Macrolides of the latest generation. Antibiotics of the macrolide group for children. Description of some macrolides

Antibiotics are waste products (natural or synthetic origin) of viral, bacterial or fungal cells that can inhibit the growth and reproduction of other cells or microorganisms. Drugs may have antibacterial, anthelmintic, antifungal, antiviral and antitumor activity. They are divided into groups depending on their chemical structure.

Macrolide antibiotics are relatively safe representatives of antimicrobial agents. They take the form of complex compounds consisting of carbon atoms that are attached in various ways to the macrocyclic lactone ring. The drugs are well tolerated by patients.

Classification

The group of macrolides has several divisions:

Depending on the number of carbon atoms attached:
- drugs having 14 carbon atoms (for example, Erythromycin, Clarithromycin, Oleandomycin);
- means with 15 carbon atoms ();
- macrolides with 16 carbon atoms attached (for example, Josamycin, Spiramycin, Roxithromycin);
- 23 atoms belong to a single drug (Tacrolimus), which simultaneously belongs to the list of macrolide drugs and immunosuppressants.
According to the method of obtaining antibiotics: natural and synthetic origin.
By effect duration:
- short-acting (Erythromycin, Spiramycin, Oleandomycin, Roxithromycin);
- average duration (Clarithromycin, Josamycin, Flurithromycin);
- “long” drugs (Azithromycin, Dirithromycin).
Depending on the generation of drugs:
- 1st generation products;
- 2nd generation macrolides;
- 3rd generation of antibiotics (latest generation macrolides);
- Ketolides are drugs whose chemical structure consists of a traditional ring with the addition of a keto group.

Efficacy of drugs

Antibiotics of this group, especially new generation macrolides, have a wide spectrum of action. They are used to combat gram-positive microorganisms ( and ). At the present stage, there is a decrease in the sensitivity of pneumococci and some types of streptococci to antibiotics having 14 and 15 carbon atoms in their composition, however, 16-membered drugs retain their activity against these bacteria.

The drugs are effective against the following pathogens:

some strains of Mycobacterium tuberculosis;
gardnerella;
chlamydia;
pathogen;
mycoplasma;
bacillus that causes the development of Haemophilus influenzae infection.

Mechanism of action and benefits

Macrolides are tissue preparations, since their use is accompanied by the fact that the concentration of active substances in soft tissues is much higher than in the bloodstream. This is due to the ability of the substance to penetrate into the middle of the cells. The drugs bind to plasma proteins, but the degree of this action varies from 20 to 90% (depending on the antibiotic).

The effect of different antibiotics on a bacterial cell

The mechanism of action is due to the fact that macrolides inhibit the process of protein production by microbial cells and disrupt the functionality of their ribosomes. In addition, they have a predominantly bacteriostatic effect, that is, they inhibit the growth and reproduction of pathogenic microorganisms. The drugs have low toxicity and do not cause the development of an allergic reaction when combined with other groups of antibiotics.

Additional advantages of the latest generation products:

long half-life of drugs from the body;
transportation to the site of infection using leukocyte cells;
no need for a long course of treatment and frequent medications;
no toxic effect on the digestive system;
when using tablet forms, absorption from the gastrointestinal tract is more than 75%.

Macrolides in ENT practice

The drugs act on a wide range of pathogens that cause diseases of the ENT organs. Antibiotics are recommended for the treatment of bacterial tonsillitis, acute inflammation of the middle ear and paranasal sinuses, as well as bronchitis and pneumonia.
Macrolides are not used in the treatment of inflammation of the epiglottis and abscess of the retropharyngeal space.

Azithromycin has become most widespread in the treatment of the upper respiratory tract. The research results confirmed the effectiveness of the drug in children with mild and moderate severity of inflammatory processes. Clinical manifestations of the effectiveness of treatment include normalization of body temperature, elimination of leukocytosis, and subjective improvement in the patient’s condition.

Reasons for choosing macrolides in otorhinolaryngology

Doctors give priority to this group of antibiotics based on the following points:

Sensitization to penicillins. In patients with rhinosinusitis or otitis media against the background of allergic rhinitis or bronchial asthma, penicillin preparations, which are given first place, cannot be used due to allergenic properties. They are replaced by macrolides.
The group has an anti-inflammatory effect and a wide spectrum of action.
The presence of infections caused by atypical bacteria. Macrolides are effective against such pathogens that cause the development of certain types of tonsillopharyngitis, chronic adenoiditis, and nasal pathologies.
A number of microorganisms can form specific films under which pathogens “live”, causing the development of chronic processes in the ENT organs. Macrolides are able to influence pathological cells while they are under such films.

Contraindications

Macrolides are considered relatively safe drugs that can be prescribed to treat children, but even they have some contraindications for use. It is not advisable to use products from this group during pregnancy and breastfeeding. The use of macrolides in children under 6 months is not recommended.

The drugs are not prescribed if there is individual hypersensitivity to the active components, or with severe pathologies of the liver and kidneys.

Side effects

Adverse reactions do not develop often. Attacks of nausea and vomiting, diarrhea, and abdominal pain may occur. With a negative effect on the liver, the patient complains of increased body temperature, yellowing of the skin and sclera, weakness, and dyspeptic symptoms.

From the central nervous system, cephalalgia, slight dizziness, and changes in the functioning of the auditory analyzer may be observed. Local reactions can develop with parenteral administration of drugs (inflammation of the veins with the formation of blood clots in them).

Group representatives

Most macrolides should be taken an hour before a meal or several hours after it, since interaction with food causes a decrease in the activity of the drugs. Liquid dosage forms are taken according to the schedule prescribed by the attending physician.

It is imperative to maintain regular intervals between antibiotic doses. If the patient misses a dose, the medicine should be taken as soon as possible. Doubling the dosage of the drug at the time of the next dose is prohibited. During the treatment period, you should definitely stop drinking alcohol.

Erythromycin

Available in oral forms, suppositories, and powder for injection. This representative can be used during pregnancy and lactation, but under the strict supervision of the attending physician. It is not prescribed for the treatment of newborns due to the possibility of developing a narrowing of the gastric outlet (pyloric stenosis).

Roxithromycin

Available in tablet form. The spectrum of activity is similar to the previous representative of the group. Its analogues are Rulid, Roxithromycin Lek. Differences from Erythromycin:

the percentage of the drug entering the blood is higher and does not depend on the intake of food into the body;
longer elimination period;
better tolerability of the drug by patients;
interacts well with drugs of other groups.

It is prescribed to combat inflammation of the tonsils, larynx, paranasal sinuses of a streptococcal nature, infections caused by mycoplasmas and chlamydia.

Clarithromycin

Available in tablets and powders for injection. Analogues – Fromilid, Klacid. Clarithromycin has high bioavailability and is well tolerated by patients. Not used to treat newborns, pregnant and nursing mothers. The drug is effective against atypical microorganisms.

Azithromycin (Sumamed)

Macrolide, belonging to the class of antibiotics with 15 carbon atoms. Available in the form of tablets, capsules, powders for injection and syrup. It differs from Erythromycin in a higher percentage of entry into the bloodstream, less dependence on food, and long-term preservation of the therapeutic effect after the end of therapy.

Spiramycin

An antibiotic of natural origin, having 16 carbon atoms in its composition. Effective in the fight against pneumonia pathogens that are resistant to other representatives of macrolides. Can be prescribed for the treatment of women during pregnancy. It is administered orally or into a vein by drip.

The active substance is midecamycin. Macrolide of natural origin, acting on those staphylococci and pneumococci that are resistant to other drugs. The drug is well absorbed from the intestinal tract and interacts well with representatives of other groups of medications.

Josamycin

It has a slightly different spectrum of action than Erythromycin. Josamycin fights against those microorganisms that are resistant to a number of macrolides, but is not able to suppress the proliferation of a number of erythromycin-sensitive bacteria. Available in the form of tablets and suspensions.

