Analysis of a group of beta-lactam antibiotics. Beta-lactam antibiotics: list of drugs Analysis of pharmacological groups of beta-lactam antibiotics

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

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

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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.

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.

Classification of antibacterial agents

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.

Beta-lactam antibiotics. Structure and mechanism of action

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.

Medicines from the penicillin group: historical background

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 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.

Penicillin drugs

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.

Brief overview of drugs belonging to the penicillin group

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 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 the effect of each other.

Four generations of bacteria fighters

Cephalosporins are also beta-lactam antibiotics. These drugs 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.

Backup remedy

"Imipenem" is a beta-lactam antibiotic belonging to the carbapenem group. It, as well as the no less well-known “Meropenem”, is even comparable to the third and fourth generations of cephalosporins in terms of its effectiveness on 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.

Backup number two

"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.

Spectrum of action of beta-lactam antibiotics

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.

What are hospital strains?

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. reserve. 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.

When are beta-lactam antibiotics prescribed?

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, 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.

Undesirable action

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.

A few words about factors that increase bacterial resistance

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 few words in conclusion

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.

Beta-lactam antibiotics are antimicrobial agents that combine 4 groups of antibiotics 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.

The beta-lactam group includes penicillin antibiotics, cephalosporins, carbapenems and mnobactams.

A similar chemical structure determines the general mechanism of antibacterial action, which consists of disrupting the synthesis process of moray eel, the main building component of the prokaryotic membrane.

The development of cross-allergy or acquired resistance in bacteria cannot be ruled out due to the common structural component.

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 one of the most commonly used groups of antibiotics and are used everywhere for drug therapy for a wide range of diseases.

General classification of beta-lactam antibiotics:

1. Penicillins:
2. Cephalosporins, 5 generations.
3. Carbapenems.
4. Monobactams.

Full list

Instructions for most of these drugs are on the website in the ““ section.

Penicillins

Penicillins are the first antimicrobial substances that were accidentally discovered by Alexander Fleming and revolutionized the world of medicine. The natural producer is Penicillium mushrooms. When the minimum inhibitory concentration is reached, beta-lactam antibiotics have bactericidal activity (destroy pathogenic microorganisms). Penicillin has low toxicity 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.

Due to the frequent use of penicillins, microorganisms have developed defense systems against the antibacterial effects of beta-lactams:

• 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.

History of discovery

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.

Indications for the use of penicillins

Penicillins are prescribed for a wide range of diseases:

• purulent;
• sinusitis;
• otitis;
• treatment of Helicobacter pylori infection (amoxicillin);
• sepsis;
• meningococcal infections;
• osteomyelitis;
• inflammatory processes;
• diphtheria;
• sexually transmitted infections (syphilis, gonorrhea);
• pyoderma;
• infections of the pelvic organs (prostatitis, adnexitis, etc.);
• and (, scarlet fever, etc.);
• malignant carbuncle.

Contraindications and side symptoms of penicillins

The main contraindication to the use of penicillins is 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 disorders of the gastrointestinal tract () and the central nervous system (weakness, drowsiness, irritability), and the oral cavity, as well as possible swelling.

It is noted that if the dosage and duration of treatment are observed, side effects are rare.

Important features of penicillins

Patients with pathologies of kidney and liver functioning are prescribed only if the benefits of the antibiotic significantly outweigh the possible risks. If there is no relief of the symptoms of the disease 48-72 hours after the start of treatment, it is recommended to prescribe drugs of an alternative group.

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

Cephalosporins

The most extensive group of beta-lactams, 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.

History of the discovery of cephalosporins

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.

Indications for the use of cephalosporins

Drugs are 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 bacterial resistance. Cephalosporins are effective against staphylococcal and streptococcal infections of the dermis, bone tissue and joints, including MRSA (5th generation cephalosporins), respiratory tract infections, meningitis, sinusitis, tonsillitis, otitis, intra-abdominal infections, genital infections, STDs (sexually transmitted diseases ) etc.

Contraindications and side symptoms of cephalosporins

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.

Before using injectable antibiotics, a test for allergic reactions (allergy tests) is performed.

Important Features

None of the cephalosporin medications are compatible with alcohol. Violation of this rule can lead to acute and severe intoxication, damage to the liver and nervous system.

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. However, it is prohibited to use antibiotics without a doctor's prescription.

Breastfeeding should be discontinued during treatment, as the substance passes into breast milk.

Carbapenems

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 bacterial cell wall.

History of the discovery of carbapenems

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.

Indications

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

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

Contraindications and side symptoms of carbapenems

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.

