What are the advantages of macrolide antibiotics over conventional drugs. Macrolides. Macrolide group

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

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

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

Macrolides are new generation antibacterial agents. 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, the active ingredient of 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 during surgical treatment of 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. Only a small number of these antibiotics are not food dependent. Therefore, please read the package insert carefully before starting treatment.

In addition, any drug in this group can be used only for medical reasons 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!

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

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

Historical reference

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 if there is in patients with individual intolerance to penicillins, the second - as a highly effective remedy, 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.

Principles of systematization

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.

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).

general description

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.

Macrolides - drugs, their characteristics, list of the most popular release forms

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

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

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

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

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

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

Another name for the drug is Midecamycin.

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

Contraindications: pregnancy, breastfeeding period. Used in pediatrics.

Josamycin

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

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

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

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

Oleandomycin

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.

Ilozon

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.

Zatrin, Lincomycin, Clindamycin, Sumamed

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

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

Features of application

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:

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.

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

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

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

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

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

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

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

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

Classification

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

Macrolide antibiotics

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

First generation

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

Second

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

Third

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

Macrolides for children

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

• Clarithromycin;
• Roximitrocin;
• Azithromycin;
• Spiramycin;
• Josamycin.

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In the modern world, infectious diseases are not uncommon, and in such cases we resort to the use of antibiotics. Broad-spectrum drugs are used against many microorganisms, but they are less effective than the latest generation of macrolides. Because for the most part, macrolides have a narrowly targeted effect on a specific disease and do not adversely affect the microflora.

Mechanism of action and list of drugs

Macrolides are a group of drugs that are classified as antibiotics. Today they are the safest and save those who are allergic to penicillin or cephalosporins; they are often used in pediatrics.

The mechanism of action of macrolides is that they suppress protein synthesis in the microbial cell by binding to the ribosome. They also activate nonspecific defense mechanisms of the body and carry out intracellular destruction of microorganisms.

The classification of this drug is as follows, according to the number of carbon atoms:

• 14 atoms:
• Clarithromycin;
• Roxithromycin;
• 15 atoms:
• Azithromycin;
• 16 atoms:
• Spiramycin;
• Josamycin;
• Midecamycin;
• Midecamycin acetate.

According to the type of origin, macrolides are divided into natural and semi-synthetic. Natural ones include:

• Spiramycin;
• Josamycin;
• Midecamycin.

All others can be classified into the second category.

If we divide macrolides by generation, we get the following picture:

• Erythromycin - first generation;
• Spiramycin, josamycin, midecamycin, clarithromycin, roxithromycin - second;
• Azithromycin is the third.

Erythromycin appeared in 1952 and became the first drug that opened the group of macrolides of the latest generation. Its advantage is that it does not harm nucleic acids. However, progress does not stand still and at the moment this type of macrolide has worse bioavailability, lower concentration in organs and tissues, and most often causes side effects.

Indications for use of erythromycin:

• infectious and inflammatory diseases:
• Diphtheria;
• Scarlet fever;
• Whooping cough;
• Otitis;
• Syphilis;
• Gonorrhea;
• Cholecystitis;
• Community-acquired respiratory tract infections:
• Pharyngitis;
• Bronchitis;
• Tonsillitis;
• Bronchopneumonia;
• Atypical pneumonia.

It can be used during pregnancy and breastfeeding, but you should not take erythromycin if you are hypersensitive to this antibiotic or take pimozide, terfenadine, colchicine, or astemizole.

Benefits of Macrolides

Macrolides have a number of undeniable advantages, for example, they are safe, effective, well tolerated, it can also be noted that these drugs:

• They have a powerful bacteriostatic effect;
• They have a great chance of defeating streptococci and staphylococci;
• Do not cause cross-allergy with B-lactams;
• Do not have a detrimental effect on the activity of the gastrointestinal tract;
• Have low toxicity;
• Create an immunomodulatory effect;
• Penetrates tissue best;
• They have an optimal course of treatment - 3-5 days.

In addition, patients always like the convenient form of macrolides: tablets, suspensions, syrups, which is even more convenient when treating small patients.

Indications and contraindications for the use of new generation antibiotics

In turn, clarithromycin will be effective in preventing infections that can cause AIDS, as well as gastrointestinal diseases. Spiramycin has a beneficial effect on toxoplasmosis.

Josamycin is best used in cases of soft tissue infections, treatment of diseases of the respiratory system, and odontogenic infections. It is also important that it can be prescribed to pregnant women.

Any macrolides can be used orally.

Contraindications for the use of these medications may include: hypersensitivity and periods of pregnancy and breastfeeding (some types of the drug).

The list of macrolide drugs is quite wide and safe among antibiotics, but, nevertheless, they are not without undesirable reactions, for example, abdominal pain, nausea, weakness, fever, dizziness, etc. Therefore, if no improvement is expected when using the medicine, and new symptoms are added, then you should immediately consult a doctor.

The new generation of macrolides certainly have many advantages in the treatment of infectious diseases, including in children. However, each drug has its own characteristics and nuances in its use, so do not try to undergo treatment on your own, be sure to consult with an experienced doctor. Only he can prescribe effective treatment that will lead to your recovery and not worsen the situation.