Antibiotics: From the golden age of miracle drugs to the post-antibiotic era and beyond

The golden age of antibiotics transformed global public health and modern medicine, drastically reducing mortality from bacterial infections and enabling life-saving advances from organ transplantation to cancer chemotherapy. However, decades of unrestrained antibiotic use across clinical, agricultural, and industrial sectors have driven the global pandemic of antimicrobial resistance (AMR), widespread environmental antibiotic contamination, and a near-total collapse of the novel antibiotic research and development (R&D) pipeline, pushing humanity to the brink of a post-antibiotic era. This comprehensive review systematically maps the full trajectory of antibiotics: from the pre-antibiotic era and golden age of discovery, to the current multifaceted AMR crisis, and emerging next-generation antibacterial alternatives, environmental remediation technologies, and global One Health mitigation strategies. We critically compare the clinical translatability of diverse antibacterial alternatives, identify persistent translational bottlenecks from bench to bedside, and highlight critical knowledge gaps in the field. This review provides an evidence-based roadmap for researchers, clinicians, and policymakers to address the global AMR crisis and safeguard effective antibacterial therapies for future generations.