Low toxic antibiotics. When and how to take modern macrolides? Therapeutic effect of Klacida

Update: October 2018

Macrolides are a group of antibacterial drugs whose structure is based on a macrocyclic lactone ring. Due to their ability to disrupt the formation of bacterial proteins, macrolide antibiotics stop their vital activity. IN high dosages the drugs completely destroy microorganisms.

Antibiotics from the macrolide group are active against:

gram-positive bacteria (streptococci, staphylococci, mycobacteria, etc.);
gram-negative bacilli (enterobacteriaceae, Helicobacter pylori, Haemophilus influenzae, etc.);
intracellular microorganisms (moraxella, legionella, mycoplasma, chlamydia, etc.).

The action of macrolides is mainly aimed at the treatment of infectious diseases respiratory tract due to atypical and gram-positive pathogens.

Popular drugs

In the list of macrolide antibiotics, there are two substances that are most commonly used at the moment:

clarithromycin;
azithromycin.

These are representatives of two different generations macrolide drugs. From these, azithromycin was later obtained. Despite the fact that they are united by the mechanism of action on microbes and belonging to the same group, there are significant differences:

Comparison parameter	Azithromycin	Clarithromycin
Microbial spectrum of action	Intracellular organisms (chlamydia, mycoplasma, ureaplasma, legionella). Streptococci. Staphylococci (except for those resistant to erythromycin - for azithromycin). Anaerobes (clostridia, bacteroides). Gram-negative bacteria (Haemophilus influenzae, Moraxella, meningococcus, pertussis).
	Gonococcus. Spirochetes.	Mycobacteria, incl. tuberculosis. Toxoplasma. Meningococcus. Helicobacter pylori.
Effect speed	Within 2-3 hours. A stable concentration of the drug in the blood appears after 5-7 days of regular use.	Within 2-3 hours. A stable concentration of the drug in the blood occurs after 2-3 days of regular use.
Efficiency	Equally effective in the treatment of Helicobacter gastritis. Azithromycin distributes better lung tissue in the treatment of pulmonary infection, however, the effectiveness of the drug is similar to clarithromycin in a similar case of prescription. Azithromycin is more effective against legionellosis.
Adverse reactions	Central and peripheral nervous system : systemic dizziness, headaches, nightmares, general excitability, hallucinations, sleep-wake rhythm disturbance. Heart and vascular bed : palpitations, tachycardia. Digestive tract : nausea, vomiting, abdominal pain, diarrhea, short-term increase in liver enzymes (alanine and aspartate aminotransferases), jaundice. Allergic manifestations : rash (urticaria), itching.
	Vaginal candidiasis. Anaphylactic shock (rarely). Increased sensitivity to ultraviolet light. Candidiasis of the oral mucosa.	Disturbance of electrical conductivity of the myocardium in the form of arrhythmias (rare). Decreased platelet count (rare). Failure renal function(rarely). Anaphylactic shock. Angioedema. Malignant exudative erythema (Stevens-Johnson syndrome).
Safety for pregnant and lactating patients	Lactation should be stopped. Use during pregnancy may be permitted if the benefits of the drug are expected to outweigh the risks to the fetus.

Thus, the advantages of azithromycin include fewer adverse reactions in the form of severe life-threatening conditions.

For clarithromycin, the advantages of use are a wider spectrum of action and rapid achievement of stable levels in the patient’s blood.

The main disadvantage for both macrolide antibiotics is their undesirable use in pregnant women, which complicates the choice of drug in this population group.

Classification of macrolides

All generations of macrolides that have appeared as scientific research has progressed are divided according to their origin into natural and semi-synthetic. The former are derivatives of natural raw materials, the latter are artificially obtained medicinal substances.

It is also important to divide drugs according to their structural features. Depending on how many carbon atoms the macrolide ring of a substance contains, they are divided into 3 large generations:

14-member

Representatives	Tradename	Method of application, price
Oleandomycin	Oleandomycin phosphate	Powder-substance . An outdated macrolide, practically not found in pharmacies.
Clarithromycin	Klacid	Pills : 0.5 g x 2 times a day, taken for 14 days. 500-800 rub.
		Granules for preparing a suspension orally in a bottle : slowly pour water to the mark, shake the bottle, drink twice a day (the bottle contains 0.125 or 0.25 g of the substance). 350-450 rub.
		Solution for intravenous administration : 0.5 g x 2 times a day ( daily dose– 1.0 g), after mixing with solvent. 650-700 rub.
	Clarithrosin	Pills : 0.25 g x 2 times a day without depending on food intake, course 14 days. 100-150 rub.
	Fromilid	Pills : 0.5 g x 2 times a day without depending on food intake, course 14 days. 290-680 rub.
	Clarithromycin-Teva	Pills : 0.25 g x 2 times a day for 7 days or increase the dose to 0.5 g x 2 times a day for 2 weeks. 380-530 rub.
Erythromycin	Erythromycin	Pills : 0.2-0.4 g four times a day before (30-60 minutes) or after meals (1.5-2 hours), washed down with water, course 7-10 days. 70-90 rub.
		Eye ointment : place behind the lower eyelid three times a day, course 14 days. 70-140 rub.
		Ointment for external use : apply a small layer to the affected skin 2-3 times a day, the duration of the course is determined individually depending on the severity of the pathology. 80-100 rub.
		Lyophilisate for the preparation of intravenous solution : 0.2 g of the substance, diluted with a solvent, 3 times a day. The maximum duration of use is 2 weeks. 550-590 rub.
Roxithromycin	Esparoxy	Pills : 0.15 g x 2 times a day 15 minutes before meals or 0.3 g once, course 10 days. 330-350 rub.
	Rulid	Pills : 0.15 g x 2 times a day, course 10 days. 1000-1400 rub.
	RoxyHEXAL	Pills : 0.15 g x 2 times a day or 0.3 mg at a time, course 10 days. 100-170 rub.

15-member

Representatives	Tradename	Method of application, price
Azithromycin	Sumamed	Pills : 0.5 g x 1 time per day an hour before or 2 hours after meals. 200-580 rub.
		: add 11 ml of water to the contents of the bottle, shake, take once a day an hour before or 1.5-2 hours after meals. 200-570 rub.
		Capsules : 0.5 g (1 capsule) once a day an hour before or 2 hours after a meal. 450-500 rub.
	Azitral	Capsules : 0.25/0.5 g x 1 time a day before or 2 hours after meals. 280-330 rub.
	Zitrolide	Capsules : 2 capsules (0.5 g) in one dose, 1 time per day. 280-350 rub.
	Azitrox	Capsules : 0.25/0.5 g x 1 time per day. 280-330 rub.
	Azitrox	Powder for oral suspension in vials : add 9.5 ml of water to the bottle, shake, take 2 times a day. 120-370 rub.

16-member

Representatives	Tradename	Method of application, price
Spiramycin	Rovamycin	Pills : 2-3 tablets (3 million IU each) or 4-6 tablets (6-9 million IU) in 2-3 doses orally per day. 1000-1700 rub.
Spiramycin	Spiramycin-vero	Pills : 2-3 tablets (3 million IU each) for 2-3 oral doses per day. 220-1700 rub.
Midecamycin	Macropen	Pills : 0.4 g x 3 times a day, course 14 days. 250-350 rub.
Josamycin	Vilprafen	Pills : 0.5 g x 2 times a day, without chewing, with a sufficient amount of water. 530-610 rub.
Josamycin	Vilprafen solutab	Pills : 0.5 g x 2 times a day, without chewing or dissolved in 20 ml of water. 670-750 rub.

The list of 14-membered macrolides is distinguished by the development of pronounced resistance of microorganisms to their action. That is why the first subgroup of macrolide antibiotics is not prescribed immediately, but only if other antibacterial agents are ineffective.

These are reserve medications. Oleandomycin and erythromycin are low toxic and almost never cause serious adverse reactions. More often you can encounter nausea, vomiting, general malaise, allergies (urticaria, etc.). The first generation of macrolides should not be prescribed to pregnant and lactating patients.

Among the list of 14-member drugs, the most active against Helicobacter pylori is clarithromycin, which made it possible to include it in one of the treatment regimens chronic gastritis in people infected with this microorganism. It is three times more active than erythromycin for coccal infections and lasts twice as long. Oleandomycin, on the contrary, is almost never used at present, since it is outdated and does not show high antimicrobial activity.