Important features of 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 for 2 weeks after drug treatment. Complete incompatibility with ganciclovir was revealed. When these drugs are used in combination, convulsions are observed.

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

Monobactams

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 bacteria. 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.

Indications for monobactams

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:

• sepsis;
• 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.

Contraindications and side symptoms of monobactams

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.

Important features of monobactams

It is not advisable to prescribe it to pregnant women, because the safety of monobactams has not been studied for this category of people. It is known that the substance can diffuse through the placenta into the fetal bloodstream. Therapy by breastfeeding women is acceptable; the level of the bactericidal substance in breast milk does not exceed 1%.

It is prescribed to children in cases where other medications have not shown their therapeutic properties. Side symptoms are similar to those in adults. It is necessary to carry out a dose adjustment with a decrease in the active component. Correction is also necessary for elderly patients, since their kidney function is already slowed down and the substance is excreted from the body to a much lesser extent.

Prescribed with caution and only in life-threatening cases for patients with liver and kidney pathologies.

On our website you can get acquainted with most groups of antibiotics, complete lists of drugs included in them, classifications, history and other important information. For this purpose, a section “” has been created in the top menu of the site.

ANTIBACTERIAL DRUGS

BETA-LACTAM ANTIBIOTICS

β-lactam antibiotics (β-lactams), which are united by the presence of a β-lactam ring in their structure, include , cephalosporins, carbapenems And monobactams having a bactericidal effect. 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.

Given 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.

PENICILLINS

Penicillins are the first antimicrobial drugs developed on the basis of biologically active substances produced by microorganisms. The ancestor of all penicillins, benzylpenicillin, was obtained in the early 40s of the 20th century. Currently, the group of penicillins includes more than ten antibiotics, which, depending on the sources of production, structural features and antimicrobial activity, are divided into several subgroups (Table 1).

Table 1. Classification of penicillins

General properties:

• Bactericidal action.
• Low toxicity.
• Excretion is mainly through the kidneys.
• Wide range of dosages.
• Cross-allergy between all penicillins and some cephalosporins and carbapenems.

NATURAL PENICILLINS

Natural penicillins include essentially only benzylpenicillin. However, based on the spectrum of activity, prolonged (benzylpenicillin procaine, benzathine benzylpenicillin) and oral (phenoxymethylpenicillin, benzathine phenoxymethylpenicillin) derivatives can also be classified in this group. All of them are destroyed by β-lactamases, so they cannot be used to treat staphylococcal infections, since in most cases staphylococci produce β-lactamases.

BENZYLPENICILLIN (PENICILLIN)

It is the first natural antibiotic. Despite the fact that many other antibiotics have been introduced in the almost 60 years since its use began, penicillin continues to be one of the important drugs.

Advantages

• Powerful bactericidal effect against a number of clinically significant pathogens (streptococci, meningococci, etc.).
• Low toxicity.
• Low cost.

Flaws

• Acquired resistance of staphylococci, pneumococci, gonococci, bacteroides.
• Highly allergenic, cross-reactive with all penicillins.

Activity spectrum

Pharmacokinetics

It is destroyed in the gastrointestinal tract, so it is ineffective when taken orally. It is well absorbed when administered intramuscularly, peak concentration in the blood is reached after 30-60 minutes. Creates high concentrations in many tissues and body fluids. It penetrates poorly through the BBB and GOB into the prostate gland. Excreted by the kidneys. T 1/2 - 0.5 hours.

Adverse reactions

• Allergic reactions: rash, Quincke's edema, fever, eosinophilia. The most dangerous is anaphylactic shock, which has a mortality rate of up to 10%.
  Prevention measures
  Careful history taking, use of freshly prepared penicillin solutions, observation of the patient for 30 minutes after the first administration of penicillin, detection of hypersensitivity by skin testing (see section VI).
• Locally irritating effect, especially with intramuscular injection of potassium salt.
• Neurotoxicity: convulsions (more often in children), when using high doses of penicillin, especially in renal failure, with endolumbar administration of more than 10 thousand units of penicillin sodium salt or potassium salt.
• Electrolyte imbalance - hyperkalemia when using high doses of potassium salt in patients with renal failure (1 million units contains 1.7 mmol of potassium). In patients with heart failure, administration of large doses of sodium salt may increase edema (1 million units contains 2.0 mmol of sodium).

Drug interactions

Synergism when combined with aminoglycosides, but their cannot be mixed in one syringe, since inactivation of aminoglycosides is noted. Combinations with other antibiotics are used, for example, with macrolides for pneumonia, with chloramphenicol for meningitis.

