Antibiotics of the penicillin series drug names. Pharmacological group - Penicillins

Antibiotics are substances that are produced by microorganisms or synthesized using medical technology from natural raw materials. These drugs are used to suppress the growth and development of colonies of pathogenic agents that have entered the human body.

Antibiotics of the penicillin group are the first drugs from this area that were used in clinical practice. And, despite the fact that almost 100 years have passed since their discovery, and the list of antimicrobial agents has been replenished with cephalosporin, fluoroquinol and other drugs, penicillin-type compounds still remain the main antibacterial drugs for stopping a huge list of infectious diseases.

A bit of history

The discovery of penicillin happened quite by accident: in 1928, a scientist working in one of the London hospitals, Alexander Fleming, discovered a mold that had grown on a nutrient medium, which was capable of destroying staphylococcus colonies.

The active substance of the microscopic mold filamentous fungus Penicillium notatum, the researcher called penicillin. Already 12 years later, the first antibiotic was isolated in its pure form, and in 1942, the Soviet microbiologist Zinaida Ermolyeva obtained a preparation from another type of fungus - Penicillium crustosum.

Since the second half of the 20th century, an unlimited amount of penicillin G (or benzylpenicillin) has become available to combat a wide variety of diseases.

Operating principle

The described active substance acts bactericidal and bacteriostatically on pathogens. The mechanism of the bactericidal scheme of the work of drugs included in the penicillin type (series) is associated with damage to the cell walls (violation of the integrity of the structure) of infectious agents, which leads to the death of microorganisms.

The bacteriostatic principle of action on pathogens is characterized by a temporary suppression of the ability of pathogens to reproduce.

The type of drug exposure is selected taking into account the severity of the development of the disease.

Most penicillins in small doses affect microbes bacteriostatically. With an increase in the amount of the drug involved, the effect changes to bactericidal. Only a doctor can choose a specific dosage of a drug of the penicillin group; it is impossible to use antibiotics for treatment on your own.

Systematization of drugs

Among the natural penicillins, in addition to benzylpenicillin (and its various salts - sodium, potassium) also include:

• Phenoxymethylpenicillin;
• Benzathine benzylpenicillin.

The basic principles for the classification of semi-synthetic types of penicillin are listed below.

• isoxazolyl-penicillins (Oxacillin, Nafcillin);
• amino-penicillins (Amoxicillin, Ampicillin);
• aminodi-penicillins (there are no medicines registered in the Russian Federation.);
• carboxy-penicillins (Carbenicillin);
• ureido-penicillins (Piperacillin, Azlocillin);
• inhibitor-protected penicillins (Piperacillin in combination with tazobactam, Ticarcillin in combination with clavulanate, Ampicillin in combination with sulbactam).

Brief description of natural medicines

Natural (natural) penicillins are drugs that have a narrow spectrum of effects on microorganisms. Due to their long (and often uncontrolled) use for medical purposes, most pathogens have managed to acquire immunity to these types of antibiotics.

Today, in the treatment of diseases, the drugs Bicillin and Benzylpenicillin are most often used, which are quite effective against some anaerobic agents, spirochetes, a number of cocci and gram-positive pathogens.

Gram-negative bacteria H.ducreyi, P.multocida, Neisseria spp., as well as Listeria, varieties of corynebacteria (in particular, C.diphtheriae) are still sensitive to natural antibiotics.

The method of using drugs to prevent the development of these pathogens is injection.

Natural penicillins, according to experts, have one major drawback: they are destroyed under the influence of beta-lactamases (enzymes that are produced by certain microorganisms). That is why natural antibiotics belonging to the penicillin group are not used to treat ailments caused by staphylococcal infections.

Description of synthesized types of drugs

A number of semi-synthetic drugs included in the penicillin antibiotic series, and united in the aminodipenicillin group, are not registered in our country. Acidocillin, Amdinocillin, Bakamdinocillin are medicines with a narrow spectrum of action and are effective against gram-negative enterobacteria.

The remaining synthesized groups of drugs are widely used in medical institutions in Russia and require more detailed consideration.

Antistaphylococcal (penicillinase-stable) drugs

Another name for this group of antibiotics is isoxazolylpenicillins. Most often, the drug Oxacillin is used in therapy. The subspecies includes several more drugs (in particular, Nafcillin, Dicloxacillin, Methicillin), which are used extremely rarely due to their high toxicity.

In terms of the spectrum of effects on pathogens, Oxacillin is similar to the drugs included in the penicillin natural series, but is slightly inferior to them in terms of activity (in particular, it is less effective against microbes that are sensitive to the effects of benzylpenicillin).

The main difference between the drug and other penicillins is resistance to beta-lactamases, which are produced by staphylococci. The practical use of Oxycillin was found in the fight against strains of this microorganism, which is the causative agent of community-acquired infections.

Aminopenicillins

This group of semi-synthetic penicillins is characterized by a wide range of effects on pathogens. The ancestor of aminopenicillins is the drug Ampicillin. In a number of parameters, it is superior to Oxycillin, but inferior to Benzylpenicillin.

Close in scope to this medication is the drug Amoxicillin.

Since these representatives of the group are susceptible to the destructive effect of beta-lactamases, medicines protected from the effects of enzymes of infectious agents by inhibitors (for example, Amoxicillin in combination with clavuanic acid, Ampicillin in combination with sulbactam) were introduced into medical practice.

The expansion of the antimicrobial spectrum of inhibitor-protected aminopenicillins occurred due to the manifestation of their activity against:

• Gram-negative bacteria (C.diversus, P.vulgaris, Klebsiella spp.);
• gonococci;
• staphylococci;
• anaerobes of the species B.fragilis.

The growth and development of microorganisms whose resistance to the penicillin type of antibiotics is not associated with the production of beta-lactamase, inhibitor-protected aminopenicillins do not affect.

Ureidopenicillins and carboxypenicillins

Representatives of these groups - semi-synthetic antibiotics of the penicillin series that stop Pseudomonas aeruginosa; the list of these drugs is quite wide, but in modern medicine they are rarely used (pathogens lose their sensitivity to them in a short time).

Medicines of the carboxypenicillin species Carbenicillin, Tikarcillin (the latter is not registered in the territory of the Russian Federation) prevent the development of colonies of gram-positive bacteria and microorganisms of the family P.aeruginosa, Enterobacteriaceae.

The most effective remedy from the group of ureidopenicillins is Piperacillin; it is used in the fight against diseases caused by Klebsiella spp.

The described antibiotics, as well as natural penicillins, are subject to the negative influence of beta-lactamases. The solution to the problem was found in the synthesis of fundamentally new antimicrobial agents, which, in addition to the active substances already mentioned, included inhibitors.

Inhibitor-protected ureidopenicillins, carboxypenicillins have a wide range of effects on most known pathogens.

Pharmacokinetics

When taken orally, the antibiotic, which is part of the penicillin series of drugs, is quickly absorbed and, penetrating into the liquid media and tissues of the body, begins to act on the colonies of pathogens.

Medicines are characterized by the ability to concentrate in the pleural, pericardial, synovial fluids and bile. Practically do not pass into the internal environment of the organs of vision and prostate, cerebrospinal fluid. In minimal proportions are found in breast milk. In small quantities penetrate the placental barrier.

If necessary (for example, when meningitis is detected in a patient), therapeutic concentrations in the cerebrospinal fluid are achieved by administering significant doses of drugs.

Part of the penicillins in tablet form is destroyed under the influence of gastrointestinal enzymes, and therefore is used parenterally.

The main indicators of the process of transporting active substances from the digestive system into the blood of frequently used medicines (in tablets) are shown in the table.

Removal of penicillins mainly (more than 60%) occurs with the help of the kidneys; some drugs are excreted in the bile. Almost all drugs of the described group are removed during hemodialysis.

Contraindications

Despite the fact that most representatives of penicillins are characterized by high efficiency in the elimination of infectious agents, it is impossible to use these drugs to treat all patients without exception.

One of the disadvantages of this kind of medication is the frequent occurrence of allergic reactions in patients (according to statistics, the percentage of manifestations of skin rashes, swelling and itching reaches 10 units).

If there is an individual intolerance to penicillin in the anamnesis, it is impossible to use medical products of this group in therapy.

Warnings

Antibiotics of the penicillin group can cause toxic side effects of non-allergic etiology, in particular:

• bouts of nausea and vomiting;
• pain in the abdomen;
• diarrhea
• pseudomembranous colitis.

When using high doses of drugs, seizures, headache, hallucinations and fever may occur.

