Antibiotic resistance is the resistance of an organism to compounds from the class of antibiotics. Currently, antibiotics are the only category of drugs whose effectiveness is gradually decreasing. It is simply impossible to exclude the fact of antibiotic resistance - this is due to the progress of life, the evolution at different stages and forms of organisms from the simplest to the most complex macro-systems.
Relevance of the issue
The antibiotic resistance of microorganisms is produced quite naturally. Initially, the level is low, gradually reaches average values, and then develops to high stability. Microscopic organisms that show an increased level of resistance to one antimicrobial drug are highly likely to be protected from other compounds. The process of acquiring stability cannot be reversed, but sensitivity can be slowly restored - though only partially.
Currently, antibiotic resistance is a global problem associated with inadequate infection control. Antimicrobial compounds are widely used in agriculture, food industry. Substances like antimicrobial drugs are widely used in everyday life. All this affects the acquisition by pathological forms of life of an increased level of resistance to those substances that were previously mortally dangerous to them.
About the nuances of the phenomenon
Antibiotic resistance of bacteria may be natural; antibiotic resistance may be acquired.
The formation and spread of the phenomenon is largely due to the free sale of antimicrobial drugs in pharmacies. According to the rules, such should be released strictly according to the doctor’s prescription, but many points sell a number of funds in free mode. Most often this applies to cases where the client is interested in acquiring gentamicin, ciprofloxacin.
One of the problems of modern medicine is the irrational use of antimicrobials, which is also one of the mechanisms that provoke the growth of antibiotic resistance. Often, the appointment of funds is unjustified and even chaotic. Normally, antibiotics are necessary before surgery, but they are often used after surgery. The purpose of the patient unreasonably low dosages, lack of infection control, improper organization of the treatment process - all this provokes an increase in antibiotic resistance of pathological microorganisms.
About problems and realities
Although scientists are working non-stop to create new drugs that are more effective and efficient, the use of antimicrobials in recent years has been faced with two serious difficulties. This antibiotic resistance, already mentioned above, as well as the expansion of the variety of dosage forms of pathogens. Antimicrobial resistance is currently relevant for all types of microscopic life forms. It is this reason - the main one, because of which drug therapy is becoming less effective. In modern medicine, special difficulties are caused by the wide distribution of Pseudomonas aeruginosa and Escherichia coli, Proteus and staphylococci resistant to antimicrobials.
As the studies show, at present the problem of antibiotic resistance is becoming more urgent: from half to 90% of all isolated strains are resistant to different compositions.
About the nuances of the problem
It was found that the level of resistance to antimicrobial compounds is formed unevenly. Quite slowly, this process proceeds relative to the preparations of the penicillin series, cycloserine, polymyxin, chloramphenicol. Against the background of a slow decline in effectiveness, the therapeutic effect of the course is weakened.
Regarding cephalosporins, tetracycline series, aminoglycosides, as scientists have found, in microscopic life forms, antibiotic resistance also forms relatively slowly. The therapeutic efficacy decreases at a similar rate.
The problem of antibiotic resistance is most relevant when infected with strains, from which rifampicin, linko- and oleandomycin, fusidine should help. Resistance to these compounds can form during the first course of treatment.
How does this happen?
The mechanisms of antibiotic resistance have long attracted the attention of scientists. If it were possible to take control of these processes, the problem of resistance of pathological microorganisms would be solved. Currently, it is revealed that quite often the phenomenon is observed due to the modification of the antimicrobial composition. The form is converted to inactive. For example, this is possible if the microorganism generates some enzyme that reacts chemically with the drug compound.
A classic example: staphylococcus is able to produce beta-lactamase. This substance affects the beta-lactam penicillin ring, opening it and making the drug safe for the pathogen.
Many gram-negative life forms show increased resistance to aminoglycosides. This is due to their ability to generate phosphorylating, acetylating compounds that destroy the antimicrobial molecule. Gram-negative pathogens can also produce acetyltransferase, which deactivates chloramphenicol.
About the mechanisms: continuing the topic
Studying the mechanisms of antibiotic resistance of microorganisms, scientists have established that such reactions are possible during which the target is transformed, the effect of the antibiotic on which should show the desired result. Protein structures are inactivated, a stable complex is formed. It was revealed that at the level of chromosomes, resistance to aminoglycosides is explained by the transformation or removal of the protein structure on the 30S subunit of the bacterial chromosome, which normally is a sensitivity receptor. Resistance to the penicillin series, cephalosporins is explained by the transformation of the penicillin-binding protein structure.
Revealing the mechanisms of formation of antibiotic resistance, we also found that in a large percentage of cases the microbe cell becomes less permeable to the active drug. For example, streptococci naturally have a barrier through which aminoglycosides cannot pass. Tetracycline drugs accumulate only in bacteria sensitive to them. With the resistance of the life form, the compounds, in principle, cannot penetrate the pathogen.
Resilience development: process nuances
When determining antibiotic resistance, it is necessary to analyze specific microorganisms not only for the possibility of producing enzymes that inhibit the activity of the drug. Some bacteria can form antibiotic-destroying compounds. In particular, there are life forms whose resistance to cycloserine is explained by the release of alanine transferase.
Another subtle point is the antibiotic resistance genes. It is known that microscopic life forms are capable of forming new metabolic mechanisms, creating the so-called metabolic shunt. This helps them avoid reactions that are affected by the drug.
In some cases, antibiotic resistance is a phenomenon associated with efflux. The term is used to denote the process of active removal of an aggressive component from a microbe cell. The most prominent representative of pathogens capable of this is Pseudomonas aeruginosa. Analysis and studies have shown that the resistant forms of this bacterium are able to actively remove carbapenems from the microbial cell.
