Group of fluoroquinolones. We explain, warn, advise

Dear pharmaceutical workers, hello!

Recently we looked at the most popular groups of antibiotics.

Today I would like to dwell on another group of extremely popular antibacterial agents. I'm talking about fluoroquinolones.

They are not antibiotics because they have no natural analogues. But in terms of efficiency they are in no way inferior.

You don't have to read any further if you quickly answer the questions:

• How many generations of fluoroquinolones are currently on the market?
• Name at least one drug from each generation of this group.
• How do generations differ from each other?
• Which fluoroquinolones are used primarily for genitourinary tract infections?
• Name a rare side effect that is caused by drugs in this group.
• At what age can fluoroquinolones be used and why?

So how? Did you manage?

If not, let's continue the conversation.

From the history of fluoroquinolones

The “parents” of fluoroquinolones are quinolones - nalidixic acid (Negram, Nevigramon), pipemidic acid (Palin), etc.

I'm sure you can tell when they are used.

Did you name it?

Right. Mainly for urinary tract infections. Quinolones are essentially uroseptics, i.e. drugs that free the bladder, kidneys, and ureters from bacterial invaders.

Recently, these drugs have been prescribed less and less often, since much more effective drugs have appeared on the market.

Quinolones were synthesized by accident during the study of an antimalarial drug called Chloroquine.

A few years after their discovery, one of the scientists came up with the idea of ​​adding a fluorine atom to the quinolone formula and seeing what would happen. What has emerged is a completely new group of antibacterial agents, which is comparable in effectiveness to cephalosporins.

Group of fluoroquinolones. Features of generations

In some publications, quinolones are considered together with fluoroquinolones and are classified as their first generation.

It turns out to be some kind of rubbish: quinolones are the 1st generation of fluoroquinolones.

But the group turned out to be completely different, with different characteristics and indications!

So I will speak as common sense tells me.

Today there are 3 generations of fluoroquinolones:

Generations of fluoroquinolones differ from each other in their spectrum of antibacterial activity.

Each new generation is superior in some way to the previous one.

The 1st generation is called “Gram-negative” because drugs belonging to this generation act on a wide range of Gram-negative bacteria. And of the gram-positive ones, only a small handful: several varieties of staphylococcus, listeria, corynebacterium, tuberculosis bacillus.

Let me remind you of gram-negative bacteria: Pseudomonas aeruginosa, Gonococcus (the causative agent of gonorrhea), meningococcus (the causative agent of purulent meningitis), Escherichia coli, Salmonella, Shigella, Proteus, Klebsiella, Enterobacter, Haemophilus influenzae, etc.

1st generation drugs can be divided into 2 groups:

Systemic: Ciprofloxacin, Lomefloxacin and Ofloxacin. They penetrate various organs and tissues, therefore they are used for infections of various locations: respiratory tract, ear, eye, paranasal sinuses, genitourinary tract, gastrointestinal tract, skin, bones, etc.

Uroseptics: Norfloxacin and Pefloxacin. These drugs create high concentrations in the urine, so they are most often used for infections of the genitourinary system.

But drugs of this generation have little effect on pneumococcus, chlamydia, mycoplasma, and anaerobes.

Norfloxacin is also included in eye and ear drops called Normax.

The 2nd generation is called “respiratory”, since the drugs related to it act not only on the same pathogens as the 1st generation, but also on most pathogens of respiratory tract infections (pneumococcus, Mycoplasma pneumoniae, etc.).

They deal well with the same enemies of the people as the 1st generation, but also with pneumococci, chlamydia, and mycoplasmas.

I will call the 3rd generation “the storm of anaerobes.”

While I was collecting material for the article, I met several representatives of this generation, but did not see them in the assortment of pharmacies. I don’t see any point in talking about “dead souls”. So I name the most popular: Moxifloxacin (trade name Avelox).

The drugs, or rather the drug, of the third generation of fluoroquinolones act on the same pathogens as the previous two, plus they are able to destroy anaerobic bacteria. Do you remember who they are?

These are unpretentious microbes that, unlike their intelligent brothers, do not need oxygen to live a full life.

