| Allergy | Drug class | Cross-reactivity risk | Basis |
|---|---|---|---|
| Penicillin | Cephalosporins | ~2% | R1 side-chain similarity (not beta-lactam ring) |
| Penicillin | Carbapenems | <1% | Distinct side chains; negligible shared epitopes |
| Penicillin | Aztreonam | <1% | Monobactam ring; different R1 chain |
| Ampicillin / Amoxicillin | Cefadroxil, Cephalexin, Cefprozil, Cefaclor | Moderate | Shared aminobenzyl R1 side chain |
| Ceftazidime | Aztreonam | High | Identical R1 side chain — treat as contraindicated |
| Cephalosporins | Carbapenems | <1% | No shared side chains; very low cross-reactivity |
| Sulfonamide antibiotics | Sulfonamide non-antibiotics | Minimal | Different aromatic amines; cross-reactivity likely overestimated |
Cross-reactivity primarily driven by R1 side-chain similarity, not the beta-lactam ring. True penicillin allergy confirmed by skin testing: ~80–90% of reported allergies are not true IgE-mediated reactions.