Complex preparations of antibiotics pharmacology. Modern classification of antibiotics. Other side effects

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Introduction

1. Classification of antibiotics

2. Beta-lactam antibiotics

3. Penicillins

4. Group of cephalosporins

5. Group of carbapenems

6. Group of monobactams

7. Tetracycline group

8. Aminoglycoside group

9. Levomycetins

10. Group of glycopeptides

11. Lincosamide group

12. Antituberculous chemotherapy drugs

13. Classification of anti-tuberculosis drugs of the International Tuberculosis Union

14. Polypeptides

Literature

Introduction

Antibiotics are substances that inhibit the growth of living cells, most often prokaryotic and protozoan. Antibiotics can be natural (natural) origin and artificial (synthetic and semi-synthetic).

Antibiotics of natural origin are most often produced by actinomycetes and molds, but they can also be obtained from bacteria (polymyxins), plants (phytoncides), and tissues of animals and fish.

Antibiotics that inhibit the growth and reproduction of bacteria are used as medicines. Antibiotics are also widely used in oncological practice as cytostatic (antineoplastic) drugs. In the treatment of diseases of viral etiology, the use of antibiotics is not advisable, since they are not able to act on viruses. However, it has been noted that a number of antibiotics (tetracyclines) are able to act on large viruses.

Antibacterial drugs are synthetic drugs that have no natural analogues and have a suppressive effect similar to antibiotics on the growth of bacteria.

The invention of antibiotics can be called a revolution in medicine. The first antibiotics were penicillin and streptomycin.

1. Classification of antibiotics

By the nature of the effect on the bacterial cell:

1. bacteriostatic drugs (stop the growth and reproduction of bacteria)

2. bactericidal drugs (destroy bacteria)

According to the method of preparation, antibiotics are distinguished:

1. natural

2. synthetic

3. semi-synthetic

According to the direction of action, there are:

1. antibacterial

2. antitumor

3. antifungal

According to the spectrum of action, there are:

1. broad spectrum antibiotics

2. narrow spectrum antibiotics

By chemical structure:

1. Beta-lactam antibiotics

Penicillins are produced by colonies of the fungus Penicillinum. There are: biosynthetic (penicillin G - benzylpenicillin), aminopenicillins (amoxicillin, ampicillin, becampicillin) and semi-synthetic (oxacillin, methicillin, cloxacillin, dicloxacillin, flucloxacillin) penicillins.

Cephalosporins are used against penicillin-resistant bacteria. There are cephalosporins: 1st (ceporin, cephalexin), 2nd (cefazolin, cefamezin), 3rd (ceftriaxone, cefotaxime, cefuroxime) and 4th (cefepime, cefpirome) generations.

Carbapenems are broad-spectrum antibiotics. The structure of carbapenems determines their high resistance to beta-lactamases. Carbapenems include meropenem (meronem) and imipinem.

Monobactams (aztreonam)

2. Macrolides are antibiotics with a complex cyclic structure that have a bacteriostatic effect. Compared to other antibiotics, they are less toxic. These include: erythromycin, oleandomycin, roxithromycin, azithromycin (Sumamed), clarithromycin, etc. Macrolides also include: azalides and ketolides.

3. Tetracyclines - used to treat infections of the respiratory and urinary tract, treatment of severe infections such as anthrax, tularemia, brucellosis. Has a bacteriostatic effect. They belong to the class of polyketides. Among them, there are: natural (tetracycline, oxytetracycline) and semi-synthetic (metacycline, chlortethrin, doxycycline) tetracyclines.

4. Aminoglycosides - drugs of this group of antibiotics are highly toxic. Used to treat severe infections such as blood poisoning or peritonitis. Has bactericidal action. Aminoglycosides are active against gram-negative aerobic bacteria. These include: streptomycin, gentamicin, kanamycin, neomycin, amikacin, etc.

5. Levomycetins - When using antibiotics of this group, there is a risk of serious complications - damage to the bone marrow that produces blood cells. Has a bacteriostatic effect.

6. Glycopeptide antibiotics disrupt the synthesis of the bacterial cell wall. It has a bactericidal effect, however, a bacteriostatic effect of antibiotics of this group is possible in relation to enterococci, streptococci and staphylococci. These include: vancomycin, teicoplanin, daptomycin, etc.

7. Lincosamides have a bacteriostatic effect. In high concentrations against highly sensitive microorganisms may exhibit a bactericidal effect. These include: lincomycin and clindamycin

8. Anti-tuberculosis drugs - Isoniazid, Ftivazid, Saluzid, Metazid, Ethionamide, Prothionamide.

9. Polypeptides - antibiotics of this group in their molecule contain residues of polypeptide compounds. These include: gramicidin, polymyxins M and B, bacitracin, colistin;

10. Polyenes include: amphotericin B, nystatin, levorin, natamycin

11. Antibiotics of different groups - Rifamycin, Ristomycin sulfate, Fuzidin-sodium, etc.

12. Antifungal drugs - cause the death of fungal cells, destroying their membrane structure. They have a lytic effect.

13. Anti-leprosy drugs - Diaphenylsulfone, Solusulfon, Diucifon.

14. Anthracycline antibiotics - these include antitumor antibiotics - doxorubicin, carminomycin, rubomycin, aclarubicin.

2. Beta-lactam antibiotics

β-lactam antibiotics (β-lactams), which are united by the presence of a β-lactam ring in the structure, include penicillins, cephalosporins, carbapenems and monobactams, which have a bactericidal effect. The similarity of the chemical structure predetermines the same mechanism of action of all β-lactams (violation of the synthesis of the bacterial cell wall), as well as cross-allergy to them in some patients.

Penicillins, cephalosporins and monobactams are sensitive to the hydrolyzing action of special enzymes - β-lactamases produced by a number of bacteria. Carbapenems are characterized by a significantly higher resistance to β-lactamases.

Given the high clinical efficacy and low toxicity, β-lactam antibiotics form the basis of antimicrobial chemotherapy at the present stage, occupying a leading position in the treatment of most infections.

3. Penicillins

Penicillins are the first antimicrobial drugs developed on the basis of biologically active substances produced by microorganisms. The ancestor of all penicillins, benzylpenicillin, was obtained in the early 40s of the XX century. Currently, the group of penicillins includes more than ten antibiotics, which, depending on the sources of production, structural features and antimicrobial activity, are divided into several subgroups (Table 1)

General properties:

1. Bactericidal action.

2. Low toxicity.

3. Excretion mainly through the kidneys.

4. Wide dosage range.

Cross-allergy between all penicillins and partially cephalosporins and carbapenems.

natural penicillins. The natural penicillins include, in essence, only benzylpenicillin. However, based on the spectrum of activity, prolonged (benzylpenicillin procaine, benzathine benzylpenicillin) and oral (phenoxymethylpenicillin,n) derivatives can also be attributed to this group. All of them are destroyed by β-lactamases, so they cannot be used to treat staphylococcal infections, since in most cases staphylococci produce β-lactamases.

Semi-synthetic penicillins:

Antistaphylococcal penicillins

Penicillins with an extended spectrum of activity

Antipseudomonal penicillins

4. Group of cephalosporins

Cephalosporins are representatives of β-lactams. They are considered one of the most extensive classes of AMS. Due to their low toxicity and high efficacy, cephalosporins are used much more often than other AMPs. Antimicrobial activity and pharmacokinetic characteristics determine the use of one or another antibiotic of the cephalosporin group. Since cephalosporins and penicillins are structurally similar, drugs of these groups are characterized by the same mechanism of antimicrobial action, as well as cross-allergy in some patients.

There are 4 generations of cephalosporins:

I generation - cefazolin (parenteral use); cephalexin, cefadroxil (oral use)

II generation - cefuroxime (parenteral); cefuroxime axetil, cefaclor (oral)

III generation - cefotaxime, ceftriaxone, ceftazidime, cefoperazone, cefoperazone / sulbactam (parenteral); cefixime, ceftibuten (oral)

IV generation - cefepime (parenteral).

Mechanism of action. The action of cephalosporins is bactricidal. Penicillin-binding proteins of bacteria, which act as enzymes at the final stage of peptidoglycan synthesis (a biopolymer, the main component of the bacterial cell wall), fall under the influence of cephalosporins. As a result of blocking the synthesis of peptidoglycan, the bacterium dies.

Activity spectrum. Cephalosporins from generations I to III are characterized by a tendency to expand the range of activity, as well as an increase in the level of antimicrobial activity against gram-negative microorganisms and a decrease in the level of activity against gram-positive bacteria.

Common to all cephalosporins - this is the absence of significant activity against L.monocytogenes, MRSA and enterococci. CNS is less sensitive to cephalosporins than S.aureus.

