Combating Resistance: How Are New Treatments Discovered?

Previously we’ve touched on the increasing threat of both anthelmintic and antibiotic resistance. Across the world, anti-microbial chemicals are an absolutely vital part of life, from medical and veterinary care, to agriculture and pest management. However, the more we use these chemicals, the more likely their targets are to develop resistance.

What is resistance?

Resistance is a trait that allows an organism, like a bacterium or a nematode worm, to survive a treatment designed to kill it. The first time a new antibiotic or anthelmintic is used, it is likely to be extremely effective against the pest. However, some organisms might be more tolerant of the treatment and so will be more likely to survive. With massively reduced competition, these tolerant organisms will thrive and multiply. The organism’s offspring inherit this genetic trait and resistance spreads in a population. Eventually, a treatment that was once effective becomes useless.

Anthelmintic resistance is a huge problem in livestock agriculture.
Anthelmintic resistance is a huge problem in livestock agriculture.

For example, before scientists developed effective anti-microbial treatment, around a quarter of all deaths were the result of tuberculosis (TB). TB was almost always fatal, but now, with treatment using a combination of antibiotics, deaths are rare. However, in recent years, drug-resistant strains of TB have developed. As of this year, 1 in 3 TB patients in Europe has a resistant form of the disease. In livestock, resistance to anthelmintic treatments – anti-parasitic agents – is extremely high.

How do we fight resistance?

A large part of combating resistance is trying to prevent it from developing or spreading further. Guidance from scientific and medical bodies, such as the WHO, advises people to only use antimicrobials when necessary, make sure treatments are specific, and make sure treatment is complete before the end of the antimicrobial course.

However, while these measures will help to reduce the spread of antimicrobial resistance, it is a natural process. As such, eventually, given enough time, microbes will become resistance to current treatments. As a result of this, it is important to develop new antimicrobial treatments.

How are new treatments discovered?

Tannins, such as those in tea, appear to have some antimicrobial properties.
Tannins, such as those in tea, appear to have some antimicrobial properties.

Unfortunately, developing new and effective drugs to treat microbial infections is not easy. While there are currently hundreds of different antimicrobials, they fall into groups of similar drugs. For example, while there are hundreds of different antibiotics, there are only 6 classes. When scientists develop new antibiotics which make it to market, they often fall into these same classes. This chemical similarity means that resistance can develop more quickly. Developing new classes of antimicrobial is even more difficult.

The natural world produces millions of different chemicals from a variety of different sources. Many current antibiotics are based on the natural products of soil bacteria, however these can be difficult to culture in a lab or commercial context. Many medicines are based on plant products, such as aspirin, and some plant products, like tannins, appear to have antimicrobial properties.

Why is it difficult to develop new antimicrobials?

Some bacteria produce antimicrobial chemicals, but they can be difficult to grow in lab conditions.
Some bacteria produce antimicrobial chemicals, but they can be difficult to grow in lab conditions.

Even when scientists discover a chemical which has antimicrobial properties, it does not necessarily mean that they will be able use it to make a new treatment. Before ever reaching patients, a chemical must undergo toxicity testing. While it’s relatively easy to find substances that damage microorganisms, they are often highly toxic to people and animals as well. If they pass toxicity tests, then a good source of the chemical is necessary. Some bacteria or plants might only produce the useful compound under highly specific circumstances, or might be difficult or impossible to grow on a large scale. Once all of these hurdles are overcome, the new drug would then have to go through years of pre-clinical and clinical trials before ever reaching patients. All in all, this process takes many years and can cost millions.

What does this mean for resistance?

At the moment, there are over 250 antibiotics under development across the world. While only 3-6 of these are likely to make it to market in the next 10 years, they could provide valuable tools in the fight against resistance. Similarly, new anthelmintic treatments are under development, giving hope for the future.

Awareness about antimicrobial resistance is rising. More people are prescribing and using antimicrobials in a way that helps to decrease the rate of resistance development. In the livestock sector, many governmental bodies have started banning the use of antibiotics as a growth promoter, which in turn helps to reduce resistance. Although antimicrobial resistance is one of the biggest threats to human and animal health, there are strategies to combat it.