The fight against antibiotic resistance

The fight against resistance to antibiotics: a multifaceted challenge to humanity

I. Fundamental foundations: understanding of resistance to antibiotics

1. Antibiotics: miracle electricalities and their origin.

   • Historical context: discovery of penicillin Fleming and its influence on medical science.
   • Classification of antibiotics according to the mechanism of action:
     • Inhibitors of the synthesis of the cell wall (penicillin, cephalosporins, vancomycin). Action: blocking the enzymes necessary for the construction of a bacterial cell wall, leading to the lysis of the bacteria.
     • Protein synthesis inhibitors (tetracycline, aminoglycosides, macrolides, lincosamides, chloramphenicol). Action: Binding with ribosomas of bacteria, disrupting the broadcast of MRNA and, therefore, the synthesis of protein.
     • Nucleic acid synthesis inhibitors (chinolons, rifampicin). Action: blocking the enzymes necessary for replication and transcription of DNA and RNA.
     • Metabolic inhibitors (sulfanilamides, trimetrome). Action: Intervention in the metabolic paths necessary for the survival of bacteria, for example, synthesis of folic acid.
     • Polymixins. Action: Destruction of the cell membrane of bacteria, leading to a leakage of cellular content and death.
   • The spectrum of action of antibiotics: narrow and wide spectrum. Determination and clinical value.
   • Principles of rational prescription of antibiotics: choice of drug based on sensitivity, dosage, duration of the course.

2. Mechanisms for the development of resistance to antibiotics.

   • Genetic mechanisms:
     • Mutations: Random changes in bacteria DNA, leading to a change in the structure of the target of the antibiotic or to an increase in the expression of genes encoding the outflow systems.
     • Acquisition of stability genes: Horizontal transfer of genes (GPG) is the main factor in the spread of stability.
       • Conjugation: Transmission of plasmide (small circular DNA molecules) through direct contact between bacteria. Plasmids often contain stability genes for several antibiotics.
       • Transduction: DNA transmission from one bacterium to another using bacteriophages (viruses infect bacteria).
       • Transformation: Absorption of DNA bacterium from the environment (for example, from the dead bacteria).
     • Transpozons (“jumping genes”): Mobile genetic elements that can be built into plasmids or chromosomes, ensuring the spread of stability genes.
   • Biochemical mechanisms:
     • Inactivation of antibiotics: The production of enzymes that destroy or modify the antibiotic, making it ineffective. Examples: beta-lactamasis (destroy penicillins and cephalosporins), aminoglycosidemidifying enzymes.
     • Changing target antibiotics: Mutations in genes encoding the target of antibiotics (for example, ribosomes, DNA gyraz), leading to a decrease in the antibiotic affinity to the target.
     • Antibiotic outflow (Efflux): Active pumping an antibiotic from a cell using specialized transport proteins.
     • Bypass targets antibiotics: The development of alternative metabolic pathways that allow bacteria to circumvent the blocking effect of the antibiotic.
   • Survival strategies:
     • Biofilers: The formation of bacteria communities enclosed in a protective matrix, which complicates the penetration of antibiotics and immune cells.
     • Persisters: Phenotypically stable bacteria that temporarily stop growth in the presence of antibiotics, but survive and resume growth after the cessation of antibiotic exposure. They do not have genetic stability, but contribute to chronic and recurrent infections.
     • Small colonies options (Small Colony Variants, SCVS): Bacteria with defects in the respiratory chain characterized by slow growth and increased resistance to antibiotics.

3. Epidemiology of resistance to antibiotics.

   • Global distribution: Antibiotic resistance is a global problem that affects all countries of the world.
   • The main factors contributing to the spread:
     • Incorrect use of antibiotics in people: The excessive and unreasonable use of antibiotics for the treatment of viral infections, self -medication, non -compliance with the antibiotic administration regime.
     • Using antibiotics in animal husbandry: The use of antibiotics as growth stimulants and for the prevention of diseases in agricultural animals.
     • Insufficient control of infections: Poor hygiene, lack of adequate precautions in medical institutions.
     • Globalization: International trips and trade contribute to the rapid spread of stable bacteria between countries.
     • Insufficient public awareness: Insufficient understanding of the problem of resistance to antibiotics among the population.
   • Geographical features: The prevalence of stable bacteria varies depending on the region, which is associated with the differences in the practice of using antibiotics, sanitary conditions and other factors.
   • The role of medical institutions: Hospitals and other medical institutions are tanks for stable bacteria, where there is an intensive exchange of genetic material between bacteria.
   • Influence on various groups of the population: Children, elderly people, faces with weakened immunity, and patients in hospitals are especially at risk of infected with stable bacteria.

