Antibiotic resistance of microorganisms: methods of determination

Antibiotics are one of the greatest achievements of medical science, saving the lives of tens and hundreds of thousands of people every year. However, as the saying goes, even an old woman can make a mistake. What used to kill pathogenic microorganisms no longer works as well as it did before. So what is the reason: have antimicrobial drugs become worse or is antibiotic resistance to blame?

Determination of antibiotic resistance

Antimicrobial drugs (AMDs), which are commonly called antibiotics, were originally created to combat bacterial infections. And since various diseases can be caused not by one, but by several types of bacteria, combined into groups, drugs effective against a certain group of infectious agents were initially developed.

But bacteria, although the simplest, are actively developing organisms, acquiring more and more new properties over time. The instinct for self-preservation and the ability to adapt to various living conditions make pathogenic microorganisms stronger. In response to a threat to life, they begin to develop the ability to resist it, secreting a secret that weakens or completely neutralizes the effect of the active substance of antimicrobial drugs.

It turns out that antibiotics that were once effective simply stop performing their function. In this case, we speak of the development of antibiotic resistance to the drug. And the issue here is not at all in the effectiveness of the active substance of the AMP, but in the mechanisms of improvement of pathogenic microorganisms, due to which bacteria become insensitive 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. This is the reason why treatment with seemingly correctly selected drugs does not give the expected results.

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The problem of antibiotic resistance

The lack of effect from antibiotic therapy, associated with antibiotic resistance, leads to the disease continuing to progress and becoming more severe, the treatment of which becomes even more difficult. Particularly dangerous are cases when the bacterial infection affects vital organs: the heart, lungs, brain, kidneys, etc., because in this case, delay is like death.

The second danger is that some diseases can become chronic if antibiotic therapy is insufficient. A person becomes a carrier of advanced microorganisms that are resistant to antibiotics of a certain group. He is now a source of infection, which is pointless to fight with old methods.

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

If someone thinks that the problem of antibiotic resistance has arisen quite recently, they are very wrong. This problem is as old as the world. Well, maybe not that old, but still, it is already 70-75 years old. According to the generally accepted theory, it appeared together with the introduction of the first antibiotics into medical practice somewhere in the 40s of the twentieth century.

Although there is a concept of an earlier emergence of the problem of microorganism resistance. Before the advent of antibiotics, this problem was not particularly addressed. After all, it is so natural that bacteria, like other living beings, tried to adapt to unfavorable environmental conditions, and did it in their own way.

The problem of resistance of pathogenic bacteria reminded us of itself when the first antibiotics appeared. True, the issue was not so urgent then. At that time, various groups of antibacterial agents were actively being developed, which was to some extent due to the unfavorable political situation in the world, military actions, when soldiers died from wounds and sepsis only because they could not be given effective help due to the lack of necessary drugs. These drugs simply did not exist yet.

The greatest number of developments were carried out in the 50-60s of the 20th century, and during the next 2 decades their improvement was carried out. Progress did not end there, but since the 80s, developments in relation to antibacterial agents have become noticeably less. Whether this is due to the high cost of this enterprise (the development and release of a new drug nowadays reaches the border of 800 million dollars) or the banal lack of new ideas regarding "militantly minded" active substances for innovative drugs, but in connection with this, the problem of antibiotic resistance is reaching a new frightening level.

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

It remains unclear how microorganisms can develop resistance to drugs that are supposed to kill them? Here we must understand that the "killing" of bacteria occurs only when the drug is used as intended. But what do we really have?

Causes of antibiotic resistance

Here we come to the main question: who is to blame that bacteria, when exposed to antibacterial agents, do not die, but are actually reborn, acquiring new properties that are far from beneficial to humanity? What provokes such changes occurring in microorganisms that are the cause of many diseases that humanity has been fighting for decades?

It is clear that the true reason for the development of antibiotic resistance is the ability of living organisms to survive in various conditions, adapting to them in different ways. But bacteria have no way to dodge a deadly projectile in the form of an antibiotic, which in theory should bring them death. So how does it happen that they not only survive, but also improve in parallel with the improvement of pharmaceutical technologies?

It is important to understand that if there is a problem (in our case, the development of antibiotic resistance in pathogenic microorganisms), then there are also provoking factors that create conditions for it. This is exactly the issue we will try to sort out now.