Conditions for prescribing drugs

For macrolide treatment to be effective, a number of rules must be followed:

Making an accurate diagnosis, which allows you to clarify the presence of local or general inflammation in the body.
Determination of the causative agent of pathology using bacteriological and serological diagnostics.
The choice of the necessary drug is based on the antibiogram, the localization of the inflammatory process and the severity of the disease.
The choice of dosage of the drug, frequency of administration, duration of treatment based on the characteristics of the drug.
Prescription of macrolides with a narrow spectrum of action for relatively mild infections and with a broad spectrum for severe diseases.
Monitoring the effectiveness of therapy.

The list of drugs is quite wide. Only a qualified specialist can select the necessary remedy that will be most effective for each specific clinical case.

Increasing the dosage helps achieve a bactericidal effect.

Macrolides belong to the class of polyketides. Polyketides are polycarbonyl compounds that are intermediate metabolic products in the cells of animals, plants and fungi.

When taking macrolides, there were no cases of selective dysfunction of blood cells, its cellular composition, nephrotoxic reactions, secondary dystrophic damage to joints, photosensitivity, manifested by hypersensitivity of the skin to ultraviolet radiation. Anaphylaxis and antibiotic-associated conditions occur in a small percentage of patients.

Macrolide antibiotics occupy a leading position among the safest antimicrobial drugs for the body.

The main direction in the use of this group of antibiotics is the treatment of nosocomial respiratory tract infections caused by gram-positive flora and atypical pathogens. A little historical information will help us systematize the information and determine which antibiotics are macrolides.

Macrolides are classified according to the method of preparation and the chemical structural basis.

In the first case, they are divided into synthetic, natural and prodrugs (erythromycin esters, oleandomycin salts, etc.). Prodrugs have a modified structure compared to the drug, but in the body, under the influence of enzymes, they are converted into the same active drug, which has a characteristic pharmacological effect.

Prodrugs have improved taste and high bioavailability. They are resistant to changes in acidity.

Classification involves dividing macrolides into 3 groups:

*ex. - Natural.
*floor - Semi-synthetic.

It is worth noting that azithromycin is an azalide because its ring contains a nitrogen atom.

Features of the structure of each macro. affect activity indicators, drug interactions with other drugs, pharmacokinetic properties, tolerability, etc. The mechanisms of influence on microbiocenosis of the presented pharmacological agents are identical.

Let's look at the main representatives of the group separately.

Er. inhibits the growth of chlamydia, legionella, staphylococcus, mycoplasma and legionella, Pseudomonas aeruginosa, Klebsiella.
Bioavailability can reach sixty percent and depends on meals. Partially absorbed in the digestive tract.

Side effects include: dyslepsy, dyspepsia, narrowing of one of the sections of the stomach (diagnosed in newborns), allergies, “shortness of breath syndrome.”

Prescribed for diphtheria, vibriosis, infectious skin lesions, chlamydia, Pittsburgh pneumonia, etc.
Treatment with erythromycin during pregnancy and lactation is excluded.

Inhibits the growth of microorganisms that produce the enzyme that breaks down beta-lactams, and has an anti-inflammatory effect. R. is resistant to acids and alkalis. The bactericidal effect is achieved by increasing the dosage. The half-life is approximately ten hours. Bioavailability is fifty percent.

Roxithromycin is well tolerated and excreted unchanged from the body.

Prescribed for inflammation of the mucous membrane of the bronchi, larynx, paranasal sinuses, middle ear, tonsils, gallbladder, urethra, vaginal segment of the cervix, infections of the skin, musculoskeletal system, brucellosis, etc.
Pregnancy, lactation and age under two months are contraindications.

Inhibits the growth of aerobes and anaerobes. Low activity is observed in relation to Koch's bacillus. Clarithromycin is superior to erythromycin in microbiological parameters. The drug is acid-resistant. The alkaline environment affects the achievement of antimicrobial action.

Clarithromycin is the most active macrolide against Helicobacter pylori, which infects various areas of the stomach and duodenum. The half-life is approximately five hours. The bioavailability of the drug does not depend on food.

K. is prescribed for wound infections, infectious diseases of the ENT organs, purulent rashes, furunculosis, mycoplasmosis, mycobacteriosis against the background of the immunodeficiency virus.
Taking clarithromycin in early pregnancy is prohibited. Infancy up to six months is also a contraindication.

Ol. inhibits protein synthesis in pathogen cells. The bacteriostatic effect is enhanced in an alkaline environment.
To date, cases of use of oleandomycin are rare, as it is outdated.
Ol. prescribed for brucellosis, abscess pneumonia, bronchiectasis, gonorrhea, inflammation of the meninges, inner lining of the heart, upper respiratory tract infections, purulent pleurisy, furunculosis, and pathogenic microorganisms entering the bloodstream.

The antibiotic demonstrates high levels of activity against Helicobacter pylori, Haemophilus influenzae, and gonococcus. Azithromycin is three hundred times more acid-resistant than erythromycin. Digestibility rates reach forty percent. Like all erythromycin antibiotics, azithromycin is well tolerated. The long half-life (more than 2 days) allows the drug to be prescribed once a day. The maximum course of treatment does not exceed five days.

Effective in the eradication of streptococcus, treatment of lobar pneumonia, infectious lesions of the pelvic organs, genitourinary system, tick-borne borreliosis, venereal diseases. During the period of bearing a child, it is prescribed according to vital indications.
Taking azithromycin by HIV-infected patients can prevent the development of mycobacteriosis.

A natural antibiotic obtained from the radiant fungus Streptomyces narbonensis. The bactericidal effect is achieved at high concentrations at the site of infection. J - n inhibits protein synthesis and suppresses the growth of pathogens.

Josamycin therapy often leads to a decrease in blood pressure. The drug is actively used in otorhinolaryngology (tonsillitis, pharyngitis, otitis), pulmonology (bronchitis, psittacosis, pneumonia), dermatology (furunculosis, erysipelas, acne), urology (urethritis, prostatitis).

Approved for use during lactation, it is prescribed for the treatment of pregnant women. The suspension form is indicated for newborns and children under fourteen years of age.

It is characterized by high levels of microbial activity and good pharmacokinetic properties. The bactericidal effect is achieved by significantly increasing the dose. The bacteriostatic effect is associated with inhibition of protein synthesis.

Pharmacological action depends on the type of harmful microorganism, drug concentration, inoculum size, etc. Midecamycin is used for infectious lesions of the skin, subcutaneous tissue, and respiratory tract.

Midecamycin is a reserve antibiotic and is prescribed to patients with beta-lactam hypersensitivity. Actively used in pediatrics.

Lactation period (passes into breast milk) and pregnancy are contraindications. Sometimes m-n is prescribed for vital indications and if the benefit to the mother outweighs the potential risk to the fetus.

It differs from other macrolides in that it regulates the immune system. The bioavailability of the drug reaches forty percent.

The activity of the drug decreases in an acidic environment and increases in an alkaline environment. Alkali helps to increase penetration: the antibiotic better gets inside pathogen cells.

It has been scientifically proven that spiramycin does not affect embryonic development, so it is permissible to take it while bearing a child. The antibiotic affects breastfeeding, so during lactation it is worth finding an alternative drug.

Macrolide antibiotics should not be administered to children by intravenous infusion.

When treated with macrolides, the occurrence of life-threatening drug reactions is excluded. ADRs in children are manifested by pain in the abdomen, a feeling of discomfort in the epigastric region, and vomiting. In general, children's bodies tolerate macrolide antibiotics well.

Drugs invented relatively recently practically do not stimulate gastrointestinal motility. Dyspeptic manifestations as a result of the use of midecamycin and midecamycin acetate are not observed at all.

Clirithromycin deserves special attention because it is superior to other macrolides in many respects. As part of a randomized controlled trial, it was found that this antibiotic acts as an immunomodulator, having a stimulating effect on the body's protective functions.

Macrolides are used for:

therapy of atypical mycobacterial infections,
hypersensitivity to β-lactams,
diseases of bacterial origin.

They have become popular in pediatrics due to the possibility of injection, in which the drug bypasses the gastrointestinal tract. This becomes necessary in emergency cases. A macrolide antibiotic is what pediatricians most often prescribe when treating infections in young patients.

