D1.20 - Challenges in Safe Alternative Selection in a Case of Amoxicillin-Induced Anaphylaxis

Background: Beta-lactamines (BL) are the most frequent culprits of drug hypersensitivity reactions (HSR), either through antigenic epitopes from the BL core, side chains, or other components. Cross-reactivity between aminopenicillins frequently occurs through common side chains. Despite confirmed penicillin IgE-mediated HSR, up to 97% patients tolerate some cephalosporins and 99% tolerate carbapenems. Unnecessarily restricting the use of the entire BL class may negatively impact prognosis and contribute to antimicrobial resistance.

Case presentation: A 54-year-old male patient was admitted for allergy work-up following three episodes of Grade 3 amoxicillin-induced anaphylaxis according to WAO criteria. Clinical manifestations included urticaria, angioedema, dyspnea and diarrhea. The first two reactions occurred after oral administration of amoxicillin, whereas the third followed the cutaneous contact with trace amounts of amoxicillin from a syringe for veterinary use. In vitro detection of specific IgEs was negative for amoxicillin and cefuroxime. However, skin prick testing was positive for amoxicillin, penicillin G, and ampicillin at concentrations of 0.002 mg/ml for all three drugs, confirming IgE-mediated hypersensitivity to penicillins. Subsequent positive intradermal tests to concentrations of  2 mg/ml of ceftriaxone and cefuroxime indicated sensitization to these cephalosporins, despite no prior history of HSR or known exposure to these drugs. Skin tests to cefazolin, ceftazidime, cefiderocol, and meropenem were negative. Tolerance to cefazolin was confirmed by a negative intravenous drug provocation test. 

Conclusion: This is a particular case of co-sensitization to penicillins and to ceftriaxone and cefuroxime, rather than classic BL cross-reactivity. Sensitization to penicillins is likely related to the thiazolidine ring, whereas the co-sensitization to ceftriaxone and cefuroxime may involve their shared methoxyimino R1 side chain, with unrecognized prior exposure remaining the most plausible explanation, given their widespread use in clinical practice. Importantly, we demonstrated tolerance to cefazolin, a cephalosporin lacking common side chains with any BL, in a patient who experienced severe HSR to traces of amoxicillin. This case underscores the importance of comprehensive allergy work-ups for defining safe BL alternatives and highlights the superior sensitivity of in vivo testing compared with in vitro assays within the drug HSR assessment.