Macrolides latest generation- the most modern representatives of the class. In particular, josamycin, with rare exceptions, does not act on bacteria that have developed resistance. It's effective and safe medicine, which is allowed during pregnancy and breastfeeding. Spiramycin is also acceptable during pregnancy, but is prohibited for lactating women, as it passes into breast milk. The drug midecamycin is a reserve macrolide and is not recommended for expectant mothers and nursing women.

Use in childhood

The use of macrolides for children is a separate section: drugs in this group are not always approved for use without restrictions. In addition, recommended dosages of medications are lower than those for the adult population, and are almost always calculated based on the baby’s body weight.

Erythromycin solution for intravenous administration can rarely cause acute toxic hepatitis in a child. The substance is prescribed at a dose of 30-40 mg per kilogram of body weight, this daily dose is divided into 2-4 doses. The duration of the course is unchanged (7-10 days).

Drugs containing the macrolide clarithromycin are limited to newborns and infants up to 6 months. For children over 12 years of age, they are prescribed 250 mg twice a day.

Azithromycin is not used in children:

up to 16 years (for infusion forms);
up to 12 years with a weight of less than 45 kg (for tablet and capsule form);
up to six months (for suspension).

In this case, the dosage for children over 12 years of age with a body weight of more than 45 kg is the same as the adult dose. And for a child 3-12 years old and weighing less than 45 kg, an antibiotic is prescribed at 10 mg per kilogram once a day.

The dose of josamycin is 40-50 mc/kg. It is evenly divided into 2-3 doses per day. It is recommended to prescribe 1-2 grams. Spiramycin tablets of 1.5 million IU are not given to children under 3 years of age, and 3 million IU tablets are not given to children under 18 years of age. The maximum dose is 300 IU per kilogram per day.

Bacterial resistance

Bacterial microorganisms are capable of developing resistance (immunity) to the action of antibiotics. Macrolides are no exception. Bacteria included in the spectrum of action of macrolides “avoid” their influence in three ways:

Modification of cellular components.
Inactivation of the antibiotic.
Active “release” of the antibiotic from the cell.

In recent years, scientists have noted a worldwide increase in the immunity of bacterial organisms to the macrolide series. In the USA, as well as Central and Southern Europe, resistance reaches 15-40%. According to the Consilium Medicum portal, in addition to macrolide resistance, there is insufficient effectiveness of aminoglycosides and methicillin (up to 30% of cases). For Turkey, Italy and Japanese lands, bacterial immunity ranges from 30-50%.

In Russia the situation is also getting worse over time. The results of the study under the supervision of the Research Clinical Institute of Otorhinolaryngology named after. L.I. Sverzhevsky states: the resistance of Staphylococcus pneumoniae (pneumococcus) in Moscow patients to 15-membered azithromycin increased by 12.9% (from 8.4% to 21.3%) in the period 2009-2016. In Yaroslavl, low resistance of S. pyogenes to erythromycin is observed (7.5-8.4%). But for Tomsk and Irkutsk this figure was higher - 15.5% and 28.3%, respectively.

Macrolide group– one of the safest at present. The wide spectrum of activity of the drugs allows them to be successfully used in the treatment of infections of varying severity, including as “reserve” drugs. But to prevent the development of microbial resistance, you should not take these medications on your own without first consulting a specialist.

Macrolides are antibiotics of natural and semi-synthetic origin, based on the chemical structure of a macrocyclic lactone ring. Depending on the number of carbon atoms in the ring structure, antibiotics are divided:

14-membered (preparations of erythromycin, roxithromycin, oleandomycin, clarithromycin);
15-membered (azithromycin preparations);
16-membered (preparations of midecamycin, spramycin and josamycin).

Natural macrolides include the drugs erythromycin, spiramycin, josamycin and midecamycin. The remaining macrolides are classified as semisynthetic antibiotics.

Macrolide drugs have a bacteriostatic effect. Inhibition of the growth of pathogenic microorganisms occurs due to inhibition of protein synthesis in ribosomes.

Increasing the dosage helps achieve a bactericidal effect.
Macrolide preparations are among the least toxic antibacterial agents. When taking macrolides, there were no cases of severe nephrotoxic reactions, secondary degenerative joint damage, or photosensitivity, manifested by hypersensitivity of the skin to ultraviolet radiation. Anaphylaxis and antibiotic-associated conditions occur in a small percentage of patients.

The main direction in the use of this group of antibiotics is the treatment of nosocomial respiratory tract infections caused by gram-positive flora and atypical pathogens (chlamdia, mycoplasma, legionella, etc.).

Modern macrolides are similar in structure to their parent, erythromycin, the differences appear only in the nature of the side chains and the number of carbon atoms (14, 15 and 16). The side chains determine activity against Pseudomonas aeruginosa. The basis of the chemical structure of macrolides is the macrocyclic lactone ring.

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

Method of obtaining

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

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

Chemical structural basis

Classification involves dividing macrolides into 3 groups:

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

It is worth noting that azithromycin ® is an azalide, since its ring contains a nitrogen atom.

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

Macrolide group of antibiotics: list of drugs

№	Name and release form
1	Azivok ® - capsule form
2	Azimicin ® – tablet form
3	Azitral ® - capsule form
4	Azitrox ® - capsule form
5	Azithromycin ® – capsules, powders
6	AzitRus ® - capsule form, powder form, tablet form
7	Azicide ® - tablet form
8	Binoclair ® - tablet form
9	Brilide ® - tablet form
10	Vero-Azithromycin ® – capsule form
11	Vilprafen ® (Josamycin ®) - tablet form
12	Grunamycin syrup ® - granules
13	ZI-Factor ® – tablets, capsules
14	Zitrolide ® - capsule form
15	Ilozon ® - suspension
16	Klabax ® – granules, tablets
17	Clarithromycin ® – capsules, tablets, powder
18	Clarithrosin ® - tablet form
19	Klacid ® — lyophilisate
20	Klacid ® – powder, tablets
21	Rovamycin ® – powder form, tablets
22	RoxyHEXAL ® – tablet form
23	Roxide ® - tablet form
24	Roxylor ® - tablet form
25	Roximizan ® - tablet form
26	Rulid ® - tablet form
27	Rulicin ® - tablet form
28	Seydon-Sanovel ® - tablet form, granules
29	CP-Klaren ® - tablet form
30	Sumazid ® - capsules
31	Sumaclid ® - capsules
32	Sumamed ® – capsules, aerosols, powder
33	Sumamecin ® – capsules, tablets
34	Sumamox ® – capsules, tablet form
35	Sumatrolide solutab ® - tablet form
36	Fromilid ® – granules, tablet form
37	Chemomycin ® – capsules, tablets, lyophilisate, powder
38	Ecositrin ® – tablet form
39	Ecomed ® - tablet form, capsules, powder
40	Erythromycin ® – lyophilisate, eye ointment, ointment for external use, powder, tablets
41	Ermiced ® – liquid form
42	Esparoxy ® - tablet form

Characteristics of each macrolide

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

Erythromycin ®

The drug inhibits the growth of chlamydia, legionella, staphylococcus, mycoplasma and legionella, Pseudomonas aeruginosa, Klebsiella, etc.

Bioavailability can reach sixty percent and depends on meals. Partially absorbed in the digestive tract.

Among side effects note: dyspepsia, nausea, narrowing of one of the sections of the stomach (diagnosed in newborns), allergies, “shortness of breath syndrome.”

Used in the treatment of tonsillitis, otitis, sinusitis, skin infections, listeriosis, gonorrhea, diphtheria, legonellosis, etc.

Treatment with erythromycin during pregnancy and lactation is contraindicated.

Roxithromycin ®

Inhibits the growth of microorganisms that produce an enzyme that breaks down beta-lactam antibiotics. The drug is resistant to acids and alkalis. The bactericidal effect is achieved by increasing the dosage. The half-life is approximately ten hours. Bioavailability is fifty percent.

Roxithromycin ® is well tolerated and excreted unchanged from the body.

Prescribed for inflammation of the mucous membrane of the bronchi, larynx, paranasal sinuses, middle ear, tonsils, gallbladder, urethra, vaginal segment of the cervix, infections of the skin, musculoskeletal system, brucellosis, etc.
Pregnancy (can be used for health reasons), lactation period and age up to two months are contraindications.

Clarithromycin ®

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

Clarithromycin ® is the most active macrolide against Helicobacter pylori, which infects various areas of the stomach, and 12 - duodenum. The half-life is approximately five hours. The bioavailability of the drug does not depend on food.

The drug is prescribed for wound infections, infectious diseases of the ENT organs, purulent rashes, pneumonia, bronchitis, furunculosis, mycoplasmosis, mycobacteriosis against the background of the immunodeficiency virus. The drug is also used as part of complex treatment regimens for stomach and duodenal ulcers.

