Catad_tema Clinical pharmacology - articles

Macrolides in modern therapy of bacterial infections. Features of the spectrum of action, pharmacological properties

S. V. BUDANOV, A. N. VASILIEV, L. B. SMIRNOVA
Scientific Center for Expertise of Medical Products of the Russian Ministry of Health, State Scientific Center for Antibiotics, Moscow

Macrolides are a large group of antibiotics (natural and semi-synthetic), the basis of the chemical structure of which is a macrocyclic lactone ring with one or more carbohydrate residues. Depending on the number of carbon atoms in the ring, macrolides are divided into 14-membered (erythromycin, clarithromycin, roxithromycin), 15-membered (azithromycin) and 16-membered (josamycin, midecamycin, spiramycin).

The first representative of this group, erythromycin, was discovered and introduced into the clinic in the early 50s of the last century, and is widely used today in the treatment of respiratory infections, diseases of the skin and soft tissues, and in recent years, its range of indications has included infections caused by intracellular “atypical” bacteria.

In terms of the spectrum and degree of antibacterial activity, representatives of this group are close, with the exception of new semisynthetic macrolides (azithromycin and clarithromycin), which exhibit greater activity against many intracellular bacteria, some pathogens of dangerous infections (brucella, rickettsia), gram-positive and gram-negative non-spore-forming anaerobes, etc. According to the mechanism of action, macrolides are inhibitors of protein synthesis. As a rule, macrolides have a bacteriostatic effect, but under certain conditions: when the pH of the medium changes, the density of the inoculum decreases, or high concentrations in the medium can act bactericidal.

Most clinically significant macrolides are 14- or 16-membered macrolides. Azithromycin is a semi-synthetic derivative of erythromycin A, in which the methyl group is replaced by a nitrogen atom, forming a new 15-membered structure, separated into a new subgroup called azalides. For a number of properties (great activity against some gram-negative bacteria, the greatest prolonged action, cellular targeting of pharmacokinetics, etc.) azithromycin differs from its predecessors.

On the Russian pharmaceutical market, azithromycin is widely represented by a drug from the Pliva company, which is produced under the trade name Sumamed.

Antimicrobial spectrum

The spectrum of action of the basic antibiotic of the macrolide group, erythromycin, largely corresponds to the spectrum of other representatives of this group. Erythromycin has preferential activity against gram-positive cocci: it is active against streptococci of groups A, B, C, G, Streptococcus pneumoniae. Strains of the latter, resistant to benzylpenicillin, are also resistant to macrolides. Staphylococcus aureus strains are usually sensitive to macrolides, but their increased resistance to betalactams does not allow macrolides to be recommended for staphylococcal infections as an alternative group of antibiotics without laboratory data. Erythromycin is active against corynebacteria, anthrax microbe, clostridia, listeria, intracellular bacteria (chlamydia, mycoplasma, legionella) and atypical mycobacterium tuberculosis. Some spore-forming gram-positive and gram-negative non-spore-forming anaerobes are sensitive to it (Table 1).

Chemical transformation of the core of the erythromycin molecule, resulting in the production of azithromycin, led to significant changes in properties compared to erythromycin: increased activity against H. influenzae, high activity against Moraxella catarrhalis, borrelia (MIC - 0.015 mg/l) and spirochetes. Among the semisynthetic macrolides, azithromycin and clarithromycin are the most widely known; registered in Russia, they are used for a wide range of indications, especially the first one. Both drugs are active against Mycobacteriumfortuitum, M.avium complex, M.chelonae. They are used long-term and effectively for the prevention and treatment of mycobacteriosis, which is a common complication in HIV-infected patients, in combination with other antibiotics and chemotherapeutic agents.

Table 1.
Antimicrobial spectrum of erythromycin

Table 2.
Comparative effectiveness of macrolides and other antibiotics for VVP caused by typical and “atypical” pathogens (modified)

Note. * Among macrolides, azithromycin is most effective against common pathogens of respiratory infections, such as H. influenzae, M. catarrhalis, C. pneumoniae, M. pneumoniae.

A distinctive property of azithromycin is its activity against many enterobacteria (Salmonella spp., Shigella spp., Escherichia coli). The MIC value of azithromycin for them ranges from 2-16 mg/l.

