Beta-lactam antibiotic: mechanism of action and classification. B-lactam antibiotics B-lactam antibiotics include

Beta-lactam antibiotics are antimicrobial drugs that act against many gram-negative and gram-positive, anaerobic and aerobic microbes.

Classification:

• penicillins;
• cephalosporins;
• non-traditional β-lactam antibiotics.

The therapeutic effect of these drugs is provided by the β-lactam ring, under the influence of which either the transpeptidase enzyme involved in the synthesis of the cell membrane is inactivated, or the action of penicillin-binding protein enzymes is stopped. In any case, the growing bacteria is destroyed. β-lactams do not affect microbes that are at rest.

The activity of exposure is influenced by the ability of β-lactams to penetrate the outer membrane of bacteria: if gram-positive microbes easily pass them through, the lipopolysaccharide layer of some gram-negative microorganisms protects against the penetration of the drug, therefore not all gram-negative bacteria are susceptible to the effects of β-lactam antibiotics.

Another barrier is the presence of the lactamase enzyme in microbes, which hydrolyzes the antibiotic, inactivating it. To prevent this from happening, the drug contains a β-lactamase inhibitor: clavulanic acid, sulbactam or tazobactam. Such antibiotics are called combination or protected β-lactams.

Characteristics of natural penicillins:

1. They have a narrow spectrum of antimicrobial effects.
2. Susceptible to beta-lactamases.
3. They disintegrate under the influence of hydrochloric acid of the stomach (administered only intramuscularly).
4. They are quickly destroyed and excreted from the body, which is why injections of the drug are necessary every 4 hours. To prolong the effect of natural penicillins, their sparingly soluble salts, for example, bicillin, were created.
5. Inactive against rickettsia, fungi, amoebas, viruses, tuberculosis pathogens.

Used to treat:

• upper respiratory tract infections;
• wound infections;
• sepsis;
• skin and soft tissue infections;
• osteomyelitis;
• genitourinary infections, including syphilis and gonorrhea.

Semi-synthetic penicillins: brief characteristics

Penicillinase-stable β-lactams act against penicillin-resistant microbes.

Aminopenicillins have a broader antimicrobial effect than natural penicillins. They are not destroyed in the stomach, so they can be used in tablet form. Aminopenicillins, as well as the combined antibiotic ampiox (ampicillin with oxacillin) are widely used for microbial infections of the upper respiratory tract.

Carboxypenicillins and ureidopenicillins (anti-pseudomonas penicillins), due to their exposure to β-lactamases and rapidly developing bacterial resistance to them, are rarely used, mainly to combat Pseudomonas aeruginosa.

Group of cephalosporins

Modern medicine uses 5 generations of β-lactam cephalosporin antibiotics:

Brief description of the group

I generation cephalosporins have the least breadth of antimicrobial activity among other cephalosporins and act on gram-positive bacteria.

Used to treat infections caused by streptococci and staphylococci. Cefazolin is also used as a prophylactic agent before surgery.

Second generation drugs are also active against gram-negative bacteria and anaerobic microorganisms.

These antimicrobial agents treat intra-abdominal infections, gynecological diseases, both aerobic and anaerobic soft tissue infections, purulent complications of diabetes mellitus.

Ineffective for nosocomial (nosocomial) infections.

The most widely used are third generation cephalosporins. They effectively fight gram-negative bacteria and are indicated for community-acquired infections caused by Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae. Nosocomial diseases are effectively treated with Ceftriaxone and Cefotaxime. To enhance the effectiveness of treatment, third generation cephalosporins are prescribed together with aminoglycoside antibiotics.

The main targets of IV cephalosporins are enterobacteriaceae and Pseudomonas aeruginosa. They are used for severe infectious diseases of internal organs and the musculoskeletal system.

The list of fifth generation antibiotics is limited to Ceftobiprol medocaril, the main advantage of which is the ability to fight methicillin-resistant Staphylococcus aureus.

Beta-lactam antibiotics (BLAs) form the basis of modern therapy for infectious diseases. They are characterized by high clinical activity, relatively low toxicity, and a wide spectrum of action.

The basis of the structure of all representatives of this group is the beta-lactam ring. It also determines antimicrobial properties, which consist in blocking the synthesis of the bacterial cell membrane.

The similarity of the chemical structure of beta-lactams also determines the possibility of cross-allergy to drugs from this group.

Antimicrobial action and manifestation of resistance

How do beta lactam antibiotics inactivate bacteria? What is their mechanism of action? The microbial cell contains the enzymes transpeptidase and carboxypeptidase, with the help of which it connects the chains of peptidoglycan, the main substance of the membrane. These enzymes have another name - penicillin-binding proteins (PBPs) because of their ability to easily form complexes with penicillin and other beta-lactam drugs.

The BLA + PSB complex blocks the integrity of the peptidoglycan structure, the membrane is destroyed, and the bacterium inevitably dies.

The activity of BLA against microbes depends on affinity properties, that is, affinity for PBP. The higher this affinity and the rate of complex formation, the lower the concentration of antibiotic required to suppress the infection and vice versa.

The advent of penicillin in the 40s revolutionized the treatment of infectious diseases and inflammation caused by various microorganisms, and saved many lives, including in wartime situations. For some time it was believed that a panacea had been found.

However, over the next ten years, the effectiveness of penicillin against entire groups of microbes decreased by half.

Nowadays, resistance against this antibiotic has increased to 60-70%. These figures may vary significantly in different regions.

Strains of streptococci, staphylococci and other microbes that cause severe forms of nosocomial infections have become the scourge of inpatient departments. Even in the same city, they can be different and respond differently to antibiotic therapy.

What is the cause of resistance to beta-lactam antibiotics? It turned out that in response to their use, microbes were able to produce beta-lactamase enzymes that hydrolyze BLA.

The creation of semi-synthetic penicillins and cephalosporins made it possible to solve this problem for some time, since they are not subject to enzymatic hydrolysis. The solution is found in the creation of protected drugs. The introduction of beta-lactamase inhibitors allows these enzymes to be inactivated, and the antibiotic freely binds to the PBP of the microbial cell.

But the emergence of new mutations in microbial strains leads to the emergence of new types of beta-lactamases that destroy the active site of antibiotics. The main source of microbial resistance is the incorrect use of antibiotics, namely:

Under these conditions, pathogens develop resistance, and subsequent infection will make them immune to the action of antibiotics.

It can be stated that in some cases the efforts of the creators of new antibiotics are aimed at getting ahead, but more often they have to look for ways to overcome changes in the resistance of microorganisms that have already occurred.

The simplicity of bacteria makes their ability to evolve almost limitless. New antibiotics become barriers to the survival of bacteria for some time. But those that do not die develop other methods of defense.

UAV classification

Beta-lactam antibiotics include both natural and synthetic drugs. In addition, combined forms have been created in which the active substance is additionally protected from enzymes produced by microorganisms that block the action of the antibiotic.

The list begins with penicillin, discovered in the 40s of the last century, which also belongs to beta-lactams:

Features of use and contraindications

The scope of application of UAVs in the treatment of infections is still high. Several types of antibiotics may be clinically active against the same type of pathogenic microorganisms.

To choose the optimal treatment method, the following approach is used:

The difficulty in choosing a suitable drug lies not only in the selectivity of the effect on a particular pathogen, but also in taking into account possible resistance, as well as side effects.

This leads to the most important rule: antibiotic treatment is prescribed only by a doctor, the patient must fully comply with the prescribed dosage, intervals between doses and course duration.

Beta-lactam antibiotics are intended primarily for parenteral administration. This way it is possible to achieve a maximum concentration sufficient to suppress the pathogen. The mechanism of elimination of BLA is through the kidneys.

If a patient has had an allergic reaction to one of the beta-lactam antibiotics, it should be expected in response to others. Allergic manifestations can be minor, in the form of a rash, itching, or serious, up to Quincke's edema, and may require anti-shock measures.

Other side effects are suppression of normal intestinal microflora, the occurrence of dyspeptic disorders in the form of nausea, vomiting, and loose stools. If a reaction occurs from the nervous system, hand tremors, dizziness, and convulsions are possible. All this confirms the need for medical supervision over the prescription and use of drugs in this group.

