Macrolide spectrum of action. The use of macrolides in children in modern conditions

A drug	Commercial names	Routes of administration and doses
erythromycin	GRUNAMICIN	Inactivated in an acidic environment, food significantly reduces bioavailability, inhibits cytochrome R-450 liver, erythromycin preparations (except estolate) can be prescribed during pregnancy and breastfeeding
CLARITRO- MYCIN*	CLABAX, KLATSID, FROMILID	Has a pronounced effect on Helicobacter pylori and atypical mycobacteria, stable in an acidic environment, undergoes presystemic elimination, forms an active metabolite, is excreted in the urine, is contraindicated in children under 6 months, during pregnancy and breastfeeding
ROSKYSTRO-MICIN	RULID	Suppresses protozoa, stable in an acidic environment, does not affect the activity of cytochrome R-450
AZITHROMYCIN	SUMAMED	More than other macrolides, it suppresses Haemophilus influenzae, is active against protozoa and some enterobacteria (Shigella, Salmonella, Vibrio cholerae), is stable in an acidic environment, undergoes presystemic elimination, creates the highest concentrations in cells, has a long half-life
JOSAMYCIN	VILPRAFEN	Suppresses some strains of streptococci and staphylococci resistant to erythromycin, does not affect the activity of cytochrome R-450, contraindicated in pregnancy and breastfeeding

End of table 6

* Clatrithromycin SR(clacid SR) is available in matrix tablets with a delayed release of the antibiotic, it is prescribed 1 time per day.

Macrolides, depending on the type of microorganisms and the dose, have a bacteriostatic or bactericidal effect. They suppress gram-positive bacteria producing β-lactamase, as well as microorganisms localized intracellularly - listeria, campylobacter, atypical mycobacteria, legionella, spirochetes, mycoplasmas, ureaplasmas. Clarithromycin is superior to other macrolides in activity against Helicobacter pylori and atypical mycobacteria, azithromycin has a stronger effect on Haemophilus influenzae. Roxithromycin, azithromycin and spiromycin suppress protozoa - toxoplasma and cryptosporidium.

Antimicrobial spectrum of macrolides: Staphylococcus aureus (methicillin-sensitive), hemolytic streptococci, pneumococci, viridescent streptococci, meningococci, gonococci, moraxella, corynebacterium diphtheria, listeria, clostridium gas gangrene, Haemophilus influenzae, causative agent of soft chancre, Helicobacter pylori, the causative agent of whooping cough, atypical microbacteria (except Mycobacterium fortuitum), bacteroids ( Bacteroides melaninogenicus, B. oralis), legionella, mycoplasma, ureaplasma, chlamydia, spirochetes.

Natural resistance to macrolides is characteristic of enterococci, intestinal microflora, Pseudomonas aeruginosa, a number of anaerobic pathogens that cause severe pyoinflammatory processes. Macrolides, without disturbing the colonization activity of intestinal bacteria, do not lead to the development of dysbacteriosis.

Secondary resistance of microorganisms to macrolides develops rapidly, so the course of treatment should be short (up to 7 days), otherwise they must be combined with other antibiotics. It should be emphasized that in the event of secondary resistance to one of the macrolides, it applies to all other antibiotics of this group and even to drugs from other groups: lincomycin and penicillins.

Pharmacokinetics. Some macrolides can be administered intravenously (erythromycin phosphate, spiramycin). The subcutaneous and intramuscular routes are not used, since injections are painful and local tissue damage is noted.

All macrolides can be administered orally. More acid-resistant are oleandomycin and antibiotics of the II and III generations, so they can be taken regardless of the meal.

Regardless of the antimicrobial action, macrolides have the following effects:

They prevent the hypersecretion of bronchial mucus, exerting a mucoregulatory effect (with a dry unproductive cough, it is recommended to additionally take mucolytic agents);

Weaken the inflammatory response as a result of the antioxidant effect and inhibition of the synthesis of prostaglandins, leukotrienes and interleukins (used to treat panbronchitis and steroid-dependent bronchial asthma);

Show immunomodulatory properties.

A unique feature of clarithromycin is its antitumor activity.

Macrolides are absorbed into the blood from the duodenum. The base of erythromycin is largely destroyed by gastric juice, so it is used in the form of esters, as well as enteric-coated tablets and capsules. The new macrolides are acid-resistant, rapidly and completely absorbed, although many drugs undergo presystemic elimination. Food reduces the bioavailability of macrolides by 40-50% (except for josamycin and spiramycin).

The relationship of macrolides with blood proteins varies from 7 to 95%. They poorly penetrate the blood-brain and blood-ophthalmic barriers, accumulate in the secretion of the prostate gland (40% of the concentration in the blood), exudate of the middle ear (50%), tonsils, lungs, spleen, liver, kidneys, bones, overcome the placental barrier (5 - 20 %), pass into breast milk (50%). The content of antibiotics is much higher inside the cells than in the blood. Macrolide-enriched neutrophils deliver these antibiotics to sites of infection.

Macrolides are used for infections of the respiratory tract, skin and soft tissues, oral cavity, genitourinary system caused by intracellular pathogens and gram-positive bacteria resistant to penicillins and cephalosporins. The main indications for their appointment are as follows:

Upper respiratory tract infections - streptococcal tonsillopharyngitis, acute sinusitis;

Infections of the lower respiratory tract - exacerbation of chronic bronchitis, community-acquired pneumonia, including atypical pneumonia (in 20-25% of patients, pneumonia is caused by mycoplasma or chlamydial infection);

Diphtheria (erythromycin in combination with antidiphtheria serum);

Infections of the skin and soft tissues;

Oral infections - periodontitis, periostitis;

Gastroenteritis caused by campylobacter (erythromycin);

eradication Helicobacter pylori with peptic ulcer (clarithromycin, azithromycin);

Trachoma (azithromycin);

Sexually transmitted infections - chlamydia, venereal lymphogranuloma, syphilis without lesions of the nervous system, soft chancre;

Lyme disease (azithromycin);

Infections caused by atypical microbacteria in AIDS patients (clarithromycin, azithromycin);

Prevention of whooping cough in people who have been in contact with patients (erythromycin);

Sanitation of carriers of meningococci (spiramycin);

Year-round prevention of rheumatism in case of allergy to benzylpenicillin (erythromycin);

Prevention of endocarditis in dentistry (clarithromycin, azithromycin).

In the future, macrolides will find application in the treatment of atherosclerosis, since the etiological factor of this disease in 55% of cases is Chlamydia pneumoniae.

Macrolides are evaluated as low-toxic antimicrobial agents. Occasionally, they cause allergic reactions in the form of fever, code rash, urticaria, eosinophilia.

Erythromycin and, to a lesser extent, josamycin and spiramycin cause dyspeptic disorders. After 10-20 days of treatment with erythromycin and clarithromycin, cholestatic hepatitis may develop with nausea, vomiting, spastic abdominal pain, fever, jaundice, and an increase in the activity of aminotransferases in the blood. Liver biopsy shows cholestasis, parenchymal necrosis, and periportal cell infiltration. With intravenous infusion of macrolides, thrombophlebitis, reversible hearing loss, prolongation of the interval may occur. Q-T and other forms of arrhythmias.

Erythromycin and clarithromycin, by inhibiting cytochrome R-450 liver, prolong and enhance the effect of drugs with metabolic clearance (tranquilizers, carbamazepine, valproates, theophylline, disopyramide, ergometrine, corticosteroids, astemizole, terfenadine, cyclosporine). New macrolides only slightly change the metabolism of xenobiotics.

Macrolides are contraindicated in hypersensitivity, pregnancy and breastfeeding. In patients with renal insufficiency, the dose of clarithromycin is reduced in accordance with creatinine clearance. In severe liver disease, dose adjustment of all macrolides is necessary. At the time of antibiotic therapy, you should stop drinking alcoholic beverages.

AMINOGLYCOSIDES

Aminoglycoside antibiotics are amino sugars linked by a glycosidic bond to a hexose (aminocyclitol ring). They are used only parenterally, poorly penetrate the cells and cerebrospinal fluid, are excreted unchanged by the kidneys. Aminoglycosides are considered the drugs of choice for infections caused by anaerobic gram-negative bacteria (tuberculosis, nosocomial infections, septic endocarditis). Their widespread use is hindered by pronounced oto-, vestibulo- and nephrotoxicity.