Combination with sulfonamides should be avoided.

Indications

• Infections caused by GABHS: tonsillopharyngitis, erysipelas, scarlet fever, acute rheumatic fever.
• Community-acquired pneumococcal pneumonia.
• Meningitis in children over 2 years of age and in adults.
• Bacterial endocarditis - necessarily in combination with gentamicin or streptomycin.
• Syphilis.
• Leptospirosis.
• Borreliosis (Lyme disease).
• anthrax
• Anaerobic infections: clostridial - gas gangrene, tetanus; non-clostridial (caused by non-spore-forming anaerobes) when the process is localized above the diaphragm.
• Actinomycosis.

Dosage

Adults

For infections of moderate severity and high sensitivity of microflora - 2-4 million units/day in 4 intramuscular injections. For tonsillopharyngitis - 500 thousand units every 8-12 hours for 10 days. For severe infections - 6-12 million units/day, intramuscularly or intravenously every 4-6 hours.

When the infection is localized in a place difficult to reach for penicillin (meningitis, endocarditis) - 18-24 million units/day, in 6 injections intravenously and/or intramuscularly.

Children

Intravenously or intramuscularly - 50-100 thousand units/kg/day in 4 administrations, for tonsillopharyngitis, 500 thousand units every 12 hours for 10 days. For meningitis - 300-400 thousand units/kg/day in 6 injections intravenously and/or intramuscularly.

Release forms

Bottles of 125, 250, 500 thousand and 1 million units of powder for the preparation of a solution for injection in the form of sodium or potassium salt.

PHENOXYMETHYLPENICILLIN

Megacillin

The spectrum of activity does not differ from penicillin, but is more stable when taken orally. Absorbed from the gastrointestinal tract by 60%, and food has little effect on bioavailability. High concentrations of the drug in the blood are not created; taking 0.5 g of phenoxymethylpenicillin orally approximately corresponds to the administration of 300 thousand units of penicillin. T 1/2 - about 1 hour.

Adverse reactions

Indications

• tonsillopharyngitis;
• Year-round prevention of rheumatic fever.
• Prevention of pneumococcal infections in persons after splenectomy.

Dosage

Adults

0.25-0.5 g every 6 hours. For streptococcal tonsillopharyngitis, 0.25 g every 8 hours or 0.5 g every 12 hours, always for 10 days. For the prevention of rheumatic fever, 0.25 g every 12 hours. Take orally 1 hour before meals.

Children

Orally - 30-50 mg/kg/day in 3-4 doses. For streptococcal tonsillopharyngitis, 0.25 g every 12 hours, always for 10 days.

Release forms

Tablets of 0.1 g, 0.25 g, 0.5 g and 1.0 g; syrup; granules for preparing a suspension.

BENZATINE PHENOXYMETHYL PENICILLIN

Ospen

It is a derivative of phenoxymethylpenicillin. Compared to it, it is more stable in the gastrointestinal tract and is absorbed faster. Bioavailability is independent of food.

Indications

• Streptococcal (GABHS) infections of mild to moderate severity:
• tonsillopharyngitis;
• skin and soft tissue infections.

Dosage

Adults

Orally - 3 million units/day in 3-4 doses, regardless of food.

Children under 10 years old

Orally - 50-100 thousand units/kg/day in 3-4 doses.

Children over 10 years old

Orally - 3 million units/day in 3-4 doses.

Release forms

Tablets of 250 thousand and 500 thousand units; suspension 750 thousand units/5 ml.

PROLONGED-LONG DRUGS PENICILLIN

Long-acting penicillin preparations (depot penicillins) include (novocaine salt of benzylpenicillin), which has an average duration of action (about 24 hours), which has a long-term effect (up to 3-4 weeks), as well as their combination preparations.

These drugs are slowly absorbed when administered intramuscularly and do not create high concentrations in the blood.

Adverse reactions

Indications

• Infections caused by microorganisms highly sensitive to penicillin:
• streptococcal (GABHS) tonsillopharyngitis;
• syphilis.
• Prevention of anthrax after exposure to the spores (benzylpenicillin procaine)
• Year-round prevention of rheumatic fever and recurrent erysipelas.

BENZYLPENICILLIN PROCAINE

When administered intramuscularly, the therapeutic concentration in the blood is maintained for 12-24 hours, but the concentrations are lower than when an equivalent dose of benzylpenicillin sodium or potassium salt is administered. T 1/2 - 24 hours.

Used for mild pneumococcal pneumonia, streptococcal tonsillopharyngitis (an alternative to benzylpenicillin if frequent injections are not possible). It has a local anesthetic effect and is contraindicated if you are allergic to procaine (Novocaine).

