<p>Antibiotic shortages are increasing worldwide. Their impact on individual health and bacterial ecology is unknown, but it could be significant, and there is a lack of epidemiological evidence. Here, we assess the impact of beta-lactam shortage management on pneumococcal resistance and the incidence of invasive pneumococcal disease (IPD). We developed a mechanistic model of <i>S. pneumoniae</i> paediatric colonization and transmission, accounting for beta-lactam and macrolide exposure. We explored the effects of four antibiotic allocation strategies following a one-year beta-lactam shortage: lowering consumption frequency, shortening treatment duration, reducing the daily dose, or substituting beta-lactams with macrolides. These strategies were analyzed in different European pharmaco-epidemiological settings. We found heterogeneous impacts of allocation strategies, amplified at high shortage intensity. The adverse outcomes of shortages increased with baseline antibiotic consumption and the main determinants of the optimal strategy were the initial prevalence of resistance. Reducing beta-lactam frequency most effectively limited resistance, lowering penicillin-non-susceptible and multidrug-resistant strains by up to 21% in Spain during a 50% shortage. The optimal strategy for minimizing IPD incidence was country-dependent: either lowering the daily dose or beta-lactam-to-macrolide substitution. However, the latter significantly increased macrolide resistance, reaching up to 26.2% in Denmark, for a 50% shortage. Our results show that public health priorities and country-specific pharmaco-epidemiological factors should guide antibiotic management strategies during antimicrobial shortages.</p>