AMR Drugs and Diagnostics Must Evolve in Tandem

Antimicrobial resistance (AMR) is not a future problem; it is unfolding now. In 2019, almost five million deaths were directly attributed to or associated with AMR, more than were attributed to HIV/AIDS and malaria combined that same year.¹ By 2050, it is expected that, without significant action, AMR will be associated with more than eight million deaths per year and will cost the world $100 trillion.^2,3 If left unchecked, AMR stands to derail global progress, weakening healthcare and threatening economic productivity, global food supplies, and shared goals to promote equity.

Addressing this threat will require a multifaceted approach, but a cornerstone must be a strengthened pipeline of antimicrobial drugs developed in parallel with innovative diagnostics to guide appropriate use. Achieving this requires a long-term, strategic approach to funding and nurturing AMR innovation. Given the urgency of the crisis, progress must be collaborative and focused. Only by working together as a global community and directing resources to the most critical areas can we truly rise to meet the challenge.

The innovation deficit in AMR

AMR began to emerge as soon as the first antimicrobials were adopted in the 1940s.⁴ While new antimicrobial compounds were developed throughout the following decades, resistance continued to emerge. Over time, the number of novel antimicrobials making it to the clinic has steadily decreased. This is due to many factors, including the scientific complexity of finding and drugging new targets, and the high costs and low returns associated with antimicrobial R&D. This reality leaves us with fewer options to treat antimicrobial-resistant infections.⁵

The latest World Health Organization (WHO) report on the state of antimicrobial development estimated that in 2023, there were 97 novel antimicrobial agents in clinical development pipelines.⁶ However, even without accounting for the high failure rates of drug development, this number falls short of what is needed to outpace AMR.

The problem extends beyond numbers. Most candidates lack true innovation and fail to address the highest priority pathogens. Of the 32 traditional small molecule drugs in development against WHO bacterial priority pathogens, only four target critical pathogens (those that are the most problematic) and also meet at least one of the WHO’s innovation criteria:^6,7,8

1. New chemical class: Derived from a chemical that has not been previously used
2. New target: Interacts with a part of the bacteria that existing drugs do not target
3. New mode of action: Kills or inhibits bacteria through a distinct mechanism
4. No cross-resistance to other classes: Effective against bacteria that have developed resistance to other classes of drugs

These criteria ensure that the drug offers a genuine therapeutic difference, a requirement for its effectiveness against evolving AMR. Considering it can take 15 years and cost over $1 billion to bring a new therapeutic to market, we must make sure that every effort counts.⁹

Diagnostic and therapeutic innovation

While developing new antimicrobials is vital, it is only part of the solution. Without accurate, rapid diagnostics to guide their use, even the newest antimicrobials risk being misused. Misuse not only delivers poorer outcomes for patients but also drives more resistance.

While some diagnostic tests do currently exist and should guide antimicrobial use, in practice, many treatment decisions across the globe are made empirically without a definitive diagnosis.¹⁰ An example is urinary tract infections (UTIs), which are one of the leading causes of global antimicrobial prescriptions. UTIs are commonly diagnosed based on symptoms or a dipstick test to confirm indirect measures of infection. More definitive tests, such as urine cultures and antimicrobial susceptibility testing, can take 24-72 hours and may not be available in all healthcare settings. This means that patients are often prescribed antimicrobials that are inappropriate for their infection, leading to longer recovery times, more strain on healthcare systems, and worsening resistance.

Innovation in diagnostic tests to enable faster, more informative results at the point of care is crucial to guide evidence-based treatment decisions that will preserve the effectiveness of existing antimicrobials and the appropriate use of new therapeutics. Emerging technologies show promise, including novel antimicrobial susceptibility systems that combine metagenomic sequencing with artificial intelligence to detect pathogens and resistance genes directly from samples. Lab-on-a-chip and nanotechnology-based platforms also represent exciting areas of development. However, the practicality of these tools at the point-of-care is still developing.

Improved diagnostics will not only help preserve the lifespan of existing drugs but also accelerate the development and clinical adoption of novel therapeutics. Several promising targeted antimicrobials are advancing through the pipeline, including antibody-based therapies, other immunotherapies, bacteriophages, and protein-based agents. However, these treatments are often narrow-spectrum, making diagnostics even more essential to identify the right patients and infections for their effective use.

While companion diagnostics are well established in fields like oncology, their role in antimicrobial therapy is still evolving. Unlike the one-to-one model seen in cancer treatment, companion diagnostics for antimicrobials may not be a single test tied to a specific drug. Instead, they may be tailored to the specific infection and the context. Regulatory interest in this area is growing as global stakeholders are increasingly recognizing the need for aligned incentives to advance both diagnostics and therapeutics in a coordinated way.¹¹

Breaking down barriers

Despite growing recognition of the AMR crisis, substantial roadblocks continue to threaten innovation. Central to this is the lack of sufficient economic incentives. Healthcare systems are accustomed to low-cost antibiotics, and this, coupled with the fact that novel antimicrobials are often subject to antimicrobial stewardship measures (those promoting responsible usage), undermines traditional R&D revenue models. This market nuance has deterred some innovators from pursuing development in this field, as it is unlikely they would be able to recover their R&D costs.¹²

Beyond funding, there are critical scientific and structural barriers. AMR isn’t a single disease; it is a threat that spans dozens of infections, each with its own pathogens, resistance mechanisms, and clinical contexts, making it difficult to design and develop one-size-fits-all interventions. In addition, the R&D process can be hampered by regulatory uncertainty, particularly for non-traditional therapeutic approaches, which often lack clearly defined pathways for approval. Clinical trials can also be challenging when testing drug-resistant infections.

