Distinctive feature Klacida is its activity against a wide range of microbes, including atypical pathogenic bacteria that cause infectious and inflammatory diseases of the respiratory tract. In addition, the antibiotic is highly effective in the treatment of acute otitis media, acute bronchitis, pneumonia, pharyngitis or tonsillitis in children.
Varieties, names, composition and release forms
Currently, the antibiotic Klacid is available in two varieties:- Klacid;
- Klacid SR.
Klacid SR is available in a single dosage form - these are extended-release (long-acting) tablets, and Klacid is available in three dosage forms, such as:
- Lyophilisate for the preparation of solution for infusion;
- Powder for the preparation of suspension for oral administration;
- Pills.
As an active substance, all dosage forms of both varieties contain clarithromycin in varying dosages. Thus, Klacid SR tablets contain 500 mg of the active substance. The lyophilisate for the preparation of solution for infusion contains 500 mg of clarithromycin per vial. Tablets of regular duration of action Klacid are available in two dosages - 250 mg and 500 mg of clarithromycin. The powder for preparing the suspension is also available in two dosages - 125 mg/5 ml and 250 mg/5 ml. This means that the finished suspension can have a concentration of active substance of 125 mg per 5 ml or 250 mg per 5 ml. In everyday life, various dosage forms, varieties and dosages of Klacid are called short and succinct names that reflect their main characteristics. Thus, tablets are often called Klacid 250 or Klacid 500, where the number next to the name reflects the dosage of the drug. Taking into account the same principle, the suspension is called Klacid 125 or Klacid 250, etc.
Tablets of both dosages of Klacid and extended-release Klacid SR have the same biconvex, oval shape and are coated with a yellow-colored coating. Tablets are available in packs of 7, 10, 14, 21 and 42 pieces.
Powder for the preparation of a suspension for oral administration is small granules, white or almost white in color and having a fruity odor. The powder is available in 42.3 g bottles complete with a dosing spoon and syringe. When the powder is dissolved in water, an opaque suspension is formed, colored white and having a fruity aroma.
Lyophilisate for the preparation of solution for infusion is available in hermetically sealed bottles and is a powder white with a light aroma.
Therapeutic effect of Klacida
Klacid is an antibiotic and, accordingly, has a detrimental effect on various pathogenic microorganisms that cause infectious and inflammatory diseases. This means that when taking Klacid, microbes die, which leads to the cure of an infectious-inflammatory disease. Klacid has a wide spectrum of action and harmful to the following types of microorganisms:
- Chlamydia pneumoniae (TWAR);
- Chlamydia trachomatis;
- Enterobacteriaceae and Pseudomonas;
- Haemophilus influenzae;
- Haemophilus parainftuenzae;
- Helicobacter (Campilobacter) pylori;
- Legionella pneumophila;
- Listeria monocytogenes;
- Moraxella catarrhalis;
- Mycobacterium leprae;
- Mycobacterium kansasii;
- Mycobacterium chelonae;
- Mycobacterium fortuitum;
- Mycobacterium avium complex (MAC) - a complex including: Mycobacterium avium, Mycobacterium intracellulare;
- Mycoplasma pneumoniae;
- Neisseria gonorrhoeae;
- Staphylococcus aureus;
- Streptococcus pneumoniae;
- Streptococcus pyogenes.
Detrimental to the following microorganisms the effect of Klacid is shown only in laboratory tests, but not confirmed by clinical practice:
- Bacteroides melaninogenicus;
- Bordetella pertussis;
- Borrelia burgdorferi;
- Campylobacter jejuni;
- Clostridium perfringens;
- Pasteurella multocida;
- Peptococcus niger;
- Propionibacterium acnes;
- Streptococcus agalactiae;
- Streptococci (groups C,F,G);
- Treponema pallidum;
- Viridans group streptococci.