They cause severe infections. Their toxins are extremely aggressive, capable of affecting vital organs and causing peritonitis, abscesses of internal organs, sepsis, osteomyelitis and other serious diseases.

Anaerobic bacteria are also the culprits of tetanus, gas gangrene, botulism, and foodborne diseases.

Thus, from generation to generation the spectrum of antibacterial activity of fluoroquinolones expands.

general characteristics

Fluoroquinolones are the name of a class of quinolone medications that exhibit antimicrobial properties. Their main purpose is etiotropic therapy of diseases of bacterial etiology. Medicines in this group have high bactericidal activity, which makes it possible to use them to treat a wide range of pathologies.

Fluorinated quinolones are classified as antibacterial agents of the latest generation.

Fluoroquinolones are chemically synthesized derivatives of quinolone.

This class of compounds is classified as a separate category of antibacterial agents, since it differs from antibiotics in several ways:

1. Origin of active ingredients
   . A distinctive feature of the group is its completely artificial origin and the absence of natural analogues.
2. Structural structure
   . The chemical structure of the derivatives is represented by a quinolone crystal lattice, which includes fluorine atoms and a piperazine ring.

Depending on the number of additional atoms, mono-, di- and trifluoroquinolones are distinguished. The introduction of several atoms into the structure (in complex with piperazine) made it possible to synthesize substances with high bioavailability.

Mechanism of action

The pharmacology of fluorinated quinolones is aimed at reducing the population of pathogenic bacterial cultures. Active substances penetrate the structure of the cell membrane and inhibit enzymes necessary for the development of bacteria. The mechanism of action depends on the structural structure of the membranes of pathogens and is aimed at suppressing DNA synthesis of microorganisms. Blocking topoisomerase II makes it possible to interrupt the formation and division of gram-negative bacteria, and disruption of RNA transcription when inhibiting topoisomerase IV leads to the destruction of gram-positive microbes.

Advantages of the fluoroquinolones group

You have probably noticed that many doctors love drugs from this group, which is why they are prescribed quite often.

What good did they find in them?

Let's list their advantages.

Fluoroquinolones:

1. They have a wide spectrum of action.
2. Penetrates deeply into various tissues.
3. They have a long half-life, so they can be used 1-2 times a day.
4. They are well absorbed from the gastrointestinal tract, so they are available in oral forms, which is more convenient and enjoyable for many patients.
5. Highly effective.
6. Well tolerated.

Indications for the use of fluoroquinolones

Fluoroquinolones have a wide, I would even say the widest, range of indications:

• Diseases of the upper and lower respiratory tract.
• Urinary tract and prostate infections: cystitis, urethritis, pyelonephritis, prostatitis. Norfloxacin and pefloxacin work especially well against them.
• Gonorrhea, chlamydia, mycoplasmosis.
• Intra-abdominal infections (peritonitis, cholecystitis, etc.).
• Intestinal infections (salmonellosis, dysentery, cholera, etc.).
• Infections of the skin, soft tissues, bones and joints.
• Sepsis.
• Meningitis.
• Tuberculosis.
• Infections of the eyes, outer ear (norfloxacin).

The choice of fluoroquinolone drug depends on the type and severity of the disease, its duration, the type of pathogen and the effectiveness of previously used drugs.

Each drug has its own advantages. For example:

Ciprofloxacin is the most active of the fluoroquinolones against gram-negative bacteria. It is superior to its “colleagues” in its effect on Pseudomonas aeruginosa. Used in combination therapy of drug-resistant forms of tuberculosis.

Ofloxacin is the most active of the 1st generation against pneumococci and chlamydia, but weaker than the 2nd and 3rd generation drugs.

Norfloxacin and pefloxacin are especially good for urinary tract and prostate infections.

Pefloxacin, in addition, penetrates the blood-brain barrier better than other fluoroquinolones, therefore it is used for meningitis (for this there is a concentrate form for intravenous administration).

Sparfloxacin is superior to other drugs in this group in terms of duration of action. Apply once a day.

Levofloxacin is an isomer of ofloxacin, 2 times more active and better tolerated.

Moxifloxacin is the most active of the entire group against pneumococci, chlamydia, mycoplasmas, and anaerobes. It can be used empirically (that is, blindly, without culturing bacteria) for severe infections of various locations.

