Abstract Background Up to 10% of hospitalized patients in Europe carry a penicillin allergy label, yet most are inaccurate. Mislabelling drives inappropriate broad-spectrum antibiotic use, increased resistance, prolonged admissions, and higher costs. Whilst local and national studies suggest that de-labelling is cost-saving, there has been no EU-wide analysis accounting for cross-country differences in antimicrobial resistance (AMR), costs, and equity. Methods We conducted a distributional cost-effectiveness analysis (DCEA) comparing Uniform versus Targeted rollout of penicillin allergy de-labelling across all 27 EU member states. Population data were sourced from Eurostat (2025) and AMR indices from ECDC EARS-Net (2023). Conservative estimates of prevalence, de-labelling effectiveness, QALY gains, and cost savings were drawn from published literature. Outcomes included incremental QALYs, costs, net health benefit (NHB), equity-weighted NHB (ENHB), and equally distributed equivalent (EDE) QALYs. Probabilistic sensitivity analysis (n = 1000) assessed robustness. Results Both strategies were dominant (health-gaining and cost-saving). Uniform rollout yielded 331 318 QALYs and €1.44 billion in savings, whilst Targeted delivered 355 561 QALYs and €1.54 billion, an incremental gain of 24 243 QALYs and €105 million. Benefits correlated strongly with AMR burden (r = 0.839). Country-level analysis revealed 2.1-fold variation in equity benefits, with the highest gains in Southern and Eastern European countries. Conclusions Penicillin allergy de-labelling is a cost-saving, equity-promoting strategy across the EU. Targeted rollout offers superior efficiency and fairness, particularly in high-AMR countries, and should be prioritized for implementation. Key messages What is already known on this topic: Penicillin allergy labels are common but mostly inaccurate, leading to broader-spectrum antibiotic use, higher costs, and increased antimicrobial resistance. De-labelling is known to be clinically safe and cost-saving in local and national studies. EU-wide evidence incorporating equity and antimicrobial resistance burden has been lacking. What this study adds: This study provides the first EU-wide distributional cost-effectiveness analysis of penicillin allergy de-labelling. Both Uniform and Targeted rollout strategies are cost-saving and health-improving across all EU member states. Targeted implementation yields additional efficiency and equity gains, especially in high-AMR countries. How this study might affect research, practice or policy: Penicillin allergy de-labelling should be prioritized as a core EU antimicrobial stewardship strategy. Targeted rollout can maximize health gains and equity in high-burden settings. These results support EU-level investment and coordinated implementation of de-labelling programmes.
Mikulić et al. (2026) studied this question.