response could also occur independently of IgE. Other immune proteins, such as immunoglobulin G, immunoglobulin M, or other immune cells such as T cells can mediate these responses. The antibodies cause cells to release chemicals that lead to symptoms such as hives, shortness of breath, and anaphylaxis.

Doctors primarily diagnose a penicillin allergy based on the person’s history and physical examination. They may use a skin test to specifically clarify whether the person has an IgE-mediated allergy. A skin test cannot diagnose any other types of drug allergy. Although 10% of individuals receive a diagnosis of a penicillin allergy, it is not a true allergy in more than 90% of these people.

In mild cases, treatment involves an antihistamine, but a person should go to an emergency room for immediate treatment in severe cases.