RESPIRATORY TRACT DISEASES

Preferanskaya Nina Germanovna St. Lecturer at the Department of Pharmacology, MMA named after. THEM. Sechenov

Previous articles (MA No. 11-12) examined the drugs of choice used for acute inflammation of viral origin.

This material provides readers with a description of the main medications used for purulent-inflammatory diseases of the respiratory tract of bacterial origin. Antibacterial drugs have no effect on viruses and cannot be used for viral diseases such as influenza, ARVI, etc.

Bacterial pathogens are characterized by great diversity and variability in species composition. The most common causative agents of respiratory tract infections are gram-positive cocci: staphylococci, streptococci, pneumococci. Other pathogens include: gram-negative bacteria, Haemophilus influenzae, mycoplasma, chlamydia and anaerobes. Microorganisms cause respiratory tract infections of any location - these are sinusitis, frontal sinusitis, sinusitis, pharyngitis, tracheitis, tonsillitis, tonsillitis, bronchitis, pleurisy, pneumonia, etc. The causative agents of respiratory tract infections differ in different natural sensitivity to antibacterial drugs; In addition, some of them become drug resistant. A rational choice of drug can only be made by the attending physician. The pharmacist can, only if the required drug is not available in the pharmacy, advise the patient to replace it. Select a synonym for an adequate substitute or a similar drug from the same pharmacological group that has the same pharmacological characteristics. Due to the fact that the range of antibacterial drugs is constantly updated and more effective drugs with specific activity appear, the pharmacist may recommend that patients consult with their doctor about the use of a new, more effective drug that has recently arrived at the pharmacy.

For bacterial infections of the respiratory tract, various antibacterial drugs - antibiotics, sulfonamides, fluoroquinolones and drugs of other groups.

Among the antibiotics , the following subgroups are mainly used: penicillins, cephalosporins, aminoglycosides, tetracyclines and macrolides.

Penicillin antibiotics are used in the treatment of diseases caused by microorganisms sensitive to it - acute and chronic pneumonia, pleural empyema, sore throat, and in the treatment of purulent-inflammatory diseases in the ear, nose and throat clinic. Benzylpenicillin , an antibiotic from the group of biosynthetic penicillins, is active against gram-positive microorganisms (Staphylococcus spp., Streptococcus spp.), as well as against Actinomycetaceae. are resistant to benzylpenicillin , since this enzyme destroys the antibiotic molecule. Benzylpenicillin is well absorbed when administered parenterally, does not have a cumulative effect, and is quickly excreted from the body in the urine. When administered intramuscularly, maximum concentrations of the drug in the blood are created after 30–60 minutes; after 3–4 hours, traces of the antibiotic are detected in the blood. The level of concentrations and duration of circulation of benzylpenicillin in the blood depends on the size of the administered dose. The antibiotic penetrates well into body tissues and fluids. 1 bottle contains 600 mg of benzylpenicillin sodium salt for injection, which corresponds to 1,000,000 IU.

A solution of the drug for intramuscular administration is prepared immediately before administration by adding 1–3 ml of water for injection or isotonic sodium chloride solution 0.9% or 0.5% novocaine solution to the contents of the bottle. Currently, most strains of staphylococci are resistant to benzylpenicillin.

For infectious and inflammatory diseases caused by microorganisms sensitive to this drug: infections of the ear, throat, nose, oral cavity, bronchopulmonary infections, ampicillin trihydrate . The dose of the drug is set individually, depending on the severity and localization of the infection, as well as the sensitivity of the pathogen to it. Orally, adults and children over 10 years of age are prescribed 250 mg - 500 mg every 6 hours. The daily dose is 2–3 g. If necessary, the dose can be doubled. Dosage form : capsules, suspension 250 mg. Amoxicillin also has a wide spectrum of action . Food does not affect the bioavailability of the drug; when taken orally, it is well absorbed and creates therapeutic concentrations in the tissues of the bronchopulmonary system. Amoxicillin has higher activity against streptococci and pneumococci compared to ampicillin. However, both drugs are destroyed by β-lactamases and have no effect on penicillin-resistant staphylococci and gram-negative bacteria. For the treatment of uncomplicated forms of acute otitis media, the drug of choice is amoxicillin orally for 7–10 days. Amoxicillin for oral use - flemoxin solutab is characterized by the highest frequency of achieving eradication of S. pneumoniae (including penicillin-resistant strains). Therefore, recently, not only antibiotics resistant to the action of β-lactamases, but also compounds that irreversibly inhibit these enzymes have been obtained. These compounds have a high affinity for type II-V β-lactamases and form a stable complex with them, preventing the enzymatic degradation of the antibiotic. The antibiotic inhibits transpeptidase of peptidoglycan, an essential cell wall protein during division and growth, causing lysis of microorganisms. When they are combined together, antimicrobial activity and pharmacotherapeutic effectiveness increase. Of the existing inhibitor-protected penicillins, they are used for respiratory tract infections: amoxicillin + clavulanic acid and ampicillin + sulbactam.