Macrolide therapy extremely rarely causes anatomical and functional changes, but side effects cannot be ruled out.

In a scientific study, which involved about 2 thousand people, it was found that the likelihood of anaphylactoid reactions when taking macrolides is minimal. No cases of cross-allergy have been recorded. Allergic reactions manifest themselves in the form of nettle fever and exanthema. In isolated cases, anaphylactic shock is possible.

Dyspeptic symptoms occur due to the prokinetic effect characteristic of macrolides. Most patients report frequent bowel movements, pain in the abdominal area, impaired taste, and vomiting. Newborns develop pyloric stenosis, a disease in which it is difficult to evacuate food from the stomach into the small intestine.

Torsade de pointes, cardiac arrhythmia, and long QT syndrome are the main manifestations of cardiotoxicity of this group of antibiotics. The situation is aggravated by advanced age, heart disease, excess dosage, and water and electrolyte disorders.

Long-term treatment and excess dosage are the main causes of hepatoxicity. Macrolides have different effects on cytochrome, an enzyme involved in the metabolism of chemicals foreign to the body: erythromycin inhibits it, josamycin affects the enzyme a little less, and azithromycin has no effect at all.

Few doctors know when prescribing a macrolide antibiotic that this is a direct threat to a person’s mental health. Neuropsychiatric disorders most often occur when taking clarithromycin.

Video about the group reviewed:

Macrolides are a promising class of antibiotics. They were invented more than half a century ago, but are still actively used in medical practice. The uniqueness of the therapeutic effect of macrolides is due to their favorable pharmacokinetic and pharmacodynamic properties and the ability to penetrate the cell wall of pathogens.

High concentrations of macrolides contribute to the eradication of pathogens such as Chlamydia trachomatis, Mycoplasma, Legionella, Campylobacter. These properties set macrolides apart from β-lactams.

Erythromycin initiated the macrolide class.

The first acquaintance with erythromycin occurred in 1952. The international American innovative company Eli Lilly & Company has expanded its portfolio of new pharmaceuticals. Its scientists derived erythromycin from a radiant fungus that lives in the soil. Erythromycin has become an excellent alternative for patients who are hypersensitive to penicillin antibiotics.

Expansion of the scope of application, development and introduction into the clinic of macrolides, modernized according to microbiological indicators, dates back to the seventies and eighties.

The erythromycin series is different:

high activity against Streptococcus and Staphylococcus and intracellular microorganisms;
low toxicity levels;
absence of cross-allergy with beta-lactim antibiotics;
creating high and stable concentrations in tissues.

Still have questions? Get a free doctor's consultation right now!

Clicking on the button will take you to a special page on our website with a feedback form with a specialist of the profile you are interested in.

Free doctor consultation

Macrolides are antibiotics whose chemical structure is based on the presence of a macrocyclic lactone ring. Antibiotics such as erythromycin, clarithromycin, roxithromycin, and flurithromycin have a 14-membered ring; 15-membered - azithromycin; 16-membered - midecamycin, spiramycin, josamycin, leukomycin, myocamycin. According to the method of production, macrolides are divided into natural (erythromycin, midecamycin, spiramycin, josamycin) and semi-synthetic (clarithromycin, roxithromycin, azithromycin, midecamycin acetate). The division of macrolides into natural and semi-synthetic is arbitrary, since a number of natural antibiotics are obtained by synthesis.

In 1949, Filipino scientist Alberto Aguilar discovered a new radiant fungus in the soil that had the ability to inhibit the growth of bacteria. In 1950, the American MacGuir isolated the first macrolide antibiotic called erythromycin from this fungus.

Macrolides in therapeutic doses have a bacteriostatic effect, but in high concentrations (increasing the dosage by 2-4 times), they can act bactericidal against beta-hemolytic streptococci, pneumococcus, pathogens of whooping cough and diphtheria.
The antibacterial effect of macrolide antibiotics is carried out by inhibiting protein synthesis in the ribosomes of growing microbial cells, and spiramycin, unlike other macrolides, is able to bind three 50S ribosomal subunits at once, due to which it has a longer antimicrobial effect. These antibiotics have no effect on microbial cells in the resting phase. The spectrum of action of macrolides is close to penicillins; they also suppress the proliferation of microbes resistant to penicillins, tetracyclines and chloramphenicol.
Macrolides have very high activity against gram-positive cocci (Streptococcus pyogenes, (Streptococcus pneumoniae, Staphylococcus aureus), intracellular pathogens (mycoplasma, Legionella spp. Chlamydia spp. Mycoplasma pneumoniae) and many gram-negative microorganisms (Haemophilus influenzae, Morahella, etc.) Azithromycin has the strongest antibacterial effect on gram-negative bacteria. Meanwhile, families such as Enterobacteriaceae, Pseudomonas spp. and Acinetobacter spp. are naturally resistant to all macrolide antibiotics. Many macrolides exhibit a post-antibiotic effect against gram-positive cocci, i.e. can inhibit the activity of bacteria after their short-term contact with a macrolide antibiotic. In this case, irreversible changes occur in the ribosomes of microbial cells, which makes it possible to enhance and prolong the overall antibacterial effect of the drug. Spiramycin has the highest post-antibiotic effect among macrolides.

Antibiotics - macrolides have the ability to accumulate in the lung parenchyma, bronchial mucosa, and tracheobronchial secretions, creating high concentrations of the antibiotic in these tissues, which ensures high bioavailability of these antibiotics. Macrolides are also resistant to β-lactamase enzymes produced by Haemophilus influenzae. In this connection, macrolides are mainly used in the treatment of: infections of the upper and lower respiratory tract (streptococcal tonsillopharyngitis, acute sinusitis), bronchitis, community-acquired pneumonia, whooping cough. They are also used for infections of the skin and soft tissues, as well as for the treatment of chlamydia, syphilis, and oral infections. Macrolides with a 15- and 16-membered lactone ring (spiramycin, azithromycin, roxithromycin, clarithromycin) are the first choice drugs for community-acquired pneumonia.
Unlike other groups of antibiotics, macrolides have an immunomodulatory and moderate anti-inflammatory effect. The immunomodulatory effect occurs due to the ability of the antibiotic to inhibit the formation of interleukin-2, which is involved in autoimmune tissue damage. This occurs due to the suppressive effect of the macrolide on T lymphocytes. Macrolides provide an anti-inflammatory effect due to their antioxidant properties. Macrolides affect the production of cytokines and promote an endogenous increase in glucocorticoids by activating the hypothalamic-pituitary-adrenal system.

Macrolides have low toxicity and are well tolerated by patients. Many are acid-resistant, which allows the widespread use of both parenteral and oral forms of drugs. Sometimes they cause undesirable effects from the gastrointestinal tract in the form of nausea, dyspepsia, loss of appetite, vomiting, diarrhea. Allergic reactions in the form of skin rashes rarely occur. All this allows the use of macrolides as an alternative to beta-lactam antibiotics in the treatment of patients with upper and lower respiratory tract infections, for the prevention of rheumatism, whooping cough (erythromycin), and for the prevention of meningitis (spiramycin).

Contraindications when taking macrolides: allergic reaction, pregnancy and lactation. Use cautiously for liver diseases.

Bolokhovets Lyubov Georgievna

c) Antibiotics of the erythromycin group

This group of antibiotics includes erythromycin and oleandomycin. produced by certain Streptomyces fungi.

In terms of their spectrum of action, erythromycin and oleandomycin are close to benzylpenicillin. They act on the same microorganisms as benzylpenicillin, and, in addition, are active against Brucella, rickettsia and chlamydia (Fig. 29).

Rice. 29. Spectra of action of antibiotics

According to the spectrum of action, erythromycin and oleandomycin are effective against purulent-septic infections (sepsis, abscesses, osteomyelitis, erysipelas, tonsillitis, purulent inflammation of the middle ear, paranasal sinuses, urinary and biliary tract, etc.), pneumonia, epidemic meningitis, gonorrhea, diphtheria, brucellosis and some diseases caused by chlamydia (trachoma, psittacosis).

