Cephalosporin Allergy

Cephalosporin allergy is a hypersensitivity reaction to cephalosporin antibiotics. It is usually side chain specific, so the allergy rarely extends to all beta lactams.

Pathophysiology. Cephalosporin allergens are mostly the R1 and R2 side chains, not the core. Immediate IgE-mediated reactions occur within an hour. Delayed benign rash is T cell mediated, and severe cutaneous reactions are rare.

Cross-reactivity between cephalosporins is determined by shared R1 side chains. Between penicillins and cephalosporins it is about 2%, and with carbapenems under 1%.

Cefazolin has unique side chains and does not cross-react with other beta lactams, so it can be given to most penicillin allergic patients.

• Urticaria, angio oedema, wheeze or anaphylaxis within 1 hour of a dose, often with ceftriaxone, cefazolin or cefuroxime
• Delayed maculopapular rash 5 to 10 days after the start
• Haemolytic anaemia and serum sickness like illness (cefaclor)
• Severe cutaneous reactions, rarely
• Perioperative anaphylaxis after cefazolin prophylaxis
• Reaction with rash in a child with a viral illness, mislabelled as allergy

• Detailed history: drug, dose, time to onset, features, treatment, and other beta lactams tolerated.
• Skin prick and intradermal tests with the culprit cephalosporin and alternatives (cefazolin, ceftriaxone, cefuroxime, cefepime), plus penicillin tests, since allergy may be to the penicillin ring: concentrations vary by agent and are set by the allergy service.
• Specific IgE is insensitive and is rarely used.
• Oral or intravenous challenge with the culprit or an alternative cephalosporin after negative tests, in a monitored setting.
• Do not challenge after severe cutaneous reactions or organ injury.
• Serum tryptase after an immediate reaction.

Differential diagnosis.

• Penicillin allergy
• Viral exanthem and infectious mononucleosis rash
• Non-allergic side effects (gastrointestinal upset, diarrhoea)
• Serum sickness like reaction
• Reaction to another drug or excipient given at the same time
• Perioperative anaphylaxis from other agents (neuromuscular blockers, chlorhexidine)

• Avoid the culprit and agents with the same R1 side chain, and use a cephalosporin with a dissimilar side chain after testing or challenge.
• Surgical prophylaxis: cefazolin 2 g intravenously within 60 minutes before incision in adults (children 30 mg/kg, maximum 2 g) is safe in most penicillin allergic patients, as its side chains are unique. In proven cefazolin allergy, use vancomycin or clindamycin under specialist direction.
• Ceftriaxone (2 g intravenously once daily in adults; children 50 to 80 mg/kg, maximum 2 g) is avoided in confirmed ceftriaxone allergy and related methoxyimino cephalosporins (cefotaxime, cefepime).
• Anaphylaxis: adrenaline 0.5 mg intramuscularly (children 0.01 mg/kg, maximum 0.5 mg) into the anterolateral thigh, repeated after 5 minutes if no improvement, plus oxygen and intravenous fluids, and observation for at least 6 hours.
• Severe delayed reactions: stop the drug, give supportive care and specialist treatment, and avoid all cephalosporins.
• Delabelling: negative tests and challenge allow the label to be removed.
• Medical alert for confirmed allergy, with the specific agents named.

Special groups.

• Patients needing cardiac, orthopaedic or other implant surgery: arrange testing before elective surgery so that effective prophylaxis can be used.

Monitoring. Observe for 1 hour after challenge, and contact if delayed rash appears.

Referral and escalation. Refer to a drug allergy service for anaphylaxis, severe cutaneous reaction, or when a cephalosporin is essential. Emergency for anaphylaxis.