Management of Penicillin and Beta-Lactam Allergy


Therapeutic Review

  • Penicillin is the most frequently reported drug allergy and is reported in 5-10% of the population
  • Studies have shown that between 80 and 95% or more of those patients reporting a penicillin allergy do not in fact have true hypersensitivity reactions and the vast majority of these patients can tolerate beta-lactams
  • The use of penicillins can be associated with a nonimmediate, nonpruritic, nonurticarial rash in up to 10% of patients that is unlikely to be IgE-mediated and most often idiopathic or T-cell mediated
  • While inconvenient, these reactions have not been associated with anaphylaxis and pose no risk of cross reactivity with other beta-lactams
  • An example is the nonpruritic maculopapular rash commonly seen after the administration of ampicillin or amoxicillin to children suffering from infectious mononucleosis secondary to the Epstein-Barr virus
  • Only a type-1 immediate (IgE-mediated) hypersensitivity reaction to a penicillin manifesting as: anaphylaxis, bronchospasm, angioedema, hypotension, urticaria or pruritic rash warrants the avoidance of other penicillins and cephalosporins with similar side chains
  • Cross-reactivity between penicillins may be due to shared common antigenic determinants based on similarities in their core ring structure that is common to all penicillins and/or the side chains that distinguish different penicillins from one another; therefore, cross-reactivity cannot be based on side chain similarities alone
  • Currently, there is one Health Canada-approved standardized penicillin skin test

    • PRE-PEN contains the major antigenic determinant of penicillin and is used to rule out a type-1 immediate (IgE-mediated) penicillin allergy
    • Available literature suggests that the skin test using both major and minor antigenic determinants are roughly 50-60% predictive of penicillin hypersensitivity with a 97-99% negative predictive value
  • When penicillin skin testing is not available, the approach to penicillin allergic patients is based on their reaction history and the need for treatment with a penicillin

  • While patients with a convincing reaction history are more likely to be allergic, those with vague histories cannot be discounted as they may also be penicillin allergic

  • The time passed since the reaction is useful because 50-80% of penicillin allergic patients lose their sensitivity after 5 and 10 years respectively

  • Skin testing, desensitization or re-challenge with a beta-lactam should not be performed in those patients with a history of Stevens-Johnson syndrome or toxic epidermal necrolysis
  • In patients with DRESS, serum sickness, immune hepatitis, hemolytic anemia or interstitial nephritis, it is recommended to consult the Medical Microbiologist/Infectious Diseases Consultant