In addition, the use of drugs of the described series is often accompanied by the development of candidiasis, intestinal dysbacteriosis, the appearance of edema, and a violation of the level of blood pressure.

It should be noted that penicillins are among the most low-toxic antibiotics, and the above side effect on the body occurs more often with independent uncontrolled use of medications (without prior consultation with a doctor).

Indications

Mostly antibiotics of the penicillin group are used to eliminate the symptoms of upper tract infections, tonsillitis, otitis media, as well as to stop the growth of colonies of infectious agents that cause inflammation of the urinary tract, the development of scarlet fever, syphilis and gonorrhea; for the prevention of rheumatism.

In addition, penicillin antibiotic therapy is involved in making such diagnoses as:

• erysipelas;
• sepsis;
• Lyme disease;
• meningitis;
• tonsillopharyngitis;
• leptospirosis;
• actinomycosis

It should be remembered that the use of drugs of the penicillin group is allowed only on prescription. Self-medication can provoke the development of superinfection or the occurrence of severe complications of the disease.

Antibiotics of the penicillin series are considered the first AMPs that were developed from the waste products of certain bacteria. In the general classification, they are in the class of beta-lactams. In addition to penicillins, this also includes carbapenems, cephalosporins, and monobactams. The similarity is due to the fact that there is a four-membered ring. All drugs from this group are used in chemotherapy. They play an important role in the treatment of infectious diseases.

Initially, all drugs of the penicillin group came from ordinary penicillin. It has been used in medicine since the 1940s. Many subgroups of both natural and synthetic origin have now been created:

1. natural penicillins.
2. Oxacillin.
3. Aminopenicillin.

Natural penicillin medicines are used in a number of cases. For example, drugs that belong to the natural group of penicillins are recommended only for the treatment of those infections whose etiology is already known. For example, this can be confirmed during diagnostic measures or by characteristic symptoms. Depending on the form and how severe the disease develops, medications are prescribed for internal or parenteral use. Penicillins from the natural group help in the treatment of rheumatism, scarlet fever, tonsillopharyngitis, erysipelas, sepsis, pneumonia.

In addition, such funds are prescribed for the treatment of other diseases that are provoked by streptococcus. For example, this applies to infectious-type endocarditis. For this disease, not only antibiotics from this group are used, but also drugs that have the following names: streptomycin, gentamicin, etc. Diseases that are caused by a meningococcal type infection can also be cured with natural penicillins. Indications for their use are leptospirosis, gangrene, Lyme disease, syphilis, actinomycosis.

By the way, it is necessary to take into account the fact that drugs with a prolonged effect do not have a high concentration in the blood, so they are not prescribed for the treatment of severe forms of the disease. The only exceptions are syphilis, tonsillopharyngitis, rheumatism and scarlet fever. If earlier medicines from this group were used to treat gonorrhea, now the causative agents of the disease have quickly adapted and become resistant to these drugs.

As for oxacillin, it is prescribed only when the disease is caused by a staphylococcal infection, and this does not depend on its location. Infection may already be confirmed in the laboratory or only suspected.

However, in any case, before prescribing such drugs to a patient, it is necessary to check whether bacteria are susceptible to their action. Medicines from the oxacillin group are prescribed in case of sepsis, pneumonia, meningitis, endocarditis caused by a bacterial infection, as well as for various lesions of bones, skin, joints, soft tissues that are caused by infections.

Aminopenicillins are prescribed in cases where the disease proceeds in a fairly mild form, and without any complications in the form of other infections. Inhibitor-protective forms of aminopenicillins are used in the case of relapses in severe illness. There are many medicines, including antibiotics in tablets. Substances are administered either orally or parenterally. Such funds are prescribed for the acute form of cystitis, pyelonephritis, pneumonia, sinusitis, exacerbation of the chronic form of bronchitis.

In addition, indications for use are intestinal diseases that are caused by infections, endocarditis, meningitis. Sometimes inhibitor-protective derivatives are prescribed by doctors for a preoperative form of prevention and in the treatment of infectious diseases of the skin and soft tissues.

What else applies?

The following drugs are also used:

1. Carboxypenicillin. Drugs from the group of carboxypenicillins are now used less and less in medicine. They can be prescribed only in the case of infections of the nosocomial type. Such drugs should be used only in complex therapy along with drugs that can affect Pseudomonas aeruginosa. As for indications for use, carboxypenicillins are prescribed for infections on the skin, bones, soft tissues, and joints. Also, these drugs will be needed for abscess, pneumonia, sepsis, infection in the pelvic organs.
2. Ureidopenicillin. Drugs from the group of ureidopenicillins are often prescribed only together with aminoglycosides. This combination helps to cope with Pseudomonas aeruginosa. Indications for use are infectious diseases of the pelvic organs, soft tissues, skin (diabetic foot is also included). In addition, such funds will be needed for peritonitis, hepatic abscess, pneumonia, lung abscess.

Mechanism of action

Preparations from the penicillin group have a bactericidal effect. They affect the penicillin-binding proteins that are found in all bacteria. These compounds act as enzymes that are already involved in the final stage of microorganism wall synthesis. As a result, the production of the substance is blocked, and the bacterium dies. In addition, clavulonic acid, tazobactam and sulbactam have been developed to inhibit certain enzymatic substances. They are part of the drugs that belong to complex penicillins.

As for the effect on the human body, carboxypenicillins, benzylpenicillins and ureidopenicillins are destroyed in the human body due to hydrochloric acid, which is part of the gastric juice. In this regard, they can only be used parenterally. Preparations that contain oxacillin, phenoxymethylpenicillin and aminopenicillin, on the contrary, are resistant to the influence of an acidic environment, and they can be used orally. By the way, amoxicillin is best absorbed through the organs of the gastrointestinal tract. As for the worst digestibility indicators, oxacillin and ampicillin have parameters of only 30%.

Substances that are part of penicillin preparations are perfectly distributed throughout the body, affecting tissues, body fluids, and organs. High concentrations will be in the kidneys, mucous membranes, intestines, lungs, genitals, fluids. A small dose can pass through breast milk and the placenta. Practically do not get to a prostate gland. Significant transformation in the liver is characteristic of ureidopenicillins and oxacillins. Other substances from this group are excreted from the body practically unchanged. In most cases, excretion is by the kidneys. The time it takes to remove the substance is about an hour. If the patient is diagnosed with renal insufficiency, then the time will increase. Almost all types of penicillins are excreted from the body through hemodialysis.

Contraindications and side effects

Like all drugs, drugs with penicillin have their own contraindications. Basically, this only applies to allergies to penicillin. People who are at risk of an allergic reaction due to intolerance to certain components should not use these medicines. The same applies to an allergic reaction to novocaine.

As for side effects, in case of overdose or improper use of drugs, there is a risk of an allergic reaction. It can be dermatitis, rash, urticaria. In rare cases, Quincke's edema, anaphylactic shock, bronchospasm, and fever appear. If a person has an anaphylactic shock, then glucocorticoids, adrenaline, oxygen therapy will be required. It is also urgent to ensure the work of the respiratory tubular organs.

As for problems with the functioning of the central nervous system, in rare cases, tremors and mental disorders appear.

Sometimes the patient has a headache, convulsions appear.

Basically, this happens in those people who suffer from kidney failure.

More often there are problems with the work of the digestive tract. A person can feel sick, there are vomiting attacks, abdominal pain, colitis. In this case, it is necessary to refuse such drugs. Additionally, if colitis is suspected, sigmoidoscopy is prescribed. To restore health, you need to return the water and electrolyte balance to normal. Sometimes taking drugs from the penicillin group also leads to a violation of these processes.

This leads to hyperkalemia, hypernatremia. As a result, blood pressure changes, edema appears. In some cases, there may be problems in the functioning of the liver, kidneys, various hematological reactions, complications of the state of the blood vessels. In rare cases, oral or vaginal candidiasis develops.

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Mushrooms are the kingdom of living organisms. Mushrooms are different: some of them get into our diet, others cause skin diseases, others are so poisonous that they can lead to death. But mushrooms of the genus Penicillium save millions of human lives from pathogenic bacteria.

Antibiotics of the penicillin series are still used in medicine.

The discovery of penicillin and its properties

In the 30s of the last century, Alexander Fleming conducted experiments with staphylococci. He studied bacterial infections. After growing a group of these pathogens in a nutrient medium, the scientist noticed that there were areas in the cup that were not surrounded by live bacteria. The investigation showed that the usual green mold, which likes to settle on stale bread, is “guilty” of these spots. The mold was called Penicillium and, as it turned out, produced a substance that kills staphylococci.

