Cross-reactivity between amoxicillin and piperacillin-tazobactam in patients with amoxicillin allergy: A prospective...

Amoxicillin (AX) is the most frequently prescribed β-lactam antibiotic in the USA and Europe and a leading cause of drug-induced hypersensitivity. Although cross-reactivity between aminopenicillins and ureidopenicillins can be considered unlikely based on side-chain dissimilarity, clinical data remain limited.

To prospectively evaluate cross-reactivity to piperacillin-tazobactam (PPZ-TZB) in patients with confirmed AX hypersensitivity.

We conducted a prospective study of 49 patients with confirmed AX hypersensitivity. Diagnosis was established through clinical history, skin testing (ST), specific IgE testing, and drug provocation testing (DPT), where indicated. All patients were systematically tested with PPZ-TZB by ST, followed by DPT in those with negative results.

Among 49 patients with confirmed AX hypersensitivity (mean age, 47.5 years; 61.2% female), 31 (63.3%) experienced immediate reactions and 18 (36.5%) experienced non-immediate reactions. Anaphylaxis was the most common presentation (49.9%). AX hypersensitivity was confirmed by positive ST result in 32 patients (65.3%), specific IgE in 3 (6.1%), DPT in 12 (24.5%), and clinical history in 2 (4.1%). All patients had negative results for penicillin major and minor determinants. PPZ-TZB hypersensitivity was diagnosed in 9 patients (18.4%), mostly by positive ST results (8 cases) and in 1 case by DPT, which elicited acute bronchospasm. Cross-reactivity occurred in both immediate and non-immediate groups.

In this cohort of patients with confirmed AX allergy, cross-reactivity to PPZ-TZB occurred in approximately one-fifth of cases, most frequently identified by ST. These results emphasize that systematic allergy workup-particularly ST followed by DPT when result is negative-is essential before prescribing PPZ-TZB in patients with AX hypersensitivity.