1st generation cephalosporins. They have a similar antimicrobial spectrum of activity with the following difference: drugs intended for parenteral administration (cefazolin) act more strongly than drugs for oral administration (cefadroxil, cephalexin). Antibiotics are susceptible to methicillin-sensitive Staphylococcus spp. and Streptococcus spp. (S.pneumoniae, S.pyogenes). First generation cephalosporins have less antipneumococcal activity than aminopenicillins and most subsequent generation cephalosporins. Cephalosporins generally have no effect on listeria and enterococci, which is a clinically important feature of this class of antibiotics. Cephalosporins have been found to be resistant to the action of staphylococcal β-lactamases, but despite this, some strains (hyperproducers of these enzymes) may show moderate sensitivity to them. First generation cephalosporins and penicillins are not active against pneumococci. I generation cephalosporins have a narrow spectrum of action and a low level of activity against gram-negative bacteria. Their action will extend to Neisseria spp., however, the clinical significance of this fact is limited. The activity of 1st generation cephalosporins against M. catarrhalis and H. influenzae is clinically insignificant. On M. catarrhalis they are naturally quite active, but they are sensitive to hydrolysis by β-lactamases, producing almost 100% of strains. Representatives of the Enterobacteriaceae family are susceptible to the influence of cephalosporins of the 1st generation: P.mirabilis, Salmonella spp., Shigella spp., E.coli, and there is no clinical significance in the activity against Shigella and Salmonella. Strains of P.mirabilis and E.coli that provoke community-acquired (especially nosocomial) infections are characterized by widespread acquired resistance due to the production of extended and broad-spectrum β-lactamase.

In other Enterobacteriaceae, non-fermenting bacteria and Pseudomonas spp. resistance was found.

B.fragilis and related microorganisms show resistance, and representatives of a number of anaerobes - sensitivity to the action of cephalosporins of the 1st generation.

CephalosporinsIIgenerations. Cefuroxime and cefaclor, two representatives of this generation, differ from each other: having a similar antimicrobial spectrum of action, cefuroxime, compared with cefaclor, showed greater activity against Staphylococcus spp. and Streptococcus spp. Both drugs are not active against Listeria, Enterococcus and MRSA.

Pneumococci show PR to penicillin and second-generation cephalosporins. Representatives of 2nd generation cephalosporins are characterized by a wider range of effects on gram-negative microorganisms than 1st generation cephalosporins. Both cefuroxime and cefaclor show activity against Neisseria spp., but only the effect of cefuroxime on gonococci has been shown to be clinically active. On Haemophilus spp. and M. catarrhalis are more strongly affected by cefuroxime, as they are resistant to hydrolysis by their β-lactamases, and these enzymes partially destroy cefaclor. Of the representatives of the Enterobacteriaceae family, not only P.mirabilis, Salmonella spp., Shigella spp., E.coli, but also C.diversus, P.vulgaris, Klebsiella spp. When the microorganisms listed above produce broad-spectrum β-lactamases, they retain sensitivity to cefuroxime. Cefaclor and cefuroxime have a peculiarity: they are destroyed by extended spectrum β-lactamases. Some strains of P.rettgeri, P.stuartii, M.morganii, Serratia spp., C.freundii, Enterobacter spp. moderate sensitivity to cefuroxime may occur in vitro, but there is no point in using this drug in the treatment of infections caused by the above bacteria. The action of II generation cephalosporins does not apply to anaerobes of the B.fragilis group, Pseudomonas and other non-fermenting microorganisms.

3rd generation cephalosporins. In cephalosporins of the III generation, along with common features, there are certain features. Ceftriaxone and cefotaxime are the basic AMPs of this group and practically do not differ from each other in their antimicrobial actions. Both drugs have an active effect on Streptococcus spp., and at the same time, a significant part of pneumococci, as well as greenish streptococci that are resistant to penicillin, remain sensitive to ceftriaxone and cefotaxime. The action of cefotaxime and ceftriaxone affects S.aureus (except for MRSA), and to a lesser extent - KNS. Corynebacteria (except C. jeikeium) tend to show sensitivity. Resistance is shown by B.cereus, B.antracis, L.monocytogenes, MRSA and enterococci. Ceftriaxone and cefotaxime demonstrate high activity against H.influenzae, M.catarrhalis, gonococci and meningococci, including strains with reduced sensitivity to penicillin, regardless of the resistance mechanism. Almost all representatives of the Enterobacteriaceae family, incl. microorganisms that produce broad-spectrum β-lactamases are susceptible to the active natural effects of cefotaxime and ceftriaxone. E. coli and Klebsiella spp. possess resistance, most often due to the production of ESBL. Hyperproduction of class C chromosomal β-lactamases usually causes resistance in P. rettgeri, P. stuartii, M. morganii, Serratia spp., C. freundii, Enterobacter spp.

Sometimes the activity of cefotaxime and ceftriaxone in vitro is manifested in relation to certain strains of P. aeruginosa, other non-fermenting microorganisms, as well as B. fragilis, but this is not enough for them to be used in the treatment of relevant infections.

Between ceftazidime, cefoperazone and cefotaxime, ceftriaxone, there are similarities in the main antimicrobial properties. Distinctive characteristics of ceftazidime and cefoperazone from cefotaxime and ceftriaxone:

Show high sensitivity to ESBL hydrolysis;

They show significantly less activity against streptococci, primarily S.pneumoniae;

Pronounced activity (especially in ceftazidime) against P. aeruginosa and other non-fermenting microorganisms.

Differences of cefixime and ceftibuten from cefotaxime and ceftriaxone:

Both drugs have no or little effect on P.rettgeri, P.stuartii, M.morganii, Serratia spp., C.freundii, Enterobacter spp.;

Ceftibuten is inactive against viridescent streptococci and pneumococci; they are little affected by ceftibuten;

There is no significant activity against Staphylococcus spp.

IV generation cephalosporins. There are many similarities between cefepime and third-generation cephalosporins in many respects. However, the peculiarities of the chemical structure allow cefepime to penetrate with greater confidence through the outer membrane of gram-negative microorganisms, and also to have a relative resistance to hydrolysis by chromosomal class C β-lactamases. Therefore, together with its properties that distinguish the basic III generation cephalosporins (ceftriaxone, cefotaxime), cefepime has the following features:

High activity against non-fermenting microorganisms and P.aeruginosa;

Increased resistance to hydrolysis of extended spectrum β-lactamases (this fact does not fully determine its clinical significance);

Influence on the following microorganisms-hyperproducers of class C chromosomal β-lactamases: P.rettgeri, P.stuartii, M.morganii, Serratia spp., C.freundii, Enterobacter spp.

Inhibitor-protected cephalosporins. Cefoperazone / sulbactam is the only representative of this group of β-lactams. Compared with cefoperazone, the combination drug has an extended spectrum of action due to the effect on anaerobic microorganisms. Also, most strains of enterobacteria that produce extended and broad spectrum β-lactamases are affected by the drug. The antibacterial activity of sulbactam allows this AMP to show high activity against Acinetobacter spp.

Pharmacokinetics. Oral cephalosporins have good absorption in the gastrointestinal tract. A particular drug is distinguished by its bioavailability, varying between 40-50% (for cefixime) and 95% (for cefaclor, cefadroxil and cephalexin). The presence of food may somewhat slow down the absorption of ceftibuten, cefixime and cefaclor. Food helps during the absorption of cefuroxime axetil to release the active cefuroxime. With the introduction of the / m observed good absorption of parenteral cephalosporins. The distribution of cephalosporins is carried out in many organs (except for the prostate gland), tissues and secrets. In peritoneal, pleural, pericardial and synovial fluids, in bones, soft tissues, skin, muscles, liver, kidneys and lungs, high concentrations are noted. Cefoperazone and ceftriaxone produce the highest levels in bile. Cephalosporins, especially ceftazidime and cefuroxime, have the ability to penetrate well into the aqueous humor without creating therapeutic levels in the posterior chamber of the eye. III generation cephalosporins (ceftazidime, ceftriaxone, cefotaxime) and IV generation (cefepime) have the greatest ability to pass through the BBB and also create therapeutic concentrations in the CSF. Cefuroxime moderately overcomes the BBB only in case of inflammation of the meninges.

Most cephalosporins (except cefotaxime, which is biotransformed to form an active metabolite) lack the ability to metabolize. The withdrawal of drugs is carried out mainly through the kidneys, while creating very high concentrations in the urine. Ceftriaxone and cefoperazone have a double route of excretion - by the liver and kidneys. Most cephalosporins have an elimination half-life of 1 to 2 hours. Ceftibuten, cefixime are distinguished by a longer period - 3-4 hours, in ceftriaxone it increases to 8.5 hours. Thanks to this indicator, these drugs can be taken 1 time per day. Renal failure entails a correction of the dosing regimen of antibiotics of the cephalosporin group (except for cefoperazone and ceftriaxone).

1st generation cephalosporins. Basically today cefazolin used as perioperative prophylaxis in surgery. It is also used for infections of soft tissues and skin.

Since cefazolin has a narrow spectrum of activity, and resistance to cephalosporins is common among potential pathogens, recommendations for the use of cefazolin for the treatment of respiratory tract infections and urinary tract infections today do not have sufficient justification.

Cefalexin is used in the treatment of streptococcal tonsillopharyngitis (as a second-line drug), as well as community-acquired infections of soft tissues and skin of mild to moderate severity.

