Penicillin and Beta-Lactam Allergy
Key Points

Key Points

Key Points

Beta-lactams are generally safe; allergic and adverse drug reactions are over diagnosed and over reported

Nonpruritic, nonurticarial rashes occur in up to 10% of patients receiving penicillins. These rashes are usually not allergic and are not a contraindication to the use of a different beta-lactam

The frequently cited risk of 8 to 10% cross-reactivity between penicillins and cephalosporins is an overestimate based on studies from the 1970’s that are now considered flawed

  • Expect new intolerances (i.e. any allergy or adverse reaction reported in a drug allergy field) to be reported after 0.5 to 4% of all antimicrobial courses depending on the gender and specific antimicrobial
  • Expect a higher incidence of new intolerances in patients with three or more prior medication intolerances
  • For type-1 immediate hypersensitivity reactions (IgE-mediated), cross-reactivity among penicillins is expected due to similar core structure and/or major/minor antigenic determinants, use not recommended without desensitization

  • For type-1 immediate hypersensitivity reactions, cross-reactivity between penicillins and cephalosporins is due to similarities in the side chains; risk of cross-reactivity will only be significant between penicillins and cephalosporins with similar side chains

  • Only type-1 immediate hypersensitivity to a penicillin manifesting as anaphylaxis, bronchospasm, angioedema, hypotension, urticaria or pruritic rash warrant the avoidance of cephalosporins with similar side chains and other penicillins

  • Patients with type-1 immediate hypersensitivity to a penicillin may be safely given cephalosporins with side chains unrelated to the offending agent

    • For example, ceFAZolin does not share a side chain with any beta-lactam and is not expected to cross react with other agents
  • Cross-reactivity between cephalosporins is low due to the heterogeneity between side chains; therefore, a patient with a cephalosporin allergy may be prescribed another cephalosporin with a dissimilar side chain

  • Cross-reactivity between penicillins and carbapenems is low. Carbapenems would be a reasonable option when antibiotics are required in patients with type-1 immediate hypersensitivity reaction to penicillins

  • Any patient with possibility of type-1 immediate hypersensitivity to a beta-lactam should be referred for allergy confirmation

Patients with one of the following reactions secondary to beta-lactam use should avoid beta-lactams and not receive beta-lactam skin testing, re-challenging or desensitization:

  • Stevens-Johnson syndrome

  • toxic epidermal necrolysis

  • drug reaction with eosinophilia and systemic symptoms

  • immune hepatitis

  • hemolytic anemia

  • serum sickness or

  • interstitial nephritis

Can be used to predict penicillin sensitivity and have a 97-99% negative predictive value

(not currently available at SAH)