Antimicrobial resistance (AMR) refers to the ability of microorganisms—bacteria, viruses, fungi, and parasites—to evolve and resist the effects of drugs that once effectively killed or inhibited them. This phenomenon poses a significant threat to public health globally, as it undermines the effectiveness of common treatments for infections, leading to longer hospital stays, increased healthcare costs, and higher mortality rates (World Health Organization, 2021).
The overuse and misuse of antibiotics, particularly in agriculture, healthcare, and in the community, are believed to be primary drivers of AMR (Centers for Disease Control and Prevention, 2019). As resistant infections become more common, the risk of treating once-manageable conditions with limited or no therapeutic options grows, prompting urgent calls for coordinated global action to mitigate the crisis (O'Neill, 2016).
In a series of upcoming articles, the Mewburn AMR team will explore a number of key issues and unique solutions in the field introduced below, and discuss how IP and incentives can be used to support researchers tackling AMR.
Unearthing natural products
The discovery of antibiotics from natural sources has played a pivotal role in the development of modern medicine. Historically, antibiotics such as penicillin, derived from the Penicillium mould, revolutionised the treatment of bacterial infections in the mid-20th century.
For instance, in recent years, the discovery of teixobactin from soil bacteria (Eleftheria terrae) has shown promise as a novel antibiotic with potent activity against Gram-positive pathogens, including drug-resistant strains (Ling et al., 2015). Similarly, researchers have identified new classes of antibiotics from bacterial niches in the deep sea, and even marine fungi themselves (highlighted in a special issue of Marine Drugs in 2023).
Natural sources, particularly soil microbes, have long been a rich reservoir for discovering new antimicrobial compounds. Despite the growing challenge of antimicrobial resistance, the continued exploration of natural environments, including soil, oceans, and even extreme ecosystems, holds potential for discovering new antibiotics to address the unmet need for effective treatments.
Byte-sized breakthroughs with AI
Artificial intelligence (AI) is rapidly transforming the field of antibiotic discovery by accelerating the identification of new compounds and optimising their design. Traditional methods of drug discovery are time-consuming and costly, but AI-driven approaches can analyse vast datasets—such as chemical libraries, biological properties, and molecular structures—to predict which molecules may be effective against resistant pathogens.
For example, machine learning algorithms have been used to discover novel antimicrobial peptides, which are short proteins that can target and disrupt bacterial membranes (Stokes et al., 2020). AI is also being employed to optimize the chemical structures of known antibiotics, enhancing their potency and reducing the likelihood of resistance development. In one notable breakthrough, researchers used AI to identify a new antibiotic. Halicin, which had originally been developed as a c-Jun N-terminal kinase inhibitor for diabetes treatment, showed promise against a broad range of resistant bacteria, including Acinetobacter baumannii (Stokes et al., 2020).
AI can design structurally novel antibiotics by utilizing advanced algorithms to predict and create molecules with unique, uncharted chemical architectures. By designing entirely new classes of antibiotics with novel mechanisms of action, we can bypass existing resistance mechanisms and provide effective treatments for infections caused by multidrug-resistant bacteria.
UTIs: persistent resistance
Urinary tract infections (UTIs) are among the most common bacterial infections, affecting millions of people worldwide. While UTIs are often treatable with antibiotics, the rise of antimicrobial resistance (AMR) has made many infections more difficult to treat, leading to longer courses of therapy and increased healthcare costs.
The problem of recurrent and resistant UTIs is known to disproportionately affect women. The increased demand for more expensive or broad-spectrum antibiotics to treat resistant and recurrent UTIs further stretches healthcare budgets, highlighting the urgent need for improved diagnostics, preventive strategies, and the development of new, effective treatments to tackle this ongoing public health challenge.
Turning the tables: they infect us, we infect them
Phage therapy, the use of bacteria-specific viruses or “bacteriophage” to treat bacterial infections, has been around for over a century, with the first clinical use having been successfully attempted as early as 1919 (Chanishvili, 2012). Much like a human virus does to our cells, phages infect susceptible bacteria, reproduce in them and then cause the bacteria to lyse (i.e. burst). With the discovery of antibiotics, interest in phage therapy largely fell away, but has been revived as antibiotic resistance becomes ever more problematic.
There have been several promising anecdotal reports of successful phage therapy, including against “superbugs” such as Pseudomonas aeruginosa (Köhler, 2023) and Acinetobacter baumannii (UCSD, 2017). With dozens of clinical trials ongoing, this technology is seeing a renaissance as a viable way to treat bacteria that are resistant to conventional antimicrobials.
Rapid response – the importance of diagnostics
One way of battling the rise of AMR is by improving the speed and accuracy of diagnosis of pathogenic microbes in patients. This could be key to reducing the overuse and, crucially, the misuse of antimicrobials.