Azithromycin and clarithromycin are active against almost all pathogens of respiratory infections, which has brought this group of antibiotics to the forefront in the treatment of infections of the upper and lower respiratory tract. They are especially often used in the empirical treatment of otitis media, pharyngitis, acute and exacerbation of chronic bronchitis, and community-acquired pneumonia (CAP). In the case of the latter, these macrolides are highly effective both in case of typical VVP and in cases caused by “atypical” pathogens (Chlamydia, Mycoplasma, Legionella, etc.) (Table 2). Guaranteeing the effective use of macrolides in the empirical treatment of respiratory infections and especially respiratory infections is only possible under the condition of constant monitoring of pathogen resistance to antibiotics at the regional and local levels, since these pathogens are often characterized by multidrug resistance, including most groups of antibiotics used in bronchopulmonary pathology.

Modern macrolides (especially semi-synthetic ones) are superior to antibiotics of other groups in terms of the breadth and characteristics of their spectrum of action. Within therapeutic concentrations, they are active against almost all groups of pathogens of community-acquired respiratory tract infections (if necessary, in combination with broad-spectrum antibiotics). They are highly effective against nosocomial infections caused by many gram-negative bacteria (Table 3). Their spectrum of action includes many intracellular pathogens of such severe infections as borreliosis, rickettsiosis; as well as mycobacteriosis caused by atypical mycobacteria. Azithromycin is active against enterobacteria in vitro and in the clinic for diseases caused by them; along with clarithromycin, it is effectively used in the treatment of helicobacteriosis and campylobacteriosis. Azithromycin is effective for acute and chronic sexually transmitted infections (C. trachomatis, Ureaplasma urealyticum); for gonococcal urethritis and cervicitis in combination with fluoroquinolones. Azithromycin and clarithromycin are widely used and are the main means of prevention and treatment (in combination with other chemotherapeutic agents) of mycobacteriosis in HIV infection.

Table 3.
Activity of new macrolides against major respiratory pathogens

When preventing rheumatic fever in cases of allergy to betalactams, azithromycin is the drug of choice, due to its bactericidal action and the effectiveness of short courses of use (once a day for 5 days).

The problem of resistance and the possibilities of macrolides

The practiced, along with macrolides, use of broad-spectrum antibiotics, including modern ones (betalactams, carbapenems, aminoglycosides, fluoroquinolones, etc.), in the treatment of severe forms of gram-positive infection has contributed to an increase in the level of their consumption and, accordingly, the selection and spread of multiple antibiotic resistance among various groups of microorganisms. Over the past 10-15 years, benzylpenicillin-resistant pneumococci (PRSP) have become widespread in many regions of Europe, North America, and Canada. The diagnosis and treatment of VVP caused by “atypical” pathogens (C.pneumoniae, M.pneumoniae, Legionella spp.) have become a serious problem. It is characteristic that pneumococci isolated during GDP were resistant not only to benzylpenicillin, but also to antibiotics of other groups, including macrolides.

Despite this, scientific communities in many countries (USA, Canada, Germany, France, etc.) have developed recommendations for empirical treatment of GDP, based on macrolides in monotherapy, in combination with betalactams, tetracyclines, fluoroquinolones, depending on the form and severity of the disease ( table 4) . All recommendations include macrolides as first-choice drugs in the treatment of VVP in patients< 60 лет без сопутствующих заболеваний.

In recent years, semisynthetic macrolides (azithromycin, clarithromycin, roxithromycin) have become firmly established in the treatment of respiratory infections and infectious and inflammatory diseases of other localizations. They are superior to natural macrolides in the spectrum and degree of antibacterial activity, pharmacokinetic properties and other parameters. Nevertheless, there are publications on the isolation of pneumococci that are resistant to new macrolides. However, these reports should be viewed critically as they are based on erythromycin susceptibility testing data. Described outbreaks of infections caused by multidrug-resistant strains of S. pneumoniae (DRSP), covering large medical centers or hospital departments, most often date back to the mid-90s of the last century (observed in Western and Central Europe, where the average frequency of DRSA isolation was 20-25 %). In Russia, strains of S. pneumoniae resistant to new macrolides are rarely isolated; the level of resistance in general does not exceed 3-7%.

