Penicillin Allergy

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About 10% of the general population believe they have a penicillin allergy, often because of a skin rash that occurred during a course of penicillin in childhood, or due to non-allergic side-effects, such as GI upset. 

Fewer than 10% of people who think they are allergic to penicillin are truly allergic. 

Patients with a label of penicillin allergy are more likely to be treated with broad spectrum, non-penicillin antibiotics, such as quinolones, vancomycin and third generation cephalosporins. Use of these antibiotics in people with an unsubstantiated label of penicillin allergy may drive antibiotic resistance and, in some cases, result in suboptimal therapy.

If a patient reports an allergy to an antimicrobial, the nature and severity of the reaction should always be asked about and documented.

Immediate, rapidly evolving reactions - severe allergy

Anaphylaxis is a severe multi-system reaction characterised by:

  • erythema, urticaria or angioedema and
  • hypotension and/or bronchospasm

Onset usually less than 1 hour after drug exposure, often within minutes (previous exposure not always confirmed)

Urticaria or angioedema without systemic features

Exacerbation of asthma 


Non-immediate reactions without systemic involvement - minor allergy

Widespread red macules or papules (exanthema-like)

Onset usually 6-10 days after first drug exposure or within 3 days of second exposure

Fixed drug eruption (localised inflamed skin)


Non-immediate reactions with systemic involvement - not IgE mediated

Drug reaction with eosinophilia and systemic symptoms (DRESS) or drug hypersensitivity syndrome (DHS) characterised by:

  • widespread red macules, papules or erythroderma
  • fever
  • lymphadenopathy
  • liver dysfunction
  • eosinophilia

Onset usually 2-6 weeks after first drug exposure or within 3 days of second exposure

Toxic epidermal necrolysis or Stevens-Johnson syndrome characterised by:

  • painful rash and fever (often early signs)
  • mucosal or cutaneous erosions
  • vesicles, blistering or epidermal detachment
  • red purpuric macules or erythema multiforme

Onset usually 7-14 days after first drug exposure or within 3 days of second exposure


The following chart applies to use of antimicrobials in true beta-lactam/penicillin allergy only: