Antibacterial drugs to treat pneumonia

The basis of treatment of acute pneumonia is the prescription of antibacterial agents. Etiotropic treatment must meet the following conditions:

• treatment should be prescribed as early as possible, before the pathogen is isolated and identified;
• treatment should be carried out under clinical and bacteriological control with determination of the pathogen and its sensitivity to antibiotics;
• Antibacterial agents should be prescribed in optimal doses and at such intervals as to ensure the creation of a therapeutic concentration in the blood and lung tissue;
• Antibacterial treatment should be continued until intoxication disappears, body temperature returns to normal (at least 3-4 days of consistently normal temperature), physical data in the lungs, and resorption of inflammatory infiltration in the lungs according to X-ray examination data. The presence of clinical and X-ray "residual" signs of pneumonia is not a reason to continue antibacterial therapy. According to the Consensus on Pneumonia of the Russian National Congress of Pulmonologists (1995), the duration of antibacterial therapy is determined by the type of pathogen causing pneumonia. Uncomplicated bacterial pneumonias are treated for another 3-4 days after normalization of body temperature (provided that the leukocyte formula has normalized) and 5 days if azithromycin is used (not prescribed if there are signs of bacteremia). The duration of antibacterial therapy for mycoplasma and chlamydial pneumonia is 10-14 days (5 days if azithromycin is used). Legionella pneumonia is treated with anti-Legionella drugs for 14 days (21 days in patients with immunodeficiency states).
• if there is no effect from the antibiotic within 2-3 days, it is changed; in severe cases of pneumonia, antibiotics are combined;
• uncontrolled use of antibacterial agents is unacceptable, since this increases the virulence of infectious agents and forms that are resistant to drugs arise;
• with prolonged use of antibiotics, the body may develop a deficiency of B vitamins as a result of a disruption of their synthesis in the intestine, which requires correction of the vitamin imbalance by additional administration of the appropriate vitamins; it is necessary to promptly diagnose candidiasis and intestinal dysbacteriosis, which can develop during treatment with antibiotics;
• During treatment, it is advisable to monitor immune status indicators, since antibiotic treatment can cause suppression of the immune system, which contributes to the long-term existence of the inflammatory process.

Criteria for the effectiveness of antibacterial therapy

The criteria for the effectiveness of antibacterial therapy are primarily clinical signs: a decrease in body temperature, a decrease in intoxication, an improvement in the general condition, normalization of the leukocyte formula, a decrease in the amount of pus in sputum, positive dynamics of auscultatory and radiological data. The effectiveness is assessed after 24-72 hours. Treatment does not change if there is no deterioration.

Fever and leukocytosis may persist for 2-4 days, physical findings - more than a week, radiographic signs of infiltration - 2-4 weeks from the onset of the disease. Radiographic findings often worsen in the initial period of treatment, which is a serious prognostic sign in patients with severe disease.

Among the antibacterial agents used as etiotropic agents in acute pneumonia, the following can be distinguished:

• penicillins;
• cephalosporins;
• monobactams;
• carbapenems;
• aminoglycosides;
• tetracyclines;
• macrolides;
• chloramphenicol;
• lincosamines;
• ansamycins;
• polypeptides;
• fusidin;
• novobiocin;
• fosfomycin;
• quinolones;
• nitrofurans;
• imidazoles (metronidazole);
• phytoncides;
• sulfonamides.

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Beta-lactam antibiotics

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Penicillin group

The mechanism of action of penicillins is to suppress the biosynthesis of the peptide glycan of the cell membrane, which protects bacteria from the environment. The beta-lactam fragment of antibiotics serves as a structural analogue of alanyl aniline, a component of muranic acid, which forms cross-links with peptide chains in the peptide glycan layer. Disruption of the synthesis of cell membranes leads to the inability of the cell to withstand the osmotic gradient between the cell and the environment, so the microbial cell swells and ruptures. Penicillins have a bactericidal effect only on multiplying microorganisms, since dormant ones do not build new cell membranes. The main defense of bacteria against penicillins is the production of the enzyme beta-lactamase, which opens the beta-lactam ring and inactivates the antibiotic.

Classification of beta-lactamases according to their effect on antibiotics (Richmond, Sykes)

• Class I β-Lactamases that break down cephalosporins
• Class II β-Lactamases that break down penicillins
• Class II β-Lactamases that break down a variety of broad-spectrum antibiotics
• lV-class
• V-class β-Lactamase that breaks down isoxazolylpenicillins (oxacillin)

In 1940, Abraham and Chain discovered an enzyme in E. coli that breaks down penicillin. Since then, a large number of enzymes have been described that break down the beta-lactam ring of penicillin and cephalosporins. They are called beta-lactamases. This is a more correct name than penicillinases. β-Lactamases differ in molecular weight, isoelectric properties, amino acid sequence, molecular structure, and relationships with chromosomes and plasmids. The harmlessness of penicillins for humans is due to the fact that human cell membranes differ in structure and are not affected by the drug.

First generation penicillins (natural penicillins)

Spectrum of action: gram-positive bacteria ( staphylococcus, streptococcus, pneumococcus, anthrax, gangrene, diphtheria, listerella); gram-negative bacteria (meningococci, gonococci, proteus, spirochetes, leptospira).

Resistant to the action of natural penicillins: gram-negative bacteria (enterobacteria, whooping cough, pseudomonas aeruginosa, klebsiella, haemophilus influenzae, legionella, as well as staphylococci that produce the enzyme beta-lactamase, causative agents of brucellosis, tularemia, plague, cholera), tuberculosis bacilli.

Benzylpenicillin sodium salt is available in vials of 250,000 U, 500,000 U, 1,000,000 U. The average daily dose is 6,000,000 U (1,000,000 every 4 hours). The maximum daily dose is 40,000,000 U or more. The drug is administered intramuscularly, intravenously, intra-arterially.

Benzylpenicillin potassium salt - the forms of release and dosage are the same, the drug cannot be administered intravenously or endolumbarly.

Benzylpenicillin novocaine salt (novocaine) - the same forms of release. The drug is administered only intramuscularly, has a prolonged effect, can be administered 4 times a day at 1 million units.

Phenoxymethylpenicillin - tablets of 0.25 g. It is taken orally (not destroyed by gastric juice) 6 times a day. The average daily dose is 1-2 g, the maximum daily dose is 3 g or more.

Second generation penicillins (semi-synthetic penicillinase-resistant antistaphylococcal antibiotics)

The second generation of penicillins is obtained by adding an acyl side chain to 6-aminopenicillanic acid. Some staphylococci produce the enzyme β-lactamase, which interacts with the β-lactam ring of penicillins and opens it, which leads to the loss of the antibacterial activity of the drug. The presence of a side acyl chain in second-generation drugs protects the beta-lactam ring of the antibiotic from the action of bacterial beta-lactamase. Therefore, second-generation drugs are intended primarily for the treatment of patients with penicillinase-producing staphylococci. These antibiotics are also active against other bacteria for which penicillin is effective, but it is important to know that benzylpenicillin is significantly more effective in these cases (more than 20 times more effective for pneumococcal pneumonia). In this regard, in case of a mixed infection, it is necessary to prescribe benzylpenicillin and a drug resistant to β-lactamase. Second-generation penicillins are resistant to pathogens that are resistant to penicillin. Indications for the use of penicillins of this generation are pneumonia and other infectious diseases of staphylococcal etiology.

Oxacillin (prostaphlin, resistopen, stapenor, bristopen, baktotsill) - is available in 0.25 and 0.5 g vials, as well as in 0.25 and 0.5 g tablets and capsules. It is used intravenously, intramuscularly, orally every 4-6 hours. The average daily dose for pneumonia is 6 g. The highest daily dose is 18 g.

Dicloxacillin (dinapen, dicill) is an antibiotic close to oxacillin, containing 2 chlorine atoms in its molecule, penetrates well into the cell. It is used intravenously, intramuscularly, orally every 4 hours. The average daily therapeutic dose is 2 g, the maximum daily dose is 6 g.

Cloxacillin (tegopen) is a drug similar to dicloxacillin, but contains one chlorine atom. It is used intravenously, intramuscularly, orally every 4 hours. The average daily therapeutic dose is 4 g, the maximum daily dose is 6 g.

Flucloxacillin is an antibiotic close to dicloxacillin, it contains one atom of chlorine and one atom of fluorine in its molecule. It is used intravenously, intramuscularly every 4-6 hours, the average daily therapeutic dose is 4-8 g, the maximum daily dose is 18 g.

Cloxacillin and flucloxacillin create higher concentrations in blood serum compared to oxacillin. The ratio of concentrations in blood after high-dose intravenous administration of oxacillin, cloxacillin, dicloxacillin is 1: 1.27: 3.32

Dicloxacillin and oxacillin are metabolized primarily in the liver, so they are preferred for use in renal failure.

Nafcillin (nafcil, unipen) - is administered intravenously, intramuscularly every 4-6 hours. The average daily dose is 6 g. The highest daily dose is 12 g.

Third generation penicillins - broad-spectrum semi-synthetic penicillins

Third-generation penicillins actively suppress gram-negative bacteria. Their activity against gram-negative bacteria is lower than that of benzylpenicillin, but slightly higher than that of second-generation penicillins. The exception is staphylococci producing beta-lactamase, which are not affected by broad-spectrum penicillin.

Ampicillin (pentrexil, omnipen) is available in tablets, capsules of 0.25 g and in vials of 0.25 and 0.5 g. It is used orally, intramuscularly, intravenously every 4-6 hours. The average daily dose of the drug is 4-6 g. The highest daily dose is 12 g. Pseudomonas aeruginosa, penicillinase-producing staphylococci and indole-positive strains of Proteus are resistant to ampicillin.

Ampicillin penetrates well into bile, sinuses and accumulates in urine, its concentrations in sputum and lung tissue are low. The drug is most indicated for urogenital infections, and it does not have a nephrotoxic effect. However, in case of renal failure, the dose of ampicillin is recommended to be reduced or the intervals between administrations of the drug should be increased. Ampicillins in optimal doses are also effective for pneumonia, but the duration of treatment is 5-10 days or more.

Cyclacillin (Cyclopen) is a structural analogue of ampicillin. It is prescribed orally every 6 hours. The average daily dose of the drug is 1-2 g.