Dosage

Adults

Intramuscularly - 600 thousand-1.2 million units/day in 1-2 injections.
For the prevention of anthrax - 1.2 million units every 12 hours for 2 months.

Children

Intramuscularly - 50-100 thousand units/kg/day in 1-2 injections.
For the prevention of anthrax - 25 thousand units/kg every 12 hours for 2 months.

Release forms

Bottles of 300 thousand, 600 thousand and 1.2 million units of powder for the preparation of solution for injection.

BENZATINE BENZYLPENICILLIN

Bicillin-1, Extensillin, Retarpen

It acts longer than benzylpenicillin procaine, up to 3-4 weeks. After intramuscular administration, peak concentrations are observed after 24 hours in children and after 48 hours in adults. T 1/2 - several days.

In recent years, pharmacokinetic studies have been carried out on domestic drugs containing benzathine benzylpenicillin (,). It has been shown that when used, the therapeutic concentration in the blood serum is maintained for no more than 14 days, which requires their more frequent administration than, for example, extensillin.

Dosage

Adults

1.2-2.4 million units once; for syphilis - 2.4 million units/day every 5-7 days (2-3 administrations); for the prevention of rheumatic fever and recurrent erysipelas - 1.2-2.4 million units once a month. The drug is administered strictly intramuscularly.

Children

Intramuscularly - 1.2 million units once; for the prevention of rheumatic fever - 600 thousand-1 million units once a month.

Release forms

Bottles of 300 thousand, 600 thousand, 1.2 million and 2.4 million units of powder for the preparation of solution for injection.

Bicillin-3

Ingredients: benzylpenicillin potassium salt, benzylpenicillin procaine and benzathine benzylpenicillin in equal quantities. Has no advantages over benzathine benzylpenicillin.

Dosage

Adults and children

Intramuscularly - 1.2 million units once.

Release forms

Bottles of 300 thousand, 600 thousand, 900 thousand and 1.2 million units of powder for the preparation of solution for injection.

Introduction

2. Bacterial complications of HIV infection and their treatment

Conclusion

Bibliography

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 antagonism.

The term was introduced into scientific literature in 1942 by Vaksman - “antibiotic - 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, delaying their growth or completely suppressing their development.”

The specificity of antibiotics in comparison with other metabolic products (alcohols, organic acids), which also suppress the growth of certain microbial species, lies in their 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 of acyclic, alicyclic structure, quinones, polypeptides, etc. are distinguished. Based on the spectrum of biological action, antibiotics can be divided into several groups:

antibacterial, having a relatively narrow spectrum of action, suppressing the development of gram-positive microorganisms and a wide spectrum of action, suppressing the development of both gram-positive and gram-negative microorganisms;

antifungal, a group of polyene antibiotics that act on microscopic fungi;

antitumor, acting on human and animal tumor cells, as well as microorganisms.

Currently, over 6,000 antibiotics have been described, but only about 150 are used in practice, since many are highly toxic to 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, cephalosporins, carbapenems and monobactams. The similarity of the chemical structure determines the same mechanism of action of all β-lactams (impaired synthesis of the bacterial cell wall), 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 effectiveness 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), ensuring 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 microbial resistance.

Due to their ability to bind to penicillin (and other BLAs), these enzymes are called 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. What is important for practice is that the lower the affinity of the interacting molecules, the higher concentrations of the antibiotic are required to suppress the function of the enzyme.

The practically important properties of beta-lactamases include:

substrate profile (the ability to preferentially hydrolyze certain BLAs, for example penicillins or cephalosporins, or both 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 a resistant clone is observed;

type of expression (constitutive or inducible). With the constitutive type, microorganisms synthesize beta-lactamases at a constant rate; with the inducible type, the amount of the synthesized enzyme increases sharply after contact with the 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 the 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, their ability to penetrate the external structures of microorganisms, and their resistance to hydrolysis by beta-lactamases.

In some betalactam-resistant bacterial strains encountered in the clinic, 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 new beta-lactam structures are promising.

When evaluating new betalactam structures, their resistance to the action of various betalactamases - renicillases and cephalosporinases of plasmid and chromosomal origin, isolated from different bacteria - is tested. If the majority of 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 beta-lactases lose the ability to hydrolyze the beta-lactam ring of antibiotics such as cephamycin C in the presence of a methoxy group or other substituents in the 6ά-position in penicillins and in the 7ά-position in cephalosporins.

The effectiveness of betalactams against gram-negative bacteria also depends on such factors 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 core 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.