The combined drug amoxicillin + clavulanic acid is produced under the trade names - Amoxiclav (Slovenia), Augmentin (Great Britain), Medoclav (Cyprus), Ranclave (India); Amoxiclav is available in the form of tablets of 375 mg/625 mg, suspension 156 mg/5 ml, suspension forte 312 mg/5 ml and powder for the preparation of injection solution in bottles of 0.6 g, 1.2 g. Children from 3 months to 1 year are prescribed 1/ 2 dosed spoons of suspension every 8 hours, children from 1 year to 7 years 1 dose. spoon (5 ml) of suspension every 8 hours, adults and children over 14 years old, 5 or 10 ml of suspension every 8 hours or 375 mg 3 times a day. The combined drug ampicillin + sulbactam is produced under the trade names Sultamicillin (USA) and Unasin (USA, Italy, Turkey), Sulacillin and Sultasin (Russia). Used for infections of the respiratory tract and ENT organs (bronchitis, pneumonia, tonsillitis, otitis media, sinusitis). The drug has no effect on oxallin-resistant staphylococci. The action of Sultamicillin develops 15-20 minutes after administration and lasts 8 hours. Administered orally, for adults - 375-700 mg 2 times a day; children - 25-50 mg/kg/day in two doses. Parenterally (IV, IM) from 1.5 g to 12 g every 6-12 hours a day, for children 150 mg/kg/day.

Penicillin antibiotics are well tolerated and side effects are mild. As a rule, these are allergic skin rashes and various dyspeptic manifestations (nausea, vomiting, diarrhea). If undesirable effects occur, the drug should be discontinued.

Cephalosporins are bactericidal antibiotics with a wide spectrum of antimicrobial action, incl. for penicillin-forming staphylococci, enterobacteria. The group of cephalosporins includes drugs derived from 7-aminocephalosporic acid. They are divided into IV generation, and according to application - into drugs for parenteral and oral administration.

All cephalosporins are characterized by a single mechanism of action, but individual representatives differ significantly in pharmacokinetic parameters, severity of antimicrobial action and stability to beta-lactamases.

In case of allergic reactions to penicillin, cephalosporins are the first-line reserve antibiotics, however, cross-allergic sensitivity is observed in 5-10% of patients.

1st generation cephalosporins have a narrow spectrum of action, most active against gram-positive bacteria and a low level of activity against gram-negative bacteria. The first and most widely used cephalosporin is cephalothin. The main indication for its use is infections caused by staphylococci. Cefalotin is superior to penicillin drugs for moderate respiratory tract infections and infections of other localizations. Cefalotin is superior to the oxacillin group in its ability to penetrate the lymph nodes. Cephalexin - used for oral administration. When administered orally, it is quickly and completely absorbed (regardless of food intake). The maximum concentration is reached after 1–1.5 hours. The spectrum of action is close to cephalothin, but the effectiveness of cephalothin administered parenterally is superior to cephalexin. Cefazolin is resistant to beta-lactamases of microorganisms and has a broad spectrum of action against gram-positive microorganisms. It is destroyed in the gastrointestinal tract, when administered intramuscularly or intravenously, it creates high concentrations in the blood, penetrates various organs and tissues and is well tolerated. The dosage regimen and duration of drug administration are determined individually depending on the sensitivity of the pathogen and the severity of the infection.