The history of the clinical use of aminoglycosides goes back about 60 years. In the early 1940s, the American microbiologist, future Nobel Prize winner Zelman Waksman, impressed by the discovery of benzylpenicillin, which suppresses pyogenic microflora, set out to create an antibiotic effective against tuberculosis. To do this, he investigated the antimicrobial effect of a large number of soil fungi. In 1943 from culture liquid Streptomyces griseus streptomycin was isolated, which is detrimental to tuberculosis bacteria, many anaerobic gram-positive and gram-negative bacteria. Since 1946, streptomycin has been widely used in clinical practice.

In 1949, Z. Waksman and his collaborators received neomycin from the culture Streptomyces fradie. In 1957, scientists at the Japan National Health Center isolated kanamycin from Streptomyces kanamyceticus.

Gentamicin (described in 1963) and netilmicin are produced by actinomycete Microspora.

Tobramycin and amikacin have been known since the early 1970s. Tobramycin is part of the aminoglycoside nebramycin, produced Streptomyces tenebrarius. Amikacin is a semi-synthetic acylated derivative of kanamycin. The search for new aminoglycoside antibiotics has been suspended due to the emergence of less toxic β-lactams and fluoroquinolones with the same antimicrobial activity as aminoglycosides.

There are 3 generations of aminoglycoside antibiotics:

I generation - streptomycin, kanamycin, neomycin (used only for the purpose of local action);

II generation - gentamicin, tobramycin, amikacin;

III generation - netilmicin (has less oto- and vestibulotoxicity).

Streptomycin and kanamycin suppress mycobacterium tuberculosis, streptomycin is active against brucella, plague and tularemia pathogens. E. coli, Klebsiella, Enterococcus species, Proteus and Enterobacter are most sensitive to neomycin. Antibiotics II - III generation are toxic to Escherichia coli, Klebsiella, Serrations, Pseudomonas aeruginosa, Proteus species, Enterobacter and Acinetobacter. All aminoglycosides inhibit 90% of strains of Staphylococcus aureus. Resistance to aminoglycosides is characteristic of anaerobic bacteria, hemolytic streptococci and pneumococci.

The bactericidal action of aminoglycosides is due to the formation of abnormal proteins and detergent effect on the lipoprotein cytoplasmic membrane of microorganisms.

Antibiotics of the β-lactam group, inhibiting the synthesis of the cell wall, potentiate the antimicrobial effect of aminoglycosides. On the contrary, chloramphenicol, blocking transport systems in the cytoplasmic membrane, weakens their action.

The mechanisms of acquired resistance of microorganisms to aminoglycosides are as follows:

Synthesized enzymes that inactivate antibiotics;

The permeability of the porin channels of the cell wall of gram-negative bacteria decreases;

The binding of aminoglycosides to ribosomes is impaired;

The release of aminoglycosides from the bacterial cell is accelerated.

Streptomycin and gentamicin lose their activity under the influence of various enzymes, so streptomycin-resistant strains of microorganisms can react to gentamicin. Kanamycin, gentamicin, tobramycin, amikacin, and netilmicin are inactivated by polyfunctional enzymes, resulting in cross-resistance between them.

1% of the dose of aminoglycosides is absorbed from the intestine, the rest is excreted unchanged in the feces. Absorption of gentamicin is increased in peptic ulcer and ulcerative colitis. Aminoglycosides can create toxic concentrations in the blood when taken orally for a long time against the background of renal failure, introduced into body cavities, applied to extensive burn surfaces and wounds. When injected into the muscles, they have a high bioavailability, creating a maximum level in the blood after 60-90 minutes.

Aminoglycosides are distributed in the extracellular fluid, bind to blood albumin to a small extent (10%), penetrate poorly into cells, cerebrospinal fluid, eye media, respiratory mucosa, slowly enter the pleural and synovial fluid, accumulate in the cortical layer of the kidneys, endolymph and perilymph of the inner ear. With meningitis and in newborns, the level of aminoglycosides in the brain reaches 25% of the content in the blood (normally 10%). Their concentration in bile is 30% of the concentration in the blood. This is due to the active secretion of antibiotics in the bile ducts of the liver.

The intake of aminoglycosides by women in late pregnancy is accompanied by an intensive intake of the drug into the blood of the fetus, which can cause sensorineural hearing loss in the child. Aminoglycosides pass into breast milk.

Aminoglycosides are excreted unchanged by filtration in the glomeruli of the kidneys, creating a high concentration in the urine (with hyperosmotic urine, antimicrobial activity is lost).

The pharmacokinetics of aminoglycosides changes in pathological conditions. With renal insufficiency, the half-life is extended by 20 to 40 times. In contrast, with fibrosis of the bladder, elimination is accelerated. Aminoglycosides are well removed from the body by hemodialysis.

Currently, aminoglycoside antibiotics are recommended to be administered once a day at a dose calculated per kilogram of body weight. The appointment of drugs once a day, without affecting the therapeutic efficacy, can significantly reduce nephrotoxicity. With meningitis, sepsis, pneumonia and other severe infections, maximum doses are prescribed, with diseases of the urinary tract - medium or minimal. In patients with renal insufficiency, reduce the dose of aminoglycosides and lengthen the intervals between their administration.

The main routes of administration: intramuscularly, if the patient does not have serious hemodynamic disorders; intravenously slowly or drip; locally (in the form of ointments and liniments); endotracheal instillations and inside.

Drugs do not penetrate inside the cells. Easily pass through the placenta, enter the tissues of the inner ear and the cortical layer of the kidneys.

Aminoglycosides are not biotransformed. They are almost completely excreted by the kidneys unchanged. Effective in alkaline environment.

The main disadvantage of this group is a rather high toxicity, their neurotoxic, primarily ototoxic, effect is especially pronounced, manifested in the development of neuritis of the auditory nerve, as well as in imbalance. Severe hearing and balance disorders often lead to complete disability, and young children, having lost their hearing, often forget speech and become deaf and dumb. Aminoglycoside antibiotics can also have a nephrotoxic effect. At the same time, necrosis develops in the epithelium of the renal tubules, ending in the death of the patient.

When taking these antibiotics inside, dyspeptic disorders are not uncommon. Anaphylactic shock is caused mainly by streptomycin sulfate, which in this respect is in second place after penicillin preparations.

Aminoglycosides can disrupt hearing, balance (in 10-25% of patients), kidney function, and cause neuromuscular blockade. At the beginning of aminoglycoside therapy, tinnitus appears, the perception of high sounds outside the frequencies of colloquial speech worsens, as the lesion progresses from the basal coil of the cochlea, where high-frequency sounds are perceived, to the apical part, which responds to low sounds. Aminoglycosides accumulate to a greater extent in the well-vascularized base of the cochlea. In severe cases, speech intelligibility is impaired, especially high-frequency whispering.

Vestibular disorders are preceded by a headache for 1 to 2 days. In the acute stage, nausea, vomiting, dizziness, nystagmus, posture instability occur. After 1 - 2 weeks. the acute stage turns into chronic labyrinthitis (unsteady gait, difficulty in doing work). After another 2 months. comes the stage of compensation. The functions of the damaged vestibular analyzer are taken over by vision and deep proprioceptive sensitivity. Disorders in the motor sphere occur only with closed eyes.

As a result, aminoglycosides cause degeneration of the auditory nerve, death of hair cells in the spiral (Corti) organ of the cochlea and the ampulla of the semicircular canals. Hearing and vestibular disorders in the later stages are irreversible, since the sensitive cells of the inner ear do not regenerate.

The toxic effect of aminoglycosides on the inner ear is more pronounced in the elderly, potentiated by diuretics - ethacrynic acid and furosemide. Streptomycin and gentamicin often cause vestibular disorders, neomycin, kanamycin and amikacin predominantly impair hearing (in 25% of patients). Tobramycin damages the auditory and vestibular analyzers equally. Less dangerous is netilmicin, which causes ototoxic complications in only 10% of patients.

In 8-26% of patients, aminoglycosides cause mild renal dysfunction after a few days of therapy. As antibiotics accumulate in the cortical layer of the kidneys, filtration and reabsorption deteriorate, proteinuria occurs, and brush border enzymes appear in the urine. Occasionally, acute necrosis of the proximal renal tubules develops. Kidney damage can be reversible, as nephrons are capable of regeneration.