In the process of treating infections with erythromycin and oleandomycin, drug resistance of microorganisms to them very quickly develops. Erythromycin and oleandomycin are used as reserve antibiotics in the treatment of infectious diseases (see Table 15).

The side effects of drugs in this group are manifested mainly by allergic reactions and dyspeptic disorders. Erythromycin sometimes causes liver dysfunction.

Erythromycin. Erythromycinum is a white powder, bitter taste, slightly soluble in water.

Assign inside 1-1 1/2 hours before meals, 0.2-0.25 g every 4-6 hours.

Higher doses(for adults): orally - single dose 0.5 g, daily dose 2 g.

For the treatment of infectious lesions of the skin and mucous membranes (pustular skin diseases, infected wounds, burns, trachoma), the drug is prescribed place in the form of an official ointment (Unguentum Erythromycini), containing 0.01 g of erythromycin per 1 g.

Release forms. tablets of 0.1 and 0.25 g; capsules of 0.1 and 0.2 g; ointment in tubes of 3; 7; 10; 15 and 30 g.

Storage. list B; in a place protected from light.

In addition, erythromycin is available in the form of a water-soluble salt - erythromycin phosphate (Erythromycini phosphas), which is intended for intravenous administration and is available in hermetically sealed bottles of 0.05; 0.1 and 0.2 g.

Oleandomycin phosphate. Oleandomycini phosphas is a white powder with a bitter taste, easily soluble in water.

Assign inside after meals, 0.25 g every 4-6 hours.

Higher doses(for adults); orally - single 0.5 g, daily 2 g.

Release form. film-coated tablets, 0.125 g each.

Storage. list B.

Description and instructions of Erythromycin

Erythromycin is a fairly well-known antibiotic. belonging to a number of macrolides. This medicine affects the ability of bacteria to reproduce. Mainly gram-positive microorganisms, such as staphylococci and streptococci, are sensitive to its action. Clostridium, Corynebacterium. For the most part, gram-negative microorganisms do not show sensitivity to Erythromycin. However, there are some infections caused by this group of bacteria that can be treated with this antibiotic. This drug is prescribed for the treatment of diseases such as diphtheria, brucellosis, whooping cough, meningitis, otitis media, syphilis and so on.

Erythromycin is produced in tablet form. Dosing features for patients of different age groups and dosage regimens are described in the drug instructions. Treatment with this drug is not indicated for patients with reactions of individual intolerance to the drug or antibiotics of the same group, or for people with severe liver dysfunction who have had hepatitis. During pregnancy or breastfeeding, the use of Erythromycin is not recommended. The few studies that have been conducted on this drug have revealed, albeit insignificant, teratogenic activity. That is, the ability to cause developmental defects in the fetus. Side effects that are possible when taking this antibiotic include various disorders of the gastrointestinal tract and allergies, including the development of anaphylactic shock.

Patients who leave their reviews about Erythromycin most often speak positively about this drug. However, there are also reports of its side effects. For example, one girl, having taken a tablet of this antibiotic due to a sore throat, felt severe spasmodic pain in the stomach area. Several other patients left similar messages. Moreover, in most of them, similar phenomena developed after the first dose of Erythromycin.

Very often, this drug is used to treat urogenital infections, such as chlamydia. It is only worth remembering that such therapy should be prescribed by a doctor. One of the blatant examples of unacceptable self-medication can be the story of one lady who, despairing of being cured of chlamydia on the recommendations of specialists, decided to prescribe medications for herself. She acted according to the principle: try all antibiotics, sequentially. She described her experience in a lengthy article. The dosages, drug regimens and their combinations in this “opus” completely contradict both pharmacological standards and common sense. The author of the “method” is confident that she “defeated” chlamydia, precisely with the help of Erythromycin. However, acquaintance with her experience leaves doubts not only about her physical, but also about her psycho-emotional health.

Not many of us dare to describe our own, proprietary methods of treatment, but, hand on heart, we have to admit that we often neglect warnings and act at our own peril and risk, having read reviews about the drug or, sometimes, even just instructions. For some conditions and medications, this is not critical. But you cannot experiment with antibiotics in general, and Erythromycin in particular. After all, these drugs have a strong, systemic effect on our body.

Sources: No comments yet!

Most antibiotics, while suppressing the development of infectious agents, simultaneously have a negative effect on the internal microbiocenosis of the human body, but, unfortunately, a number of diseases cannot be cured without the use of antibacterial agents.

The optimal way out of the situation is drugs from the macrolide group, which occupy leading positions in the list of the safest antimicrobial drugs.

The first representative of this class of antibiotics was Erythromycin, obtained from soil bacteria in the middle of the last century. As a result of research activities, it was discovered that the basis of the chemical structure of the drug is a lactone macrocyclic ring to which carbon atoms are attached; This feature determined the name of the entire group.

The new product almost immediately gained wide popularity; it was involved in the fight against diseases caused by gram-positive bacteria. Three years later, the list of macrolides was supplemented with Oleandomycin and Spiramycin.

The development of the next generations of antibiotics in this series was due to the discovery of the activity of early drugs of the group against campylobacteria, chlamydia and mycoplasmas.

Today, almost 70 years after their discovery, Erythromycin and Spiramycin are still present in therapeutic regimens. In modern medicine, the first of these drugs is more often used as the drug of choice in patients with individual intolerance to penicillins, the second - as a highly effective drug characterized by a long-term antibacterial effect and the absence of terratogenic effects.

Oleandomycin is used much less frequently: many experts consider this antibiotic to be obsolete.

There are currently three generations of macrolides; Research into the properties of the drugs continues.

The classification of drugs included in the described group of antibiotics is based on the chemical structure, method of preparation, duration of exposure and generation of the drug.

Details about the distribution of drugs are in the table below.

Number of carbon atoms attached
14	15	16
Oleandomycin; Dirithromycin; Clarithromycin; Erythromycin.	Azithromycin	Roxithromycin; Josamycin; Midecamycin; Spiromycin.
Length of therapeutic effect
short	average	long-term
Roxithromycin; Spiramycin; Erythromycin.	Flurithromycin (not registered in our country); Clarithromycin.	Dirithromycin; Azithromycin.
Generation
first	second	third
Erythromycin; Oleandomycin.	Spiramycin; Roxithromycin; Clarithromycin.	Azithromycin;

This classification should be supplemented with three points:

The list of drugs in the group includes Tacrolimus, a medication that has 23 atoms in its structure and at the same time belongs to the immunosuppressants and to the series under consideration.

The structure of Azithromycin includes a nitrogen atom, so the drug is an azalide.
Macrolide antibiotics have both natural and semi-synthetic origin.

Natural medications, in addition to those already indicated in the historical reference, include Midecamycin and Josamycin; artificially synthesized - Azithromycin, Clarithromycin, Roxithromycin, etc. Prodrugs with a slightly modified structure are distinguished from the general group:

esters of Erythromycin and Oleandomycin, their salts (propionyl, troleandomycin, phosphate, hydrochloride);
salts of esters of the first representative of a number of macrolides (estolate, acystrate);
Midekamycin salts (Myocamycin).

All the drugs under consideration have a bacteriostatic type of action: they inhibit the growth of colonies of infectious agents by disrupting protein synthesis in pathogen cells. In some cases, clinic specialists prescribe increased dosages of medications to patients: the medications used in this way acquire a bactericidal effect.

Antibiotics of the macrolide group are characterized by:

a wide range of effects on pathogens (including drug-sensitive microorganisms - pneumococci and streptococci, listeria and spirochetes, ureaplasma and a number of other pathogens);
minimal toxicity;
high activity.

As a rule, the drugs in question are used in the treatment of sexually transmitted infections (syphilis, chlamydia), oral diseases of bacterial etiology (periodontitis, periostitis), diseases of the respiratory system (whooping cough, bronchitis, sinusitis).

The effectiveness of medications related to macrolides has also been proven in the fight against folliculitis and furunculosis. In addition, antibiotics are prescribed for:

gastroenteritis;
cryptosporidiosis;
atypical pneumonia;
acne (severe disease).

