Antibiotic resistance of microorganisms: methods for determining

Antibiotics - one of the greatest achievements of medical science, which annually saves lives of tens and hundreds of thousands of people. However, as wisdom says, an old woman also has an erudition. What previously killed pathogenic microorganisms, today does not work the way it used to. So what's the reason: did antimicrobials become worse or because of antibiotic resistance?

Determination of antibiotic resistance

Antimicrobials (APMs), which are called antibiotics, were originally created to combat bacterial infection. And due to the fact that different diseases can cause not one but several varieties of bacteria grouped together, the development of drugs effective against a certain group of infectious agents was initially carried out.

But bacteria, though the simplest, but actively developing organisms, eventually acquire more and more new properties. The instinct of self-preservation and the ability to adapt to different conditions of life make pathogenic microorganisms stronger. In response to the threat to life, they begin to develop in themselves the ability to resist it, highlighting a secret that weakens or completely neutralizes the effect of the active substance of antimicrobials.

It turns out that once effective antibiotics simply cease to fulfill their function. In this case, they talk about the development of antibiotic resistance to the drug. And the point here is not at all the effectiveness of the active substance of AMP, but in the mechanisms for the improvement of pathogenic microorganisms, through which bacteria become not sensitive to antibiotics designed to fight them.

So, antibiotic resistance is nothing more than a decrease in the susceptibility of bacteria to antimicrobial drugs that were created to destroy them. It is for this reason that treatment, it would seem, correctly selected preparations does not give the expected results.

[1], [2], [3], [4], [5], [6],

The problem of antibiotic resistance

The lack of antibiotic therapy, associated with antibiotic resistance, leads to the fact that the disease continues to progress and turns into a heavier form, the treatment of which becomes even more difficult. Particularly dangerous are cases when a bacterial infection affects vital organs: the heart, lungs, brain, kidneys, etc., because in this case the delay in death is similar.

The second danger is that some diseases with chronic antibiotic therapy may become chronic. A person becomes a carrier of improved microorganisms resistant to antibiotics of a certain group. He is now the source of infection, to combat which the old methods become meaningless.

All this pushes the pharmaceutical science to the invention of new, more effective means with other active substances. But the process again goes around with the development of antibiotic resistance to new drugs from the category of antimicrobial agents.

If someone seems to think that the problem of antibiotic resistance has arisen quite recently, he is very mistaken. This problem is old as the world. Well, maybe not so much, and yet she is already 70-75 years old. According to the generally accepted theory, it appeared along with the introduction of the first antibiotics into medical practice somewhere in the 40s of the 20th century.

Although there is a concept of an earlier appearance of the problem of resistance of microorganisms. Before the advent of antibiotics, this problem was not specifically addressed. It's so natural that bacteria, like other living things, tried to adapt to unfavorable environmental conditions, did it their own way.

The problem of resistance of pathogenic bacteria recalled itself when the first antibiotics appeared. However, then the question was not so important. At that time, various groups of antibacterial drugs were being actively developed, which was in some way caused by the unfavorable political situation in the world, by military actions, when the soldiers died from wounds and sepsis only because they could not be effectively helped because of the lack of necessary drugs. Just these drugs did not exist yet.

The greatest number of developments was carried out in the 50-60 years of the twentieth century, and during the next 2 decades their improvement was carried out. Progress on this has not ended, but since the 80s, developments with respect to antibacterial agents have become noticeably less. The fault is that the high cost of this enterprise (the development and release of a new drug now reaches the border of $ 800 million) or the banal lack of new ideas for "militantly" active substances for innovative drugs, but in this regard the problem of antibiotic resistance is coming out to a new frightening level.

While developing promising AMPs and creating new groups of such drugs, scientists hoped to defeat multiple types of bacterial infection. But everything turned out to be not so simple "thanks" to antibiotic resistance, which develops quite rapidly in individual strains of bacteria. Enthusiasm is gradually drying up, but the problem remains unsolved for a long time.

It remains unclear how microorganisms can develop resistance to drugs, which in theory were supposed to kill them? Here it is necessary to understand that the "killing" of bacteria occurs only when the drug is used for its intended purpose. And what do we really have?

Causes of antibiotic resistance

Here we come to the main question, who is to blame for the fact that bacteria do not die when antibacterial agents are exposed to them, but they are directly degenerated, acquiring new properties that are far from helping humanity? What provokes such changes occurring with microorganisms that are the cause of many diseases with which mankind has been struggling for more than a decade?

