Penicillin Allergy Testing Procedures

Gloved hands performing an allergy prick test on a patient's arm

National Institutes of Health / Stocktrek Images / Getty Images

Penicillin and related antibiotics are some of the oldest and most commonly used antibiotics available. They are active against a wide variety of infections, are inexpensive, and are generally well tolerated. Unfortunately, many people think they are allergic to penicillin, with up to 10% of the population reporting an allergy. Studies show, however, that when people who report being allergic to penicillin are tested for the allergy, nearly 90% are not allergic and are able to take the medicine just fine. This occurs for at least two reasons. First, in many cases, patients are miscategorized as having an allergy to penicillin. In addition, even when a patient has a penicillin allergy, it can be outgrown with time.

Testing for penicillin allergy is available, is a relatively simple procedure, and most often leads a person who thought they were allergic to penicillin to find out that they are not actually allergic to the antibiotic, or are no longer allergic. Most allergists have the ability to perform penicillin allergy testing.

Avoiding Penicillin Can Lead to Other Problems

Most people with a penicillin allergy simply avoid taking penicillin and related antibiotics, as there are a wide variety of other antibiotics to take should an infection occur. But is this the right approach to take? Various studies show that when a person is labeled as penicillin-allergic, numerous complications may arise as a result of being given other antibiotics.

First, the cost of taking non-penicillin antibiotics goes up dramatically. Studies show that the average cost of antibiotics in a hospital patient with a penicillin allergy is about 63 times greater than in those without a penicillin allergy. Second, the use of non-penicillin antibiotics, especially in a hospital setting, increases the risk for the development of infections by antibiotic-resistant bacteria, such as vancomycin-resistant Enterococcus. Lastly, the use of non-penicillin antibiotics may also put a person at higher risk of developing Clostridioides difficile colitis, a dangerous infection of the intestines caused by the use of strong antibiotics.

Penicillin Is Good at Causing Allergic Reactions

Penicillin is able to easily trigger allergic reactions in people due to its ability to bind to proteins in the blood and on cells in the body in order to stimulate the immune system. This process, called haptenization, leads to the body’s immune system being better at recognizing the penicillin as an allergen. Sensitization, or the development of allergic antibodies, to penicillin then occurs, which can lead to allergic reactions when a person is exposed to penicillin in the future.

Components of the Penicillin Allergy Test

Penicillin allergy testing involves the use of various skin-testing techniques, including skin prick testing and intradermal skin testing, to penicillin and penicillin metabolites. Allergy physicians typically perform skin testing with penicillin G (an injectable form of penicillin that is in liquid form) and Pre-Pen (benzylpenicilloyl polylysine)—the major metabolite of penicillin after the body breaks down the drug. Some allergy physicians may also add a minor determinant mixture (MDM) containing other "minor" metabolites.

MDM is not available commercially at this time, although some allergists—such as those working in university settings—will make a "homemade" version. The theory behind using MDM in penicillin testing is that it may increase the sensitivity of the testing. (Sensitivity describes the likelihood that a real allergy would be picked up by the test.)

Allergy blood tests are also available for penicillin allergy testing, but they are not very accurate and generally should not be used as a substitute for penicillin allergy skin testing.

How Testing Is Performed

Generally, skin prick testing is performed first, which is able to identify the most sensitive penicillin-allergic people. If skin prick testing is positive, then the person is considered to be allergic to penicillin, and no additional testing is done. If prick testing is negative, then intradermal skin testing is performed with the same materials. Intradermal skin testing identifies more people with penicillin allergy but is potentially dangerous in the most sensitive people. This is the reason why skin prick testing is performed first.

If skin testing to penicillin and related metabolites is negative using both prick and intradermal techniques, then the chance of the person being allergic to penicillin is very low. Most physicians then feel comfortable prescribing penicillin and penicillin-related antibiotics to that person, although some physicians still recommend giving the first dose of penicillin under medical supervision and monitoring for an hour or two. Some physicians will even go a step further and perform an oral challenge to a penicillin antibiotic (typically amoxicillin) under medical supervision to ensure that the person can tolerate the antibiotic.

If any of the above-mentioned tests are positive, then a person should consider himself or herself allergic to penicillin. In this situation, penicillin and related antibiotics should be avoided, unless there is a special need for penicillin and the use of other antibiotics won’t be sufficient. Desensitization to penicillin can be performed, sometimes in a medical office setting, but usually in a hospital setting, so that a person can tolerate a course of penicillin. It is important to realize, however, that desensitization only lasts for a few days, so desensitization does not lead to an allergy cure but only a short-term tolerance of the medication.

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.
  1. Centers for Disease Control and Prevention. Evaluation and diagnosis of penicillin allergy for healthcare professionals.

  2. Cleveland Clinic. Think you’re allergic to penicillin? Why you may be mistaken.

  3. Mirakian R, Leech SC, Krishna MT, et al. Management of allergy to penicillins and other beta-lactamsClin Exp Allergy. 2015;45(2):300-27. doi:10.1111/cea.12468

  4. Brown KA, Khanafer N, Daneman N, Fisman DN. Meta-analysis of antibiotics and the risk of community-associated Clostridium difficile infectionAntimicrob Agents Chemother. 2013;57(5):2326-32. doi:10.1128/AAC.02176-12

  5. Żukiewicz-Sobczak WA, Wróblewska P, Adamczuk P, et al. Drugs as important factors causing allergiesPostepy Dermatol Alergol. 2015;32(5):388-392. doi:10.5114/pdia.2014.44021

  6. Adkinson NF, Mendelson LM, Ressler C, Keogh JC. Penicillin minor determinants: History and relevance for current diagnosis. Ann Allergy Asthma Immunol. 2018;121(5):537-544. doi:10.1016/j.anai.2018.09.459

  7. UpToDate. Allergy to penicillin and related antibiotics.

Additional Reading

By Daniel More, MD
Daniel More, MD, is a board-certified allergist and clinical immunologist. He is an assistant clinical professor at the University of California, San Francisco School of Medicine and currently practices at Central Coast Allergy and Asthma in Salinas, California.