2025-06-13T09:09:05Z

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The alarming rise of antimicrobial resistance (AMR) has become a pressing global health crisis, prompting researchers at King's College London to advocate for urgent reforms in the development of new antibiotics. Their comprehensive review, published in npj Antimicrobials and Resistance, delves into the myriad scientific, economic, and regulatory challenges that are hindering advancements in combating infections caused by highly resistant bacteria.

According to the review, AMR is currently responsible for nearly 5 million deaths each year worldwide. If decisive actions are not taken, this figure is projected to double to 10 million annual deaths by the year 2050. The review highlights that some of the most dangerous threats arise from Gram-negative bacteria, particularly species such as Klebsiella pneumoniae, known for causing severe bloodstream infections from routine medical procedures, and Acinetobacter baumannii, which is linked to ventilator-associated pneumonia.

Despite the urgent need for new antibiotics, the last two decades have seen a startlingly low number of new drugs introduced to the market. The complexity of the antibiotic development process, coupled with significant economic barriers, has made it increasingly difficult for pharmaceutical companies to invest in antibiotic research.

One of the major economic challenges stems from the nature of antibiotic usage. Typically, antibiotics are prescribed for short durations and are only utilized when absolutely necessary to mitigate the development of resistance. This limited usage results in significantly lower revenue compared to medications targeting chronic diseases, such as cancer, which are administered over extended periods and yield higher profits.

This economic landscape has led many large pharmaceutical companies, including notable names like AstraZeneca, Johnson & Johnson, and Pfizer, to withdraw from antibiotic research and development. To address this issue, the authors of the review propose that innovative business models are necessary to make the development of antibiotics more appealing to the pharmaceutical sector. They suggest decoupling profits from the volume of antibiotics sold, alongside a combination of 'push' incentives—such as research grants and tax breaks—and 'pull' incentives, which could include market entry rewards or subscription payments for successful products.

A prime example of a forward-thinking initiative is the UK's Antimicrobial Product Subscription Model, which was launched in 2022. This model provides pharmaceutical companies with a fixed annual fee for access to newly developed antibiotics, irrespective of how much of the drug is ultimately utilized. A similar approach is being proposed in the United States through the PASTEUR Act.

Regulatory hurdles further complicate the antibiotic development landscape. Clinical trials for new antibiotics are often fraught with challenges, being large, complex, and costly, particularly due to the difficulty of recruiting appropriate patient populations. Additionally, varying regulatory standards across countries add another layer of complexity to the approval process. The authors advocate for enhanced global cooperation and clearer guidance on the design and evaluation of clinical trials, aiming to make these processes more efficient and predictable.

Furthermore, several scientific hurdles impede the creation of new antibiotics specifically targeting Gram-negative bacteria. These organisms possess a formidable outer membrane that protects them from many potential drugs. They also employ resistance mechanisms such as efflux pumps to expel antibiotics and enzymes that can degrade them. Identifying new drug targets and discovering effective compounds capable of eliminating these resilient bacteria remains a significant challenge.

The review emphasizes the importance of interdisciplinary collaboration to revitalize the antibiotic discovery pipeline. New scientific methodologies, such as the use of artificial intelligence for identifying promising molecular candidates, exploring under-researched environments like the deep sea, and studying rare microbiomes, are suggested as potential avenues for innovation. Additionally, alternative strategies such as phage therapy are being investigated, despite their own set of challenges.

Lead author Miraz Rahman, who serves as the Professor of Medicinal Chemistry and the Antimicrobial Research Theme Group Lead at King's College London, stressed the need for collective efforts across academia, industry, policy, and global health sectors. He stated, "Reviving the antibiotic pipeline will require cooperation across academia, industry, policy, and global health systems. We need not only innovative science but also a supportive economic and regulatory environment to bring new antibiotics to patients."

The review ultimately serves as a rallying cry for action, urging scientists, pharmaceutical developers, governments, and all stakeholders involved in the antibiotic development pipeline to collaborate effectively. By outlining the current challenges faced and proposing a pragmatic path forward, the authors seek to safeguard the future of modern medicine against the rising tide of antimicrobial resistance.

For additional insight, refer to the full review: Gargate, N., et al. Current economic and regulatory challenges in developing antibiotics for Gram-negative bacteria. npj Antimicrobials and Resistance (2025). doi.org/10.1038/s44259-025-00123-1