Beta-lactam antibiotics originate from the most prim of countries - England, where a pharmacist who served at the court of kings used mold as a treatment for various inflammatory processes on the skin. It’s hard to imagine, but previously a person could die from the simplest scratch or cut, since there was no panacea for the simplest substances. The discoverer of penicillin as an antibiotic was the Scottish doctor A. Fleming, who worked as a bacteriologist in a London hospital. The mechanism of action of penicillin was so powerful that it could kill a dangerous bacterium - staphylococcus, which previously caused the death of many people.

For a long time, penicillin was used for diagnostic purposes until it began to be used as an antibacterial drug.

Beta-lactam antibiotics have a bactericidal effect, destroying pathogenic organisms at the cellular level. Among these are the penicillin group, cephalosporins, carbapenem and monobactam. All drugs related to beta-lactams have a similar chemical structure, the same destructive effect on bacteria and individual intolerance to the components in some people.

Antibiotics of the beta-lactam group have gained wide popularity due to their minimal negative impact on the body's microflora, while having a broad effect on a number of pathogens that become a common cause of bacterial infection.

Penicillin as an antibiotic is the first in the series of beta-lactams. Over time, the range of penicillin drugs has expanded significantly, and now there are more than 10 similar drugs. Penicillin is produced in nature by different types of mold - penicillium. All penicillin drugs are absolutely ineffective as a treatment for viral infections, Koch's bacillus, fungal infections and many gram-negative microbes.

Classification of this group:

1. Natural penicillin. It includes benzylpenicillins (Procaine and Benzathine), Phenoxymethylpenicillin, Benzathine phenoxymethylpenicillin.
2. Semi-synthetic penicillin. Oxacillin (an antistaphylococcal drug), Ampicillin and Amoxicillin (a group of broad-spectrum antibiotics), antipseudomonal drugs (Carbenicillin, Azlocillin, etc.), inhibitor-protected (Amoxicillin clavulanate, Ampicillin sulbactam, etc.).

All drugs in this group share similar properties. Thus, all lactams have low toxicity, a high bactericidal effect, and a wide range of dosages, so they can be used to treat various diseases in young children and the elderly. Antibiotics are eliminated primarily through the urinary system, in particular through the kidneys.

Benzylpenicillin begins a number of natural antibiotics, which are still used as a treatment for many diseases. It has a number of advantages - it is suitable for the treatment of meningococcal and streptococcal infections, has low toxicity and is accessible due to its low cost. Disadvantages include acquired immunity or resistance to staphylococci, pneumococci, bacteroides and gonococci.

It appears after long-term use of antibacterial drugs or as a result of not completing a course of therapy, as a result of which the body develops immunity to penicillin and in the future the substance will no longer be able to negatively affect the bacterium.

The ranks of organisms affected by penicillin are replenished by: listeria, treponema pallidum, borrelia, diphtheria pathogens, clostridia, etc.

Penicillin must be administered only intramuscularly, since when it enters the gastrointestinal tract it is simply destroyed. When absorbed into the blood, its effect begins after 40 minutes.

Thanks to lactams, you can get rid of many infections by observing the correct dosage. Otherwise, side effects may occur in the form of allergic reactions (rash, fever, anaphylactic shock, etc.). To reduce the likelihood of undesirable effects, a test is carried out to identify sensitivity to the drug, the patient's history is carefully studied, and the patient is also monitored after administration of the drug. In some cases, seizures and electrolyte imbalance may occur.

Penicillin antibiotics should not be taken together with sulfonamides.

Indications for use of Benzylpenicillin:

• pneumococcal pneumonia;
• scarlet fever;
• meningitis in adults and children 3 years of age and older;
• borreliosis (an infectious disease caused by a tick bite);
• leptospirosis;
• syphilis;
• tetanus;
• bacterial angina, etc.

The drug Megacillin also belongs to the natural antibiotic beta-lactams. It is similar to penicillin, but can be taken into the gastrointestinal tract. May cause diarrhea, so it is necessary to take beneficial bacteria (lacto and bifidobacteria) along with it.

Suitable as a treatment for tonsillitis, pharyngitis. The drug is also taken for skin therapy.

Megacillin is used as a prophylaxis if there is a risk of pneumococcal infection and rheumatic fever.

Benzylpenicillin procaine is administered only intramuscularly, once a day, since the effect of the drug upon entering the body lasts for 24 hours. The medicine is used for mild pneumococcal pneumonia, tonsillitis, and pharyngitis.

In addition to the negative effect on bacteria, it has an analgesic effect on the body. You cannot use the drug if you have an individual intolerance to novocaine. Benzylpenicillin procaine is used as anthrax prophylaxis.

The cephalosporin series of beta-lactam antibiotics are produced from cephalosporin fungi. Due to their low toxicity, they are among the most commonly used agents among all antimicrobial drugs. Cephalosporins are similar to penicillins in their effect on bacteria and allergic reactions, which can be observed in some patients.

According to the classification, cephalosporins are divided into 4 generations:

• 1st generation drugs: Cefazolin, Cefadroxil;
• 2nd generation drugs: Cefuroxime, Cefaclor;
• 3rd generation drugs: Ceftriaxone, Cefotaxime, Cefoperazone, Ceftibuten;
• 4th generation drug: Cefepime.

Among the 1st generation drugs are Cefazolin for intramuscular administration and Cefadroxil and Cephalexin for oral use. The injection version has a stronger effect on microorganisms in contrast to oral agents.

1st generation cephalosporin antibiotics have a limited spectrum of action against gram-negative bacteria, listeria, and enterococci. They are used as a treatment for mild forms of streptococcal or staphylococcal infections.

2nd generation cephalosporins are generally similar to 1st generation antibiotics, with one difference - they are more active against gram-negative bacteria.

The drug Ceftriaxone is used to treat many infectious diseases and belongs to group 3 cephalosporins. It is administered predominantly intramuscularly and begins to act 25-50 minutes after entering the blood.

The drug Cefotoxime has similar properties. Both antibiotics have a destructive effect on the cells of streptococcal and pneumococcal bacteria.

4th generation cephalosporins are among the most powerful antibiotics in terms of their effect on bacteria and microorganisms. A substance of this group penetrates the membrane faster and is used as a treatment for many diseases (sepsis, joint infections, tract infections, intra-abdominal infections, etc.).

Carbapenems are beta-lactam antibiotics that are used to treat severe forms of various diseases. Classification of action: gram-positive microorganisms, gram-negative, anaerobic. Carbapenems are used to treat diseases caused by bacteria such as:

• coli;
• enterobacter;
• citrobacter;
• morganella;
• streptococci;
• meningococci;
• gonococci.

Bacterial resistance after long-term use of carbapenem is practically not observed, which is their distinguishing feature compared to other antibiotics. Their side effects are similar to penicillin drugs (Quincke's edema, rash, suffocation). In some cases, it causes the formation of blood clots in venous vessels.

Gastrointestinal disorders, dizziness, loss of consciousness, and hand tremors may occur. To eliminate the negative symptoms that arise while taking an antibiotic, sometimes it is enough to simply reduce the dosage of the drug.

Drugs in this group cannot be used during the lactation period, in newborns, or in mature people. During pregnancy, antibiotics are prescribed if there is a threat to the life and health of the pregnant woman or the baby in the womb.

Carbapenems cannot be combined with penicillins, cephalosporins and monobacts.

Among the monobactam group, only one antibiotic is used in medical practice, which is called Aztreonam. Used to treat many infectious diseases, sepsis. Injected only intramuscularly, it has a destructive effect on the cell walls of bacteria.

The drug should not be used if you are hypersensitive to beta-lactam antibiotics, in order to avoid the development of allergic reactions.

Antibiotics can have both positive and negative effects on the body, therefore, in order to avoid negative consequences, such drugs are prescribed only by a doctor after a thorough examination of the medical history.

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Antibiotics are a group of drugs that have an etiotropic mechanism of action. In other words, these drugs act directly on the cause of the disease (in this case, the causative microorganism) and do this in two ways: they destroy microbes (bactericidal drugs - penicillins, cephalosporins) or prevent their reproduction (bacteriostatic - tetracyclines, sulfonamides).

There are a huge number of drugs that are antibiotics, but the most extensive group among them are beta-lactams. These are the ones that will be discussed in this article.