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Factors in the development of antibiotic resistance

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

The doctor has a large selection of medications, but how can you determine the drug that will really help you cope with the infection? On the one hand, to justify the prescription of an antimicrobial drug, you must first find out the type of pathogen, according to the etiotropic concept of drug selection, which is considered the most correct. But on the other hand, this can take up to 3 or more days, while the most important condition for successful treatment is considered to be timely therapy in the early stages of the disease.

The doctor has no choice but to act practically at random in the first days after the diagnosis is made, in order to somehow slow down the disease and prevent it from spreading to other organs (empirical approach). When prescribing outpatient treatment, the practicing doctor assumes that the causative agent of a particular disease may be certain types of bacteria. This is the reason for the initial choice of the drug. The prescription may undergo changes depending on the results of the analysis for the causative agent.

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

It turns out that if the antibiotic is chosen incorrectly or the dosage and administration regimen of the drug are ineffective, pathogenic microorganisms may not die, but may change or acquire previously uncharacteristic capabilities. Reproducing, such bacteria form entire populations of strains resistant to antibiotics of a specific group, i.e. antibiotic-resistant bacteria.

Another factor that negatively affects the susceptibility of pathogenic microorganisms to the effects of 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 identification of the pathogen in most cases is not carried out or is carried out late, because antibiotics are mainly used to treat animals in a rather serious condition, when time is of the essence, and it is not possible to wait for test results. And in the village, the veterinarian does not always even have such an opportunity, so he acts "blindly".

But that would be nothing, except there is another big problem – the human mentality, when everyone is their own doctor. Moreover, the development of information technology and the ability to buy most antibiotics without a doctor's prescription only exacerbate this problem. And if we consider that we have more unqualified self-taught doctors than those who strictly follow the doctor's orders and recommendations, the problem is becoming global in scale.

In our country, the situation is aggravated by the fact that most people remain financially insolvent. They do not have the opportunity to purchase effective but expensive new generation drugs. In this case, they replace the doctor's prescription with cheaper old analogues or drugs recommended by their best friend or all-knowing friend.

"It helped me, and it will help you!" - can you argue with that if the words come from the lips of a neighbor who is wise with rich life experience and who went through the war? And few people think that thanks to well-read and trusting people like us, pathogenic microorganisms have long since adapted to survive under the influence of drugs recommended in the past. And what helped grandpa 50 years ago may turn out to be 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 a disease with suitable symptoms turns up. And why all these doctors, if there are such wonderful drugs that we learn about from newspapers, TV screens and Internet pages. Only the text about self-medication has become so boring to everyone that now few people pay attention to it. And very much in vain!

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Mechanisms of antibiotic resistance

Antibiotic resistance has recently become the number one problem in the pharmaceutical industry, which develops antimicrobial drugs. The fact is that it is characteristic of almost all known types of bacteria, which is why antibiotic therapy is becoming less and less effective. Such common pathogens as staphylococci, E. coli, Pseudomonas aeruginosa, and Proteus have resistant strains that are more common than their ancestors, which are susceptible to antibiotics.

Resistance to different groups of antibiotics, and even to individual drugs, develops differently. Good old penicillins and tetracyclines, as well as newer developments in the form of cephalosporins and aminoglycosides, are characterized by a slow development of antibiotic resistance, and their therapeutic effect decreases in parallel with this. The same cannot be said about such drugs, the active substance of which is streptomycin, erythromycin, rimfampicin and lincomycin. Resistance to these drugs develops rapidly, due to which the prescription has to be changed even during the course of treatment, without waiting for its completion. The same applies to oleandomycin and fusidin.

All this gives grounds to assume that the mechanisms of development of antibiotic resistance to different drugs differ significantly. Let's try to figure out what properties of bacteria (natural or acquired) do not allow antibiotics to produce their irradiation, as originally intended.

First, let's define that resistance in bacteria can be natural (protective functions given to it initially) and acquired, which we discussed above. Until now, we have mainly talked about true antibiotic resistance associated with the characteristics of the microorganism, and not with the incorrect choice or prescription of the drug (in this case, we are talking about false antibiotic resistance).

Every living creature, including protozoa, has its own unique structure and some properties that allow it to survive. All this is genetically determined and passed on from generation to generation. Natural resistance to specific active substances of antibiotics is also genetically determined. Moreover, in different types of bacteria, resistance is directed to a certain type of drug, which is why various groups of antibiotics that affect a particular type of bacteria are developed.