Indications for use
Both varieties and all dosage forms of Klacid have the same the following readings for use: - Infections of the lower areas respiratory system(bronchitis, pneumonia, bronchiolitis, etc.);
- Infections upper sections respiratory system (pharyngitis, tonsillitis, sinusitis, otitis media, etc.);
- Infections of the skin and soft tissues (folliculitis, erysipelas, infectious cellulitis, furunculosis, impetigo, wound infection, etc.);
- Infections caused by mycobacteria;
- Prevention of Mycobacterium avium complex (MAC) infection in HIV-infected people;
- Eradication of H. pylori to cure gastritis and gastric or duodenal ulcers;
- Treatment and reduction of the frequency of relapses of duodenal ulcers;
- Infections of the teeth and oral cavity (dental granuloma, stomatitis, etc.);
- Infections caused by Chlamydia trachomatis, Ureaplasma urealyticum (urethritis, colpitis, etc.).
The drug is effective against many microorganisms - gram-negative (meningococci, gonococci, Haemophilus influenzae, Helicobacter pylori, etc.) and gram-positive (staphylococci, streptococci, pneumococci, corynebacterium diphtheria, etc.). It is also prescribed to combat intracellular microorganisms (chlamydia, mycoplasma, ureaplasma, etc.), as well as some anaerobic bacteria (peptococci, peptostreptococci, bacteroides and clostridia).
Vilprafen is quickly absorbed from the digestive tract. Within an hour its maximum concentration in the blood is reached. At the same time, Vilprafen has a long-term therapeutic effect.
The drug crosses the placental barrier and can be excreted in breast milk.
The medicine is inactive against enterobacteriaceae, and therefore has virtually no effect on the intestinal microflora.
80% of Vilprafen is excreted in bile, 20% in urine.
Macrolides are not only safe, but also quite effective. They have a huge potential for antimicrobial activity, as well as excellent pharmacokinetic action, which makes it much easier to tolerate their effects in childhood. The very first macrolide antibiotic was erythromycin. After another 3 years, two more drugs were released - spiramycin And oleandomycin. Today there are the best antibiotics of this group for children in the face azithromycin, roxithromycin, clarithromycin, spiramycin and some others. It is these antibiotic drugs that are used by modern pediatricians to fight infections in children.
To boost the child’s immune system and strengthen his body, it is very important to purchase special dietary supplements from the Tiens Corporation for him, such as: Biocalcium for children, Biozinc, Antilipid tea and so on.
Erythromycin is an antibiotic that should be taken for legionellosis, for the purpose of preventing acute rheumatic fever (if penicillin is not possible), and intestinal decontamination before colorectal surgery.
Clarithromycin is used for the treatment and prevention of opportunistic infections in AIDS caused by some atypical mycobacteria, including the eradication of Helicobacter pylori in gastrointestinal diseases.
Spiramycin is used to treat toxoplasmosis, particularly in pregnant women.
Josamycin is suitable for the treatment of various respiratory diseases, soft tissue infections, and odontogenic infections.
The use of josamycin during pregnancy and breastfeeding is allowed according to indications. The European branch of WHO recommends josamycin as a means for proper treatment of chlamydial infection in women expecting a child.
All macrolides are allowed to be taken orally.
The advantages of clarithromycin, spiramycin, roxithromycin, midecamycin and josamycin over erythromycin are better pharmacokinetics, better tolerability and lower frequency of use.
Contraindications to the use of macrolides include hypersensitivity, pregnancy (josamycin, roxithromycin, midecamycin, clarithromycin), breastfeeding (josamycin, spiramycin, clarithromycin, midecamycin, roxithromycin).
Macrolides pass through the placenta and are absorbed into breast milk.
Side effects. These drugs are well tolerated and are one of the most harmless groups of antimicrobial drugs.
This group of macrolides consists of natural antibiotics (oleandomycin, erythromycin, spiramycin, etc.), as well as semisynthetic drugs (azithromycin, roxithromycin, clarithromycin, etc.).
The basis of the chemical structure of these drugs is the lactone ring, which in different antibiotics consists of 14-16 carbon atoms. A variety of substituents are attached to the lactone rings, which greatly affect the properties of individual compounds.