Pivampicillin - pivaloyloxymethyl ether of ampicillin - is hydrolyzed by non-specific esterases in the blood and intestine to ampicillin. The drug is absorbed from the intestine better than ampicillin. It is used orally in the same doses as ampicillin.

Bacampicillin (penglab, spectrobid) - refers to precursors that release ampicillin in the body. It is prescribed orally every 6-8 hours. The average daily dose is 2.4-3.2 g.

Amoxicillin is an active metabolite of ampicillin, taken orally every 8 hours. The average daily dose is 1.5-3 g. The drug is more easily absorbed in the intestines than ampicillin and, when administered in the same dose, creates a double concentration in the blood, its activity against sensitive bacteria is 5-7 times higher, and it is superior to ampicillin in terms of penetration into the lung tissue.

Augmentin is a combination of amoxicillin and clavulanic acid.

Clavulanic acid is a β-lactam derivative produced by Streptomyces clavuligerus. Clavulanic acid binds (inhibits) β-lactamase (penicillinase) and thus competitively protects penicillin, potentiating its action. Amoxicillin potentiated by clavulanic acid is suitable for the treatment of respiratory and urinary tract infections caused by β-lactamase-producing microorganisms, as well as in cases of infection resistant to amoxicillin.

Available in tablets, one tablet contains 250 mg of amoxicillin and 125 mg of clavulanic acid. Prescribed 1-2 tablets 3 times a day (every 8 hours).

Unasin is a combination of sodium sulbactam and ampicillin in a 1:2 ratio. It is used for intramuscular and intravenous injections. It is available in 10 ml vials containing 0.75 g of the substance (0.25 g of sulbactam and 0.5 g of ampicillin); in 20 ml vials containing 1.5 g of the substance (0.5 g of sulbactam and 1 g of ampicillin); in 20 ml vials with 3 g of the substance (1 g of sulbactam and 2 g of ampicillin). Sulbactam irreversibly inhibits most β-lactamases responsible for the resistance of many types of bacteria to penicillins and cephalosporins.

Sulbactam prevents the destruction of ampicillin by resistant microorganisms and has a pronounced synergism when administered with it. Sulbactam also inactivates penicillin-binding proteins of bacteria such as Staph. aureus, E. coli, P. mirabilis, Acinetobacter, N. gonorrheae, H. influenzae, Klebsiella, which leads to a sharp increase in the antibacterial activity of ampicillin. The bactericidal component of the combination is ampicillin. The spectrum of action of the drug: staphylococci, including penicillinase-producing), pneumococcus, enterococcus, certain types of streptococci, Haemophilus influenzae, anaerobes, Escherichia coli, Klebsiella, Enterobacter, Neisseria. The drug is diluted with water for injection or 5% glucose, administered intravenously slowly by jet stream for 3 minutes or by drip for 15-30 minutes. The daily dose of unazin is from 1.5 to 12 g for 3-4 administrations (every 6-8 hours). The maximum daily dose is 12 g, which is equivalent to 4 g of sulbactam and 8 g of ampicillin.

Ampiox is a combination of ampicillin and oxacillin (2:1), combines the action spectra of both antibiotics. It is available in tablets, capsules C for oral administration of 0.25 g and in vials of 0.1, 0.2 and 0.5 g. It is prescribed orally, intravenously, intramuscularly every 6 hours. The average daily dose is 2-4 g. The maximum daily dose is 8 g.

Fourth generation penicillins (carboxypenicillins)

The spectrum of action of fourth-generation penicillins is the same as that of ampicillin, but with the additional property of destroying Pseudomonas aeruginosa, Pseudomonas and indole-positive Proteus. They act weaker than ampicillin on other microorganisms.

Carbenicillin (pyopen) - spectrum of action: the same non-positive bacteria that are sensitive to penicillin, and gram-negative bacteria sensitive to ampicillin, in addition, the drug acts on Pseudomonas aeruginosa and Proteus. The following are resistant to carbenicillin: penicillinase-producing staphylococci, causative agents of gas gangrene, tetanus, protozoa, spirochetes, fungi, rickettsia.

Available in 1 g vials. It is administered intravenously and intramuscularly every 6 hours. The average daily dose intravenously is 20 g, the maximum daily dose is 30 g. The average daily dose intramuscularly is 4 g, the highest daily dose is 8 g.

Carindacillin is an indanyl ether of carbenicillin, administered orally at 0.5 g 4 times a day. After absorption from the intestine, it is quickly hydrolyzed to carbenicillin and indole.

Carfecillin is a phenyl ether of carbenicillin, taken orally at 0.5 g 3 times a day, in severe cases the daily dose is increased to 3 g. Effective for pneumonia and urinary tract infections.

Ticarcillin (Tikar) is similar to carbenicillin, but is 4 times more active against Pseudomonas aeruginosa. It is administered intravenously and intramuscularly. It is administered intravenously every 4-6 hours, the average daily dose is 200-300 mg / kg, the maximum daily dose is 24 g. It is administered intramuscularly every 6-8 hours, the average daily dose is 50-100 mg / kg, the maximum daily dose is 8 g. Ticarcillin is destroyed by beta-lactamases produced by Pseudomonas aeruginosa, Haemophilus influenzae, Escherichia coli, Proteus, Maraxella (Neisseria). The spectrum of action of ticarcillin increases with a combination of ticarcillin with clavulanic acid (timentin). Timentin is highly effective against β-lactamase-producing and beta-lactamase-negative strains of non-negative bacteria.

The fifth generation of penicillins - ureido- and piperazino-penicillins

In ureidopenicillins, a side chain with a urea residue is attached to the ampicillin molecule. Ureidopenicillins penetrate the walls of bacteria, suppress their synthesis, but are destroyed by β-lactamases. The drugs have a bactericidal effect and are especially effective against Pseudomonas aeruginosa (8 times more active than carbenicillin).

Azlocymin (azlin, securalen) is a bactericidal antibiotic, available in 0.5, 1, 2 and 5 g vials, administered intravenously as a 10% solution. It is dissolved in distilled water for injection: 0.5 g is dissolved in 5 ml, 1 g in 10 ml, 2 g in 20 ml, 5 g in 50 ml, administered intravenously by slow jet or intravenously by drip. 10% glucose can be used as a solvent.

Spectrum of action of the drug: gram-positive flora (pneumococcus, streptococcus, staphylococcus, enterococcus, corynebacteria, clostridia), gram-negative flora (pseudomonas, klebsiella, enterobacter, E. coli, salmonella, shigella, Pseudomonas aeruginosa, neisseria, proteus, hemophilus).

The average daily dose is from 8 g (4 times 2 g) to 15, (3 times 5 g). The maximum daily dose is from 20 g (4 times 5 g) to 24 g.

Mezocillin - compared to azlocillin, it is less active against Pseudomonas aeruginosa, but more active against common gram-negative bacteria. It is administered intravenously every 4-6 hours, intramuscularly every 6 hours. The average daily dose intravenously is 12-16 g, the maximum daily dose is 24 g. The average daily dose intramuscularly is 6-8 g, the maximum daily dose is 24 g.

Piperacillin (pipracil) - has a piperazine group in its structure and belongs to piperazinopenicillins. The spectrum of action is close to carbenicillin, it is active against Pseudomonas aeruginosae, Klebsiellae, Enterobacter, H.influenzae, Neisseriae, Pseudomonas aeruginosa. β-lactamases produced by S.aureus destroy piperacillin. Piperacillin is administered intravenously every 4-6 hours, while the average daily therapeutic dose is 12-16 g, the maximum daily dose is 24 g. The drug is administered intramuscularly every 6-12 hours, while the average daily therapeutic dose is 6-8 g, the maximum daily dose is 24 g.

The release of a combination drug of piperacillin with the beta-lactamase inhibitor tazobactam, which is most successfully used in the treatment of purulent lesions of the abdominal cavity, is reported.

The sixth generation of penicillins - amidinopenicillins and tetracycline

Sixth-generation penicillins have a broad spectrum of action, but are particularly active against gram-negative bacteria, including those resistant to ampicillin.

Amdinocillin (coactin) is administered intravenously and intramuscularly at intervals of 4-6 hours. The average daily dose of the drug is 40-60 mg/kg.

Temocillin is a semisynthetic beta-lactam antibiotic. It is most effective against enterobacteria, Haemophilus influenzae, and gonococcus. P. aeruginosae and B. fragilis are resistant to temocillin. It is resistant to most β-lactamases. It is used intravenously at 1-2 g every 12 hours.

The drug is not metabolized in the body and is excreted unchanged by the kidneys. It is most often used for gram-negative sepsis and urinary infection.

All penicillins can cause allergic reactions: bronchospasm, Klinker's edema, urticaria, itchy rashes, anaphylactic shock.

Drugs taken orally can cause dyspeptic symptoms, pseudomembranous colitis, and intestinal dysbacteriosis.

Cephalosporin group

The cephalosporin group of drugs is based on 7-aminocephalosporinic acid, the spectrum of antimicrobial action is wide, at present they are increasingly considered as drugs of choice. Antibiotics of this group were first obtained from the cephalosporium fungus, isolated from sea water taken in Sardinia near the place of discharge of waste water.

The mechanism of action of cephalosporins is close to the mechanism of action of penicillins, since both groups of antibiotics contain a β-lactam ring: disruption of the synthesis of the cell wall of dividing microorganisms due to acetylation of membrane transpeptidases. Cephalosporins have a bactericidal effect. The spectrum of action of cephalosporins is wide: gram-positive and non-negative microorganisms (streptococci, staphylococci, including penicillinase-producing, pneumococci, meningococci, gonococci, diphtheria and anthrax bacilli, causative agents of gas gangrene, tetanus, treponema, borrelia, a number of strains of Escherichia coli, Shigella, Salmonella, Klebsiella, certain types of Proteus). The bactericidal effect of cephalosporins is enhanced in an alkaline environment.