Fleming went deeper into this issue and soon isolated pure penicillin, which became the world's first antibiotic. The principle of action of the drug is as follows: when a bacterial cell divides, each half restores its cell membrane with the help of a special chemical element - peptidoglycan. Penicillin blocks the formation of this element, and the bacterial cell simply "resolves" in the environment.

Ask your question to a neurologist for free

Irina Martynova. Graduated from the Voronezh State Medical University. N.N. Burdenko. Clinical intern and neurologist of BUZ VO \"Moscow Polyclinic\".

But difficulties soon arose. Bacterial cells learned to resist the drug - they began to produce an enzyme called beta-lactamase, which destroys beta-lactams (the basis of penicillin).

Expert opinion

Astafiev Igor Valentinovich

Neurologist - City Pokrovskaya Hospital. Education: Volgograd State Medical University, Volgograd. Kabardino-Balkarian State University named after A.I. HM. Berbekova, Nalchik.

The next 10 years there was an invisible war between pathogens that destroy penicillin, and scientists that modify this penicillin. So many modifications of penicillin were born, which now form the entire penicillin series of antibiotics.

Pharmacokinetics and principle of action

The drug for any method of application spreads rapidly throughout the body, penetrating almost all its parts. Exceptions: cerebrospinal fluid, prostate gland and visual system. In these places, the concentration is very low, under normal conditions it does not exceed 1%. With inflammation, a rise of up to 5% is possible.

Antibiotics do not affect the cells of the human body, since the latter do not contain peptidoglycan.

The drug is quickly excreted from the body, after 1-3 hours most of it is excreted through the kidneys.

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Classification of antibiotics

All drugs are divided into: natural (short and prolonged action) and semi-synthetic (anti-staphylococcal, broad-spectrum drugs, antipseudomonal).

Natural

These drugs obtained directly from the mold. At the moment, most of them are outdated, as pathogens have developed immunity to them. In medicine, benzylpenicillin and Bicillin are most often used, which are effective against gram-positive bacteria and cocci, some anaerobic bacteria and spirochetes. All these antibiotics are used only in the form of injections into the muscles, since the acidic environment of the stomach quickly destroys them.

Benzylpenicillin in the form of sodium and potassium salts is a short-acting natural antibiotic. Its action stops after 3-4 hours, so frequent repeated injections are necessary.

Trying to eliminate this drawback, pharmacists have created natural long-acting antibiotics: Bicillin and novocaine salt of benzylpenicillin. These drugs are called "depot forms" because after injection into the muscle they form a "depot" in it, from which the drug is slowly absorbed into the body.

Expert opinion

Mitrukhanov Eduard Petrovich

Doctor - neurologist, city polyclinic, Moscow. Education: Russian State Medical University, Russian Medical Academy of Postgraduate Education of the Ministry of Health of the Russian Federation, Volgograd State Medical University, Volgograd.

Examples of drugs: benzylpenicillin salt (sodium, potassium or novocaine), Bicillin-1, Bicillin-3, Bicillin-5.

Semi-synthetic antibiotics of the penicillin group

Several decades after receiving penicillin pharmacists were able to isolate its main active ingredient, and the modification process began. Most drugs, after improvement, acquired resistance to the acidic environment of the stomach, and semi-synthetic penicillins began to be produced in tablets.

Isoxazolpenicillins are drugs that are effective against staphylococci. The latter have learned to produce an enzyme that destroys benzylpenicillin, and drugs from this group prevent their production of the enzyme. But you have to pay for the improvement - drugs of this type are less absorbed in the body and have a smaller spectrum of action compared to natural penicillins. Examples of drugs: Oxacillin, Nafcillin.

Aminopenicillins are broad-spectrum drugs. Inferior to benzylpenicillins in strength in the fight against gram-positive bacteria, but cover a larger range of infections. Compared to other drugs, they stay in the body longer and better penetrate some of the body's barriers. Examples of drugs: Ampicillin, Amoxicillin. You can often find Ampiox - Ampicillin + Oxacillin.

Carboxypenicillins and ureidopenicillins antibiotics effective against Pseudomonas aeruginosa. At the moment, they are practically not used, since infections quickly acquire resistance to them. Occasionally, you can find them as part of a comprehensive treatment.

Examples of drugs: Ticarcillin, Piperacillin

List of drugs

Pills

Sumamed

Active ingredient: azithromycin.

Indications: Respiratory infections.

Contraindications: intolerance, severe renal failure, children under 6 months of age.

Price: 300-500 rubles.

Oxacillin

Active ingredient: oxacillin.

Indications: infections sensitive to the drug.

Price: 30-60 rubles.

Amoxicillin Sandoz

Indications: respiratory tract infections (including tonsillitis, bronchitis), infections of the genitourinary system, skin infections, other infections.

Contraindications: intolerance, children under 3 years of age.

Price: 150 rubles.

Ampicillin trihydrate

Indications: pneumonia, bronchitis, tonsillitis, other infections.

Contraindications: hypersensitivity, liver failure.

Price: 24 rubles.

Phenoxymethylpenicillin

Active ingredient: phenoxymethylpenicillin.

Indications: streptococcal diseases, infections of mild and moderate severity.

Price: 7 rubles.

Amoxiclav

Active ingredient: amoxicillin + clavulanic acid.

Indications: infections of the respiratory tract, urinary system, infections in gynecology, other infections sensitive to amoxicillin.

Contraindications: hypersensitivity, jaundice, mononucleosis and lymphocytic leukemia.

Price: 116 rubles.

injections

Bicillin-1

Active ingredient: benzathine benzylpenicillin.

Indications: acute tonsillitis, scarlet fever, wound infections, erysipelas, syphilis, leishmaniasis.

Contraindications: hypersensitivity.

Price: 15 rubles per injection.

Ospamox

Active ingredient: amoxicillin.

Indications: infections of the lower and upper respiratory tract, gastrointestinal tract, genitourinary system, gynecological and surgical infections.

Contraindications: hypersensitivity, severe gastrointestinal infections, lymphocytic leukemia, mononucleosis.

Price: 65 rubles.

Ampicillin

Active ingredient: ampicillin.

Indications: infections of the respiratory and urinary tract, gastrointestinal tract, meningitis, endocarditis, sepsis, whooping cough.

Contraindications: hypersensitivity, impaired renal function, childhood, pregnancy.

Price: 163 rubles.

Benzylpenicillin

Indications: severe infections, congenital syphilis, abscesses, pneumonia, erysipelas, anthrax, tetanus.

Contraindications: intolerance.

Price: 2.8 rubles per injection.

Benzylpenicillin novocaine salt

Active ingredient: benzylpenicillin.

Indications: Similar to benzylpenicillin.

Contraindications: intolerance.

Price: 43 rubles for 10 injections.

For the treatment of children, Amoxiclav, Ospamox, Oxacillin are suitable. But Before using the medicine, you must always consult with your doctor to adjust the dose.

Indications for use

Antibiotics of the penicillin group are prescribed for infections, the type of antibiotics is selected based on the type of infection. It can be various cocci, bacilli, anaerobic bacteria, and so on.

Most often, antibiotics treat infections of the respiratory tract and genitourinary system.

Application features

In the case of treating children, you need to follow the instructions of the doctor, who will prescribe the desired antibiotic and adjust the dose.

In case of pregnancy, antibiotics should be used with extreme caution, as they penetrate the fetus. During lactation, it is better to switch to mixtures, as the medicine also penetrates into milk.

For the elderly, there are no special instructions, although the doctor should take into account the condition of the patient's kidneys and liver when prescribing treatment.

Contraindications and side effects

The main and often the only contraindication is individual intolerance. It occurs frequently - in about 10% of patients. Additional contraindications depend on the specific antibiotic and are prescribed in its instructions for use.

List of side effects

• The development of allergies - from itching and fever to anaphylactic shock and coma.
• Instantaneous development of an allergic reaction in response to the introduction of the drug into a vein.
• Dysbacteriosis, candidiasis.

In case of side effects, you should immediately seek medical help, stop the drug and carry out symptomatic treatment.

Antibiotics of the penicillin group are the first drugs created from the waste products of certain types of bacteria. In the general classification, penicillin antibiotics belong to the class of beta-lactam drugs. In addition to them, non-penicillin antibiotics are also included here: monobactams, cephalosporins and carbapenems.

The similarity is due to the fact that these drugs contain four-membered ring. All antibiotics of this group are used in chemotherapy and play an important role in the treatment of infectious diseases.