II generation cephalosporins

Cefuroxime used:

With community-acquired pneumonia requiring hospitalization;

With community-acquired infections of soft tissues and skin;

With infections of the urinary tract (pyelonephritis of moderate and severe severity); antibiotic cephalosporin tetracycline anti-tuberculosis

As a perioperative prophylaxis in surgery.

cefaclor, cefuroxime axetil used:

With infections of the URT and NDP (community-acquired pneumonia, exacerbation of chronic bronchitis, acute sinusitis, CCA);

With community-acquired infections of soft tissues and skin of mild, moderate severity;

Infections of the urinary tract (acute cystitis and pyelonephritis in children, pyelonephritis in women during lactation, pyelonephritis of mild and moderate severity).

Cefuroxime axetil and cefuroxime can be used as stepwise therapy.

3rd generation cephalosporins

Ceftriaxone, cefotaxime used for:

Community-acquired infections - acute gonorrhea, CCA (ceftriaxone);

Severe nosocomial and community-acquired infections - sepsis, meningitis, generalized salmonellosis, infections of the pelvic organs, intra-abdominal infections, severe infections of the joints, bones, soft tissues and skin, severe forms of urinary tract infections, infections of the NDP.

Cefoperazone, ceftazidime prescribed for:

Treatment of severe community-acquired and nosocomial infections of various localization in case of confirmed or possible etiological effects of P. aeruginosa and other non-fermenting microorganisms.

Treatment of infections against the background of immunodeficiency and neutropenia (including neutropenic fever).

Third-generation cephalosporins can be used parenterally as monotherapy or together with antibiotics of other groups.

ceftibuten, cefixime effective:

In urinary tract infections: acute cystitis and pyelonephritis in children, pyelonephritis in women during pregnancy and lactation, pyelonephritis of mild to moderate severity;

In the role of the oral stage of the stepwise therapy of various severe nosocomial and community-acquired infections caused by gram-negative bacteria, after obtaining a lasting effect from drugs intended for parenteral administration;

With infections of the upper respiratory tract and the upper respiratory tract (reception of ceftibuten in case of a possible pneumococcal etiology is not recommended).

Cefoperazone/sulbactam apply:

In the treatment of severe (mainly nosocomial) infections caused by mixed (aerobic-anaerobic) and multiresistant microflora - sepsis, NDP infections (pleural empyema, lung abscess, pneumonia), complicated urinary tract infections, intra-abdominal infections of the small pelvis;

With infections against the background of neutropenia, as well as other immunodeficiency states.

IV generation cephalosporins. It is used for severe, mainly nosocomial, infections provoked by multidrug-resistant microflora:

intra-abdominal infections;

Infections of the joints, bones, skin and soft tissues;

Complicated infections of the urinary tract;

NDP infections (pleural empyema, lung abscess, pneumonia).

Also, IV generation cephalosporins are effective in the treatment of infections against the background of neutropenia, as well as other immunodeficiency states.

Contraindications

Do not use in allergic reactions to cephalosporins.

5. Carbapenem group

The carbapenems (imipenem and meropenem) are β-lactams. Compared with penicillins and cephalosporins, they are more resistant to the hydrolyzing action of bacterial in-lactamase, including ESBL, and have a wider spectrum of activity. They are used for severe infections of various localization, including nosocomial, more often as a reserve drug, but for life-threatening infections may be considered as first line empirical therapy.

Mechanism of action. Carbapenems have a powerful bactericidal effect due to a violation of the formation of the bacterial cell wall. Compared to other β-lactams, carbapenems are able to penetrate the outer membrane of gram-negative bacteria faster and, in addition, exert a pronounced PAE against them.

Activity spectrum. Carbapenems act on many gram-positive, gram-negative and anaerobic microorganisms.

Staphylococci are sensitive to carbapenems (except MRSA), streptococci, including S.pneumoniae(in terms of activity against ARP, carbapenems are inferior to vancomycin), gonococci, meningococci. Imipenem acts on E.faecalis.

Carbapenems are highly active against most gram-negative bacteria of the family Enterobacteriaceae(E. coli, Klebsiella, Proteus, Enterobacter, Citrobacter, Acinetobacter, Morganella), including against strains resistant to cephalosporins III-IV generation and inhibitor-protected penicillins. Slightly lower activity against proteus, serration, H.influenzae. Most Strains P.aeruginosa initially sensitive, but in the process of using carbapenems, an increase in resistance is noted. Thus, according to a multicenter epidemiological study conducted in Russia in 1998-1999, resistance to imipenem in nosocomial strains P.aeruginosa in ICU was 18.8%.

Carbapenems have relatively little effect on B.cepacia, stable is S. maltophilia.

Carbapenems are highly active against spore-forming (except C.difficile) and non-spore-forming (including B. fragilis) anaerobes.

Secondary resistance of microorganisms (except P.aeruginosa) rarely develops to carbapenems. For resistant pathogens (except P.aeruginosa) is characterized by cross-resistance to imipenem and meropenem.

Pharmacokinetics. Carbapenems are used only parenterally. They are well distributed in the body, creating therapeutic concentrations in many tissues and secretions. With inflammation of the meninges, they penetrate the BBB, creating concentrations in the CSF equal to 15-20% of the level in the blood plasma. Carbapenems are not metabolized, they are excreted mainly by the kidneys in unchanged form, therefore, with renal failure, a significant slowdown in their elimination is possible.

Due to the fact that imipenem is inactivated in the renal tubules by the enzyme dehydropeptidase I and does not create therapeutic concentrations in the urine, it is used in combination with cilastatin, which is a selective inhibitor of dehydropeptidase I.

During hemodialysis, carbapenems and cilastatin are rapidly removed from the blood.

Indications:

1. Severe infections, mostly nosocomial, caused by multiresistant and mixed microflora;

2. AndNDP infections(pneumonia, lung abscess, pleural empyema);

3. Complicated urinary tract infection;

4. Andintra-abdominal infections;

5. Andpelvic infections;

6. FROMepsis;

7. Andskin and soft tissue infections;

8. And bone and joint infections(only imipenem);

9. Eendocarditis(only imipenem);

10. Bacterial infections in neutropenic patients;

11. Meningitis(only meropenem).

Contraindications. Allergic reaction to carbapenems. Imipenem/cilastatin should also not be used in patients with an allergic reaction to cilastatin.

6. Group of monobactams

Of the monobactams, or monocyclic β-lactams, one antibiotic is used in clinical practice - aztreonam. It has a narrow spectrum of antibacterial activity and is used to treat infections caused by aerobic Gram-negative flora.

Mechanism of action. Aztreonam has a bactericidal effect, which is associated with a violation of the formation of the bacterial cell wall.

Activity spectrum. The peculiarity of the antimicrobial spectrum of action of aztreonam is due to the fact that it is resistant to many β-lactamases produced by aerobic gram-negative flora, and at the same time is destroyed by β-lactamases of staphylococci, bacteroides and ESBL.

The activity of aztreonam against many microorganisms of the family Enterobacteriaceae (E.coli, Enterobacter, Klebsiella, Proteus, Serration, Citrobacter, Providence, Morganella) and P.aeruginosa, including against nosocomial strains resistant to aminoglycosides, ureidopenicillins and cephalosporins.

Aztreonam has no effect on Acinetobacter, S. maltophilia, B.cepacia, gram-positive cocci and anaerobes.

Pharmacokinetics. Aztreonam is used only parenterally. It is distributed in many tissues and environments of the body. It passes through the BBB during inflammation of the meninges, through the placenta and into breast milk. It is very slightly metabolized in the liver, excreted mainly by the kidneys, 60-75% unchanged. The half-life with normal kidney and liver function is 1.5-2 hours, with cirrhosis of the liver it can increase to 2.5-3.5 hours, with renal failure - up to 6-8 hours. During hemodialysis, the concentration of aztreonam in the blood decreases by 25-60%.

Indications. Aztreonam is a reserve drug for the treatment of infections of various localization caused by aerobic gram-negative bacteria:

1. NDP infections (community-acquired and nosocomial pneumonia);

2. intra-abdominal infections;

3. infections of the pelvic organs;

4. infections of the urinary tract;

5. infections of the skin, soft tissues, bones and joints;

6. sepsis.

Given the narrow antimicrobial spectrum of aztreonam, in the empirical treatment of severe infections, it should be prescribed in combination with AMPs that are active against gram-positive cocci (oxacillin, cephalosporins, lincosamides, vancomycin) and anaerobes (metronidazole).

Contraindications. Allergic reactions to aztreonam in history.

7. Tetracycline group

Tetracyclines are one of the early classes of AMPs, the first tetracyclines were obtained in the late 40s. Currently, due to the emergence of a large number of microorganisms resistant to tetracyclines and numerous HP, which are characteristic of these drugs, their use is limited. Tetracyclines (natural tetracycline and semi-synthetic doxycycline) retain their greatest clinical significance in chlamydial infections, rickettsiosis, some zoonoses, and severe acne.

Mechanism of action. Tetracyclines have a bacteriostatic effect, which is associated with impaired protein synthesis in the microbial cell.

spectrum of activity. Tetracyclines are considered AMPs with a wide spectrum of antimicrobial activity, however, in the course of their long-term use, many bacteria have acquired resistance to them.