Infancy up to six months is a contraindication.

Oleandomycin ®

Oleandomycin ® inhibits protein synthesis in pathogen cells. The bacteriostatic effect is enhanced in an alkaline environment.

To date, cases of use of oleandomycin are rare, as it is outdated.
The drug is prescribed for brucellosis, abscess pneumonia, bronchiectasis, gonorrhoea, inflammation of the meninges, inner lining of the heart, upper respiratory tract infections, purulent pleurisy, furunculosis.

Azithromycin ®

This is an azalide antibiotic, which differs in structure from classical macrolides. K – n inhibits gram+, gram-flora, aerobes, anaerobes and acts intracellularly.

The antibiotic has a wide spectrum of action.

Josamycin ® (Vilprafen Solutab ®)

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

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

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

Midecamycin ® (Macropen ®)

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

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

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

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

Spiramycin ®

The bioavailability of the drug reaches forty percent.

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

It has been scientifically proven that spiramycin ® does not affect embryonic development, so it is acceptable to take it while pregnant.

Breastfeeding is stopped for the duration of antibacterial therapy.

Antibiotics of the macrolide group: names of drugs for children

Macrolides are well tolerated and rarely cause severe adverse reactions. Undesirable effects in children may include pain in the abdomen, discomfort in the epigastric region, vomiting, nausea, and allergic reactions.

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

Clarithromycin ® deserves special attention because it is superior to other macrolides in many respects. Children under 12 years old this drug It is recommended to administer it in the form of a suspension.

Macrolides are used for:

therapy of atypical mycobacterial infections,
hypersensitivity to β-lactams,
diseases of bacterial origin (sinusitis, otitis, tonsillitis, bronchitis, skin and soft tissue infections, acne, Helicobacter pylori infection, etc.).

However, macrolide antibiotics should only be prescribed by a pediatrician. Self-medication is unacceptable.

Adverse drug reactions

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

Allergy

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

Gastrointestinal tract

Dyspeptic symptoms occur due to the prokinetic effect characteristic of macrolides. Most patients note frequent bowel movements, painful sensations in the abdominal area, impaired taste, vomiting. In newborns, the evacuation of food from the stomach into the small intestine may be impaired.

The cardiovascular system

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

Structural and functional liver disorders

CNS

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

History and development

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

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

Erythromycin ® marked the beginning of the macrolide class.

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

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

The erythromycin series is different:

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

On our website you can get acquainted with most groups of antibiotics, full lists the drugs they contain, classifications, history and other important information. For this purpose, a section “” has been created in the top menu of the site.

For quotation: Strachunsky L.S., Kozlov S.N. CLINICAL PHARMACOLOGY OF MACROLIDES // Breast Cancer. 1997. No. 21. S. 4

The article is devoted to macrolide antibiotics. More than 40 years have passed since the first marolid, erythromycin, was obtained, and despite this, it is widely used in clinical practice for the treatment of infections of the respiratory tract, skin and soft tissues. An increase in interest in macrolides occurred in the 70-89s after mycoplasma, chlamydia, campylobacter and legionella. This served as a powerful incentive for the development of new macrolides with improved microbiological and pharmacokinetic parameters compared to erythromycin.

The paper deals with macrolide antibiotics. Despite the fact that more than 40 years have passed since the preparation of the first macrolide erythromycin, it is in wide clinical use to treat infections of the airway, skin, and soft tissues. Interest in macrolides grew in 1970-1989 when Mycoplasma, Chlamydia, Campylobacter, and Legionnella were discovered. This provided powerful impetus to the development of new macrolides having better microbiological and pharmacokinetic properties than erythromycin.
The paper gives a detailed account of the pharmacokinetics and clinical application of currently available macrolide antibiotics.

Prof. L.S. Strachunsky, associate professor S.N. Kozlov
Department clinical pharmacology Smolensk Medical Academy
Prof. L.S. Strachunsky, Associate Professor
S.N. Kozlov, Department of Clinical Pharmacology, Smolensk Medical Academy

M acrolides are antibiotics whose chemical structure is based on a macrocyclic lactone ring. The first of the macrolides, erythromycin, obtained in 1952, is still widely used in clinical practice, most often for the treatment of infections of the respiratory tract, skin and soft tissues. An increase in interest in macrolides and, accordingly, an expansion in the scope of their use occurred in the 70s and 80s after the discovery of pathogens such as mycoplasma, chlamydia, campylobacter and legionella. This served as one of the incentives for the development of new macrolide antibiotics with improved pharmacokinetic and microbiological parameters compared to erythromycin, as well as a more favorable tolerability profile.

Classification

Currently, the class of macrolides includes more than ten different drugs, which, depending on the number of carbon atoms in the lactone ring, are divided into 3 groups:
1) 14-membered macrolides: erythromycin, oleandomycin, roxithromycin, dirithromycin, clarithromycin, flurithromycin;
2) 15-membered: azithromycin (is an azalide, since there is a nitrogen atom in the ring);
3) 16-membered: spiramycin, josamycin, midecamycin, myocamycin, rokitamycin.
Based on their origin, macrolides are divided into natural, semi-synthetic and prodrugs (Table 1). The latter, being esters, salts and ester salts of natural macrolides, are characterized by improved taste, greater acid resistance and higher and more stable oral bioavailability compared to the original products produced in the form of bases.
Structural features primarily determine differences in the pharmacokinetics of drugs. In addition, they determine some nuances of their antibacterial activity, tolerability and drug interactions. At the same time, all macrolides have the same mechanism of action and have generally similar antimicrobial spectra. The mechanisms of development of microflora resistance to them are also similar.

Mechanism of action

Macrolides inhibit protein synthesis in the cells of sensitive microorganisms by binding to the catalytic peptidyltransferase center of the ribosomal 50S subunit. In this case, the reactions of translocation and transpeptidation are inhibited, as a result of which the process of formation and extension of the peptide chain is disrupted. Binding to the 50S ribosomal subunits is also characteristic of antibiotics such as lincosamides, streptogramins and chloramphenicol, therefore, when macrolides are combined with these drugs, competition between them is possible and a weakening of the antimicrobial effect.
Macrolides are weak bases, their activity increases in an alkaline environment (pH 5.5 - 8.5), since they are less ionized and penetrate better into the microbial cell, and sharply decreases in an acidic environment. The nature of the antimicrobial action of macrolides is usually bacteriostatic. However, in high concentrations, at a relatively low microbial density and especially in relation to those microorganisms that are in the growth phase, they can have a bactericidal effect. Macrolides usually exhibit this effect against b- group A hemolytic streptococcus and pneumococcus.

Antibacterial activity

Erythromycin, which is the “gold standard” of macrolides, has high activity against gram-positive cocci such as b- group A hemolytic streptococcus (S. pyogenes), pneumococcus (S. pneumoniae), Staphylococcus aureus (S. aureus), excluding methicillin-resistant strains of the latter. It has a good effect on the causative agent of whooping cough (Bordetella pertussis), diphtheria bacillus (Corynebacte r ium diphtheriae), the causative agent of erythrasma (Corynebacterium minutissimum), moraxella (Moraxella catarrhalis), legionella (Legionella spp.), campylobacter spp., listeria (Listeria monocytogenes), chlamydia (Chlamydia trachomatis), mycoplasma(Mycoplasma pneumoniae), ureaplasma (Ureaplasma urealyticum).
Erythromycin is moderately active against Haemophilus influenzae, Borrelia burgdorferi, wound infections caused by animal bites (Pasteurella multocida, Ei k enella corrodens) and some bacteroides, including Bacteroides fragilis. It has virtually no effect on gram-negative bacteria of the Enterobacteriaceae family, Pseudomonas spp. and Acinetobacter spp., since it does not penetrate the cell membrane of these microorganisms.
Other macrolides, while generally similar in spectrum and severity of antimicrobial action to erythromycin, have some peculiarities.

Activity against pyogenic cocci

Macrolides have no fundamental differences in their effect on rapidly reproducing pyogenic cocci (Table 2). Azithromycin has some superiority over other drugs in activity against N. gonorrhoeae. For S. aureus best effect exhibits clarithromycin. It should be emphasized that neither one of the macrolides has virtually no effect on strains Staphylococcus aureus resistant to erythromycin. Methicillin-resistant S. aureus strains are resistant to all macrolides.
Clarithromycin is superior to other macrolides in its activity against S. pyog enes and S. agalactiae, the second most effective is erythromycin. All drugs have approximately equivalent activity against pneumococcus. According to some data, 16-membered macrolides - spiramycin and josamycin - can act on penicillin-resistant strains of pneumococcus. Clarithromycin, azithromycin, josamycin and spiramycin are most active against anaerobic cocci.

