Antibiotic therapy, crucial for treating infections, significantly influences the development of antimicrobial resistance (AMR), a global health threat. In ICUs, where up to 70% of patients receive antibiotics, mostly beta-lactams, AMR risk is high. Reducing AMR emergence can be achieved by shortening antibiotic therapy and ensuring adequate dosing. However, short courses are not yet common practice in ICUs, and current dosing often results in subtherapeutic drug concentrations. This study aims to confirm the non-inferiority of a short, high-dose antibiotic course compared to standard treatment in ICU patients across 14 hospitals in the Netherlands and Belgium. The study will involve 1242 patients with specific infections. If successful, the findings could change ICU antibiotic therapy guidelines, reducing antibiotic exposure while maintaining treatment effectiveness.