Classification of cephalosporins used parenterally

1st generation	II generation	III generation	IV generation
Cefazolin (kefzol) Cephalotin (Keflin) Cephradine Cephaloridine (ceporia) Cefapirin (Cefadil) Cephaton Cefzedon Cefadroxil (Duracef)	Cefuroxime sodium (ketocef) Cefuroxime acoetyl (zinnate) Cefamandole Ceforanide (precef) Cefonicid (monocid) Cefmenoxime	Cefotaxime sodium (claforan) Cefoperazone (cephobid) Cefsulodin (cefomonide) Cefduperazome Ceftazidime (Fortune) Ceftracaxone (Longacef) Ceftieoksmm (cefizone) Cefazidime (mod) Ceflimizole	Cefazaflur Cefpirome (Keyten) Cefmetazole Cefotetan Cefoxitin Cefsulodin (cefomonide) Moxalactam (latamoxef)
High activity against gram-positive bacteria	High activity against gram-negative bacteria	High activity against Pseudomonas aeruginosa	High activity against bacteroides and other anaerobes

Some new cephalosporins are effective against mycoplasmas, Pseudomonas aeruginosa. They do not act on fungi, rickettsia, tuberculosis bacilli, protozoa.

Cephalosporins are resistant to penicillinase, although many of them are destroyed by cephalosporinase beta-lactamase, which, unlike penicillinase, is produced not by gram-positive but by some non-gram-negative pathogens).

Cephalosporins used parenterally.

First generation cephalosporins

First-generation cephalosporins have high activity against gram-positive cocci, including Staphylococcus aureus and coagulase-negative staphylococci, beta-hemolytic streptococcus, pneumococcus, and viridans streptococcus. First-generation cephalosporins are resistant to staphylococcal beta-lactamase, but are hydrolyzed by β-lactamase of gram-negative bacteria, and therefore drugs of this group are not very active against gram-negative flora (E. coli, Klebsiella, Proteus, etc.).

First-generation cephalosporins penetrate well into all tissues, easily pass through the placenta, are found in high concentrations in the kidneys, pleural, peritoneal and synovial exudates, in smaller quantities in the prostate gland and bronchial secretions and practically do not penetrate the blood-brain barrier;

Cefoloridine (ceporin, loridine) is available in 0.25, 0.5 and 1 g vials. It is administered intramuscularly and intravenously every 6 hours. The average daily dose is 1-2 g, the maximum daily dose is 6 g or more.

Cephaeolin (kefzol, cefamezin, acef) - is available in vials of 0.25, 0.5, 1, 2 and 4 g, administered intravenously, intramuscularly at intervals of 6-8 hours. The average daily dose is 3-4 g, the maximum daily dose

Cephalotin (keflin, ceffin) - is available in 0.5, 1 and 2 g vials. It is administered intramuscularly and intravenously at intervals of 4-6 hours. The average daily dose is 4-6 g, the maximum daily dose is 12 g.

Cephapirin (cefadil) - is administered intravenously, intramuscularly every 6 hours. The average daily dose of the drug is 2-4 g, the maximum daily dose is 6 g or more.

Second generation cephalosporins

Second-generation cephalosporins have predominantly high activity against gram-negative bacteria (E. coli, Klebsiella, Proteus, Enterobacter, Haemophilus influenzae, etc.), as well as gonococci and Neisseria. The drugs of this group are resistant to several or all beta-lactamases formed and to several chromosomal beta-lactamases produced by gram-negative bacteria. Some second-generation cephalosporins are resistant to beta-lactamases and other bacteria.

Cefamandole (mandol) - is available in vials of 0.25; 0.5; 1.0 g, used intravenously, intramuscularly at intervals of 6 hours. The average daily dose is 2-4 g, the maximum daily dose is 6 g or more.

Ceforanide (precef) - is administered intravenously, intramuscularly at 12-hour intervals. The average daily dose is 1 g, the maximum daily dose is 2 g.

Cefuroxime sodium (ketocef) - is available in vials containing 0.75 g and 1.5 g of dry substance. It is administered intramuscularly or intravenously after dilution with the supplied solvent at intervals of 6-8 hours. The average daily dose is 6 g, the maximum is 9 g.

Cefonicid (monicide) - is used intravenously, intramuscularly once a day at a dose of 2 g.

Third generation cephalosporins

Third-generation drugs have high gram-negative activity, i.e. they are highly active against indole-positive strains of Proteus, Pseudomonas aeruginosa, bacteroids (anaerobes that play an important role in the development of aspiration pneumonia, wound infections, osteomyelitis), but are inactive against coccal infections, in particular staphylococcal and enterococcal. They are highly resistant to the action of β-lactamases.

Cefotaxime (claforan) - is available in 1 g vials, used intravenously, intramuscularly at intervals of 6-8 hours. The average daily dose is 4 g, the maximum daily dose is 12 g.

Ceftriaxone (Longacef) - is used intravenously, intramuscularly at intervals of 24 hours. The average daily dose is 2 g, the maximum is 4 g. Sometimes it is used at intervals of 12 hours.

Ceftizoxime (cefizone, epocelin) - is available in 0.5 and 1 g vials, administered at 8-hour intervals. The average daily dose is 4 g, the maximum daily dose is 9-12 g. Epocelin, on the recommendation of the company that produces it (Japan), is used in a daily dose of 0.5-2 g in 2-4 injections, in severe cases - up to 4 g per day.

Cefadizim (Modivid) is a broad-spectrum drug due to the presence of an iminomethoxy and aminothiazole group and a dihydrothiazine ring in the structure of the cephalosporin core. It is effective against non-positive and gram-negative microorganisms, including both aerobes and anaerobes (Staphylococcus aureus, pneumococcus, streptococcus, Neisseria, Escherichia coli, Proteus, Salmonella, Haemophilus influenzae). It is resistant to most beta-lactamases, is not metabolized, is excreted mainly through the kidneys, and is recommended for use in urology and pulmonology. Modivid significantly stimulates the immune system, increases the number of T-lymphocytes-hellers, as well as phagocytosis. The drug is ineffective against pseudomonas, mycoplasma, chlamydia.

The drug is administered intravenously or intramuscularly 2 times a day at a daily dose of 2-4 g.

Cefoperazone (cefobid) - is administered intravenously, intramuscularly every 8-12 hours, the average daily dose is 2-4 g, the maximum daily dose is 8 g.

Ceftazidime (kefadim, fortum) - is available in ampoules of 0.25, 0.5, 1 and 2 g. It is dissolved in water for injection. It is administered intravenously, intramuscularly at intervals of 8-12 hours. It is possible to prescribe 1 g of the drug every 8-12 hours. The average daily dose is 2 g, the maximum daily dose is 6 g.

Ceftazidime (Fortum) is well combined in one injection with metrogyl: 500 mg of Fortum in 1.5 ml of water for injection + 100 ml of 0.5% solution (500 mg) of metrogyl.

Fourth generation cephalosporins

Fourth-generation drugs are resistant to the action of β-lactamases, are characterized by a broad spectrum of antimicrobial action (gram-positive bacteria, non-negative bacteria, bacteroids), as well as antipseudomonal activity, but enterococci are resistant to them.

Moxalactom (moxam, latamocef) - has high activity against most gram-positive and gram-negative aerobes, anaerobes, Klebsiella, Escherichia coli, Pseudomonas aeruginosa, moderately active against Staphylococcus aureus. It is used intravenously, intramuscularly every 8 hours, the average daily dose is 2 g, the maximum daily dose is 12 g. Possible side effects are diarrhea, hypoprothrombinemia.

Cefoxitin (mefoxin) - is active primarily against bacteroids and related bacteria. It is less active against non-positive and gram-negative microorganisms. It is most often used for anaerobic infections intramuscularly or intravenously every 6-8 hours, 1-2 g.

Cefotetan is quite active against gram-positive and gram-negative microbes, inactive against enterococci. It is used intravenously, intramuscularly 2 g 2 times a day, the highest daily dose is 6 g.

Cefpirome (Keyten) - is characterized by a well-balanced activity against both gram-positive and gram-negative microorganisms. Cefpirome is the only cephalosporin antibiotic that has significant activity against enterococci. The drug significantly exceeds all third-generation cephalosporins in activity against staphylococci, enterobacteria, Klebsiella, Escherichia, is comparable to ceftazidime in activity against Pseudomonas aeruginosa, and has high activity against Haemophilus influenzae. Cefpirome is highly resistant to the main beta-lactamases, including broad-spectrum plasmid β-lactamases that inactivate cefazidime, cefotaxime, ceftriaxone and other third-generation cephalosporins.

Cefpirome is used for severe and extremely severe infections of various localizations in patients in intensive care units and resuscitation departments, for infectious and inflammatory processes that have developed against the background of neutropenia and immunosuppression, for septicemia, severe infections of the bronchopulmonary system and urinary tract.

The drug is used only intravenously by jet or drip.

The contents of the vial (1 or 2 g of cefpirome) are dissolved in 10 or 20 ml of water for injection, respectively, and the resulting solution is administered intravenously over 3-5 minutes. Drip administration into a vein is carried out as follows: the contents of the vial (1 or 2 g of cefpirome) are dissolved in 100 ml of isotonic sodium chloride solution or 5% glucose solution and administered intravenously over 30 minutes.

The drug is well tolerated, however, in rare cases allergic reactions, skin rashes, diarrhea, headache, drug fever, pseudomembranous colitis are possible.

First generation oral cephalosporins

Cephalexin (ceporex, keflex, oracef) - is available in capsules of 0.25 g, taken orally every 6 hours. The average daily dose is 1-2 g, the maximum daily dose is 4 g.

Cephradine (Anspor, Velocef) - is taken orally at intervals of 6 hours (according to some data - 12 hours). The average daily dose is 2 g, the maximum daily dose is 4 g.

Cefadroxil (Duracef) - is available in capsules of 0.2 g, taken orally at 12-hour intervals. The average daily dose is 2 g, the maximum daily dose is 4 g.

Second generation oral cephalosporins

Cefaclor (tseklor, panoral) - is available in capsules of 0.5 g, taken orally at intervals of 6-8 hours. For pneumonia, 1 capsule is prescribed 3 times a day, in severe cases - 2 capsules 3 times a day. The average daily dose of the drug is 2 g, the maximum daily dose is 4 g.

Cefuroxime axetil (Zinnat) - is available in tablets of 0.125; 0.25 and 0.5 g. It is used at 0.25-0.5 g 2 times a day. Cefuroxime axetil is a prodrug form, which after absorption is converted into active cefuroxime.

Loracarbef - taken orally at 0.4 g 2 times a day.

Third generation oral cephalosporins

Cefsulodin (monaspor, cefomonide) - is taken orally at intervals of 6-12 hours. The average daily dose is 2 g, the maximum daily dose is 6 g.