For the purpose of prevention, a group of macrolides is used to sanitize carriers of meningococcus during surgical manipulations in the lower intestine.

Modern medicine actively uses Erythromycin, Clarithromycin, Ilozon, Spiramycin and a number of other representatives of this group of antibiotics in treatment regimens. The main forms of their release are indicated in the table below

Drug names	Packing type
Drug names	Capsules, tablets	Granules	Suspension	Powder
Azivok	+
Azithromycin	+	+
Josamycin	+
Zitrolide	+
Ilozon	+	+	+	+
Clarithromycin	+	+		+
Macropen	+	+
Rovamycin	+			+
Rulid	+
Sumamed	+			+
Hemomycin	+			+
Ecomed	+			+
Erythromycin	+			+

Pharmacy chains also offer consumers Sumamed in the form of an aerosol, lyophilisate for infusion, and Hemomycin in the form of a powder for the preparation of injection solutions. Erythromycin liniment is packaged in aluminum tubes. Ilozon is available in the form of rectal suppositories.

A brief description of popular remedies is in the material below.

Resistant to alkalis and acids. Prescribed mainly for diseases of the ENT organs, genitourinary system, and skin.

Contraindicated in pregnant and lactating women, as well as in young patients under 2 months of age. The half-life is 10 hours.

Under the strict supervision of a doctor, the use of the medication in the treatment of pregnant women (in difficult cases) is allowed. The bioavailability of the antibiotic directly depends on food intake, so you should drink the drug before meals. Side effects include allergic reactions, disruption of the functioning of the gastrointestinal tract (including diarrhea).

Another name for the drug is Midecamycin.

Used if the patient has an individual intolerance to beta-lactams. Prescribed to suppress the symptoms of diseases affecting the skin and respiratory organs.

Contraindications: pregnancy, breastfeeding period. Used in pediatrics.

Used in the treatment of pregnant and lactating women. In pediatrics it is used in the form of a suspension. May lower the patient's blood pressure. It is taken regardless of the time of eating.

Relieves symptoms of diseases such as tonsillitis, bronchitis, furunculosis, urethritis, etc.

It is characterized by increased activity against pathogens that cause inflammatory processes in the gastrointestinal tract (among them Helicobacter pylori).

Bioavailability does not depend on the time of consumption of food. Contraindications include the first trimester of pregnancy and infancy. The half-life is short, does not exceed five hours.

The effect of using the medication increases when it enters an alkaline environment.

Involved when:

bronchiectasis;
purulent pleurisy;
brucellosis;
diseases of the upper respiratory tract.

New generation drug. Acid resistant.

The structure of the antibiotic differs from most medications belonging to the described group. When used in the treatment of HIV-infected people, it prevents mycobacteriosis.

The half-life is more than 48 hours; this feature reduces the use of the drug to 1 r./day.

Incompatible with Clindamycin, Lincomycin, Chloramphenicol; reduces the effectiveness of beta-lactams and hormonal contraceptives. In severe cases of the disease, it is administered intravenously. Do not use during pregnancy, hypersensitivity to the components of the drug, or during lactation.

Characterized by the ability to regulate the immune system. Does not affect the fetus during gestation; it is used in the treatment of pregnant women.

Safe for children (the dosage is determined by the doctor taking into account the weight, age of the patient and the severity of his illness). Does not undergo cellular metabolism and is not broken down in the liver.

Low-toxic macrolides of the latest generation. They are actively used in the therapy of adults and small (from 6 months) patients, since they do not have a significant negative effect on the body. They are characterized by the presence of a long half-life, as a result of which they are used no more than once in 24 hours.

New generation macrolides have virtually no contraindications and are well tolerated by patients when used in therapeutic regimens. The duration of treatment with these drugs should not exceed 5 days.

Macrolides cannot be used independently in the treatment of diseases.

It should be remembered: using antibiotics without first consulting a doctor means being irresponsible about your health.

Most drugs in the group are characterized by slight toxicity, but the information contained in the instructions for use of macrolide medications should not be ignored. According to the annotation, when using medications, the following may occur:

disturbances in the functioning of the gastrointestinal tract (nausea, vomiting, dysbacteriosis), kidneys, liver and central nervous system;
allergic reactions;
visual and hearing disorders;
arrhythmia, tachycardia.

If the patient has a history of individual intolerance to macrolides, medical products of this series cannot be used in treatment.

Forbidden:

drink alcohol during treatment;
increase or decrease the prescribed dosage;
skip taking a pill (capsule, suspension);
stop taking it without re-testing;
use expired medications.

If there is no improvement or new symptoms appear, you should immediately contact your doctor.

Medical terms are often incomprehensible to the general population unfamiliar with narrow concepts. It can be difficult for a non-specialist to understand what a doctor prescribes, since the name of the drug or group of drugs does not tell the patient anything. What is hidden behind the word “macrolides”, what drugs are included in this group and what they are needed for - all this is in the article.

Macrolides are a group of antibiotics. They are the latest generation drugs.

Chemical structure of macrolides:

The backbone is a macrocyclic 14- or 16-membered lactone ring. The members of the ring are lactones - cyclic esters of hydroxy acids containing a certain group of elements (-C(O)O-) in their ring.
Several (maybe one) carbohydrate residues are attached to the base of the structure.

For quotation: Klyuchnikov S.O., Boldyrev V.B. The use of macrolides in children in modern conditions // RMZh. 2007. No. 21. S. 1552

In modern chemotherapy of bacterial infections in children, antibiotics and their semisynthetic and synthetic analogues occupy a leading place. Today, more than 6,000 antibiotics have been described, of which about 50 have found use in medicine. The most widely used are b-lactams (penicillins and cephalosporins), macrolides (erythromycin, azithromycin, etc.), aminoglycosides (streptomycin, kanamycin, gentamicin, and etc.), tetracyclines, polypeptides (bacitracin, polymyxins, etc.), polyenes (nystatin, amphotericin B, etc.), steroids (fusidine), etc.

