Innovative perspectives on the discovery of small molecule antibiotics

Antibiotics are essential to modern medicine, but multidrug-resistant (MDR) bacterial infections threaten their efficacy. Resistance evolution shortens antibiotic lifespans, limiting investment returns and slowing new approvals. Consequently, the WHO defines four innovation criteria: new chemical class, target, mode of action (MoA), and lack of cross-resistance. This review explores innovative discovery approaches, including AI-driven screening, metagenomics, and target-based strategies, to develop novel antibiotics that meet these criteria and combat MDR infections.