Ceftibuten - is taken orally at 0.4 g 2 times a day. It has pronounced activity against gram-negative bacteria and is resistant to beta-lactamases.

Cefpodoxime proxetil - taken orally at 0.2 g 2 times a day.

Cefetamet pivoxil - is taken orally at 0.5 g 2 times a day. Effective against pneumococcus, streptococcus, Haemophilus influenzae, Moraxella; ineffective against staphylococci, enterococci.

Cefixime (suprax, cefspan) - is used orally at 0.2 g 2 times a day. Pneumococci, streptococci, Haemophilus influenzae, Escherichia coli, Neisseria are highly sensitive to cefixime; enterococci, Pseudomonas aeruginosa, staphylococci, and Enterobacter are resistant.

Cephalosporins can cause the following side effects: cross-allergy with penicillins in 5-10% of patients;

• allergic reactions - urticaria, measles-like rash, fever, eosinophilia, serum sickness, anaphylactic shock;
• in rare cases - leukopenia, hypoprothrombinemia and bleeding;
• increased levels of transaminases in the blood; dyspepsia.

Monobactam group

Monobactams are a new class of antibiotics derived from Pseudomonas acidophilus and Chromobacterinum violaceum. Their structure is based on a simple beta-lactam ring, unlike related penicillins and cephalosporins, which are constructed from a beta-lactam ring conjugated with a thiazolidine ring, and for this reason the new compounds were called monobactams. They are exceptionally resistant to the action of β-lactamases produced by non-negative flora, but are destroyed by beta-lactamase produced by staphylococci and bacteroids.

Aztreonam (azactam) - the drug is active against a large number of gram-negative bacteria, including E. coli, Klebsiella, Proteus and Pseudomonas aeruginosa, may be active in case of infection with resistant microorganisms or hospital infections caused by them; however, the drug does not have significant activity against staphylococci, streptococci, pneumococci, bacteroids. It is administered intravenously, intramuscularly at intervals of 8 hours. The average daily dose is 3-6 g, the maximum daily dose is 8 g.

Carbapenem group

Imipenem-cilastin (tienam) is a broad-spectrum beta-lactam drug, consisting of two components: thienamycin antibiotic (carbapenem) and cilastin, a specific enzyme that inhibits the metabolism of imipenem in the kidneys and significantly increases its concentration in the urinary tract. The ratio of imipenem and cilastin in the drug is 1:1.

The drug has a very broad spectrum of antibacterial activity. It is effective against gram-negative flora (Enterobacter, Haemophilus influenzae, Klebsiella, Neisseria, Proteus, Pseudomonas, Salmonella, Yersinia, Acinetobacter, gram-positive flora (all staphylococci, streptococci, pneumococci), as well as against anaerobic flora. Imipenem has pronounced stability to the action of β-lactamases (penicillinases and cephalosporinases) produced by gram-positive and gram-negative bacteria. The drug is used in severe gram-positive and gram-negative infections caused by multidrug-resistant and hospital-acquired bacterial strains: sepsis, peritonitis, staphylococcal lung destruction, hospital-acquired pneumonia caused by Klebsiella, Acinetobacter, Enterobacter, Haemophilus influenzae, serratia, E. coli. Imipenem is especially effective in the presence of polymicrobial flora.

Aminoglycoside group

Aminoglycosides contain amino sugars in their molecules, linked by a glycosidic bond. The above-mentioned structural features of aminoglycosides explain the name of this group of antibiotics. Aminoglycosides have bactericidal properties, they act inside the cell of microorganisms, binding to ribosomes and disrupting the amino acid sequence in peptide chains (the resulting abnormal proteins are harmful to microorganisms). They can have varying degrees of nephrotoxic (in 17% of patients) and ototoxic effects (in 8% of patients). According to D. R. Lawrence, hearing loss occurs more often during treatment with amikacin, neomycin and kanamycin, vestibular toxicity is characteristic of streptomycin, gentamicin, tobramycin. Tinnitus can serve as a warning of damage to the auditory nerve. The first signs of vestibular involvement are headaches associated with movement, dizziness, nausea. Neomycin, gentamicin, amikacin are more nephrotoxic than tobramycin and netilmicin. The least toxic drug is netilmicin.

To prevent side effects of aminoglycosides, it is necessary to monitor the level of aminoglycosides in the blood serum and record an audiogram once a week. For early diagnosis of the nephrotoxic effect of aminoglycosides, it is recommended to determine the fractional excretion of sodium, N-acetyl-beta-D-glucosaminidase and beta2-microglobulin. Aminoglycosides should not be prescribed in case of impaired renal function and hearing. Aminoglycosides have a bactericidal effect, the severity of which depends on the concentration of the drug in the blood. In recent years, it has been suggested that a single administration of an aminoglycoside in a higher dose is quite effective due to increased bactericidal activity and an increase in the duration of the post-antibacterial effect, while the incidence of side effects decreases. According to Tulkens (1991), a single administration of netilmicin and amikacin was not inferior in effectiveness to 2-3-fold administration, but was less often accompanied by impaired renal function.

Aminoglycosides are broad-spectrum antibiotics: they affect gram-positive and gram-negative flora, but their high activity against most gram-negative bacteria is of greatest practical importance. They have a pronounced bactericidal effect on gram-negative aerobic bacteria (Pseudomonas, Enterobacter, Escherichia coli, Proteus, Klebsiella), but are less effective against Haemophilus influenzae.

The main indications for prescribing aminoglycosides are quite severe infections (in particular, hospital-acquired infections caused by non-negative bacteria (pneumonia, urinary tract infections, septicemia), for which they are the drugs of choice. In severe cases, aminoglycosides are combined with antipseudomonal penicillins or cephalosporins.

When treating with aminoglycosides, the development of microflora resistance to them is possible, which is due to the ability of microorganisms to produce specific enzymes (5 types of aminoglycoside acetyltransferases, 2 types of aminomycoside phosphate transferases, aminoglycoside nucleotidyl transferase), which inactivate aminoglycosides.

Aminoglycosides of the second and third generations have higher antibacterial activity, a broader antimicrobial spectrum and greater resistance to enzymes that inactivate aminoglycosides.

Resistance to aminoglycosides in microorganisms is partially cross-resistant. Microorganisms resistant to streptomycin and kanamycin are also resistant to monomycin, but are sensitive to neomycin and all other aminoglycosides.

Flora resistant to first-generation aminoglycosides is sensitive to gentamicin and third-generation aminoglycosides. Gentamicin-resistant strains are also resistant to monomycin and kanamycin, but are sensitive to third-generation aminoglycosides.

There are three generations of aminoglycosides.

First generation aminoglycosides

Of the first generation drugs, kanamycin is most widely used. Kanamycin and streptomycin are used as anti-tuberculosis agents, neomycin and monomycin are not used parenterally due to their high toxicity, they are prescribed orally. for intestinal infections. Streptomycin is available in 0.5 and 1 g vials and is administered intramuscularly every 12 hours. The average daily dose is 1 g, the maximum daily dose is 2 g. It is currently almost never used to treat pneumonia, but is used primarily for tuberculosis.

Kanamycin is available in 0.25 g tablets and in 0.5 and 1 g vials for intramuscular administration. Like streptomycin, it is used primarily for tuberculosis. It is administered intramuscularly at 12-hour intervals. The average daily dose of the drug is 1-1.5 g, the maximum daily dose is 2 g.

Monomycin is available in 0.25 g tablets, 0.25 and 0.5 g vials. It is administered intramuscularly at 8-hour intervals. The average daily dose is 0.25 g, the maximum daily dose is 0.75 g. It has a weak effect on pneumococci and is used primarily for intestinal infections.

Neomycin (colimicin, micirin) - is available in tablets of 0.1 and 0.25 g and vials of 0.5 g. It is one of the most active antibiotics that suppress intestinal bacterial flora in liver failure. It is used orally at 0.25 g 3 times a day orally or intramuscularly at 0.25 g 3 times a day.

Second generation aminoglycosides

The second generation of aminoglycosides is represented by gentamicin, which, unlike the first generation drugs, has high activity against Pseudomonas aeruginosa and acts on strains of microorganisms that have developed resistance to first generation aminoglycosides. The antimicrobial activity of gentamicin is higher than that of kanamycin.

Gentamicin (Garamycin) is available in ampoules of 2 ml of 4% solution, vials of 0.04 g of dry substance. It is used intramuscularly, in severe cases intravenously at intervals of 8 hours. The average daily dose is 2.4-3.2 mg / kg, the maximum daily dose is 5 mg / kg (this dose is prescribed for severe patient conditions). Usually used in a dose of 0.04-0.08 g intramuscularly 3 times a day. Gentamicin is active against aerobic gram-negative bacteria, E. coli, enterobacteria, pneumococci, Proteus, Pseudomonas aeruginosa, but is weakly active against streptococci, enterococci and is inactive in anaerobic infections. In the treatment of septicemia, gentamicin is combined with one of the beta-lactam antibiotics or antianaerobic drugs, such as metronidazole, or both.

Third generation aminoglycosides

The third generation of aminoglycosides suppresses Pseudomonas aeruginosa more strongly than gentamicin, and secondary resistance of flora to these drugs occurs much less frequently than to gentamicin.

Tobramycin (brulamycin, obracin) - is available in 2 ml ampoules as a ready-made solution (80 g of the drug). It is used intravenously, intramuscularly at intervals of 8 hours. The doses are the same as gentamicin. The average daily dose for pneumonia is 3 mg / kg, the maximum daily dose is 5 mg / kg

Sizomycin is available in ampoules of 1, 1.5 and 2 ml of 5% solution. It is administered intramuscularly at intervals of 6-8 hours, intravenous administration should be by drip in a 5% glucose solution. The average daily dose of the drug is 3 mg/kg. The maximum daily dose is 5 mg/kg.

Amikacin (amikin) - is available in 2 ml ampoules containing 100 or 500 mg of the drug, administered intravenously, intramuscularly at intervals of 8-12 hours. The average daily dose is 15 mg / kg, the maximum daily dose is 25 mg / kg. Amikacin is the most effective drug among third-generation aminoglycosides, unlike all other aminoglycosides, it is sensitive to only one inactivating enzyme, while the rest are at least five. Strains resistant to amikacin are resistant to all other aminoglycosides.

Netilmicin is a semisynthetic aminoglycoside, active against infection with some strains resistant to gentamicin and tobramycin, it is less oto- and nephrotoxic. It is administered intravenously, intramuscularly at intervals of 8 hours. The daily dose of the drug is 3-5 mg/kg.

