Antibiotic resistance is a big problem – The Post

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The recent announcement of the development of zosurabalpin – a next-generation antibiotic believed to be effective against a very difficult-to-treat bacterium – has been hailed as an important new advance in tackling the problem of antibiotic resistance, the ability of some bacteria to resist drugs and transmit sometimes fatal infections aftermath. This phenomenon has been known for a long time and, according to the World Health Organization (WHO), it is one of the biggest risks to public health, because over time it produces drugs that in the twentieth century made it possible to save the world’s increasingly less effective lives of millions of people.

In general, antibiotics are substances produced by a microorganism capable of killing another or limiting its reproduction. The antibiotics properly speaking, they are those which are produced in this way by some micro-organisms to act against others, while non-antibiotic antibacterial substances they are substances obtained in a laboratory. However, both have the same property of killing or preventing the growth of specific bacteria, which is why the umbrella term “antibiotics” is commonly used for both types of substances.

The development of antibiotics, starting with Alexander Fleming’s first experiments with penicillin in the late 1920s, led to the identification of approximately 15 classes, which gave rise to the production of antibiotics we still use today. The range of these substances is not very wide, and this lack became one of the causes of antibiotic resistance, together with the extensive and often excessive use of antibiotics in the second half of the twentieth century.

Some antibiotic resistance by bacteria has always existed and was fundamental to the discovery of the antibiotics we use. Bacteria are single-celled organisms and must defend themselves against external agents that could damage them and threaten their colonies. For this, over millions of years, they have developed the ability to produce their own antibiotics, i.e. substances that harm, for example, other types of bacteria that could otherwise destroy and replace them. It is a process that also applies to fungi and was the basis of the first works of Fleming, who obtained penicillin from mold (molds belong to the kingdom of fungi).

The study of bacteria and their defenses has led to the development of a wide range of antibiotics: some are broad-spectrum, i.e. they fight against different types of bacteria, while others are more specialized for only one or a few types of these microorganisms. Different types of antibiotics are used precisely to try to evade the bacteria’s defenses and eliminate them to help the patient’s immune system overcome the infection.

Bacteria reproduce continuously, even several times in a single hour, by copying their genetic material. In this process, mutations can occur, i.e. errors in the process of copying genetic material. Most mutations are harmless and have no consequences, but some can, on the contrary, lead to greater resistance of the bacterium to one or more antibiotics. Antibiotic treatment thus eliminates bacteria without the mutation, while proving ineffective against those that have accidentally developed some resistance. These can then mutate and produce bacteria with another type of resistance, which is why their elimination with antibiotics is even more difficult.

A simplified example of the development of antibiotic resistance (Federal Office of Public Health of the Swiss Confederation)

Bacteria resist antibiotics differently depending on how they are made and the mutations they have accumulated. Some simply expel the antibiotic that has entered the cell material, while others make their membrane waterproof so that the antibiotic cannot go any further. There are other cases where bacteria modify the structure of the antibiotic, making it inactive, or even modify some of the bacterial proteins that the antibiotic was intended to target.

As we have seen, antibiotic resistance is a characteristic feature of bacteria linked to the way they mutate and evolve, however, excessive or inappropriate use of antibiotics can facilitate the emergence of increasingly resistant bacteria. Antibiotics are often used incorrectly or not at all adequately, often to treat diseases that are not caused by bacteria, but by viruses, against which antibiotics can do nothing. In the most acute stages of the coronavirus pandemic, a certain tendency to resort to antibiotics without reason has clearly emerged, despite the fact that all major international institutions recommend against the use of this type of drug to treat COVID-19, a viral disease in all respects.

Antibiotic resistance can also be promoted by the incorrect use of antibiotics, for example, when you decide to shorten the duration of therapy or reduce the dose of antibiotics and do it yourself without consulting a doctor. The effect of most antibiotics is relatively short, and for this reason therapies often involve taking a dose twice or thrice daily to achieve full coverage during treatment. Taking less or irregularly can facilitate the survival of bacteria and their proliferation with an increased risk of mutations.

Bacteria that develop significant resistance can cause many types of infections that can become chronic or, in the most severe cases, fatal. Among the most frequently recurring and difficult to treat infections are urinary tract infections, pneumonia, skin infections, some forms of diarrhea and infections of the circulatory system. Hospitalized people are also at a higher risk of contracting bacterial infections, starting with those from Acinetobacter baumanniibacteria that can be highly resistant to antibiotics, including carbapenems, a class of broad-spectrum antibiotics that are considered “last line” (ie

Treatment of infections caused by resistant bacteria is often very difficult and requires the administration of different types of antibiotics, which can be progressively more powerful and targeted, but also more expensive. Finding the right therapy takes time at a stage where any delay poses a problem for the patient, which meanwhile gets worse due to the progression of the infection and other related problems. Complications can be fatal, especially in the case of bacterial strains that develop resistance to several different classes of antibiotics. The risk is that over time some bacteria will become resistant to it each antibiotics available today, undoing the progress made in the field in the twentieth century.

Data collected by the European Center for Disease Prevention and Control (ECDC) indicates that antibiotic resistance is becoming a problem in many European countries. In recent years, an increase in resistance has been observed in particular Escherichia coli to the usually most commonly used antibiotics with a subsequent increase in cases of chronic urinary tract infections and even more serious infections. In southern European countries, this phenomenon seems to be more widespread than in Scandinavian countries and the Netherlands. In general, countries where historically there has been a more cautious use of antibiotics are also countries where the phenomenon of antibiotic resistance is less present.

However, the problem of antibiotic overuse is a global one, and the WHO has launched various initiatives and projects to raise awareness among governments and national health authorities about the problem, with repeated calls to reduce antibiotic use. In many countries, including Italy, restrictions on the ability to buy antibiotics in pharmacies without a prescription have been strengthened to prevent a do-it-yourself approach.

Antibiotics are not only consumed directly by humans, but also indirectly through the food chain. Antibiotics are often widely used on farms to ensure rapid and healthy growth of animals, thereby reducing the risk of infection. The substances used are the same as in humans and there are studies that have revealed the effective passage of some of them in those who eat meat. Research on this topic is still ongoing, but transmission is thought to be minimal compared to treatment-induced transmission in humans.

The use of antibiotics only when absolutely necessary and more accurate diagnostic tests to quickly determine the correct antibiotic therapy are considered the most important tools to address the problem of antibiotic resistance. But according to the WHO, an integrated approach must also include the development of new-generation antibiotics to treat the most difficult cases, such as Acinetobacter baumannii. As reported in a recent editorial published by a scientific journal NatureDeveloping new antibiotics is not easy and has strong economic implications.

It is estimated that only one in 30 antibiotic candidates make it through the laboratory validation phase and then begin testing in patients. The whole process from development to regulatory approval can cost around a billion euros, but since we try to use antibiotics as little as possible to avoid antibiotic resistance, the return for the pharmaceutical company that has invested so much is generally low, often less. than 100 million euros per year. As a result, pharmaceutical companies are reluctant to make large investments in the sector unless there are incentives and purchase promises from governments to keep their research and development activities sustainable.

The issue will be addressed at the next UN General Assembly in September, at a series of meetings dedicated to antimicrobial resistance (the problem also affects fungi and viruses in a different way), which follows on from the last one held eight years ago. Meetings of this type usually serve to establish common commitments and rules, but also to take stock of the situation after the first series of initiatives adopted in 2016 by more than 150 countries to reduce and make antibiotic consumption more responsible.

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