It is clear that the true cause of development of antibiotic resistance is the ability of living organisms to survive in different conditions, adapting to them in different ways. But the ability to dodge a deadly projectile in the face of an antibiotic, which in theory should carry death to them, the bacteria do not. So how does it turn out that they not only survive, but also improve along with the improvement of pharmaceutical technologies?

It should be understood that if there is a problem (in our case, the development of antibiotic resistance in pathogenic microorganisms), then there are provoking factors that create conditions for it. Just in this matter, we now try to understand.

[7], [8], [9], [10], [11],

Factors of development of antibiotic resistance

When a person comes to a doctor with complaints about his health, he expects qualified help from a specialist. If it comes to an infection of the respiratory tract or other bacterial infections, the doctor's task is to prescribe an effective antibiotic that will not let the disease progress, and determine the dosage necessary for this purpose.

The choice of medicines at the doctor is big enough, but how to determine exactly the drug that really helps to cope with the infection? On the one hand, to justify the appointment of an antimicrobial drug, it is necessary to first determine the type of pathogen, according to the etiotropic concept of drug selection, which is considered to be the most correct. But on the other hand, this can take up to 3 or more days, while the most important condition for successful cure is considered timely therapy in the early stages of the disease.

The doctor has nothing left to do, after the diagnosis was made, to act in the first days at random, in order to somehow slow down the disease and prevent it from spreading to other organs (an empirical approach). When appointing an outpatient treatment, the practitioner proceeds from the assumption that certain bacteria can be the causative agent of a particular disease. This is the reason for the initial choice of the drug. The purpose may vary depending on the results of the assay for the pathogen.

And it's good if the doctor's appointment is confirmed by the results of the tests. Otherwise, not only time will be lost. The matter is that for successful treatment there is one more necessary condition - complete deactivation (in medical terminology there is a concept of "irradication") of pathogenic microorganisms. If this does not happen, the surviving microbes simply "get sick", and they will develop a kind of immunity to the active substance of the antimicrobial drug that caused their "illness". This is just as natural as the production of antibodies in the human body.

It turns out that if the antibiotic is picked up incorrectly or ineffective the dosing and receiving regimen will turn out, pathogenic microorganisms can not perish, but change or acquire previously uncharacteristic possibilities. Breeding, such bacteria form whole populations of strains resistant to antibiotics of a particular group, i.e. Antibiotic-resistant bacteria.

Another factor that adversely affects the susceptibility of pathogenic microorganisms to antibacterial drugs is the use of AMP in animal husbandry and veterinary medicine. The use of antibiotics in these areas is not always justified. In addition, the definition of the causative agent of the disease in most cases is not carried out or is carried out with delay, because antibiotics are treated mainly animals that are in a rather serious condition, when everything is decided by time, and waiting for the results of the analysis is not possible. And in a village, a veterinarian does not always even have this opportunity, so he acts "blindly."

But it would be nothing, only there is another big problem - the human mentality, when everyone is a doctor to himself. Moreover, the development of information technology and the opportunity to purchase most antibiotics without a doctor's prescription only aggravate this problem. And if we take into account that we have more than unqualified self-taught doctors than those who strictly follow the doctor's prescriptions and recommendations, the problem acquires a global dimension.

In our country, the situation is aggravated by the fact that most people remain financially bankrupt. They do not have the opportunity to purchase effective, but expensive drugs of a new generation. In this case, they substitute the appointment of a doctor with cheaper old analogues or drugs, which the best friend or omniscient friend advised.

"It helped me, and will help you!" - can you argue with this if the words sound from the lips of a neighbor who has mastered the rich life experience, who passed the war? And few people think that thanks to such well-read and trustful, pathogenic microorganisms have long adapted to survive under the action of drugs recommended in earlier times. And what helped the grandfather 50 years ago, may prove ineffective in our time.

And what can we say about advertising and the inexplicable desire of some people to try innovations on themselves as soon as the symptom-appropriate illness turns out. And why all these doctors, if there are such wonderful drugs, which we learn about from newspapers, TV screens and Internet pages. Only the text about self-medication has already become so boring that few people pay attention to it now. And very vain!

[12], [13], [14], [15], [16], [17], [18], [19], [20],

Mechanisms of antibiotic resistance

Recently, antibiotic resistance has become the number one problem in the pharmacological industry that develops antimicrobials. The thing is that it is inherent in almost all known varieties of bacteria, so antibiotic therapy is becoming less effective. Such common pathogens as Staphylococci, Escherichia coli and Pseudomonas aeruginosa, the proteins have resistant strains that are more common than their ancestors exposed to antibiotics.