II. Clinical consequences of antibiotic resistance

1. Increased incidence and mortality.

   • Sustainable infections are more difficult to treat, which leads to an increase in the duration of the disease, the frequency of hospitalization and the risk of complications.
   • The need for the use of more expensive and toxic antibiotics is increasing.
   • An increase in mortality from infections that previously easily lendered to treatment. Examples: pneumonia, sepsis, urinary tract infections.

2. Economic consequences.

   • Increased healthcare costs: a longer stay in the hospital, more expensive antibiotics, additional diagnostic tests.
   • Reducing labor productivity due to illness.
   • Risk to the global economy: slowdown in economic growth, increase in poverty.

3. Influence on medical procedures.

   • Increasing the risk of infections during surgical interventions, organs, chemotherapy and other medical procedures requiring immunosuppression.
   • Limiting the possibilities for treating patients with serious diseases.

4. Problems in veterinary medicine and agriculture.

   • An increase in the incidence and mortality of animals.
   • Reducing livestock productivity.
   • The risk of transmitting stable bacteria from animals to people.

5. Impact on pregnancy and childbirth.

   • Increased risk of infections in pregnant women and newborns.
   • Limiting the possibilities for treating infections during pregnancy.
   • The risk of transmitting stable bacteria from mother to child.

III. Modern methods of diagnosing resistance to antibiotics

1. Traditional methods.

   • Determination of the minimum overwhelming concentration (MPC): In vitro method that determines the minimum concentration of the antibiotic necessary to suppress the growth of bacteria.
   • Diffusion methods (disk method): Assessment of the sensitivity of bacteria to antibiotics based on the size of the growth zone around the growth around disks impregnated with antibiotics.
   • E-tests: The use of strips with a gradient of the concentration of the antibiotic to determine the MPC.
   • Advantages and disadvantages of traditional methods: Simplicity, accessibility, but relatively slow and do not always allow you to identify complex stability mechanisms.

2. Molecular methods.

   • Polymerase chain reaction (PCR): Detection of stability genes in bacteria DNA. High sensitivity and specificity allows you to quickly identify the presence of stability genes.
   • DNA sequencing: Determination of the sequence of bacteria DNA to identify mutations leading to stability, and to track the spread of stable strains.
   • Multilo -bustic sequencing of the sequence (MLST): Determination of genetic relationships between bacterial strains based on the analysis of sequences of several conservative genes.
   • Metagenomica: Analysis of genetic material directly from the environment (for example, from soil, water or intestinal microbioma) to detect stability genes.
   • Advantages and disadvantages of molecular methods: High speed, sensitivity and specificity, but more expensive and require specialized equipment and personnel.

3. Automated systems.

   • Automatic sensitivity analyzers to antibiotics: A quick and accurate assessment of the sensitivity of bacteria to antibiotics. Examples: Vitek, Microscan.
   • Advantages and disadvantages of automated systems: High capacity, reducing risk of errors, but require regular maintenance and quality control.

4. New technologies.

   • Mass spectrometry (Maldi-Tof MS): Fast identification of bacteria based on the analysis of their protein profile. It can be used to identify some stability mechanisms.
   • Microfluidika: Development of microchips for microbiological tests, including determining sensitivity to antibiotics.
   • CRISPR-CAS-based technologies: Using CRISPR-CAS systems to identify stability genes and to develop new antibiotics.
   • Advantages and disadvantages of new technologies: High speed, sensitivity and potential for automation, but are under development and require further validation.

IV. Strategies for the fight against resistance to antibiotics

1. Rational use of antibiotics.

   • In medicine:
     • The appointment of antibiotics only with bacterial infections justified by clinical indications and the results of microbiological studies.
     • Avoiding the prescription of antibiotics in viral infections (colds, flu).
     • The choice of an antibiotic with a narrow range of action, effective against a particular pathogen.
     • The use of manuals and protocols for rational purpose of antibiotics.
     • Education of doctors and other medical workers with the rules for prescribing antibiotics.
     • Implementation of antibiotics control programs in medical institutions (Antibiotic Stewardship Programs).
   • In animal husbandry:
     • Limiting the use of antibiotics as growth stimulants.
     • The use of antibiotics only for the treatment of bacterial infections in animals under the control of a veterinarian.
     • Improving the conditions of content and hygiene of animals to reduce incidence.
     • Vaccination of animals for the prevention of infectious diseases.
   • Population education:
     • Information of the population about the problem of resistance to antibiotics and the rules for the use of antibiotics.
     • Antibiotic self -medication.
     • An explanation that antibiotics are not effective against viral infections.
     • The call for compliance with the recommendations of the doctor to receive antibiotics (dosage, duration of the course).

