There is increasing evidence that the majority of patients who think they have a penicillin allergy actually do not. Those with a penicillin allergy often receive more broad spectrum antibiotics that carry higher rates of morbidity. Research indicates that an unconfirmed penicillin allergy may be associated with a longer hospital stay and a higher prevalence of drug-resistant infections. 

The Centers for Disease Control and Prevention (CDC) suggest that doctors evaluate patients who report penicillin allergy for true allergy. About 10% of hospital patients in the United States state they are allergic to penicillin but most are not. In fact, <1% of the population has a true allergy to penicillin. Moreover, about 80% of patients with a penicillin allergy lose their sensitivity by 10 years following their reaction. 

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The CDC guide for hospitals states that hospitals should “establish guidance for antibiotic allergy assessment (eg, a penicillin allergy assessment protocol) including recommendations on which patients might benefit from skin testing.” Testing for penicillin allergy is one of the major ways to improve antibiotic stewardship in hospitals across the country.

Katherine Fleming-Dutra, MD, CDC epidemiologist, advises physicians on how to rule out a penicillin allergy prior to prescribing an alternative or broad-spectrum antibiotic (eg, fluoroquinolones). Physicians should ask specific questions of patients who claim to be penicillin-allergic:

  • What medication(s) were you taking when the reaction occurred?
  • What kind of reaction occurred? (ie, rash, hives, diarrhea, difficulty breathing)
  • What treatment was given? Was epinephrine used?

Pre-Pen (benzylpenicilloyl polylysine injection; ALK-Abello) is the only FDA-approved skin test for the diagnosis of penicillin allergy. This skin test antigen reagent reacts specifically with benzylpenicilloyl IgE antibodies initiating the release of chemical mediators which produce an immediate wheal and flare reaction at the test site. A negative skin test to Pre-Pen is associated with an incidence of immediate allergic reactions of less than 5% after the administration of therapeutic penicillin, whereas the incidence may be more than 50% in a history-positive patient with a positive skin test to Pre-Pen.

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