Penicillin, Amoxicillin, and Cephalosporin Allergy: What to Know

Penicillin is perhaps the most well-known member of a group of antibiotics called beta-lactams, which refers to a particular structure in their chemical makeup. The structure is also shared by semi-synthetic penicillin (amoxicillin), cephalosporins, and other antibiotics, such as imipenem. Penicillins and cephalosporins are the antibiotics most commonly used to treat common bacterial infections.

Unfortunately, penicillins and cephalosporins are also the most common causes of drug allergy. About 10% of Americans report having an allergy to penicillin or a related antibiotic. In fact, however, the number of people who have a true penicillin allergy is much lower.

While penicillin allergy most frequently occurs in young adults, reactions can occur at any age. Women appear to be at higher risk than men. Reactions to penicillin may include anaphylaxis, hives, below-the-skin swelling, and asthma symptoms, as well as non-allergic symptoms such as serum sickness, certain forms of anemia, and other drug rashes.

Mother Giving Penicillin Medicine to His Sick baby Boy
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Family of Antibiotics

The family of penicillin antibiotics includes:

  • Penicillin VK
  • Penicillin G
  • Dicloxacillin
  • Oxacillin
  • Nafcillin
  • Amoxicillin
  • Ampicillin
  • Augmentin (amoxicillin/clavulanate)
  • Unasyn (ampicillin/sulbactam)
  • Zosyn (pipercillin/tazobactam)

The family of cephalosporins includes:

  • Keflex (cephalexin)
  • Ancef (cefazolin)
  • Ceftin (cefuroxime)
  • Cefzil (cefprozil)
  • Omnicef (cefdinir)
  • Vantin (cefpodoxime)
  • Many other antibiotics beginning with “cef-“ or “ceph-“

How Is Penicillin Allergy Diagnosed?

While many people report having an allergy to penicillin, less than 5% of the population actually has a true allergy to the drug. Some patients who have been labeled as "penicillin allergic" may in fact have experienced non-allergic reactions or side effects to the drug, such as gastrointestinal upset, headache, or nausea, and mistaken it for a true allergy. Furthermore, most people lose their penicillin allergy over time—even patients with a history of severe reactions, such as anaphylaxis.

Oral challenge (administering a dose of the drug) is the best, most effective method for diagnosing a penicillin allergy. However, healthcare providers often perform skin testing first to avoid the risk of allergic reaction, particularly among those with a medical history that indicates penicillin sensitivity.

An extract called Pre-Pen (benzylpenicilloyl polylysine injection) is the only FDA-approved skin test for the diagnosis of penicillin allergy. Penicillin skin testing identifies the presence or absence of IgE antibodies to this injection and identifies the majority of cases of true clinical penicillin allergy. This information will allow a health care provider to determine if penicillin or an alternative antibiotic should be given.

Testing usually takes about an hour to complete. The skin is injected with weak solutions of various preparations of penicillin and observed for a reaction. This may cause itching, although it is not painful.

A positive skin reaction is indicated by an itchy, red bump that forms within about 30 minutes. A positive test indicates that a person is is more likely to be allergic to penicillin. (Not every test that is positive represents a true penicillin allergy, however; there are false positives in penicillin skin testing.) People with a positive test are usually advised to continue avoidance of penicillins.

It is important to identify who is truly allergic to penicillin and who is not, because patients who are labeled penicillin-allergic are more likely to receive broad-spectrum, very powerful antibiotics, which kill both good and bad bacteria and have more side effects than more tailored antibiotics. People labeled as allergic to penicillin are also more likely to develop certain difficult-to-treat, resistant infections and require longer stays in hospitals, compared with patients who do not report a history of penicillin allergy.

How Is Penicillin Allergy Treated?

Other than the immediate treatment of drug allergy symptoms, the main treatment for penicillin allergy is avoidance of future use of penicillin and related antibiotics. However, if penicillin is required, people with penicillin allergy can also be admitted to a hospital for a desensitization procedure.

Penicillin Allergy and Other Antibiotics

Cephalosporins can cause allergic reactions in people with penicillin allergy. The overall rate of allergy to cephalosporins in people with penicillin allergy is approximately 5% to 10%, although rates may be higher for certain people. Allergic reactions to cephalosporins can be severe and even life-threatening.

If you have a penicillin allergy, you should talk with your healthcare provider about whether you also need to avoid cephalosporins. Most patients with true penicillin allergy can tolerate cephalosporins, but there are some cases where both penicillin antibiotics and cephalosporins need to be avoided.

Similarly, ask your allergist about whether it is safe to take imipenem, another beta-lactam antibiotic, if you have a history of penicillin allergy. Most patients with a true penicillin allergy will be able to tolerate imipenem, but depending on your history, a medically supervised graded-dose challenge or other precautions may be recommended.

People with penicillin allergy are also at higher risk of developing an allergy to a different class of drugs called sulfa drugs, which include antibiotics as well as other medications.

Managing Penicillin Allergy When Medically Necessary

There may be certain cases when a person with a history of penicillin allergy absolutely needs penicillin or cephalosporin. In these situations, an allergist can perform skin testing and, if the test is negative, give the patient a small amount of the drug under close monitoring to determine how much—if any—he or she can tolerate (known as an oral challenge).

If a person who is truly allergic to penicillin has an infection that requires treatment with penicillin, a desensitization process can be performed in a hospital. This entails giving small amounts of the drug and gradually increasing doses over a number of hours until the person can tolerate a full therapeutic dose.

It is important to recognize that desensitization only lasts for as long as the medication is being taken regularly. For example, if a person is desensitized to penicillin for the treatment of an infection and then requires penicillin again for another infection a year later, repeat desensitization would likely be needed.

A Word From Verywell

If you have any concerns about whether you are allergic to penicillin or a related drug, ask your healthcare provider about the possibility of being tested.

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7 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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  7. Centers for Disease Control. Management of Persons Who Have a History of Penicillin Allergy. Updated June 4, 2015.