Beta-Lactam Allergy

Beta lactam allergy is a hypersensitivity reaction to penicillins, cephalosporins, carbapenems or monobactams. Most patients with the label are not allergic, and cross-reactivity between classes is low.

Pathophysiology. Immediate reactions are IgE-mediated against the shared beta lactam core, or more often against the side chains. Delayed reactions are T cell mediated and include benign rash and severe cutaneous reactions.

Cross-reactivity between penicillins and cephalosporins is about 2%, driven by shared side chains rather than the ring. With carbapenems it is under 1%.

Aztreonam shares a side chain with ceftazidime and cefiderocol, and not with penicillins.

• Immediate: urticaria, angio oedema, wheeze, stridor, hypotension within 1 hour of a dose
• Delayed benign rash: maculopapular exanthem days after the start of treatment
• Severe cutaneous reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS, AGEP
• Organ reactions: interstitial nephritis, haemolytic anaemia, hepatitis, serum sickness like illness
• Reaction during an infection with rash from the illness itself (viral exanthem, infectious mononucleosis), mislabelled as allergy
• A family history or vague childhood label with no details

• Detailed history: drug, date, time to onset, features, treatment needed, repeat exposures and tolerated beta lactams since.
• Risk score (PEN-FAST): allergy within 5 years (2 points), anaphylaxis, angio oedema or severe cutaneous reaction (2 points), treatment needed (1 point). A score under 3 is low risk.
• Direct oral challenge in low risk patients: amoxicillin 500 mg in adults (children 25 mg/kg, maximum 500 mg), observe for 1 hour, with resuscitation equipment available.
• Skin prick and intradermal tests in higher risk patients: benzylpenicilloyl polylysine, minor determinant mixture, penicillin G, amoxicillin and the culprit drug, followed by oral challenge if negative. Specific IgE is less sensitive.
• Do not challenge after severe cutaneous reactions, organ injury or haemolysis.
• Cross-reactivity check by side chain for any alternative beta lactam.

Differential diagnosis.

• Viral exanthem and drug virus interaction rash
• Non-allergic side effects (gastrointestinal upset, headache, candidiasis)
• Serum sickness like reaction
• Allergy to another co-prescribed drug
• Chronic spontaneous urticaria
• Mast cell disorder

• Delabel by testing whenever possible, and record the result in the notes and the allergy record.
• Active allergy: avoid the culprit and chemically similar drugs. Use a beta lactam with a dissimilar side chain after an uneventful challenge, since this preserves first line treatment.
• Carbapenems: can usually be given to penicillin allergic patients without testing, with observation for the first dose.
• Severe cutaneous reactions: avoid all beta lactams permanently, stop the drug, and give supportive and specialist treatment.
• 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.
• Desensitisation when a beta lactam is essential (for example syphilis in pregnancy, enterococcal endocarditis): stepwise dose escalation in a monitored setting, repeated whenever therapy is interrupted for over 24 hours.
• Medical alert for confirmed allergy.

Special groups.

• Children: most reactions are benign rashes during viral illness, so oral challenge is usually safe.
• Pregnancy: penicillin is needed for syphilis and group B streptococcal prophylaxis, so test early.

Monitoring. Observe for 1 hour after challenge, and contact if delayed rash appears. No routine monitoring after delabelling.

Referral and escalation. Refer to a drug allergy service for anaphylaxis, severe cutaneous reaction history, multiple drug allergy labels, or when a beta lactam is essential. Emergency for anaphylaxis.