Based on their mechanism of action, these drugs are divided into six main groups:

1. Antibiotics that disrupt the synthesis of cell membrane components: penicillins, cephalosporins, etc.
2. Medicines that interfere with the normal functioning of the cell wall: polyenes, polymyxins.
3. Drugs that inhibit protein synthesis: macrolides, tetracyclines, aminoglycosides, etc.
4. Suppressing RNA synthesis at the stage of action of RNA polymerase: rifampicins, sulfonamides.
5. Suppressing RNA synthesis at the stage of action of DNA polymerase: actinomycins, etc.
6. DNA synthesis blockers: anthracyclines, nitrofurans, etc.

However, this classification is not very convenient. In clinical practice, the following division of antibacterial drugs is accepted:

1. Penicillins.
2. Cephalosporins.
3. Macrolides.
4. Aminoglycosides.
5. Polymyxins and polyenes.
6. Tetracyclines.
7. Sulfonamides.
8. Aminoquinolone derivatives.
9. Nitrofurans.
10. Fluoroquinolones.

This is a group of drugs with a bactericidal effect and a fairly wide list of indications for use. Beta-lactam antibiotics include penicillins, cephalosporins, carbapenems, and monobactams. All of them are characterized by high efficiency and relatively low toxicity, which makes them the drugs most often prescribed for the treatment of many diseases.

The mechanism of action of beta-lactam antibiotics is determined by their structure. There is no need for unnecessary details here; it is worth mentioning only the most important element, which gave the name to the entire group of drugs. The beta-lactam ring included in their molecules provides a pronounced bactericidal effect, which is manifested by blocking the synthesis of elements of the pathogen’s cell wall. However, many bacteria are able to produce a special enzyme that disrupts the structure of the ring, thereby depriving the antibiotic of its main weapon. That is why the use of drugs that do not have protection against beta-lactamases in treatment is ineffective.

Nowadays, beta-lactam antibiotics protected from the action of bacterial enzymes are becoming increasingly common. They contain substances that block the synthesis of beta-lactamases, for example, clavulonic acid. This is how protected beta-lactam antibiotics (such as Amoxiclav) are created. Other bacterial enzyme inhibitors include Sulbactam and Tazobactam.

Drugs of this series were the first antibiotics, the therapeutic effect of which became known to people. For a long time they were widely used to treat various diseases and in the first years of use they were almost a panacea. However, it soon became clear that their effectiveness was gradually decreasing, since the evolution of the bacterial world did not stand still. Microorganisms can quickly adapt to a variety of difficult living conditions, giving rise to generations of antibiotic-resistant bacteria.

The prevalence of penicillins has led to the rapid growth of microbial strains that are insensitive to them, so in their pure form, drugs of this group are now ineffective and are almost never used. They are best used in combination with substances that enhance their bactericidal effect, as well as suppress the protective mechanisms of bacteria.

These are beta-lactam antibiotics, the classification of which is quite extensive:

1. Natural penicillins (for example, Benzylpenicillin).
2. Antistaphylococcal (“Oxacillin”).
3. Extended-spectrum penicillins (“Ampicillin”, “Amoxicillin”).
4. Antipseudomonal (Azlocillin).
5. Protected penicillins (combined with clavulonic acid, Sulbactam, Tazobactam).
6. Preparations containing several penicillin antibiotics.

Natural penicillins can successfully suppress the activity of both gram-positive and gram-negative microorganisms. Of the latter, streptococci and the causative agent of meningitis are the most sensitive to this group of beta-lactam antibiotics. The remaining bacteria have now acquired defense mechanisms. Natural penicillins are also effective against anaerobes: clostridia, peptococci, peptostreptococci, etc. These drugs are the least toxic and have a relatively small number of undesirable effects, the list of which is reduced mainly to allergic manifestations, although in case of an overdose, the development of convulsive syndrome and the appearance of symptoms of poisoning with sides of the digestive system.

Of the antistaphylococcal penicillins, the most important is the beta-lactam antibiotic Oxacillin. This is a drug for narrow use, as it is intended primarily to combat Staphylococcus aureus. It is against this pathogen (including penicillin-resistant strains) that “Oxacillin” is most effective. Side effects are similar to those of other representatives of this group of drugs.

In addition to gram-positive, gram-negative flora and anaerobes, extended-spectrum penicillins are also active against pathogens of intestinal infections. Side effects do not differ from those listed above, although these drugs are characterized by a slightly higher likelihood of disorders of the digestive system.

The beta-lactam antibiotic Azlocillin (a representative of the fourth group of penicillins) is intended to combat Pseudomonas aeruginosa. However, at present, this pathogen has shown resistance to drugs of this series, which makes their use not so effective.

Protected penicillins have already been mentioned above. Due to the fact that these drugs include substances that inhibit bacterial beta-lactamase, they are more effective in treating many diseases.

The last group is a combination of several representatives of the penicillin series, mutually reinforcing each other’s effects.

Cephalosporins are also beta-lactam antibiotics. These drugs, like penicillins, are distinguished by their broad spectrum of action and insignificant side effects.

There are four groups (generations) of cephalosporins:

1. The most prominent representatives of the first generation are Cefazolin and Cephalexin. They are intended primarily to combat staphylococci, streptococci, meningococci and gonococci, as well as some gram-negative microorganisms.
2. The second generation is the beta-lactam antibiotic Cefuroxime. Its area of ​​responsibility includes mainly gram-negative microflora.
3. “Cefotaxime”, “Ceftazidime” are representatives of the third group of this classification. They are very effective against enterobacteriaceae, and are also capable of destroying nosocomial flora (hospital strains of microorganisms).
4. The main drug of the fourth generation is Cefepime. It has all the advantages of the above drugs, in addition, it is extremely resistant to the action of bacterial beta-lactamases and has activity against Pseudomonas aeruginosa.

Cephalosporins and beta-lactam antibiotics in general are characterized by a pronounced bactericidal effect.

Of the undesirable reactions to the administration of these drugs, the most noteworthy are a variety of allergic reactions (from minor rashes to life-threatening conditions, such as anaphylactic shock); in some cases, disorders of the digestive system are possible.

Imipenem is a beta-lactam antibiotic belonging to the carbapenem group. It, as well as the equally well-known Meropenem, can outperform even the third and fourth generations of cephalosporins in terms of their effectiveness in affecting microflora resistant to other drugs.

A beta-lactam antibiotic from the carbapenem group is a drug used in particularly severe cases of disease when pathogens cannot be treated with other drugs.

Aztreonam is the most prominent representative of monobactams; it is characterized by a rather narrow spectrum of action. This beta-lactam antibiotic is most effective against gram-negative aerobes. However, it should be noted that, like Imipenem, Aztreonam is practically insensitive to beta-lactamases, which makes it the drug of choice for severe forms of diseases caused by these pathogens, especially when treatment with other antibiotics is ineffective.

To summarize the above, it should be noted that the drugs of these groups have an effect on a huge number of varieties of pathogenic microorganisms. The mechanism of action of beta-lactam antibiotics is such that it leaves no chance for microbes to survive: blocking cell wall synthesis is a death sentence for bacteria.

Gram-positive and gram-negative organisms, aerobes and anaerobes... There is a highly effective drug for all these representatives of pathogenic flora. Of course, among these antibiotics there are also highly specialized agents, but the majority are still ready to fight with several pathogens of infectious diseases at once. Beta-lactam antibiotics are able to resist even representatives of nosocomial flora, which are the most resistant to treatment.

We are talking about microorganisms that exist in medical institutions. The sources of their appearance are patients and medical staff. Hidden, sluggish forms of diseases are especially dangerous. The hospital is an ideal place where carriers of all possible types of infectious diseases gather. And violations of sanitary rules and regulations are fertile ground for this flora to find a niche for existence, where it can live, reproduce and acquire resistance to drugs.

The high resistance of hospital strains is primarily due to the fact that, having chosen a hospital institution as their habitat, the bacteria have the opportunity to come into contact with various drugs. Naturally, the effect of drugs on microorganisms occurs accidentally, without the purpose of destruction, and in small doses, and this contributes to the fact that representatives of hospital microflora can develop protection against mechanisms that are destructive to them, and learn to resist them. This is how strains appear, which are very difficult to fight, and sometimes it seems impossible.

Beta-lactam antibiotics, to one degree or another, try to solve this difficult problem. Among them there are representatives that can quite successfully fight even the most drug-insensitive bacteria. These are reserve drugs. Their use is limited, and they are prescribed only when it is really necessary. If these antibiotics are used unreasonably often, then, most likely, this will end in a decrease in their effectiveness, because then bacteria will have the opportunity to interact with small doses of these drugs, study them and develop methods of protection.