Currently, in most regions of the world, resistance to macrolides remains at a low level (usually less than 25%). It should be noted that in most cases, the spread of pneumococcal resistance to macrolides was associated with their unreasonably frequent prescription, without sufficient indications. Limiting the use of erythromycin only to strict indications is accompanied by a decrease in the level of resistance to the drug used and to new macrolides. It should be noted that in terms of the spectrum of action and degree of activity against most types of microorganisms in vitro, macrolides - natural and semi-synthetic - differ little. Differences in the chemotherapeutic efficacy of new macrolides in vivo and in the clinic are mainly due to the characteristics of pharmacokinetics and associated pharmacodynamic parameters.

Pharmacokinetics and pharmacodynamics of macrolides

If the optimization of erythromycin treatment regimens is based on an assessment of the time (T) during which the level of antibiotic concentration in the blood exceeds its MIC for the isolated pathogen (i.e., T > MIC), then this approach is unacceptable for azithromycin. This is due to the fact that the clinical effectiveness of azithromycin is determined mainly by the ratio of the area under the pharmacokinetic curve AUC and the sensitivity of the pathogen to it in the MIC values ​​of the antibiotic (i.e. AUC/MIC). Due to the low concentrations of azithromycin in the blood (Cmax 0.4-0.7 mg/l, depending on the dose), the T>MIC indicator cannot serve as a measure of its effectiveness in vivo (i.e., be a predictor of effectiveness). For clarithromycin, the assessed indicator, as in the case of erythromycin, remains T > MIC. The Cmax values ​​of clarithromycin, depending on the dose taken - 250 and 500 mg, ranged from 0.6-1 mg/l to 2-3 mg/l, respectively, exceeding the MIC90 values ​​for the main pathogens of GDP (S. pneumoniae, H. infleuenzae, M .catarrhalis) provided that the drug is administered twice a day (every 12 hours).

A comparison of the results of the clinical effectiveness of azithromycin with in vivo data (in experimental infections) shows that they are more significant than those obtained when determining the sensitivity of the isolated pathogen in vitro. The most important role in predicting the effectiveness of azithromycin (to a lesser extent clarithromycin, roxithromycin) is played by the duration of exposure of the pathogen to high intracellular concentrations of the antibiotic at the site of infection, in neutrophils, monocytes of peripheral blood. Moreover, the concentration of the antibiotic in tissues significantly exceeds its MIC90 value for almost all pathogens of GDP for 8 days or more after a single oral dose per day in a standard dosing regimen.

The high level of tissue penetration of new macrolides, especially azithromycin, and their long stay at the site of infection make it possible to optimize the regimes of their use based on pharmacodynamic parameters.

Tissue and cellular kinetics of macrolides

Modern semisynthetic macrolides (azithromycin, clarithromycin, roxithromycin) have fundamental advantages over natural macrolides: an expanded spectrum and activity against most “pulmonary” pathogens, activity not only against gram-positive, but also many gram-negative bacteria (H. influenzae, M. catarrhalis , “atypical” pathogens), antianaerobic activity, as well as high cellular and tissue penetration. This is the basis for their widespread use for infections of the upper and lower respiratory tract and other infectious and inflammatory diseases. The noted rapid increase in the resistance of pneumococci to macrolides in vitro is not always accompanied by a decrease in the effectiveness of drugs in the clinic. This is due to the fact that in the implementation of the clinical effect of azithromycin, and to a lesser extent other macrolides, their pharmacokinetic (P/K) and pharmacodynamic (P/D) properties, which differ significantly from those characteristic of other groups of antibiotics, are of greater importance.

Table 5.
Distinctive characteristics of azalides and macrolides

Rice. 1.
Concentration of macrolides in blood serum.

Here and in Fig. 2, 3: - azithromycin (Az), - clarithromycin (Clar).

Rice. 2. Concentration of macrolides in granulocytes.

Rice. 3.
Concentration of macrolides in monocytes.