In order of decreasing antimicrobial action, aminoglycosides are arranged as follows: amikacin - netilmicin - gentamicin - tobramycin - streptomycin - neomycin - kanamycin - monomycin.

Tetracycline group

Antibiotics of this group have a broad spectrum of bacteriostatic action. They affect protein synthesis by binding to ribosomes and stopping the access of complexes consisting of transport RNA with amino acids to complexes of messenger RNA with ribosomes. Tetracyclines accumulate inside the bacterial cell. By origin, they are divided into natural (tetracycline, oxytetracycline, chlortetracycline or biomycin) and semi-synthetic (metacycline, doxycycline, minocycline, morphocycline, rolitetracycline). Tetracyclines are active against almost all infections caused by gram-negative and gram-positive bacteria, with the exception of most strains of Proteus and Pseudomonas aeruginosa. If resistance of microflora develops during treatment with tetracyclines, it is of a complete cross-type (with the exception of minocycline), therefore all tetracyclines are prescribed for uniform indications. Tetracyclines can be used for many common infections, especially mixed ones, or in cases where treatment is started without identifying the pathogen, i.e. bronchitis and bronchopneumonia. Tetracyclines are especially effective for mycoplasma and chlamydia infections. In average therapeutic concentrations, tetracyclines are found in the lungs, liver, kidneys, spleen, uterus, tonsils, prostate gland, and accumulate in inflamed and tumor tissues. In combination with calcium, they are deposited in bone tissue and tooth enamel.

Natural tetracyclines

Tetracycline is available in tablets of 0.1 and 0.25 g, prescribed at intervals of 6 hours. The average daily dose is 1-2 g, the maximum daily dose is 2 g. It is administered intramuscularly at 0.1 g 3 times a day.

Oxytetracycline (terramycin) - is used internally, intramuscularly, intravenously. For oral administration, it is available in tablets of 0.25 g. The drug is used internally at intervals of 6 hours, the average daily dose is 1-1.5 g, the maximum daily dose is 2 g. Intramuscularly, the drug is administered at intervals of 8-12 hours, the average daily dose is 0.3 g, the maximum dose is 0.6 g. Intravenously, the drug is administered at intervals of 12 hours, the average daily dose is 0.5-1 g, the maximum is 2 g.

Chlortetracycline (biomycin, aureomycin) - is used internally, there are forms for intravenous administration. It is used internally at intervals of 6 hours, the average daily dose of the drug is 1-2 g, the maximum is 3 g. It is used intravenously at intervals of 12 hours, the average and maximum daily doses are 1 g.

Semi-synthetic tetracyclines

Metacycline (rondomycin) is available in capsules of 0.15 and 0.3 g, taken orally at intervals of 8-12 hours. The average daily dose is 0.6 g, the maximum is 1.2 g.

Doxycycline (vibramycin) is available in capsules of 0.5 and 0.1 g, in ampoules for intravenous administration of 0.1 g. It is taken orally at 0.1 g 2 times a day, in the following days - 0.1 g per day, in severe cases the daily dose on the first and subsequent days is 0.2 g.

For intravenous infusion, 0.1 g of vial powder is dissolved in 100-300 ml of isotonic sodium chloride solution and administered intravenously by drip over 30-60 minutes 2 times a day.

Minocycline (clinomycin) - is taken orally at 12-hour intervals. On the first day, the daily dose is 0.2 g, on subsequent days - 0.1 g, briefly the daily dose can be increased to 0.4 g.

Morphocycline is available in vials for intravenous administration of 0.1 and 0.15 g, administered intravenously at 12-hour intervals in a 5% glucose solution. The average daily dose of the drug is 0.3 g, the maximum daily dose is 0.45 g.

Rolitetracycline (velacycline, recoverin) - the drug is administered intramuscularly 1-2 times a day. The average daily dose is 0.25 g, the maximum daily dose is 0.5 g.

The frequency of side effects when using tetracyclines is 7-30%. Toxic complications caused by the catabolic action of tetracyclines predominate - hypotrophy, hypovitaminosis, liver damage, kidney damage, gastrointestinal ulcers, skin photosensitivity, diarrhea, nausea; complications associated with the suppression of saprophytes and the development of secondary infections (candidiasis, staphylococcal enterocolitis). Tetracyclines are not prescribed to children under 5-8 years of age.

When treating with tetracyclines, V. G. Kukes recommends taking the following into account:

• There is cross-allergy between them; patients with allergies to local anesthetics may react to oxytetracycline (often administered with lidocaine) and tetracycline hydrochloride for intramuscular injections;
• Tetracyclines may cause increased excretion of catecholamines in the urine;
• they cause an increase in the level of alkaline phosphatase, amylase, bilirubin, and residual nitrogen;
• It is recommended to take tetracyclines orally on an empty stomach or 3 hours after a meal, with 200 ml of water, which reduces the irritating effect on the wall of the esophagus and intestines and improves absorption.

Macrolide group

The drugs of this group contain a macrocyclic lactone ring in the molecule, linked to carbohydrate residues. These are mainly bacteriostatic antibiotics, but depending on the type of pathogen and concentration, they can exhibit a bactericidal effect. Their mechanism of action is similar to that of tetracyclines and is based on binding to ribosomes and preventing the access of the complex of transport RNA with amino acid to the complex of messenger RNA with ribosomes, which leads to the suppression of protein synthesis.

Non-positive cocci (pneumococcus, pyogenic streptococcus), mycoplasma, legionella, chlamydia, whooping cough bacillus Bordetella pertussis, and diphtheria bacillus are highly sensitive to macrolides.

Haemophilus influenzae and staphylococcus are moderately sensitive to macrolides; bacteroides, enterobacteria, and rickettsia are resistant.

The activity of macrolides against bacteria is related to the structure of the antibiotic. There are 14-membered macrolides (erythromycin, oleandomycin, flurithromycin, clarithromycin, megalomycin, dirithromycin), 15-membered (azithromycin, roxithromycin), 16-membered (spiramycin, josamycin, rosamycin, turimycin, myokamecin). 14-membered macrolides have higher bactericidal activity than 15-membered ones against streptococci and whooping cough bacilli. Clarithromycin has the greatest effect against streptococci, pneumococci, diphtheria bacilli, azithromycin is highly effective against Haemophilus influenzae.

Macrolides are highly effective in respiratory infections and pneumonia, as they penetrate well into the mucous membrane of the bronchopulmonary system, bronchial secretions and sputum.

Macrolides are effective against pathogens located intracellularly (in tissues, macrophages, leukocytes), which is especially important in the treatment of legionella and chlamydial infections, since these pathogens are located intracellularly. Resistance to macrolides can develop, so they are recommended for use as part of combination therapy in severe infections, in resistance to other antibacterial drugs, in allergic reactions or hypersensitivity to penicillins and cephalosporins, as well as in mycoplasma and chlamydial infections.

Erythromycin is available in tablets of 0.1 and 0.25 g, capsules of 0.1 and 0.2 g, vials for intramuscular and intravenous administration of 0.05, 0.1 and 0.2 g. It is administered orally, intravenously, and intramuscularly.

It is administered orally at intervals of 4-6 hours, the average daily dose is 1 g, the maximum daily dose is 2 g. It is administered intramuscularly and intravenously at intervals of 8-12 hours, the average daily dose is 0.6 g, the maximum is 1 g.

The drug, like other macrolides, exhibits its action more actively in an alkaline environment. There is evidence that in an alkaline environment, erythromycin turns into a broad-spectrum antibiotic that actively suppresses gram-negative bacteria that are highly resistant to many chemotherapeutic agents, in particular, Pseudomonas aeruginosa, Escherichia coli, Proteus, and Klebsiella. This can be used for urinary tract infections, biliary tract infections, and local surgical infections.

D. R. Lawrence recommends the use of erythromycin in the following cases:

• for mycoplasma pneumonia in children - the drug of choice, although tetracycline is preferable for the treatment of adults;
• for the treatment of patients with Legionella pneumonia as a first-line drug alone or in combination with rifampicin;
• for chlamydial infection, diphtheria (including carriage) and whooping cough;
• for gastroenteritis caused by campylobacter (erythromycin promotes the elimination of microorganisms from the body, although it does not necessarily reduce the duration of clinical manifestations);
• in patients infected with Pseudomonas aeruginosa, pneumococcus, or with an allergy to penicillin.

Erycycline is a mixture of erythromycin and tetracycline. It is available in capsules of 0.25 g, prescribed 1 capsule every 4-6 hours, the daily dose of the drug is 1.5-2 g.

Oleandomycin - is available in 0.25 g tablets. Take every 4-6 hours. The average daily dose is 1-1.5 g, the maximum daily dose is 2 g. There are forms for intravenous and intramuscular administration, the daily doses are the same.

Oletetrin (tetraolin) is a combination drug consisting of oleandomycin and tetracycline in a ratio of 1:2. It is available in capsules of 0.25 g and in vials of 0.25 g for intramuscular and intravenous administration. It is prescribed orally at 1-1.5 g per day in 4 doses at 6-hour intervals.

For intramuscular administration, the contents of the vial are dissolved in 2 ml of water or isotonic sodium chloride solution and 0.1 g of the drug is administered 3 times a day. For intravenous administration, a 1% solution is used (0.25 or 0.5 g of the drug is dissolved in 25 or 50 ml of isotonic sodium chloride solution or water for injection, respectively, and administered slowly). Intravenous drip infusion can be used. The average daily intravenous dose is 0.5 g 2 times a day, the maximum daily dose is 0.5 g 4 times a day.

In recent years, so-called "new" macrolides have appeared. Their characteristic feature is a wider spectrum of antibacterial action and stability in an acidic environment.

Azithromycin (Sumamed) - belongs to the antibiotics of the azamide group, close to macrolides, available in tablets of 125 and 500 mg, capsules of 250 mg. Unlike erythromycin, it is a bactericidal antibiotic with a wide spectrum of activity. It is highly effective against gram-positive microbes (pyogenic streptococci, staphylococci, including those producing beta-lactamases, the causative agent of diphtheria), moderately active against enterococci. Effective against gram-negative pathogens (Haemophilus influenzae, whooping cough, Escherichia coli, Shigella, Salmonella, Yersiniosis, Legionella, Helicobacter, Chlamydia, Mycoplasma), the causative agent of gonorrhea, spirochetes, many anaerobes, toxoplasma. Azithromycin is prescribed orally, usually on the first day they take 500 mg once, from the 2nd to the 5th day - 250 mg once a day. The duration of the course of treatment is 5 days. When treating acute urogenital infections, a single dose of 500 mg of azithromycin is sufficient.