Indications for the use of this group of drugs are determined primarily by their spectrum of action. It is most advisable to prescribe a beta-lactam antibiotic for an infection whose pathogen is sensitive to the action of this medicine.

Penicillins have proven themselves in the treatment of pharyngitis, tonsillitis, pneumonia, scarlet fever, meningitis, bacterial endocarditis, actinomycosis, anaerobic infections, leptospirosis, salmonellosis, shigellosis, infectious diseases of the skin and soft tissues. Don’t forget about drugs that can fight Pseudomonas aeruginosa.

Cephalosporins have a similar spectrum of action, therefore the indications for them are almost the same as for penicillins. However, it should be said that the effectiveness of cephalosporins, especially the last two generations, is much higher.

Monobactams and carbapenems are designed to combat the most severe and difficult-to-treat diseases, including those caused by hospital strains. They are also effective in sepsis and septic shock.

As already mentioned, beta-lactam antibiotics (drugs belonging to this group are listed above) have a relatively small number of harmful effects on the body. Rarely occurring seizures and symptoms of digestive system disorders do not pose a threat to life. Severe allergic reactions to the administration of beta-lactam antibiotics can become truly dangerous.

Rashes, skin itching, rhinitis and conjunctivitis do not pose a threat to life, although they are very unpleasant. What you really should be wary of are such severe reactions as Quincke's edema (especially in the larynx, which is accompanied by severe suffocation up to the inability to breathe) and anaphylactic shock. Therefore, the drug can be administered only after an allergy test has been performed.

Cross reactions are also possible. Beta-lactam antibiotics, the classification of which implies the presence of a large number of groups of drugs, are very similar in structure to each other, which means that if one of them is intolerant, all the others will also be perceived by the body as an allergen.

The gradual decrease in the effectiveness of antibacterial drugs (including beta-lactam antibiotics) is due to their unreasonably frequent and often incorrect prescription. An incomplete course of treatment and the use of small therapeutic doses do not contribute to recovery, but they give microorganisms the opportunity to “train,” invent and practice methods of protection against drugs. So is it any wonder that the latter become ineffective over time?

Although antibiotics are now not available in pharmacies without a prescription, you can still get them. This means that self-medication and the problems associated with it (using the same drug all the time, unjustified interruption of the course of therapy, incorrectly selected doses, etc.) will remain, creating conditions for the cultivation of resistant strains.

Hospital flora is not going anywhere either, having the ability to actively contact various drugs and invent new ways to counteract them.

What to do? Do not self-medicate, follow the recommendations of your doctor: take medications for as long as required and in the correct doses. It is, of course, more difficult to combat nosocomial flora, but it is still possible. Tightening sanitary standards and their strict implementation will reduce the likelihood of creating favorable conditions for the proliferation of resistant flora.

A very broad topic is beta-lactam antibiotics. Pharmacology (the science of drugs and their effect on the body) devotes several chapters to them, which include not only a general description of the group, but also contain a description of its most famous representatives. This article does not pretend to be complete, it only tries to introduce the main points that you simply need to know about these medications.

Be healthy and do not forget: before using any antibiotic, carefully read the instructions and strictly follow the recommendations, or even better, consult a specialist.

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Beta-lactam antibiotics are antimicrobial agents that combine 4 groups of antibiotic substances of different origin and spectrum of antimicrobial activity, but united by one common feature - the content of the beta-lactam ring in the molecular formula.

A similar chemical structure determines the general mechanism of the destructive effect, mainly on gram-positive microorganisms, which consists of damaging the synthesis process of moray eel, the main building component of the prokaryotic membrane. The development of cross-allergy due to the common structural component cannot be ruled out.

It has been noted that the lactam ring is highly sensitive to the destructive effects of beta-lactamase proteins. Each of the representatives of the 4 classes is characterized by its own degree of stability and can differ significantly between natural and semi-synthetic representatives.

Currently, lactam antibiotics are the foundation of all antimicrobial therapy and are used everywhere for drug therapy for a wide range of diseases.

General classification of beta-lactam antibiotics:

1. Penicillins:
   - natural;
   - semi-synthetic.
2. Cephalosporins, 5 generations.
3. Carbapenems.
4. Monobactams.

Penicillins

Penicillins are the first antimicrobial substances that were accidentally discovered by Alexander Fleming and made a powerful revolution in the world of medicine. The natural producer is Penicillium fungi – soil cosmopolitans. When the minimum inhibitory concentration is reached, lactam antibiotics have bactericidal activity. Penicillin is absolutely safe for mammals, since they lack the main target for action – peptidoglycan (murein). However, individual intolerance to the drug and the development of an allergic reaction are possible.

Microorganisms have developed defense systems against the harmful effects of penicillins:

• active synthesis of beta-lactamases;
• rearrangement of peptidoglycan proteins.

Therefore, scientists modified the chemical formula of the substance and in the 21st century, semi-synthetic penicillins, which are harmful to a large number of gram-positive and gram-negative bacteria, became widespread. There is not a single area of ​​medicine where they would not be applicable.

The British bacteriologist A. Fleming, as he himself later admitted, did not plan to revolutionize medicine by discovering antibiotics. However, he succeeded, and quite by accident. But, as you know, luck bestows only on prepared minds, which he was. By 1928, he had already established himself as a competent microbiologist and conducted a comprehensive study of bacteria of the Staphylococcaceae family. However, A. Fleming was not distinguished by his passion for ideal order.

Having prepared Petri dishes with staphylococcal cultures for slaughter, he left them on his table in the laboratory and went on vacation for a month. Upon his return, he noticed that there was no bacterial growth in the area where the mold had fallen from the ceiling onto the cup. On September 28, 1928, the greatest discovery in the history of medicine was made. It was possible to obtain the substance in its pure form by 1940, through the joint efforts of Fleming, Flory and Chain, for which they were awarded the Nobel Prize.

Prescribed for diseases caused by gram-positive and gram-negative cocci and bacilli, spirochetes and some anaerobic bacteria. For example:

• pneumonia;
• purulent pleurisy;
• blood poisoning with infectious agents;
• meningococcal infections;
• osteomyelitis;
• inflammatory processes of the urinary tract;
• tonsillitis;
• diphtheria;
• ENT diseases;
• erysipelas;
• streptococcal lesions;
• malignant carbuncle, actinomycosis.

Individual intolerance and allergies to all lactam antimicrobial drugs. It is prohibited to inject into the lumen between the membrane of the spinal cord and the periosteum to people diagnosed with epilepsy.

Side symptoms include gastrointestinal disorders (nausea, vomiting, loose stools) and central nervous system (weakness, drowsiness, irritability). Candidiasis of the vagina and oral cavity, as well as dysbacteriosis. Possible swelling. It is noted that if the dosage and duration of treatment are observed, side effects are rare.

Patients with pathologies in the functioning of the kidneys, heart and pregnant women are prescribed only if the benefits of the antibiotic significantly outweigh the possible risks. If there is no relief of symptoms of the disease after a week of therapy, it is recommended to prescribe drugs from an alternative group. It has been established that the combined use of an antibiotic and an immunostimulant has the most positive effect on the human body.

Self-medication with lactam drugs is prohibited due to the rapid rate of development of resistance of pathogenic strains to them.

For children, the daily dose must be adjusted and reduced from 12 g per day (adults) to 300 mg per day.

The most extensive group, leading in the number of medications. To date, 5 generations of drugs have been developed. Each subsequent generation is characterized by greater resistance to lactamases and an expanded list of antimicrobial activity.

The 5th generation is of particular interest, but many of the discovered drugs are still at the stage of preclinical and clinical trials. It is assumed that they will be active against a strain of Staphylococcus aureus that is resistant to all known antimicrobial agents.

They were discovered in 1948 by the Italian scientist D. Brotzu, who was researching typhus. He noted that in the presence of C. acremonium there was no growth of the S. typhi culture on a Petri dish. Later, the substance was obtained in its pure form and is actively used in many areas of medicine and is being improved by microbiologists and pharmacological companies.

It is prescribed by a doctor after isolation, identification of the causative agent of inflammation and determination of sensitivity to antibiotics. Self-medication is unacceptable; this can lead to serious consequences for the human body and the spread of uncontrolled resistance of prokaryotes. Effective against staphylococcal and streptococcal infections of the dermis, bone tissue and joints, including MRSA (5th generation).