The factors that determine natural resistance may be different. For example, the structure of the protein shell of a microorganism may be such that an antibiotic is unable to cope with it. But antibiotics can only affect the protein molecule, destroying it and causing the death of the microorganism. The development of effective antibiotics involves taking into account the structure of the proteins of the bacteria against which the drug is aimed.

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

The entire surface of the microbe is covered with receptors, with certain types of which AMPs bind. A small number of suitable receptors or their complete absence lead to the fact that binding does not occur, and therefore the antibacterial effect is absent.

Among other receptors, there are those that serve as a kind of beacon for the antibiotic, 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 remove AMP from the cell. This ability is called efflux and it characterizes the resistance of Pseudomonas aeruginosa to carbapenems.

Biochemical mechanism of antibiotic resistance

In addition to the above-mentioned natural mechanisms for the development of antibiotic resistance, there is another one that is associated not with the structure of the bacterial cell, but with its functionality.

The fact is that the bacteria in the body can produce enzymes that can have a negative effect on the molecules of the active substance of the AMP and reduce its effectiveness. Bacteria also suffer when interacting with such an antibiotic, their effect is noticeably weakened, which creates the appearance of recovery from the infection. However, the patient remains a carrier of the 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 against this type of bacteria. The enzymes produced by different types of bacteria may differ. Staphylococci are characterized by the synthesis of beta-lactamase, which provokes a break in the lactem ring of penicillin antibiotics. The production of acetyltransferase can explain the resistance of gram-negative bacteria to chloramphenicol, etc.

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Acquired antibiotic resistance

Bacteria, like other organisms, are not immune to evolution. In response to "military" actions against them, microorganisms can change their structure or begin to synthesize such an amount of enzyme substance that is capable of not only reducing the effectiveness of the drug, but also destroying it completely. For example, active production of alanine transferase makes "Cycloserine" ineffective against bacteria that produce it in large quantities.

Antibiotic resistance can also develop as a result of modification of the cell structure of a protein that is also its receptor, with which the AMP should bind. That is, this type of protein may be absent from 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 the penicillin-binding protein causes insensitivity to penicillins and cephalosporins.

As a result of the development and activation of protective functions in bacteria previously exposed to the destructive action of a certain type of antibiotic, the permeability of the cell membrane changes. This can be achieved by reducing the channels through which the active substances of AMP can penetrate into the cell. It is this property that causes the insensitivity of streptococci to beta-lactam antibiotics.

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

Sometimes bacteria resort to a certain trick. By attaching themselves to a dense substance, they unite into communities called biofilms. Within the community, they are less sensitive to antibiotics and can easily tolerate doses that are lethal for a single bacterium living outside the “collective”.

Another option is the unification of microorganisms into groups on the surface of a semi-liquid medium. Even after cell division, part of the bacterial "family" remains inside the "group", which is not affected by antibiotics.

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Antibiotic resistance genes

There are concepts of genetic and non-genetic drug resistance. We deal with the latter when we consider bacteria with an inactive metabolism, not prone to reproduction under normal conditions. Such bacteria can develop antibiotic resistance to certain types of drugs, however, this ability is not passed on to their offspring, since it is not genetically determined.

This is typical of pathogenic microorganisms that cause tuberculosis. A person can become infected and not suspect the disease for many years until his immunity fails for some reason. This is the impetus for the reproduction of mycobacteria and the progression of the disease. But the same drugs are used to treat tuberculosis, because the bacterial offspring still remains sensitive to them.

The same is true for the loss of protein in the cell wall of microorganisms. Let us recall, again, about bacteria sensitive to penicillin. Penicillins inhibit the synthesis of protein used to build the cell membrane. Under the influence of penicillin-type AMPs, microorganisms can lose the cell wall, the building material of which is penicillin-binding protein. Such bacteria become resistant to penicillins and cephalosporins, which now have nothing to bind to. This is a temporary phenomenon, not associated with gene mutation and the transmission of the modified gene by inheritance. With the appearance of the cell wall characteristic of previous populations, antibiotic resistance in such bacteria disappears.

Genetic antibiotic resistance is said to occur when changes in cells and metabolism within them occur at the gene level. Gene mutations 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 bacterial cell receptors.

There are 2 ways of development of events: chromosomal and extrachromosomal. If a gene mutation occurs in the chromosome section responsible for sensitivity to antibiotics, it is called chromosomal antibiotic resistance. Such a mutation itself occurs extremely rarely, usually it is caused by the action of drugs, but again not always. It is very difficult to control this process.