Less dangerous is the introduction of antibiotics once a day in an intermittent course. Neomycin has a high nephrotoxicity (it is used exclusively locally), in descending order of pathogenic effects on the kidneys, tobramycin, gentamicin and streptomycin follow. The nephrotoxicity of aminoglycosides is enhanced by amphotericin B, vancomycin, cyclosporine, cisplatin, potent diuretics, weakened by calcium ions. Against the background of kidney damage, the excretion of aminoglycosides decreases, which potentiates their oto- and vestibulotoxicity.

Against the background of anesthesia with the use of antidepolarizing muscle relaxants, aminoglycosides, independently causing neuromuscular blockade, can prolong paralysis of the respiratory muscles. The most dangerous in this regard are injections of antibiotics into the pleural and peritoneal cavities, although a complication also develops when injected into a vein and muscles. Pronounced neuromuscular blockade is caused by neomycin, kanamycin, amikacin, gentamicin, tobramycin and streptomycin are less toxic. The risk group are patients with myasthenia gravis and parkinsonism.

In neuromuscular synapses, aminoglycosides weaken the stimulating effect of calcium ions on the release of acetylcholine through the presynaptic membrane, reduce the sensitivity of nicotine-sensitive cholinergic receptors of the postsynaptic membrane. As antagonists, calcium chloride and anticholinesterase agents are infused into the vein.

Streptomycin can damage the optic nerve and narrow visual fields, as well as cause paresthesia and peripheral neuritis. Aminoglycosides have low allergenicity, only occasionally, when administered, fever, eosinophilia, skin rash, angioedema, exfoliative dermatitis, stomatitis develop, and anaphylactic shock develops.

Aminoglycosides are contraindicated in hypersensitivity, botulism, myasthenia gravis, Parkinson's disease, drug parkinsonism, hearing and balance disorders, severe kidney disease. Their use during pregnancy is allowed only for health reasons. At the time of treatment stop breastfeeding.

Increasing the dosage helps to achieve a bactericidal effect.

Macrolides belong to the class of polyketides. Polyketides are polycarbonyl compounds that are metabolic intermediates in animal, plant, and fungal cells.

When taking macrolides, there were no cases of selective dysfunction of blood cells, its cellular composition, nephrotoxic reactions, secondary dystrophic damage to the joints, photosensitivity, manifested by hypersensitivity of the skin to ultraviolet radiation. Anaphylaxis and the occurrence of 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 infections of the respiratory tract caused by gram-positive flora and atypical pathogens. A little background information will help us systematize 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 turn into the same active drug, which has a characteristic pharmacological effect.

Prodrugs have improved palatability and high bioavailability. They are acid resistant.

The classification implies the division of macrolides into 3 groups:

* ex. - Natural.
*pol.- Semi-synthetic.

It is worth noting that azithromycin is an azalide, since 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 in the presented pharmacological agents are identical.

Consider the main representatives of the group separately.

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

Among the side effects noted: 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 an enzyme that breaks down beta-lactams, 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 about 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, palatine tonsils, gallbladder, urethra, vaginal segment of the cervix, infections of the skin, musculoskeletal system, brucellosis, etc.
Pregnancy, lactation and age up to two months are contraindications.

Inhibits the growth of aerobes and anaerobes. There is low activity in relation to the Koch stick. Clarithromycin is superior to erythromycin in microbiological parameters. The drug is acid-resistant. 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 about five hours. The bioavailability of the drug does not depend on food.

K. is prescribed for infection of wounds, infectious diseases of the upper respiratory tract, purulent rashes, furunculosis, mycoplasmosis, mycobacteriosis against the background of the immunodeficiency virus.
Clarithromycin should not be taken in early pregnancy. Infant age 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 the use of oleandomycin are rare, as it is outdated.
Ol. prescribed for brucellosis, abscess pneumonia, bronchiectasis, gonorrhea, inflammation of the meninges, the inner lining of the heart, infections of the upper respiratory tract, purulent pleurisy, furunculosis, the ingress of pathogenic microorganisms into the bloodstream.

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

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

A natural antibiotic derived from the radiant fungus Streptomyces narbonensis. Bactericidal action is achieved at high concentrations in the focus of infection. J - n inhibits protein synthesis and inhibits the growth of pathogens.

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

Approved for use during lactation, it is prescribed for the treatment of pregnant women. Newborns and children under fourteen years of age are shown a suspension form.

Differs in high indicators of microbial activity and good pharmacokinetic properties. The bactericidal effect is achieved by a significant increase in the dose. The bacteriostatic effect is associated with the inhibition of protein synthesis.

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

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

The period of lactation (penetrates 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 one. Alkali contributes to an increase in penetrating ability: the antibiotic gets better inside the cells of pathogens.

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

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

In the treatment of macrolides, the occurrence of life-threatening drug reactions is excluded. NLR in children are manifested by pain in the abdomen, discomfort in the epigastrium, vomiting. In general, the children's body tolerates macrolide antibiotics well.

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

Clirithromycin deserves special attention, surpassing 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 protective functions of the body.

Macrolides are used for:

• treatment 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 emergencies. A macrolide antibiotic is what the pediatrician most often prescribes when treating infections in young patients.

Therapy with macrolides rarely causes anatomical and functional changes, but the occurrence of side effects is not excluded.

In the course of a scientific study, in which about 2 thousand people took part, it was found that the likelihood of anaphylactoid reactions when taking macrolides is minimal. No cases of cross-allergy have been reported. Allergic reactions are manifested in the form of nettle fever and exanthema. In rare cases, anaphylactic shock is possible.

Dyspeptic phenomena occur due to the prokinetic effect inherent in macrolides. Most patients note frequent bowel movements, pain in the abdomen, impaired taste sensations, and vomiting. Newborns develop pyloric stenosis, a disease in which the evacuation of food from the stomach into the small intestine is difficult.

Pirouette ventricular tachycardia, cardiac arrhythmia, long QT interval syndrome are the main manifestations of cardiotoxicity of this group of antibiotics. The situation is aggravated by advanced age, heart disease, overdose, water and electrolyte disorders.

A long course of treatment, excess dosage are the main causes of hepatoxicity. Macrolides act differently 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 does not have any 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 in question:

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 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 favorably distinguish macrolides against the background of β-lactams.

Erythromycin marked the beginning of the macrolide class.

The first acquaintance with erythromycin occurred in 1952. Eli Lilly & Company, an international American innovative company, has replenished its portfolio of the latest pharmaceuticals. Her scientists derived erythromycin from a radiant fungus that lives in the soil. Erythromycin has become an excellent alternative for patients with hypersensitivity to penicillin antibiotics.

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

The erythromycin series is different:

• high activity against Streptococcus and Staphylococcus and intracellular microorganisms;
• low rates of toxicity;
• no cross-allergy with beta-lactim antibiotics;
• creating high and stable concentrations in tissues.

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Many believe that antibiotics should be used only in extreme cases. However, this is not an entirely correct opinion, since the list of such drugs is replenished with drugs that are relatively safe - macrolides. Such antibiotics, basically, without having a negative impact on the human body, are able to overcome the infection “in no time”. The safe profile allows prescribing macrolides to patients undergoing outpatient and inpatient treatment, as well as to children aged 6 months and older (under medical supervision).

Few people know about the properties, origin and effect of such "harmless" remedies. And if you want to get acquainted with such drugs and find out in more detail what a macrolide antibiotic is, we suggest reading our article.

It should be noted right away that macrolides belong to the group of antibiotic drugs that are the least toxic to the human body and are well tolerated by patients.

Antibiotics such as macrolides, from the point of view of biochemistry, are complex compounds of natural origin, which consist of carbon atoms, which are in different amounts in the macrocyclic lactone ring.

If we take this criterion, which is responsible for the number of carbon atoms, as the basis for the classification of drugs, then we can divide all such antimicrobial agents into:

• 14-membered, which include semi-synthetic drugs - Roxithromycin and Clarithromycin, as well as natural - Erythromycin;
• 15-membered, represented by a semi-synthetic agent - Azithromycin;
• 16-membered, including a group of natural drugs: Midecamycin, Spiramycin, Josamycin, as well as semi-synthetic Midecamycin acetate.