Compounding these issues is the fact that, currently, 86% of AMR pipeline innovation is being led by small biotech companies and academic groups.¹³ Although these organizations are making game-changing contributions in the AMR space, they require broader support and sustained investment to scale development; otherwise, even the most promising breakthroughs may not make it to patients.

Collaboration is vital

Since the first United Nations General Assembly commitment on AMR in 2016, global action has intensified. Several initiatives have emerged to stimulate innovation, ranging from “push” incentives, like CARB-X¹⁴, GARDP¹⁵, and Gr-ADI¹⁶, to “pull” mechanisms, such as the NHS subscription model in the U.K., which decouples reimbursement from sales.¹⁷

Amid this ecosystem, PACE (Pathways to Antimicrobial Clinical Efficacy), a £30-million initiative between LifeArc, Innovate U.K., and Medicines Discovery Catapult, was formed to plug a specific gap and play an important role.¹⁸ It focuses specifically on driving and supporting early-stage translation and targeting high-potential innovations that may otherwise struggle to access funding or the right support to ensure success.¹⁹ PACE recognizes that skills development is just as important as funding, and acts as a learning partner, providing tailored support, guidance, and technical expertise, as well as important connections to the AMR network for delivery or downstream support.

By pooling expertise and resources, initiatives like PACE help to accelerate promising science into viable interventions, in turn strengthening the global AMR pipeline. They foster cross-sector innovation and learning, which is critical in AMR, as progress depends on expertise spanning multiple disciplines. Just as importantly, these partnerships contribute to skills and capacity strengthening, helping to address shortages in the talent needed to drive innovation forward.

Now more than ever, we must work together to tackle antimicrobial resistance. By prioritizing and supporting the right projects, we can drive the innovation needed to safeguard future generations.

References

1. Antimicrobial Resistance Collaborators. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022; 399 (10325): 629–655. doi:10.1016/S0140-6736(21)02724-0.

2. GRAM Project. Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050. Lancet. 2024.

3. World Health Organization. Time to act to curb antimicrobial resistance now. 2022. Accessed August 15, 2025.

4. Hunt D, Kates OS. A Brief History of Antimicrobial Resistance. Journal of Ethics | American Medical Association. 2024. Accessed August 15, 2025.

5. Ventola CL. The antibiotic resistance crisis: part 1: causes and threats. Pharmacy & Therapeutics. 2015; 40(4): 277-283.

6. World Health Organization. 2023 Antibacterial agents in clinical and preclinical development: an overview and analysis. 2024. Accessed August 15, 2025.

7. World Health Organization. WHO Bacterial Priority List. 2024. Accessed August 15, 2025.

8. World Health Organization. Antibacterial products in clinical development for priority pathogens. 2022. Accessed August 15, 2025.

9. Wellcome Trust. Why is it so hard to develop new antibiotics? 2020. Accessed August 15, 2025.

10. Ku TSN, Al Mohajer M, Newton JA, et al. Improving antimicrobial use through better diagnosis: The relationship between diagnostic stewardship and antimicrobial stewardship. Infect Control Hosp Epidemiol. 2023; 44(12): 1901-1908. doi:10.1017/ice.2023.156.

11. World Innovation Summit for Health (WISH). Tackling antimicrobial resistance: How to keep antibiotics working for the next century. 2024. Accessed August 15, 2025.

12. Bhavnani SM, Krause KM, Ambrose PG. A Broken Antibiotic Market: Review of Strategies to Incentivize Drug Development. Open Forum Infect Dis. 2020; 7(7). doi:10.1093/ofid/ofaa083.

13. World Health Organization. Antibacterial pipeline trends and recommendations to enhance research and development. 2024. Accessed August 15, 2025.

14. Carb-X. Home. Accessed August 15, 2025.

15. GARDP. Global Antibiotic Research and Development Partnership. Accessed August 15, 2025.

16. Bill & Melinda Gates Foundation. Partnership announces antimicrobial resistance solutions by discovery of new treatments. Published February 12, 2025. Accessed August 15, 2025.

17. NHS England. Antimicrobial Products Subscription Model: guidance on commercial arrangements. 2024. Accessed August 15, 2025.

18. PACE-AMR. Pathways to Antimicrobial Clinical Efficacy. Accessed August 15, 2025.

19. PACE-AMR. What are the greatest unmet needs in antimicrobial diagnostics? Accessed August 15, 2025.

Beverley Isherwood, PhD, is strategy leader for infectious diseases at Medicines Discovery

Catapult and director of Pathways to Antimicrobial Clinical Efficacy (PACE).