Among gram-positive cocci, pneumococcus is the most susceptible (with the exception of ARP). At the same time, more than 50% of strains are resistant S.pyogenes, more than 70% of nosocomial strains of staphylococci and the vast majority of enterococci. The most susceptible Gram-negative cocci are meningococci and M.catarrhalis, and many gonococci are resistant.

Tetracyclines act on some Gram-positive and Gram-negative rods - Listeria, H.influenzae, H.ducreyi, Yersinia, Campylobacter (including H. pylori), brucella, bartonella, vibrios (including cholera), pathogens of inguinal granuloma, anthrax, plague, tularemia. Most strains of Escherichia coli, Salmonella, Shigella, Klebsiella, Enterobacter are resistant.

Tetracyclines are active against spirochetes, leptospira, borrelia, rickettsia, chlamydia, mycoplasmas, actinomycetes, and some protozoa.

Among the anaerobic flora, clostridia are sensitive to tetracyclines (except C.difficile), fusobacteria, p.acnes. Most strains of bacteroids are resistant.

Pharmacokinetics. When taken orally, tetracyclines are well absorbed, with doxycycline being better than tetracycline. The bioavailability of doxycycline does not change, and tetracycline - 2 times decreases under the influence of food. The maximum concentrations of drugs in the blood serum are created 1-3 hours after ingestion. With intravenous administration, significantly higher blood concentrations are rapidly achieved than with oral administration.

Tetracyclines are distributed in many organs and environments of the body, and doxycycline creates higher tissue concentrations than tetracycline. Concentrations in CSF are 10-25% of serum levels, concentrations in bile are 5-20 times higher than in blood. Tetracyclines have a high ability to pass through the placenta and penetrate into breast milk.

Excretion of hydrophilic tetracycline is carried out mainly by the kidneys, therefore, in renal failure, its excretion is significantly impaired. More lipophilic doxycycline is excreted not only by the kidneys, but also by the gastrointestinal tract, and in patients with impaired renal function, this pathway is the main one. Doxycycline has a 2-3 times longer half-life compared to tetracycline. With hemodialysis, tetracycline is removed slowly, and doxycycline is not removed at all.

Indications:

1. Chlamydial infections (psittacosis, trachoma, urethritis, prostatitis, cervicitis).

2. Mycoplasma infections.

3. Borreliosis (Lyme disease, relapsing fever).

4. Rickettsiosis (Q fever, Rocky Mountain spotted fever, typhus).

5. Bacterial zoonoses: brucellosis, leptospirosis, anthrax, plague, tularemia (in the last two cases - in combination with streptomycin or gentamicin).

6. Infections of the NDP: exacerbation of chronic bronchitis, community-acquired pneumonia.

7. Intestinal infections: cholera, yersiniosis.

8. Gynecological infections: adnexitis, salpingo-oophoritis (in severe cases, in combination with β-lactams, aminoglycosides, metronidazole).

9. Acne.

10. Rosacea.

11. Wound infection after animal bites.

12. STIs: syphilis (allergic to penicillin), inguinal granuloma, venereal lymphogranuloma.

13. Eye infections.

14. Actinomycosis.

15. Bacillary angiomatosis.

16. Eradication H. pylori with peptic ulcer of the stomach and duodenum (tetracycline in combination with antisecretory drugs, bismuth subcitrate and other AMPs).

17. Prevention of tropical malaria.

Contraindications:

Age up to 8 years.

Pregnancy.

Lactation.

Severe liver disease.

Renal failure (tetracycline).

8. Aminoglycoside group

Aminoglycosides are one of the earliest classes of antibiotics. The first aminoglycoside, streptomycin, was obtained in 1944. Currently, there are three generations of aminoglycosides.

The main clinical significance of aminoglycosides is in the treatment of nosocomial infections caused by aerobic gram-negative pathogens, as well as infective endocarditis. Streptomycin and kanamycin are used in the treatment of tuberculosis. Neomycin, as the most toxic among aminoglycosides, is used only orally and topically.

Aminoglycosides have potential nephrotoxicity, ototoxicity, and may cause neuromuscular blockade. However, taking into account risk factors, a single administration of the entire daily dose, short courses of therapy and TDM can reduce the degree of manifestation of HP.

Mechanism of action. Aminoglycosides have a bactericidal effect, which is associated with impaired protein synthesis by ribosomes. The degree of antibacterial activity of aminoglycosides depends on their maximum (peak) concentration in blood serum. When combined with penicillins or cephalosporin, synergism is observed against some gram-negative and gram-positive aerobic microorganisms.

Activity spectrum. Aminoglycosides II and III generation are characterized by dose-dependent bactericidal activity against gram-negative microorganisms of the family Enterobacteriaceae (E.coli, Proteus spp., Klebsiella spp., Enterobacter spp., Serratia spp. etc.), as well as non-fermenting gram-negative rods ( P.aeruginosa, Acinetobacter spp.). Aminoglycosides are active against staphylococci, except for MRSA. Streptomycin and kanamycin act on M.tuberculosis, while amikacin is more active against M.avium and other atypical mycobacteria. Streptomycin and gentamicin act on enterococci. Streptomycin is active against the pathogens of plague, tularemia, brucellosis.

Aminoglycosides are inactive against S.pneumoniae, S. maltophilia, B.cepacia, anaerobes ( Bacteroides spp., Clostridium spp. and etc.). Moreover, resistance S.pneumoniae, S. maltophilia and B.cepacia to aminoglycosides can be used in the identification of these microorganisms.

Although aminoglycosides in vitro active against hemophilus, shigella, salmonella, legionella, clinical efficacy in the treatment of infections caused by these pathogens has not been established.

Pharmacokinetics. When taken orally, aminoglycosides are practically not absorbed, therefore they are used parenterally (except for neomycin). After i / m administration, they are absorbed quickly and completely. Peak concentrations develop 30 minutes after the end of the intravenous infusion and 0.5-1.5 hours after the intramuscular injection.

Peak concentrations of aminoglycosides vary in different patients, as they depend on the volume of distribution. The volume of distribution, in turn, depends on body weight, the volume of fluid and adipose tissue, and the patient's condition. For example, in patients with extensive burns, ascites, the volume of distribution of aminoglycosides is increased. On the contrary, with dehydration or muscular dystrophy, it decreases.

Aminoglycosides are distributed into the extracellular fluid, including serum, abscess exudates, ascitic, pericardial, pleural, synovial, lymphatic, and peritoneal fluids. Able to create high concentrations in organs with good blood supply: liver, lungs, kidneys (where they accumulate in the cortical substance). Low concentrations are observed in sputum, bronchial secretions, bile, breast milk. Aminoglycosides do not pass well through the BBB. With inflammation of the meninges, the permeability increases slightly. In newborns, higher concentrations are achieved in the CSF than in adults.

Aminoglycosides are not metabolized, they are excreted by the kidneys by glomerular filtration in unchanged form, creating high concentrations in the urine. The rate of excretion depends on the age, renal function and comorbidity of the patient. In patients with fever, it can increase, with a decrease in kidney function, it slows down significantly. In the elderly, as a result of a decrease in glomerular filtration, excretion may also slow down. The half-life of all aminoglycosides in adults with normal renal function is 2-4 hours, in newborns - 5-8 hours, in children - 2.5-4 hours. In renal failure, the half-life can increase to 70 hours or more.

Indications:

1. Empiric Therapy(in most cases prescribed in combination with β-lactams, glycopeptides or anti-anaerobic drugs, depending on the suspected pathogens):

Sepsis of unknown etiology.

Infective endocarditis.

Post-traumatic and postoperative meningitis.

Fever in neutropenic patients.

Nosocomial pneumonia (including ventilation).

Pyelonephritis.

intra-abdominal infections.

Infections of the pelvic organs.

Diabetic foot.

Postoperative or post-traumatic osteomyelitis.

Septic arthritis.

Local Therapy:

Eye infections - bacterial conjunctivitis and keratitis.

2. Specific therapy:

Plague (streptomycin).

Tularemia (streptomycin, gentamicin).

Brucellosis (streptomycin).

Tuberculosis (streptomycin, kanamycin).

Antibiotic prophylaxis:

Intestinal decontamination before elective colon surgery (neomycin or kanamycin in combination with erythromycin).

Aminoglycosides should not be used to treat community-acquired pneumonia in both outpatient and inpatient settings. This is due to the lack of activity of this group of antibiotics against the main pathogen - pneumococcus. In the treatment of nosocomial pneumonia, aminoglycosides are prescribed parenterally. Endotracheal administration of aminoglycosides, due to unpredictable pharmacokinetics, does not lead to an increase in clinical efficacy.

It is erroneous to prescribe aminoglycosides for the treatment of shigellosis and salmonellosis (both orally and parenterally), since they are clinically ineffective against pathogens localized intracellularly.

Aminoglycosides should not be used to treat uncomplicated urinary tract infections unless the pathogen is resistant to other less toxic antibiotics.