Midecamycin (macropen) - is available in 0.4 g tablets, has a bacteriostatic effect. The spectrum of antimicrobial action is close to sumamed. It is used orally in a daily dose of 130 mg / kg of body weight (in 3-4 doses).

Iosamycin (josamycin, vilprafen) - available in tablets of 0.05 g; 0.15 g; 0.2 g; 0.25 g; 0.5 g. Bacteriostatic drug, antimicrobial spectrum close to the spectrum of azithromycin. Prescribed 0.2 g 3 times a day for 7-10 days.

Roxithromycin (rulid) is a macrolide antibiotic with bacteriostatic action, available in tablets of 150 and 300 mg, the antimicrobial spectrum is close to the spectrum of azithromycin, but the effect on Helicobacter pylori and whooping cough bacilli is weaker. Pseudomonas aeruginosa, Escherichia coli, Shigella, and Salmonella are resistant to roxithromycin. It is prescribed orally at 150 mg 2 times a day, in severe cases the dose may be increased by 2 times. The course of treatment lasts 7-10 days.

Spiramycin (rovamycin) - is available in tablets of 1.5 million IU and 3 million IU, as well as in suppositories containing 1.3 million IU (500 mg) and 1.9 million IU (750 mg) of the drug. The antimicrobial spectrum is close to the spectrum of action of azithromycin, but compared to other macrolides, it is less effective against chlamydia. Enterobacteria and pseudomonas are resistant to spiramycin. It is prescribed orally at 3-6 million IU 2-3 times a day.

Kitazycin is a bacteriostatic macrolide antibiotic, available in tablets of 0.2 g, capsules of 0.25 g, in ampoules of 0.2 g of the substance for intravenous administration. The spectrum of antimicrobial action is close to the spectrum of action of azithromycin. Prescribed at 0.2-0.4 g 3-4 times a day. In severe infectious and inflammatory processes, 0.2-0.4 g is administered intravenously 1-2 times a day. The drug is dissolved in 10-20 ml of a 5% glucose solution and administered intravenously slowly over 3-5 minutes.

Clarithromycin is a bacteriostatic macrolide antibiotic, available in tablets of 0.25 g and 0.5 g. The spectrum of antimicrobial action is close to that of azithromycin. The drug is considered the most effective against legionella. It is prescribed at 0.25 g 2 times a day, in severe cases of the disease the dose can be increased.

Dirithromycin - is available in 0.5 g tablets. When taken orally, dirithromycin undergoes non-enzymatic hydrolysis to erythromycylamine, which has an antimicrobial effect. The antibacterial effect is similar to that of erythromycin. It is prescribed orally at 0.5 g once a day.

Macrolides may cause side effects (not common):

• dyspepsia (nausea, vomiting, abdominal pain);
• diarrhea;
• skin allergic reactions.

There are also antifungal macrolides.

Amphotericin B is administered only intravenously by drip at intervals of 72 hours, the average daily dose is 0.25-1 mg/kg, the maximum daily dose is 1.5 mg/kg.

Flucytosine (ancoban) - is administered orally at 6-hour intervals. The average daily dose is 50-100 mg/kg, the maximum daily dose is 150 mg/kg.

Levomycetin group

Mechanism of action: inhibits protein synthesis in microorganisms, inhibiting the synthesis of the enzyme that transfers the peptide chain to a new amino acid on the ribosome. Levomycetin exhibits bacteriostatic activity, but has a bactericidal effect on most strains of Haemophilus influenzae, pneumococcus, and some types of Shigella. Levomycetin is active against non-positive, gram-negative, aerobic and anaerobic bacteria, mycoplasma, chlamydia, rickettsia, but Pseudomonas aeruginosa is resistant to it.

Levomycetin (chlorocid, chloramphenicol) is available in tablets of 0.25 and 0.5 g, extended-release tablets of 0.65 g, capsules of 6.25 g. It is taken orally at intervals of 6 hours, the average daily dose is 2 g, the maximum daily dose is 3 g.

Levomycetin succinate (chlorocid C) is a form for intravenous and intramuscular administration, available in 0.5 and 1 g vials. It is administered intravenously or intramuscularly at intervals of 8-12 hours, the average daily dose of the drug is 1.5-2 g, the maximum daily dose is 4 g.

Levomycetin group drugs may cause the following side effects: dyspeptic disorders, aplastic conditions of the bone marrow, thrombocytopenia, agranulocytosis. Levomycetin drugs are not prescribed to pregnant women and children.

Lincosamine group

Mechanism of action: lincosamines bind to ribosomes and inhibit protein synthesis like erythromycin and tetracycline, in therapeutic doses they have a bacteriostatic effect. The drugs of this group are effective against gram-positive bacteria, staphylococci, streptococci, pneumococci, diphtheria bacilli and some anaerobes, including the causative agents of gas gangrene and tetanus. The drugs are active against microorganisms, especially staphylococci (including those producing beta-lactamase), resistant to other antibiotics. They do not act on gram-negative bacteria, fungi, viruses.

Lincomycin (lincocin) - is available in capsules of 0.5 g, in ampoules of 1 ml with 0.3 g of the substance. It is prescribed orally, intravenously, intramuscularly. It is used orally at intervals of 6-8 hours, the average daily dose is 2 g, the maximum daily dose is 3 g.

It is used intravenously and intramuscularly at intervals of 8-12 hours, the average daily dose is 1-1.2 g, the maximum daily dose is 1.8 g. With rapid intravenous administration of the drug, especially in large doses, the development of collapse and respiratory failure has been described. Contraindicated in severe liver and kidney diseases.

Clindamycin (dalacin C) - is available in 0.15 g capsules and 2 ml ampoules with 0.3 g of the substance in one ampoule. It is used internally, intravenously, intramuscularly. The drug is a chlorinated derivative of lincomycin, has high antimicrobial activity (2-10 times more active against gram-positive staphylococci, mycoplasma, bacteroids) and is more easily absorbed from the intestine. In low concentrations it exhibits bacteriostatic, and in high concentrations - bactericidal properties.

It is taken orally at intervals of 6 hours, the average daily dose is 0.6 g, the maximum is 1.8 g. It is administered intravenously or intramuscularly at intervals of 6-12 hours, the average daily dose is 1.2 g, the maximum is 2.4 g.

Ansamycin group

The ansamycin group includes ansamycin and rifampicins.

Anzamycin is used orally in an average daily dose of 0.15-0.3 g.

Rifampicin (rifadin, benemycin) - kills bacteria by binding to DNA-dependent RNA polymerase and inhibiting RNA biosynthesis. It is active against tuberculosis mycobacteria, leprosy, and non-positive flora. It has a bactericidal effect, but does not affect non-negative bacteria.

Available in capsules of 0.05 and 0.15 g, taken orally 2 times a day. The average daily dose is 0.6 g, the highest daily dose is 1.2 g.

Rifamycin (rifocin) - the mechanism of action and spectrum of antimicrobial effect is the same as rifampicin. Available in ampoules of 1.5 ml (125 mg) and 3 ml (250 mg) for intramuscular administration and 10 ml (500 mg) for intravenous administration. It is administered intramuscularly at intervals of 8-12 hours, the average daily dose is 0.5-0.75 g, the maximum daily dose is 2 g. It is administered intravenously at intervals of 6-12 hours, the average daily dose is 0.5-1.5 g, the maximum daily dose is 1.5 g.

Rifametoprim (rifaprim) - is available in capsules containing 0.15 g rifampicin and 0.04 g trimethoprim. The daily dose is 0.6-0.9 g, taken in 2-3 doses for 10-12 days. Effective against mycoplasma and legionella pneumonia, as well as pulmonary tuberculosis.

The drugs rifampicin and rifocin can cause the following side effects: flu-like syndrome (malaise, headache, fever), hepatitis, thrombocytopenia, hemolytic syndrome, skin reactions (reddening of the skin, itching, rash), dyspeptic phenomena (diarrhea, abdominal pain, nausea, vomiting). When treated with rifampicin, urine, tears, sputum acquire an orange-red color.

Group of polypeptides

Polymyxins

They act primarily on gram-negative flora (intestinal, dysentery, typhoid bacilli, paratyphoid flora, pseudomonas, Pseudomonas aeruginosa), but do not affect Proteus, diphtheria, clostridia, or fungi.

Polymyxin B is available in 25 and 50 mg vials. It is used for sepsis, meningitis (administered intralumbarly), pneumonia, urinary tract infections caused by pseudomonas. For infections caused by other non-negative flora, polymyxin B is used only in case of polyresistance of the pathogen to other less toxic drugs. It is prescribed intravenously and intramuscularly. It is administered intravenously at intervals of 12 hours, the average daily dose is 2 mg/kg, the maximum daily dose is 150 mg/kg. It is administered intramuscularly at intervals of 6-8 hours, the average daily dose is 1.5-2.5 mg/kg, the maximum daily dose is 200 mg/kg.

Side effects of polymyxin: when administered parenterally, it has a nephrotoxic and neurotoxic effect, blockade of neuromuscular conduction and allergic reactions are possible.

Glycopeptides

Vancomycin - obtained from the fungus Streptomyces orientalis, acts on dividing microorganisms, suppressing the formation of the peptide glycan component of the cell membrane and DNA. It has a bactericidal effect on most pneumococci, non-positive cocci and bacteria (including beta-lactamase-forming staphylococci), addiction does not develop.

Vancomycin is used:

• for pneumonia and enterocolitis caused by clostridia or, less commonly, staphylococci (pseudomembranous colitis);
• for severe infections caused by staphylococci resistant to conventional antistaphylococcal antibiotics (multiple resistance), streptococci;
• for severe staphylococcal infections in individuals with allergies to penicillins and cephalosporins;
• in streptococcal endocarditis in patients with an allergy to penicillin. In this case, vancomycin is combined with some aminoglycoside antibiotic;
• in patients with gram-positive infection and allergy to β-lactams.

