Non-Traditional Antibacterial Agents Relevant to the WHO 2024 Priority Pathogens: A Structured Update of the Clinical...

Antimicrobial resistance (AMR) is an urgent global threat, with bacteria developing resistance against most antibiotics currently in clinical use. Non-traditional antibacterials-including bacteriophages, antimicrobial peptides (AMPs), monoclonal antibodies (mAbs), live biotherapeutic products (LBPs) and anti-virulence small molecules-act through mechanisms distinct from traditional antibiotics and may exhibit mechanism-dependent differences in the propensity for resistance development. Despite growing interest, the landscape of non-traditional candidates in active clinical development against WHO priority pathogens has not been recently systematically mapped. This review aimed to characterize the current non-traditional antibacterial clinical pipeline targeting pathogens on the WHO Bacterial Priority Pathogens List (BPPL) 2024.

Candidates were identified from the WHO antibacterial clinical pipeline report (October 2025) and verified through the Global AMR R&D Hub, ClinicalTrials.gov, and targeted searches of peer-reviewed publications, conference abstracts, and company communications. Candidates were included if they showed documented clinical activity since January 2023.

Twenty-seven candidates met the inclusion criteria, of which 20 remain in active clinical development and seven have been discontinued or paused or have unverified status. The pipeline is dominated by bacteriophages and markedly skewed toward carbapenem-resistant Pseudomonas aeruginosa (CRPA) and methicillin-resistant Staphylococcus aureus (MRSA), with few or no candidates targeting carbapenem-resistant Acinetobacter baumannii (CRAB), Shigella or Salmonella.

Non-traditional antibacterials represent a promising but underfunded and unevenly distributed pipeline-with public and philanthropic investment in antibacterial R&D totaling just $2.51 billion across 2017-2023, a seven-year total, against an estimated $251-276 billion in global pharmaceutical R&D spending in a single recent year. Realizing their potential will require substantially greater investment and more deliberate prioritization toward the WHO priority pathogens currently underserved by the non-traditional pipeline.