Activity against gram-negative bacteria

Azithromycin is superior to other drugs in its action against H. influenzae, M. catarrhalis, C. jejuni and P. multocida. Clarithromycin is most active against L. pneumophila and Helicobacter pylori. All macrolides, except dirithromycin, have a moderate effect on Bacteroides spp. and B.fragilis. Microflora of the family Enterobacteriaceae, Pseudomonas spp . and Acinetobacter spp. have natural resistance to macrolides.

Activity against chlamydia and mycoplasma

Macrolides have fairly high activity against most chlamydia, mycoplasmas and ureaplasmas (Table 3). Midecamycin has the most distinct microbiological activity against genital mycoplasmas (M. hominis). Clarithromycin is superior to other drugs in its action against C. trachomatis.

Activity against Toxoplasma and other protozoa

Almost all macrolides have an inhibitory effect on T. gondii, but do not cause their complete death. Spiramycin, azithromycin, clarithromycin and roxithromycin have the highest activity. Spiramycin, azithromycin and roxithromycin are active against cryptosporidium (Cryptosporidium parvum).

Activity against atypical mycobacteria

Clarithromycin, azithromycin and roxithromycin are superior to erythromycin in their action on the intracellular complex of M. avium, which is a common causative agent of opportunistic infections in patients with AIDS. The most active is clarithromycin, which in vitro is 4 times more active than azithromycin. In addition, clarithromycin is better than erythromycin and azithromycin against M. leprae.

Activity against other microflora

Azithromycin, clarithromycin, roxithromycin, and dirithromycin are superior to erythromycin against B. burgdorferi. Midecamycin has a slightly stronger effect on C. diphtheriae than erythromycin.

Mechanisms of microflora resistance

Acquired resistance to macrolides can be caused by three factors.
1. Modification of the target at the level of the bacterial cell, which is caused by methylation of adenine in the 23S RNA of the 50S ribosomal subunit. This process is catalyzed by special enzymes - methylases. As a result, the ability of macrolides to bind to ribosomes is disrupted and they are blocked antibacterial effect. This type of resistance is called the "MLS type" because it may underlie microflora resistance not only to macrolides, but also to lincosamides and streptogramins. MLS-type resistance can be either natural (constitutive) or acquired (inducible), and its inducers are 14-membered macrolides, especially erythromycin and oleandomycin, which enhance the synthesis of methylases. It is characteristic of some strains of group A streptococcus, Staphylococcus aureus, mycoplasmas, listeria, campylobacter and other microorganisms. MLS-type resistance is not developed to 16-membered macrolides, since they are not methylase inducers.
2. Active elimination of macrolide from the microbial cell. For example, Staphylococcus epidermidis has this ability.
3. Inactivation of macrolides through enzymatic cleavage of the lactone ring by esterases or phosphotransferases from bacteria of the Enterobacteriaceae family.

Pharmacokinetics

Suction

After oral administration, macrolides are partially destroyed by gastric acid. This is most true for erythromycin and oleandomycin. Enteric dosage forms and some esters, such as erythromycin stearate, have increased resistance to acid. Newer macrolides, especially clarithromycin, are also characterized by higher acid stability.
Food can have a significant effect on the bioavailability of macrolides. The absorption of erythromycin in the presence of food is sharply reduced; slightly smaller changes in absorption are characteristic of spiramycin, dirithromycin and clarithromycin. Food slows the rate of absorption of roxithromycin and azithromycin without affecting its volume.

Blood concentration

Peak concentrations of macrolides in blood serum after oral administration and values reflecting the area under the pharmacokinetic curve depend on the type of drug and dose (Table 4). As the dose of an antibiotic increases, its bioavailability usually increases. The highest serum concentrations are observed when taking roxithromycin, which can be associated with its relatively low tissue affinity. The most low concentrations in the blood are characteristic of azithromycin, which theoretically could create problems in infections accompanied by bacteremia.
An important element of the pharmacokinetics of macrolides, which is noted quite often, is the presence of two concentration peaks in the blood. The phenomenon of the second peak is due to the fact that a significant part of the drug, initially deposited in the gallbladder, subsequently enters the intestine and is absorbed. For erythromycin, the magnitude of the second serum peak may exceed the level of the first. When azithromycin is used, parallel to the second peak in serum, a repeated increase in concentration is observed in other biological fluids, in particular in lymph.
When administered intravenously, high concentrations of macrolides in the blood are formed very quickly. They exceed the levels achieved with oral administration of drugs, since in in this case There is no loss during absorption and initial passage of antibiotics through tissue. Our data indicate that when erythromycin is administered intravenously to newborns, high concentrations in the blood are maintained for a longer period than in older children.
Macrolides bind to plasma proteins to varying degrees, mainly to a1-glycoproteins. The highest binding is characterized by roxithromycin (92 - 96%), the least by spiramycin.(10 - 18%).

Distribution

All macrolide antibiotics are well distributed in the body, penetrating into many organs, tissues and environments. In terms of their ability to pass through various histohematic barriers (with the exception of the blood-brain barrier), macrolides are superior to b- lactams and aminoglycosides. The advantage of macrolides is their ability to create very high and stable concentrations in tissues, exceeding the level of drugs in the blood serum. Thus, tissue concentrations of erythromycin are 5 to 10 times higher than serum concentrations. The highest tissue levels, 10 to 100 times higher than blood concentrations, are characteristic of azithromycin. The exception is roxithromycin, the concentration of which in tissues is lower than in the blood, which is apparently due to the high degree of binding of the drug to plasma proteins.
Table 1. Classification of macrolides

Natural	Prodrugs	Semi-synthetic
Erythromycin	Erythromycin esters	Myocamycin
	Propionyl	(Midecamycin acetate)
	Ethyl succinate
Oleandomycin	Erythromycin salts	Flurithromycin
	Stearate
Spiramycin	Erythromycin ester salts	Roxithromycin
	Estolate
Josamycin	Propionyl mecaptosuccinate	Clarithromycin
	Acistrate
Midecamycin	Acetylcysteinate	Azithromycin
	Oleandomycin esters
	Troleandomycin	Dirithromycin
	Triacetyoleandomycin
	Rokitamycin
	Leukomycin A5 propionyl ester

Macrolides accumulate in the tonsils, middle ear, paranasal sinuses, lungs, bronchopulmonary secretions, pleural and peritoneal fluid, lymph nodes, pelvic organs (including prostate gland), and during inflammation, the permeability of drugs into the corresponding focus increases. Concentrations of macrolide antibiotics created in these organs and environments exceed their MICs for major pathogens.
Unlike many other antibiotics, macrolides penetrate well into cells and create high intracellular concentrations, which is important in the treatment of infections caused by intracellular pathogens (Mycoplasma spp., Chlamydia spp., Legionella spp., etc.). It is also significant that macrolides (mostly azithromycin and clarithromycin) are able to penetrate into phagocytic cells, such as macrophages, fibroblasts, polymorphonuclear granulocytes, and are transported with them to the inflammatory focus.

Metabolism and excretion

Macrolides are metabolized in the liver with the participation of cytochrome P-450 (isoform CYP3A4) with the formation of both inactive metabolites and compounds with antibacterial properties (for example, 14-hydroxyclarithromycin). Metabolites are excreted primarily in bile and then in feces. Renal excretion is 5 - 10%. The half-life varies from 1.5 (erythromycin, josamycin) to 65 (dirithromycin) hours. If renal function is impaired, the half-life of most macrolides (with the exception of clarithromycin and roxithromycin) does not change, so no adjustment of dosage regimens is required. In liver cirrhosis, the half-life of erythromycin and josamycin may increase significantly.