Vancomycin is administered intravenously at intervals of 8-12 hours, the average daily dose is 30 mg/kg, the maximum daily dose is 3 g. The main side effects: damage to the VIII pair of cranial nerves, nephrotoxic and allergic reactions, neutropenia.

Ristomycin (ristocetin, spontin) - has a bactericidal effect on gram-positive bacteria and staphylococci resistant to penicillin, tetracycline, chloramphenicol. It has no significant effect on gram-negative flora. It is administered only intravenously by drip in a 5% glucose solution or isotonic sodium chloride solution 2 times a day. The average daily dose is 1,000,000 IU, the maximum daily dose is 1,500,000 IU.

Teicoplanin (teicomycin A2) is a glycopeptide antibiotic similar to vancomycin. It is effective only against gram-positive bacteria. It is most active against Staphylococcus aureus, pneumococcus, and viridans streptococcus. It is capable of affecting staphylococci located inside neutrophils and macrophages. It is administered intramuscularly at 200 mg or 3-6 mg/kg of body weight once a day. Oto- and nephrotoxic effects are possible (rare).

Fusidin

Fusidin is an antibiotic active against non-negative and gram-positive cocci, many strains of listeria, clostridia, and mycobacteria are sensitive to it. It has a weak antiviral effect, but does not affect streptococci. Fusidin is recommended for use in case of infection with staphylococcus producing β-lactamase. In normal doses, it acts bacteriostatically, and when the dose is increased 3-4 times, it has a bactericidal effect. The mechanism of action is the suppression of protein synthesis in microorganisms.

Available in 0.25 g tablets. It is administered orally at intervals of 8 hours, the average daily dose is 1.5 g, the maximum daily dose is 3 g. There is also a form for intravenous administration. It is administered intravenously at intervals of 8-12 hours, the average daily dose is 1.5 g, the maximum daily dose is 2 g.

Novobiocin

Novobiocin is a bacteriostatic drug, intended primarily for the treatment of patients with persistent staphylococcal infection. The main spectrum of action: gram-positive bacteria (especially staphylococci, streptococci), meningococci. Most gram-negative bacteria are resistant to the action of Novobiocin. It is prescribed orally and intravenously. It is used orally at intervals of 6-12 hours, the average daily dose is 1 g, the maximum daily dose is 2 g. It is used intravenously at intervals of 12-24 hours, the average daily dose is 0.5 g, the maximum daily dose is 1 g.

Fosfomycin

Fosfomycin (phosphocin) is a broad-spectrum antibiotic that has a bactericidal effect on gram-positive and gram-negative bacteria and microorganisms resistant to other antibiotics. It is virtually non-toxic. It is actively concentrated in the kidneys. It is used primarily for inflammatory diseases of the urinary tract, but also for pneumonia, sepsis, pyelonephritis, and endocarditis. It is available in 1 and 4 g vials and is administered intravenously slowly by jet or, better, by drip at intervals of 6-8 hours. The average daily dose is 200 mg/kg (i.e. 2-4 g every 6-8 hours), the maximum daily dose is 16 g. 1 g of the drug is dissolved in 10 ml, 4 g in 100 ml of isotonic sodium chloride solution or 5% glucose solution.

Fluoroquinolone drugs

Currently, fluoroquinolones, along with cephalosporins, occupy one of the leading places in the treatment of bacterial infections. Fluoroquinolones have a bactericidal effect, which is due to the suppression of bacterial topoisomerase type 2 (DNA gyrase), which leads to a violation of genetic recombination, repair and DNA replication, and when using high doses of drugs - inhibition of DNA transcription. The consequence of these effects of fluoroquinolones is the death of bacteria. Fluoroquinolones are broad-spectrum antibacterial drugs. They are effective against gram-positive and gram-negative bacteria, including streptococci, staphylococci, pneumococci, pseudomonas, Haemophilus influenzae, anaerobic bacteria, campylobacter, chlamydia, mycoplasma, legionella, gonococcus. With respect to gram-negative bacteria, the effectiveness of fluoroquinolones is more pronounced compared to the effect on gram-positive flora. Fluoroquinolones are usually used to treat infectious and inflammatory processes in the bronchopulmonary and urinary systems due to their ability to penetrate well into these tissues.

Resistance to fluoroquinolones develops rarely and is associated with two reasons:

• structural changes in DNA gyrase, in particular topoisomer-A (for pefloxacin, ofloxacin, ciprofloxacin)
• changes in the permeability of the bacterial wall.

Strains of Serratia, Citrobacter, Escherichia coli, Pseudomonas, and Staphylococcus aureus resistant to fluoroquinolones have been described.

Ofloxacin (tarivid, zanocin, flobocin) - is available in tablets of 0.1 and 0.2 g, for parenteral administration - in vials containing 0.2 g of the drug. Most often, it is prescribed orally at 0.2 g 2 times a day, in case of severe recurrent infections, the dose can be doubled. In case of very severe infections, sequential (alternate) treatment is used, i.e. therapy begins with intravenous administration of 200-400 mg, and after the condition improves, they switch to oral administration. Intravenous ofloxacin is administered drip in 200 ml of isotonic sodium chloride solution or 5% glucose solution. The drug is well tolerated. Allergic reactions, skin rashes, dizziness, headache, nausea, vomiting, increased blood levels of alanine aminotransferase are possible.

High doses have a negative effect on articular cartilage and bone growth, so it is not recommended for children under 16 years of age, pregnant and breastfeeding women to take Tarivid.

Ciprofloxacin (Ciprobay) - the mechanism of action and spectrum of antimicrobial effect are similar to those of utarivid. Release forms: tablets of 0.25, 0.5 and 0.75 g, vials of 50 ml of infusion solution containing 100 mg of the drug; vials of 100 ml of infusion solution containing 200 mg of the drug; ampoules of 10 ml of infusion solution concentrate containing 100 mg of the drug.

It is used internally and intravenously 2 times a day; intravenously it can be administered slowly by jet or drip.

The average daily dose when taken orally is 1 g, when administered intravenously - 0.4-0.6 g. In case of severe infection, the oral dose can be increased to 0.5 g 3 times a day.

The same side effects as ofloxacin are possible.

Norfloxacin (nolitsin) - is available in 0.4 g tablets. It is prescribed orally before meals at 200-400 mg 2 times a day. Reduces the clearance of theophylline, H2-blockers, may increase the risk of side effects of these drugs. Simultaneous administration of non-steroidal anti-inflammatory drugs with norfloxacin may cause convulsions, hallucinations. Dyspeptic phenomena, arthralgia, photosensitivity, increased blood transaminase levels, abdominal pain are possible.

Enoxacin (Penetrax) is available in tablets of 0.2-0.4 g. It is prescribed orally at 0.2-0.4 g 2 times a day.

Pefloxacin (Abactal) - is available in 0.4 g tablets and in ampoules containing 0.4 g of the drug. It is prescribed orally at 0.2 g 2 times a day, in severe cases it is initially administered intravenously by drip (400 mg in 250 ml of 5% glucose solution), and then switched to oral administration.

Compared with other fluoroquinolones, it has high biliary excretion and reaches high concentrations in bile, and is widely used to treat intestinal infections and infectious and inflammatory diseases of the biliary tract. Headache, nausea, vomiting, abdominal pain, diarrhea, thirst, and photodermatitis are possible during treatment.

Lomefloxacin (Maxaquin) - is available in 0.4 g tablets. It has a pronounced bactericidal effect on most gram-negative, many non-positive (staphylococci, streptococci) and intracellular (chlamydia, mycoplasma, legionella, brucella) pathogens. Prescribed at 0.4 g once a day.

Sparfloxacin (zagam) is a new difluorinated quinolone, has a structure similar to ciprofloxacin, but contains two additional methyl groups and a second fluorine atom, which significantly increases the activity of this drug against gram-positive microorganisms, as well as intracellular anaerobic pathogens.

Fleroxacin is highly active against gram-negative bacteria, especially enterobacteria, and against gram-positive microorganisms, including staphylococci. Streptococci and anaerobes are less sensitive or resistant to fleroxacin. Combination with fosfomycin increases activity against pseudomonas. It is prescribed once a day orally at 0.2-0.4 g. Side effects are rare.

Quinoxoline derivatives

Quinoxidine is a synthetic bactericidal antibacterial drug, active against Proteus, Klebsiella (Friedlander's bacillus), Pseudomonas aeruginosa, Escherichia coli and dysentery bacilli, Salmonella, Staphylococcus, Clostridia. It is prescribed orally after meals, 0.25 g 3-4 times a day.

Side effects: dyspepsia, dizziness, headache, muscle cramps (most often calf cramps).

Dioxidine - the spectrum and bactericidal mechanism of action of dioxidine are similar to those of quinoxidine, but the drug is less toxic and can be administered intravenously. It is used for severe pneumonia, sepsis intravenously by drip at 15-30 ml of 0.5% solution in 5% glucose solution.

Nitrofuran drugs

The bacteriostatic effect of nitrofurans is provided by the aromatic nitro group. There is also evidence of a bactericidal effect. The spectrum of action is wide: the drugs suppress the activity of non-positive and non-negative bacteria, anaerobes, and many protozoa. The activity of nitrofurans is preserved in the presence of pus and other tissue decay products. Furazolidone and furagin are most widely used for pneumonia.

Furazolidone is prescribed orally at 0.15-0.3 g (1-2 tablets) 4 times a day.

Furagin is prescribed in tablets of 0.15 g 3-4 times a day or intravenously by drip of 300-500 ml of a 0.1% solution.

Solafur is a water-soluble preparation of furagin.

Imidazole drugs

Metronidazole (Trichopolum) - in anaerobic microorganisms (but not in aerobic ones, into which it also penetrates) is converted into an active form after the reduction of the nitro group, which binds to DNA and prevents the formation of nucleic acids.

The drug has a bactericidal effect. It is effective against anaerobic infections (the proportion of these microorganisms in the development of sepsis has increased significantly). Trichomonas, lamblia, amoebas, spirochetes, and clostridia are sensitive to metronidazole.

Prescribed in tablets of 0.25 g 4 times a day. For intravenous drip infusions, metrogyl - metronidazole in 100 ml (500 mg) vials is used.

Phytoncidal preparations

Chlorophyllipt is a phytoncide with a broad spectrum of antimicrobial action, has an antistaphylococcal effect. Obtained from eucalyptus leaves. It is used as a 1% alcohol solution of 30 drops 3 times a day for 2-3 weeks or intravenously by drip 2 ml of 0.25% solution in 38 ml of isotonic sodium chloride solution.