Properties of penicillin and its discovery

Before the discovery of antibiotics, many diseases seemed simply incurable, scientists and doctors around the world wanted to find a substance that could help defeat pathogenic microorganisms, while not causing damage to human health. People died from sepsis, wounds infected with bacteria, gonorrhea, tuberculosis, pneumonia and other dangerous and serious diseases.

A key moment in medical history is 1928 It was in this year that penicillin was discovered. Millions of human lives for this discovery are due to Sir Alexander Fleming. The accidental appearance of mold on the nutrient medium of the Penicillium notatum group in Fleming's laboratory and the observation of the scientist himself gave a chance to fight against infectious diseases.

After the discovery of penicillin, scientists faced only one task - to isolate this substance in its pure form. This case turned out to be quite complicated, but in the late 30s of the 20th century, two scientists Ernst Cheyne and Howard Flory managed to create a drug with an antibacterial effect.

Properties of antibiotics of the penicillin group

antibiotic penicillin inhibits the emergence and development pathogenic organisms such as:

This is only a small list of those pathogenic bacteria in which penicillin and all drugs of the penicillin series suppress vital activity.

The antibiotic effect of penicillin is bactericidal or bacteriostatic. In the latter case, we are talking about the complete destruction of pathogenic organisms that caused the disease, most often acute and extremely severe. For diseases of moderate severity, antibiotics with a bacteriostatic effect are used - they do not allow bacteria to divide.

Penicillin is an antibiotic with a bactericidal effect. Microbes in their structure have a cell wall in which the main substance is peptidoglycan. This substance gives the bacterial cell stability, preventing it from dying even in very unsuitable conditions for life. By acting on the cell wall, penicillin destroys its integrity and disables its work.

In the human body, cell membranes do not contain peptidoglycan and therefore antibiotics of the penicillin group do not have a negative effect on our body. Also, we can talk about a small toxicity of these funds.

Penicillins have a wide range of dosages used, which is safer for the human body, since it makes it possible for a particular patient to choose a therapeutic dosage with minimal side effects.

The main part of penicillin is excreted from the body by the kidneys with urine (more than 70%). Some antibiotics of the penicillin group are excreted using the biliary system, that is, they are excreted with bile.

List of drugs and classification of penicillins

The basis of the chemical compound of the penicillin group is beta-lactam ring, therefore they belong to beta-lactama drugs.

Since penicillin has been used in medical practice for more than 80 years, some microorganisms have developed resistance to this antibiotic in the form of the beta-lactamase enzyme. The mechanism of the enzyme's work consists in the connection of the hydrolytic enzyme of a pathogenic bacterium with the beta-lactam ring, which in turn facilitates their binding, and as a result, the inactivation of the drug.

To date, semi-synthetic antibiotics are most often used: the chemical composition of a natural antibiotic is taken as a basis and subjected to useful modifications. Due to this, humanity can still resist various bacteria that constantly produce different antibiotic resistance mechanisms.

To date, the Federal Guidelines for the Use of Medicinal Products provides such a classification of penicillins.

Short acting natural antibiotics

Natural antibiotics do not contain beta-lactamase inhibitors, so they are never used against diseases caused by staphylococcus aureus.

Benzylpenicillin is active during treatment:

Side effects: for all antibiotics of the penicillin series, the main side effect is an allergic response of the body in the form of urticaria, anaphylactic shock, hyperthermia, Quincke's edema, skin rashes, nephritis. Possible failures in the work of the heart. During the introduction of significant dosages - convulsions (in children).

Restrictions on use and contraindications: hay fever, allergy to penicillin, impaired kidney function, arrhythmia, bronchial asthma.

Natural antibiotics with prolonged action

Benzylpenicillin benzathine is used in cases of:

• inflammation of the tonsils;
• syphilis;
• wound infections;
• scarlet fever.

It is also used to prevent complications after surgery.

Side effects: anemia, allergic response, abscess at the injection site of the antibiotic, headache, thrombocytopenia and leukopenia.

Contraindications: hay fever, bronchial asthma, propensity to allergies to penicillin.

Benzylpenicillin procaine is used in the treatment of:

It is used for relapses of erysipelas and rheumatism.

Side effect: convulsions, nausea, allergic reaction.

Contraindications: hypersensitivity to procaine and penicillin.

Antistaphylococcal agents

Oxacillin is the main representative of this group of antibiotics. The result of treatment is similar to benzylpenicillin, but unlike the second, this drug can destroy staphylococcal infections.

Side effects: skin rashes, urticaria. Rarely - anaphylactic shock, edema, fever, digestive disorders, vomiting, nausea, hematuria (in children), jaundice.

Contraindications: allergic reactions to penicillin.

Broad spectrum drugs

As an active substance, ampicillin is used in many antibiotics. Used to treat acute infections of the urinary and respiratory tract, infectious diseases of the digestive system, chlamydial infections, endocarditis, meningitis.

List of antibiotics that contain ampicillin: Ampicillin sodium salt, Ampicillin trihydrate, Ampicillin-Inotec, Ampicillin AMP-Forte, Ampicillin-AKOS, etc.

Amoxicillin is modified derivative of ampicillin. It is considered the main antibiotic, which is taken orally only. It is used for meningococcal infections, acute respiratory diseases, Lyme disease, inflammation of the gastrointestinal tract. It is used to prevent anthrax in women during pregnancy and children.

List of antibiotics that contain amoxicillin: Amoxicillin Sandoz, Amoxicar, Amoxicillin DS, Amoxicillin-ratiopharm, etc.

Side effects: dysbacteriosis, dyspeptic disorders, allergies, candidiasis, superinfection, CNS disorders.

Contraindications for this group of penicillins: hypersensitivity, mononucleosis, impaired liver function. Ampicillin is prohibited for newborns up to one month.

Antipseudomonal antibiotics

Carboxypenicillins contain active ingredient - carbenicillin. In this case, the name of the antibiotic is the same as the active ingredient. It is used in the treatment of diseases that are caused by Pseudomonas aeruginosa. Today, they are almost never used in medicine due to the availability of more powerful drugs.

Ureidopenicillins include: Azlocillin, Piperacillin, Mezlocillin.

Side effect: nausea, eating disorders, urticaria, vomiting. Possible headache, drug-induced fever, superinfection, impaired renal function.

Contraindications: pregnancy, high sensitivity to penicillin.

Features of the use of antibiotics of the penicillin group in children

The use of antibiotics in children's treatment is constantly given great attention, since the child's body has not yet fully formed and most organs and systems still not fully functional. Therefore, the choice of antibiotics for infants and growing children, doctors must be treated with great responsibility.

Penicillin in newborns is used for toxic diseases and sepsis. In the first years of life in children, it is used to treat otitis, pneumonia, meningitis, pleurisy.

With angina, SARS, cystitis, bronchitis, sinusitis, as a rule, children are prescribed Flemoxin, Amoxicillin, Augmentin, Amoxiclav. These antibiotics in relation to the child's body are the least toxic and the most effective.

Dysbacteriosis is one of the complications of antibiotic therapy, since beneficial microflora in children dies simultaneously with pathogenic microorganisms. Therefore, antibiotic treatment must be combined with the intake of probiotics. A rare side effect is an allergy to penicillin. in the form of a skin rash.

In infants, the excretory work of the kidneys is not sufficiently developed and the accumulation of penicillin is likely in the body. The result of this is the appearance of seizures.

Treatment with any antibiotics, even the latest generation, always has a significant impact on health. Naturally, they relieve the main infectious disease, but overall immunity is also significantly reduced. Since not only pathogenic bacteria die, but also healthy microflora. Therefore, it will take some time to restore the protective forces. If side effects are pronounced, especially those associated with the gastrointestinal tract, then a sparing diet is necessary.

Be sure to use probiotics and prebiotics (Bifidumbacterin, Linex, Bifiform, Acipol, etc.). The beginning of the reception must occur simultaneously with the start of the use of an antibacterial agent. At the same time, after a course of antibiotics, prebiotics and probiotics must be used for about 14 more days to populate the stomach with beneficial bacteria.

When antibiotics have a toxic effect on the liver, the use of hepatoprotectors can be recommended. These drugs will protect healthy liver cells and repair damaged ones.

Since immunity is reduced, the body is particularly susceptible to colds. Therefore, you need to take care of yourself and not overcool. Use immunomodulators, while it is desirable that they be of plant origin (purple Echinacea, Immunal).

