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Why Are Penicillin Allergies So Common?

Penicillins tend get a bad rap because allergies to this class of antibiotics are one of the most commonly reported drug allergies. 

Penicillin refers both to a specific antibiotic and to a group of antibiotics (“penicillins”) that includes penicillin, ampicillin and amoxicillin. Penicillins are commonly used in pregnancy because they are safe for the fetus. Additionally, they kill their target bacteria without killing too many of the other bacteria that live on and in our bodies. And, they generally have very few side effects. 

Inaccurate self-reporting of penicillin allergy is a major health issue. Ninety to 95% of people who report an allergy to penicillin are not actually allergic. These may include patients who report:

  • Non-allergic intolerance, such as stomach upset (nausea/vomiting), antibiotic-associated yeast infection, skin rash/itching without hives or headache.
  • Unknown childhood reaction (it is unlikely to have been a severe allergic reaction if the patient cannot recall it).
  • Non-personal family history of penicillin allergy, including penicillin allergy in a parent or sibling (penicillin allergy is not genetically heritable).

Patients with a true allergy to penicillin experience reactions mediated by the immune system. These patients absolutely should not receive an antibiotic in the penicillin class:

  • Allergic reactions including hives, throat swelling, facial swelling, lung/airway spasms and anaphylaxis. (These patients may be able to tolerate other antibiotics called cephalosporins, which are related to but distinct from penicillins.)
  • Delayed hypersensitivity reactions including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), hemolytic anemia, nephritis and vasculitis.

Can’t someone with a penicillin allergy get an alternative antibiotic?

Alternative antibiotics are available to treat many conditions. But the reason it is important to determine whether someone has a true penicillin allergy goes back to the reason penicillins are used first-line in many conditions of pregnancy.

First-line antibiotic regimens are designed to provide the best bacterial coverage with the least collateral damage (i.e., killing extra bacteria and side effects). Alternative regimens for those with allergies are designed to be comparable to these first-line regimens, but the coverage they provide may be suboptimal (not killing all of the target bacteria) or excessively broad (leading to superinfection, the development of antibiotic resistance or increased side effects).

Additionally, some alternative antibiotics are not recommended during pregnancy, limiting choices available to treat infection. Alternative antibiotics should only be used for patients who truly cannot tolerate the recommended regimen.

So, if you think you’ve got a penicillin allergy, talk to your healthcare provider about your reaction. They can help determine if your penicillin reaction was a “true” allergy. Then, take one of the following steps:

  • If you both agree your reaction was not a true penicillin allergy, your healthcare provider can remove the penicillin reaction from your allergy list.
  • If you are not sure if your reaction was a true penicillin allergy, your healthcare provider can refer you to an allergist for a penicillin skin test as an outpatient procedure.   
  • If you both agree your reaction was a true penicillin allergy but it happened more than 10 years ago, your healthcare provider can refer you to an allergist for a penicillin skin test as an outpatient procedure. Many penicillin allergic reactions become less severe or even fade away entirely after 10 years.

Ultimately, an accurate record of your tolerance for all antibiotics, but especially penicillins, will provide you (and your baby, if you’re pregnant) with the best care. 


  1. Stone CA Jr, et al. The challenge of de-labeling penicillin allergy. Allergy. 2020;75:273-288.
  2. Shenoy ES, et al. Evaluation and Management of Penicillin Allergy: A Review. JAMA. 2019;321(2):188-199.
  3. Zagursky RJ and Pichichero ME. Cross-reactivity in Beta-Lactam Allergy. J Allergy Clin Immunol Pract. 2018;6(1):72-81.
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