Contraindications are similar to penicillins. At the same time, the frequency of side effects is lower than in the previous group. A patient's history of allergy to penicillins serves as a warning for use.

Frequent repeated intravenous administration is fraught with the formation of excess heat in the patient’s body and painful sensations in the smooth muscles. Recently, isolated reports have begun to appear that 5th generation cephalosporins have a negative effect on hematopoiesis.

None of the cephalosporin medications are compatible with alcohol. Violation of this rule entails acute intoxication of the entire body. The permissible dose per day for children is from 50 to 100 mg; for meningitis, an increase to 200 mg is allowed. Prescribed to newborns as a component of combined drug therapy with ampicillin.

There is no correlation between food intake and drug intake. When taking lactam antibiotics orally, it is recommended to drink plenty of water. Despite the fact that special studies aimed at establishing the safety of cephalosporins for pregnant women have not been conducted, nevertheless, it is successfully used for pregnant women. There were no complications during pregnancy or pathologies in the fetus. But still, it cannot be used without a doctor’s prescription. Reception during breastfeeding is limited, as the substance penetrates into breast milk and can change the baby’s intestinal microflora.

Leaders in the degree of immunity to the action of lactamases. This fact explains the huge list of pathogenic bacteria for which carbapenems are harmful. An exception is the enzyme NDM-1, identified in cultures of E. coli and K. pneumoniae. They are bactericidal to representatives of the Enterohacteriaceae and Staphylococcaceae families, Pseudomonas aeruginosa and many anaerobic bacteria.

Toxicity does not exceed permissible standards, and their pharmacokinetic parameters are quite high. The effectiveness of the antimicrobial substance was established and confirmed in independent studies in the treatment of inflammation of varying severity and location. Their mechanism of action, like all lactams, is aimed at inhibiting the biosynthesis of the cell wall of prokaryotes.

40 years after the beginning of the “penicillin era,” scientists sounded the alarm about growing levels of resistance and actively began work to find new antimicrobial agents, one of the results of which was the discovery of a group of carbapenems. First, imipenem was discovered, which met all the requirements for bactericidal substances. Since its opening in 1985, more than 26 million patients have been cured with it. Carbapenems have not lost their importance and today there is no area of ​​medicine where they are not used.

The drug is indicated for hospitalized patients with infections of various organ systems, with:

• hospital pneumonia;
• blood poisoning;
• fever;
• inflammation of the lining of the heart and soft tissues;
• infections of the abdominal area;
• osteomyelitis.

The safety of the substance has been confirmed by numerous studies. The frequency of manifestation of negative symptoms (nausea, vomiting, rash, seizures, drowsiness, pain in the temporal region, upset stool) is less than 1.8% of the total number of patients. Negative phenomena stop immediately when you stop taking the medication. There are isolated reports of a decrease in the concentration of neutrophils in the blood during treatment with carbapenems.

Beta-lactam antibiotics have been successfully used for effective therapy for more than 70 years, however, it is necessary to strictly follow the doctor’s prescriptions and instructions for use. Carbapenems are not compatible with alcohol and it is worth limiting its intake 2 weeks before and after drug treatment. Complete incompatibility with ganciclovir was revealed. When these drugs are used in combination, convulsions are observed.

Safety for newborns has not been established, so its use is excluded. It has been noted that in children the half-life of the active substance increases.

Pregnant and breastfeeding women are prescribed for life-threatening pathologies.

A distinctive feature is the absence of an aromatic ring associated with a beta-lactam ring. This structure guarantees them complete immunity to lactamases. They have bactericidal activity mainly against gram-negative aerobic prokaryotes. This fact is explained by the structural features of their cell wall, which consists of a thinner layer of peptidoglycan when compared to gram-positive microbes.

An important feature of monobactams is that they do not cause cross-allergy to other lactam antibiotics. Therefore, their use is permissible in case of individual intolerance to other lactam antibiotics.

The only medicine that has been introduced into medical practice is aztreonam with a limited spectrum of activity. Aztreonam is considered a “young” antibiotic; it was approved in 1986 by the Ministry of Food and Drug Administration.

It is characterized by a narrow spectrum of action and belongs to the group of antibiotic drugs used for inflammatory processes caused by gram-negative pathogenic bacteria:

• blood poisoning;
• hospital and community-acquired pneumonia;
• infections of the urinary ducts, abdominal organs, dermis and soft tissues.

In order to achieve maximum results, combination therapy with drugs that destroy gram-positive microbial cells is recommended. Exclusively parenteral administration.

The only limitation to prescribing aztreonam is individual intolerance and allergies. Undesirable reactions from the body are possible, manifested in the form of jaundice, abdominal discomfort, confusion, sleep disturbances, rash and nausea. As a rule, they all disappear when therapy is stopped. Any, even the most minor, negative reactions from the body are a reason to immediately consult a doctor and adjust the treatment.

• INTRODUCTION
• 1. Distinctive properties of new beta-lactam antibiotics
• 2. Bacterial complications of HIV infection and their treatment
• Conclusion