Resistance to various groups of antibiotics, and even to individual drugs, develops in different ways. Old good penicillins and tetracyclines, as well as newer developments in the form of cephalosporins and aminoglycosides, are characterized by a slow development of antibiotic resistance, in parallel with these, their therapeutic effect also decreases. What can not be said about such drugs, the active substance of which is streptomycin, erythromycin, rifampicin and lincomycin. Resistance to these drugs develops at a rapid pace, in connection with which the appointment has to be changed even during the course of treatment, without waiting for its termination. The same goes for preparations of oleandomycin and fusidine.

All this gives grounds to assume that the mechanisms of development of antibiotic resistance to various drugs are significantly different. Let's try to understand which properties of bacteria (natural or acquired) do not allow antibiotics to produce their irradiation, as originally conceived.

To begin with, we determine that the resistance of a bacterium can be natural (protective functions given to it initially) and acquired, which we discussed above. So far, we have mainly talked about the true antibiotic resistance associated with the characteristics of the microorganism, and not with the incorrect choice or prescription of the drug (in this case it is a false antibiotic resistance).

Every living being, including the simplest, has its own unique structure and some properties that allow it to survive. All this is laid down genetically and transmitted from generation to generation. The natural resistance to specific active substances of antibiotics is also laid down genetically. And in different types of bacteria, resistance is directed to a certain type of drugs, which is why development of various groups of antibiotics affecting a particular type of bacteria is associated.

Factors that cause natural resistance may be different. For example, the structure of the protein membrane of a microorganism can be such that an antibiotic can not cope with it. But antibiotics can only be affected by a protein molecule, destroying it and causing the death of a microorganism. The development of effective antibiotics implies taking into account the structure of the proteins of bacteria against which the action of the drug is directed.

For example, the antibiotic resistance of staphylococci to aminoglycosides is due to the fact that the latter can not penetrate the microbial membrane.

The whole surface of the microbe is covered with receptors, with certain types of which are associated with AMP. A small number of suitable receptors or their complete absence lead to the fact that there is no binding, and hence the antibacterial effect is absent.

Among other receptors there are also those that for the antibiotic serve as a kind of beacon signaling the location of the bacteria. The absence of such receptors allows the microorganism to hide from danger in the form of AMP, which is a kind of disguise.

Some microorganisms have a natural ability to actively withdraw AMP from the cell. This ability is called effluksom and it characterizes the resistance of Pseudomonas aeruginosa against carbapenems.

Biochemical mechanism of antibiotic resistance

In addition to the natural mechanisms of development of antibiotic resistance listed above, there is one more that is related not with the structure of the bacterial cell, but with its functional.

The fact is that in the body of bacteria, enzymes can be produced that can have a negative effect on molecules of the active substance AMP and reduce its effectiveness. Bacteria when interacting with such antibiotic also suffer, their effect is markedly weakened, which creates the appearance of curing infection. Nevertheless, the patient remains a carrier of bacterial infection for some time after the so-called "recovery".

In this case, we are dealing with a modification of the antibiotic, as a result of which it becomes inactive with respect to this type of bacteria. Enzymes produced by different types of bacteria may differ. Staphylococcus is characterized by the synthesis of beta-lactamase, which provokes the rupture of the lactem ring of antibiotics of the penicillin series. The development of acetyltransferase can explain the resistance to chloramphenicol gram-negative bacteria, etc.

[21], [22], [23]

Acquired antibiotic resistance

Bacteria, like other organisms, are not alien to evolution. In response to "military" actions against them, microorganisms can change their structure or start synthesizing so much of an enzyme substance that can not only reduce the effectiveness of the drug, but also destroy it completely. For example, the active production of alanine transferase makes "Cycloserine" ineffective against bacteria that produce it in large quantities.

Antibiotic resistance can also develop due to a modification in the cell structure of the protein, which is also its receptor, to which AMP should bind. Those. This kind of protein may be absent in the bacterial chromosome or change its properties, as a result of which the connection between the bacterium and the antibiotic becomes impossible. For example, the loss or modification of a penicillin-binding protein causes insensitivity to penicillins and cephalosporins.

As a result of the development and activation of protective functions in bacteria previously susceptible to the destructive effect of a particular type of antibiotics, the permeability of the cell membrane changes. This can be done by reducing the channels through which the active substances of AMP can penetrate into the cell. It is these properties due to the insensitivity of streptococci to beta-lactam antibiotics.

