Clinical Development of Antibacterial Drugs: Recent Progress and Future Outlook

The growing burden of antibiotic resistance demands the development of new antibacterials, including those with novel targets and mechanisms of action. This review summarizes key antibacterials that were in clinical development from 2010 to 2026, highlighting their antibacterial classes, mechanisms of action, antibacterial spectrum, clinical applications, development status, and resistance concerns. Antibacterial development during this period encompasses improvements to established antibiotic classes, new β-lactam/β-lactamase inhibitor combinations, siderophore cephalosporins, antibiotic hybrids, antibody-antibiotic conjugates, narrow-spectrum antibacterials, and antibacterials with novel chemical scaffolds, targets, and mechanisms of action. Successful clinical translation, promising emerging antibacterials, and innovations in antibacterial design and delivery are discussed. Lessons from discontinued development programs, including barriers related to safety, efficacy, and emerging resistance, are also highlighted to inform future antibacterial design and clinical trials. Continued investment in antibacterial discovery, early assessment of resistance potential and safety, exploration of nontraditional treatments, application of machine learning and artificial intelligence-guided methods, antibiotic stewardship, and implementation of One Health approaches will be important for addressing the growing challenge of antibiotic resistance.