INTRODUCTION Antibiotics (antibiotic substances) are metabolic products of microorganisms that selectively suppress the growth and development of bacteria, microscopic fungi, and tumor cells. The formation of antibiotics is one of the forms of manifestation of antagonism. The term was introduced into the scientific literature in 1942 by Vaksman - “antibiotic is against life.” According to N.S. Egorov: “Antibiotics are specific products of the vital activity of organisms, their modifications, which have high physiological activity against certain groups of microorganisms (bacteria, fungi, algae, protozoa), viruses or malignant tumors, retarding their growth or completely suppressing their development.” Specificity of antibiotics in comparison with other metabolic products (alcohols, organic acids), which also suppress the growth of certain microbial species, it has extremely high biological activity. There are several approaches to the classification of antibiotics: by type of producer, structure, nature of action. Based on their chemical structure, antibiotics are distinguished as acyclic, alicyclic, quinones, polypeptides, etc. Based on the spectrum of biological action, antibiotics can be divided into several groups: antibacterial, with a relatively narrow spectrum of action, suppressing the development of gram-positive microorganisms and a broad spectrum of action, suppressing the development of both gram-positive and and gram-negative microorganisms; antifungal, a group of polyene antibiotics acting on microscopic fungi; antitumor, acting on human and animal tumor cells, as well as microorganisms. Currently, over 6,000 antibiotics have been described, but in practice only about 150 are used, since many have high toxicity for humans, others are inactivated in the body, etc. Beta-lactam antibiotics (β-lactam antibiotics, β-lactams) are a group of antibiotics that are united by the presence of a β-lactam ring in their structure. Beta-lactams include subgroups of penicillins and cephalosporins , carbapenems and monobactams. The similarity of the chemical structure determines the same mechanism of action of all β-lactams (impaired bacterial cell wall synthesis), as well as cross-allergy to them in some patients. Penicillins, cephalosporins and monobactams are sensitive to the hydrolyzing action of special enzymes - β-lactamases, produced by a number of bacteria. Carbapenems are characterized by significantly higher resistance to β-lactamases. Taking into account their high clinical efficacy and low toxicity, β-lactam antibiotics form the basis of antimicrobial chemotherapy at the present stage, occupying a leading place in the treatment of most infections. Beta-lactam antibiotics, which are spatially similar to the reaction substrate D-alanyl-D-alanine, form a covalent acyl bond with the active site of transpeptidase and irreversibly inhibit it. Therefore, transpeptidases and similar enzymes involved in transpeptidation are also called penicillin-binding proteins. Almost all antibiotics that inhibit the synthesis of bacterial cell walls are bactericidal - they cause the death of bacteria as a result of osmotic lysis. In the presence of such antibiotics, autolysis of the cell wall is not balanced by restoration processes, and the wall is destroyed by endogenous peptidoglycan hydrolases (autolysins), which ensure its restructuring during normal bacterial growth. 1. Distinctive properties of new beta-lactam antibiotics Beta-lactam antibiotics (BLA) are the basis of modern chemotherapy, as they occupy a leading or important place in the treatment of most infectious diseases. In terms of the number of drugs used in the clinic, this is the largest group among all antibacterial agents. Their diversity is explained by the desire to obtain new compounds with a wider spectrum of antibacterial activity, improved pharmacokinetic characteristics and resistance to constantly emerging new mechanisms of resistance of microorganisms. Due to the ability to bind to penicillin (and other BLAs), these enzymes have received a second name - penicillin-binding proteins (PBPs). PBPs molecules are tightly bound to the cytoplasmic membrane of the microbial cell; they form cross-links. The binding of BLA to PBPs leads to the inactivation of the latter, cessation of growth and subsequent death of the microbial cell. Thus, the level of activity of specific BLAs against individual microorganisms is primarily determined by their affinity for PBPs. For practice, it is important that the lower the affinity of the interacting molecules, the higher concentrations of the antibiotic are required to suppress the enzyme function. The practically important properties of beta-lactamases include: substrate profile (the ability to preferentially hydrolyze certain BLAs, for example penicillins or cephalosporins or those and others equally); localization of coding genes (plasmid or chromosomal). This characteristic determines the epidemiology of resistance. With plasmid localization of genes, rapid intra- and interspecific spread of resistance occurs; with chromosomal localization, the spread of the resistant clone is observed; the type of expression (constitutive or inducible). In the constitutive type, microorganisms synthesize beta-lactamases at a constant rate; in the inducible type, the amount of the synthesized enzyme increases sharply after contact with an antibiotic (induction); sensitivity to inhibitors. Inhibitors include substances of beta-lactam nature that have minimal antibacterial activity, but are capable of irreversibly binding to beta-lactamases and, thus, inhibiting their activity (suicidal inhibition). As a result, with the simultaneous use of BLA and beta-lactamase inhibitors, the latter protect antibiotics from hydrolysis. Dosage forms that combine antibiotics and beta-lactamase inhibitors are called combined, or protected, beta-lactams. Three inhibitors have been introduced into clinical practice: clavulanic acid, sulbactam and tazobactam. Thus, the individual properties of individual BLAs are determined by their affinity for PSB, the ability to penetrate the external structures of microorganisms and resistance to hydrolysis by beta-lactamases. Some betalactam-resistant strains found in the clinic have bacterial resistance manifests itself at the level of PBPs, that is, the targets reduce their affinity for the “old” betalactams. Therefore, new natural and semisynthetic beta-lactams are tested for their affinity for the PBPs of these strains. High affinity means that new beta-lactam structures are promising. When evaluating new beta-lactam structures, their resistance to the action of various beta-lactamases - renicillases and cephalosporinases of plasmid and chromosomal origin, isolated from different bacteria - is tested. If most of the betalactamases used do not inactivate the new betalactam structure, then it is considered promising for the clinic. Chemists have created semisynthetic penicillins that are insensitive to penicillinases common in staphylococci: methicillin, oxacillin, and carbenicillin, which is insensitive to the enzyme from Pseudomonas aeruginosa. These semisynthetic penicillins were obtained after 6APA (6-aminopenicillic acid) was isolated from benzylpenicillin. The indicated antibiotics were obtained by its acylation. Many betalactases lose the ability to hydrolyze the betalactam ring of antibiotics such as cephamycin C in the presence of a methoxy group or other substituents in the 6b-position in penicillins and in the 7b-position in cephalosporins. The effectiveness of betalactams against gram-negative bacteria depends on on factors such as the rate of passage through porin thresholds. Advantages include compact molecules that can pass through cation-selective and anion-selective channels, such as imipenem. Its valuable properties also include resistance to a number of betalactamases. Betalactams, in which substituent molecules introduced into the nucleus create a cationic center, are highly active against many intestinal bacteria due to the cation selectivity of porin channels in bacteria living in the intestinal tract, for example, the drug ceftazidime. Often modifications affect the structure of the betalactam-fused five- or six-membered ring. If sulfur is replaced by oxygen or carbon, then such compounds are called “non-classical” betalactams (for example, imipenem). “Non-classical” also includes those betalactams in which the betalactam ring is not condensed with another ring. They are called "monobactams". The most famous drug from the “monobactams” is aztreonam. Natural compounds with high antibacterial activity and a wide spectrum of action are of great interest. Upon contact with the target, their gamma-lactam ring is cleaved and acylation of one of the amino acid residues in the active center of transpeptinases occurs. Betalactams can also inactivate gammalactams, but the greater stability of the five-membered gammalactam ring expands the possibilities of chemical synthesis, that is, the production of synthetic gammalactams with spatial protection of the gammalactam ring from betalactamases. The range of betalactam synthetic antibiotics is growing rapidly and is used to treat a wide variety of infections. 2. Bacterial complications of HIV infection and their treatment HIV - human immunodeficiency virus, which causes a viral disease - HIV infection, the last stage of which is known as acquired immunodeficiency syndrome (AIDS) - in contrast to congenital immunodeficiency. HIV primarily infects cells of the immune system (CD4+ T-lymphocytes, macrophages and dendritic cells), as well as some other cell types. CD4+ T lymphocytes infected with HIV gradually die. Their death is mainly due to three factors: direct destruction of cells by the virus; programmed cell death; killing of infected cells by CD8+ T lymphocytes. Gradually, the subpopulation of CD4+ T lymphocytes is reduced, as a result of which cellular immunity decreases, and when the number of CD4+ T lymphocytes reaches a critical level the body becomes susceptible to opportunistic (opportunistic) infections. Bacterial pneumonia in HIV-infected people is observed more often than in the rest of the population, and, like Pneumocystis pneumonia, leaves behind scars in the lungs. This often leads to restrictive breathing problems that persist for years. Bacterial pneumonia also occurs in the early stages of HIV infection, but as immunodeficiency worsens, its risk increases. Bacterial pneumonia significantly worsens the long-term prognosis. Therefore, bacterial pneumonia that occurs more than once a year is considered an AIDS indicator disease. The most common pathogens are pneumococci and Haemophilus influenzae. Against the background of HIV infection, Staphylococcus aureus, Moraxella catarrhalis are sown more often than with normal immunity, and in the later stages, when the number of CD4 lymphocytes does not exceed 100 μl -1, also Pseudomonas spp. If there is a slowly increasing infiltrate in the lungs with a decay cavity, the rare infection caused by Rhodococcus equi and pulmonary nocardiosis should be suspected. In 10-30% of patients, there are several causative agents of pneumonia, and one of them may be Pneumocystis jiroveci, which complicates diagnosis. According to recommendations for patients with community-acquired pneumonia and concomitant diseases, a second-generation cephalosporin (for example, cefuroxime) or a third generation (for example, cefotaxime) is prescribed and ceftriaxone) or a combination drug of aminopenicillin and a lactamase inhibitor - ampicillin/sulbactam or amoxicillin/clavulanate (for example, Augmentin® at a dose of 875/125 mg 2 times a day). In areas where the incidence of legionellosis is increased, a macrolide is added to these drugs, for example Klacid at a dose of 500 mg 2 times a day. Among bacterial infections, disseminated tuberculosis is often observed in patients in the AIDS-AK stage. Peripheral lymph nodes affect the skin, lungs, digestive tract, central nervous system, and other organs. This is considered the main cause of death for HIV-infected patients in regions where the incidence of tuberculosis is increased. The worsening epidemiological situation of tuberculosis in the world is associated with the rapid increase in the scale of the HIV pandemic. The lack of reliable means of prevention and treatment of the latter allows us to classify this problem as one of the most pressing at the present stage, since the high infection rate with Mycobacterium tuberculosis and the rapid spread of HIV in the same environment make the prognosis of the combined pathology extremely unfavorable. In countries with a high HIV infection rate, 30-50% of patients with HIV infection develop tuberculosis. Tuberculosis is detected with damage to the respiratory organs: infiltrative, focal, fibrinous-cavernous, cavernous tuberculosis, tuberculoma. Extrapulmonary forms of tuberculosis are often found: damage to the lymph nodes, exudative pleurisy, disseminated tuberculosis, tuberculous meningitis, generalized. When diagnosing tuberculosis and its treatment in HIV-infected people, it should be taken into account that the clinical manifestations of tuberculosis are often atypical: damage to the lymph nodes is noted, a generalized enlargement of the lymph nodes is often observed, which is not typical for other forms of tuberculosis; a milliary process occurs, mycobacteria can be isolated by culturing blood, which never happens with ordinary tuberculosis; with the pulmonary process of tuberculosis, there are no typical signs of lung damage, often there is an increase in the shadow of the mediastinal lymph nodes, pleural effusions. It is impossible to start treatment for tuberculosis and HIV infection at the same time due to the overlap of side effects of the drugs used, adverse drug interactions.1. If the CD4 lymphocyte count<200 мкл-1: начать ВААРТ с эфа-вирензом через 2-8 недель после начала противотуберкулезной терапии.2. Количество лимфоцитов CD4 200-350 мкл-1, то решение о назна-чении ВААРТ принимается индивидуально. Если принято положительное решение о ВААРТ, ее начинают после завершения начальной фазы противотуберкулезной терапии. Применяют либо схемы, содержащие эфавиренз в дозе 600-800 мг/сут, либо ИП-содержащие схемы, одновременно заменяя в схеме противотуберкулезной терапии рифампин на рифабутин и корректируя дозы препаратов исходя из лекарственных взаимодействий.При нокардиозе назначают: имипенем + амикацин; сульфаниламид + амикацин или миноциклин; цефтриаксон + амикацин.Другими заболеваниями, которые могут быть следствием развития СПИДа, являются сепсис, менингит, поражение костей и суставов, абсцесс, отит и другие воспалительные процессы, вызванные бактериями родов Haemophilus и Streptococcus (включая Streptococcus pneumoniae) или другими гноеродными бактериями.Антибактериальная терапия сепсиса определяется видом предполагаемого или установленного возбудителя. Если сепсис вызван грамотрицательными микроорганизмами, больному назначают карбенициллин (20-30 г/сут В/в капельно или струйно за 6-8 введений), по-прежнему продолжая применение гентамицина.При стафилококковом сепсисе терапию целесообразно начинать с применения антибиотика из группы цефалоспоринов вместе с гентамицином. Гентамицин можно заменить амикацином (500 мг 2-3 раза в день) или тобрамицином (80 мг 2-3 раза в день).У ВИЧ-инфицированных наиболее часто встречаются следующие виды стафилококковых инфекций: фурункулез, пиомиозит - типичная гнойная инфекция мышечной ткани, вызываемая S. aureus, как правило, чувствительными к метициллину штаммами; стафилококковые инфекции, связанные с введением наркотиков инъекционным путем.Лечение: при инфекции, вызванной метициллинчувствительными S. aureus (MSSA) используют антистафилококковые беталактамы (нафциллин, оксациллин, цефазолин, цефтриаксон); как правило, стафилококки чувствительны также к клиндамицину, фторхиноло-нам и ТМП-СМК. Внутрь назначается: цефалексин 500 мг 4 раза в сутки, диклоксациллин 500 мг 4 раза в сутки, клиндамицин 300 мг 3 раза в сутки или фторхинолон.Цефалоспориновые антибиотики сегодня занимают одно из ведущих мест при лечении бактериальных инфекций. Широкий спектр микробной активности, хорошие фармакокинетические свойства, низкая токсичность, синергизм с другими антибиотиками - делают цефалоспорины препаратами выбора при многих инфекционно-воспалительных заболеваниях.К III поколению цефалоспоринов относятся препараты, обладающие высокой активностью в отношении семейства Enterobacte-riaceae. гемофильной палочки, гонококков, менингококков, и меньше - в отношении грамположительных микроорганизмов.Одним из представителей цефалоспоринов III-поколения является цефтриаксон (офрамакс. "Ranbaxy", Индия). Цефтриаксон имеет более широкий спектр антимикробной активности. Антибиотик обладает стабильностью по отношению к в - лактамазам и высокой проницаемостью через стенку грамотрицательных микроорганизмов.Conclusion The problem of the development of bacterial resistance to antibiotics requires the development of antibacterial drugs with new mechanisms of action. Cell division proteins may be candidates for the role of targets for broad-spectrum antibiotics, since almost all of them are necessary for reproduction, and, therefore, for the existence of bacterial colonies. Although these proteins are evolutionarily conserved among bacteria, they differ from each other and may have slight homology with human proteins, which complicates the development of safe broad-spectrum antibiotics. For the successful development of antibiotics in the future, in addition to screening chemical substances, it is necessary to use new approaches aimed at creating drugs that act on known potential targets. Large-scale screenings of libraries of chemical compounds have made it possible to discover several candidate cell division inhibitor molecules. They turned out to be compounds that block the functioning of the most conservative cell division proteins: FtsZ and FtsA. At the moment, the FtsZ and FtsA proteins are the most attractive targets for the search for antibacterial drugs. Since multiple protein-protein interactions occur during cell division, the ability to influence these interactions may be useful for the creation of drugs. Technologies for searching for substances that affect protein-protein interactions are being intensively developed and some of them may be effective in the search for new antibiotics. At the same time, emerging progress in the field of targeted drug delivery may increase the effectiveness of antibacterial drugs in the future. Bibliography