Adverse reactions

Macrolides are considered one of the safest groups of antibiotics, very rarely causing serious adverse reactions. The most typical reactions for macrolides are reactions from the upper gastrointestinal tract in the form of pain, nausea and vomiting, which most often occur with oral administration of high doses of drugs, but can also be observed with intravenous administration. The development of dyspeptic disorders is most typical for erythromycin and oleandomycin, which is associated with their stimulating effect on gastrointestinal motility. It has been established that these drugs are agonists of receptors sensitive to the endogenous motilin stimulant. Other 14-membered macrolides (roxithromycin, clarithromycin), azalides (azithromycin) and 16-membered drugs (spiramycin, josamycin) are less likely to cause dyspeptic symptoms. Adverse reactions from the lower intestine are rare, although cases of diarrhea have been described.
Table 2. Activity of macrolides against cocci (MIC50, mg/l)

A drug	S. aureus	S. pyogenes	S. pneumoniae	Enterococcus spp.	N.gonorrhoeae	Anaerobic cocci
Erythromycin	0,12	0,03	0,03		0,25
Clarithromycin	0,06	0,015	0,015		0,25	0,25
Roxithromycin	0,25	0,06	0,03
Dirithromycin	0,25	0,12	0,06
Azithromycin	0,12	0,12	0,06		0,03	0,25
Josamycin		0,12	0,06			0,25
Spiramycin		0,12	0,03	0,25		0,25
Note: MIC is the minimum inhibitory concentration.

With long-term use of erythromycin and troleandomycin, cholestatic hepatitis accompanied by jaundice, paroxysmal pain in the abdomen, eosinophilia and high levels of liver transaminases in the blood serum. In rare cases, when high doses of erythromycin and clarithromycin are prescribed, especially to patients with impaired renal function, reversible ototoxic reactions are observed, manifested by hearing impairment and ringing in the ears.
With intravenous administration of macrolides, thrombophlebitis may occur, the risk factors for the development of which are rapid administration and high concentration of solutions. It is possible to develop a superinfection (Candida, gram-negative bacteria) in the gastrointestinal tract or vagina. Hypersensitivity to macrolide antibiotics is very rare.

Drug interactions

During the process of biotransformation, 14-membered macrolide antibiotics are capable of being converted into nitrosoalkane forms, which bind to cytochrome P-450 and form inactive complexes with it. Thus, macrolides can inhibit the metabolism of other drugs in the liver:2:(s:4:"TEXT";s:72666:"TV drugs, increasing their concentration in the blood and enhancing not only therapeutic effects, but also the risk of toxicity. The most potent inhibitor of cytochrome P-450 is troleandomycin. Other drugs, according to the severity of this effect, can be arranged in the following order: clarithromycin > erythromycin > roxithromycin > azithromycin > spiramycin. Most reports of clinically significant drug interactions between macrolides concern erythromycin and clarithromycin (Table 5). Their use in combination with warfarin, carbamazepine or theophylline is fraught with the development of undesirable reactions characteristic of the latter.
Concomitant use of erythromycin (and possibly other macrolides) and cyclosporine should be avoided. When erythromycin is combined with lovastatin, cases of severe myopathy and rhabdomyolysis have been reported. The antihistamines terfenadine and astemizole, as well as the prokinetic drug cisapride, are contraindicated in patients taking erythromycin or clarithromycin due to high risk development of fatal disorders heart rate.
Table 3. Activity of macrolides against chlamydia, mycoplasma and ureaplasma (MIC90, mg/l)

A drug	C. pneumoniae	C. psittaci	C. trachomatis	M. pneumoniae	M. hominis	U. urealyticum
Erythromycin	0,06		0,06	J 0.01	> 32	0,12 - 2,0
Roxithromycin	0,05 - 0,125	0,025 - 2	0,03	J 0.01-0.03	8 ® 64	0,06 - 1,0
Dirithromycin			0,01 - 0,02
Clarithromycin		0,05	0,007	J 0.01 - 0.05	8 - 64	0,025 - 1,0
Azithromycin	0,06	0,02	0,125	J 0.01	2 - 16	0,12 - 1,0
Josamycin	0,25	0,25	0,03	Ј 0.01 - 0.02	0,02 - 0,5
Midecamycin			0,06	J 0.01	0,008 - 0,12	0,03 - 0,25
Spiramycin				0,05 - 1		3 (MPC 50) - 15 (MPC 90)*
*Drug Invest. 6(Suppl. 1)1993.

Macrolides are able to increase the bioavailability of digoxin when taken orally due to the suppression of colon microflora (Eubacterium lentum), which inactivates digoxin.
The absorption of some macrolides, especially azithromycin, from the gastrointestinal tract may be impaired when taking antacids.
In general, the problem of interaction of macrolides with other drugs is dynamic developing area clinical pharmacology. New information constantly appears in it, which is associated with the expansion of the number of patients receiving these antibiotics.

Clinical Application

The main indications for the use of macrolide antibiotics and doses for various categories of patients are summarized in table. 6, 7.

Respiratory tract infections

Macrolides are most widely used for respiratory tract infections. They are effective in 80 - 70% of patients with bronchitis, acute otitis media, sinusitis, tonsillopharyngitis and community-acquired pneumonia. Macrolides more often than b- lactam antibiotics are given healing effect in cases where it is not possible to identify the causative agent of infection. Comparative controlled clinical studies have shown that macrolides are not inferior and sometimes superior in effectiveness to oral antibiotics of some other classes (ampicillin, amoxicillin, co-amoxiclav, cefixime, ciprofloxacin, doxycycline) in patients with community-acquired pneumonia.
Table 4. Comparative pharmacokinetics of macrolides

A drug	Dose, mg	T max , h	C max , mg/l	AUC, mg/(tsp)	T 1/2 , h
Azithromycin		2 - 3			35 - 54
Clarithromycin		2 - 3		18,9
Dirithromycin		4 - 4,5	0,1 - 0,5		16 - 65
Erythromycin base		1 - 5	1,9 - 3,8	5,8 - 11,2	1,5 - 2,5
Josamycin	1000				1,5 - 2,5
Roxithromycin		1 - 3	5,4 - 7,9	53,0 - 81	10,5
			10,8		11,3
Spiramycin	3000	5 - 10	1,6 - 2,8	13,6	8/14*
Note: Tmax is the time to reach the peak concentration in the blood, Cmax is the value of the peak concentration, AUC is the area under the pharmacokinetic curve, T1/2 is the half-life. * When administered intravenously at a dose of 15 - 20 mg/kg.

The high effectiveness of macrolides in respiratory tract infections is associated, firstly, with the fact that the spectrum of their antimicrobial activity includes most of the main respiratory pathogens, such as S. pneumoniae, M. catarrhalis, H. influenzae, and secondly, with the ability to create high concentrations in the corresponding foci of inflammation and, thirdly, with activity against atypical pathogens. For the action of macrolides, the production of b-lactamases by some microorganisms (M. catarrhalis, H. influenzae), which determine their resistance to aminopenicillins, does not matter.

Table 5. Clinically significant drug interactions between macrolides

Interacting drug	Macrolide	Result of interaction
Warfarin	Erythromycin	Increased hypoprothrombinemia
	Clarithromycin	Increased hypoprothrombinemia
Carbamazepine	Erythromycin	Increased concentration of carbamazepine in the blood 2 - 4 times, increasing its toxicity
Carbamazepine	Clarithromycin
	Josamycin
Cyclosporine	Erythromycin	An increase in the concentration of cyclosporine in the blood, an increase in its nephrotoxicity
	Roxithromycin
	Josamycin
Digoxin	Erythromycin	Increased digoxin concentration in the blood, increased risk of toxicity*

Terfenadine	Erythromycin	Increasing the concentration of antihistamine drug in the blood, quinidine-like effect, high risk of ventricular arrhythmias
Astemizole	Clarithromycin

Theophylline	Erythromycin	Increasing theophylline concentration in the blood by 10 - 25%, increased toxicity actions on the central nervous system and gastrointestinal tract
	Roxithromycin
	Clarithromycin

Triazolam	Erythromycin	Increased benzodiazepine concentrations in the blood, increased sedative effect
Midazolam	Roxithromycin
Disopyramide	Erythromycin	Increasing the concentration of disopyramide in blood
		Increasing the concentration of disopyramide in blood
Ergot alkaloids	Erythromycin	Increased concentration of alkaloids ergot in the blood, severe spasm peripheral vessels with possible ischemia and gangrene of the limbs
Methylprednisolone	Erythromycin	Increased AUC of methylprednisolone, it is possible to prolong its effect

Valproic	Erythromycin	Increasing the concentration of valproic acid acids in the blood, drowsiness
acid
Bromocriptine	Erythromycin	Increased AUC of bromocriptine
*The interaction is not due to inhibition of cytochrome P-450. Note: AUC is the area under the pharmacokinetic curve.

It is known that community-acquired pneumonia can be caused not only by typical pathogens, but also by pathogens such as M. pneumoniae, C. pneumoniae, C. psittaci, L. pneumophila and Coxiella burnetii, which is why the term “atypical” pneumonia appeared. Bacteriological identification of the listed microorganisms is not always possible, and therefore in many cases the prescription of antibiotics is empirical. Taking into account the characteristics of the spectrum of antimicrobial activity and a successful pharmacokinetic profile, macrolides are considered the drugs of choice for “atypical” pneumonia and, according to the results of numerous controlled studies, are highly effective in patients with this pathology.