Sulfanilamide drugs

Sulfanilamides are derivatives of sulfanilic acid. All sulfanilamides have a single mechanism of action and a virtually identical antimicrobial spectrum. Sulfanilamides are competitors of para-aminobenzoic acid, which is necessary for most bacteria to synthesize folic acid, which is used by microbial cells to form nucleic acids. By the nature of their action, sulfanilamides are bacteriostatic drugs. The antimicrobial activity of sulfanilamides is determined by the degree of their affinity for microbial cell receptors, i.e., the ability to compete for receptors with para-aminobenzoic acid. Since most bacteria cannot utilize folic acid from the external environment, sulfanilamides are broad-spectrum drugs.

Spectrum of action of sulfonamides

Highly sensitive microorganisms:

• streptococcus, staphylococcus, pneumococcus, meningococcus, gonococcus, Escherichia coli, salmonella, cholera vibrio, anthrax bacillus, hemophilic bacteria;
• chlamydia: causative agents of trachoma, psittacosis, ornithosis, inguinal lymphogranulomatosis;
• protozoa: malaria plasmodium, toxoplasma;
• pathogenic fungi, actinomycetes, coccidia.

Moderately sensitive microorganisms:

• microbes: enterococci, viridans streptococcus, proteus, clostridia, pasteurella (including the causative agent of tularemia), brucellae, mycobacteria leprae;
• Protozoa: Leishmania.

Sulfonamide-resistant pathogens: salmonella (some species), pseudomonas, whooping cough and diphtheria bacilli, mycobacterium tuberculosis, spirochetes, leptospira, viruses.

Sulfonamides are divided into the following groups:

1. Short-acting drugs (T1/2 less than 10 hours): norsulfazole, etazole, sulfadimezine, sulfazoxazole. They are taken orally at 1 g every 4-6 hours, 1 g is often recommended for the first dose. Etazole is available in ampoules as a sodium salt for parenteral administration (10 ml of 10% solution in an ampoule), sodium salt of norsulfazole is also administered intravenously at 5-10 ml of 10% solution. In addition, these drugs and other short-acting sulfonamides are available in tablets of 0.5 g.
2. Medium-acting drugs (T1/2 10-24 h): sulfazine, sulfamethoxazole, sulfomoxal. Not widely used. Available in 0.5 g tablets. Adults are given 2 g for the first dose, then 1 g every 4 hours for 1-2 days, then 1 g every 6-8 hours.
3. Long-acting drugs (T1/2 24-48 h): sulfapyridazine, sulfadimethoxine, sulfamonomethoxine. Available in 0.5 g tablets. Prescribed to adults on the first day at 1-2 g depending on the severity of the disease, the next day give 0.5 or 1 g once a day and spend the entire course at this maintenance dose. The average duration of the course of treatment is 5-7 days.
4. Ultra-long-acting drugs (T _1/2 more than 48 hours): sulfalen, sulfadoxine. Available in 0.2 g tablets. Sulfalen is prescribed orally daily or once every 7-10 days. It is prescribed daily for acute or rapidly progressing infections, once every 7-10 days for chronic, long-term infections. When taken daily, adults are prescribed 1 g on the 1st day, then 0.2 g per day, taken 30 minutes before meals.
5. Local action drugs that are poorly absorbed in the gastrointestinal tract: sulgin, phthalazole, phthazin, disulformin, salazosulfapyridine, salazopyridazine, salazodimethoxin. They are used for intestinal infections, but are not prescribed for pneumonia.

A combination of sulfonamides with the antifolic drug trimethoprim is highly effective. Trimethoprim enhances the action of sulfonamides by disrupting the reduction of trihydrofolic acid to tetrahydrofolic acid, which is responsible for protein metabolism and division of microbial cells. The combination of sulfonamides with trimethoprim provides a significant increase in the degree and spectrum of antimicrobial activity.

The following drugs containing sulfonamides in combination with trimethoprim are produced:

• Biseptol-120 - contains 100 mg sulfamethoxazole and 20 mg trimethoprim.
• Biseptol-480 - contains 400 mg sulfamethoxazole and 80 mg trimethoprim;
• Biseptol for intravenous infusions, 10 ml;
• proteseptil - contains sulfadimezine and trimethoprim in the same doses as biseptol;
• sulfatene - a combination of 0.25 g of sulfamonomethoxine with 0.1 g of trimethoprim.

The most widely used is Biseptol, which, unlike other sulfonamides, has not only a bacteriostatic but also a bactericidal effect. Biseptol is taken once a day at 0.48 g (1-2 tablets per dose).

Side effects of sulfonamides:

• crystallization of acetylated metabolites of sulfonamides in the kidneys and urinary tract;
• alkalization of urine increases the ionization of sulfonamides, which are weak acids; in ionized form, these drugs dissolve much better in water and urine;
• alkalization of urine reduces the likelihood of crystalluria, helps maintain high concentrations of sulfonamides in urine. To ensure a stable alkaline reaction of urine, it is enough to prescribe soda at 5-10 g per day. Crystalluria caused by sulfonamides can be asymptomatic or cause renal colic, hematuria, oliguria and even anuria;
• allergic reactions: skin rashes, exfoliative dermatitis, leukopenia;
• dyspeptic reactions: nausea, vomiting, diarrhea; in newborns and infants, sulfonamides can cause methemoglobinemia due to oxidation of fetal hemoglobin, accompanied by cyanosis;
• in case of hyperbilirubinemia, the use of sulfonamides is dangerous, since they displace bilirubin from its protein binding and promote the manifestation of its toxic effect;
• When using Biseptol, a picture of folic acid deficiency (macrocytic anemia, gastrointestinal tract damage) may develop; to eliminate this side effect, it is necessary to take folic acid. Currently, sulfonamides are rarely used, mainly in cases of intolerance to antibiotics or resistance of microflora to them.

Combined administration of antibacterial drugs

Synergism is observed when combining the following drugs:

Penicillins	+ Aminoglycosides, cephalosporins
Penicillins (penicillinase-resistant)	+ Penicillins (penicillinase-unstable)
Cephalosporins (except cephaloridine)	+ Aminoglycosides
Macrolides	+ Tetracyclines
Levomycetin	+ Macrolides
Tetracycline, macrolides, lincomycin	+ Sulfonamides
Tetracyclines, lincomycin, nystatin	+ Nitrofurans
Tetracyclines, nystatin	+ Oxyquinolines

Thus, synergism of action is observed when combining bactericidal antibiotics, when combining two bacteriostatic antibacterial drugs. Antagonism is observed when combining bactericidal and bacteriostatic drugs.

Combined administration of antibiotics is performed in severe and complicated cases of pneumonia (pneumonia substitution, pleural empyema), when monotherapy may be ineffective.

Selection of antibiotics in different clinical situations

Clinical situation	Probable causative agent	1st line antibiotic	Alternative drug
Primary lobar pneumonia	Pneumococcus	Penicillin	Erythromycin and other macrolides, azithromycin, cephalosporins
Primary atypical pneumonia	Mycoplasma, Legionella, Chlamydia	Erythromycin, semisynthetic macrolides, erythromycin	Fluoroquinolones
Pneumonia against the background of chronic bronchitis	Haemophilus influenzae, streptococci	Ampicillin, macrolides, erythromycin	Leaomycetin, fluoroquinolones, cephaloslorins
Pneumonia against the background of influenza	Staphylococcus, pneumococcus, hemophilus influenzae	Ampiox, penicillins with beta-lactamase inhibitors	Fluoroquinolones, cephaloslorins
Aspiration pneumonia	Enterobacteria, anaerobes	Aminoglycosides + metronidazole	Cephaloslorins, fluoroquinolones
Pneumonia in the context of artificial ventilation of the lungs	Enterobacteria, Pseudomonas aeruginosa	Aminoglycosides	Imipenem
Pneumonia in immunocompromised individuals	Enterobacteria, Staphylococcus, Saprophytes	Penicillins with beta-lactamase inhibitors, ampiox, aminoglycosides	Cephaloslorins, fluoroquinolones

Features of antibacterial therapy of atypical and hospital-acquired (nosocomial) pneumonia

Atypical pneumonias are pneumonias caused by mycoplasma, chlamydia, legionella, and characterized by certain clinical manifestations that differ from typical community-acquired pneumonia. Legionella causes pneumonia in 6.4%, chlamydia - in 6.1% and mycoplasma - in 2% of cases. Atypical pneumonias are characterized by the intracellular location of the pathogen. In this regard, for the treatment of "atypical" pneumonia, antibacterial drugs should be used that penetrate well into the cell and create high concentrations there. These are macrolides (erythromycin and new macrolides, in particular, azithromycin, roxithromycin, etc.), tetracyclines, rifampicin, fluoroquinolones.

Hospital-acquired nosocomial pneumonia is pneumonia that develops in a hospital, provided that during the first two days of hospital stay there were no clinical or radiological signs of pneumonia.

Hospital-acquired pneumonia differs from community-acquired pneumonia in that it is more often caused by gram-negative flora: Pseudomonas aeruginosa, Haemophilus influenzae, Legionella, mycoplasma, chlamydia, is more severe and more often results in death.

About half of all cases of nosocomial pneumonia develop in intensive care units and postoperative departments. Intubation with mechanical ventilation increases the incidence of hospital-acquired infection by 10-12 times. In 50% of patients on mechanical ventilation, pseudomonas is isolated, in 30% - acinetobacter, in 25% - klebsiella. Less common pathogens of nosocomial pneumonia are Escherichia coli, Staphylococcus aureus, Serratia, and Citrobacter.

Hospital pneumonia also includes aspiration pneumonia. They are most often found in alcoholics, in people with cerebrovascular accidents, in cases of poisoning, chest trauma. Aspiration pneumonia is almost always caused by gram-negative flora and anaerobes.

Broad-spectrum antibiotics (third-generation cephalosporins, ureidopenicillins, monobactams, aminoglycosides), fluoroquinolones are used to treat nosocomial pneumonia. In severe cases of nosocomial pneumonia, first-line drugs are considered to be a combination of aminoglycosides with third-generation cephalosporins or monobactams (aztreonam). If there is no effect, second-line drugs are used - fluoroquinolones, imipenem is also effective.

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