How new antibiotics are being developed around the world

What Happens to Antibiotic Resistance in Different Countries

Antibiotic resistance is growing in the world.

Europe regularly reports strengtheningantibiotic resistance, and this is with their severe restrictions on the dispensing of drugs and the prevalence of modern diagnostic equipment. Antibiotic resistance is lowest in Denmark and highest in the Balkan Peninsula. So, for Helicobacter pylori (causative agent of gastritis - "Hi-Tech") in Italy, Greece and Croatia, the indicator is in the range of 30-40% against the EU average of 21.6%. And in Denmark only 5%. Traditionally high rates of resistance in the countries of Eastern Europe, Russia and Asia. But even Europe accounts for 23% of cases of multidrug-resistant tuberculosis, but the success of their treatment remains high - 75%.

Of particular concern is the increase in casesineffectiveness of antibiotics in the treatment of serious diseases such as tuberculosis, sepsis, bacterial pneumonia, infections of the intestine and genitourinary tract. WHO has identified three groups of the most dangerous and highly resistant bacteria (high priority, high priority and medium priority), emphasizing the priority of developing new approaches to their treatment.

Why does antibiotic resistance occur?

Antibiotics are the only group of drugsthe effectiveness of which has been actively declining since its inception. As living organisms adapt to adverse influences, the use of antibiotics inevitably leads to mutations, resulting in the emergence of populations of bacteria that are insensitive to the effects of drugs. Among the most pressing problems are Pseudomonas aeruginosa (the causative agent of nosocomial infections - "Hightech") in the treatment of fluoroquinolones, Staphylococcus aureus (Staphylococcus aureus) in the treatment of almost any antibiotic, as well as with Enterococcus faecalis, Enterococcus faecium and others.

The main reason for the deterioration of the situation withresistance - unjustified prescription and inadequate medication intake: leading medical publications regularly write about this. According to statistics, antibiotics are prescribed and taken incorrectly in almost 50% of cases. It is common practice in the world to use broad-spectrum antibacterial drugs for prophylactic purposes, without even identifying the causative agent of the infection and without assessing the sensitivity to the drug. In the United States, at least 30% of antibiotic prescriptions were not justified. This does not increase the effectiveness of the treatment, but it does increase the resistance of the bacteria. A significant contribution to the development of resistance is made by self-medication in countries where pharmacies sell antibiotics, despite the lack of a prescription: this is mostly common in Russia and Eastern Europe.

Another reason for the emergence of resistance toantibiotics - the almost uncontrolled use of antibacterial agents in animal husbandry, fisheries and the production of plant products. People from infancy receive most of antibiotics not in the course of treatment, but with daily food. For example, according to the WHO, in the EU until 1986 they were used as a growth stimulant for livestock. Denmark banned the use of avoparcin in 1997, and in 2000 banned antibiotics altogether. This has led to a decrease in bacterial resistance in a single country, although the link between this fact and the ban on avoparcin is disputed in the United States. However, in 2006 the EU introduced a similar ban on the use of antibacterial drugs in raising livestock. But outside of Europe, the situation is becoming more dangerous: a study of Vietnamese farms found that 84% of antibiotic use was associated with disease prevention, not treatment.

How resistance is reduced in the world and in Russia

WHO has developed a plan to contain growthantibiotic resistance, the main goal of which is to reduce the use of this class of drugs. The strategy includes five main directions, where the key is work with the population. Governments are invited to communicate the importance of combating antibiotic resistance and the need for everyone to contribute to this process. Explain that if nothing is done, then soon even sore throat will not be able to cope, and it will be the same dangerous disease as in the 19th century - tuberculous meningitis. In parallel, it is necessary to improve infection control. It should include the collection and analysis of data on the prevalence of resistance, the transfer of information to a common database.

WHO focuses on:it is necessary to completely prevent the spread of infections. This is planned to be achieved by expanding the coverage of immunization for children and adults, including new vaccines that have passed the necessary tests into the national immunization schedule. And all this simultaneously with the rational prescription and use of antibiotics according to strict indications and regimens.

To this end, WHO uses the AWaRe tool -a list of three groups of antibacterial drugs: the first and second choice, as well as the last reserve. It helps to understand which agents should be used primarily in routine treatment, and which ones should be left exclusively for difficult cases.

The final point in WHO's strategy concernsinvestments in new developments and the safety of medical care. The desire to treat an increasing number of patients with reduced funding, as well as to reduce the number of bed-days create favorable conditions for the spread of resistant microbes. The doctor is simply not ready to carry out therapy to the end, therefore he gives a strong antibiotic, just to close the sick leave faster.

Russia has also defined its strategy by itsfight resistance until 2030. It included standards for the content of antibiotics in food, education of the population, a gradual reduction in the consumption of antibiotics and the prohibition of their advertising, as well as an emphasis on protecting immunity. Our scientists have developed a convenient interactive map showing the levels of resistance of pathogens to certain drugs in different countries - ResistoMap. The closer the color of the highlighted area on the map to brown, for example, the higher the resistance potential of the intestinal microbiota in the population. You can also explore countries by type of antibiotic. For example, France has the highest rate for fluoroquinolones. The Russian development also confirms the studies of foreign scientists, which show that Denmark is on the bottom lines in terms of antibiotic resistance (due to its rare use).

