27 October 2014

The past, present and future of antibiotics

5 facts about the effectiveness of drugs, producing strains and the development of new drugsKonstantin Miroshnikov, Post-science

In recent years, quite a lot has been said that medicine in its modern sense is on the verge of disaster.

Antibiotics stop working, and this is a really big and very serious problem. But in order to understand why they began to work worse and whether the situation is really so tragic, we need to figure out what antibiotics are and how they are used in human life.

1. Discovery of antibioticsThe history of the discovery of antibiotics is quite anecdotal.

In 1928, the English scientist Alexander Fleming forgot a cup of sown culture on the table, and it became moldy. It turned out that this mold – Penicillium fungi – secretes a certain substance that is harmful to bacteria. Later it turned out that antibiotics are secreted by fungi, other bacteria, plants, and animals. This is a kind of semi-preventive measure that organisms use in order to win their niche in the ecological community and scare off opponents. The development of antibiotics was subsequently based on the principle of searching for a substance that is maximally harmful to certain microorganisms, mainly pathogens.

2. Producing strainsFor a long time, so-called producer strains were searched and cultivated, that is, a fungus or a bacterium was selected that isolated the largest amount of something poisonous for bacteria.

Then this antimicrobial substance was collected, chemically characterized, many different medical tests and checks were done and, if necessary, subjected to some small chemical modification. So a great many derivatives were born from a rather small initial number of compounds. In the modern sense, antibiotics are quite small molecules by biological standards. They are divided into classes based on their chemical structure.

3. Antibiotics – generators of conditional pathogensIt is no exaggeration to say that in the twentieth century, hundreds of millions of human lives were saved with the help of antibiotics.

At that time, it was really a panacea. But even the discoverer of penicillin, Alexander Fleming, said that microorganisms adapt quite quickly to the action of antibiotics and that after several generations of bacterial cell division, those that do not die from the action of the same penicillin are formed. Accordingly, they gain an evolutionary advantage, grow, and penicillin stops working.

For a long time there was a kind of competition between nature and human intelligence and skill. As microorganisms adapted to existing antibiotics, people manufactured more and more new classes. But this concept was most likely ruined not even by medical use, but by the fact that it became cheap to synthesize antibiotics, and they began to be actively used in agriculture. The bill went to tens of thousands of tons per year. They were used for the prevention of diseases, pollination of stalls, poultry houses, all this got into the water and soil, and it turned out that not only pathogenic bacteria, against which they were used in medicine, but also completely harmless microbes that live in the environment began to adapt to the constant presence of antibiotics. That is, they have become conditional pathogens.

Let conditional pathogens pose no particular danger to a healthy person, but interacting with an organism that has weakened immunity, that is, with patients of hospitals, maternity hospitals, nursing homes, burn centers, they grow with terrible force, and people get more and more seriously ill, up to the most tragic consequences. In addition, such nosocomial infections persist in the hospital. Bacteria begin to live in the nooks and crannies of beds, hospital appliances, reusable instruments, even in disinfectant solutions. And a person who gets into this hospital with one disease eventually becomes ill with something else, for example, after getting into the hospital with a burn, after a couple of days he gets an intestinal infection. This is a very serious problem.

4. Microbes against antibioticsThe development of new classes of antibiotic drugs became more and more expensive, more and more difficult, and eventually fundamentally new drugs stopped appearing.

Now the microbes are winning. Already in 2012, humanity's capitulation to pathogenic microbes was signed at the highest level in rather tragic tones. The head of the World Health Organization, Margaret Chan, said that this is the end of modern medicine.

As things stand, of course, there will be enough reserves of current developments for some time. It is necessary to treat the matter responsibly. For example, in agriculture since 2005 in the West it is forbidden to use antibiotics for preventive purposes, but only for the treatment of sick animals or plants. It is necessary to urge doctors not to prescribe antibiotics for prevention, not to use them in the treatment of viral infections, because they do not act on viruses, but only act on bacteria. Very often, antibiotics for influenza or severe acute respiratory viral infections are prescribed just in case, because when the body is weakened from a viral infection, then, for example, microbes can settle in an inflamed throat, which already have to be treated with antibiotics. But until the microbial infection is confirmed, antibiotics should not be used. And there are specialized antiviral drugs for viruses.

Nevertheless, the situation is quite depressing, because if microbes do adapt to all existing classes of antibiotics - and this is quite likely – then we will return to the situation that existed until the second half of the nineteenth century, when infection was considered something given from above and it was not considered necessary to protect against it. For example, back then, during a surgical operation, doctors did not have to wash their hands. At the moment, there are some types of Staphylococcus aureus that are resistant to about 2/3 of the existing types of antibiotics. There is also gonococcus, which is treated with only one antibiotic out of all existing ones.

5. The future of antibioticsIt should be particularly noted that with the existing system of certification of a medicinal product, which takes many years, rather economic reasons are important.

Drug development is really expensive, only large companies can do it, and, of course, these companies rely on those drugs that will have a stable market. Thus, in recent decades, the pharmaceutical industry has been focusing more on the stabilization of chronic diseases. As for antibiotics, on the one hand, no one is immune from catching some kind of infection, but on the other hand, the demand for these drugs is fickle, because there are always many alternatives. There are always some combined and incongruous courses of antibiotics, first-choice antibiotics and reserve antibiotics. And this is one of the important reasons why no fundamentally new antibiotic drugs have appeared since the 80s.

But the situation is not hopeless. Now vaccinology, various hygienic and preventive procedures are developing very actively, so there is an opportunity to make more efforts to avoid diseases. The possibilities of antibiotics themselves are also far from being exhausted. Combinatorial chemistry and systems for testing potential drugs are being improved. Molecular modeling methods make it possible to create such antibiotics that act simultaneously on several systems of bacterial vital activity, and so-called prodrugs, that is, substances that become active only when they enter the target microorganism. It is more difficult for microbes to adapt to such "superantibiotics". In a word, the scientific basis for further development of antibiotics exists. But it will be possible to implement them only if the economic dogmas existing in pharmacology are corrected.

About the author: Konstantin Miroshnikov – Candidate of Biological Sciences, Acting Head of the Laboratory of Molecular Bioengineering of the Institute of Bioorganic Chemistry named after Shemyakin and Ovchinnikov RAS.

Portal "Eternal youth" http://vechnayamolodost.ru27.10.2014

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