, 2nd generation cephalosporins have a wider spectrum of action and are active not only against gram-positive, but also gram-negative bacteria. This group includes: Cefamandol (Mandokef) and Cefuroxime (Zinacef, Ketocef), etc. For oral use of 2nd generation cephalosporins, Cefaclor (Alfacet), Cefuroxime axetil (Zinnat) are used. The main representatives of 2nd generation cephalosporins are indicated for the treatment of the upper and lower respiratory tract. Cefamandole is highly effective against infections caused by Haemophilus influenzae. It can be combined with penicillins and aminoglycosides. Cefuroxime, unlike cefaclor, has a higher level of activity against streptococci and staphylococci. Pneumococci exhibit cross-resistance to 2nd generation cephalosporins.

3rd generation cephalosporins are highly active against most gram-negative bacteria, including those resistant to other antibiotics. They are active against streptococci, less active against staphylococci, and are highly resistant to beta-lactamases. Some 3rd generation cephalosporins are active against Pseudomonas aeruginosa (Cefoperazone, Ceftazidime, Ceftriaxone). This group includes many antibiotics, some of which actually have significant clinical advantages: Cefotaxime (Claforan), Cceftriaxone (Azaran, Longocef, Rocefin, Cefaxone), Ceftazidime (Fortum, Tizim), Ccefoperazone (Cefobid). For oral use, Cefixime (Suprax, Cefspan) is used. Cefotaxime (Claforan) is the most important representative of the 3rd generation cephalosporins. It is characterized by high antimicrobial activity, a wide spectrum of action, including viridans streptococci, pneumococci, anaerobic bacteria, enterobacteria, Klebsiella, Pseudomonas aeruginosa, Proteus. In the body, up to 30% of the antibiotic is inactivated, which explains the sometimes observed discrepancy between high activity in vitro and effectiveness in the clinic. Indications for use are infections of the upper and lower respiratory tract (acute sinusitis, bronchitis, pneumonia).

Ceftriaxone (Rocefin), identical in antimicrobial activity, but differs from cefotaxime in the duration of concentrations achieved in the patient’s body (8 hours or more after a single administration), which allows it to be administered 1–2 times a day. The drug is highly stable during storage; 40–60% of the antibiotic is excreted in bile and urine.

Ceftazidime (Fortum) and Cefoperazone (Cefobid) are similar in their antimicrobial properties to other 3rd generation drugs. They are characterized by significantly less activity against streptococci. Like all cephalosporins, they are bactericidal. Used for respiratory infections.

4th generation cephalosporins Cefepime (Maxipim), Cefpirome are close to 3rd generation cephalosporins in activity against gram-negative bacteria, but have an increased ability to penetrate their outer membrane. In addition, they are active against some gram-positive microorganisms. They are more highly resistant to hydrolysis by beta-lactamases and have an immunostimulating effect. They are used in the same cases as 3rd generation drugs, especially indicated for infections in patients with weakened immune systems.

As a rule, cephalosporins are well tolerated, their allergenic effect is relatively weak. Side effects when using cephalosporins: allergic reactions, leukocytopenia and thrombocytopenia, pain at the site of intramuscular injection. Overdose of cephaloridine (and sometimes cephalothin) and their combination with potentially nephrotoxic substances can lead to kidney damage. Gastrointestinal disorders following oral administration are rare and transient. With the simultaneous administration of cephalosporins and alcohol, Antabuse-like (Teturam-like) reactions are observed.

Aminoglycoside antibiotics - all drugs in this group are nephrotoxic and have a toxic effect on the auditory nerve (ototoxicity). Given the side effects of these antibiotics, they are rarely prescribed and used for these diseases.

Gentamicin is the main and most widely used aminoglycoside drug; it has a broad spectrum of action, inhibiting the growth of most gram-positive and gram-negative bacteria. The most important is its activity against staphylococci resistant to benzylpenicillin. Resistance of microorganisms to Gentamicin develops slowly. The bactericidal effect of gentamicin is associated with inhibition of protein synthesis on ribosomes. By binding to the 30S ribosomal subunit, Gentamicin disrupts the reading of mRNA, thereby losing the ability to form functional proteins and disrupting bacteriostasis.

