Evaluating the innovative potential of the global antibacterial pipeline

BackgroundResistance burden varies widely among WHO regions, and the potential impact of new antibiotics differs in addressing the WHO's critical priority pathogens' resistance challenge.ObjectivesAnalyse the current global clinical pipeline in line with public and global health concerns and define innovation in antibacterial drug discovery.SourcesMonitoring clinical pipelines since 2006, integrating peer-reviewed MEDLINE publications on clinical development of new antibacterial agents, supplemented with disclosed data from developers.ContentThe current clinical pipeline is dominated by derivatives of established antibiotic classes, primarily β-lactamase inhibitor (BLI) combinations in Phase 3 (6 out of 10 which also include 2 beta-lactams without BLI). This pattern extends to Phase 1. Although incremental improvements in susceptibility rates among derivatives benefit patients in advanced healthcare systems within specific geographical regions, these concepts are not adequate for carbapenem-resistant strains of Enterobacterales (especially Klebsiella and E. coli), Acinetobacter, and Pseudomonas. This limitation arises from the diverse distribution of resistance mechanisms across global regions. Innovation in this context refers to absence of cross-resistance due to class-specific resistance mechanisms. This can most likely be achieved by exploring new chemical classes and new targets/binding sites, and new mode of action. An initial glimpse of progress is evident as innovative agents progressed to Phase 1 clinical trials. However, an influx of more agents advancing to clinical development is essential given the inherent risks associated with novel chemistry and targets.ImplicationsThe limited innovation in the global clinical pipeline inadequately serves public and global health interests. The complexities of antibacterial drug discovery, from scientific challenges to financial constraints, underscore the need for collective researcher efforts and public support to drive innovation for patients globally.