If the disease is of viral etiology, then in this case antibiotics are powerless, even the latest generation and a wide spectrum of action. They can only serve as a prophylaxis in joining a bacterial viral infection. Antivirals are used to treat viruses.

To reduce the need to use antibiotics and get sick less often, it is necessary to lead a healthy lifestyle. The most important thing is not to overdo it with the use of antibacterial agents in order to prevent the development of bacterial resistance to them. Otherwise, it will not be possible to cure any infection. Therefore, always consult your doctor before using any antibiotic.

Penicillins (penicillina)- a group of antibiotics produced by many types of molds of the genus penicillium, active against most gram-positive, as well as some gram-negative microorganisms (gonococci, meningococci and spirochetes). Penicillins belong to the so-called. beta-lactam antibiotics (beta-lactams).

Beta-lactams are a large group of antibiotics, which have in common the presence of a four-membered beta-lactam ring in the molecule structure. Beta-lactams include penicillins, cephalosporins, carbapenems, monobactams. Beta-lactams are the most numerous group of antimicrobial drugs used in clinical practice, which occupies a leading position in the treatment of most infectious diseases.

Historical information. In 1928, the English scientist A. Fleming, who worked at St. Mary`s Hospital in London, discovered the ability of a green mold filamentous fungus (Penicillium notatum) cause the death of staphylococci in cell culture. The active substance of the fungus, which has antibacterial activity, A. Fleming called penicillin. In 1940, in Oxford, a group of researchers led by H.W. Flory and E.B. Cheyna isolated in pure form significant amounts of the first penicillin from culture Penicillium notatum. In 1942, the outstanding domestic researcher Z.V. Yermolyeva received penicillin from a mushroom Penicillium crustosum. Since 1949, practically unlimited quantities of benzylpenicillin (penicillin G) have become available for clinical use.

The penicillin group includes natural compounds produced by various types of molds. Penicillium, and a number of semi-synthetic ones. Penicillins (like other beta-lactams) have a bactericidal effect on microorganisms.

The most common properties of penicillins include: low toxicity, a wide range of dosages, cross-allergy between all penicillins and partially cephalosporins and carbapenems.

Antibacterial effect beta-lactams is associated with their specific ability to disrupt the synthesis of the bacterial cell wall.

The cell wall of bacteria has a rigid structure, it gives the microorganisms their shape and protects them from destruction. It is based on a heteropolymer - peptidoglycan, consisting of polysaccharides and polypeptides. Its cross-linked mesh structure gives the cell wall strength. The composition of polysaccharides includes such amino sugars as N-acetylglucosamine, as well as N-acetylmuramic acid, which is found only in bacteria. Amino sugars are associated with short peptide chains, including some L- and D-amino acids. In gram-positive bacteria, the cell wall contains 50-100 layers of peptidoglycan, in gram-negative bacteria - 1-2 layers.

About 30 bacterial enzymes are involved in the process of peptidoglycan biosynthesis, this process consists of 3 stages. It is believed that penicillins disrupt the late stages of cell wall synthesis, preventing the formation of peptide bonds by inhibiting the transpeptidase enzyme. Transpeptidase is one of the penicillin-binding proteins that beta-lactam antibiotics interact with. In addition to transpeptidases, penicillin-binding proteins, enzymes involved in the final stages of bacterial cell wall formation, include carboxypeptidases and endopeptidases. They are present in all bacteria (for example, in Staphylococcus aureus there are 4 of them Escherichia coli- 7). Penicillins bind to these proteins at different rates to form a covalent bond. In this case, inactivation of penicillin-binding proteins occurs, the strength of the bacterial cell wall is impaired, and the cells undergo lysis.

Pharmacokinetics. When taken orally, penicillins are absorbed and distributed throughout the body. Penicillins penetrate well into tissues and body fluids (synovial, pleural, pericardial, bile), where they quickly reach therapeutic concentrations. The exceptions are the cerebrospinal fluid, the internal environment of the eye and the secret of the prostate gland - here the concentrations of penicillins are low. The concentration of penicillins in the cerebrospinal fluid may be different depending on the conditions: normally - less than 1% of serum, with inflammation it can increase up to 5%. Therapeutic concentrations in the cerebrospinal fluid are created with meningitis and the administration of drugs in high doses. Penicillins are rapidly excreted from the body, mainly by the kidneys by glomerular filtration and tubular secretion. Their half-life is short (30-90 minutes), the concentration in the urine is high.

There are several classifications Drugs belonging to the group of penicillins: by molecular structure, by sources of production, by spectrum of activity, etc.

According to the classification presented by D.A. Kharkevich (2006), penicillins are classified as follows (the classification is based on a number of features, including differences in the ways of obtaining):

I. Preparations of penicillins obtained by biological synthesis (biosynthetic penicillins):

I.1. For parenteral administration (destroyed in the acidic environment of the stomach):

Short acting:

benzylpenicillin (sodium salt),

benzylpenicillin (potassium salt);

Long lasting:

benzylpenicillin (novocaine salt),

Bicillin-1,

Bicillin-5.

I.2.

phenoxymethylpenicillin (penicillin V).

II. Semi-synthetic penicillins

II.1. For parenteral and enteral administration (acid-resistant):

Penicillinase resistant:

oxacillin (sodium salt),

nafcillin;

Broad spectrum of action:

ampicillin,

amoxicillin.

II.2. For parenteral administration (destroyed in the acidic environment of the stomach)

Broad spectrum of action, including Pseudomonas aeruginosa:

carbenicillin (disodium salt),

ticarcillin,

azlocillin.

II.3. For enteral administration (acid-resistant):

carbenicillin (indanyl sodium),

carfecillin.

According to the classification of penicillins given by I.B. Mikhailov (2001), penicillins can be divided into 6 groups:

1. Natural penicillins (benzylpenicillins, bicillins, phenoxymethylpenicillin).

2. Isoxazolpenicillins (oxacillin, cloxacillin, flucloxacillin).

3. Amidinopenicillins (amdinocillin, pivamdinocillin, bacamdinocillin, acidocillin).

4. Aminopenicillins (ampicillin, amoxicillin, talampicillin, bacampicillin, pivampicillin).

5. Carboxypenicillins (carbenicillin, carfecillin, carindacillin, ticarcillin).

6. Ureidopenicillins (azlocillin, mezlocillin, piperacillin).

The source of receipt, the spectrum of action, as well as the combination with beta-lactamases, were taken into account when creating the classification given in the Federal Guide (formular system), edition VIII.

1. Natural:

benzylpenicillin (penicillin G),

phenoxymethylpenicillin (penicillin V),

benzathine benzylpenicillin,

benzylpenicillin procaine,

benzathine phenoxymethylpenicillin.

2. Antistaphylococcal:

oxacillin.

3. Extended spectrum (aminopenicillins):

ampicillin,

amoxicillin.

4. Active towards Pseudomonas aeruginosa:

Carboxypenicillins:

ticarcillin.

Ureidopenicillins:

azlocillin,

piperacillin.

5. Combined with beta-lactamase inhibitors (inhibitor-protected):

amoxicillin / clavulanate,

ampicillin/sulbactam,

ticarcillin/clavulanate.

Natural (natural) penicillins are narrow-spectrum antibiotics that affect Gram-positive bacteria and cocci. Biosynthetic penicillins are obtained from a culture medium on which certain mold strains are grown. (Penicillium). There are several varieties of natural penicillins, one of the most active and persistent of them is benzylpenicillin. In medical practice, benzylpenicillin is used in the form of various salts - sodium, potassium and novocaine.

All natural penicillins have similar antimicrobial activity. Natural penicillins are destroyed by beta-lactamases, therefore, they are ineffective for the treatment of staphylococcal infections, because. in most cases, staphylococci produce beta-lactamase. They are effective mainly against gram-positive microorganisms (incl. Streptococcus spp., including Streptococcus pneumoniae, Enterococcus spp.), Bacillus spp., Listeria monocytogenes, Erysipelothrix rhusiopathiae, Gram-negative cocci (Neisseria meningitidis, Neisseria gonorrhoeae), some anaerobes (Peptostreptococcus spp., Fusobacterium spp.), spirochete (Treponema spp., Borrelia spp., Leptospira spp.). Gram-negative organisms are usually resistant, except Haemophilus ducreyi and Pasteurella multocida. With regard to viruses (causative agents of influenza, poliomyelitis, smallpox, etc.), mycobacterium tuberculosis, the causative agent of amoebiasis, rickettsia, fungi, penicillins are ineffective.