2. Strengthening control of infections.

   • Hand hygiene: Thorough wash with soap or the use of hand antiseptics.
   • Isolation of patients with infections caused by stable bacteria: Prevention of the spread of stable bacteria in medical institutions.
   • Sterilization and disinfection of medical equipment and premises: The destruction of bacteria and other microorganisms on surfaces and equipment.
   • Screening for the presence of stable bacteria: Identification of patients who are carriers of stable bacteria to take measures to prevent the spread of infection.
   • Epidemiological supervision: Monitoring of the spread of stable bacteria and the identification of flashes of infections.

3. Development of new antibiotics and alternative treatment methods.

   • Search for new targets for antibiotics: The study of metabolic pathways and structures of bacteria to identify new targets, which can be influenced by antibiotics.
   • Development of antibiotics with a new action mechanism: The creation of antibiotics that act on bacteria in a new way, to which bacteria has not yet developed stability.
   • Using bacteriophages: The use of bacteriophages (viruses infect bacteria) to destroy stable bacteria.
   • Development of immunotherapy drugs: Stimulation of the immune system to combat bacterial infections.
   • Using antimicrobial peptides: Development of peptides with antimicrobial activity.
   • Using probiotics and prebiotics: Strengthening intestinal microbioma to prevent infections and reduce antibiotics need.

4. Improving sanitary conditions and hygiene.

   • Ensuring access to pure water and sanitation: Reducing the spread of infectious diseases.
   • Improving hygiene in schools and other public places: Prevention of the spread of infections among the population.
   • Food quality control: Prevention of the spread of bacteria through food.

5. International cooperation.

   • Exchange of information and experience: Cooperation between countries to exchange data on the spread of stable bacteria and experience in combating stability.
   • Joint scientific research: Conducting joint research on the development of new antibiotics and alternative treatment methods.
   • Harmonization of standards and rules: Coordination of standards and rules for the use of antibiotics and control of infections.
   • Support for developing countries: Assistance to developing countries in the fight against resistance to antibiotics.

V. The future of the fight against resistance to antibiotics

1. Development of new diagnostic and treatment technologies.

   • Fast diagnosis of resistance to antibiotics: The development of tests that allow you to quickly and accurately determine the sensitivity of bacteria to antibiotics.
   • Personalized therapy: The choice of an antibiotic based on the individual characteristics of the patient and the characteristics of the pathogen.
   • New antibiotics and alternative treatment methods: Development of new drugs and treatment methods that are effective against stable bacteria.

2. Strengthening epidemiological supervision.

   • Creating global monitoring networks: Monitoring the spread of stable bacteria in different countries of the world.
   • Using big data and artificial intelligence: Analysis of data on the distribution of stable bacteria to predict flashes of infections and develop effective strategies for the fight.

3. Changing people’s behavior.

   • Improving public awareness: Information of the population about the problem of resistance to antibiotics and the rules for the use of antibiotics.
   • Motivation of doctors and other medical workers for rational prescription antibiotics: The introduction of incentives for the rational use of antibiotics.
   • Improving hygiene and sanitation: Maintaining high standards of hygiene and sanitation in medical institutions and in society as a whole.

4. Development of new politicians and strategies.

   • Implementation of national plans to combat resistance to antibiotics: Development of complex strategies for the fight against stability at the national level.
   • Strengthening the regulation of the use of antibiotics in animal husbandry: Limiting the use of antibiotics as growth stimulants and for the prevention of diseases.
   • Investments in scientific research: Financing research on the development of new antibiotics and alternative treatment methods.
   • International cooperation: Strengthening cooperation between countries to combat resistance to antibiotics.

5. Integration of approaches “Unified Health”.

   • Recognition of the relationship of human health, animals and the environment: Accounting for the influence of environmental factors on the spread of stable bacteria.
   • Cooperation between specialists in the field of medicine, veterinary medicine and environmental protection: Development of comprehensive strategies for the fight against stability, taking into account all aspects of the problem.
   • Development of sustainable food production systems: Reducing the use of antibiotics in livestock and agriculture.
   • Environmental protection from pollution by antibiotics and stable bacteria: Prevention of the spread of stable bacteria through wastewater and other sources.

The fight against resistance to antibiotics requires coordinated efforts on the part of all interested parties: governments, medical workers, scientists, livestock breeders and the public. Only by joint efforts can we maintain the effectiveness of antibiotics for future generations.