WHO published a report on the state of development of antibacterial drugs

The World Health Organization (WHO) published its latest today report on antibacterial agents, including antibiotics, in clinical and preclinical development worldwide. Although the number of antibacterial agents in the clinical pipeline has increased from 80 in 2021 to 97 in 2023, there is an urgent need for new, innovative drugs for serious infections and to replace those that are becoming ineffective due to widespread use.

First published in 2017, this annual report assesses whether current research and development (R&D) projects are properly addressing infections caused by drug-resistant bacteria that pose the greatest threat to human health, as detailed in 2024 WHO priority list of bacterial pathogens (BPPL). Both documents aim to direct antibacterial research and development to better counter the growing threat of antimicrobial resistance (AMR).

AMR occurs when bacteria, viruses, fungi and parasites no longer respond to drugs, making people sicker and increasing the risk of spreading hard-to-treat infections, disease and death. AMR is mainly caused by the misuse and overuse of antimicrobials, but at the same time, many people around the world do not have access to basic antimicrobials.

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

Not only are there too few antibacterial drugs in the pipeline, given the time required for research and development and the likelihood of failure, there is also not enough innovation. Of the 32 antibiotics being developed to treat BPPL infections, only 12 can be considered innovative. Furthermore, only 4 of these 12 are active against at least 1 WHO 'critical' pathogen – critical is BPPL's ​​highest risk category, above 'high' and 'medium' priority. There are gaps throughout the process, including products for children, oral formulations more suitable for outpatients, and means to address growing drug resistance.

Encouragingly, non-traditional biological agents, such as bacteriophages, antibodies, antiviral agents, immune-modulating agents, and microbiome-modulating agents, are increasingly being explored as adjuncts and alternatives to antibiotics. However, studying and regulating non-traditional agents is not straightforward. Further efforts are needed to facilitate clinical studies and evaluations of these products, to help determine when and how to use these agents clinically.

Looking at newly approved antibacterial drugs, as of July 1, 2017, 13 new antibiotics have received marketing approval, but only 2 represent a new chemical class and can be called innovative, highlighting the scientific and technical challenge in discovering new antibacterial drugs that are effective against bacteria and safe for humans.

In addition, 3 non-traditional means, all faecal-based products, have been approved to restore the intestinal microbiota, in order to prevent recurrence Clostridioides difficile infections (CDI) after antibiotic treatment in adults.

The pre-clinical program is active and innovative, with many non-traditional approaches, as part of a stable number of pre-clinical candidates over the last 4 years. His focus continues to be gram-negative pathogens, which are resistant to last-line antibiotics. Gram-negative bacteria have a built-in ability to find new ways to resist treatment and can transfer genetic material that allows other bacteria to also become drug-resistant.

The shift toward antibacterial agents targeting a single pathogen appears to have stalled. Agents that target a single pathogen increase the need for widely available and affordable rapid diagnostics to ensure that the relevant bacteria are present in the infections to be treated.

Greater transparency in preparation would: facilitate collaboration on potentially innovative but challenging projects, help scientists and drug developers, and generate more interest and funding for drug development for new antibacterial agents.

Efforts to develop new antibacterial agents should be accompanied by parallel efforts to ensure equitable access, especially in low- and middle-income countries. Universal access to quality and affordable tools to prevent, diagnose and treat infections is key to mitigating the public health and economic impact of AMR, according to WHO Strategic and operational priorities for addressing AMR in the human health sector, the Resolution on AMR adopted at the 77th World Health Assembly and A people-centred approach to addressing AMR and a core package of interventions against AMR.