Through chemical and microbiological transformation, so-called semi-synthetic antibiotics have been created, which have new properties valuable for medicine: acid and enzyme resistance, an expanded spectrum of antimicrobial action, better distribution in tissues and body fluids, and fewer side effects.
Based on the type of antimicrobial action, antibiotics are divided into bacteriostatic and bactericidal, which is of practical importance when choosing the most effective therapy.
A comparative analysis of antibiotics is based on indicators of their effectiveness and safety, determined by the severity of the antimicrobial effect in the body, the rate of development of resistance of microorganisms during treatment, the absence of cross-resistance in relation to other chemotherapy drugs, the degree of penetration into lesions, the creation of therapeutic concentrations in the patient’s tissues and fluids, and the duration of their maintenance, the preservation of action in various environmental conditions. Important properties are also stability during storage, ease of use with different methods of administration, high chemotherapeutic index, absence or mild toxic side effects, as well as allergization of the patient.
A discussion of the place of antibiotics in the treatment of bacterial infections in childhood cannot be complete without addressing the problem of antimicrobial resistance. Due to the repeated and often unjustified prescription of antibiotics, the incidence of infections caused by microorganisms that have become insensitive to the antibiotics used is increasing throughout the world. The growth in the number of patients with immunodeficiency, the introduction of new invasive medical techniques, mutations of the microorganisms themselves, and some others also play a role in the formation of resistance.
Antibiotic resistance is currently leading to increased morbidity, mortality and healthcare costs worldwide. Due to the rapid increase in resistance, problems arise in the treatment of bacterial infections in childhood. Of particular importance is the resistance to penicillin and cephalosporin of Streptococcus pneumoniae, the multidrug resistance of Haemophilus influenzae (insensitive to ampicillin, chloramphenicol, tetracycline and trimethoprim), the rapid spread of penicillin-resistant Neisseria meningitidis. Methicycline-resistant strains of Staphylococcus aureus are increasingly being discovered; All over the world, doctors are faced with multi-resistance Enterobacteriaceae (thus, the number of isolated cultures of Klebsiella and Enterobacter species that are insensitive to third-generation cephalosporins is increasing). Resistance of Salmonella and Shigella species is developing, in particular, to trimethoprim and cephalosporins, enterococci to vancomycin, and group A streptococci to erythromycin.
Although the emergence of antibiotic resistance may be an inevitable result of widespread use, in practice it is certainly possible to reduce the resistance problem. For example, in Holland the use of systemic antibiotics is limited by the state program and the problem of resistance is not so acute.
In recent years, many new antibiotics of different pharmacological groups have been introduced into medical practice. However, the group of macrolides currently attracting the greatest attention from clinicians. This is facilitated by the increasing frequency of drug allergies to penicillins and cephalosporins in the pediatric population, as well as the ineffectiveness of b-lactams for infections caused by intracellular pathogens.
Macrolides are now one of the most rapidly developing classes of antibiotics due to their high efficiency and relative safety. They have a wide spectrum of antimicrobial activity and favorable pharmacokinetic properties, combine high efficiency in the treatment of infections and good tolerance by patients.
The first macrolide antibiotic synthesized in 1952 was erythromycin, obtained by Wak-s-man from the soil fungus Streptomyces erythreus.
Three years later, two more macrolide drugs appeared - spiramycin and oleandomycin. For a long time, erythromycin remained the only alternative in the treatment of many bacterial infections in children allergic to b-lactams. In recent years, a real scientific breakthrough has occurred: several, in a certain sense, unique in their qualities, drugs have been created that hold a “high bar” to this day: azithromycin (Zithrocin, etc.), roxithromycin, clarithromycin, spiramycin, etc.
Macrolides get their name due to the presence of a macrocyclic lactone core. Depending on the number of carbon atoms in the lactone ring, macrolides are divided into 3 subgroups:
. 14-membered (erythromycin, oleandomycin, roxithromycin, clarithromycin);
. 15-membered (azithromycin);
. 16-membered (spiramycin, josamycin, midecamycin).
One of the general properties of macrolides is a bacteriostatic effect, which is caused by disruption of protein synthesis in the microbial cell through reversible binding to the 50S ribosomal subunit. The bacteriostatic effect in this case has its own characteristics. On the one hand, the microbial agent is not completely destroyed, but on the other hand, there is no effect of additional intoxication of the body due to the action of toxins released from the destroyed microbial cell. When high concentrations of the antibiotic accumulate at the site of infection, macrolides have a so-called post-antibiotic effect, which means suppression of bacterial activity when the effect of the drug has theoretically ceased. The mechanism of this effect is not fully understood.
Macrolides are weak bases, their antimicrobial activity increases in an alkaline environment. At a pH of 5.5-8.5, they penetrate more easily into the microbial cell and are less ionized. Macrolides are metabolized in the liver, and, as a rule, more active metabolites are formed. The main route of elimination is through the gastrointestinal tract (about 2/3 of the drug), the remaining amount is excreted through the kidneys and lungs, so dose adjustment of macrolides is required only in cases of severe liver failure.
14-membered macrolides have an important additional property: they exhibit an anti-inflammatory effect by increasing the production of endogenous glucocorticoids and changing the cytokine profile due to activation of the hypothalamic-pituitary-adrenal system. In addition, the stimulating effect of macrolides on neutrophil phagocytosis and killing has been established.
Food has a multidirectional effect on the bioavailability of macrolides: it does not affect the absorption of telithromycin, clarithromycin, josamycin and midecamycin acetate; slightly reduces the bioavailability of midecamycin, azithromycin and significantly - erythromycin and spiramycin. Concomitant use with lipid-rich food increases the bioavailability of the tablet form of azithromycin. The pharmacokinetics of macrolides is characterized by a pronounced dependence on the pH of the environment, when it decreases, ionization at the site of inflammation increases and part of the drug is converted into inactive forms. The optimal effect of erythromycin, clarithromycin and especially azithromycin occurs at pH>7.5.
Macrolides penetrate well into the cells of the human body, where they create high concentrations, which is fundamentally important for the treatment of infectious diseases caused by intracellular pathogens (Mycoplasma spp., Chlamydia spp., Legionella spp., Campylobacter spp.). With the exception of roxithromycin, the content of macrolides in monocytes, macrophages, fibroblasts and polymorphonuclear leukocytes is tens, and for azithromycin hundreds of times higher than their serum concentration. An important feature of macrolides is their ability to accumulate in phagocytes with subsequent release at the site of infection under the influence of bacterial stimuli and the active recapture of the drug “unutilized” by microorganisms. The maximum accumulation of macrolides is observed in lung tissue, fluid lining the mucous membranes of the bronchi and alveoli, bronchial secretions, saliva, tonsils, middle ear, sinuses, gastrointestinal mucosa, prostate gland, conjunctiva and eye tissues, skin, bile, urethra, uterus, appendages and placenta. Metabolism of macrolides is carried out in the liver by enzymes of the cytochrome P450 system.
According to the degree of affinity for enzymes, all macrolides can be divided into three groups: a) oleandomycin and erythromycin have the greatest affinity; b) clarithromycin, midecamycin, josamycin and roxithromycin are characterized by weak affinity; c) when using azithromycin, dirithromycin and spiramycin, competitive binding with enzymes does not occur.
The half-life (T1/2) differs for different macrolides and may depend on the dose: azithromycin has the longest T1/2 - up to 96 hours, the shortest - erythromycin and josamycin - 1.5 hours (Table 1). Macrolides are excreted from the body mainly with bile, undergoing enterohepatic recirculation.
In addition to the direct antimicrobial effect on the cell, some macrolides are distinguished by properties that enhance their effectiveness in the conditions of the macroorganism. Among them:
.?postantibiotic effect, manifested in the absence of the effect of bacterial growth resumption, despite the removal of the antibiotic from the body.
.?subinhibitory effect, but it is difficult to use in therapeutic regimens, since the use of antibiotics in subinhibitory concentrations may cause an increase in resistance to it. It is used as a test to assess the distribution of a bacterial population according to the degree of antibiotic sensitivity and the proportion of resistant individuals in it, a high number of which may indicate signs of the formation of resistance.
Macrolides are an undisputed alternative in case of allergy to b-lactams in the treatment of tonsillitis, sinusitis, otitis, bronchitis, pneumonia, skin and soft tissue infections (Table 1). Considering that macrolides have an equally good effect on both extracellular and intracellular pathogens, they have become first-line antibiotics in the treatment of many urogenital infections and so-called atypical bronchopulmonary infections caused by chlamydia, mycoplasma, etc. Macrolides are also used in gastroenterology and are increasingly included in treatment regimens for chronic gastroduodenitis associated with H. pylori (for example, clarithromycin). Macrolides are first-line antibiotics in the treatment of whooping cough in children (moderate and severe forms), and are included in the complex of therapeutic measures for diphtheria of the pharynx.
Resistance to macrolides does not yet pose serious problems in most regions of Russia, as evidenced by the results of the multicenter study PeGAS-I. According to the data presented, the prevalence of resistant clinical strains of S. pneumoniae is within 4%.