Benzylpenicillin is active mainly against gram-positive cocci. The spectra of antibacterial action of benzylpenicillin and phenoxymethylpenicillin are almost identical. However, benzylpenicillin is 5-10 times more active than phenoxymethylpenicillin against sensitive Neisseria spp. and some anaerobes. Phenoxymethylpenicillin is prescribed for infections of moderate severity. The activity of penicillin preparations is determined biologically by the antibacterial effect on a specific strain of Staphylococcus aureus. The activity of 0.5988 μg of chemically pure crystalline sodium salt of benzylpenicillin is taken per unit of action (1 ED).

Significant disadvantages of benzylpenicillin are its instability to beta-lactamases (when the beta-lactam ring is enzymatically cleaved by beta-lactamases (penicillinases) with the formation of penicillanic acid, the antibiotic loses its antimicrobial activity), slight absorption in the stomach (necessitates injection routes of administration) and relatively low activity against most Gram-negative organisms.

Under normal conditions, benzylpenicillin preparations do not penetrate well into the cerebrospinal fluid, however, with inflammation of the meninges, the permeability through the BBB increases.

Benzylpenicillin, used in the form of highly soluble sodium and potassium salts, acts for a short time - 3-4 hours, because. is rapidly excreted from the body, and this requires frequent injections. In this regard, poorly soluble salts of benzylpenicillin (including novocaine salt) and benzathine benzylpenicillin have been proposed for use in medical practice.

Prolonged forms of benzylpenicillin, or depot-penicillins: Bicillin-1 (benzathine benzylpenicillin), as well as combined drugs based on them - Bicillin-3 (benzathine benzylpenicillin + benzylpenicillin sodium + benzylpenicillin novocaine salt), Bitsillin-5 (benzathine benzylpenicillin + benzylpenicillin novocaine salt) ), are suspensions that can only be administered intramuscularly. They are slowly absorbed from the injection site, creating a depot in muscle tissue. This allows you to maintain the concentration of the antibiotic in the blood for a significant time and thus reduce the frequency of drug administration.

All salts of benzylpenicillin are used parenterally, tk. they are destroyed in the acidic environment of the stomach. Of the natural penicillins, only phenoxymethylpenicillin (penicillin V) has acid-stable properties, although to a weak degree. Phenoxymethylpenicillin differs chemically from benzylpenicillin by the presence of a phenoxymethyl group instead of a benzyl group in the molecule.

Benzylpenicillin is used for infections caused by streptococci, including Streptococcus pneumoniae(community-acquired pneumonia, meningitis), Streptococcus pyogenes(streptococcal tonsillitis, impetigo, erysipelas, scarlet fever, endocarditis), with meningococcal infections. Benzylpenicillin is the antibiotic of choice in the treatment of diphtheria, gas gangrene, leptospirosis, and Lyme disease.

Bicillins are indicated, first of all, if it is necessary to maintain effective concentrations in the body for a long time. They are used for syphilis and other diseases caused by pale treponema (yaws), streptococcal infections (excluding infections caused by group B streptococci) - acute tonsillitis, scarlet fever, wound infections, erysipelas, rheumatism, leishmaniasis.

In 1957, 6-aminopenicillanic acid was isolated from natural penicillins and the development of semi-synthetic drugs began on its basis.

6-Aminopenicillanic acid - the basis of the molecule of all penicillins ("penicillin core") - a complex heterocyclic compound consisting of two rings: thiazolidine and beta-lactam. A side radical is associated with the beta-lactam ring, which determines the essential pharmacological properties of the resulting drug molecule. In natural penicillins, the structure of the radical depends on the composition of the medium on which they grow. Penicillium spp.

Semi-synthetic penicillins are obtained by chemical modification by adding various radicals to the molecule of 6-aminopenicillanic acid. Thus, penicillins were obtained with certain properties:

Resistant to the action of penicillinases (beta-lactamase);

Acid-resistant, effective when administered orally;

Possessing a wide spectrum of action.

Isoxazolpenicillins (isoxazolyl penicillins, penicillinase-stable, antistaphylococcal penicillins). Most staphylococci produce a specific enzyme beta-lactamase (penicillinase) and are resistant to benzylpenicillin (80-90% of strains are penicillinase-forming). Staphylococcus aureus).

The main antistaphylococcal drug is oxacillin. The group of penicillinase-resistant drugs also includes cloxacillin, flucloxacillin, methicillin, nafcillin and dicloxacillin, which, due to high toxicity and / or low efficacy, have not found clinical use.

The spectrum of antibacterial action of oxacillin is similar to that of benzylpenicillin, but due to the resistance of oxacillin to penicillinase, it is active against penicillinase-forming staphylococci that are resistant to benzylpenicillin and phenoxymethylpenicillin, as well as resistant to other antibiotics.

By activity against gram-positive cocci (including staphylococci that do not produce beta-lactamase), isoxazolpenicillins, incl. oxacillin are significantly inferior to natural penicillins, therefore, in diseases caused by microorganisms sensitive to benzylpenicillin, they are less effective than the latter. Oxacillin is not active against gram-negative bacteria (except Neisseria spp.), anaerobes. In this regard, drugs of this group are indicated only in cases where it is known that the infection is caused by penicillinase-forming strains of staphylococci.

The main pharmacokinetic differences between isoxazolpenicillins and benzylpenicillin:

Rapid, but not complete (30-50%) absorption from the gastrointestinal tract. You can use these antibiotics both parenterally (in / m, in / in) and inside, but 1-1.5 hours before meals, because. they have low resistance to hydrochloric acid;

A high degree of binding to plasma albumin (90-95%) and the inability to remove isoxazolpenicillins from the body during hemodialysis;

Not only renal, but also hepatic excretion, no need to adjust the dosing regimen in mild renal failure.

The main clinical value of oxacillin is the treatment of staphylococcal infections caused by penicillin-resistant strains. Staphylococcus aureus(excluding infections caused by methicillin-resistant Staphylococcus aureus, MRSA). It should be borne in mind that strains are common in hospitals Staphylococcus aureus resistant to oxacillin and methicillin (methicillin, the first penicillinase-resistant penicillin, has been discontinued). Nosocomial and community-acquired strains Staphylococcus aureus Oxacillin/methicillin-resistant bacteria are usually multi-resistant—they are resistant to all other beta-lactams, and often to macrolides, aminoglycosides, and fluoroquinolones. The drugs of choice for MRSA infections are vancomycin or linezolid.

Nafcillin is slightly more active than oxacillin and other penicillinase-resistant penicillins (but less active than benzylpenicillin). Nafcillin penetrates through the BBB (its concentration in the cerebrospinal fluid is sufficient to treat staphylococcal meningitis), is excreted mainly with bile (the maximum concentration in bile is much higher than serum), to a lesser extent - by the kidneys. Can be used orally and parenterally.

Amidinopenicillins - These are penicillins of a narrow spectrum of action, but with predominant activity against gram-negative enterobacteria. Amidinopenicillin preparations (amdinocillin, pivamdinocillin, bacamdinocillin, acidocillin) are not registered in Russia.

Penicillins with an extended spectrum of activity

In accordance with the classification presented by D.A. Kharkevich, semi-synthetic broad-spectrum antibiotics are divided into the following groups:

I. Drugs that do not affect Pseudomonas aeruginosa:

Aminopenicillins: ampicillin, amoxicillin.

II. Drugs active against Pseudomonas aeruginosa:

Carboxypenicillins: carbenicillin, ticarcillin, carfecillin;

Ureidopenicillins: piperacillin, azlocillin, mezlocillin.

Aminopenicillins - broad-spectrum antibiotics. All of them are destroyed by beta-lactamases of both gram-positive and gram-negative bacteria.

Amoxicillin and ampicillin are widely used in medical practice. Ampicillin is the ancestor of the aminopenicillin group. With regard to gram-positive bacteria, ampicillin, like all semi-synthetic penicillins, is inferior in activity to benzylpenicillin, but superior to oxacillin.

Ampicillin and amoxicillin have similar action spectra. Compared to natural penicillins, the antimicrobial spectrum of ampicillin and amoxicillin extends to susceptible strains of enterobacteria, Escherichia coli, Proteus mirabilis, Salmonella spp., Shigella spp., Haemophilus influenzae; better than natural penicillins act on Listeria monocytogenes and susceptible enterococci.

Of all oral beta-lactams, amoxicillin has the highest activity against Streptococcus pneumoniae, resistant to natural penicillins.

Ampicillin is not effective against penicillinase-forming strains Staphylococcus spp., all strains Pseudomonas aeruginosa, most strains Enterobacter spp., Proteus vulgaris(indole positive).

