Hello everyone and welcome to this week's blog post which is the first in a two-part series on the subject of antibiotic-resistant bacteria. This week, we will look at the role of antibiotics and the problems with developing new antibiotics. Make sure to subscribe so that you get notified about next week's post, which will look at phage therapy as an alternative to antibiotics.
For the last several decades, antibiotics have been crucial in treating bacterial infections, however, due to antibiotic overuse and the increasing cost of developing antibiotics, it is highly likely that the world will soon 'run out' of effective antibiotics.
The first antibiotic, penicillin, was discovered by Alexander Fleming in 1928, but it wasn't until World War 2 that penicillin could be manufactured in sufficient quantities for large scale treatments. Following the war, due to increased funding and improvements in technology, there was a golden era of antibiotics. During this period between 1940 - 1962, most of the modern classes of antibiotics were discovered, including many beta-lactam antibiotics.
Since then, however, antibiotic resistance has increased dramatically. This is due to a number of reasons. Firstly, antibiotics are now used more much more commonly. In 2015, 34.8 billion doses of antibiotics were consumed, which marked a 65% increase from 21.1 billion doses in 2000. This increases the chance that bacteria will encounter antibiotics and develop resistance.
Bacteria can encounter antibiotics in 4 main settings: in the body, in hospitals, in the environment and in farming. Despite increased funding towards educating people about how to use antibiotics, many people use antibiotics incorrectly, for example by not completing the course of antibiotics or by using them unnecessarily. This is most notable in countries such as India, where antibiotics can be obtained without a prescription.
Antibiotic-resistant strains of bacteria are highly likely to develop in hospitals, due to the high volume of infected people and the substantial use of antibiotics. To limit the development of antibiotic-resistant strains of bacteria, good hygiene practices in hospitals are crucial. Moreover, antibiotic-resistant strains of bacteria are far more deadly in hospitals, since most patients have weakened immune systems, so it is even more important to make sure that transmission of these strains is limited.
Bacteria can also be exposed to antibiotics in the environment. This is most prevalent in areas with poor waste management systems or areas which use antibiotics in farming. For more information about the use of antibiotics in farming, read my blog post here.
Due to the reasons outlined above, the need for new antibiotics is greater than ever. Resistance to antibiotics is a global health emergency, killing around 700,000 people every year. Indeed, at current rates, the number of deaths could grow to 10 million deaths per year by 2050. Nonetheless, the development of antibiotics is at an all-time low. Indeed, according to the World Health Organisation, there are only 50 antibiotics currently in development, with the majority only having limited benefits compared to existing antibiotics.
During the golden age of antibiotics, many new classes of antibiotics were discovered, This was due to two main reasons. Firstly, very few antibiotics existed, meaning that any antibiotic which was discovered would be incredibly lucrative for the developer. Secondly, it was relatively cheap to carry out research and conduct trials for new medication. This meant that a huge number of chemicals could be tested for the same cost as testing a few chemicals today.
Modern research and development is incredibly expensive and often fails. To find and produce a new antibiotic, a pharmaceutical company must first find thousands of substances which may have antibiotic properties, before testing them all to find those which both kill bacteria and are safe to use in humans.
Once the most promising substances are identified, they then must undergo clinical trials. These clinical trials have three phases. In phase 1, the drug is tested on a small group of people to ensure that the drug is safe for use and to obtain preliminary evidence that it offers therapeutic value. In phase 2, which is conducted on a larger group of volunteers, the efficacy of the medicine is tested. This is where evidence is collected about how effective the medicine is and its optimal dosage. Finally, in phase 3, which is conducted on thousands of volunteers, the safety and efficacy of the medicine are confirmed, side effects are identified and knowledge about the medicine is improved.
After these original trials, approval needs to be obtained from the regulator of every single country the medication is prescribed in before it can be launched. After launching a new drug, additional trials need to be conducted and more money has to also be spent on marketing. Additionally, there is no guarantee that a drug will make it to market. Indeed, the vast majority of drugs fail pre-clinical trials, with even more failing clinical trials, adding to the cost of producing a new medicine.
As a consequence, this process is extremely expensive and time-consuming - it is estimated that the process of developing new antibiotics can last over 10-15 years, with a cost of over $1 billion.
This has three main effects on antibiotic production. Firstly, in order to reduce costs, pharmaceutical companies often adapt pre-existing substances, either by improving their efficacy or by using them for other diseases. This dramatically reduces the cost of development. As a result, since the 1980s, no new classes of antibiotics have been discovered. This increases the risk of running out of antibiotics as, if a bacterium develops resistance to one antibiotic, it is likely that it will also have some resistance to other antibiotics in the same class.
In addition, the high cost of antibiotics to the consumer means that developing countries are unlikely to be able to afford them, meaning that antibiotic-resistant strains of bacteria can't be easily treated in those countries.
The high cost of antibiotic production also disincentives pharmaceutical companies from producing new antibiotics. This is because it is incredibly difficult to make money out of them. Drug patents last for 20 years, so the pharmaceutical companies who've spent billions of dollars researching the drug can only make money from these drugs for 20 years before other companies can duplicate the drug, drastically reducing their prices. In fact, to ensure other companies steal their research, pharmaceutical companies often patent drugs early in their development, years before they get approval to market them. This means that the 20 year period is shortened.
Because of that, most pharmaceutical companies have shut down their antibiotic programs. Indeed, as of 2018, there were only 4 pharmaceutical companies with antibiotic programs. This has resulted in only 12 new antibiotics being approved since 2000.
In conclusion, the threat of antibiotic-resistant bacteria is extremely significant. If we run out of antibiotics, which is likely due to the increase in resistance and a decrease in the number of new antibiotics, then bacterial infections will kill huge numbers of people around the world.
To mitigate this problem, two steps must be taken. Firstly, increased funding should be given to educating people about how and when to use antibiotics. This will ensure that antibiotic-resistant bacteria are less likely to develop and that our present supply of antibiotics lasts as long as possible. Moreover, the government needs to provide incentives to pharmaceutical companies to continue research in this area, for example by providing subsidies or increasing patent length. Alternatively, the government could also fund its own research in collaboration with the pharmaceutical industry. As part of this research, new sources of antibiotics would need to be found.
Sources:
Comments