In contrast to clarithromycin, the concentration of azithromycin in the blood rarely exceeded the average values ​​of its MIC, even against antibiotic-sensitive strains of S. pneumoniae, which led to the conclusion that it was insufficiently clinically effective against pneumococcal infection. However, in connection with the decisive role of high cellular concentrations of new macrolides in the implementation of the clinical effect, it becomes clear that there is no correlation between the detected resistance of S. pneumoniae to macrolides in vitro and the manifestation of their clinical effectiveness. Despite the low concentrations of azithromycin in the blood detected after completion of administration, resistance of pathogens to it does not develop. The patient is completely cured clinically and bacteriologically with complete eradication of the pathogen due to the bactericidal effect of high intracellular concentrations of the antibiotic (Fig. 1-3).

In contrast to the low levels of azithromycin and moderate clarithromycin in blood serum, their content in granulocytes, monocytes, lymphocytes and fibroblasts is found in concentrations many times higher than the MIC values ​​of antibiotics for many microorganisms.

Macrolides penetrate and concentrate in the acidic organelles of phagocytes, with azithromycin in the highest concentrations. Higher levels of azithromycin in cells are due to the peculiarities of its chemical structure - the presence in its 15-membered ring, along with oxygen and carbon, of a nitrogen atom, which is absent in 14- and 16-membered macrolides (Fig. 4). As a result of modification of the molecule, azithromycin behaves as a dibasic compound, unlike monobasic macrolides (Table 5). It is characterized by a prolonged retention in cells in high concentrations for 7-10 or more days after the end of treatment and a prolonged T1/2 (68 hours). Higher intracellular concentrations of azithromycin compared to 14- and 16-membered macrolides are due to its strong association with acidic cell organelles. In this case, cellular kinetics mimic the rise and fall of blood concentrations before each repeated administration, as is the case with clarithromycin treatment.

Rice. 4.
Structure of macrolides.

The low concentrations of modern azalides found in serum have raised concerns about treatment failure for bacteremia. However, all macrolides, especially azithromycin, are present in high concentrations at the site of infection, in circulating PMNs, which phagocytose and rid the body of the pathogen upon its contact with high bactericidal concentrations of the antibiotic in the cell. High concentrations of azithromycin in PMN ensure its presence in them in high concentrations for several days after completion of treatment. From the point of view of the activity of azithromycin at the site of infection, data on the dependence of its accumulation on the presence of inflammation in tissues is important. A comparative study of the interstitial fluid of the inflammation site using a model of infected or intact blisters in volunteers showed that the concentration of azithromycin in the infected blister is significantly higher than in the uninfected one (Fig. 5). It has also been shown that the concentration of azithromycin in lung tissue during inflammation is 5-10 times higher than that found in a biopsy of healthy lung tissue for diagnostic purposes.

Rice. 5.
AUC values ​​0-24 of azithromycin in blood serum and blister with inflammation and its absence.

In the absence of inflammation - I, with inflammation - II.

Long-term preservation of azithromycin in high concentrations intracellularly in inflamed tissues is important from a clinical point of view, since it allows optimizing its activity at the site of infection due to maximum AUC/MIC and T > MIC.

PMN and other blood and tissue cells are involved in the clearance of bacteria from sites of infection or blood. Lysosomes with the antibiotic accumulated in them and phagosomes with phagocytosed bacteria form phagolysosomes in the cell, where the pathogen comes into contact with very high concentrations of the drug (see Fig. 2, 3). Here, the activity of azithromycin is maximum not only against sensitive pathogens, but also against moderately sensitive ones, for which the MIC of the antibiotic is 32 mg/l. The high peak level of azithromycin in PMN (> 80 mg/l), in monocytes (100 mg/l) and its long-term persistence (> 12 days) at the level of 16-32 mg/l ensure rapid release of cells from pathogens. Within these concentrations, it is possible to optimize antibiotic use regimens according to the pharmacodynamic criteria of AUC/MIC and T > MIC.

The maximum intracellular concentrations of clarithromycin are significantly lower than those found when taking azithromycin, its peak concentrations are 20-25 mg/l, decreasing to 5 mg/l before repeated administration (after 8-12 hours). With MIC values ​​of this antibiotic up to 4-8 mg/l against S.pneumoniae, pharmacodynamic parameters may be unfavorable and be accompanied by clinical failures.