Controlled clinical studies of new macrolides in comparison with another, “early” macrolide - spiramycin - have not been conducted.
Macrolides are the drugs of choice for the treatment of chlamydial respiratory tract infections in newborns and children, since the administration of tetracyclines to them is contraindicated. It should be taken into account that there are strains (especially among C. psittaci) that are resistant to macrolides.
Table 6. Indications for the use of macrolides

Disease	A drug
Tonsillopharyngitis	Any of the macrolides
Acute otitis media
Acute sinusitis	Any of the macrolides (except erythromycin)*
Exacerbation chronic bronchitis	Any of the macrolides (except erythromycin)*
Pneumonia	Any of the macrolides
Whooping cough	Erythromycin
Diphtheria	Erythromycin (in combination with anti-diphtheria serum)
Legionellosis	Erythromycin
	Any of the macrolides
Acne	Erythromycin
Erythrasma	Erythromycin
Chlamydial conjunctivitis	Any of the macrolides
Acute chlamydial urethritis/cervicitis	Any macrolide (azithromycin single dose)
Gonorrhea	Azithromycin
Syphilis	Erythromycin, azithromycin**
Soft chancroid (chancroid)	Any of the macrolides
Gastroenteritis caused by C. jejuni	Any of the macrolides
Cryptosporidiosis	Spiramycin
Eradication of H. pylori	Clarithromycin (in combination with other antibiotics and antisecretory drugs)
Toxoplasmosis	Spiramycin, roxithromycin, clarithromycin, azithromycin (for severe forms in combination with pyrimethamine and/or sulfadiazine)
Infections caused by M. avium complex	Clarithromycin, azithromycin
Lyme disease	Azithromycin, clarithromycin
Meningococcal meningitis (prevention)	Spiramycin
Periodontitis	Spiramycin
Rheumatism (prevention)	Erythromycin
Surgeries on the colon and rectum (infection prevention)	Erythromycin in combination with neomycin
Prevention of endocarditis	Erythromycin
Erythromycin has little effect on H. influenzae. In the USA, it is recommended to combine it with sulfonamides, but their use is fraught with the development of severe adverse reactions. *The effectiveness of azithromycin has not been confirmed by controlled studies.

Although several classes of antibiotics are active in vitro against L. pneumophila, macrolides have the best effect in vivo, presumably due to their accumulation in phagocytes. The drug of choice for legionellosis remains erythromycin, which is initially prescribed intravenously in high doses (up to 4 g per day), and then switched to oral administration. In the most severe cases, it is used in combination with rifampicin. Clarithromycin, azithromycin, and roxithromycin are also effective.
Table 7. Doses of macrolides for the most common infections

A drug	Adults	Children
Erythromycin	Orally: 0.25 - 0.5 g	40 - 50 mg/kg per day in 4 divided doses
	4 times a day 1 hour before meals	(introductions)
	Intravenously: 0.5 - 1 g 4 times a day
Spiramycin (Rovamycin)	Orally: 6 - 9 million IU	Orally: 1.5 million IU
	(2-3 g) per day in 2 divided doses	for 10 kg of weight per day in 2 doses
	Intravenously: 4.5 - 9 million IU
	per day in 2 administrations
Josamycin (vilprafen)	Orally: 0.8 - 2 g	30 - 50 mg/kg per day in 3 divided doses
	per day in 3 doses
Midecamycin (macropen tablets)*	Orally: 0.4 g 3 times a day
Midecamycin acetate		Orally: 50 mg/kg per day in 3 divided doses
(macropen suspension)*
Roxithromycin (Rulid)	Orally: 0.15 g 2 times a day	5 - 8 mg/kg per day in 2 divided doses
Clarithromycin (clacid)	Orally: 0.25 - 0.5 g 2 times a day	7.5 mg/kg per day in 2 divided doses
Azithromycin (sumamed)	Orally: 0.5 g 1 time per day within 3 days; 1 g once (for acute urogenital chlamydia)	10 mg/kg 1 time per day for 3 days
Dirithromycin (dinabac)	Orally: 0.5 g 1 time per day
* Midecamycin (tablets) and midecamycin acetate (suspension) are registered in Russia under the same trade name "Macropen".

Macrolides are traditionally considered as an alternative to penicillins for tonsillopharyngitis caused by S. pyogenes. Clinical and bacteriological studies have shown that they are as effective in eradicating streptococcus from the tonsils (more than 70%) as phenoxymethylpenicillin, therefore, they provide completely reliable prevention of serious complications of tonsillopharyngitis - rheumatism and glomerulonephritis. However, in some regions there are strains of group A streptococcus that are resistant to erythromycin and have cross-resistance to other macrolides. According to our data, the frequency of such streptococci (MIC > 0.5 μg/ml) is 13%.
For otitis media, macrolides can be used as an alternative to aminopenicillins and co-trimoxazole. Considering that erythromycin has a relatively weak effect on H. influenzae, it is recommended to combine it with sulfonamides or use other macrolides, which also have advantages over erythromycin in patients with sinusitis. Azithromycin is effective in patients with otitis and sinusitis when administered in a short 3-day course.
In children with whooping cough, macrolides, although they do not affect the duration of the disease, reduce the severity of its clinical manifestations and cause rapid eradication of Bordetella pertussis from the nasopharynx. The drug of choice is erythromycin, which can be prescribed not only for therapeutic purposes, but also for prophylactic purposes. Erythromycin is also used for the treatment of diphtheria as an adjunct to the use of anti-diphtheria serum.

Skin and soft tissue infections

Macrolides are very successfully used for staphylococcal infections of the skin and soft tissues (impetigo, furunculosis, folliculitis, cellulitis, paronychia), not inferior in effectiveness to the antistaphylococcal penicillins - cloxacillin and dicloxacillin. However, it must be kept in mind that there are strains of S. aureus that are resistant to erythromycin. For streptococcal infections (erysipelas, streptoderma), benzylpenicillin remains the drug of choice. The use of macrolides is an alternative treatment option in such situations.
The need for systemic use of antibiotics may occur in moderate/severe forms of acne (acne vulgaris). Oral erythromycin is an effective and inexpensive treatment option acne, and long-term use the drug does not lead to the selection of resistant strains of Propionibacterium acne, which plays an important role in the etiology of this infection. However, erythromycin is better tolerated than tetracycline. Erythromycin is also used to treat erythrasma (caused by C. minutissimum).

Sexually transmitted infections

Due to their unique antimicrobial spectrum and distribution characteristics, macrolides are considered antibiotics that are almost ideal for the treatment of sexually transmitted infections.
Macrolides have high activity in vitro against C. trachomatis and are widely used for chlamydia of the genital tract in both women and men. Erythromycin and spiramycin are considered the drugs of choice for the treatment of chlamydial infections in pregnant women and children. In controlled studies conducted in patients with non-gonococcal urethritis and cervicitis (causative agents - C. trachomatis, U. urealyticum), the high effectiveness of erythromycin, spiramycin, clarithromycin, roxithromycin and azithromycin was revealed. Azithromycin for acute chlamydia can be used in a dose of 1 g once. Macrolides can cause eradication of U.urealyticum from the genitourinary tract of men, including 10% of isolates resistant to tetracyclines. At the same time, they do not lead to the eradication of this microorganism from the female genital tract.
Erythromycin remains a reserve drug for the treatment of primary and secondary syphilis in patients who, for some reason, cannot take penicillin or tetracyclines. Due to the fact that it is somewhat inferior in effectiveness to the latter, the condition of patients should be carefully monitored. Data have been obtained on the successful use of azithromycin in primary syphilis. Prescribing it at a dose of 500 mg per day for 1 0 days or 500 mg every other day up to a total dose of 3 g is accompanied by faster positive clinical dynamics than with the use of benzylpenicillin and erythromycin. In terms of the rate of eradication of treponemes, azithromycin was superior to erythromycin, but inferior to penicillin.
There is evidence of the possibility of using macrolides for soft chancroid (chancroid), which is caused by Haemophilus ducreyi. Many strains of this pathogen are resistant to penicillins, tetracyclines and sulfonamides.
The question of the use of macrolides for gonorrhea remains controversial. Because many strains of N. gonorrhoeae are resistant to erythromycin, this drug is currently used to treat gonococcal infections does not apply . Azithromycin, as the most active among macrolides against gonococcus, can be used for acute gonorrheal urethritis and cervicitis. Some controlled studies have established a fairly high effectiveness (90 - 95%) with a single dose of 1 g. Azithromycin is especially indicated for mixed etiology of urethritis (gonococcus, chlamydia).