What technologies are used to synthesize new antibiotics

Antibiotics are obtained either naturally,through the search for bacteria (usually actinomycetes), or artificially - they create synthetic structures to stop the biosynthesis of protein, cell wall or division of bacterial DNA. Less commonly, antibiotics are obtained from phytoncides and living organisms. However, for almost 100 years of existence of these drugs, all of the above methods of "killing" bacteria have been studied so much that new antibiotics have not been discovered for 25 years.

Actinomycetes - gram-positive bacteria, similar in structure and function to molds. Capable of forming mycelium: vegetative body.

Phytoncides - biologically active substances with antibacterial properties that suppress the development of pathogenic microorganisms. Allocated by plants.

In addition, in laboratories, many bacterialiving in a natural environment, you can not cultivate. As a result, in order to discover a new antibiotic, it is necessary to sort out about 1 million actinomycetes, and their spontaneous mutations can negate the process at any moment. Therefore, the process turns out to be very expensive: for 10 years GlaxoSmithKline spent $ 1 billion, but apart from hepotidacin (the first triazaacenaphthylene antibiotic, effective against skin infections - "Hi-Tech"), it could not imagine anything. Scientists today have created the conditions for working with "unculturable" bacteria in order to grow them in a test tube, but this is also not cheap.

In addition, modern technologies are activelyhelp in development: Russian scientists have created the VarQuest algorithm, which in a few hours revealed 10 times more variations in peptide antibiotics than many years of research. And at MIT, artificial intelligence has helped scientists find an effective drug among millions of options. We are talking about halicin, a substance that affects a wide range of bacteria, including those resistant to most antibiotics. But this is not yet the story of the creation of a new drug: at this stage, a potentially effective substance was simply discovered. However, even without AI, three new strong drugs of different pharmacological groups have already appeared.

Antibiotics that emerged in the era of resistance:

Teixobactin - antibiotic showing high efficiencyagainst a multi-resistant strain of Staphylococcus aureus (studies were carried out on mice), tubercle bacillus, anthrax, while not causing side effects.

Bedaquiline - an anti-tuberculosis drug that inhibitsenzymes involved in the cellular respiration of mycobacteria. It is effective against strains with multiple, pre-wide and wide resistance, has a bactericidal and bacteriostatic (kills or blocks activity) effect depending on the dose.

SkQ1 - mitochondria targeted antioxidant,which, in the research of the Research Institute of Physical Chemistry and Biology, Moscow State University, showed antibacterial activity, affecting the membrane of bacteria. At the moment, there is information about its effectiveness against Bacillus subtilis, Mycobacterium sp. and Staphylococcus aureus.

Alternative to antibiotics

After the discovery of penicillin in 1928, medicinecompletely switched to studying a new group of drugs. The bulk of the development was carried out specifically in relation to antibiotics, because they solved the problem of many serious diseases: from tuberculous meningitis and pneumonia (30% of cases before the appearance of penicillin ended in death) to Lyme disease. However, now scientists are again studying substances that can have the same effect, but more safely and effectively.

First of all, these are drugs for active andpassive immunization - vaccines and antibodies. DNA vaccines against tuberculosis, salmonellosis and HIV have already been developed and are being tested. Genetic immunization should help provide the body with lifelong protection, literally "build" into it the correct response to viruses. Also being tested are "reverse" vaccines that do not contain the disease-causing virus particles. They will have to work against meningococcal, streptococcal, staphylococcal infections, the causative agent of malaria and HIV.

Another alternative to antibiotics is bacteriophages:part of the natural intestinal microflora, capable of killing individual bacteria. They have been used in medicine since the beginning of the 20th century, but not too actively. First, it is difficult to predict adverse reactions from such treatment, since the phage genome is not fully understood. Secondly, even if a bacteriophage is effective against one strain of bacteria, it is not a fact that it will help against the rest.

Phage therapy also includes the use ofphagolysins - protein substances that are in every living organism. They destroy the cell wall of bacteria, after which bacteriophages and antibiotics are used. In fact, it is a complementary treatment method that allows you to reduce the resistance of the microbe to the main drugs. The most famous phagolysin substance is lysozyme, which is used in topical throat remedies. It has an antibacterial effect and is able to work even with resistant bacteria, depriving them of their natural defenses. Lysozyme is used in particular against throat diseases.

Another potentially effective substancebecame antimicrobial peptides - molecules that can kill cells of pathogenic microorganisms. They are part of the innate immunity and primary defense against infections. They can also be produced by microorganisms themselves: for example, Lactococcus casea, which is part of fortified yoghurts, produces the peptide nisin. In 2007, clinical trials were carried out on the peptide drug ramoplanin, which was supposed to help against bacterial strains that are resistant to vancomycin (glycopeptide antibiotic - "Hi-Tech") or metronidazole (antiprotozoal substance with antibacterial activity - "Hi-tech"). Ramoplanin showed high activity, and in 2018 there was even talk about its release based on Russian components, however, it is still not in the Register of Medicines of Russia. Thus, it is not yet possible to find what will replace vancomycin in case of resistance to it.

New developments require large financialinvestments - on average $ 1.3 billion, but investments in such research are becoming a vital necessity. If we do not take care of the problem of antibiotic resistance, in the coming decades we will have to forget not only about complex operations, but also about such simple things as the removal of appendicitis or a bad tooth. Even having babies will carry a much higher risk of infection and death.

See also:

20 new species of animals and plants found in the Andes

There are highways in space for fast travel. How will flights change?

Named a plant that is not afraid of climate change. It feeds a billion people