Antibiotics can influence the cellular metabolism of bacteria. In response, some microorganisms learned to do without chemical reactions, which are affected by the antibiotic, which is also a separate mechanism for the development of antibiotic resistance, which requires constant monitoring.

Sometimes bacteria go to a certain trick. By joining to a dense substance they are united in communities called biofilms. Within the community, they are less susceptible to antibiotics and can safely tolerate dosages killing for a single bacterium that lives outside the "collective".

Another option is to combine microorganisms into groups on the surface of a semiliquid medium. Even after cell division, a part of the bacterial "family" remains inside the "grouping", which can not be influenced by antibiotics.

[24], [25], [26], [27], [28], [29], [30]

Genes of antibiotic resistance

There are concepts of genetic and non-genetic drug resistance. With the latter, we are dealing with when we consider bacteria with inactive metabolism, not prone to multiplication under normal conditions. Such bacteria can develop antibiotic resistance to certain types of drugs, nevertheless, this ability is not transmitted to their offspring, since it is not genetically incorporated.

This is characteristic of pathogenic microorganisms that cause tuberculosis. A person can get infected and not suspect about the disease for many years, until his immunity for some reason will not fail. This is the trigger for multiplication of mycobacteria and the progression of the disease. But all the same drugs are used to treat tuberculosis, the bacterial progeny still remains sensitive to them.

The same is true with the loss of protein in the cell wall of microorganisms. Remember, again about bacteria that are sensitive to penicillin. Penicillins inhibit the synthesis of the protein that serves to build the cell membrane. Under the influence of AMP penicillin series microorganisms can lose the cell wall, the building material of which is the penicillin-binding protein. Such bacteria become resistant to penicillins and cephalosporins, which now have nothing to communicate with. This phenomenon is temporary, not related to the mutation of genes and the transfer of the mutated gene by inheritance. With the appearance of the cell wall, which is characteristic of previous populations, the antibiotic resistance in such bacteria disappears.

The genetic antibiotic resistance is said to occur when changes in the cells and metabolism within them occur at the gene level. Mutations of genes can cause changes in the structure of the cell membrane, provoke the production of enzymes that protect bacteria from antibiotics, and also change the number and properties of the receptors of the bacterial cell.

There are 2 ways of development of events: chromosomal and extrachromosomal. If a gene mutation occurs on that part of the chromosome that is responsible for sensitivity to antibiotics, they speak of chromosomal antibiotic resistance. By itself, such a mutation occurs extremely rarely, usually it causes the effects of drugs, but again, not always. It is very difficult to control this process.

Chromosomal mutations can be transmitted from generation to generation, gradually forming certain strains (varieties) of bacteria resistant to one or another antibiotic.

Culprits of extrachromosomal resistance to antibiotics are genetic elements that exist outside the chromosomes and are called plasmids. It is these elements that contain the genes responsible for the production of enzymes and the permeability of the bacterial wall.

Antibiotic resistance is most often the result of horizontal gene transfer, when some bacteria transmit some genes to others that are not their descendants. But sometimes unconnected point mutations can be observed in the genome of the pathogen (size 1 in 108 for one process of copying the DNA of the mother cell, which is observed when replicating chromosomes).

So in the fall of 2015, scientists from China described the gene MCR-1, found in pig meat and swine intestines. A feature of this gene is the possibility of its transmission to other organisms. After a while, the same gene was found not only in China, but also in other countries (USA, England, Malaysia, European countries).

The antibiotic resistance genes are able to stimulate the production of enzymes that were not previously produced in the body of bacteria. For example, the enzyme NDM-1 (metal beta-lactamase 1), found in bacteria Klebsiella pneumoniae in 2008. At first it was found in bacteria from India. But in subsequent years, an enzyme providing antibiotic resistance against most AMP was detected in microorganisms in other countries (Great Britain, Pakistan, USA, Japan, Canada).

Pathogenic microorganisms can be resistant to certain drugs or groups of antibiotics, as well as to different groups of drugs. There is such a thing as cross-antibiotic resistance, when microorganisms become insensitive to drugs with a similar chemical structure or mechanism of action on bacteria.

Antibiotic resistance of staphylococci

Staphylococcal infection is considered one of the most common among community-acquired infections. However, even in a hospital on the surfaces of various objects, it is possible to detect about 45 different strains of staphylococcus. This suggests that the fight against this infection is almost the first priority of health workers.

