How the world is developing new antibiotics

Developing new antibiotics: Antibiotics are no longer a panacea: bacteria evolve, ceasing to respond to once-powerful drugs. Our body’s resistance to antibiotics is also developing. In 2019, according to the WHO, the number of cases of tuberculosis resistant to several drugs at once in Russia was 5.4 per 100 thousand people. How much in the rest of the world or Europe? Every year, 700 thousand lives are claimed by infections that have become incurable due to antimicrobial resistance. If nothing is done, this number could grow to 10 million by 2050. Not to mention the fact that childbirth can again become life-threatening, and medicine can return to the level of the beginning of the XX century.

What happens to antibiotic resistance in different countries

Antibiotic resistance in the world is growing. Europe regularly reports an increase in antibiotic resistance, and this is despite their strict restrictions on the supply of drugs and the prevalence of modern diagnostic equipment. The rate of antibiotic resistance is lowest in Denmark, and higher in the Balkan Peninsula. So, for Helicobacter pylori (the causative agent of gastritis — “High-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, the countries of Eastern Europe, Russia and Asia have high rates of resistance. But even Europe accounts for 23% of cases of multidrug-resistant tuberculosis, but the success rate of their treatment remains at a high level — 75%.

Of particular concern is the increase in cases of ineffectiveness of antibiotics in the treatment of serious diseases such as tuberculosis, sepsis, bacterial pneumonia, intestinal and genitourinary infections. 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 drugs whose effectiveness has been actively declining since their creation. Since living organisms adapt to adverse effects, the use of antibiotics inevitably leads to mutations, which result in 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) in the treatment of fluoroquinolones, Staphylococcus aureus (Staphylococcus aureus) in the treatment of almost any antibiotics, as well as with Enterococcus faecalis, Enterococcus faecium and others.

The main reason for the deterioration of the situation with resistance is the unjustified prescription and inadequate intake of medicines: this is regularly written by leading medical publications. According to statistics, antibiotics are prescribed and taken incorrectly in almost 50% of cases. In the world, it is common practice to use broad-spectrum antibacterial drugs for preventive purposes, even without determining the causative agent of the infection and without making an assessment of sensitivity to the drug. In the United States, at least 30% of prescriptions for antibiotics were not justified. This does not increase the effectiveness of the treatment, but leads to an increase in bacterial resistance. Self-medication makes a significant contribution to the development of resistance in countries where pharmacies sell antibiotics, despite the lack of a prescription: this is mainly common in Russia and in Eastern European countries.

What technologies are used for the synthesis of new antibiotics

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

  • Actinomycetes are Gram-positive bacteria, similar in structure and function to mold fungi. Capable of forming mycelium: the vegetative body.
  • Phytoncides are biologically active substances with antibacterial properties that inhibit the development of pathogenic microorganisms. They are distinguished by plants.

In addition, many naturally occurring bacteria cannot be cultured in laboratories. As a result, 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 time. Therefore, the process turns out to be very expensive: for 10 years, GlaxoSmithKline has spent $1 billion, but in addition to hepotidacin (the first triazaacenaftilene antibiotic, effective against skin infections — “High-Tech”), it has not yet been able to present anything. Today, scientists have created the conditions for working with “uncultivated” bacteria to grow them in a test tube, but this is also not cheap.

developing new antibiotics

In addition, modern technologies actively help in the development: Russian scientists have created the Everquest algorithm, which in a few hours revealed 10 times more variations of peptide antibiotics than many years of research. And at MIT, artificial intelligence 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 creating a new drug: at this stage, a potentially effective substance has just been discovered. However, even without AI, three new strong drugs of different pharmacological groups have already appeared.

Alternative to antibiotics

After the discovery of penicillin in 1928, medicine completely switched to the study of a new group of drugs (for example, amoxil). The bulk of the development was carried out in relation to antibiotics, because they solved the problem of many serious diseases: from tuberculosis 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 and passive 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 “embed” in it the correct response to viruses. “Reverse” vaccines that do not contain disease-causing virus particles are also being tested. They will have to work against meningococcal, streptococcal, staphylococcal infections, the causative agent of malaria and HIV.

Another alternative to antibiotics is bacteriophages: a part of the natural intestinal microflora that can kill individual bacteria. In medicine, they have been used since the beginning of the XX 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, if the bacteriophage is effective against one strain of the bacterium, it is not a fact that it will help against the rest.

New developments require large financial investments-an average of $ 1.3 billion, but investment in such research is 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 the birth of children will be accompanied by a much higher risk of infection and death.

How the world is developing new antibiotics

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