The main feature of semisynthetic macrolides is their qualitative pharmacokinetic properties with increased (broad spectrum) antibacterial activity. They are well absorbed and form a long-lasting high concentration in the blood and tissues, which helps reduce the number of administrations per day to one or two times, reduce the duration of the course, frequency and severity side effects. They are effective against respiratory tract infections, diseases of the genital organs and urinary tract, soft tissues, skin and other diseases that arose due to gram-negative and gram-positive microorganisms, atypical bacteria, and various anaerobes.
penicillin. A distinctive property of these antibiotics was that various gram-positive microorganisms that were not susceptible to penicillin, tetracycline, etc. became sensitive to them. It is not for nothing that macrolides in the clinical field have received the place of “reserve” antibiotics. The emergence of new generations of these drugs has only strengthened the position of this pharmacological group antibacterial drugs. But, nevertheless, this did not indicate a complete refusal to use erythromycin, which is well known in clinical settings. In fact, erythromycin is still suitable for use against a large number of types of microorganisms.
However, the antimicrobial activity of erythromycin in vitro is high. One should not ignore the bioavailability of the antibiotic, which is not so great compared to new macrolides/azalides, the high possibility of undesirable effects, as well as the formation of resistant microorganisms.
The choice of macrolide antibiotics becomes especially important, taking into account the pathogen, the characteristics of clinical manifestations and the course of the disease.
A necessary feature of these first-generation drugs was their lack of effectiveness against gram-negative bacteria, including fungi, Brucella, and Nocardia. New generations of these drugs are more effective in the fight against gram-negative microorganisms and are constantly attracting attention.
Macrolides are certain lactones in which the number of atoms in the ring is eight or more; they can contain various substituents, namely functional groups, including 1 or 2 C=C bonds. They exist with 2 or more lactone groups. This is usually solids, which dissolve quite well in organic solutions and solvents, but are poorly soluble in water. Their chemical properties are similar to lower lactones, but they are not as reactive.
Most macrolides are obtained from bacterial strains, mainly actinomycetes and streptomycetes. Of these substances, the best known are oleandomycin, erythromycin, tetranactin and rosamycin.
Such macrolides are obtained from culture filtrates by extraction with organic solvents and purified by chromatographic methods. There are also similar substances that are obtained through bacteria, after which they are converted biochemically or chemically, for example, triacetyleandomycin. Chemically, as a rule, synthesize unsubstituted macrolides. They can be made using lactonization of w-halogen acids or various hydroxy acid esters.
The chemical synthesis of these substances, similar to that produced by bacteria, is very difficult. It includes the production of a hydroxy acid, which has some substituents, and its direct lactonization. Thus, tylosin and some erythromycin derivatives were synthesized. Macrolide antibiotics stop the growth of gram-positive penicillin allergies, legionella and rickettsial infections. In case of community-acquired pneumonia, macrolides can become first aid antibiotics.
Lincomycin (not a macrolide) has bacteriostatic capabilities that are similar to the work of erythromycin.
Tetracyclines are now used mainly in the treatment of patients with atypical pneumonia due to the development of microbial resistance to them. Tetracyclines affect bacterial ribosomes, stopping bacterial protein synthesis. Doxycycline is properly transported to the lungs (alveolar macrophages), white blood cells and is therefore suitable in the fight against intracellular pathogens (eg Legionella).
A major challenge is the presence of toxicity in tetracyclines. Thus, tetracyclines often provoke the appearance of gastrointestinal diseases in patients, affect the appearance of candidiasis and damage to the liver and kidneys, mainly in older people. It is not correct to start therapy for patients with ambulatory pneumonia with tetracyclines.
Pediatrics. Information about the harm or benefit of clarithromycin for children under six months is not known. The half-life of roxithromycin in children can be increased to twenty hours.
Geriatrics. There are no restrictions on the use of macrolides for elderly people, but one should remember the fact that age-related changes in liver function are possible, as well as a high risk of hearing impairment when using erythromycin.