About the reasons and mechanisms
Currently, the problem of antibiotic resistance in Russia and in the world is becoming increasingly widespread. It is customary to single out the genetic and non-such resistance of pathological life forms. The activity of bacterial replication largely determines the effectiveness of medications. Inactive in terms of metabolic processes, non-breeding bacteria are resistant to the influence of drug compounds, but the offspring will still be sensitive.
It has been established that mycobacterium, which provokes tuberculosis, for a long time (years) exists in the organic tissues of an infected person. All this period it is useless to fight it with chemotherapy - the pathogen is resistant to any drugs. But at the moment when the immunity of the carrier is weakened, and mycobacteria begins to multiply actively, its offspring receive sensitivity to drugs.
In some cases, the loss of antibiotic resistance is due to the loss of a specific target. Some microscopic life forms sensitive to the penicillin series can transform into protoplasts when an antibiotic enters the microorganism, as a result of which the cell wall is lost. In the future, microbes may again become sensitive to those drugs that inhibit the synthesis of the cell wall: upon returning to the parent form, the synthesis processes should resume, which leads to overcoming antibiotic resistance.
About genetics
Genetic antibiotic resistance is a phenomenon formed as a result of genetic transformations taking place in a microscopic organism. In some cases, resistance is explained by the specificity of metabolism. This form of resistance is divided into two groups: chromosomal and not being such.
Chromosomal Resistance
This phenomenon can form as a result of a random mutation in the chromosome of the bacterium responsible for the susceptibility of drugs. Antibiotics affect some specific mechanisms, while resistance is gradually formed. Mutants have absolute protection; under the influence of an external factor, receptor structures are not rearranged.
As a rule, a narrow chromosomal region has genes in which antimicrobial receptors are encoded. For streptomycin, for example, this is the P12 protein structure on the 30S subunit. With gene mutations, in which the characteristics of the reactions with P12 change, resistance to streptomycin appears. Gene mutations can cause an exception to the structure of the microorganism of the receptor. It was revealed that some microorganisms became resistant to penicillin preparations because they no longer contain receptors capable of perceiving penicillin in their structure.
Extra- and extrachromosomal resistance
The development of such features is explained by genetic elements outside the chromosome. It can be round DNA molecules, plasmids, which account for up to 3% of the total weight of the chromosome. They have unique genes, genes of other plasmids. Free plasmids are located in the bacterial cytoplasm or integrate into the chromosome. At their expense, the pest usually gains resistance to the penicillin series, cephalosporins, since the ability to form beta-lactamase is inherent in the genes. They also explain the enzyme compounds that provide acetylation, phosphorylation of aminoglycosides. According to this logic, it is possible to develop resistance to the tetracycline series due to the impermeability of the microbial cell to the substance.
To transmit genetic information, plasmids resort to processes of change, transduction, conjugation, transposition.
Cross resistance is possible. This is said when the microscopic life form gains resistance to various means, the mechanisms of influence of which on microbes are similar to each other. This is more typical for preparations having a similar chemical structure. In some cases, a cross phenomenon is also characteristic of substances whose chemical structures differ quite strongly. A typical example: erythromycin and lincomycin.
What to do?
As the problem of antibiotic resistance becomes more and more urgent, the scientific community is making efforts to formulate new principles and treatment methods that allow overcoming complexity. As a rule, they use the possibilities of combination therapy, but it has certain disadvantages, and in the first place - an increased frequency of side effects. In some cases, a positive effect is observed with the use of fundamentally new drugs that show good results with the resistance of the strains to previously used drugs.
In order for the resistance of microorganisms to be overcome, and the effectiveness of the therapeutic course to be increased, it is reasonable to resort to proven combinations of drugs. If infection with life forms producing beta-lactamase is detected, such preparations should be used, which contain components that inhibit the activity of the enzyme. For example, a similar feature was revealed in clavulan, tazobactam. These substances have a rather weak antibacterial effect, but the inhibition process is irreversible, which protects the main antibiotic from the enzyme. Most often, clavulanic acid is prescribed in combination with amoxicillin or ticarcillin. In pharmacies, such drugs are presented under the trade names "Augmentin" and "Timentip". Another reliable drug, Unazin, is based on ampicillin, which was protected through sulbactam.
Price of treatment
Often, when choosing a therapy, they decide on the simultaneous administration of several types of drugs that have different mechanisms of influence on pathological life forms. It is customary to say that the most effective antibiotic is one that, in a minimal amount, provides a sufficient effect without provoking negative phenomena in the macroorganism. At present, there is simply no ideally matching means in nature; in addition to the desired result, a negative effect is always observed.
In some cases, the side effects are quite strong, and this completely excludes the use of the antimicrobial drug in accordance with its intended use. As can be seen from the statistics, up to 40% of all cases of antibiotic use lead to complications, of which the predominant part (8 cases out of 10) are allergic reactions, another 7% are poisoning. The classification of side effects on allergic, and also explained by the effect of the drug on the macroorganism and the effect on the immune system, positive microflora is accepted.
What will help?
Since resistance to various forms of drugs in microorganisms is becoming increasingly widespread, before prescribing a therapeutic course, it is necessary to resort to modern methods for determining antibiotic resistance, so that the selected program shows the desired effect and relieves the patient of the pathogen. To verify the alleged effectiveness, it is necessary to isolate the culture of the pathological form of life and study it for the susceptibility of a particular drug. Take into account that in laboratory conditions and in practical application, the results can be different. There are several explanations for this phenomenon, including the acidity of the body environment, cultivation conditions, and the size of the colonies.
The main method for determining antibiotic resistance is laboratory tests. Recently, rapid tests have appeared for certain forms of pathogens.