Analysis of pharmacodynamic criteria for resistance to macrolides and azithromycin indicates the greatest importance in realizing the clinical effect of the concentrations of these antibiotics in PMN and other cells. Errors and miscalculations in the treatment of macrolides are observed at low intracellular concentrations of drugs such as erythromycin and other natural macrolides, and the use of the first of them is most often accompanied by the development of resistance. The most favorable F/C and F/D indicators are characterized by azithromycin, which has the best intracellular penetration, the longest retention time in the cell in high concentrations, which ensures rapid clearance of the pathogen from the patient’s body and prevents the development of resistance. That is, the tissue and cellular orientation of the pharmacokinetics of macrolides and azalides is an important difference between them and other groups of antibiotics. If for betalactams the main parameter determining their clinical effectiveness is the degree of sensitivity of bacteria to their action (expressed in MIC values), then for new macrolides the predictor of effectiveness is P/D indicators: time (T) and area under the pharmacokinetic curve (AUC), exceeding the MIC values ​​of antibiotics for the isolated pathogens (T > MIC and AUC/MIC). Simply determining the degree of excess of the MIC against the pathogen and comparing its value with the concentration of the antibiotic in the blood, as is the case for betalactams and aminoglycosides, is insufficient in the case of macrolides. For them, it is necessary to calculate F/D criteria taking into account the concentrations of drugs in immunocompetent cells found under standard regimens of use, which ensure clinical effectiveness or positive clinical dynamics of the disease and eradication of the pathogen.

When analyzing the literature for 10 years of use of azithromycin and the previous 40 years of experience in treatment with natural macrolides, no reports were found of the occurrence of cases of bacteremia associated with macrolides and the risk of sepsis. Increasing resistance is a general biological problem affecting all groups of antibacterial drugs and all types of pathogens, however, it has not yet thoroughly touched azithromycin, which is due to the peculiarities of its chemical structure, strong connection with cell organelles, and the creation of high concentrations of the antibiotic in the PMN and other immunocompetent cells. Rapid killing and clearance of pathogens from the site of inflammation, high cellular concentrations of azithromycin under standard treatment regimens prevent the formation and spread of resistance to its action, as evidenced by the low frequency of isolation of resistant S. pneumoniae compared to resistance to penicillins. Observations about increasing resistance to macrolides most often apply to old natural antibiotics of this group, characterized by a low T1/2 value and rapid elimination from the body. Concerns regarding the lack of effectiveness of old macrolides and the risk of complications, including bacteremia, with long-term use of this group of antibiotics are not unfounded, which limits the indications for their use to moderate infections and short courses.

conclusions

1. Modern semi-synthetic macrolides (azithromycin, clarithromycin, roxithromycin, registered in Russia) are characterized by an ultra-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.

2. 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-day courses of oral administration in a standard dose.

3. The tissue and cellular direction of kinetics, the prolonged action of new macrolides, the possibility of their effective use in short courses without the risk of developing serious adverse reactions determine a low risk of the development and spread of antibiotic resistance.

4. Semi-synthetic macrolides are characterized by high compliance, improved cost-effectiveness indicators (lower cost of a bed-day, lower costs for medicinal and laboratory supplies, staff salaries, etc.)

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

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

It is worth noting right away that macrolides belong to the group of antibiotic drugs that are the least toxic to the human body and are well tolerated by patients.

Antibiotics such as macrolides, from a biochemical point of view, are complex compounds of natural origin that consist of carbon atoms that are found in varying quantities in the macrocyclic lactone ring.

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

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

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

Mechanism of action and scope of application

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

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

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

In particular, macrolide drugs have become widespread in the treatment and as prophylactics for the following diseases:

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

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

Contraindications for use

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

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

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

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

• vomit;
• nausea;
• headache and pain in the abdominal area;
• visual impairment, hearing impairment;
• an allergic reaction in the form of a rash, urticaria (most often occurs in children).

To avoid problems and undesirable consequences after using drugs from the macrolide group, you must strictly follow the doctor’s recommendations, strictly adhere to the dosage and refrain from drinking alcohol. It is also strictly forbidden to combine the use of new generation antibiotics with antacids. It is also important not to miss appointments.