Renal dysfunction. When creatinine clearance decreases to less than 30 ml/min, the half-life of clarithromycin can increase to twenty hours, and its active metabolite - up to forty hours. The half-life of roxithromycin can increase to fifteen hours when creatinine clearance decreases to 10 ml/min. In such cases, it may be necessary to change the dosage regimen of such macrolides.
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 alkaline environment.
To date, cases of use of oleandomycin are rare, as it is outdated.
Ol. prescribed for brucellosis, abscess pneumonia, bronchiectasis, gonorrhoea, inflammation of the meninges, inner lining of the heart, upper respiratory tract infections, purulent pleurisy, furunculosis, entry of pathogenic microorganisms into 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 skin lesions, subcutaneous tissue, 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 mycoses bacterial 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, painful sensations in the abdominal area, violation taste sensations, 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 mental health person. 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.
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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 for widespread use of both parenteral and oral forms drugs. Sometimes they cause undesirable effects from the gastrointestinal tract in the form of nausea, dyspepsia, loss of appetite, vomiting, diarrhea. Rarely happen allergic reactions in the form of skin rashes. 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 nose, 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.
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Most antibiotics, while suppressing the development of infectious agents, simultaneously have negative impact and on the internal microbiocenosis of the human body, but, unfortunately, a number of diseases are simply impossible to cure 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 | |||
| 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 is allowed (in difficult cases). 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.
Characterized by increased activity against pathogens that cause inflammatory processes in the gastrointestinal tract (including 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 treatment of adults and small (from 6 months) patients, since they do not have a significant negative influence 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.
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Macrolides - antibacterial agents new generation. The basis of the structure of this type of antibiotic is the macrocyclic lactone ring. This fact gave the name to a 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 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 macrolide antibiotics, names, applications, indications for use, we are considering - you will find out all this, we will find out and discuss:
Names of macrolide antibiotics
The group of these drugs includes many drugs - new generation antibiotics. 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 prescribed drugs are: Vilprafen, Kitazamicin, Midecamycin. The pharmacy will most likely recommend the following names to you: 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, active substance The well-known drug "Azitrox" is the macrolide Azithromycin. Well, the drug “Zinerit” contains the macrolide antibiotic Erythromycin.
What do macrolide antibiotics help with? Indications for use
This group of drugs has a wide spectrum of action. Most often they are prescribed for 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, and are used for exacerbations of chronic bronchitis.
Infectious diseases of soft tissues and skin: folliculitis, furunculosis, paronychia.
Sexual infections: chlamydia, syphilis.
Bacterial infections of the mouth: periostitis, periodontitis.
In addition, drugs of this group are prescribed for the treatment of toxoplasmosis, gastroenteritis, cryptosporidiosis, as well as for the treatment of severe acne. Prescribed for other infectious diseases. They can also be recommended for use for the prevention of infections in dental practice, rheumatology, as well as in surgical treatment on the colon.
How and for how long to take macrolide antibiotics? Application, dosage
The group of macrolide antibiotics is presented in different dosage forms: tablets, granules, suspensions. Pharmacies will also offer: suppositories, powder in bottles and the drug in the form of syrup.
Regardless of the dosage form, drugs intended for internal use are prescribed to be taken by the hour, maintaining an equal period of time. They are usually taken 1 hour before a meal or 2 hours after it. Not just a large number of The names of these antibiotics do not depend on food intake. Therefore, please read the package insert carefully before starting treatment.
In addition, any drug in this group can only be used according to medical indications as prescribed by a doctor. After making a diagnosis, the doctor will prescribe the remedy that will help specifically 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 medications, 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 compared to other antibiotics.
However, they are contraindicated for pregnant women, nursing mothers, and babies under 6 months. They cannot be used if the body is individually sensitive to the components of the drug. These drugs should be prescribed with caution to people with serious liver and kidney dysfunctions.
If prescribed incorrectly or uncontrolled, side effects may occur: headache, dizziness. Hearing may be impaired, nausea and vomiting often occur, abdominal discomfort is felt, 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!