Gastrointestinal tract infections

Bacterial diarrhea may be more often caused by Campylobacter (C. jejuni) than by Salmonella or Shigella. A characteristic property of Campylobacter diarrhea is that it often goes away on its own and does not require the use of antibiotics. However, in cases where the symptoms are persistent, there is fever or blood in the stool, the administration of macrolides no later than the fourth day from the onset of clinical manifestations leads to a decrease in the severity of the disease and the cessation of excretion of C. jejuni in feces.
In people with immunodeficiency, such as those with AIDS, intestinal damage by Cryptosporidium spp. may occur, accompanied by persistent diarrhea. There is positive experience with the use of spiramycin in such cases, which significantly improves the condition of patients. Spiramycin was also shown to be effective in a placebo-controlled study for diarrhea caused by cryptosporidium in nonimmunocompromised neonates.

Toxoplasmosis

Spiramycin is the first macrolide to be used to treat toxoplasmosis in pregnant women. Its administration orally at a dose of 2–3 g per day in the form of two 3-week courses with a 2-week interval was accompanied by a significant reduction in the risk of intrauterine infection. Roxithromycin, clarithromycin and azithromycin are considered promising for the treatment of toxoplasmosis.
Given that the effect of macrolide antibiotics against T. gondii is protozoastatic, in most severe forms of infection, especially encephalitis and in patients with AIDS, they should be used in combination with pyrimethamine and/or sulfadiazine.

Infections caused by mycobacteria

Clarithromycin and azithromycin are effective against opportunistic infections caused by M. avium complex in patients with AIDS. For the treatment of disseminated infection, it is recommended to use clarithromycin at a dose of 500 mg twice daily in combination with ethambutol and rifabutin. Azithromycin is considered as an alternative drug, but its optimal dosage regimen has not yet been developed. Prophylactic administration of these macrolides for AIDS reduces the risk of infection with M. avium and reduces the mortality of patients. The dose of azithromycin is 1200 mg once a week.
There are reports of effective application macrolides for leprosy (pathogen - M. leprae) both as monotherapy and in combination with minocycline. Recently, data have appeared indicating the possibility of using macrolides for infections caused by the so-called fast-growing mycobacteria - M. chelonae. They usually manifest themselves as post-injection or post-operative abscesses in patients with severe immunodeficiency, in particular with AIDS.
The question of the possible role of macrolide antibiotics in the treatment of tuberculosis remains open, although some encouraging data have emerged in this regard. Clarithrimycin has been found to have synergism with isoniazid and rifampicin against M. tuberculosis.

Other diseases

Macrolides are widely and with high efficiency used for chlamydial conjunctivitis in newborns and children.
Azithromycin and clarithromycin are considered alternative drugs for the treatment of Lyme disease, which is caused by Borrelia burgdorferi. Controlled studies have shown that these macrolides reduce the severity of clinical symptoms of the disease and reduce the frequency of relapses.
Macrolides are used to treat various odontogenic infections (periodontitis, periostitis, etc.). Most preferred drug Spiramycin, which accumulates in high concentrations in saliva and penetrates deep into the gums and bone tissue, is considered.
Clarithromycin is used to eradicate H. pylori in patients with peptic ulcer disease (in combination with other antibiotics and antisecretory drugs).

Prophylactic use

WITH for preventive purposes Erythromycin is more commonly used. As already

Macrolides are part of the pharmacological group of antibiotics wide range, aimed at suppressing pathogenic microbes that cause various kinds 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, and among the disadvantages - high price medicines - 1371 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. Primary area of impact infection suppression respiratory organs, is 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 drugs. 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 side similar medicines 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 substance: "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!

Most likely, each of you knows about antibiotics and their properties. The word "antibiotics" is translated from Greek...

Macrolides in the fight against... Today, in the fight against various bacterial diseases Children take first place...

Pregnancy. There is information about the negative effects of clarithromycin on the fetus. Data proving...

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Rovamycin Antibiotic Rovamycin The drug Rovamycin is a natural antibiotic. Belongs to the group of macrolides. For microorganisms...

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A distinctive feature of Klacid is its activity against a wide range of microbes, including atypical pathogenic bacteria that cause infectious and inflammatory diseases of the respiratory tract. In addition, the antibiotic is highly effective in the treatment of acute otitis media, acute bronchitis, pneumonia, pharyngitis or tonsillitis in children.

Varieties, names, composition and release forms

Currently, the antibiotic Klacid is available in two varieties:

Klacid;
Klacid SR.

The Klacid SR variety differs from Klacid in that it is a long-acting tablet. There are no other differences between Klacid and Klacid SR, therefore, as a rule, both types of the drug are combined under the same name “Klacid”. We will also use the name "Klacid" to refer to both types of the drug, specifying which one we are talking about only if necessary.

Klacid SR is available in a single dosage form - these are extended-release (long-acting) tablets, and Klacid is available in three dosage forms, such as:

Lyophilisate for the preparation of solution for infusion;
Powder for the preparation of suspension for oral administration;
Pills.

As an active substance, all dosage forms of both varieties contain clarithromycin in varying dosages. Thus, Klacid SR tablets contain 500 mg of the active substance. The lyophilisate for the preparation of solution for infusion contains 500 mg of clarithromycin per vial. Tablets of regular duration of action Klacid are available in two dosages - 250 mg and 500 mg of clarithromycin. The powder for preparing the suspension is also available in two dosages - 125 mg/5 ml and 250 mg/5 ml. This means that the finished suspension can have a concentration of active substance of 125 mg per 5 ml or 250 mg per 5 ml.

In everyday life, various dosage forms, varieties and dosages of Klacid are called short and succinct names that reflect their main characteristics. Thus, tablets are often called Klacid 250 or Klacid 500, where the number next to the name reflects the dosage of the drug. Taking into account the same principle, the suspension is called Klacid 125 or Klacid 250, etc.

Tablets of both dosages Klacid and extended-release Klacid SR have the same biconvex, oval shape and are coated with a colored film. yellow. Tablets are available in packs of 7, 10, 14, 21 and 42 pieces.

Powder for the preparation of a suspension for oral administration is small granules, white or almost white in color and having a fruity odor. The powder is available in 42.3 g bottles complete with a dosing spoon and syringe. When the powder is dissolved in water, an opaque suspension is formed, colored white and having a fruity aroma.

The lyophilisate for preparing a solution for infusion is available in hermetically sealed bottles and is a white powder with a slight aroma.

Therapeutic effect of Klacida

Klacid is an antibiotic and, accordingly, has a detrimental effect on various pathogenic microorganisms, causing infectious and inflammatory diseases. This means that when taking Klacid, microbes die, which leads to the cure of an infectious-inflammatory disease.

Klacid has a wide spectrum of action and harmful to the following types of microorganisms:

Chlamydia pneumoniae (TWAR);
Chlamydia trachomatis;
Enterobacteriaceae and Pseudomonas;
Haemophilus influenzae;
Haemophilus parainftuenzae;
Helicobacter (Campilobacter) pylori;
Legionella pneumophila;
Listeria monocytogenes;
Moraxella catarrhalis;
Mycobacterium leprae;
Mycobacterium kansasii;
Mycobacterium chelonae;
Mycobacterium fortuitum;
Mycobacterium avium complex (MAC) - a complex including: Mycobacterium avium, Mycobacterium intracellulare;
Mycoplasma pneumoniae;
Neisseria gonorrhoeae;
Staphylococcus aureus;
Streptococcus pneumoniae;
Streptococcus pyogenes.

Klacid will be effective for the treatment of infectious and inflammatory diseases various organs, only if they are caused by any of the above microorganisms that are sensitive to its action. And since microbes sensitive to the action of Klacid usually cause diseases of certain organs and systems to which they have an affinity, the drug is usually used to treat infections of a number of organs.

Detrimental to the following microorganisms the effect of Klacid is shown only in laboratory tests, but not confirmed by clinical practice:

Bacteroides melaninogenicus;
Bordetella pertussis;
Borrelia burgdorferi;
Campylobacter jejuni;
Clostridium perfringens;
Pasteurella multocida;
Peptococcus niger;
Propionibacterium acnes;
Streptococcus agalactiae;
Streptococci (groups C,F,G);
Treponema pallidum;
Viridans group streptococci.