Erythromycin, an antibiotic of the macrolide group, was one of the first to be discovered, in 1952. New generation drugs appeared a little later, in the 70s. Since they showed excellent results in the fight against infections, research on this group of drugs has continued actively, so that today we have a fairly extensive list of drugs that can be used to treat both adults and children.

http://youtu.be/-PB2xZd-qWE

The antimicrobial effect is achieved by affecting the ribosomes of microbial cells, disrupting protein synthesis. Of course, under such an attack of macrolides, the infection weakens and “surrenders”. In addition, antibiotics of this group of drugs are able to regulate immunity, providing immunomodulatory activity. Also, these drugs have anti-inflammatory properties, affecting both the body of adults and children, quite moderately.

Means of the group of antibacterial agents of the new generation are able to cope with atypical microbacteria, gram-positive cocci and similar misfortunes, which often become the causative agents of diseases such as bronchitis, whooping cough, diphtheria, pneumonia, etc.

No less popular are macrolides in the situation that has developed over the past few years, due to the addiction of a large number of microbes to antibiotics (resistance). This is due to the fact that new generation drugs belonging to this group are able to maintain their activity against a variety of pathogens.

In particular, macrolide preparations are widely used in the treatment and as prophylactic agents for the following diseases:

• Chronical bronchitis;
• acute sinusitis;
• periostitis;
• periodontitis;
• rheumatism;
• endocarditis;
• gastroenteritis;
• severe forms of toxoplasmosis, acne, mycobacteriosis.

The list of diseases that can be overcome using new generation antibiotics, which have a common name - macrolides, can be supplemented by sexually transmitted infections - syphilis, chlamydia and infections that affect soft tissues and skin - furunculosis, folliculitis, paronychia.

If your doctor prescribes a similar antibiotic for you, immediately read its contraindications indicated in the instructions for the drug. Unlike most conventional antibiotics, new generation drugs - macrolides are safe, including for children, and less toxic. Therefore, the list of undesirable effects of antibiotics in this group is not as large as that of similar drugs.

First of all, it is not recommended to use macrolides for pregnant women and mothers during lactation. The use of such drugs in children under 6 months is contraindicated, since the reaction to the drug has not yet been studied. You should not use such drugs as a treatment for people who have individual sensitivity.

Antibiotics of the macrolide group with special attention should be prescribed by doctors to patients of mature age. This is due to the fact that most of the older generation have disorders in the functioning of the kidneys, liver and heart.

Side effects can also occur when using macrolides in a mild form - weakness and malaise that appear after taking them. But there may also be:

• vomit;
• nausea;
• headache and pain in the abdomen;
• impaired vision, hearing;
• an allergic reaction in the form of a rash, urticaria (most often occurs in children).

In order to avoid problems and undesirable consequences after the use of drugs of the macrolide group, it is necessary to strictly follow the doctor's recommendations, strictly observe the dosage and refrain from drinking alcohol. It is also strictly forbidden to combine the intake of new generation antibiotics with antacids. It is also important not to skip appointments.

Basically, new generation antibiotics should be taken 1 hour before a meal, or 2 hours after a meal. Take the tablets with a whole glass of water. If the doctor has prescribed you an antibiotic of the macrolide group, the release form of which is a powder for the preparation of a suspension, strictly follow the instructions for preparing the medicine and strictly follow the doctor's instructions.

In the fight against bacterial and other diseases that have arisen in children, the first place today is occupied by antibiotics - macrolides. This is one of the few groups of drugs that have earned the respect of specialists and are boldly used in pediatrics. The advantage of such medications, unlike other similar ones, is that they practically do not cause allergic reactions in young patients. In particular, this applies to drugs that have names - "Penicillin" and "Cefalosporin".

Despite the fact that macrolides are safe for children, they have a fairly effective effect. Their impact in a mild form on the child's body is provided by the pharmacokinetic properties inherent in the preparations. Some of the most popular means that represent the macrolide group are:

• Erythromycin;
• Clarithromycin;
• Roxithromycin;
• Spiramycin etc.

The dosage of the use of such drugs for children depends on the type of disease and the weight of the child. Therefore, try to follow the doctor's recommendations. In general, the produced forms of such funds are very convenient to use. Some of them are in the form of ointments for external use, and are also intended for parenteral use of the form, which, in turn, is relevant for children in emergency situations.

Summing up, we can safely say that macrolides, like antibiotics, are “white and fluffy”. Virtually no side effects and undesirable consequences, these new generation drugs have found their acceptance among many doctors and specialists. Effective, and able to cope even with severe forms of diseases, such antibiotics are used even in the treatment of children.

Macrolide antibiotics are antibacterial agents widely used in modern medical practice for the treatment of infectious diseases. This group of drugs belongs to the least toxic antibiotics, which have less pronounced side effects than other antibacterial drugs.

Clinical studies confirm that macrolides have a persistent post-antibiotic effect, that is, for a long time after ingestion, they suppress the vital activity of bacterial microorganisms. In addition, the drugs of this group have non-antibacterial activity, which is expressed in the form of anti-inflammatory and prokinetic action (the ability to stimulate the motility of the gastrointestinal tract).

Most often, macrolide antibiotics are used in the treatment of the following diseases:

• respiratory infections (whooping cough, diphtheria, sinusitis, tonsillitis, exacerbation of chronic bronchitis);
• skin and soft tissue infections (furunculosis, folliculitis);
• bacterial infections of the oral cavity (periodontitis, periostitis);
• sexually transmitted infections (chlamydia, syphilis);
• gastroenteritis;
• urinary tract infections;
• severe forms of acne.

In addition, macrolide antibiotics can be used to prevent infectious diseases in rheumatological and dental practices. They are also used to prevent post-operative infections after certain surgeries.

Macrolide antibiotics are classified according to their chemical structure and method of preparation. Depending on the chemical structure, macrolides are divided into:

• 14-membered (erythromycin, clarithromycin, roxithromycin, oleandomycin, dirithromycin);
• 15-membered (azithromycin);
• 16-membered (spiramycin, midecamycin, josamycin).

This classification is necessary to assess the safety of drugs, which largely depends on the characteristics of their chemical structure. For example, 14-membered macrolides have a stimulating effect on the motility of the gastrointestinal tract, which can provoke various intestinal disorders. 15-membered and 16-membered macrolides can also cause this undesirable effect, however, it is much less pronounced.

Depending on the method of preparation, preparations of the macrolide group are divided into natural and synthetic. The list of natural antibacterial agents includes erythromycin, midecamycin, oleandomycin, spiramycin, josamycin. Semi-synthetic drugs include clarithromycin, azithromycin, roxithromycin.

Antibiotics from the macrolide group are among the safest types of antibacterial agents. They have a relatively low toxicity, do not have a pronounced effect on the body's immune system and are well tolerated by patients. Compared with antibiotics of other groups, macrolides are less likely to cause allergic reactions. Currently, they are widely used in the treatment of infectious diseases in newborns, children and pregnant patients.

At the same time, this type of antimicrobial drugs can cause a number of undesirable effects:

• gastrointestinal disorders (nausea, vomiting, diarrhea, abdominal pain);
• increased risk of severe cardiac disorders;
• pressure drop;
• abnormal liver function (cholestatic hepatitis);
• reversible hearing loss;
• allergic reactions.

Roxithromycin has the best tolerance among macrolides. It is followed by azithromycin, then by spiramycin and clarithromycin, and after them by erythromycin. As for contraindications for use, they are set on an individual basis, depending on the type and characteristics of the course of the disease, the patient's condition and the form of release of the drug.

Some macrolide antibiotics should not be used in children, pregnant or lactating women, or in patients with severe hepatic impairment.

Other drugs in this group can be prescribed to elderly patients, newborns, young children and women during pregnancy and breastfeeding. However, such an appointment is allowed only if there are strict indications and requires careful medical supervision during the entire period of treatment.

International name:

Dosage form:

Pharmachologic effect:

Indications:

International name:

Dosage form:

Pharmachologic effect:

Indications:

International name: Roxithromycin (Roxithromycin)

Dosage form: dispersible tablets, coated tablets

Pharmachologic effect: Semi-synthetic macrolide antibiotic for oral administration. Has a bacteriostatic effect: binding to the 50S subunit of ribosomes.