For quotation: Klyuchnikov S.O., Boldyrev V.B. The use of macrolides in children modern conditions// RMJ. 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 remedy 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 state program and the problem of resistance is not so acute.
In recent years in medical practice Many new antibiotics of different pharmacological groups have been introduced. However, the group of macrolides currently attracting the greatest attention from clinicians. This is facilitated by an increase in frequency 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 mucosa 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 for the treatment of whooping cough in children (moderate and severe forms), and are included in the complex therapeutic measures with diphtheria of the pharynx.
Resistance to macrolides is not yet known 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 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 in their own way pharmacological properties are significantly ahead of both erythromycin and midecamycin, having a more prolonged effect, 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 ones, undoubtedly, more quality drugs, to more affordable generics, some of which also differ good quality(zitrocin, clerimed, roxihexal, etc.), which ensures the availability of drugs in 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, however clinical significance this occurs 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, significantly exceeding concentrations in the blood (tissue orientation of pharmacokinetics), and other properties that significantly distinguish it from antibiotics of the macrolide group.
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 repeat courses antibacterial therapy it is necessary to take into account the properties of azithromycin to accumulate in body tissues, which allows reducing the duration 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 introduced into 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.
Tissue and cellular orientation of kinetics, prolonged action of new macrolides, their possibility effective application short courses without the risk of developing serious adverse reactions cause a low incidence of antibiotic resistance.
Update: October 2018
Macrolides are a group of antibacterial drugs whose structure is based on a macrocyclic lactone ring. Due to their ability to disrupt the formation of bacterial proteins, macrolide antibiotics stop their vital activity. In high dosages, the drugs completely destroy microorganisms.
Antibiotics from the macrolide group are active against:
- gram-positive bacteria (streptococci, staphylococci, mycobacteria, etc.);
- gram-negative bacilli (enterobacteriaceae, Helicobacter pylori, Haemophilus influenzae, etc.);
- intracellular microorganisms (moraxella, legionella, mycoplasma, chlamydia, etc.).
The action of macrolides is mainly aimed at the treatment of infectious diseases of the respiratory tract due to atypical and gram-positive pathogens.
Popular drugs
In the list of macrolide antibiotics, there are two substances that are most commonly used at the moment:
- clarithromycin;
- azithromycin.
These are representatives of two different generations of macrolide drugs. From these, azithromycin was later obtained. Despite the fact that they are united by the mechanism of action on microbes and belonging to the same group, there are significant differences:
| Comparison parameter | Azithromycin | Clarithromycin |
| Microbial spectrum of action |
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| Effect speed | Within 2-3 hours. A stable concentration of the drug in the blood appears after 5-7 days of regular use. | Within 2-3 hours. A stable concentration of the drug in the blood occurs after 2-3 days of regular use. |
| Efficiency | Equally effective in the treatment of Helicobacter gastritis. Azithromycin distributes better throughout the lung tissue when treating a pulmonary infection, however, the effectiveness of the drug is similar to clarithromycin in a similar case of administration. Azithromycin is more effective against legionellosis. | |
| Adverse reactions |
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| Safety for pregnant and lactating patients |
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Thus, the advantages of azithromycin include fewer adverse reactions in the form of severe life-threatening conditions.
For clarithromycin, the advantages of use are a wider spectrum of action and rapid achievement of stable levels in the patient’s blood.
The main disadvantage for both macrolide antibiotics is their undesirable use in pregnant women, which complicates the choice of drug in this population group.
Classification of macrolides
All generations of macrolides that have appeared as scientific research has progressed are divided according to their origin into natural and semi-synthetic. The former are derivatives of natural raw materials, the latter are artificially obtained medicinal substances.