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

Application and purpose for children

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

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

• Clarithromycin;
• Roxithromycin;
• Spiramycin, etc.

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

To summarize, we can safely say that macrolides, like antibiotics, are “white and fluffy.” Practically causing no side effects or undesirable consequences, these new generation drugs have found recognition among many doctors and specialists. Effective and capable of coping with even severe forms of diseases, such antibiotics are even used in the treatment of children.

Macrolides are part of the pharmacological group of broad-spectrum antibiotics aimed at suppressing pathogens that cause various types of infectious diseases. The list of macrolide drugs includes some medications approved for use during pregnancy and lactation, which is an undeniable advantage of antibiotics in this group.

Latest generation of macrolidesToday it is considered the most effective. This is expressed in a milder effect on the human immune system and gastrointestinal tract with high antimicrobial activity. The main effect of macrolides is the ability to influence harmful intracellular microorganisms by disrupting their intracellular protein synthesis. In small therapeutic doses, drugs effectively reduce the proliferation of pathogenic bacteria, and in high concentration doses has a strong bactericidal effect.

Current list of macrolide drugs

1. "Sumamed".A active substance: Azithromycin. Manufacturer: Teva, Israel. Effectively suppresses infections of the respiratory tract, soft tissues and genitourinary system. A special feature of the macrolide drug is its low threshold of side effects, less than 1%. It is produced in the form of capsules, tablets, powder and suspension. The most popular are tablets and capsules. Adults take 500 mg at a time. The cost of a pack (3 pieces x 500 mg) is 480 rubles.

Analogues of "Sumamed" are(for comparison, the price is shown for a package of 3 pieces x 500 milligrams in capsules or tablets):

• "Azitral"- (India) 290 rub.;
• "Azitrus Forte"(Russia) - 130 rubles;
• "Azitrox"(Russia) - 305 rub.
• "Azithromycin"(Russia) - 176 rub.

2. "Rulid"(active ingredient: "Roxithromycin"). Medicine manufactured by: Sanofi-Aventis, France. Broad-spectrum antibiotic. Available in tablets of 150 mg and 10 pieces per package. The daily norm is 300 milligrams; adults can take it according to the instructions once or twice a day. Among the advantages, a small list of side effects can be noted; among the disadvantages, the high cost of the medicine is 1,371 rubles.

Analog "Roxithromycin" significantly lower in cost and amounts to 137 rubles. It is produced in a pack similar to “Rulid” in terms of the quantity and content of the active substance in 1 tablet (10 pcs. x 150 mg), but has an impressive list of drug prohibitions and side effects.

3. Clarithromycin(active substance: Clarithromycin). Available in tablets of seven, ten and fourteen pieces. The main area of ​​effect is suppression of respiratory infections, also effective against infectious skin diseases. It is used in combination with other drugs for peptic ulcers of the stomach and duodenum caused by Helicobacter pylori.

There is a small list of contraindications. The usual dose for adults is 500 milligrams, divided into two doses. Produced by several pharmacological enterprises. To compare prices, the cost of a package of tablets (14 x 500) from the manufacturer:

• Russia - 350 rubles;
• Israel - 450 rub.

4. "ECOsitrine"("Clarithromycin"). "Avva Rus" is produced in Russia. Used to treat respiratory infections, pneumonia, and some skin diseases. It has a small list of contraindications. The daily norm is 500 ml per day.

The manufacturer of this medicine positions it as the first “eco-antibiotic”, the use of which does not cause dysbacteriosis. The drug contains the active substance that inhibits pathogenic bacteria plus the prebiotic lactulose “anhydro” in a special form. This macrolide drug from the entire list presented has a high degree of safety. The presence of a beneficial prebiotic in the composition provides maintaining healthy gastrointestinal microflora.

It works like this: clarithromycin inhibits the intestinal flora, but “anhydro” simultaneously restores and promotes the growth of intestinal normal flora.

Perhaps the prefix “ECO” is a marketing technique, but on the Internet you can find many positive reviews of people who have undergone treatment with “Ecositrin”, those who previously constantly suffered from irritable bowel syndrome and dysbiosis after taking antibacterial medications. Available in tablets (pack 14 x 500 ml). Cost 635 rub.

