The World Health Organization (WHO) has released its latest annual report on the development of antibacterial agents, including antibiotics, revealing both progress and persistent challenges in the fight against antimicrobial resistance (AMR). The number of antibacterial agents in clinical development has increased from 80 in 2021 to 97 in 2023. Despite this growth, there is a significant need for new and innovative treatments to combat serious infections and replace those losing effectiveness due to widespread antimicrobial use.

Focus on Antimicrobial Resistance

AMR, a condition where bacteria, viruses, fungi, and parasites become resistant to treatments, poses a growing threat to public health. This resistance leads to more severe illnesses, increased transmission of infections, and higher mortality rates. AMR is mainly driven by the misuse and overuse of antimicrobials, while many people still lack access to essential medicines.

Pipeline Evaluation and Challenges

First published in 2017, the WHO's annual report assesses the research and development (R&D) pipeline against the needs identified in the 2024 WHO bacterial priority pathogen list (BPPL). The report aims to guide R&D towards addressing the most critical threats to human health posed by drug-resistant bacteria.

Dr. Yukiko Nakatani, WHO’s Assistant Director-General for Antimicrobial Resistance ad interim, emphasized the urgency of the situation: “Antimicrobial resistance is only getting worse yet we’re not developing new trailblazing products fast enough to combat the most dangerous and deadly bacteria.”

Lack of Innovation

The current pipeline reveals a lack of sufficient innovation. Out of 32 antibiotics under development to address BPPL infections, only 12 are considered innovative, and just 4 target at least one 'critical' pathogen from the BPPL. This critical category represents the highest risk level. The pipeline also shows significant gaps, including the need for products suitable for children, convenient oral formulations for outpatients, and treatments for rising drug resistance.

Exploring Non-Traditional Agents

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

Recent Approvals and Future Directions

Since July 2017, 13 new antibiotics have received marketing authorization, but only 2 represent a new chemical class and can be termed innovative. Additionally, 3 non-traditional agents have been approved, all fecal-based products for restoring 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. These bacteria can develop resistance quickly and transfer resistance genes to other bacteria.

Need for Better Diagnostics

The shift towards antibacterial agents targeting a single pathogen highlights the necessity for rapid diagnostics that are widely available and affordable, ensuring that the specific bacteria are present in the infections being treated.

Call for Collaboration and Access

Greater transparency in the pipeline could facilitate collaboration, generate more interest and funding, and help advance challenging projects. Alongside developing new antibacterial agents, it is crucial to ensure equitable access to these treatments, particularly in low- and middle-income countries. Universal access to quality and affordable tools for preventing, diagnosing, and treating infections is essential to mitigate AMR's impact on public health and the economy.

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 emphasize the need for a coordinated global effort to tackle this pressing health issue.