• IgE-mediated (allergic) immediate hypersensitivity is characterised by the development of urticaria,
angioedema, bronchospasm or anaphylaxis (with objectively demonstrated hypotension, hypoxia or
elevated mast-cell tryptase concentration) within 1 to 2 hours of exposure to a drug. Anaphylaxis is more
likely with parenteral rather than oral administration. For penicillin, anaphylaxis occurs at an estimated
frequency of 1 to 4 cases per 10 000 courses, with up to 10% of these reactions being fatal. A clear history
of an IgE-mediated reaction means the drug should not be administered again without appropriate
precautions (eg desensitisation).
• IgE-independent (non-allergic) immediate hypersensitivity refers to any acute or immediate reaction
that does not involve an IgE-mediated mechanism, usually caused by direct mast-cell degranulation (e.g.
vancomycin infusion–related reactions such as 'red-man' syndrome). The reaction may be ameliorated by
prophylactic antihistamines and slowing the infusion rate.
• Delayed-type (nonimmediate) hypersensitivity reactions are characterised by macular, papular or
morbilliform rash, occurring several days after starting treatment. They are more common than immediate
reactions, and may be caused by the infection or its treatment. Such reactions are usually T-cell (not IgE)
mediated. Delayed-type reactions commonly occur in patients with intercurrent infection, and such reactions
may not be reproducible upon a supervised challenge when the patient is well. Delayed rash due to
penicillins, especially amoxy/ampicillin, is not strongly predictive of a future reaction, and repeat exposure
to beta lactams is not necessarily contraindicated.
Three kinds of delayed-type reaction warrant special mention:
• Serum sickness — characterised by vasculitic rash, arthralgia/arthritis, influenza-like symptoms, and
sometimes fever and proteinuria. Serum sickness is triggered more commonly with cefaclor than other
cephalosporins, and also by sulfonamides, and commences several days after starting treatment drug rash
with eosinophilia and systemic symptoms (DRESS)—characterised by peripheral blood eosinophilia,
desquamative dermatitis and liver dysfunction.
• Stevens–Johnson syndrome / toxic epidermal necrolysis (SJS/TEN) — a very rare, acute and
potentially fatal skin reaction characterised by sheet-like skin and mucosal loss.
• DRESS and SJS/TEN are contraindications to further drug exposure (including desensitisation) because
this can be fatal. Patients with a known severe hypersensitivity should be strongly advised to wear an alert
bracelet or necklace
Consultation
Key stakeholders who reviewed this version:
• Pharmacist Advanced - Antimicrobial Stewardship Pharmacist (CHQ)
• Director of IMPS, immunology and rheumatology (CHQ)
• Infection specialists, IMPS (CHQ)
• Chief of Surgery (CHQ)
• Director – Paediatric Intensive care Medicine (CHQ)
• Director- Anaesthetics (CHQ)
• Senior Staff Specialist Paediatric Surgeon (CHQ)
• Consultant Cardiac Surgeon (CHQ)
• Pharmacist Clinical Lead – Surgical
• CNC – Surgical Clinical reviewer, ACS NSQIP