Chromosomal mutations can be passed on from generation to generation, gradually forming certain strains (varieties) of bacteria that are resistant to a particular antibiotic.

Extrachromosomal antibiotic resistance is caused by genetic elements that exist outside the chromosomes and are called plasmids. These elements contain genes responsible for enzyme production and bacterial wall permeability.

Antibiotic resistance is most often the result of horizontal gene transfer, when one bacterium passes on some genes to others that are not its descendants. But sometimes, unrelated point mutations can be observed in the pathogen genome (size 1 in 108 per process of copying the DNA of the mother cell, which is observed during chromosome replication).

Thus, in the fall of 2015, scientists from China described the MCR-1 gene, found in pork and pig intestines. The peculiarity of this gene is the possibility of its transmission to other organisms. After some time, the same gene was found not only in China, but also in other countries (USA, England, Malaysia, European countries).

Antibiotic resistance genes can stimulate the production of enzymes that have not previously been produced in the body of bacteria. For example, the NDM-1 enzyme (metallo-beta-lactamase 1), discovered in Klebsiella pneumoniae bacteria in 2008. It was first discovered in bacteria from India. But in subsequent years, the enzyme that provides antibiotic resistance to most AMPs was also found in microorganisms in other countries (Great Britain, Pakistan, USA, Japan, Canada).

Pathogenic microorganisms can show resistance both to certain drugs or groups of antibiotics, and 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 hospital conditions, about 45 different strains of staphylococcus can be found on the surfaces of various objects. This means that the fight against this infection is almost the primary task of health workers.

The difficulty of this task is that most strains of the most pathogenic staphylococci 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 undergo multiple genetic mutations depending on their habitat makes them virtually invulnerable. Mutations are passed on to their descendants, and entire generations of antimicrobial-resistant infectious agents from the genus staphylococci appear in short periods of time.

The biggest problem is methicillin-resistant strains, which 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 only be destroyed with the help of glycopeptides. Currently, the problem of antibiotic resistance of such strains of staphylococcus is solved by a new type of AMP - oxazolidinones, a prominent representative of which is linezolid.

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Methods for determining antibiotic resistance

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

Antibiotic resistance testing can be performed using a variety of methods, the most popular of which are:

• The disk method, or diffusion of AMP into agar according to Kirby-Bayer
• Serial dilution method
• Genetic identification of mutations causing drug resistance.

The first method is currently considered the most common due to its low cost and ease of implementation. The essence of the disk method is that the bacterial strains isolated as a result of research are placed in a nutrient medium of sufficient density and covered with paper disks soaked in an AMP solution. The concentration of the antibiotic on the disks is different, so when the drug diffuses into the bacterial environment, a concentration gradient can be observed. The size of the zone of no microorganism growth can be used to judge the activity of the drug and calculate the effective dosage.

A variant of the disk method is the E-test. In this case, instead of disks, polymer plates are used, onto which a certain concentration of antibiotic is applied.

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

The serial dilution method is based on the creation of several variants of a liquid or solid medium containing different concentrations of the drug being studied. Each variant 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 assessed. This method allows one 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 required to inactivate bacteria.

The serial dilution method is rightfully considered the gold standard for determining antibiotic resistance. However, due to its high cost and labor intensity, it is not always applicable in domestic pharmacology.

The mutation identification method provides information about the presence of modified genes in a particular bacterial strain that contribute to the development of antibiotic resistance to specific drugs, and in this regard, to systematize emerging situations taking into account the similarity of phenotypic manifestations.

This method is characterized 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 studying antibiotic resistance are, they cannot fully reflect the picture that will unfold in a living organism. And if we also take into account the fact that each person's body is individual, and the processes of distribution and metabolism of drugs can occur differently in it, the experimental picture can be very far from the real one.

Ways to overcome antibiotic resistance

No matter how good a drug is, given our current attitude to treatment, we cannot rule out the fact that at some point the sensitivity of pathogenic microorganisms to it may change. The creation of new drugs with the same active ingredients also does not solve the problem of antibiotic resistance. And the sensitivity of microorganisms to new generations of drugs gradually weakens with frequent unjustified or incorrect prescriptions.

