Rise of the Post-Antibiotic Era
Reflections on antimicrobial resistance and what scientists can do next to rise to this challenge.
Upcoming Event: Join me this weekend for a free, open to the public event at the Sharon Forks Library (Sunday, April 21, 2:00pm - 3:00pm, Sharon Forks Library, 2820 Old Atlanta Road, Cumming, GA 30041). I’ll be speaking about medicinal plants, herbaria, and my book, The Plant Hunter. More details can be found on their website. I’ll have copies of The Plant Hunter available for sale and signings, plus some treasures from the Emory Herbarium on display.
In 2016, the O’Neill report “Tackling Drug-Resistant Infections Globally” announced an alarming prediction that there would be 10 million deaths annually across the globe by mid-century due to antimicrobial resistant infections. More recently, a 2022 publication in The Lancet, ‘Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis’ found that 1.7 million deaths were directly attributed to bacterial antimicrobial resistance (AMR), and more than 3.5 million deaths associated with bacterial AMR. In other words, we are right on track to reaching 10 million deaths per year by 2050.
How did we get here?
The rise of AMR has been attributed to many factors, chief among these being the misuse and overuse of these precious drugs. Overuse extends far beyond the medical clinic and into farmers’ fields. We still employ antibiotics to an alarming degree in agriculture, not only in livestock but also in certain crops. Moreover, we have hit a wall in terms of discovery and development. In fact, the last new antibiotic class brought to market was discovered in the 1980s! The majority of our current antibiotic classes in clinical use today were discovered in the 1950s and 1960s. Primarily, these are microbial natural products—molecules found in nature—that originate from microbes found in soil samples collected across the globe.
What led to the antibiotic discovery void?
Drug discovery research is challenging in its own right. Scientists need to find new molecules that are effective against their disease target, while also maintaining a good safety profile and reaching the part(s) of the body most important to the disease. When it comes to antibiotics, scientists face the very real challenge of inevitable resistance. Bacteria reproduce at an incredibly rapid rate—some as fast as every 15 minutes. That opens up many opportunities for mutations conferring resistance to arise by chance and then spread in the microbial population. The end result: a drug that no longer works.
In addition to these very real scientific challenges, one must also consider the economic challenges. Antibiotics present a very low return on investment for pharmaceutical companies. If one considers that it can cost anywhere from $800 million to $1 billion to bring a new drug to market, placing that bet on a drug guaranteed to lose efficacy the more it is used presents a disincentive for investors and companies alike.
Despite the scientific and economic odds stacked against antibiotic discovery and development researchers, their work has never been more important. The epidemiologic evidence is clear: more AMR is coming, and more people will die because of it if we don’t do something about it.
Where should we focus antibiotic discovery efforts?
Given the urgency of the issue and limitations in funding sources to pursue antibiotic discovery research, it is important to prioritize which drug resistant bacteria and fungi to focus on. The WHO and CDC have both created a list of priority pathogens, ranked by level of importance based on risk and human impact.
What about plants as a source of new antibiotics?
As mentioned above, antibiotics in the clinic today are primarily derived from microbial natural products (molecules made by microbes). However, throughout systems of traditional medicine, people have used plants to treat infection for centuries.
So, what do we know about plant-derived antibiotics? There is a lot of preclinical data (in test tubes and in animals), but few clinical studies on these. My lab published a comprehensive review of the literature (Ethnobotany and the Role of Plant Natural Products in Antibiotic Drug Discovery) in Chemical Reviews and found that there are at least 459 plant-derived compounds with promise. This is an exciting starting point, but we have much to do to mine this resource for druggable molecules.
The Takeaway
AMR is a challenge to medicine that is here to stay. To meet this challenge, we need to fill the antibiotic discovery pipeline. Natural products (molecules from nature) will be critical in this process, and we can do more to explore more sources of these molecules, moving beyond microbes to include plants and mushrooms.
Yours in health, Dr. Quave
Cassandra L. Quave, Ph.D. is a scientist, author, speaker, podcast host, wife, mother, explorer, and professor at Emory University School of Medicine. She teaches college courses and leads a group of research scientists studying medicinal plants to find new life-saving drugs from nature. She hosts the Foodie Pharmacology podcast and writes the Nature’s Pharmacy newsletter to share the science behind natural medicines. To support her effort, consider a paid or founding subscription, with founding members receiving an autographed 1st edition hardcover copy of her book, The Plant Hunter.
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