It is not sufficiently absorbed from the gastrointestinal tract, so the drug is prescribed mainly intramuscularly and locally. The maximum amount of Gentamicin in the blood plasma when administered into muscles accumulates after 60 minutes. Antimicrobial concentrations remain in the body for 8-12 hours. It is excreted by the kidneys mainly unchanged. Gentamicin sulfate (Garamycin) is used mainly for infections caused by pathogens resistant to other antibiotics. Active for respiratory tract infections (pneumonia, pleurisy, lung abscesses). The third generation drug Amikacin (Hematsin) has a similar effect and application.

Framecitin is an antibiotic from the group of aminoglycosides for topical use in infectious and inflammatory processes in the upper respiratory tract and ENT organs. Active against gram-positive and gram-negative bacteria, causes rapid death of microorganisms. Used intranasally for rhinitis, sinusitis, nasopharyngitis for up to 7 days, instilling 1-2 drops into each nasal passage 4-6 times a day with an interval of 2-3 hours. When used, skin allergic reactions are possible; there are no systemic side effects.

Tetracycline antibiotics are well absorbed in the gastrointestinal tract, Metacycline (Rondomycin) maintains the active concentration of the drug in the blood for 12 hours, Doxycycline (Vibramycin) is prescribed once a day, because slowly eliminates. For injections, hydrochlorides of tetracycline, oxytetracycline, and morphocycline, which are highly soluble in water, are used. Tetracyclines penetrate tissues well, but the bioavailability of natural tetracyclines is reduced by 2 times under the influence of food. It is recommended to take tetracyclines on an empty stomach or 2 hours after meals. When treating with tetracyclines, you should not eat foods rich in calcium or iron, as complexes that are difficult to absorb are formed. Active concentrations of these drugs after a single dose are observed in the lungs, liver, kidneys, spleen, as well as the heart, intestinal wall, and bones. In the lungs, they accumulate in quantities exceeding the concentration in the blood, which explains the high effectiveness of tetracyclines in the treatment of pulmonary diseases. After repeated doses, tetracyclines accumulate in the mucous membrane of the gastrointestinal tract, liver, bones and teeth. Accumulating in the intestinal mucosa, tetracyclines disrupt the processes of digestion and absorption of food, absorption of fatty acids, iron salts, calcium, with which tetracyclines form insoluble complex compounds. The hepatotoxic effect of tetracyclines is more often noticed in young children and pregnant women. Tetracyclines accumulate in bone tissue (the linear growth of bones slows down), teeth and their anlages (the teeth turn yellow or brown and a defect in the tooth enamel occurs), as they are able to form complex compounds with calcium. This leads to impaired dental development in children. Therefore, they should not be prescribed to children under 8 years of age. Tetracyclines have a phototoxic effect (photosensitization: under the influence of sunlight, skin and nails are damaged). Tetracyclines have a teratogenic effect (cause fetal deformities) and are contraindicated in pregnant women.

Macrolide/azalide antibiotics contain a macrocyclic lactone ring in the molecule associated with carbohydrate residues - amino sugars. Today, of all existing antibiotics, macrolides are the safest, do not suppress the immune system and are therefore widely used. Macrolide antibiotics are divided into two large groups: natural - Erythromycin (Sinerit, Eritran), Josamycin (Vilprafen), Spiramycin (Rovamycin) and semi-synthetic - Roxithromycin (Rulid, Brilid), Clarithromycin (Klacid, Kriksan), Azithromycin (Azivok, Sumamed, Zitrolide, Hemomycin), Midecamycin (Macropen) . The antimicrobial effect is due to disruption of protein synthesis by the ribosomes of the microbial cell. Depending on the type of microorganism and the concentration of the drug, macrolides have a dose- and time-dependent bacteriostatic or bactericidal effect.

Macrolide antibiotics inhibit mainly gram-positive bacteria, suppress the development of most gram-negative strains and are active against some protozoa. The peculiarity of their action is their bacteriostatic effect against forms of bacteria resistant to such widely used antibiotics as penicillins, streptomycins, and tetracyclines. This has important practical implications. The main side effects are gastrointestinal disorders, the risk of which does not exceed 5%. In rare cases, allergic reactions develop, and less commonly, cholestatic hepatitis. Food does not affect the absorption of semi-synthetic macrolides and significantly reduces bioavailability when taking natural macrolides. Semi-synthetic drugs are also less likely to cause side effects.