Indications: Infections of the upper and lower respiratory tract (pharyngitis, bronchitis, pneumonia, bacterial infections in COPD, panbronchiolitis, bronchiectasis.

International name: Clarithromycin (Clarithromycin)

Dosage form: granules for suspension for oral administration, capsules, lyophilisate for solution for infusion, powder for suspension for oral administration, film-coated tablets, prolonged-release film-coated tablets

Pharmachologic effect: Semi-synthetic broad-spectrum macrolide antibiotic. Violates protein synthesis of microorganisms (binds to the 50S subunit of the membrane.

Indications: Bacterial infections caused by susceptible microorganisms: infections of the upper respiratory tract (laryngitis, pharyngitis, tonsillitis, sinusitis).

International name: Roxithromycin (Roxithromycin)

Dosage form: dispersible tablets, coated tablets

Pharmachologic effect: Semi-synthetic macrolide antibiotic for oral administration. Has a bacteriostatic effect: binding to the 50S subunit of ribosomes.

Indications: Infections of the upper and lower respiratory tract (pharyngitis, bronchitis, pneumonia, bacterial infections in COPD, panbronchiolitis, bronchiectasis.

International name: Josamycin (Josamycin)

Dosage form:

Pharmachologic effect:

Indications:

International name: Erythromycin (Erythromycin)

Dosage form: granules for suspension for oral administration, granules for suspension for oral administration, lyophilisate for solution for intravenous administration, powder for solution for injection, rectal suppositories [

Pharmachologic effect: A bacteriostatic antibiotic from the macrolide group, reversibly binds to the 50S subunit of ribosomes, which disrupts the formation of peptide bonds.

Indications: Bacterial infections caused by susceptible pathogens: diphtheria (including bacterial carriage), whooping cough (including prevention), trachoma.

International name: Josamycin (Josamycin)

Dosage form: oral suspension, coated tablets

Pharmachologic effect: An antibiotic from the group of macrolides, acts bactericidal. It binds to the 50S subunit of the ribosomal membrane and prevents fixation of the transport membrane.

Indications: Infectious and inflammatory diseases caused by susceptible microorganisms: otitis media, sinusitis, tonsillitis, pharyngitis, laryngitis, diphtheria.

International name: Dirithromycin (Dirithromycin)

Pharmachologic effect: Macrolide antibiotic. Suppresses intracellular protein synthesis in sensitive microorganisms. Active against gram-positive.

Indications: Infectious and inflammatory diseases caused by susceptible pathogens: pharyngitis; tonsillitis; bronchitis (acute and exacerbation); pneumonia; skin and soft tissue infections; cholecystitis, cholangitis.

Macrolides are a new generation of antibacterial agents. The basis of the structure of this type of antibiotics is the macrocyclic lactone ring. This fact gave the name to the whole group of drugs. Depending on the number of carbon atoms contained in the ring, all macrolides are: 14, 15, and 15-membered.

Antibiotics - macrolides are active against gram-positive cocci, as well as against intracellular pathogens: mycoplasmas, chlamydia, campylobacter, legionella. This group of drugs belongs to the least toxic antibiotics, and the list of drugs included in it is quite extensive.

Today we will talk about antibiotics macrolides, names, use, indications for use, we are considering - you will also find out all this, find out and discuss:

Names of macrolide antibiotics

The group of these drugs includes many drugs - antibiotics of the new generation. The most famous of them:

Natural macrolides: Oleandomycin phosphate, Erythromycin, Erycycline spiramycin, as well as midecamycin, leukomycin and josamycin.

Semi-synthetic macrolides: Roxithromycin, Clarithromycin, Dirithromycin. This group also includes: Flurithromycin, Azithromycin and Rokitamycin.

Often prescribe drugs such as: Vilprafen, Kitazamicin, Midecamycin. In a pharmacy, you will most likely be recommended the following names: Roxithromycin, Sumamed, Tetraolean and Eriderm.

It must be said that the names of antibiotic drugs often differ from the names of the macrolides themselves. For example, the active ingredient of the well-known drug "Azitrox" is the macrolide Azithromycin. Well, the drug "Zinerit" contains the antibiotic macrolide Erythromycin.

What are macrolide antibiotics good for? Indications for use

This group of drugs has a wide spectrum of action. Most often they are prescribed in the treatment of the following diseases:

Infectious diseases of the respiratory system: diphtheria, whooping cough, acute sinusitis. They are prescribed for the treatment of atypical pneumonia, used for exacerbations of chronic bronchitis.

Infectious diseases of soft tissues, skin: folliculitis, furunculosis, paronychia.

Sexual infections: chlamydia, syphilis.

Bacterial infections of the mouth: periostitis, periodontitis.

In addition, drugs of this group are prescribed in the treatment of toxoplasmosis, gastroenteritis, cryptosporidiosis, as well as in the treatment of severe acne. Assign for other infectious diseases. They can also be recommended for the prevention of infections in dental practice, rheumatology, as well as in surgical treatment of the colon.

How and how much to take macrolide antibiotics? Application, dosage

The group of macrolide antibiotics is represented by different dosage forms: tablets, granules, suspensions. Pharmacies will also offer: suppositories, powder in vials and a preparation in the form of a syrup.

Regardless of the dosage form, drugs intended for internal use are prescribed to drink by the hour, observing an equal period of time. Usually they are taken 1 hour before a meal, or 2 hours after it. Only a small number of these antibiotics are not dependent on food intake. Therefore, before starting treatment, carefully read the package leaflet.

In addition, any drug in this group can be used only for medical reasons as prescribed by a doctor. After establishing the diagnosis, the doctor will prescribe the remedy that will help with your disease, and exactly the dosage that you need. The dosage regimen takes into account the age, body weight of the patient, the presence of chronic diseases, etc.

Who are macrolide antibiotics dangerous for? Contraindications, side effects

Like most serious drugs, macrolides have a number of contraindications for use. They also have side effects. However, it should be noted that their number is significantly less than that of antibiotics of other groups. Macrolides are less toxic and therefore safer than other antibiotics.

However, they are contraindicated in pregnant women, nursing mothers, babies under 6 months. They can not be used in case of individual sensitivity of the body to the components of the drug. With caution, these drugs are prescribed to people with serious violations of the liver and kidneys.

With improper use or uncontrolled use, side effects may occur: headache, dizziness. Hearing may be disturbed, often there is nausea, vomiting, discomfort in the abdomen, and diarrhea appears. Allergic manifestations are observed: rash, urticaria.

Remember that self-prescribing, taking antibiotics without a doctor's prescription, can seriously aggravate the patient's condition. Be healthy!

Macrolides are a class of antibiotics whose chemical structure is based on a macrocyclic lactone ring. Depending on the number of carbon atoms in the ring, macrolides are divided into 14-membered (erythromycin, roxithromycin, clarithromycin), 15-membered (azithromycin) and 16-membered (midecamycin, spiramycin, josamycin). The main clinical significance is the activity of macrolides against gram-positive cocci and intracellular pathogens (mycoplasmas, chlamydia, campylobacter, legionella). Macrolides are among the least toxic antibiotics.

Macrolide classification

Mechanism of action

The antimicrobial effect is due to a violation of protein synthesis on the ribosomes of a microbial cell. As a rule, macrolides have a bacteriostatic effect, but in high concentrations they can act bactericidal against GABHS, pneumococcus, whooping cough and diphtheria pathogens. Macrolides exhibit PAE against Gram-positive cocci. In addition to the antibacterial action, macrolides have immunomodulatory and moderate anti-inflammatory activity.

Activity spectrum

Macrolides are active against Gram-positive cocci such as S.pyogenes, S.pneumoniae, S. aureus(except MRSA). In recent years, an increase in resistance has been noted, but at the same time, 16-mer macrolides in some cases can retain activity against pneumococci and pyogenic streptococci that are resistant to 14- and 15-mer drugs.

Macrolides act on whooping cough and diphtheria pathogens, moraxella, legionella, campylobacter, listeria, spirochetes, chlamydia, mycoplasma, ureaplasma, anaerobes (excluding B. fragilis).