The difficulty in accomplishing this task is that most strains of the most pathogenic staphylococcus Staphylococcus epidermidis and Staphylococcus aureus are resistant to many types of antibiotics. And the number of such strains is growing every year.

The ability of staphylococci to multiple genetic mutations, depending on the habitat conditions, makes them virtually invulnerable. Mutations are transmitted to descendants and in a short time there are whole generations of infectious agents resistant to antimicrobial preparations from the genus Staphylococci.

The biggest problem is methicillin-resistant strains that are resistant not only to beta-lactams (β-lactam antibiotics: certain subgroups of penicillins, cephalosporins, carbapenems and monobactams), but also to other types of AMP: tetracyclines, macrolides, lincosamides, aminoglycosides, fluoroquinolones, chloramphenicol.

For a long time, the infection could be destroyed only with the help of glycopeptides. At present, the problem of antibiotic resistance of such strains of staphylococcus is solved by means of a new type of AMP - oxazolidinones, whose bright representative is linezolid.

[31], [32], [33], [34], [35], [36], [37], [38]

Methods for determining antibiotic resistance

When creating new antibacterial drugs, it is very important to clearly define its properties: how they work and what bacteria are effective. This can be determined only through laboratory research.

Analysis for antibiotic resistance can be carried out using various methods, the most popular of which are:

• Disc method, or diffusion of AMP in agar according to Kirby-Bayer
• Method of serial dilutions
• Genetic identification of mutations that cause drug resistance.

The first method to date is considered the most common due to the cheapness and simplicity of execution. The essence of the method of discs is that the strains of bacteria isolated as a result of research are placed in a nutrient medium of sufficient density and covered with impregnated AMP solution with paper discs. The concentration of the antibiotic on the discs is different, so when the drug diffuses into the bacterial medium, a concentration gradient can be observed. By the size of the zone of non-growth of microorganisms, one can judge the activity of the preparation and calculate the effective dosage.

A variant of the disc method is the E-test. In this case, instead of discs, polymeric plates are used, on which a certain concentration of antibiotic is applied.

The disadvantages of these methods is the inaccuracy of the calculations associated with the dependence of the concentration gradient on various conditions (density of the medium, temperature, acidity, calcium and magnesium content, etc.).

The method of serial dilutions is based on the creation of several variants of a liquid or dense medium containing different concentrations of the test preparation. Each of the variants is populated with a certain amount of the bacterial material being studied. At the end of the incubation period, the growth of bacteria or its absence is estimated. This method allows you to determine the minimum effective dose of the drug.

The method can be simplified by taking as a sample only 2 media, the concentration of which will be as close as possible to the minimum necessary to inactivate the bacteria.

The serial dilution method is rightly considered the gold standard for determining antibiotic resistance. But because of the high cost and laboriousness, it is not always applicable in domestic pharmacology.

The method for identifying mutations provides information on the presence of mutated genes in a strain of bacteria that promote the development of antibiotic resistance to specific drugs, and in this regard, systematize emerging situations, taking into account the similarity of phenotypic manifestations.

This method is distinguished by the high cost of test systems for its implementation, however, its value for predicting genetic mutations in bacteria is undeniable.

No matter how effective the above methods of antibiotic resistance testing, they can not fully reflect the picture that unfolds in the living body. And if we also take into account the fact that the organism of each person is individual, the processes of distribution and metabolism of medicines can take place differently in it, the experimental picture is very far from the real.

Ways to overcome antibiotic resistance

No matter how good this or that drug is, but with the attitude to treatment that we have, one can not exclude the fact that at some point the sensitivity of pathogenic microorganisms to it can change. The creation of new drugs with the same active substances also does not solve the problem of antibiotic resistance. And to new generations of drugs the sensitivity of microorganisms with frequent unjustified or incorrect appointments is gradually weakening.

A breakthrough in this regard is considered the invention of combined preparations, which are called protected. Their use is justified for bacteria that produce destructive enzymes for common antibiotics. Protection of popular antibiotics is carried out by including special agents in the new preparation (for example, enzyme inhibitors dangerous for a certain type of AMP), which stop the production of these enzymes by bacteria and prevent the removal of the drug from the composition of the cell by means of a membrane pump.

As inhibitors of beta-lactamases, it is customary to use clavulanic acid or sulbactam. They are added in beta-lactam antibiotics, which increases the effectiveness of the latter.

