WHO Report Highlights Urgent Need for Innovative Antibacterial Agents Amid Rising AMR Threat

AMR occurs when bacteria, viruses, fungi, and parasites no longer respond to medicines, leading to more severe illnesses, increased spread of infections, and higher mortality rates.

The World Health Organization (WHO) has released its latest report on antibacterial agents, including antibiotics, in clinical and preclinical development worldwide. The report shows an increase in antibacterial agents in the clinical pipeline from 80 in 2021 to 97 in 2023. However, there remains a pressing need for new, innovative agents to treat serious infections and replace those that are becoming ineffective due to widespread use.

First published in 2017, this annual report assesses whether the current research and development (R&D) pipeline adequately addresses infections caused by the most threatening drug-resistant bacteria, as detailed in the 2024 WHO bacterial priority pathogen list (BPPL). Both documents aim to guide antibacterial R&D efforts to better counter the growing threat of antimicrobial resistance (AMR).

AMR occurs when bacteria, viruses, fungi, and parasites no longer respond to medicines, leading to more severe illnesses, increased spread of infections, and higher mortality rates. It is largely driven by the misuse and overuse of antimicrobials, while many people globally still lack access to essential antimicrobial medicines.

“Antimicrobial resistance is only getting worse, yet we’re not developing new trailblazing products fast enough to combat the most dangerous and deadly bacteria,” said Dr. Yukiko Nakatani, WHO’s Assistant Director-General for Antimicrobial Resistance ad interim. “Innovation is badly lacking, and even when new products are authorized, access remains a serious challenge. Antibacterial agents are simply not reaching the patients who desperately need them, in countries of all income levels.”

Despite the increase in antibacterial agents in the pipeline, innovation remains insufficient. Of the 32 antibiotics under development to address BPPL infections, only 12 are considered innovative. Furthermore, just four of these 12 are active against at least one WHO ‘critical’ pathogen – the highest risk category in the BPPL. There are significant gaps in the pipeline, including products for children, oral formulations for outpatients, and agents to combat rising drug resistance.

Encouragingly, non-traditional biological agents, such as bacteriophages, antibodies, anti-virulence agents, immune-modulating agents, and microbiome-modulating agents, are increasingly being explored as alternatives and complements to antibiotics. However, studying and regulating these non-traditional agents is complex. Further efforts are needed to facilitate clinical studies and assessments of these products to determine their clinical use.

Since July 2017, 13 new antibiotics have received marketing authorization, but only two represent new chemical classes and can be termed innovative. This highlights the scientific and technical challenges in discovering novel antibacterials that are both effective and safe for humans. Additionally, three non-traditional agents have been authorized, all faecal-based products for restoring the gut microbiota to prevent recurrent Clostridioides difficile infection (CDI) following antibiotic treatment in adults.

The preclinical pipeline remains active and innovative, focusing primarily on Gram-negative pathogens resistant to last-resort antibiotics. Gram-negative bacteria have inherent abilities to resist treatment and can transfer genetic material to other bacteria, spreading drug resistance.

The trend towards antibacterial agents targeting a single pathogen appears to have plateaued. Such agents increase the need for widely available and affordable rapid diagnostics to ensure the relevant bacteria are present in the infections being treated.

Greater transparency in the pipeline would facilitate collaboration on potentially innovative but challenging projects, assist scientists and drug developers, and generate more interest and funding for novel antibacterial agents' development.

Efforts to develop new antibacterial agents must be accompanied by parallel efforts to ensure equitable access, particularly in low- and middle-income countries. Universal access to quality and affordable tools for preventing, diagnosing, and treating infections is crucial to mitigating AMR’s impact on public health and the economy, as outlined in WHO’s Strategic and Operational Priorities for Addressing AMR in the Human Health Sector, the AMR resolution adopted by the 77th World Health Assembly, and the People-centred approach to addressing AMR and core package of AMR interventions.