Superbugs Rising, Antibiotics Fading

Developing new antibiotics is complex and costly. Still, initiatives and advances are emerging that invite cautious optimism.

The World Health Organization (WHO) considers antimicrobial resistance (AMR) as one of the top ten global health threats. In 2017, it published a list of priority pathogens for which new antibiotics are urgently needed. This list was updated in 2024, and most of the bacteria in the critical and high priority groups are multidrug-resistant.

Many major pharmaceutical companies have reduced or eliminated their antibiotic research and development programs due to high costs and low returns

Discovering new antimicrobial therapies—especially against Gram-negative bacteria—is a complex challenge. Moreover, bacteria often develop resistance shortly after a new antibiotic reaches the market. Currently, the clinical pipeline includes 57 antibiotics and 40 non-traditional antibacterial agents. The latter include bacteriophages, antivirulence antibodies, immunomodulatory therapies, and microbiota modulators. However, only 12 of the 57 antibiotics belong to truly novel classes, meaning they target bacterial mechanisms that have not yet been exploited.

Historically, only around 20% of antibiotics entering clinical trials make it to market, reflecting a discouraging outlook for antibiotic development.

What are the main obstacles?

One of the major challenges is scientific. There are several methods to discover new antibiotics, including:

• Screening synthetic compounds against multidrug-resistant bacteria, especially Gram-negative ones, whose cell walls are more complex than those of Gram-positive bacteria.
• Screening natural products (chemical compounds produced by living organisms in diverse ecosystems). However, this often leads to rediscovering already known compounds or minor variations of existing antibiotics.
• Overcoming resistance mechanisms such as biofilm formation and the rapid emergence of resistant mutants.

Another major obstacle is economic: the lack of return on investment. Many major pharmaceutical companies have reduced or eliminated their antibiotic R&D programs due to high costs and limited profits.

Countries such as the United Kingdom have adopted subscription-based payment models, where companies are compensated based on the value of the antibiotic for public health rather than on sales volume

Developing a new antibiotic can cost between 800 million and 1 billion US dollars. Since antibiotics are used for short periods and their effectiveness declines over time as resistance develops, recouping that investment is difficult.

Reasons for optimism

Despite these challenges, there are promising developments:

1. Innovation from biotech companies. Many small firms are investing in antibiotic development. Although they often face difficulties advancing to clinical trials, they bring innovative approaches to the field.
2. New financial models. Countries like the United Kingdom have adopted subscription-based payment models, where companies are compensated based on the antibiotic’s value to public health, rather than sales volume.
3. Artificial intelligence (AI) and machine learning. Although still in their early stages, these technologies can accelerate drug discovery by identifying promising molecules or repurposing existing drugs to treat infections.
4. International cooperation. The Transatlantic Taskforce on Antimicrobial Resistance (TATFAR), created by the United States and the European Union, promotes collaboration in research, regulation, and funding to overcome scientific and economic barriers.
5. Support initiatives:
   • SPARK (Shared Platform for Antibiotic Research and Knowledge): An online platform for sharing data on Gram-negative bacteria to avoid duplication in research.
   • GARDP (Global Antibiotic Resistance Partnership): A platform that develops strategies against AMR tailored to low- and middle-income countries.
   • ISGlobal (Barcelona Institute for Global Health): Through our Antimicrobial Resistance Initiative, we work on antibiotic development, rapid diagnostics, policy analysis, and technical support.

An urgent cause

The current antibiotic development landscape presents major scientific and economic challenges. However, there are reasons for cautious optimism: innovative financing models, technological advances, and increasing global collaboration offer hope for overcoming the AMR crisis.

The future of antibiotic development will undoubtedly depend on these ongoing efforts and on our collective commitment to this urgent cause.