Currently, the development of drugs that can affect not only the individual bacteria, but also those that have merged into groups. The fight against bacteria in the biofilm can only be carried out after its destruction and the release of organisms previously linked together by chemical signals. In terms of the possibility of destruction of biofilm, scientists are considering such a form of drugs as bacteriophages.

Struggle against other bacterial "groupings" is conducted by transferring them to a liquid medium, where microorganisms begin to exist separately, and now they can be combated with conventional drugs.

Faced with the phenomenon of resistance in the process of drug treatment, doctors solve the problem of prescribing various drugs effective against the isolated bacteria, but with different mechanisms of action on the pathogenic microflora. For example, concomitantly use drugs with bactericidal and bacteriostatic action or replace one drug with another, from another group.

Prevention of antibiotic resistance

The main task of antibiotic therapy is the complete destruction of the population of pathogenic bacteria in the body. This task can be solved only by the appointment of effective antimicrobial agents.

The effectiveness of the drug, respectively, is determined by the spectrum of its activity (whether the pathogen is included in this spectrum), the possibilities for overcoming the mechanisms of antibiotic resistance, the optimal dosage regimen at which the pathogenic microflora is killed. In addition, when prescribing a drug, the likelihood of developing side effects and the availability of treatment for each individual patient should be considered.

With an empirical approach to the therapy of bacterial infections, it is not possible to take all these points into account. It requires a high professionalism of the doctor and constant monitoring of information on infections and effective drugs to combat them, so that the appointment was not unjustified and did not lead to the development of antibiotic resistance.

The creation of high-tech medical centers allows one to practice etiotropic treatment when the pathogen is first detected in a shorter time, and then an effective drug is administered.

Prevention of antibiotic resistance can also be considered control of prescribing. For example, in ARVI, the appointment of antibiotics is not justified, but it contributes to the development of antibiotic resistance of microorganisms that are for the time being in a "sleeping" state. The fact that antibiotics can provoke a weakening of immunity, which in turn will cause the reproduction of a bacterial infection that is buried inside the body or got into it from the outside.

It is very important that the prescribed drugs meet the goal to be achieved. Even a drug prescribed for prophylactic purposes should have all the properties necessary to destroy the pathogenic microflora. The choice of the drug at random can not only not give the expected effect, but also aggravate the situation by developing resistance to the preparation of a certain type of bacteria.

Particular attention should be paid to dosage. Small doses, ineffective to fight infection, again lead to the formation of antibiotic resistance in pathogens. But there is also no need to overdo it, because with antibiotic therapy, the likelihood of developing toxic effects and anaphylactic reactions dangerous for the patient's life is great. Especially if the treatment is carried out on an outpatient basis with no control by the medical staff.

Through the media it is necessary to convey to people the danger of self-medication with antibiotics, as well as unfinished treatment, when bacteria do not die, but only become less active with the developed mechanism of antibiotic resistance. The same effect is also provided by cheap, unlicensed drugs that illegal pharmaceutical companies position as budgetary counterparts of already existing drugs.

A highly effective measure for the prevention of antibiotic resistance is the continuous monitoring of existing infectious agents and the development of antibiotic resistance in them not only at the level of a region or region, but also on a national scale (and even the whole world). Alas, this has only to dream.

In Ukraine, the system of infection control as such does not exist. Only certain provisions have been adopted, one of which (still in 2007!), Concerning obstetric hospitals, involves the introduction of various methods of monitoring nosocomial infections. But everything again rests on finance, and on the ground such studies are mostly not conducted, not to mention doctors from other branches of medicine.

In the Russian Federation, the problem of antibiotic resistance has been treated with greater responsibility, and the proof is the project "Map of Russia's Antimicrobial Resistance." Research in this field, the collection of information and its systematization for filling the map of antibiotic resistance were carried out by such large organizations as the Scientific Research Institute of Antimicrobial Chemotherapy, the Interregional Association of Microbiology and Antimicrobial Chemotherapy, and the Scientific and Methodological Center for Monitoring Antimicrobial Resistance, created at the initiative of the Federal Agency for Public Health and social development.

Information provided within the framework of the project is constantly updated and is available to all users who need information on antibiotic resistance and effective treatment of infectious diseases.

Understanding how relevant the issue of reducing the sensitivity of pathogenic microorganisms and finding a solution to this problem today is coming gradually. But this is already the first step in the way of an effective fight against a problem called "antibiotic resistance". And this step is extremely important.