It is also important to divide drugs according to their structural features. Depending on how many carbon atoms the macrolide ring of a substance contains, they are divided into 3 large generations:
14-member
| Representatives | Tradename | Method of application, price |
| Oleandomycin | Oleandomycin phosphate | Powder-substance . An outdated macrolide, practically not found in pharmacies. |
| Clarithromycin | Klacid | Pills : 0.5 g x 2 times a day, taken for 14 days. 500-800 rub. |
| Granules for preparing a suspension orally in a bottle : slowly pour water to the mark, shake the bottle, drink twice a day (the bottle contains 0.125 or 0.25 g of the substance). 350-450 rub. | ||
| Solution for intravenous administration : 0.5 g x 2 times a day (daily dose – 1.0 g), after mixing with solvent. 650-700 rub. | ||
| Clarithrosin | Pills : 0.25 g x 2 times a day without depending on food intake, course 14 days. 100-150 rub. | |
| Fromilid | Pills : 0.5 g x 2 times a day without depending on food intake, course 14 days. 290-680 rub. | |
| Clarithromycin-Teva | Pills : 0.25 g x 2 times a day for 7 days or increase the dose to 0.5 g x 2 times a day for 2 weeks. 380-530 rub. | |
| Erythromycin | Erythromycin | Pills : 0.2-0.4 g four times a day before (30-60 minutes) or after meals (1.5-2 hours), washed down with water, course 7-10 days. 70-90 rub. |
| Eye ointment : place behind the lower eyelid three times a day, course 14 days. 70-140 rub. | ||
| Ointment for external use : apply a small layer to the affected skin 2-3 times a day, the duration of the course is determined individually depending on the severity of the pathology. 80-100 rub. | ||
| Lyophilisate for preparation intravenous solution : 0.2 g of the substance, diluted with a solvent, 3 times a day. The maximum duration of use is 2 weeks. 550-590 rub. | ||
| Roxithromycin | Esparoxy | Pills : 0.15 g x 2 times a day 15 minutes before meals or 0.3 g once, course 10 days. 330-350 rub. |
| Rulid | Pills : 0.15 g x 2 times a day, course 10 days. 1000-1400 rub. | |
| RoxyHEXAL | Pills : 0.15 g x 2 times a day or 0.3 mg at a time, course 10 days. 100-170 rub. |
15-member
| Representatives | Tradename | Method of application, price |
| Azithromycin | Sumamed | Pills : 0.5 g x 1 time per day an hour before or 2 hours after meals. 200-580 rub. |
| : add 11 ml of water to the contents of the bottle, shake, take once a day an hour before or 1.5-2 hours after meals. 200-570 rub. | ||
| Capsules : 0.5 g (1 capsule) once a day an hour before or 2 hours after a meal. 450-500 rub. | ||
| Azitral | Capsules : 0.25/0.5 g x 1 time a day before or 2 hours after meals. 280-330 rub. | |
| Zitrolide | Capsules : 2 capsules (0.5 g) in one dose, 1 time per day. 280-350 rub. | |
| Azitrox | Capsules : 0.25/0.5 g x 1 time per day. 280-330 rub. | |
| Powder for oral suspension in vials : add 9.5 ml of water to the bottle, shake, take 2 times a day. 120-370 rub. |
16-member
| Representatives | Tradename | Method of application, price |
| Spiramycin | Rovamycin | Pills : 2-3 tablets (3 million IU each) or 4-6 tablets (6-9 million IU) in 2-3 doses orally per day. 1000-1700 rub. |
| Spiramycin-vero | Pills : 2-3 tablets (3 million IU each) for 2-3 oral doses per day. 220-1700 rub. | |
| Midecamycin | Macropen | Pills : 0.4 g x 3 times a day, course 14 days. 250-350 rub. |
| Josamycin | Vilprafen | Pills : 0.5 g x 2 times a day, without chewing, with a sufficient amount of water. 530-610 rub. |
| Vilprafen solutab | Pills : 0.5 g x 2 times a day, without chewing or dissolved in 20 ml of water. 670-750 rub. |
The list of 14-membered macrolides is distinguished by the development of pronounced resistance of microorganisms to their action. That is why the first subgroup of macrolide antibiotics is not prescribed immediately, but only if other antibacterial agents are ineffective.
