Metabolomics-driven prediction of antibiotic resistance: a perspective on pre-genetic intervention

Antibiotic resistance is surging, demanding approaches that detect resistance before genetic fixation, since MIC, sequencing, and culture assays detect resistance late. We present Metabolomics-Driven Intervention Antibiotic Design (MDAD), which stages resistance evolution from metabolic compensation to sub-lethal adaptation to genetic fixation. A brief pulse challenge with a targeted metabolomics panel yields a pre-genetic risk index, interpreted with time-kill assays to situate early survival behaviours and guide mechanism-aware treatment and surveillance.