Combined preparations are produced, for example, Ampiox (ampicillin + oxacillin). The combination of ampicillin or benzylpenicillin with oxacillin is rational, because. the spectrum of action with this combination becomes wider.

The difference between amoxicillin (which is one of the leading oral antibiotics) and ampicillin is its pharmacokinetic profile: when taken orally, amoxicillin is more quickly and well absorbed in the intestine (75-90%) than ampicillin (35-50%), bioavailability does not depend on food intake . Amoxicillin penetrates better into some tissues, incl. into the bronchopulmonary system, where its concentration is 2 times higher than the concentration in the blood.

The most significant differences in the pharmacokinetic parameters of aminopenicillins from benzylpenicillin:

Possibility of appointment inside;

Insignificant binding to plasma proteins - 80% of aminopenicillins remain in the blood in free form - and good penetration into tissues and body fluids (with meningitis, concentrations in the cerebrospinal fluid can be 70-95% of concentrations in the blood);

The multiplicity of appointment of combined drugs - 2-3 times a day.

The main indications for the appointment of aminopenicillins are infections of the upper respiratory tract and ENT organs, infections of the kidneys and urinary tract, infections of the gastrointestinal tract, eradication Helicobacter pylori(amoxicillin), meningitis.

A feature of the undesirable effect of aminopenicillins is the development of an "ampicillin" rash, which is a maculopapular rash of a non-allergic nature, which quickly disappears when the drug is discontinued.

One of the contraindications to the appointment of aminopenicillins is infectious mononucleosis.

Antipseudomonal penicillins

These include carboxypenicillins (carbenicillin, ticarcillin) and ureidopenicillins (azlocillin, piperacillin).

Carboxypenicillins - These are antibiotics that have a spectrum of antimicrobial activity similar to aminopenicillins (with the exception of the action on Pseudomonas aeruginosa). Carbenicillin is the first antipseudomonal penicillin, inferior in activity to other antipseudomonas penicillins. Carboxypenicillins act on Pseudomonas aeruginosa (Pseudomonas aeruginosa) and indole-positive proteus species (Proteus spp.) resistant to ampicillin and other aminopenicillins. The clinical significance of carboxypenicillins is currently declining. Although they have a wide spectrum of action, they are inactive against most strains. Staphylococcus aureus, Enterococcus faecalis, Klebsiella spp., Listeria monocytogenes. Almost do not pass through the BBB. Multiplicity of appointment - 4 times a day. Secondary resistance of microorganisms develops rapidly.

Ureidopenicillins - these are also antipseudomonal antibiotics, their spectrum of action coincides with carboxypenicillins. The most active drug from this group is piperacillin. Of the drugs in this group, only azlocillin retains its importance in medical practice.

Ureidopenicillins are more active than carboxypenicillins in relation to Pseudomonas aeruginosa. They are also used in the treatment of infections caused by Klebsiella spp.

All antipseudomonal penicillins are destroyed by beta-lactamases.

Pharmacokinetic features of ureidopenicillins:

Enter only parenterally (in / m and / in);

Excretion involves not only the kidneys, but also the liver;

Multiplicity of application - 3 times a day;

Secondary bacterial resistance develops rapidly.

Due to the emergence of strains with high resistance to antipseudomonal penicillins and the lack of advantages over other antibiotics, antipseudomonal penicillins have practically lost their significance.

The main indications for these two groups of antipseudomonal penicillins are nosocomial infections caused by susceptible strains. Pseudomonas aeruginosa, in combination with aminoglycosides and fluoroquinolones.

Penicillins and other beta-lactam antibiotics have high antimicrobial activity, but many of them can develop microbial resistance.

This resistance is due to the ability of microorganisms to produce specific enzymes - beta-lactamases (penicillinases), which destroy (hydrolyze) the beta-lactam ring of penicillins, which deprives them of antibacterial activity and leads to the development of resistant strains of microorganisms.

Some semi-synthetic penicillins are resistant to the action of beta-lactamases. In addition, to overcome acquired resistance, compounds have been developed that can irreversibly inhibit the activity of these enzymes, the so-called. beta-lactamase inhibitors. They are used in the creation of inhibitor-protected penicillins.

Beta-lactamase inhibitors, like penicillins, are beta-lactam compounds, but they themselves have minimal antibacterial activity. These substances bind irreversibly to beta-lactamases and inactivate these enzymes, thereby protecting beta-lactam antibiotics from hydrolysis. Beta-lactamase inhibitors are most active against beta-lactamases encoded by plasmid genes.

Inhibitor-protected penicillins are a combination of a penicillin antibiotic with a specific beta-lactamase inhibitor (clavulanic acid, sulbactam, tazobactam). Beta-lactamase inhibitors are not used alone, but are used in combination with beta-lactams. This combination allows you to increase the resistance of the antibiotic and its activity against microorganisms that produce these enzymes (beta-lactamases): Staphylococcus aureus, haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Escherichia coli, Klebsiella spp., Proteus spp., anaerobes, incl. Bacteroides fragilis. As a result, strains of microorganisms resistant to penicillins become sensitive to the combined drug. The spectrum of antibacterial activity of inhibitor-protected beta-lactams corresponds to the spectrum of penicillins contained in their composition, only the level of acquired resistance differs. Inhibitor-protected penicillins are used to treat infections of various localizations and for perioperative prophylaxis in abdominal surgery.

Inhibitor-protected penicillins include amoxicillin/clavulanate, ampicillin/sulbactam, amoxicillin/sulbactam, piperacillin/tazobactam, ticarcillin/clavulanate. Ticarcilin/clavulanate has antipseudomonal activity and is active against Stenotrophomonas maltophilia. Sulbactam has its own antibacterial activity against gram-negative cocci of the family Neisseriaceae and families of non-fermenting bacteria Acinetobacter.

Indications for the use of penicillins

Penicillins are used for infections caused by susceptible pathogens. They are mainly used for infections of the upper respiratory tract, in the treatment of tonsillitis, scarlet fever, otitis media, sepsis, syphilis, gonorrhea, gastrointestinal infections, urinary tract infections, etc.

It is necessary to use penicillins only as directed and under the supervision of a physician. It must be remembered that the use of insufficient doses of penicillins (as well as other antibiotics) or too early termination of treatment can lead to the development of resistant strains of microorganisms (especially natural penicillins). If resistance occurs, further antibiotic therapy should be continued.

The use of penicillins in ophthalmology. In ophthalmology, penicillins are applied topically in the form of instillations, subconjunctival and intravitreal injections. Penicillins do not pass well through the blood-ophthalmic barrier. Against the background of the inflammatory process, their penetration into the internal structures of the eye increases and the concentrations in them reach therapeutically significant. Thus, when instilled into the conjunctival sac, therapeutic concentrations of penicillins are determined in the stroma of the cornea; when applied topically, they practically do not penetrate into the moisture of the anterior chamber. With subconjunctival administration, drugs are determined in the cornea and moisture of the anterior chamber of the eye, in the vitreous body - concentrations below therapeutic.

Solutions for topical application are prepared extempore. Penicillins are used to treat gonococcal conjunctivitis (benzylpenicillin), keratitis (ampicillin, benzylpenicillin, oxacillin, piperacillin, etc.), canaliculitis, especially caused by actinomycetes (benzylpenicillin, phenoxymethylpenicillin), orbital abscess and phlegmon (ampicillin / clavulanate, ampicillin / sulbactam, phenoxy, phenoxy). etc.) and other eye diseases. In addition, penicillins are used to prevent infectious complications in eyelid and orbit injuries, especially when a foreign body penetrates into the tissues of the orbit (ampicillin / clavulanate, ampicillin / sulbactam, etc.).

The use of penicillins in urological practice. In urological practice, inhibitor-protected drugs are widely used among penicillin antibiotics (the use of natural penicillins, as well as the use of semi-synthetic penicillins as drugs of choice, is considered unjustified due to the high level of resistance of uropathogenic strains.

Side effects and toxic effects of penicillins. Penicillins have the lowest toxicity among antibiotics and a wide range of therapeutic effects (especially natural ones). Most serious side effects are associated with hypersensitivity to them. Allergic reactions are observed in a significant number of patients (according to various sources, from 1 to 10%). Penicillins are more likely than drugs of other pharmacological groups to cause drug allergies. In patients who had allergic reactions to the introduction of penicillins in history, with subsequent use, these reactions are observed in 10-15% of cases. Less than 1% of people who have not previously experienced such reactions develop an allergic reaction to penicillin with repeated administration.