5. "EKOmed". A active substance: "Azithromycin". P Produced by: Avva Rus, Russia. This medicine is produced by several pharmacological enterprises and all of them are absolute analogues "Sumamed", But"EKOmed" differs from them in that it contains a “prebiotic” that restores intestinal flora. In the fourth point of our list of macrolides, you can read in detail how the medicine helps maintain healthy gastrointestinal microflora, since this drug is produced by the same manufacturer as "ECOsitrine" and contains the same “prebiotic” complex.

The cost of a pack of three pieces of 500 milligrams is 244 rubles, which is significantly higher than analogues. On the one hand, similar medications are cheaper, but are more aggressive and can cause irritable bowel syndrome. On the other hand, if the problem of dysbiosis is not relevant, you can save a lot: Azithromycin produced by Kern Pharma will cost only 85 rubles and is the most affordable medicine from the entire list of macrolide drugs.

Macrolides for children and pregnant women

"Vilprafen solutab" . Active ingredient: "Josamycin". Antibiotic with a wide range of applications. Manufacturer: Astellas, Netherlands. This macrolide drug can be used to treat newborns, as well as when indicated during pregnancy and lactation. The cost of a pack (10 x 500) is 540 rubles.

All prices are indicated as of the date of writing. A review of antibiotics has been compiled for informational purposes only. All drugs have a number of contraindications. Do not self-medicate - it is dangerous!

Unfortunately, no one is immune from diseases, including quite serious ones, the treatment of which must be carried out with antibiotic therapy. Macrolide antibiotics are recognized as one of the most effective and safe, capable of quickly combating infection. They have virtually no side effects and are therefore acceptable for use even for small children.

Antibiotics of the macrolide group are polythequides in their chemical composition. These are polycarbonyl substances, which are metabolic products of plant, fungal and animal cells. Modern pharmacy has a dozen drugs of a number of macrolides. The ancestor of the entire group of antibacterial drugs is Erythromycin, and the drugs themselves differ in the number of carbon atoms included in their composition.

The classification of macrolides is as follows:

• 14 carbon atoms include drugs such as Erythromycin, Kdarithromycin, Oleandomycin.
• Azithromycin contains 15 carbon atoms.
• 16 carbon atoms in the composition are characteristic of antibiotics such as Josamycin, Roxithromycin.
• 23 – the composition includes the drug Tacrolimus, which is both an antibacterial agent and an immunosuppressant.

The group of macrolides includes natural and semi-synthetic medications with a wide spectrum of action. By generation, macrolides are divided into first, second and third, also called azalides.

Mechanism of action

Medicines from the macrolide group of antibiotics have a bacteriostatic, i.e., inhibit the growth of microorganisms, as well as a bactericidal effect. The antibacterial effect is achieved through the influence of the active substance on the ribosomes of microbial cells, which leads to disruption of protein formation. In high concentrations, the drugs lead to the death of pneumococci, streptococci, as well as bacteria that cause whooping cough and diphtheria.

In addition, macrolide preparations have an anti-inflammatory and immunomodulatory effect, which speeds up the recovery process from infectious diseases in both adults and children.

When taking these medications, the concentration of antibiotics in soft tissues exceeds their content in the blood, which allows these drugs to be classified as tissue preparations. This is due to the fact that macrolides are able to penetrate into cells.

Antibiotic effectiveness

The macrolide group of antibiotics refers to drugs with a wide spectrum of effects. These drugs are used against diseases caused by gram-positive microorganisms - S.pyogenes, S.pneumoniae, S.aureus, except for the methicillin-resistant strain. Despite the increasing incidence of bacterial drug resistance, 16-membered antibiotics retain their activity against most pneumococci and streptococci.

The list of microorganisms that macrolides act on includes:

• Causative agents of whooping cough.
• Bacteria that causes diphtheria.
• Legionnaires' bacilli.
• Moraxell.
• Listeria.
• Chlamydia.
• Mycoplasma.
• Ureaplasma.
• Anaerobic microorganisms.

A subgroup of antibiotics, azalides (Azithromycin), are effective in eliminating Haemophilus influenzae. Clarithromycin and Erythromycin are part of complex antibiotic therapy used for the eradication of Helicobacter pylori. Azithromycin and roxithromycin are active against some protozoan microorganisms - Trichomonas, cryptosporidium.