Azithromycin is superior to other macrolides in activity against H.influenzae and clarithromycin against H. pylori and atypical mycobacteria ( M.avium and etc.). The action of clarithromycin on H.influenzae and a number of other pathogens enhances its active metabolite - 14-hydroxyclarithromycin. Spiramycin, azithromycin and roxithromycin are active against some protozoa ( T. gondii, Cryptosporidium spp.).

Microorganisms of the family Enterobacteriaceae, Pseudomonas spp. and Acinetobacter spp. are naturally resistant to all macrolides.

Pharmacokinetics

The absorption of macrolides in the gastrointestinal tract depends on the type of drug, dosage form and the presence of food. Food significantly reduces the bioavailability of erythromycin, to a lesser extent - roxithromycin, azithromycin and midecamycin, practically does not affect the bioavailability of clarithromycin, spiramycin and josamycin.

Macrolides are classified as tissue antibiotics, since their serum concentrations are significantly lower than those of tissues and vary with different drugs. The highest serum concentrations are observed in roxithromycin, the lowest in azithromycin.

Macrolides are bound to plasma proteins to varying degrees. The greatest binding to plasma proteins is observed in roxithromycin (more than 90%), the smallest - in spiramycin (less than 20%). They are well distributed in the body, creating high concentrations in various tissues and organs (including the prostate gland), especially during inflammation. In this case, macrolides penetrate into cells and create high intracellular concentrations. Poorly pass through the BBB and blood-brain barrier. Pass through the placenta and pass into breast milk.

Macrolides are metabolized in the liver with the participation of the cytochrome P-450 microsomal system, metabolites are excreted mainly with bile. One of the metabolites of clarithromycin has antimicrobial activity. Metabolites are excreted mainly with bile, renal excretion is 5-10%. The half-life of drugs ranges from 1 hour (midecamycin) to 55 hours (azithromycin). In renal failure, most macrolides (except clarithromycin and roxithromycin) do not change this parameter. With cirrhosis of the liver, a significant increase in the half-life of erythromycin and josamycin is possible.

Adverse reactions

Macrolides are one of the safest groups of AMPs. HPs are generally rare.

GIT: pain or discomfort in the abdomen, nausea, vomiting, diarrhea (most often they are caused by erythromycin, which has a prokinetic effect, less often - spiramycin and josamycin).

Liver: transient increase in transaminase activity, cholestatic hepatitis, which can be manifested by jaundice, fever, general malaise, weakness, abdominal pain, nausea, vomiting (more often with erythromycin and clarithromycin, very rarely with spiramycin and josamycin).

CNS: headache, dizziness, hearing impairment (rarely with intravenous administration of large doses of erythromycin or clarithromycin).

A heart: prolongation of the QT interval on the electrocardiogram (rarely).

Local reactions: phlebitis and thrombophlebitis with intravenous administration, caused by a local irritant effect (macrolides cannot be administered in a concentrated form and in a stream, they are administered only by slow infusion).

allergic reactions(rash, urticaria, etc.) are very rare.

Indications

STIs: chlamydia, syphilis (except neurosyphilis), chancroid, lymphogranuloma venereum.

Oral infections: periodontitis, periostitis.

Severe acne (erythromycin, azithromycin).

Campylobacter gastroenteritis (erythromycin).

eradication H. pylori with peptic ulcer of the stomach and duodenum (clarithromycin in combination with amoxicillin, metronidazole and antisecretory drugs).

Toxoplasmosis (usually spiramycin).

Cryptosporidiosis (spiramycin, roxithromycin).

Prevention and treatment of mycobacteriosis caused by M.avium in patients with AIDS (clarithromycin, azithromycin).

Preventive use:

prevention of whooping cough in people who have been in contact with patients (erythromycin);

sanitation of carriers of meningococcus (spiramycin);

year-round prevention of rheumatism in case of allergy to penicillin (erythromycin);

prevention of endocarditis in dentistry (azithromycin, clarithromycin);

decontamination of the intestine before colon surgery (erythromycin in combination with kanamycin).

Contraindications

Allergic reaction to macrolides.

Pregnancy (clarithromycin, midecamycin, roxithromycin).

Breastfeeding (josamycin, clarithromycin, midecamycin, roxithromycin, spiramycin).

Warnings

Pregnancy. There is evidence of an undesirable effect of clarithromycin on the fetus. There is no information demonstrating the safety of roxithromycin and midecamycin for the fetus, so they should also not be prescribed during pregnancy. Erythromycin, josamycin and spiramycin do not have a negative effect on the fetus and can be prescribed to pregnant women. Azithromycin is used during pregnancy if absolutely necessary.

Lactation. Most macrolides pass into breast milk (data are not available for azithromycin). Safety information for the breastfed infant is only available for erythromycin. The use of other macrolides in women who are breastfeeding should be avoided whenever possible.

Pediatrics. The safety of clarithromycin in children under 6 months of age has not been established. The half-life of roxithromycin in children may increase up to 20 hours.

Geriatrics. There are no restrictions on the use of macrolides in the elderly, however, possible age-related changes in liver function, as well as an increased risk of hearing impairment when using erythromycin, must be taken into account.

Impaired kidney function. With a decrease in creatinine clearance of less than 30 ml / min, the half-life of clarithromycin may increase to 20 hours, and its active metabolite - up to 40 hours. The half-life of roxithromycin may increase to 15 hours with a decrease in creatinine clearance to 10 ml / min. In such situations, it may be necessary to adjust the dosing regimen of these macrolides.

Impaired liver function. In severe liver disease, macrolides should be used with caution, as the half-life may increase and the risk of hepatotoxicity may increase, especially drugs such as erythromycin and josamycin.

Heart disease. Use with caution when prolonging the QT interval on the electrocardiogram.

Drug Interactions

Most drug interactions of macrolides are based on their inhibition of cytochrome P-450 in the liver. According to the severity of its inhibition, macrolides can be distributed in the following order: clarithromycin > erythromycin > josamycin = midecamycin > roxithromycin > azithromycin > spiramycin. Macrolides inhibit metabolism and increase the blood concentration of indirect anticoagulants, theophylline, carbamazepine, valproic acid, disopyramide, ergot drugs, cyclosporine, which increases the risk of developing adverse reactions characteristic of these drugs, and may require correction of their dosing regimen. It is not recommended to combine macrolides (except spiramycin) with terfenadine, astemizole and cisapride due to the risk of developing severe cardiac arrhythmias due to prolongation of the QT interval.

Macrolides may increase the oral bioavailability of digoxin by attenuating its inactivation by intestinal microflora.

Antacids reduce the absorption of macrolides, especially azithromycin, from the gastrointestinal tract.

Rifampicin enhances the metabolism of macrolides in the liver and lowers their concentration in the blood.

Macrolides should not be combined with lincosamides due to a similar mechanism of action and possible competition.

Erythromycin, especially when administered intravenously, is able to enhance the absorption of alcohol in the gastrointestinal tract and increase its concentration in the blood.

Information for patients

Most macrolides should be taken orally 1 hour before or 2 hours after a meal, and only clarithromycin, spiramycin, and josamycin can be taken with or without food.

Erythromycin, when taken orally, should be taken with a full glass of water.

Prepare and take liquid dosage forms for oral administration in accordance with the attached instructions.

Strictly follow the regimen and treatment regimen during the entire course of therapy, do not skip the dose and take it at regular intervals. If you miss a dose, take it as soon as possible; do not take if it is almost time for the next dose; do not double the dose. Maintain the duration of therapy, especially with streptococcal infections.

Do not use drugs that have expired.

Consult your doctor if there is no improvement within a few days or if new symptoms appear.

Do not take macrolides with antacids.

Do not drink alcohol during treatment with erythromycin.