If infection caused by any of the above microbes, the sensitivity of which to Klacid has been shown only in laboratory conditions, it is better to abandon the use of this antibiotic and replace it with another.

Indications for use

Both varieties and all dosage forms of Klacid have the same following indications for use:

Infections of the lower parts of the respiratory system (bronchitis, pneumonia, bronchiolitis, etc.);
Infections of the upper respiratory system (pharyngitis, tonsillitis, sinusitis, otitis media, etc.);
Infections skin and soft tissues (folliculitis, erysipelas, infectious cellulitis, furunculosis, impetigo, wound infection, etc.);
Infections caused by mycobacteria;
Prevention of Mycobacterium avium complex (MAC) infection in HIV-infected people;
Eradication of H. pylori to cure gastritis and gastric or duodenal ulcers;
Treatment and reduction of the frequency of relapses of duodenal ulcers;
Infections of the teeth and oral cavity (dental granuloma, stomatitis, etc.);
Infections caused by Chlamydia trachomatis, Ureaplasma urealyticum (urethritis, colpitis, etc.).

The drug is effective against many microorganisms - gram-negative (meningococci, gonococci, Haemophilus influenzae, Helicobacter pylori, etc.) and gram-positive (staphylococci, streptococci, pneumococci, corynebacterium diphtheria, etc.). It is also prescribed to combat intracellular microorganisms (chlamydia, mycoplasma, ureaplasma, etc.), as well as some anaerobic bacteria(peptococci, peptostreptococci, bacteroides and clostridia).

Vilprafen is quickly absorbed from the digestive tract. Within an hour its maximum concentration in the blood is reached. At the same time, Vilprafen has a long-term therapeutic effect.

The drug crosses the placental barrier and can be excreted in breast milk.

The medicine is inactive against enterobacteriaceae, and therefore has virtually no effect on the intestinal microflora.

80% of Vilprafen is excreted in bile, 20% in urine.

Macrolides are not only safe, but also quite effective. They have a huge potential for antimicrobial activity, as well as excellent pharmacokinetic action, which makes it much easier to tolerate their exposure in childhood. The very first macrolide antibiotic was erythromycin. After another 3 years, two more drugs were released - spiramycin And oleandomycin. Today there are the best antibiotics of this group for children in the face azithromycin, roxithromycin, clarithromycin, spiramycin and some others. It is the data antibiotic drugs are used by modern pediatricians to combat infections in children.

To boost the child’s immune system and strengthen his body, it is very important to purchase special dietary supplements from the Tiens Corporation for him, such as: Biocalcium for children, Biozinc, Antilipid tea and so on.

Erythromycin is an antibiotic that should be taken for legionellosis, for the purpose of preventing acute rheumatic fever (if penicillin is not possible), and intestinal decontamination before colorectal surgery.

Clarithromycin is used for the treatment and prevention of opportunistic infections in AIDS caused by some atypical mycobacteria, including the eradication of Helicobacter pylori in gastrointestinal diseases.

Spiramycin is used to treat toxoplasmosis, particularly in pregnant women.

Josamycin is suitable for the treatment of various respiratory diseases, soft tissue infections, and odontogenic infections.
The use of josamycin during pregnancy and breastfeeding is allowed according to indications. The European branch of WHO recommends josamycin as a means for proper treatment of chlamydial infection in women expecting a child.

All macrolides are allowed to be taken orally.

The advantages of clarithromycin, spiramycin, roxithromycin, midecamycin and josamycin over erythromycin are better pharmacokinetics, better tolerability and lower frequency of use.

Contraindications to the use of macrolides include hypersensitivity, pregnancy (josamycin, roxithromycin, midecamycin, clarithromycin), breastfeeding (josamycin, spiramycin, clarithromycin, midecamycin, roxithromycin).

Macrolides pass through the placenta and are absorbed into breast milk.

Side effects. These drugs are well tolerated and are one of the most harmless groups of antimicrobial drugs.

This group macrolides are natural antibiotics (oleandomycin, erythromycin, spiramycin, etc.), as well as semisynthetic drugs (azithromycin, roxithromycin, clarithromycin, etc.).
The basis of the chemical structure of these drugs is the lactone ring, which in different antibiotics consists of 14-16 carbon atoms. A variety of substituents are attached to the lactone rings, which greatly affect the properties of individual compounds.

The main feature of semisynthetic macrolides is their qualitative pharmacokinetic properties with increased (broad spectrum) antibacterial activity. They are well absorbed and form a long-lasting high concentration in the blood and tissues, which helps reduce the number of administrations per day to one or two times, reduce the duration of the course, frequency and severity side effects. They are effective against respiratory tract infections, diseases of the genital organs and urinary tract, soft tissues, skin and other diseases that arose due to gram-negative and gram-positive microorganisms, atypical bacteria, and various anaerobes.
penicillin. A distinctive property of these antibiotics was that various gram-positive microorganisms that were not susceptible to penicillin, tetracycline, etc. became sensitive to them. It’s not just that macrolides are in clinical field took the place of “reserve” antibiotics. The emergence of new generations of these drugs has only strengthened the position of this pharmacological group antibacterial drugs. But, nevertheless, this did not indicate a complete refusal to use erythromycin, which is well known in clinical settings. In fact, erythromycin is still suitable for use against large quantity types of microorganisms.

However, the antimicrobial activity of erythromycin in vitro is high. One should not ignore the bioavailability of the antibiotic, which is not so great compared to new macrolides/azalides, the high possibility of undesirable effects, as well as the formation of resistant microorganisms.

The choice of macrolide antibiotics becomes especially important, taking into account the pathogen, the characteristics of clinical manifestations and the course of the disease.

A necessary feature of these first-generation drugs was their lack of effectiveness against gram-negative bacteria, including fungi, Brucella, and Nocardia. New generations of these drugs are more effective in the fight against gram-negative microorganisms and are constantly attracting attention.

Macrolides are certain lactones in which the number of atoms in the ring is eight or more; they can contain various substituents, namely functional groups, including 1 or 2 C=C bonds. They exist with 2 or more lactone groups. These are, as a rule, solid substances that dissolve quite well in organic solutions and solvents, but are poorly soluble in water. Their chemical properties are similar to lower lactones, but they are not as reactive.

Most macrolides are obtained from bacterial strains, mainly actinomycetes and streptomycetes. Of these substances, the best known are oleandomycin, erythromycin, tetranactin and rosamycin.
Such macrolides are obtained from culture filtrates by extraction with organic solvents and purified by chromatographic methods. There are also similar substances that are obtained through bacteria, after which they are converted biochemically or chemically, for example, triacetyleandomycin. Unsubstituted macrolides are usually synthesized chemically. They can be made using lactonization of w-halogen acids or various hydroxy acid esters.

The chemical synthesis of these substances, similar to that produced by bacteria, is very difficult. It includes the production of a hydroxy acid, which has some substituents, and its direct lactonization. Thus, tylosin and some erythromycin derivatives were synthesized. Macrolide antibiotics stop the growth of gram-positive penicillin allergies, legionella and rickettsial infections. At community-acquired pneumonia macrolides can become first aid antibiotics.

Lincomycin (not a macrolide) has bacteriostatic capabilities that are similar to the work of erythromycin.

Tetracyclines are now used mainly in the treatment of patients atypical pneumonia due to the formation of microbial resistance to them. Tetracyclines affect bacterial ribosomes, stopping bacterial protein synthesis. Doxycycline is properly transported to the lungs (alveolar macrophages), white blood cells and is therefore suitable in the fight against intracellular pathogens (eg Legionella).

A major challenge is the presence of toxicity in tetracyclines. Thus, tetracyclines often provoke the appearance of gastrointestinal diseases in patients, affect the appearance of candidiasis and damage to the liver and kidneys, mainly in older people. It is not correct to start therapy for patients with ambulatory pneumonia with tetracyclines.

Pediatrics. Information about the harm or benefit of clarithromycin for children under six months is not known. The half-life of roxithromycin in children can be increased to twenty hours.

Geriatrics. There are no restrictions on the use of macrolides for elderly people, but one should remember the fact that age-related changes in liver function are possible, as well as a high risk of hearing impairment when using erythromycin.

Renal dysfunction. When creatinine clearance decreases to less than 30 ml/min, the half-life of clarithromycin can increase to twenty hours, and its active metabolite - up to forty hours. The half-life of roxithromycin can increase to fifteen hours when creatinine clearance decreases to 10 ml/min. In such cases, it may be necessary to change the dosage regimen of such macrolides.