Erythromycin is produced by actinomycetes (radiant fungi). The mechanism of its antimicrobial action is the inhibition of protein synthesis in microbial cells. It is well absorbed from the gastrointestinal tract. In the acidic environment of the stomach, it is partially destroyed, so erythromycin should be administered in acid-resistant capsules or in the form of enteric tablets. The drug easily penetrates various tissues, including the placental barrier. After a single oral dose, the maximum concentration in the blood is reached after 2–3 hours. To maintain therapeutic levels in the blood, erythromycin should be administered 4 times a day. Resistance of microorganisms to Erythromycin quickly develops. It is prescribed orally (erythromycin base), intravenously (erythromycin phosphate) and locally. Erythromycin in tablets and capsules is most widely used in outpatient practice, especially in pediatrics, for the treatment of pneumonia, bronchitis of various etiologies, scarlet fever, tonsillitis, purulent otitis and other infections. In case of severe infection, the drug is administered intravenously. Topically (in the form of an ointment) it is used to treat purulent skin diseases, infected wounds, bedsores and burns. Erythromycin has low toxicity and rarely causes side effects. Sometimes dyspeptic disorders (nausea, vomiting) and allergic reactions occur.

The combination drug Oletetrin is produced (a drug consisting of a mixture of 1 part oleandomycin phosphate and 2 parts tetracycline).

New macrolides - Clarithromycin, Roxithromycin, Azithromycin, Josamycin - are similar to erythromycin in their spectrum of action, although there are some differences between them. An important advantage of semisynthetic macrolides is their longer half-life, which allows them to be prescribed 1-2 times a day. The half-life of Erythromycin is 2 hours with normal renal function, short for Josamycin, 10 hours for Roxithromycin, and 35 to 50 hours for Azithromycin. 24–96 hours after taking Azithromycin at a dose of 500 mg, its concentration in the bronchial mucosa is 200 times higher, and in the fluid lining the epithelium, 80 times higher than serum levels. Macrolides/azalides are localized due to their high lipophilicity, mainly intracellularly, accumulating in large quantities in macrophages, neutrophils, monocytes, fibroblasts, forming a stable depot and increasing the activity of natural phagocytosis. High concentration in various bronchopulmonary structures, selective distribution in the infectious focus of inflammation, low resistance of S. pneumoniae and H. influenzae to drugs and high activity against the main pathogens of respiratory tract infections (S. pneumoniae, H. influenzae, M. catarrhalis, S. aureus , Enterobactericae), a pronounced anti-inflammatory effect, allows us to classify this group of drugs as the drugs of choice, which becomes of paramount importance and puts them in first place in terms of frequency of use. The high activity of new generation macrolides, especially Azithromycin and Clarithromycin, against atypical pathogens significantly increases their role in the treatment of respiratory tract infections. Azithromycin is so far the only antibacterial drug recommended for a 3-day course of treatment for upper and lower respiratory tract infections.

Antibiotic from the group of glycopeptides Vancomycin . Acts bactericidal. It disrupts the synthesis of the cell wall of microorganisms, the permeability of the cytoplasmic membrane and RNA synthesis. Affects gram-positive flora. Active against staphylococci (including penicillinase-forming and methicillin-resistant strains), streptococci, corynebacteria, enterococci, actinomycetes. Does not have cross-resistance with antibiotics of other groups. Severe infectious and inflammatory diseases caused by drug-sensitive pathogens with ineffectiveness or intolerance to penicillins and cephalosporins. Administered intravenously. Adults: 500 mg every 6 hours or 1 g every 12 hours. With rapid intravenous administration, arterial hypotension and redness of the face, neck and upper body are possible. To avoid collaptoid reactions, the duration of infusion should be at least 60 minutes. Children are prescribed a daily dose of 40 mg/kg, each dose should be administered over at least 60 minutes. In patients with impaired renal excretory function, the dose is reduced. For pseudomembranous colitis, Vancomycin is prescribed orally in the form of a solution: for adults in a daily dose of 500 mg - 2 g (in 3-4 doses), for children - 40 mg/kg (in 3-4 doses). After IV administration, phlebitis, fever, rash, nausea, neutropenia, eosinophilia, and sometimes anaphylactoid reactions are possible. Skin itching, urticaria, and chills are also possible. In rare cases, ototoxicity and nephrotoxicity.