Table. Preparations of the macrolide group.
Main characteristics and application features

INN	Lekform LS	F (inside), %	T ½, h *	Dosing regimen	Features of drugs
Erythromycin	Tab. 0.1 g; 0.2 g; 0.25 g and 0.5 g Gran. for susp. 0.125 g/5 ml; 0.2 g/5 ml; 0.4 g/5 ml Candles, 0.05 g and 0.1 g (for children) Susp. d / ingestion 0.125 g/5 ml; 0.25 g/5 ml Since. d / in. 0.05 g; 0.1 g; 0.2 g per vial.	30-65	1,5-2,5	Inside (1 hour before meals) Adults: 0.25-0.5 g every 6 hours; with streptococcal tonsillopharyngitis - 0.25 g every 8-12 hours; for the prevention of rheumatism - 0.25 g every 12 hours Children: up to 1 month: see the section "The use of AMP in children"; older than 1 month: 40-50 mg / kg / day in 3-4 doses (can be used rectally) I/V Adults: 0.5-1.0 g every 6 hours Children: 30 mg/kg/day in 2-4 injections Before intravenous administration, a single dose is diluted with at least 250 ml of 0.9% sodium chloride solution, administered within 45-60 minutes	Food significantly reduces oral bioavailability. Frequent development of HP from the gastrointestinal tract. Clinically significant interaction with other drugs (theophylline, carbamazepine, terfenadine, cisapride, disopyramide, cyclosporine, etc.). Can be used during pregnancy and lactation
Clarithromycin	Tab. 0.25 g and 0.5 g Tab. slow down vysv. 0.5 g Since. for susp. 0.125 g/5 ml Pore. d / in. 0.5 g in vial.	50-55	3-7	Adults: 0.25-0.5 g every 12 hours; for the prevention of endocarditis - 0.5 g 1 hour before the procedure Children over 6 months: 15 mg/kg/day in 2 divided doses; for the prevention of endocarditis - 15 mg / kg 1 hour before the procedure I/V Adults: 0.5 g every 12 hours Before intravenous administration, a single dose is diluted with at least 250 ml of 0.9% sodium chloride solution, administered over 45-60 minutes	Differences from erythromycin: - higher activity against H. pylori and atypical mycobacteria; - better oral bioavailability; - the presence of an active metabolite; - with renal failure, an increase in T ½ is possible; - not applicable in children under 6 months, during pregnancy and lactation
Roxithromycin	Tab. 0.05 g; 0.1 g; 0.15 g; 0.3 g	50	10-12	Inside (1 hour before meals) Adults: 0.3 g/day in 1 or 2 divided doses Children: 5-8 mg/kg/day in 2 divided doses	Differences from erythromycin: - higher bioavailability; - higher concentrations in the blood and tissues; - food does not affect absorption; - in severe renal failure, an increase in T ½ is possible; - better tolerated;
Azithromycin	Caps. 0.25 g Tab. 0.125 g; 0.5 g Since. for susp. 0.2 g/5 ml in vial. 15 ml and 30 ml; 0.1 g/5 ml in vial. 20 ml Syrup 100 mg/5 ml; 200 mg/5 ml	37	35-55	Inside (1 hour before meals) Adults: 0.5 g / day for 3 days or 0.5 g on the 1st day, 0.25 g on days 2-5, in one dose; with acute chlamydial urethritis and cervicitis - 1.0 g once Children: 10 mg / kg / day for 3 days or on the 1st day - 10 mg / kg, days 2-5 - 5 mg / kg, in one dose; at OSA - 30 mg/kg once or 10 mg/kg/day for 3 days	Differences from erythromycin: - more active towards H.influenzae; - acts on some enterobacteria; - bioavailability is less dependent on food intake, but preferably taken on an empty stomach; - the highest concentrations among macrolides in tissues, but low in the blood; - better tolerated; - taken 1 time per day; - short courses (3-5 days) are possible; - in acute urogenital chlamydia and CCA in children, it can be used once
Spiramycin	Tab. 1.5 million IU and 3 million IU Gran. for susp. 1.5 million IU; 375 thousand IU; 750 thousand IU in pack. Since. liof. d / in. 1.5 million IU	10-60	6-12	Inside (regardless of food intake) Adults: 6-9 million IU/day in 2-3 divided doses Children: body weight up to 10 kg - 2-4 pack. 375 thousand IU per day in 2 divided doses; 10-20 kg - 2-4 bags 750 thousand IU per day in 2 divided doses; more than 20 kg - 1.5 million IU / 10 kg / day in 2 divided doses I/V Adults: 4.5-9 million IU/day in 3 doses Before intravenous administration, a single dose is dissolved in 4 ml of water for injection, and then 100 ml of 5% glucose solution is added; introduce within 1 hour	Differences from erythromycin: - active against some streptococci resistant to 14- and 15-membered macrolides; - creates higher concentrations in tissues; - better tolerated; - clinically significant drug interactions have not been established; - used for toxoplasmosis and cryptosporidiosis; - children are prescribed only inside;
Josamycin	Tab. 0.5 g Susp. 0.15 g / 5 ml in vial. 100 ml and 0.3 g / 5 ml in a vial. 100 ml	ND	1,5-2,5	inside Adults: 0.5 g every 8 hours For chlamydia in pregnant women - 0.75 mg every 8 hours for 7 days Children: 30-50 mg/kg/day in 3 divided doses	Differences from erythromycin: - active against some erythromycin-resistant strains of streptococci and staphylococci; - food does not affect bioavailability; - better tolerated; - drug interactions are less likely; - not applicable when breastfeeding
Midecamycin	Tab. 0.4 g	ND	1,0-1,5	Inside (1 hour before meals) Adults and children over 12 years: 0.4 g every 8 hours	Differences from erythromycin: - bioavailability is less dependent on food, but it is advisable to take 1 hour before meals; - higher concentrations in tissues; - better tolerated; - drug interactions are less likely; - not applicable during pregnancy and lactation
Midecamycin acetate	Since. for susp. d / ingestion 0.175 g / 5 ml in a vial. 115 ml	ND	1,0-1,5	Inside (1 hour before meals) Children under 12: 30-50 mg / kg / day in 2-3 doses	Differences from midecamycin: - more active in vitro; - better absorbed in the gastrointestinal tract; - creates higher concentrations in the blood and tissues

* With normal kidney function

These are bacteriostatically effective antibiotics, but in high concentrations they can also have a bactericidal effect. This group of antibiotics has a wide spectrum of action. The prototype of macrolide antibiotics is erythromycin, derived from fungi.

In order to improve the pharmacokinetic properties of macrolides, semi-synthetic derivatives have been obtained that have better acid stability, a wider spectrum of activity in the gram-negative range and a longer half-life. That is why macrolide antibiotics are divided by generation:

• 1 generation - oleandomycin;
• 2 generation -;
• 3rd generation - (sumamed).

Macrolides inhibit bacterial protein biosynthesis by attaching to the 50S subunit of ribosomes. Further migration and growth of the resulting polypeptide chain, due to the blockade of the enzyme translocase, stops. So macrolides have a bacteriostatic effect bacteria with an active metabolism. Macrolides are not very effective against dormant bacteria.

Interactions and uses

Macrolide antibiotics should not be washed down with grapefruit juice!

Macrolides are metabolized in the liver, due to the biotransformation of cytochrome P450 - the CYP3A4 isoenzyme. Interactions may occur when macrolides are taken with drugs or products that are also metabolized by CYP3A4 (eg, cimetidine, statins, cyclosporine, grapefruit). Macrolides inhibit the metabolism of other drugs via CYP3A4 and thus increase their effect on efficacy.

Macrolides are used intravenously, intramuscularly and orally. They penetrate well into the lung tissue, pleural, synovial and peritoneal cavities, into the fluid of the middle and inner ear, into the adenoids, tonsils. Accumulate in macrophages and enhance phagocytosis. Easily penetrate into milk. Bad - through the BBB (blood-brain barrier), placenta.

Use during pregnancy should be carried out only under strict indications.

Development of resistance and spectrum of action

Antibiotic resistance to macrolides is widespread among bacteria. Resistance is relatively easy for bacteria, as they modify the systems of ribosomal enzymes. It is believed that if a bacterium is resistant to a macrolide, it is also resistant to all other antibiotics (cross-resistance).

However, ketolides, according to recent studies, have been shown to be effective when applied to bacteria resistant to azithromycin.

Macrolides have a bactericidal effect in a relationship:

• chlamydia,
• mycoplasma,
• gram positive cocci,
• corynebacterium.

Bacteriostatic effect:

• neisseria,
• legionella,
• haemophilus influenzae,
• treponema,
• clostridia,
• rickettsia.

Second generation macrolides are more effective against gram negative bacteria. Third generation + Toxoplasma, Haemophilus influenzae.