1. Albert A. Selective toxicity. Physico-chemical foundations of therapy: in two volumes / Transl. from English M.: Medicine, 1989.

2. Alberts B, Bray D, Lewis J et al. Molecular biology of cells: in two volumes. M.: Mir, 1994.

3. Belousov Yu.B., Moiseev V.S., Lepakhin V.K. Clinical pharmacology and pharmacotherapy. Guide for doctors. M.: Universum Publishing, 1997.

4. Gause G.F. Molecular basis of antibiotic action. /Trans. from English M.: “Mir”, 1975.

5. Egorov N.S. Fundamentals of the doctrine of antibiotics. M.: Higher School, 1986.

6. Elinov N.P. Chemical microbiology. M.: Higher School, 1989.

7. M.D. Mashkovsky. Medicines. M., 1993, vol. 1, pp. 313-314.

8. Materials of the scientific and practical conference “Antibacterial drugs in the practice of a therapist.” St. Petersburg, May 16-17, 2000.

9. Mikhailov I.B. Clinical pharmacology. St. Petersburg: Foliant, 1999.

10. Strachunsky L.S., Kozlov S.N. Antibiotics: clinical pharmacology. Smolensk: Amipress, 1994.

11. Yakovlev V.P. Antibacterial chemotherapy in a non-infectious clinic: new betalactams, monobactams and quinolones. // Results of science and technology. Moscow, 1992, 201 pp.

Dear friends, hello!

Today we will continue the conversation about antibiotics that we started earlier.

We have already discussed which drugs are classified as antibiotics, how they act, what types they are, why microbes become resistant to them, and what rational antibiotic therapy should be.

Today we will talk about two popular groups of antibiotics, consider their general characteristics, indications for use, contraindications and the most common side effects.

Then let's go!

First, let's figure out what it is...

Beta-lactams

Beta-lactams are a group of antibiotics whose chemical formula contains a beta-lactam ring.

It looks like this:

The beta-lactam ring binds the antibiotic to a microbial enzyme necessary for the synthesis of the cell wall.

After the formation of this union, its synthesis becomes impossible. As a result, the boundaries of the bacterial house are destroyed, liquid from the environment begins to penetrate into the cell, and the bacterium dies without even having time to call a notary. 🙂

But last time we already said that bacteria are quite creative guys who love life very much. They are not at all warmed by the prospect of bursting like a soap bubble from the swelling of themselves, their loved one, when the cell wall is destroyed by an antibiotic.

To prevent this, they come up with various tricks. One of them is the production of enzymes (beta-lactamases, or penicillinases), which combine with the beta-lactam ring of the antibiotic and make it inactive. As a result, the antibiotic cannot carry out its terrorist act.

But in the microbial world everything happens like in humans: there are bacteria that are more creative and less creative, i.e. Some have a higher ability to produce beta-lactamases, others have a lower ability. Therefore, the antibiotic works on some bacteria and not on others.

Now that I have explained these extremely important things to you, you can proceed directly to the analysis of groups of antibiotics.

The most common beta-lactams doctors prescribe are penicillins and cephalosporins.

Penicillins

Penicillins are divided into natural and semi-synthetic.

Natural ones include benzylpenicillin, bicillin, phenoxymethylpenicillin.

They act on a very limited range of bacteria: streptococci, which cause scarlet fever, erysipelas; pathogens of gonorrhea, meningitis, syphilis, diphtheria.

Benzylpenicillin It is destroyed by hydrochloric acid of the stomach, so taking it by mouth is pointless. It is administered only parenterally, and to maintain the required concentration in the blood it is administered every 4 hours.