Aminoglycosides should also not be used topically in the treatment of skin infections due to the rapid formation of resistance in microorganisms.

The use of aminoglycosides for flow drainage and abdominal irrigation should be avoided due to their severe toxicity.

Dosing rules for aminoglycosides. In adult patients, there are two regimens for prescribing aminoglycosides: traditional when they are administered 2-3 times a day (for example, streptomycin, kanamycin and amikacin - 2 times; gentamicin, tobramycin and netilmicin - 2-3 times), and single administration of the entire daily dose.

A single administration of the entire daily dose of aminoglycoside allows you to optimize therapy with this group of drugs. Numerous clinical trials have shown that the effectiveness of treatment with a single regimen of aminoglycosides is the same as with the traditional one, and nephrotoxicity is less pronounced. In addition, with a single administration of a daily dose, economic costs are reduced. However, this aminoglycoside regimen should not be used in the treatment of infective endocarditis.

The choice of dose of aminoglycosides is influenced by such factors as the patient's body weight, the location and severity of the infection, and renal function.

For parenteral administration, doses of all aminoglycosides should be calculated per kilogram of body weight. Considering that aminoglycosides are poorly distributed in adipose tissue, in patients with a body weight exceeding the ideal by more than 25%, a dose adjustment should be carried out. In this case, the daily dose calculated for the actual body weight should be empirically reduced by 25%. At the same time, in malnourished patients, the dose is increased by 25%.

With meningitis, sepsis, pneumonia and other severe infections, the maximum doses of aminoglycosides are prescribed, with infections of the urinary tract - minimal or average. Maximum doses should not be given to the elderly.

In patients with renal insufficiency, the dose of aminoglycosides must necessarily be reduced. This is achieved either by reducing the single dose, or by increasing the intervals between injections.

Therapeutic drug monitoring. Since the pharmacokinetics of aminoglycosides is unstable and depends on a number of reasons, TDM is performed to achieve the maximum clinical effect while reducing the risk of developing AR. At the same time, peak and residual concentrations of aminoglycosides in the blood serum are determined. Peak concentrations (60 minutes after intramuscular injection or 15-30 minutes after the end of intravenous administration), on which the effectiveness of therapy depends, should be at least 6-10 mcg / ml for gentamicin, tobramycin and netilmicin in the usual dosing regimen. , for kanamycin and amikacin - at least 20-30 mcg / ml. Residual concentrations (before the next administration), which indicate the degree of cumulation of aminoglycosides and allow monitoring the safety of therapy, for gentamicin, tobramycin and netilmicin should be less than 2 μg / ml, for kanamycin and amikacin - less than 10 μg / ml. TDM is especially necessary in patients with severe infections and in the presence of other risk factors for the toxic effects of aminoglycosides. When prescribing a daily dose in the form of a single injection, the residual concentration of aminoglycosides is usually controlled.

Contraindications: Allergic reactions to aminoglycosides.

9. Levomycetins

Levomycetinums are antibiotics with a wide range of action. The group of levomycetins includes Levomycetin and Synthomycin. The first natural antibiotic, levomycetin, was obtained from a culture of the radiant fungus Streptomyces venezualae in 1947, and in 1949 the chemical structure was established. In the USSR, this antibiotic was called "levomycetin" due to the fact that it is a left-handed isomer. The dextrorotatory isomer is not effective against bacteria. The antibiotic of this group, obtained synthetically in 1950, was named "Synthomycin". The composition of synthomycin included a mixture of left-handed and right-handed isomers, which is why the effect of synthomycin is 2 times weaker compared to chloramphenicol. Synthomycin is used exclusively externally.

Mechanism of action. Levomycetins are characterized by bacteriostatic action, and specifically they disrupt protein synthesis, are fixed on ribosomes, which leads to inhibition of the reproduction function of microbial cells. The same property in the bone marrow causes a stop in the formation of erythrocytes and leukocytes (can lead to anemia and leukopenia), as well as oppression of hematopoiesis. Isomers have the ability to have the opposite effect on the central nervous system: the left-handed isomer depresses the central nervous system, and the right-handed isomer moderately excites it.

Activity Circle. Antibiotics-levomycetins are active against many gram-negative and gram-positive bacteria; viruses: Chlamydia psittaci, Chlamydia trachomatis; Spirochaetales, Rickettsiae; strains of bacteria that are not amenable to the action of penicillin, streptomycin, sulfonamides. They have a slight effect on acid-resistant bacteria (pathogens of tuberculosis, some saprophytes, leprosy), Protozoa, Clostridium, Pseudomonas aeruginosa. The development of drug resistance to antibiotics of this group is relatively slow. Levomycetins are not able to cause cross-resistance to other chemotherapeutic drugs.

Prendering. Levomycetins are used in the treatment of trachoma, gonorrhea, various types of pneumonia, meningitis, whooping cough, rickettsiosis, chlamydia, tularemia, brucellosis, salmonellosis, dysentery, paratyphoid fever, typhoid fever, etc.

10. Group of glycopeptides

Glycopeptides are natural antibiotics vancomycin and teicoplanin. Vancomycin has been used in clinical practice since 1958, teicoplanin - since the mid-80s. Recently, interest in glycopeptides has increased due to an increase in the frequency nosocomial infections caused by Gram-positive bacteria. Currently, glycopeptides are the drugs of choice for infections caused by MRSA, MRSE, as well as enterococci resistant to ampicillin and aminoglycosides.

Mechanism of action. Glycopeptides disrupt the synthesis of the bacterial cell wall. They have a bactericidal effect, however, against enterococci, some streptococci and KNS act bacteriostatically.

Activity spectrum. Glycopeptides are active against gram-positive aerobic and anaerobic microorganisms: staphylococci (including MRSA, MRSE), Streptococcus, Pneumococcus (including ARP), Enterococcus, Peptostreptococcus, Listeria, Corynebacterium, Clostridium (including C.difficile). Gram-negative microorganisms are resistant to glycopeptides.

According to the spectrum of antimicrobial activity, vancomycin and teicoplanin are similar, but there are some differences in the level of natural activity and acquired resistance. Teicoplanin in vitro more active towards S. aureus(including MRSA), streptococci (including S.pneumoniae) and enterococci. Vancomycin in vitro more active towards KNS.

In recent years, several countries have identified S. aureus with reduced sensitivity to vancomycin or to vancomycin and teicoplanin.

Enterococci tend to develop resistance to vancomycin more rapidly: current ICU resistance rates in the US are E.faecium to vancomycin is about 10% or more. However, it is clinically important that some VRE remain sensitive to teicoplanin.

Pharmacokinetics. Glycopeptides are practically not absorbed when taken orally. Bioavailability teicoplanin with i / m administration is about 90%.

Glycopeptides are not metabolized, they are excreted by the kidneys unchanged, therefore, in case of renal failure, dose adjustment is required. Drugs are not removed by hemodialysis.

Half-life vancomycin with normal kidney function is 6-8 hours, teicoplanin - from 40 hours to 70 hours. The long half-life of teicoplanin makes it possible to prescribe it once a day.

Indications:

1. Infections caused MRSA, MRSE.

2. Staphylococcal infections in case of allergy to β-lactams.

3. Severe infections caused Enterococcus spp., C.jeikeium, B.cereus, F.meningosepticum.

4. Infective endocarditis caused by viridescent streptococci and S. bovis, with allergies to β-lactams.

5. Infective endocarditis caused by E.faecalis(in combination with gentamicin).

6. Meningitis caused by S.pneumoniae, resistant to penicillins.

Empiric treatment of life-threatening infections with suspected staphylococcal etiology:

Infective endocarditis of the tricuspid valve or prosthetic valve (in combination with gentamicin);

New generation antibiotics

The risk of using antibiotics due to modern medical developments is practically reduced to zero. New antibiotics have an improved formula and principle of action, due to which their active components affect only the pathogenic agent at the cellular level, without disturbing the beneficial microflora of the human body. And if earlier such agents were used in the fight against a limited number of pathogenic agents, today they will be effective immediately against a whole group of pathogens.

Antibiotics are divided into the following groups:

tetracycline group - Tetracycline;
a group of aminoglycosides - Streptomycin;
amphenicol antibiotics - Chloramphenicol;
penicillin series of drugs - Amoxicillin, Ampicillin, Bilmicin or Ticarcycline;
antibiotics of the carbapenem group - Imipenem, Meropenem or Ertapenem.

The type of antibiotic is determined by the doctor after a thorough examination of the disease and the study of all its causes. Treatment with a drug prescribed by a doctor is effective and without complications.

Important: Even if the use of this or that antibiotic helped you earlier, this does not mean that if you experience similar or completely identical symptoms, you should take the same drug.

The best new-generation broad-spectrum antibiotics

Tetracycline

Has the widest range of applications;

What does tetracycline help with?

with bronchitis, tonsillitis, pharyngitis, prostatitis, eczema and various infections of the gastrointestinal tract and soft tissues.

The most effective antibiotic for chronic and acute diseases;

Country of origin - Germany (Bayer);

The drug has a very wide range of applications and is included by the Ministry of Health of the Russian Federation in the list of essential medicines;

Virtually no side effects.