Side effects

Macrolide antibiotics are among the safest antibiotics. The usual side effects are harmless, serious side effects are very rare. Common side effects include gastrointestinal disorders: dyspepsia - nausea, vomiting, diarrhea, rarely - pseudomembranous colitis. Allergic reactions and liver damage are very rare. The least number of complications, according to statistics, gives the 3rd generation of macrolides.

If there is abnormal liver function and known allergy to macrolides, other antibiotics should be used.

generation:

• Spiramycin (rovamycin);
• Roxithromycin (rulide);
• Josamycin (Vilprafen);
• Clarithromycin (clacid);
• Midecamycin (macrofoam);
• Dirithromycin (dynabac).

generation:

• Azithromycin (Sumamed).

Azithromycin is chemically classified as an azalide. Their division is based on the spectrum of action, pharmacokinetic characteristics and undesirable effects. The spectrum of action of dirithromycin coincides with that of erythromycin.

Macrolides a group of antibiotics for children

Indications for the use of macrolides

Pharmacodynamics: Macrolides for children inhibit RNA synthesis at the level of the 50-S subunit of ribosomes. Pharmacological effect - bacteriostatic. It should be noted that the drugs are capable of exerting an immunomodulating effect on the functions of peripheral blood phagocytes (increased chemotaxis, etc.). This effect is associated with the anti-inflammatory effect of some macrolides (erythromycin, roxithromycin and clarithromycin), due to their antioxidant activity and the ability to reduce the processes of oxidative metabolism ("oxidative burst") in phagocytes, reducing the formation of superoxide ion. "Oxidative burst" is one of the most powerful mechanisms of intracellular digestion of bacteria.

However, in a number of cases, the processes of oxidative metabolism, reaching their maximum manifestation, themselves have a damaging effect on the human body, making the inflammation reaction inadequate to the cause that causes it. On an experimental model of inflammation, it was shown that the anti-inflammatory effect of drugs is due to a decrease in the activity of cyclooxygenase and lipoxygenase of cells.

How to use macrolides

The spectrum of action of this group of antibiotics is wide. Moreover, antibiotics have a bactericidal effect on some microorganisms highly sensitive to macrolides: Gr. "+" cocci (methicillin-sensitive staphylococci, streptococci, pneumococci), Gr. "+" rods (corynebacteria), Gr. "-" sticks (moraxella), chlamydia, ureaplasma and mycoplasma. Macrolides affect other microorganisms bacteriostatically: Neisseria, Legionella, Haemophilus influenzae, Brucella, Treponema, Clostridia (except CI. difficile), Bacteroids (except Bact. fragilis) and Rickettsia.

Macrolides II and III generations have a wider spectrum. So, to drugs of the second generation: josamycin and clarithromycin, high sensitivity of Helicobacter pylori was revealed; to spiramycin and roxithromycin - toxoplasma. Preparations of the II and III generations were effective against Campylobacter, Listeria, Gardnerella and some mycobacteria.

The secondary resistance of microorganisms to macrolides develops rapidly, so the course of treatment of the child should be short (up to 7 days), otherwise they must be combined with other antibiotics. It should be emphasized that in the event of secondary resistance to one of the macrolides, it applies to all other antibiotics of this group and even to drugs from other groups: lincosamides (lincomycin, clindamycin) and penicillins, which are destroyed by staphylococcal beta-lactamase.

Pharmacokinetics of macrolides

Some macrolides can be administered intravenously to children (erythromycin phosphate, spiramycin and clarithromycin), other routes of parenteral administration (subcutaneously, intramuscularly) are not used, since injections are painful and local tissue damage occurs. These drugs can be administered orally. The bioavailability of drugs ranges from 30% to 70%. More acid-resistant are oleandomidin and antibiotics of the II and III generation, so they can be taken regardless of the meal. It is recommended to drink tablets with Borjomi mineral water or sodium bicarbonate solution. There are preparations (ointments) for topical use.

The time of occurrence of the maximum concentration of drugs in the blood plasma is 1.5 - 2 hours (when taken orally). At the same time, most macrolides bind to plasma proteins by 60-70%. However, these antibiotics have low affinity for blood proteins, so they are very quickly and easily cleaved from them, entering various tissues. In preparations of the II and III generation, the penetrating ability is higher than that of erythromycin and oleandomycin.

These drugs penetrate well into the adenoids and tonsils of the child; tissues and fluids of the middle and inner ear; lung tissue, bronchi, bronchial secretions and sputum; pleural, peritoneal, synovial fluid; skin. They are able to accumulate in phagocytic cells (polymorphonuclear leukocytes, pulmonary macrophages), where their concentration can be 13-20 times greater than in the extracellular fluid. Thus, macrolides help fight intracellular infection (legionella, chlamydia, mycoplasma, listeria, brucella, toxoplasma, etc.), which is manifested by a protracted, recurrent and atypical course of the inflammatory process.

This is very important for debilitated patients, to prevent recurrence of the disease. It should be noted that capture of macrolides by macrophages promotes the transport of antibiotics to the foci of infection. Moreover, the release of macrolides from phagocytes occurs only in the presence of an infectious factor, which makes these drugs safe for uninfected tissue cells of the patient.

Macrolides cross the placenta, but their concentration in the blood of the fetus is only 20-25% of the level in the mother's blood. Since these are low-toxic antibiotics, if necessary, they can be used in pregnant women. The drugs pass into the mother's milk, where they accumulate intensively, so it is necessary to interrupt breastfeeding. All drugs of this group of antibiotics penetrate the blood-brain barrier very poorly, so sanitation of the cerebrospinal fluid does not occur with meningitis.

With urine after ingestion, only 2-3% of the antibiotic from the administered dose is excreted. However, when administered intravenously, the amount of the drug in the urine can reach 12-15%. This concentration is sufficient to suppress microflora sensitive to macrolides, but urine must be alkalized.

Macrolide Interactions

Macrolides cannot be administered in the same syringe with B vitamins, ascorbic acid, cephalothin, tetracyclines, levomycetin, heparin, diphenylhydantoin (difenin), as complexes are formed that precipitate. Macrolides are not prescribed simultaneously with terfenadine and astemizole because of the risk of hepatotoxicity and the occurrence of ventricular arrhythmias.

The interaction of macrolides with levomycetin is contraindicated, since it also disrupts RNA synthesis at the level of the SO-S subunit of ribosomes, so antagonism occurs between them (1+1=0.75). It is known that I generation macrolides can more often cause the so-called transient effects: ototoxicity and neuromuscular block. Therefore, the summation of the above undesirable effects is possible when macrolides are combined with aminoglycosides, polymyxins, glycopeptide and polyene antibiotics, which also cause these effects.

Macrolides of the 1st generation and, to a lesser extent, of the 2nd generation inhibit the activity of enzymes of the monooxygenase system in the liver due to the formation of stable compounds with some P-450 cytochromes. As a result, biotransformation in the liver of a number of simultaneously named drugs is disrupted and the rate of their elimination decreases. This is accompanied by the accumulation of these substances in the body and the occurrence of undesirable effects, sometimes life-threatening. These drugs include: theophylline, chloramphenicol, bromocriptine, warfarin, cimetidine, carbamazepine, dihydroergotamine, antipyrine, methylprednisolone, etc.

The interaction of macrolides with bacteriostatic drugs with a different mechanism of action is possible. For example, with tetracyclines that disrupt RNA synthesis at the level of the 30-S-ribosomal subunit; or with sulfonamides, which compete with para-aminobenzoic acid.

Side effects of macrolides

Side effects of macrolides

Macrolides are low-toxic drugs. Complications with the use of drugs of the first generation occur on average in 4.1% of patients, with the use of the second generation - in 2.6% of patients, with the use of the third generation - in 0.7% of patients.

• Dyspeptic symptoms (nausea, vomiting, diarrhea);
• Stomatitis, gingivitis;
• cholestasis;
• With intravenous administration - phlebitis. In order to avoid irritation and inflammation of the veins, it is recommended to dilute 1 mg of the antibiotic in 1 ml of isotonic sodium chloride solution or 5% glucose solution and inject it by infusion over 30-60 minutes;
• Rarely - cardiac arrhythmias, prolongation of the Q-T interval; and with intravenous administration - temporary deafness.