Presently, routine diagnostic tests require sending a patient sample to a laboratory, where the microbes from the sample are cultured and then tested to determine susceptibility to a given antimicrobial. This process can take a number of days. However, some infections (e.g., sepsis) require immediate treatment, meaning administering broad-spectrum antimicrobials is the only option. In most cases, the infecting organism would be susceptible to more targeted therapeutics, but time is of the essence. For less urgent infections, antimicrobials are often prescribed whilst the patient waits for the results of the diagnostic tests, with some ultimately being taken unnecessarily or inappropriately.
New technology is paving the way for faster and more accurate infection diagnosis and antimicrobial susceptibility testing, essential for effective infection management and accurate and targeted treatment, which will help preserve both existing and new antimicrobials.
Extra burden for low- and middle-income countries
Antimicrobial resistance (AMR) poses a particularly severe threat to low- and middle-income countries (LMICs), where the burden of infectious diseases is already high and healthcare resources are often limited. In these regions, widespread misuse of antibiotics, such as over-prescription, self-medication and lack of access to quality medicines, accelerates the development of resistance. Inadequate diagnostic facilities and limited availability of alternative treatments further exacerbate the problem, leaving healthcare providers with few options to treat resistant infections.
The WHO recognises that various social and economic pressures can drive the problem of AMR. Antimicrobial Stewardship (AMS) programmes aim to educate and support healthcare professionals to improve patient outcomes and reduce AMR and healthcare-associated infections. The programmes encourage following evidence-based guidelines for prescribing and administering antimicrobials and highlight the importance of a holistic approach to tackling AMR, particularly in regions with limited resources.
By focusing on affordable diagnostics, several low-cost tools have been developed or adapted to better diagnose infections in resource-constrained settings, for example paper-based lateral flow assays for AMR detection (Boutal, 2022), which are both affordable and portable.
Investing in innovation
One major challenge facing researchers in the field is that the current market for antibiotics is often not financially attractive to pharmaceutical companies; antibiotics are typically short-course treatments with lower profit margins compared to chronic disease drugs, and a push for responsible use of antibiotics means new drugs may be developed simply to sit in reserve for some time.
It will be interesting to see how the idea of economic incentives might spur development. These include "push" mechanisms like government funding or subsidies for early-stage research, which help offset the high costs of developing new drugs, as well as "pull" mechanisms such as market entry rewards or guaranteed pricing and purchasing agreements that provide a financial return once a new antibiotic reaches the market.
The concept of “delinkage” is important; by decoupling the price of antibiotics from sales volume, companies can be compensated for developing effective antibiotics regardless of the frequency of their use.
Intellectual property (IP) plays a crucial role in creating economic incentives for R&D in AMR. By aligning IP strategies with global health goals, these mechanisms could make the development of new antibiotics more attractive to pharmaceutical companies while ensuring access to essential treatments in the fight against AMR.
References:
- World Health Organization (WHO). (2021). Antimicrobial resistance. https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance
- Centers for Disease Control and Prevention (CDC). (2019). Antimicrobial resistance (AMR) — Overview. https://www.cdc.gov/drugresistance/about.html
- O'Neill, J. (2016). Tackling drug-resistant infections globally: Final report and recommendations. Review on Antimicrobial Resistance.
- Ling, L. L., Schneider, T., Peoples, A. J., et al. (2015). A new antibiotic kills pathogens without detectable resistance. Nature, 517(7535), 455–459. https://doi.org/10.1038/nature14098
- Tortorella E, Tedesco P, Palma Esposito F, January GG, Fani R, Jaspars M, de Pascale D. Antibiotics from Deep-Sea Microorganisms: Current Discoveries and Perspectives. Mar Drugs. 2018 Sep 29;16(10):355. doi: 10.3390/md16100355. PMID: 30274274; PMCID: PMC6213577.
- Stokes, J. M., Yang, K., Swanson, K., et al. (2020). A deep learning approach to antibiotic discovery. Cell, 180(4), 688–702. https://doi.org/10.1016/j.cell.2020.01.016
- Chanishvili N. Phage therapy--history from Twort and d’Herelle through Soviet experience to current approaches. Adv Virus Res. 2012;83:3–40.
- Köhler et al., Nature Communications 14: 3629, 2023
- University of California San Diego. "Novel Phage Therapy Saves Patient with Multidrug-Resistant Bacterial Infection." UC San Diego News Center, 2017, https://today.ucsd.edu/story/novel_phage_therapy_saves_patient_with_multidrug_resistant_bacterial_infect.
- Boutal, H.; Moguet, C.; Pommiès, L.; Simon, S.; Naas, T.; Volland, H. The Revolution of Lateral Flow Assay in the Field of AMR Detection. Diagnostics 2022, 12, 1744. https://doi.org/10.3390/diagnostics12071744