Amoxicillin

The most harmless and versatile drug;

It is used both for diseases with a characteristic increase in temperature, and for other diseases;

Most effective for:

infections of the respiratory tract and ENT organs (including sinusitis, bronchitis, tonsillitis, otitis media);
gastrointestinal infections;
skin and soft tissue infections;
infections of the genitourinary system;
Lyme disease;
dysentery;
meningitis;
salmonellosis;
sepsis.

Country of manufacture - Great Britain;

What helps?

bronchitis, tonsillitis, sinusitis, as well as various respiratory tract infections.

Amoxiclav

An effective drug with a very wide range of applications, practically harmless;

Main advantages:

minimum contraindications and side effects;
pleasant taste;
speed;
does not contain dyes.

Fast-acting drug with a very wide range of applications;

It is most effective in fighting infections that affect the respiratory tract, such as tonsillitis, sinusitis, bronchitis, pneumonia. It is also used in the fight against infectious diseases of the skin and soft tissues, genitourinary, as well as intestinal diseases.

Highly active against gram-negative microorganisms;

Country of manufacture - Russia;

It is most effective in the fight against gram-positive and gram-negative bacteria, mycoplasmas, legionella, salmonella, as well as sexually transmitted pathogens.

Avikaz

Fast-acting drug with virtually no side effects;

Country of manufacture - USA;

Most effective in the treatment of diseases of the urinary tract and kidneys.

The device is distributed in ampoules (injections), one of the fastest acting antibiotics;

The most effective drug in the treatment of:

pyelonephritis and inf. urinary tract;
infect. diseases of the small pelvis, endometritis, postoperative inf-yah and septic abortions;
bacterial lesions of the skin and soft tissues, including diabetic foot;
pneumonia;
septicemia;
abdominal infections.

Doriprex

Synthetic antimicrobial drug with bactericidal activity;

Country of origin - Japan;

This drug is most effective in the treatment of:

nosocomial pneumonia;
severe intra-abdominal infections;
complicated inf. urinary system;
pyelonephritis, with a complicated course and bacteremia.

Classification of antibiotics according to the spectrum of action and purpose of use

Modern classification of antibiotics by groups: table

Main group	Subclasses
Beta lactams
1. Penicillins	natural; Antistaphylococcal; Antipseudomonal; With an extended spectrum of action; inhibitor-protected; Combined.
2. Cephalosporins	4 generations; Anti-MRSA cephems.
3. Carbapenems	-
4. Monobactams	-
Aminoglycosides	Three generations.
macrolides	Fourteen-membered; Fifteen-membered (azoles); Sixteen members.
Sulfonamides	Short action; Average duration of action; Long acting; Extra long; Local.
Quinolones	Non-fluorinated (1st generation); Second; Respiratory (3rd); Fourth.
Anti-tuberculosis	Main row; reserve group.
Tetracyclines	natural; Semi-synthetic.

The following are the types of antibiotics of this series and their classification in the table.

Group	According to the active substance, preparations are isolated:	Titles
Natural	Benzylpenicillin	Benzylpenicillin Na and K salts.
	Phenoxymethylpenicillin	Methylpenicillin
	With prolonged action.
	Benzylpenicillin procaine	Benzylpenicillin novocaine salt.
	Benzylpenicillin/ Benzylpenicillin procaine/ Benzathine benzylpenicillin	Benzicillin-3. Bicillin-3
	Benzylpenicillin procaine/Benzathine benzylpenicillin	Benzicillin-5. Bicillin-5
Antistaphylococcal	Oxacillin	Oxacillin AKOS, sodium salt of Oxacillin.
penicillinase-resistant	Cloxapcillin; Alucloxacillin.
Spread Spectrum	Ampicillin	Ampicillin
Spread Spectrum	Amoxicillin	Flemoxin Solutab, Ospamox, Amoxicillin.
With antipseudomonal activity	Carbenicillin	Disodium salt of carbenicillin, Carfecillin, Carindacillin.
	Uriedopenicillins
	Piperacillin	Picillin, Pipracil
	Azlocillin	Azlocillin sodium salt, Securopen, Mezlocillin..
inhibitor-protected	Amoxicillin/clavulanate	Co-amoxiclav, Augmentin, Amoxiclav, Ranklav, Enhancin, Panklav.
	Amoxicillin sulbactam	Trifamox IBL.
	Amlicillin/sulbactam	Sulacillin, Unazine, Ampisid.
	Piperacillin/tazobactam	Tazocin
	Ticarcillin/clavulanate	Timentin
Combination of penicillins	Ampicillin/oxacillin	Ampiox.

Antibiotics by duration of action:

Groups of antibiotics and names of the main drugs of the generation.

Generations	Preparation:	Name
1st	Cefazolin	Kefzol.
	Cephalexin*	Cefalexin-AKOS.
	Cefadroxil*	Durocef.
2nd	Cefuroxime	Zinacef, Cefurus.
	Cefoxitin	Mefoksin.
	Cefotetan	Cefotetan.
	Cefaclor*	Zeklor, Vercef.
	Cefuroxime-axetil*	Zinnat.
3rd	Cefotaxime	Cefotaxime.
	Ceftriaxone	Rofecin.
	Cefoperazone	Medocef.
	Ceftazidime	Fortum, Ceftazidime.
	Cefoperazone/sulbac-tama	Sulperazon, Sulzoncef, Bakperazon.
	Cefditorena*	Spectracef.
	Cefixime*	Suprax, Sorcef.
	Cefpodoxime*	Proksetil.
	Ceftibuten*	Cedex.
4th	cefepima	Maxim.
4th	Cefpiroma	Caten.
5th	Ceftobiprol	Zefter.
5th	Ceftaroline	Zinforo.

Antibiotics- a group of compounds of natural origin or their semi-synthetic and synthetic analogues with antimicrobial or antitumor activity.

To date, several hundred such substances are known, but only a few of them have found application in medicine.

The main classifications of antibiotics

Based on the classification of antibiotics There are also several different principles.

According to the method of obtaining them, they are divided:

on natural;
synthetic;
semi-synthetic (at the initial stage they are obtained naturally, then the synthesis is carried out artificially).

Producers of antibiotics:

predominantly actinomycetes and mold fungi;
bacteria (polymyxins);
higher plants (phytoncides);
tissues of animals and fish (erythrin, ekteritsid).

Direction of action:

antibacterial;
antifungal;
antitumor.

According to the spectrum of action - the number of types of microorganisms that antibiotics act on:

broad-spectrum drugs (3rd generation cephalosporins, macrolides);
narrow-spectrum drugs (cycloserine, lincomycin, benzylpenicillin, clindamycin). In some cases, they may be preferable, since they do not suppress the normal microflora.

Classification by chemical structure

By chemical structure antibiotics are divided into:

for beta-lactam antibiotics;
aminoglycosides;
tetracyclines;
macrolides;
lincosamides;
glycopeptides;
polypeptides;
polyenes;
anthracycline antibiotics.

backbone of the molecule beta-lactam antibiotics forms a beta-lactam ring. These include:

penicillins ~ a group of natural and semi-synthetic antibiotics, the molecule of which contains 6-aminopenicillanic acid, consisting of 2 rings - thiazolidone and beta-lactam. Among them are:

Biosynthetic (penicillin G - benzylpenicillin);

aminopenicillins (amoxicillin, ampicillin, becampicillin);

Semi-synthetic "anti-staphylococcal" penicillins (oxacillin, methicillin, cloxacillin, dicloxacillin, flucloxacillin), the main advantage of which is resistance to microbial beta-lactamases, primarily staphylococcal ones;

cephalosporins are natural and semi-synthetic antibiotics derived from 7-aminocephalosporic acid and containing a cephem (also beta-lactam) ring,

i.e. in structure they are close to penicillins. They are divided into iephalosporins:

1st generation - tseporin, cephalothin, cephalexin;

2nd generation - cefazolin (kefzol), cefamezin, cefaman-dol (mandol);
3rd generation - cefuroxime (ketocef), cefotaxime (claforan), cefuroxime axetil (zinnat), ceftriaxone (longa-cef), ceftazidime (fortum);
4th generation - cefepime, cefpir (cephrom, keiten), etc.;
monobactams - aztreonam (azactam, nonbactam);
carbopenems - meropenem (meronem) and imipinem, used only in combination with a specific inhibitor of renal dehydropeptidase cilastatin - imipinem / cilastatin (thienam).

Aminoglycosides contain amino sugars linked by a glycosidic bond to the rest (aglycone fragment) of the molecule. These include:

synthetic aminoglycosides - streptomycin, gentamicin (garamycin), kanamycin, neomycin, monomycin, sisomycin, tobramycin (tobra);
semi-synthetic aminoglycosides - spectinomycin, amikacin (amikin), netilmicin (netillin).

backbone of the molecule tetracyclines is a polyfunctional hydronaphthacene compound with the generic name tetracycline. Among them are:

natural tetracyclines - tetracycline, oxytetracycline (clinimycin);
semi-synthetic tetracyclines - metacycline, chlortethrin, doxycycline (vibramycin), minocycline, rolitetracycline. Group drugs macrolead contain in their molecule a macrocyclic lactone ring associated with one or more carbohydrate residues. These include:
erythromycin;
oleandomycin;
roxithromycin (rulide);
azithromycin (sumamed);
clarithromycin (clacid);
spiramycin;
dirithromycin.

