Antimicrobial use in intensive care units (ICUs) is exceptionally high. Simultaneously, the global rise in multi-drug resistant organisms has driven increased reliance on last-resort antimicrobial treatments (AMT). Most current knowledge about the ecological impact of AMT comes from in-vitro studies, animal models, and small cohort research. However, the complex interplay between patient characteristics, antimicrobial exposure, and environmental factors—particularly in critically ill patients—remains poorly understood. Antimicrobial stewardship strategies often lack robust evidence on their ability to limit resistance and preserve future treatment options. Our research aims to evaluate the ecological effects of different AMT strategies, providing a scientific basis to support informed treatment decisions. A pilot project is underway, and additional funding would support personnel and laboratory materials to advance this critical work.