Impact of amoxicillin shortage on pneumococcal resistance and IPD in children: evaluation of different management strategies in European countries

Antibiotic shortages are increasing worldwide, with potential major consequences for both individual health and bacterial ecology. 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 S. pneumoniae paediatric colonisation 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. Our findings reveal heterogenous impacts of allocation strategies, amplified at high shortage intensity. Shortage-induced consequences increased with baseline antibiotic consumption levels. Reducing beta-lactam consumption frequency was the most effective approach to managing pneumococcal resistance across Europe, decreasing penicillin-non-susceptible and multidrug-resistant strains by up to -21.4% in Spain, for 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, with a relative rise by 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.