Range of applications

Macrolide antibiotics are broad-spectrum drugs. Effective in the treatment of acute and chronic inflammatory diseases of the respiratory tract, ENT organs and skin.

Indications for use:

• Bronchitis.
• Pneumonia.
• Sinusitis.
• Periodontitis.
• Endocarditis.
• Gastroenteritis.
• Eradication of Helicobacter pylori.
• As part of complex therapy for the treatment of sexually transmitted infections - trichomoniasis, chlamydia, ureaplasmosis.
• For severe forms of acne and furuncleosis, Erythromycin and ointments based on it are most often used.

The drugs are most widely used to treat diseases of the ENT organs. Macrolide drugs are used to treat tonsillitis, tonsillopharyngitis, otitis, inflammation of the paranasal sinuses (sinusitis, sinusitis, polysinusitis).

Benefits of Macrolides

Experts most often give preference to this group of antibacterial drugs for therapy in adults and children. It's connected with:

1. Development of bacterial resistance to many other drugs.
2. Sensitization to penicillins. In patients with infectious diseases associated with allergic rhinitis, bronchitis or asthma, drugs of the penicillin group are not used to avoid the development of allergic reactions.


3. Anti-inflammatory and immunomodulatory properties of drugs.
4. Effective against atypical microorganisms.
5. A good result in the treatment of chronic diseases of the ENT organs and respiratory tract, in which pathogenic bacteria “hide” under specific films that protect them from other antibacterial drugs. To do this, it is necessary to use antibiotics together with mucolytic agents.

Macrolides have also earned popularity due to their good tolerability, low number of side effects and availability.

Contraindications for use

Macrolides are modern, low-toxic antibiotics that are widely used both for adults and for the treatment of children, since they have virtually no contraindications for use. However, there are a number of cases in which treatment with these drugs cannot be carried out:

• The use of macrolides during pregnancy and lactation is not recommended.
• For the treatment of children under 6 months of age.
• An antibiotic should not be prescribed in case of individual intolerance to the active substance or auxiliary components of the product.

The need for treatment with an antibacterial drug, dosage, frequency and duration of administration should be determined only by the attending physician after a thorough examination and establishment of the correct diagnosis.

Side effects

When treated with macrolides, as with any medicine, adverse reactions may occur. The most common side effects of macrolides are:

• Weakness, increased fatigue.
• Drowsiness.
• Nausea.
• Vomit.
• Heaviness and pain in the abdominal area.
• Diarrhea.
• Headache.
• Allergic rash.
• Hives.
• Quincke's edema and anaphylactic shock in case of individual intolerance to drugs.

Dosage forms and application features

The list of macrolides includes drugs in tablet form, in injections, and also prescribed topically, in the form of creams or ointments.

1. For treatment at home, the most common drugs for oral administration are Azithromycin, Sumamed, Sumatrolin, Erythromycin. They must be taken an hour before meals with 200 ml of clean boiled water. 1-2 hours after eating, it is necessary to take a drug that normalizes the intestinal microflora (Linex, Bifidumbacterin), as well as mucolytics in the treatment of respiratory diseases.


2. Macrolides for children are used in liquid forms. If the names of the drugs contain the word “solutab”, this means that the tablet can be dissolved in water to form a syrup that is pleasant to the taste. The child can also be given a suspension containing an antibiotic.
3. When treating severe forms of diseases in a hospital setting, macrolides are prescribed by injection.
4. Erythromycin ointment is used for pustular diseases of the skin - acne, furunculosis, as well as for the treatment of infections of the mucous membranes of the eye.

It is important to remember that despite their safety, these antibiotics are serious medications that should not be prescribed to yourself. If a disease occurs, it is important to consult a doctor in a timely manner to establish the correct diagnosis and choose effective treatment.

When taking antibiotics, you must strictly adhere to the prescribed dosage and complete the full course of treatment to avoid the emergence of resistant forms of bacteria.

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.

Mechanism of action of macrolides

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.

These are the least toxic antibiotics, safe and well tolerated by patients. 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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