To lincosamide include lincomycin and clindamycin. The pharmacological and biological properties of these antibiotics are very close to macrolides, and although chemically they are completely different drugs, some medical sources and pharmaceutical companies that produce chemotherapy drugs, such as delacin C, classify lincosamines as macrolides.

Group drugs glycopeptides contain substituted peptide compounds in their molecule. These include:

vancomycin (vankacin, diatracin);
teicoplanin (targocid);
daptomycin.

Group drugs polypeptides in their molecule contain residues of polypeptide compounds, these include:

gramicidin;
polymyxins M and B;
bacitracin;
colistin.

Group drugs irrigation contain several conjugated double bonds in their molecule. These include:

amphotericin B;
nystatin;
levorin;
natamycin.

to anthracycline antibiotics Anticancer antibiotics include:

doxorubicin;
carminomycin;
rubomycin;
aclarubicin.

There are several other antibiotics widely used in practice that do not belong to any of the listed groups: fosfomycin, fusidic acid (fusidin), rifampicin.

The basis of the antimicrobial action of antibiotics, as well as other chemotherapeutic agents, is a violation of the metabolism of microbial cells.

Mechanism of antimicrobial action of antibiotics

According to the mechanism of antimicrobial action antibiotics can be divided into the following groups:

cell wall synthesis inhibitors (murein);
causing damage to the cytoplasmic membrane;
inhibitory protein synthesis;
nucleic acid synthesis inhibitors.

To inhibitors of cell wall synthesis relate:

beta-lactam antibiotics - penicillins, cephalosporins, monobactams and carbopenems;
glycopeptides - vancomycin, clindamycin.

The mechanism of blockade of bacterial cell wall synthesis by vancomycin. differs from that of penicillins and cephalosporins and, accordingly, does not compete with them for binding sites. Since there is no peptidoglycan in the walls of animal cells, these antibiotics have a very low toxicity to the macroorganism, and they can be used in high doses (megatherapy).

To antibiotics that cause damage to the cytoplasmic membrane(blocking of phospholipid or protein components, violation of the permeability of cell membranes, changes in membrane potential, etc.), include:

polyene antibiotics - have a pronounced antifungal activity, changing the permeability of the cell membrane by interacting (blocking) with the steroid components that make up it in fungi, and not in bacteria;
polypeptide antibiotics.

The largest group of antibiotics is inhibiting protein synthesis. Violation of protein synthesis can occur at all levels, starting with the process of reading information from DNA and ending with interaction with ribosomes - blocking the binding of transport t-RNA to goiter-subunits of ribosomes (aminoglycosides), with 508-subunits of ribosomes (macrolides) or with information i-RNA (on the 308 subunit of ribosomes - tetracyclines). This group includes:

aminoglycosides (for example, the aminoglycoside gentamicin, by inhibiting protein synthesis in a bacterial cell, can disrupt the synthesis of the protein coat of viruses and therefore may have an antiviral effect);
macrolides;
tetracyclines;
chloramphenicol (levomycetin), which disrupts protein synthesis by a microbial cell at the stage of amino acid transfer to ribosomes.

Nucleic acid synthesis inhibitors possess not only antimicrobial, but also cytostatic activity and therefore are used as antitumor agents. One of the antibiotics belonging to this group, rifampicin, inhibits DNA-dependent RNA polymerase and thereby blocks protein synthesis at the transcriptional level.

Antibiotics are chemical compounds of biological origin that have a selective damaging or destructive effect on microorganisms.

In 1929, A. Fleming first described the lysis of staphylococci on Petri dishes contaminated with fungi of the genus Penicillium, and in 1940 the first penicillins were obtained from a culture of these microorganisms. According to official estimates, several thousand tons of penicillins have been introduced to mankind over the past forty years. It is with their widespread use that the devastating consequences of antibiotic therapy are associated, in a sufficient percentage of cases carried out not according to indications. To date, 1-5% of the population of most developed countries are hypersensitive to penicillins. Since the 1950s, clinics have become sites for the proliferation and selection of beta-lactamase-producing staphylococci, which currently prevail and account for about 80% of all staphylococcal infections. The constant development of resistance of microorganisms is the main stimulating reason for the creation of new and new antibiotics, complicating their classification.

Classification of antibiotics

1. Antibiotics having a beta-lactam ring in the structure

a) penicillins (benzylpenicillin, phenoxymethylpenicillin, methicillin,

oxacillin, ampicillin, carboxylicillin)

b) Cephalosporins (cefazolin, cephalexin)

c) Carbapenems (imipenem)

d) Monobactams (aztreonam)

2. Macrolides containing a macrocyclic lactone ring (erythromi

cin, oleandomycin, spiramycin, roxithromycin, azithromycin)

4. Tetracyclines containing 4 six-membered cycles (tetracycline, metacycline

lin, doxycycline, morphocycline) Aminoglycosides containing amino sugar molecules in the structure (gentami-

cyn, kanamycin, neomycin, streptomycin)

5. Polypeptides (polymyxins B, E, M)

6. Antibiotics of different groups (vancomycin, famicidin, levomycetin, rifa-

micin, lincomycin, etc.)

Beta lactam antibiotics

Penicillins

Although historically penicillins were the first antibiotics, to date they remain the most widely used drugs of this class. The mechanism of antimicrobial action of penicillins is associated with impaired cell wall formation.

Allocate natural (benzylpenicillin and its salts) and semi-synthetic penicillins. In the group of semi-synthetic antibiotics, in turn, there are:

Penicillinase-resistant drugs with a predominant effect on

gram-positive bacteria (oxacillin),

Broad-spectrum drugs (ampicillin, amoxicillin),

Broad-spectrum drugs effective against synergy

nail sticks (carbenicillin).

Benzylpenicillin is the drug of choice for infections caused by pneumococci, streptococci, meningococci, treponema pallidum, and staphylococci that do not produce beta-lactamase. Most of these pathogens are sensitive to benzylpenicillin in daily doses of 1-10 million units. Most gonococci are characterized by the development of resistance to penicillins, and therefore, at present, they are not the drugs of choice for the treatment of uncomplicated gonorrhea.

Oxacillin is similar in its spectrum of action to benzylpenicillin, but it is also effective against staphylococci that produce penicillinase (beta-lactamase). Unlike benzylpenicillin, oxacillin is also effective when taken orally (acid-resistant), and when used together, it significantly increases the effectiveness of ampicillin (combined preparation Ampiox). Ampicillin is used in doses of 250-500 mg 4 times a day, used for the oral treatment of banal urinary tract infections, the main causative agents of which are usually gram-negative bacteria, and for the treatment of mixed or secondary infections of the upper respiratory tract (sinusitis, otitis, bronchitis ). The main distinguishing advantage of carbenicillin is its effectiveness against Pseudomonas aeruginosa and Proteus, and, accordingly, it can be used in putrefactive (gangrenous) infectious processes.

Penicillins can be protected from the action of bacterial beta-lactamases by co-administration with beta-lactamase inhibitors, such as clavulanic acid or sulbactam. These compounds are similar in structure to beta-lactam antibiotics, but they themselves have negligible antimicrobial activity. They effectively inhibit the beta-lactamase of microorganisms, thereby protecting hydrolyzable penicillins from inactivation by these enzymes and thereby increasing their effectiveness.

Undoubtedly, penicillins are the least toxic of all antibiotics, but allergic reactions occur more often than other antibiotics. Usually these are not dangerous skin reactions (rash, redness, itching), life-threatening severe anaphylactic reactions are rare (about 1 case in 50,000 patients) and usually with intravenous administration. All drugs in this group are characterized by cross-hypersensitivity.

All penicillins in large doses irritate the nervous tissue and sharply increase the excitability of neurons. In this regard, at present, the introduction of penicillins into the spinal canal is considered unjustified. In rare cases, when the dose of benzylpenicillin is exceeded by more than 20 million units per day, signs of irritation of the brain structures appear.

The irritating effect on the gastrointestinal tract of oral penicillins is manifested by dyspeptic symptoms, in particular nausea, vomiting, diarrhea, and is most pronounced in broad-spectrum drugs, since superinfection (candidiasis) often occurs when they are used. The irritating effect along the routes of administration is manifested with intramuscular injection by compaction, local pain, and with intravenous administration - thrombophlebitis.

Cephalosporins

The core of the structure of cephalosporins is 7-aminocephalosporan acid, which is extremely similar to 6-aminopenicillanic acid, the basis of the structure of penicillins. This chemical structure predetermined the similarity of antimicrobial properties with penicillins with resistance to the action of beta-lactamases, as well as antimicrobial activity not only against gram-positive, but also against gram-negative bacteria.

The mechanism of antimicrobial action is completely similar to that of penicillins. Cephalosporins are traditionally divided into "generations", which determine the main spectrum of their antimicrobial activity.