A breakthrough in this regard is the invention of combined drugs, which are called protected. Their use is justified in relation to bacteria that produce enzymes that are destructive to conventional antibiotics. Protection of popular antibiotics is achieved by including special agents in the composition of the new drug (for example, inhibitors of enzymes that are 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 cell via a membrane pump.

Clavulanic acid or sulbactam are commonly used as beta-lactamase inhibitors. They are added to beta-lactam antibiotics, thereby increasing the effectiveness of the latter.

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

The fight against other bacterial “groups” is carried out by transferring them into a liquid environment, where the microorganisms begin to exist separately, and now they can be fought with conventional drugs.

When faced with the phenomenon of resistance during treatment with the drug, doctors solve the problem by prescribing various drugs that are effective against the isolated bacteria, but with different mechanisms of action on pathogenic microflora. For example, they simultaneously use drugs with bactericidal and bacteriostatic action or replace one drug with another from a different group.

Prevention of antibiotic resistance

The main goal of antibiotic therapy is considered to be the complete destruction of the population of pathogenic bacteria in the body. This task can only be solved by prescribing effective antimicrobial drugs.

The effectiveness of the drug is determined by its spectrum of activity (whether the identified pathogen is included in this spectrum), the ability to overcome antibiotic resistance mechanisms, and the optimally selected dosage regimen that kills pathogenic microflora. In addition, when prescribing a drug, the likelihood of side effects and the availability of treatment for each individual patient must be taken into account.

It is not possible to take all these aspects into account in an empirical approach to the treatment of bacterial infections. High professionalism of the doctor and constant monitoring of information about infections and effective drugs to combat them are required so that the prescription is not unjustified and does not lead to the development of antibiotic resistance.

The creation of medical centers equipped with high-tech equipment makes it possible to practice etiotropic treatment, when the pathogen is first identified in a shorter period of time, and then an effective drug is prescribed.

Prevention of antibiotic resistance can also be considered control over the prescription of drugs. For example, in case of ARVI, the prescription of antibiotics is not justified in any way, but it contributes to the development of antibiotic resistance of microorganisms that are in a "dormant" state for the time being. The fact is that antibiotics can provoke a weakening of the immune system, which in turn will cause the proliferation of a bacterial infection hidden inside the body or entering it from outside.

It is very important that the prescribed drugs correspond to the goal that needs to be achieved. Even a drug prescribed for preventive purposes must have all the properties necessary to destroy pathogenic microflora. Choosing a drug at random may not only fail to give the expected effect, but also worsen the situation by developing resistance to the drug of a certain type of bacteria.

Particular attention should be paid to the dosage. Small doses that are ineffective in fighting infection again lead to the development of antibiotic resistance in pathogenic microorganisms. But you should not overdo it either, because antibiotic therapy is highly likely to cause toxic effects and anaphylactic reactions that are dangerous to the patient's life. Especially if the treatment is carried out on an outpatient basis without supervision by medical personnel.

The media should convey to people the dangers of self-medication with antibiotics, as well as unfinished treatment, when bacteria do not die, but only become less active with a developed mechanism of antibiotic resistance. Cheap unlicensed drugs, which illegal pharmaceutical companies position as budget analogues of existing drugs, have the same effect.

A highly effective measure for preventing antibiotic resistance is considered to be constant monitoring of existing infectious agents and the development of antibiotic resistance in them not only at the district or regional level, but also on a national (and even global) scale. Alas, we can only dream about this.

In Ukraine, there is no infection control system as such. Only individual provisions have been adopted, one of which (back in 2007!), concerning obstetric hospitals, provides for the introduction of various methods of monitoring hospital-acquired infections. But everything again comes down to finances, and such studies are generally not carried out locally, not to mention doctors from other branches of medicine.

In the Russian Federation, the problem of antibiotic resistance was treated with greater responsibility, and the project "Map of Antimicrobial Resistance of Russia" is proof of this. Such large organizations as the Research Institute of Antimicrobial Chemotherapy, the Interregional Association of Microbiology and Antimicrobial Chemotherapy, as well as the Scientific and Methodological Center for Monitoring Antimicrobial Resistance, created on the initiative of the Federal Agency for Health and Social Development, were engaged in research in this area, collecting information and systematizing it to fill the antibiotic resistance map.

The information provided within the project is constantly updated and is available to all users who need information on issues of 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 is today comes gradually. But this is already the first step towards effectively combating the problem called "antibiotic resistance". And this step is extremely important.