Modern macrolides have convenient release forms: from tablets with different dosages to suspensions and syrups, which can be prescribed to children even at an early age. Some macrolides are available in the form of ointments for external use (erythromycin), and also have forms for parenteral administration (erythromycin, clarithromycin, azithromycin), which makes their use possible in emergency situations.
All new macrolides are significantly superior in their pharmacological properties to both erythromycin and midecamycin, have a more prolonged effect, are designed to be taken 1-2 times a day, and have significantly fewer side effects. But in other qualities these drugs have differences, sometimes significant. The absorption of azithromycin depends on the timing of meals. Bioavailability is considered to be greatest for roxithromycin (72-85%) and clarithromycin (52-55%) compared to azithromycin (37%), spiramycin (35%), etc.
From the 50s of the last century to the present day, macrolides have been used with high efficiency, especially for pathologies of the upper respiratory tract. In terms of frequency of use, macrolides occupy third place among all classes of antibiotics, and in the treatment of tonsillitis they compete with penicillins.
According to T.I. Garashchenko and M.R. Bogomilsky, this is due to a number of reasons:
1. High degree of accumulation of macrolides in lymphoid tissue.
2. Efficiency (up to 90%) in patients with tonsillopharyngitis.
3. Increased frequency of isolation from the tonsils (especially with recurrent tonsillopharyngitis) of microorganisms producing b-lactamases capable of destroying penicillins, first generation cephalosporins (M. catarrhalis, St. aureus) and high activity of macrolides against these pathogens.
4. An increase in the frequency of atypical pathogens (M. pneumoniae, CI. pneumoniae) in the etiology of acute and recurrent tonsillopharyngitis, adenoids (up to 43%), inaccessible to penicillins (including protected ones), cephalosporins, aminoglycosides, lincosamides.
5. Few side effects compared to other antibiotics.
6. No effect on the microflora of the intestines and pharynx, moderate antifungal effect.
7. High safety range, allowing the dose of macrolide (azithromycin) to be doubled to achieve a bactericidal effect.
8. High compliance due to short courses of treatment (3-5 days for azithromycin) and ease of administration of the drug (once a day for azithromycin).
9. Activity of some macrolides against H. influenzae (azithromycin).
10. The absence of competitive interaction between azalides and antifungal and antihistamine drugs, which allows for combination therapy in children with allergic manifestations and mycoses.
11. High activity of macrolides not only against nonspecific pathogens of pharyngeal diseases (GABHS, St. aureus, Str. pneumonia), but also specific ones - N. meningitides, N. gonorrhoeas, Treponema pallidum, Legionella pneumonia, Lisferia monocytogenes, Corynebacterium diphtheriae, activity against anaerobes - causative agents of paratonsillitis.
12. Immunomodulatory effect.
Despite the large number of positive criteria, in the last few years there has been some caution regarding the use of macrolide antibiotics due to reports of an increase in resistance to them in vitro in a number of countries (France, Italy, Spain), which, however, is not accompanied by reports of corresponding this increase in clinical ineffectiveness of macrolide antibiotics. Moreover, the high safety of macrolide antibiotics, and primarily azithromycin, allows the use of new dosage regimens (treatment of acute otitis media with a single dose) and their improvement to achieve a better bactericidal effect in patients with a burdened premorbid background. Thus, R. Cohen [cit. according to 4], analyzing the clinical and bacteriological effectiveness of treatment of chronic tonsillitis with azithromycin at a course dose of 30 and 60 mg/kg, taken for 3 days, notes that bacteriological effectiveness at a dose of 30 mg/kg was registered only in 58% of cases, whereas with 60 mg/kg - achieved 100% bacteriological eradication of the pathogen, comparable to a 10-day course of penicillin (95%).
The cost of macrolides in the modern pharmaceutical market varies widely: from expensive original drugs, undoubtedly of higher quality, to more affordable generics, some of which are also of good quality (zitrocin, clerimed, roxihexal, etc.), which ensures accessibility drugs of this group to all segments of the population.
But the doctor should not only be guided by the price of the drug when prescribing treatment for a child. An analysis of the clinical effectiveness of various representatives of macrolides shows that the unreasonable and frequent prescription of a popular drug in one region during the year can negate the antimicrobial effect, since under these conditions protoplasts and L-forms are quickly formed.
Macrolides are well tolerated and can be successfully used in children from birth. However, this does not apply to clarithromycin and azithromycin suspension, the safety and effectiveness of which have not been studied in children under 6 months of age. Macrolide doses used in children are presented in Table 2.
Adverse reactions requiring discontinuation of the drug: allergic reactions - anaphylaxis and Quincke's edema (extremely rare); acute cholestatic hepatitis; cardiotoxic effect (prolongation of the QT interval, arrhythmias); pseudomembranous colitis; acute interstitial nephritis; reversible hearing loss.
Adverse reactions that require attention if they persist for a long time and/or are poorly tolerated: allergic reactions (urticaria, itchy skin); pain at the injection site; reactions from the gastrointestinal tract (nausea, vomiting, changes in taste, pain and discomfort in the abdomen, diarrhea); dizziness and headache (extremely rare).
The most typical adverse reactions are observed in the gastrointestinal tract. In the case of azithromycin and clarithromycin, their frequency rarely reaches 12%, but when using erythromycin base it can increase to 32%. When using josamycin, clarithromycin, spiramycin and high doses of erythromycin (? 4 mg/day), acute cholestatic hepatitis may develop. When high doses of erythromycin are prescribed within a period of 36 hours to 8 days, reversible hearing loss is possible. High doses of erythromycin, telithromycin and spiramycin can cause prolongation of the QT interval and the occurrence of torsades de pointes. Cross-allergic reactions to all macrolides are extremely rare. Although macrolides can contribute to changes in intestinal biocenosis, this becomes clinically significant in very rare cases with the development of Clostridium dificille-associated pseudomembranous colitis, diarrhea, vaginal or oral candidiasis.
Among macrolide drugs, azithromycin, obtained and introduced into clinical practice in the early 90s of the 20th century, occupies a special place. This is the first representative of a new subgroup of antibiotics - azalides, whose lactone ring structure contains a nitrogen atom. This rearrangement of the erythromycin molecule gave the resulting compound new properties, including expanding the spectrum of antimicrobial action, creating high levels in tissues and cells that significantly exceed concentrations in the blood (tissue-oriented pharmacokinetics), and other properties that significantly distinguish it from macrolide antibiotics.
Along with maintaining activity against gram-positive cocci, azithromycin (Zitrocin, etc.) exceeds the activity of erythromycin against Haemophilus influenzae, Moraxella catarrhalis, Neisseria spp., Campylobacler jejuni, Helicobacter pylori, Borrelia burgdorferi. It is also active against some enterobacteria: its MIC90 value against Salmonella, Shigella, E.coli ranges from 4-16 mg/l. Azithromycin (Zitrocin, etc.) exhibits activity against some “atypical” microorganisms, as well as intracellular pathogens - Chlamydia spp., Mycoplasma spp. and etc.
Azithromycin is more stable at different pH values than erythromycin. After taking a single dose, more than 37% of azithromycin is absorbed from the stomach compared to 25% of erythromycin. Food or concomitant use of antacids reduces the bioavailability of azithromycin, and therefore it should be taken at least 1 hour before or 2 hours after meals.
The concentration of azithromycin in tissues and cells exceeds that found in the blood by 10-100 times; intracellularly concentrated in lysosomes. The average T1/2 of azithromycin is 2-4 days. With recommended treatment regimens (3 and 5 days), the drug is maintained in effective concentrations for 7 days or more. When deciding on repeated courses of antibacterial therapy, it is necessary to take into account the properties of azithromycin to accumulate in body tissues, which allows reducing the duration of the course of treatment with azithromycin and providing a post-antibiotic effect.
Azithromycin is quickly incorporated into white blood cells (polynuclear cells, monocytes, lymphocytes), in high concentrations and is found for a long time in alveolar macrophages and fibroblasts. When migrating to the site of infection, polynuclear cells play a transport role, providing a high and long-lasting level of antibiotic in tissues and cells. Even when administered in maximum doses, azithromycin creates low concentrations in the blood, but has high penetration into polynuclear cells (phagocytes), responsible for the clearance of pathogens from the site of infection and the bloodstream.
The drug is not metabolized in the patient's body and does not suppress isoenzymes of the cytochrome P450 system. It is excreted from the patient's body mainly in feces and partially (~ 20%) in urine.
Thus, modern synthetic macrolides (azithromycin, clarithromycin, roxithromycin) are characterized by a wide spectrum of action: they are active against most gram-positive microorganisms, many gram-negative bacteria, “atypical” intracellular pathogens of respiratory infections; their spectrum of action also includes atypical mycobacteria, causative agents of a number of dangerous infectious diseases (rickettsia, brucella, borrelia, etc.) and some protozoa. They are superior to natural macrolides not only in the breadth of their spectrum and degree of antibacterial activity, but also in their bactericidal effect on many pathogens.
New macrolides (especially azithromycin) have improved pharmacokinetic properties: prolonged pharmacokinetics (T1/2 of azithromycin, depending on the dose, is 48-60 hours), the ability to accumulate and remain for a long time in immunocompetent cells for 8-12 days after completion of 3-5 - daily courses of oral administration in a standard dose.
Pediatricians' interest in azithromycin is due to its high degree of accumulation in lymphoid tissue and long-lasting concentrations of the drug, providing a bactericidal effect, as well as rare side effects, lack of influence on the normal microflora of the oral cavity and intestines, and a low likelihood of drug interactions.
The tissue and cellular orientation of the kinetics, the prolonged action of new macrolides, and the possibility of their effective use in short courses without the risk of developing serious adverse reactions determine the low incidence of antibiotic resistance.