First-generation cephalosporins (cephalexin, cephradin, and cefadroxil) are very active against gram-positive cocci, including pneumococci, viridescent streptococcus, hemolytic streptococcus, and staphylococcus aureus; as well as in relation to gram-negative bacteria - Escherichia coli, Klebsiella, Proteus. They are used to treat urinary tract infections, localized staphylococcal infections, polymicrobial localized infections, soft tissue abscesses. Second-generation cephalosporins (cefuroxime, cefamandol) are characterized by a wider spectrum of action against gram-negative bacteria and better penetrate most tissues. Third-generation drugs (cefotaxime, ceftriaxone) have an even wider spectrum of action, but are less effective against gram-positive bacteria; a feature of this group is their ability to penetrate the blood-brain barrier and, accordingly, high efficiency in meningitis. Fourth-generation cephalosporins (cefpirom) are considered as reserve antibiotics and are used for infections caused by multi-resistant bacterial strains and severe persistent nosocomial infections.

Side effects. As well as to penicillins, hypersensitivity to cephalosporins is often manifested in all variants. In this case, cross-sensitivity to penicillins and cephalosporins is also possible. In addition, local irritant effects, hypoprothrombinemia and increased bleeding associated with impaired vitamin K metabolism, and teturam-like reactions are possible (the metabolism of ethyl alcohol is disturbed with the accumulation of extremely toxic acetaldehyde).

Carbapenems

This is a new class of drugs that are structurally similar to beta-lactam antibiotics. The first representative of this class of compounds is imipenem. The drug is characterized by a wide spectrum of antimicrobial action and high activity against both gram-positive, gram-negative, and anaerobic microorganisms. Imipenem is resistant to beta-lactamase.

The main indications for the use of imipenem are currently being specified. It is used for resistant ™ to other antibiotics available. Pseudomonas aeruginosa quickly develops resistance to imipenem, so it must be combined with aminoglycosides. This combination is effective for the treatment of febrile patients with neutropenia. Imipenem should be a reserve antibiotic and is intended only for the treatment of severe nosocomial infections (sepsis, peritonitis, pneumonia), especially in microbial resistance to other antibiotics or an unidentified pathogen, in patients with agranulocytosis, immunodeficiency.

The effectiveness of imipenem can be increased by combining it with cilastatin, which reduces its renal excretion (combination drug thienam).

Side effects are manifested in the form of nausea, vomiting, skin rashes, irritation at the injection site. Patients with hypersensitivity to penicillins may also be hypersensitive to imipenem.

Monobactams

A representative of this group of antibiotics is aztreonam, which is a highly effective antibiotic against gram-negative microorganisms (E. coli, Salmonella, Klebsiella, Haemophilus influenzae, etc.). It is used to treat septic diseases, meningitis, infections of the upper respiratory and urinary tract caused by such flora.

Aminoglycosides

Antibiotics of this group are water-soluble compounds that are stable in solution and more active in an alkaline environment. They are poorly absorbed when taken orally, so they are most often used parenterally. They have a bactericidal effect due to the irreversible inhibition of protein synthesis on the ribosomes of the microorganism after the penetration of the drug into the microbial cell. Aminoglycosides are effective against most Gram-positive and many Gram-negative bacteria.

All aminoglycosides act only on extracellular microorganisms, and their penetration into a microbial cell is an active transport, energy, pH and oxygen dependent process. Aminoglycosides are effective only against microorganisms that carry out such a mechanism on the cell surface, an example of which is Escherichia coli. Bacteria that do not have such a mechanism are not sensitive to aminoglycosides. This explains the lack of activity of aminoglycosides in relation to anaerobes, the absence of the effect of aminoglycosides in abscesses (in the abscess cavity, in areas of tissue necrosis), infections of bones, joints, soft tissues, when there is an acidification of the microbial habitat, reduced oxygen supply, reduced energy metabolism. Aminoglycosides are effective where normal pH, pO2, sufficient energy supply - in the blood, in the kidneys. The process of penetration of aminoglycosides into the microbial cell is greatly facilitated by drugs that act on the cell wall, such as penicillins, cephalosporins.

Aminoglycosides are used to treat infections caused by gram-negative intestinal bacteria (pneumonia, bacterial endocarditis) or when sepsis is suspected due to gram-negative and bacteria resistant to other antibiotics. Streptomycin and kanamycin are effective antituberculous drugs.

Side effects are that all aminoglycosides have oto- and nephrotoxic effects of varying severity. Ototoxicity is manifested first by a decrease in hearing (damage to the cochlea) regarding high-frequency sounds or vestibular disorders (impaired coordination of movements, loss of balance). Nephrotoxic action is diagnosed by an increase in the level of creatinine in the blood or an increase in the clearance of creatinine by the kidneys. In very high doses, aminoglycosides have a curare-like effect up to paralysis of the respiratory muscles.

Tetracyclines

Tetracyclines are a large family of antibiotics that share a similar structure and mechanism of action. The name of the group comes from a chemical structure that has four fused rings.

The mechanism of antibacterial action is associated with the inhibition of protein synthesis in ribosomes, that is, to achieve it, the penetration of the drug into the microorganism is necessary. All tetracyclines have a bacteriostatic effect and have a wide spectrum of antibacterial action. Their spectrum of action includes many gram-positive and gram-negative bacteria, as well as rickettsia, chlamydia, and even amoeba.

Unfortunately, at present, many bacteria have developed resistance to this group of antibiotics due to their initially unreasonably wide use. Resistance, as a rule, is associated with the prevention of the penetration of tetracyclines into the microorganism.

Tetracyclines are fairly well absorbed from the upper small intestine, but the simultaneous intake of milk, foods rich in calcium, iron, manganese or aluminum cations, as well as a strongly alkaline environment significantly weaken their absorption. The drugs are relatively evenly distributed in the body, but poorly penetrate the blood-brain barrier. However, the drugs penetrate well through the hematoplacental barrier and are able to bind to the growing bones and teeth of the fetus. Excreted mainly by bile and partially by the kidneys.

Side effects - nausea, vomiting, diarrhea due to suppression of one's own intestinal flora. Violation of the development of bones and teeth in children due to the binding of calcium ions. With prolonged use, a toxic effect on the liver and kidneys is possible, as well as the development of photosensitivity.

macrolides

Representatives of the old generation of this group of antibiotics are erythromycin and oleandomycin. They are narrow spectrum antibiotics, effective mainly against gram-positive bacteria by inhibiting protein synthesis. The drugs are poorly soluble in water, so they are used, as a rule, inside. However, the tablet must be coated to protect against the damaging effects of gastric juice. The drug is excreted mainly by the kidneys. Erythromycin is the drug of choice for diphtheria, as well as chlamydial infections of the respiratory tract and genitourinary system. In addition, due to a very similar spectrum of action, this group of drugs is a substitute for penicillins in case of allergy to them.

In recent years, new generation drugs from this group have been introduced - spiramycin (rovamycin), roxithromycin (rulid), azithromycin (sumamed). They are broad-spectrum drugs, providing mainly a bactericidal effect. They have good bioavailability when taken orally, penetrate well into tissues and specifically accumulate at the sites of the infectious and inflammatory process. They are used for non-severe forms of infectious diseases of the upper respiratory tract, otitis media, sinusitis, etc.

Macrolides are generally low-toxic drugs, but as a result of irritant action, they can cause dyspepsia when taken orally and phlebitis when administered intravenously.

Polymyxins

This group includes antibiotics of a polypeptide nature effective against gram-negative flora. Due to severe nephrotoxicity, all polymyxins except B and E are not recommended for use. The mechanism of their action is to adhere to the cell wall of gram-negative microorganisms and because of this, the violation of its permeability for nutrients. Gram-positive bacteria are resistant to the action of polymyxins, since they do not contain lipoids in the wall, which are necessary for the fixation of these antibiotics. They are not absorbed from the intestine, and when administered parenterally, their strong nephrotoxicity is manifested. Therefore, they are used either locally or locally - the pleural cavity, articular cavity, etc. They are excreted mainly by the kidneys. Other side effects include vestibular disorders and sensory disturbances.

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6. Group of monobactams

Mechanism of action. Aztreonam has a bactericidal effect, which is associated with a violation of the formation of the bacterial cell wall.

Activity spectrum. The peculiarity of the antimicrobial spectrum of action of aztreonam is due to the fact that it is resistant to many β-lactamases produced by aerobic gram-negative flora, and at the same time is destroyed by β-lactamases of staphylococci, bacteroides and ESBL.

Indications. Aztreonam is a reserve drug for the treatment of infections of various localization caused by aerobic gram-negative bacteria:

Contraindications. Allergic reactions to aztreonam in history.

7. Tetracycline group

Mechanism of action. Tetracyclines have a bacteriostatic effect, which is associated with impaired protein synthesis in the microbial cell.

spectrum of activity. Tetracyclines are considered AMPs with a wide spectrum of antimicrobial activity, however, in the course of their long-term use, many bacteria have acquired resistance to them.

Indications:

Contraindications:

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