Penicillins can cause an allergic reaction at any dose and in any dosage form.

When using penicillins, both immediate and delayed allergic reactions are possible. It is believed that the allergic reaction to penicillins is associated mainly with the intermediate product of their metabolism - the penicillin group. It is called the major antigenic determinant and is formed when the beta-lactam ring is broken. Small antigenic determinants of penicillins include, in particular, unchanged molecules of penicillins, benzylpenicilloate. They are formed in vivo, but are also determined in solutions of penicillins prepared for administration. It is believed that early allergic reactions to penicillins are mediated mainly by IgE antibodies to small antigenic determinants, delayed and late (urticaria) - usually by IgE antibodies to a large antigenic determinant.

Hypersensitivity reactions are caused by the formation of antibodies in the body and usually occur a few days after the start of penicillin use (the timing can vary from several minutes to several weeks). In some cases, allergic reactions are manifested in the form of skin rash, dermatitis, fever. In more severe cases, these reactions are manifested by swelling of the mucous membranes, arthritis, arthralgia, kidney damage and other disorders. Possible anaphylactic shock, bronchospasm, pain in the abdomen, swelling of the brain and other manifestations.

A severe allergic reaction is an absolute contraindication to the introduction of penicillins in the future. The patient must be explained that even a small amount of penicillin that has entered the body with food or during a skin test can be deadly for him.

Sometimes the only symptom of an allergic reaction to penicillins is fever (it can be constant, remittent or intermittent in nature, sometimes accompanied by chills). Fever usually disappears within 1-1.5 days after discontinuation of the drug, but sometimes it can last for several days.

All penicillins are characterized by cross-sensitization and cross-allergic reactions. Any preparations containing penicillin, including cosmetics and foods, may cause sensitization.

Penicillins can cause various side and toxic effects of a non-allergic nature. These include: when taken orally - an irritant effect, incl. glossitis, stomatitis, nausea, diarrhea; with the / m introduction - pain, infiltration, aseptic necrosis of the muscles; with a / in the introduction - phlebitis, thrombophlebitis.

It is possible to increase the reflex excitability of the central nervous system. When using high doses, neurotoxic effects may occur: hallucinations, delusions, dysregulation of blood pressure, convulsions. Seizures are more likely in patients receiving high doses of penicillin and/or in patients with severe hepatic impairment. Due to the risk of severe neurotoxic reactions, penicillins cannot be administered endolumbally (with the exception of benzylpenicillin sodium salt, which is administered extremely carefully, according to vital indications).

In the treatment of penicillins, the development of superinfection, candidiasis of the oral cavity, vagina, intestinal dysbacteriosis is possible. Penicillins (more often ampicillin) can cause antibiotic-associated diarrhea.

The use of ampicillin leads to the appearance of an "ampicillin" rash (in 5-10% of patients), accompanied by itching, fever. This side effect occurs more frequently on days 5-10 of high-dose ampicillin use in children with lymphadenopathy and viral infections or with concomitant allopurinol, as well as in almost all patients with infectious mononucleosis.

Specific adverse reactions when using bicillins are local infiltrates and vascular complications in the form of Onet's syndromes (ischemia and gangrene of the extremities with accidental injection into the artery) or Nicolau (embolism of the pulmonary and cerebral vessels when injected into a vein).

When using oxacillin, hematuria, proteinuria, and interstitial nephritis are possible. The use of antipseudomonal penicillins (carboxypenicillins, ureidopenicillins) may be accompanied by the appearance of allergic reactions, symptoms of neurotoxicity, acute interstitial nephritis, dysbacteriosis, thrombocytopenia, neutropenia, leukopenia, eosinophilia. When using carbenicillin, hemorrhagic syndrome is possible. Combined drugs containing clavulanic acid can cause acute liver damage.

Application during pregnancy. Penicillins pass through the placenta. Although adequate and strictly controlled safety studies in humans have not been conducted, penicillins, incl. inhibitor-protected, are widely used in pregnant women, with no complications reported.

In studies on laboratory animals with the introduction of penicillins at doses 2-25 (for different penicillins) exceeding therapeutic, fertility disorders and effects on reproductive function were not found. No teratogenic, mutagenic, embryotoxic properties have been identified with the introduction of penicillins to animals.

In accordance with the generally recognized recommendations of the FDA (Food and Drug Administration), which determine the possibility of using drugs during pregnancy, penicillin drugs in terms of their effect on the fetus belong to the FDA category B (the study of reproduction in animals did not reveal an adverse effect of drugs on the fetus, but adequate and strictly controlled studies in pregnant women have not been conducted).

When prescribing penicillins during pregnancy, one should (as with any other means) take into account the duration of pregnancy. During therapy, it is necessary to strictly monitor the condition of the mother and fetus.

Use during breastfeeding. Penicillins pass into breast milk. Although no significant complications have been reported in humans, the use of penicillins by nursing mothers can lead to sensitization of the child, changes in the intestinal microflora, diarrhea, the development of candidiasis and the appearance of skin rashes in infants.

Pediatrics. When using penicillins in children, specific pediatric problems have not been registered, however, it should be borne in mind that insufficiently developed kidney function in newborns and young children can lead to cumulation of penicillins (in this regard, there is an increased risk of neurotoxicity with the development of seizures).

Geriatrics. No specific geriatric problems have been reported with the use of penicillins. However, it should be remembered that older people are more likely to age-related impairment of kidney function, and therefore dose adjustment may be required.

Impaired kidney and liver function. With renal / hepatic insufficiency, cumulation is possible. With moderate and severe insufficiency of kidney and / or liver function, dose adjustment and an increase in the periods between antibiotic injections are required.

Interaction of penicillins with other drugs. Bactericidal antibiotics (including cephalosporins, cycloserine, vancomycin, rifampicin, aminoglycosides) have a synergistic effect, bacteriostatic antibiotics (including macrolides, chloramphenicol, lincosamides, tetracyclines) have an antagonistic effect. Care must be taken when combining penicillins active against Pseudomonas aeruginosa (Pseudomonas aeruginosa), with anticoagulants and antiplatelet agents (potential risk of increased bleeding). It is not recommended to combine penicillins with thrombolytics. When combined with sulfonamides, the bactericidal effect may be weakened. Oral penicillins may reduce the effectiveness of oral contraceptives due to impaired enterohepatic estrogen circulation. Penicillins can slow down the excretion of methotrexate from the body (inhibit its tubular secretion). The combination of ampicillin with allopurinol increases the likelihood of a skin rash. The use of high doses of the potassium salt of benzylpenicillin in combination with potassium-sparing diuretics, potassium preparations, or ACE inhibitors increases the risk of hyperkalemia. Penicillins are pharmaceutically incompatible with aminoglycosides.

Due to the fact that with long-term oral administration of antibiotics, the intestinal microflora that produces vitamins B 1, B 6, B 12, PP can be suppressed, it is advisable for patients to prescribe vitamins of group B to prevent hypovitaminosis.

In conclusion, it should be noted that penicillins are a large group of natural and semi-synthetic antibiotics with a bactericidal effect. The antibacterial action is associated with a violation of the synthesis of peptidoglycan of the cell wall. The effect is due to the inactivation of the transpeptidase enzyme, one of the penicillin-binding proteins located on the inner membrane of the bacterial cell wall, which is involved in the later stages of its synthesis. Differences between penicillins are associated with the features of their spectrum of action, pharmacokinetic properties and the spectrum of undesirable effects.

Over several decades of successful use of penicillins, problems have arisen associated with their misuse. Thus, the prophylactic administration of penicillins at risk of bacterial infection is often unreasonable. Incorrect treatment regimen - incorrect selection of the dose (too high or too low) and the frequency of administration can lead to the development of side effects, reduced efficacy and the development of drug resistance.

Thus, at present, most strains Staphylococcus spp. resistant to natural penicillins. In recent years, the frequency of detection of resistant strains has increased. Neisseria gonorrhoeae.

The main mechanism of acquired resistance to penicillins is associated with the production of beta-lactamase. To overcome the acquired resistance that is widespread among microorganisms, compounds have been developed that can irreversibly inhibit the activity of these enzymes, the so-called. beta-lactamase inhibitors - clavulanic acid (clavulanate), sulbactam and tazobactam. They are used in the creation of combined (inhibitor-protected) penicillins.

It should be remembered that the choice of one or another antibacterial drug, incl. penicillin, should be due, first of all, to the sensitivity of the pathogen that caused the disease to it, as well as the absence of contraindications to its appointment.