Understanding all the disadvantages of benzylpenicillin, scientists continued to work on improving this group, and on the farm. Bicillin entered the market. It is also used only parenterally, but it creates a depot of the antibiotic in muscle tissue, so it has a long-lasting effect. It is administered 1-2 times a week, and Bicillin-5 even less often: once every 4 weeks.

Well, then he appeared phenoxymethylpenicillin - penicillin for oral use.

Although it is also not particularly acid-resistant, it is more than benzylpenicillin.

But it still has no effect on staphylococcus, which is the cause of many infections.

And all because staphylococcus produces the same beta-lactamase enzymes that make the antibiotic inactive. Therefore, all natural penicillins have practically no effect on it.

It was necessary to create something that would destroy this “beast” too.

Therefore, a semi-synthetic penicillin was developed - Oxacillin, which is resistant to beta-lactamases of most staphylococci.

But again a problem arose: its activity against other bacteria turned out to be purely symbolic. And given that identification of the pathogen that caused a particular disease is rarely carried out in our country (at least in an outpatient setting), the use of oxacillin is not justified at all.

Years passed. Work on penicillins continued. Each subsequent drug was superior in some way to the previous ones, but problems remained.

And finally, Ampicillin appeared in pharmacies, still dearly loved by many patients, and perhaps even doctors. It was already a broad-spectrum penicillin: it acted on streptococci and some staphylococci, E. coli, pathogens, meningitis and gonorrhea.

In combination with oxacillin (the drug Ampiox), its effectiveness has increased.

And after it Amoxicillin entered the market. Compared to ampicillin, it is absorbed 2 times better in the intestine, and its bioavailability does not depend on food intake. Plus, it penetrates better into the bronchopulmonary system.

Only the problem of developing bacterial resistance to these drugs still remained.

And then “protected” penicillins appeared, nullifying the microbes’ strategy. The additional substances included in their composition bind to the beta-lactamases of bacteria, neutralizing them.

The most popular in the group of “protected” penicillins are preparations of amoxicillin with clavulanic acid ( Augmentin, Amoxiclav, Panclave, Flemoklav and etc.).

This is how they work.

Clavulanic acid offers beta-lactamases a “hand and heart”, i.e. connects with them. They become “soft and fluffy” and completely forget about their great mission to make the antibiotic inactive.

While clavulanic acid “kills” beta-lactamases, amoxicillin, meanwhile, quietly and quietly binds the microbial enzyme involved in the synthesis of the cell wall. The cell wall is destroyed. Through it, fluid from the environment rushes into the cell, and... voila... the bacterium dies in its prime from ascites and self-edema.

Indications for the use of penicillins

Friends, in order not to lump everything into a heap, here I am naming those indications for which this group is used most often.

So, here are the indications for the use of penicillins:

• Infections of the respiratory tract and ENT organs: sore throat, bronchitis, pneumonia.
• Urinary tract infections: , pyelonephritis.
• Condition after tooth extraction.
• Gastric ulcer, since amoxicillin is included in Helicobacter Pylori eradication regimens.

The most common side effects of penicillins:

• Allergic reactions.
• Candidiasis, intestinal dysbiosis.
• Dysfunction (amoxicillin + clavulanic acid).
• Nausea, vomiting (most often when taking amoxicillin with clavulanic acid).

When amoxicillin with clavulanic acid is sold, recommend taking it with food.

Main contraindications to the use of penicillins

I will name only one absolute contraindication:

Hypersensitivity to penicillins and other beta-lactam antibiotics.

Pregnant, nursing, children (only as prescribed by a doctor!)

• For children - in age-appropriate dosages.
• Pregnant women can.
• For nursing mothers, be careful: the baby may develop a rash and candidiasis.

Cephalosporins

They also belong to beta-lactam antibiotics and also have a bactericidal effect. Compared to penicillins, they are more resistant to beta-lactamases, which is why many doctors give preference to this group in their prescriptions.

In addition, they act on those bacteria that are not sensitive or weakly sensitive to penicillins. In particular, they cope with staphylococcus, Klebsiella, Proteus, Pseudomonas aeruginosa, etc.

Cephalosporins were isolated from a fungus Cephalosporium acremonium in the middle of the 20th century and, like penicillins, by accident.

Now 5 generations of cephalosporins are known. Why did they open so many of them, you ask?

Yes, all for the same reason: to obtain the ideal cephalosporin that would meet all the needs of doctors and patients.

But there is no limit to perfection, and I think that this work will never end.

Look at examples of cephalosporins of different generations:

Generations differ from each other in the spectrum of action and level of antimicrobial activity.

For example, the first generations act well on gram-positive bacteria and are rather weak on gram-negative ones.

And the latest representatives of cephalosporins are active against a wide range of both gram-positive and gram-negative bacteria.

By the way, do you remember what gram-positive and gram-negative bacteria are?

Then I’ll add a drop of microbiology to our conversation.

What are gram-positive and gram-negative bacteria?

A long time ago, in the 19th century, there lived in Denmark a biologist named Gram. And then one day, one beautiful day for all medical science, he conducted an experiment, staining a group of bacteria in a special way.

Before him, many scientists tried to somehow systematize this company of microorganisms unfriendly to humans, but nothing good came of it.

And then... It’s done! As a result, one part of the bacteria turned bright purple (they were called gram-positive by the author), while others remained colorless (gram-negative), and an additional dye was needed to color the latter. In pictures, gram-positive bacteria are depicted as purple or blue, and gram-negative bacteria as pink:

It turned out that gram-positive microbes have a thicker cell wall that absorbs the dye well.

Gram-negative bacteria have a thinner cell wall, but it contains lipopolysaccharides, which give it special strength and protect it from the penetration of antibiotics, saliva, gastric juice, and lysozyme. Therefore, gram-negative bacteria are more resistant to antibiotics.

Look at the representatives of both:

But let's return to the conversation about cephalosporin drugs.

They also differ in bioavailability. For example, for cefixime (Suprax) it is 40-50%, and for cephalexin it reaches 95%.

Their behavior in the body is also different. For example, 1st generation drugs do not pass through the blood-brain barrier well, so they are not used for meningitis, while 3rd generation drugs are more successful in this matter than their pharmaceutical counterparts. group.

So the choice of cephalosporin directly depends on the pathogen, the clinical situation and the severity of the disease.

Indications for the use of cephalosporins

1st generation cephalosporins are most often used in the following cases:

• Infections caused by staphylococci or streptococci (if penicillins are ineffective).
• Uncomplicated skin and soft tissue infections of mild to moderate severity.

2nd generation cephalosporins:

• Infections of the respiratory tract and ENT organs - in case of ineffectiveness of penicillins or hypersensitivity to them.
• Skin and soft tissue infections.
• Gynecological infections.
• Uncomplicated urinary tract infections.

3rd generation cephalosporins:

• Complicated skin and soft tissue infections.
• Severe urinary tract infections.
• Infections caused by Pseudomonas aeruginosa.
• Nosocomial infections.
• Meningitis, sepsis.

4th generation cephalosporins:

• Nosocomial infections.
• Severe respiratory tract infections.
• Severe infections of the skin, soft tissue, bones and
• Sepsis.

5th generation cephalosporins:

• Complicated infections of the skin and its appendages, including infected diabetic foot.

General contraindications to the use of cephalosporins

• history of cephalosporins.
• When prescribing 1st generation cephalosporins, an allergy to penicillins, since in some cases cross-allergy is observed: i.e. a person with an allergic reaction to penicillins can also give it to 1st generation cephalosporins.

Most common side effects

• Allergic reactions. But their frequency is less than when using penicillins.
• Nausea, vomiting, diarrhea (for oral medications).
• Nephrotoxicity.
• Increased bleeding.
• Candidiasis of the oral cavity and vagina.

ATTENTION!

Antacids reduce the absorption of oral cephalosporins from the gastrointestinal tract, so at least 2 hours should pass between taking the antacid and the cephalosporin.

Pregnant, nursing, children (strictly as prescribed by a doctor!)

• Pregnant women can.
• Breastfeeding carefully.
• This group is also widely used in pediatric practice.

We'll probably finish our conversation for today.

It’s not an easy task to sort out antibiotics.

Next time we will continue this topic.

If you want to add, comment, or ask something, write in the comments box below.

And I say goodbye to you.

Until next time on the blog “!”

With love to you, Marina Kuznetsova

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