These are reserve medications. Oleandomycin and erythromycin are low toxic and almost never cause serious adverse reactions. More often you can encounter nausea, vomiting, general malaise, allergies (urticaria, etc.). The first generation of macrolides should not be prescribed to pregnant and lactating patients.
Among the list of 14-member drugs, the most active against Helicobacter pylori is clarithromycin, which made it possible to include it in one of the treatment regimens for chronic gastritis in people infected with this microorganism. It is three times more active than erythromycin for coccal infections and lasts twice as long. Oleandomycin, on the contrary, is almost never used at present, since it is outdated and does not show high antimicrobial activity.
The latest generation macrolides are the most modern representatives of the class. In particular, josamycin, with rare exceptions, does not act on bacteria that have developed resistance. This is an effective and safe medicine that is approved during pregnancy and breastfeeding. Spiramycin is also acceptable during pregnancy, but is prohibited for lactating women, as it passes into breast milk. The drug midecamycin is a reserve macrolide and is not recommended for expectant mothers and nursing women.
Use in childhood
The use of macrolides for children is a separate section: drugs in this group are not always approved for use without restrictions. In addition, recommended dosages of medications are lower than those for the adult population, and are almost always calculated based on the baby’s body weight. 
Erythromycin solution for intravenous administration can rarely cause acute toxic hepatitis in a child. The substance is prescribed at a dose of 30-40 mg per kilogram of body weight, this daily dose is divided into 2-4 doses. The duration of the course is unchanged (7-10 days).
Drugs containing the macrolide clarithromycin are limited to newborns and infants up to 6 months. For children over 12 years of age, they are prescribed 250 mg twice a day.
Azithromycin is not used in children:
- up to 16 years (for infusion forms);
- up to 12 years with a weight of less than 45 kg (for tablet and capsule form);
- up to six months (for suspension).
In this case, the dosage for children over 12 years of age with a body weight of more than 45 kg is the same as the adult dose. And for a child 3-12 years old and weighing less than 45 kg, an antibiotic is prescribed at 10 mg per kilogram once a day.
The dose of josamycin is 40-50 mc/kg. It is evenly divided into 2-3 doses per day. It is recommended to prescribe 1-2 grams. Spiramycin tablets of 1.5 million IU are not given to children under 3 years of age, and 3 million IU tablets are not given to children under 18 years of age. The maximum dose is 300 IU per kilogram per day.
Bacterial resistance
Bacterial microorganisms are capable of developing resistance (immunity) to the action of antibiotics. Macrolides are no exception. Bacteria included in the spectrum of action of macrolides “avoid” their influence in three ways:
- Modification of cellular components.
- Inactivation of the antibiotic.
- Active “release” of the antibiotic from the cell.
In recent years, scientists have noted a worldwide increase in the immunity of bacterial organisms to the macrolide series. In the USA, as well as Central and Southern Europe, resistance reaches 15-40%. According to the Consilium Medicum portal, in addition to macrolide resistance, there is insufficient effectiveness of aminoglycosides and methicillin (up to 30% of cases). For Turkey, Italy and Japanese lands, bacterial immunity ranges from 30-50%.
In Russia the situation is also getting worse over time. The results of the study under the supervision of the Research Clinical Institute of Otorhinolaryngology named after. L.I. Sverzhevsky states: the resistance of Staphylococcus pneumoniae (pneumococcus) in Moscow patients to 15-membered azithromycin increased by 12.9% (from 8.4% to 21.3%) in the period 2009-2016. In Yaroslavl, low resistance of S. pyogenes to erythromycin is observed (7.5-8.4%). But for Tomsk and Irkutsk this figure was higher - 15.5% and 28.3%, respectively.
Macrolide group– one of the safest at present. The wide spectrum of activity of the drugs allows them to be successfully used in the treatment of infections of varying severity, including as “reserve” drugs. But to prevent the development of microbial resistance, you should not take these medications on your own without first consulting a specialist.
