Penicillin Allergy Cross-Reactivity — RACP Adult Medicine MCQ

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ModerateInfectious DiseasesPenicillin Allergy Cross-ReactivityRACP Adult Medicine

A 40-year-old woman with confirmed penicillin allergy (anaphylaxis to amoxicillin with positive skin test) requires antibiotics for community-acquired pneumonia. She has no cephalosporin allergy history. What is the safest beta-lactam choice?

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Correct answer: B — Ceftriaxone (3rd generation cephalosporin)

Cross-reactivity between penicillins and cephalosporins is ~1-2% (previously overestimated at 10%). Third and fourth generation cephalosporins have the lowest cross-reactivity with penicillins (<0.5%) due to dissimilar R1 side chains. First generation cephalosporins (cephalexin) share more structural similarity and have higher cross-reactivity (~1-2%). Carbapenems have very low cross-reactivity (<1%). A graded challenge is recommended.

Reference: ASCIA – 2024 – Drug Allergy; eTG Antibiotic 2025