Content

A group of drugs whose structure is based on a macrocyclic lactone ring of 14 or 16 members is called macrolide antibiotics. They belong to naturally occurring polyketides. Their use helps stop the growth and development of harmful bacteria.

The group of macrolides includes azalides (15-membered substances) and ketolides (14-membered drugs), nominally these include the immunosuppressant tacrolimus (23-membered). The antimicrobial effect of the drugs is associated with a disruption of protein synthesis on the ribosomes of the microbial cell. Therapeutic doses of drugs have a bacteriostatic effect; in high concentrations they are bactericidal against the pathogens of whooping cough, diphtheria, and pneumococci.

Macrolides are effective against gram-positive cocci and have immunomodulatory and anti-inflammatory activity.

When taking them, there is no hematotoxicity, nephrotoxicity, development of chondro- and arthropathy, or photosensitivity. The use of the drugs does not lead to anaphylactic reactions, severe allergies, or diarrhea.

Macrolides are distinguished by high concentrations in tissues (higher than in blood plasma) and the absence of cross-allergy with beta-lactams. They act on streptococci, mycoplasmas, staphylococci, chlamydia, legionella, capmylobacteria. Enterobacteriaceae, pseudomonas, and acinetobacteria are resistant to the agents. Indications for the use of antibiotics are:

tonsillopharyngitis, acute sinusitis;
exacerbation of chronic bronchitis, community-acquired atypical pneumonia;
whooping cough;
chlamydia, syphilis;
periodontitis, periostitis.

Macrolides are used with caution in severe liver diseases. Contraindications to their use are intolerance to the components of the composition, pregnancy, and lactation. Possible side effects are indicated in the instructions:

hepatitis, jaundice;
fever, general malaise;
hearing impairment;
thrombophlebitis, phlebitis;
allergies, rash, urticaria.

Classification

Antibiotics of a number of macrolides are divided according to the method of production into natural and synthetic, according to the chemical structure into 14-, 15- and 16-membered, according to generations into the first, second and third, according to the duration of action into rapid and long-lasting. Main classification:

	14-member	15-membered (azalides)	16-member
Natural	Erythromycin, oleandomycin (first generation)		Midecamycin, spiramycin, leukomycin, josamycin (third generation)
Prodrugs	Propionyl, ethyl succinate, stearate, phosphate, ascorbate, erythromycin succinate, troleandomycin, hydrochloride, oleandomycin phosphate		Myocamycin (midecamycin acetate)
Semi-synthetic	Roxithromycin, clarithromycin, flurithromycin, ketolide telithromycin	Azithromycin (second generation)	Rokimitacin

Macrolide antibiotics

Antimicrobial drugs of the macrolide group are presented in tablets, capsules, oral suspensions, and parenteral solutions. Oral forms are used for mild cases of the disease, intravenous and intramuscular for severe cases or when it is impossible to take pills.

First generation

First-generation macrolides are limited in monotherapy because microbial resistance to them quickly develops. The drugs are acid-resistant, taken orally, and combined with broad-spectrum tetracyclines. The drugs quickly reach maximum concentration in the blood, last up to 6 hours, penetrate well into tissues, and are excreted in feces and bile. Group representatives:

Name of the drug		Oleandomycin
Release form	Tablets, ointment, powder for solution	Pills
Indications for use	Laryngitis, tracheitis, trophic ulcers, cholecystitis, chlamydia, syphilis, gonorrhea, scarlet fever	Tonsillitis, brucellosis, phlegmon, osteomyelitis, sepsis
Contraindications	Hearing loss, age up to 14 years, lactation	Jaundice, liver failure
Mode of application	Orally 250-500 mg every 4-6 hours 1.5 hours before or 3 hours after meals	Orally after meals, 250-500 mg every 5 hours for 5-7 days
Side effects	Nausea, skin rash, candidiasis, ototoxicity, tachycardia	Skin itching, urticaria
Cost, rubles	90 for 20 tablets 250 mg	80 for 10 pcs. 250 mg

Second

Second generation macrolides are more highly active against enterobacteria, influenza bacteria, pseudomonads, and anaerobes. They are resistant to acid hydrolysis, are better absorbed in the stomach, and have a long-lasting effect. Their prolonged half-life allows the drugs to be used 1-2 times a day. Group representatives:

Name of the drug	Azithromycin		Macropen
Release form	Capsules, tablets, powder	Tablets, capsules, dispersible tablets, powder	Tablets, granules	Pills
Indications for use	Pharyngitis, otitis media, pneumonia, otitis media, erysipelas, urethritis, Lyme disease, dermatosis, impetigo	Tonsillitis, bronchitis, erythema, cervicitis	Enteritis, diphtheria, whooping cough	Cervicovaginitis, sinusitis, pneumonia
Contraindications	Lactation, renal, liver failure	Liver dysfunction	Renal dysfunction	Concomitant use of ergotamine
Mode of application	500 mg per day in a course of 3 days orally 1.5 hours before or 2 hours after meals	500 mg once a day for 3 days	400 mg three times a day for 1-2 weeks	150 mg every 12 hours
Side effects	Diarrhea, dyspepsia, constipation, palpitations, dizziness, photosensitivity, nephritis	Chest pain, headache	Stomatitis, vomiting, jaundice, urticaria, diarrhea	Bronchospasm, skin hyperemia, nausea, hepatitis, pancreatitis, superinfection
Cost, rubles	1420 for 6 capsules 250 mg	445 for 3 pcs. 500 mg	270 for 8 pcs. 400 mg	980 for 10 pcs. 150 mg

Third

The latest generation of macrolides are well tolerated, resistance to them develops very slowly, and they are better absorbed. By inhibiting microbial cell protein synthesis, they lead to bacteriostasis. The drugs penetrate well into tissues, especially bones, are excreted by the kidneys, with bile, and act for up to 12 hours. Group representatives:

Name of the drug	Lincomycin	Clindamycin
Release form	Ointment, ampoules, capsules	Capsules, vaginal cream, solution for parenteral administration
Indications for use	Sepsis, osteomyelitis, lung abscess, pleurisy, otitis, purulent arthritis, pyoderma, furunculosis	Pharyngitis, pneumonia, chlamydia, abscess, felon, peritonitis
Contraindications	Pregnancy, lactation, age up to 3 years	Myasthenia gravis, ulcerative colitis, breastfeeding, age up to 8 years
Mode of application	Intramuscularly 500 mg twice a day; orally 1 pc. 2-3 times a day	Intramuscularly 150-450 mg every 6 hours, orally in the same dose every 4-6 hours
Side effects	Dizziness, hypotension, glossitis, enterocolitis	Esophagitis, leukopenia, fever, decreased blood pressure, phlebitis, dermatitis, vaginitis, candidiasis
Cost, rubles	45 for 20 capsules 250 mg	175 for 16 capsules 150 mg

Macrolides for children

Antibiotics of the macrolide group are used in children for initial treatment of atypical respiratory infections (bronchitis, pneumonia caused by mycoplasmas, chlamydia) with intolerance to beta-lactam drugs. In children under five years of age, drugs are used to treat bronchitis, sore throat, and pharyngitis. Children can be given oral or parenteral forms of drugs for otitis, tonsillopharyngitis, diphtheria, and whooping cough. Popular group products for use in pediatrics:

Clarithromycin;
Roximitrocin;
Azithromycin;
Spiramycin;
Josamycin.

Video

Found an error in the text?
Select it, press Ctrl + Enter and we will fix everything!