Fluoroquinolones. The introduction of one or more fluorine atoms, as well as various radicals, into the quinolone molecule made it possible not only to enhance the antibacterial properties of the drugs, but also to expand the spectrum of action and change the duration of development of their effects. Depending on the number of fluorine atoms, fluoroquinolones are classified: monofluorinated: Ciprofloxacin (Tsifran, Tsiprobay), Ofloxacin (Tarivid, Zanotsin), Pefloxacin (Abaktal), Gemifloxacin (Faktiv), Gatifloxacin (Gatispan); difluorinated: Lomefloxacin (Maxaquin, Tavanic, Floracid), Sparfloxacin (Respara, Sparflo), Moxifloxacin (Avelox); trifluorinated: Fleroxacin, Tosufloxacin, Trovafloxacin. The mechanism of action of fluoroquinolones is explained by the ability of these drugs to inhibit the vital enzyme of the microbial cell, DNA hydrase. As a result, the stage of microbial cell division is disrupted and it loses its ability to reproduce. DNA hydrase is responsible for superspirilization - DNA unwinding; as a result of its inhibition, DNA is converted into a covalent - closed circular structure. The growth and reproduction of the microbial cell is suspended, leading to its death. Fluoroquinolones are broad-spectrum drugs that cover both gram-positive (streptococci, staphylococci, etc.) and gram-negative microflora. Pneumococci, intracellular microorganisms (chlamydia, mycoplasma), as well as fast-growing atypical mycobacteria are moderately sensitive to fluoroquinolones. The disadvantages of early fluoroquinolones include insignificant activity against gram-positive bacteria, primarily pneumococci and streptococci, which limits their use in community-acquired respiratory tract infections. New drugs Moxifloxacin, Trovafloxacin have high activity against clinical strains of gram-positive bacteria - streptococci, pneumococci, staphylococci, corynebacteria and moderate activity against enterococci. The activity of Moxifloxacin against staphylococci and pneumococci is 4-16 times higher than that of Ciprofloxacin and Ofloxacin . The half-life of Moxifloxacin is 12-14 hours; it is administered orally at a dose of 400 mg once a day. Based on controlled studies, effective treatment periods have been established: 10 days for community-acquired pneumonia and acute sinusitis, 5 days for exacerbation of chronic bronchitis.

May cause rare side effects that are unique to fluoroquinolones, such as impaired development of cartilage tissue, tendon rupture, or myalgia. Quite often, candidiasis of the oral mucosa develops, which depends on the method of introducing drugs into the body. Fluoroquinolones are contraindicated in pregnant women and during lactation; children under 15–16 years of age (until the skeleton is fully formed), difluorinated and trifluorinated - up to 18 years of age.

Sulfa drugs. The antimicrobial effect of sulfonamide drugs is explained by their competitive antagonism with para-aminobenzoic acid (PABA). It is known that PABA is part of folic acid, a vitamin necessary for the synthesis of nucleic acids and proteins. Due to the similarity of PABA to sulfonamide substances, they displace it from the process of folic acid synthesis. Sulfonamide drugs inhibit the enzyme dihydropteroate synthetase, disrupting the synthesis of dihydrofolic acid, which leads to disruption of the synthesis of purine and pyrimidine bases and protein synthesis in microorganisms. The growth and reproduction of microorganisms is suspended. In terms of effectiveness, sulfonamides are significantly inferior to modern chemotherapeutic agents, since microorganisms quickly develop resistance to them. The spectrum of antimicrobial action of sulfonamides is quite wide: they inhibit the growth and reproduction of bacteria (streptococci, pneumococci, E. coli), large viruses, etc. When taken orally, they are well absorbed from the intestines, which occurs mainly in the small intestine.

The distribution of sulfonamides in the body after absorption occurs evenly. Depending on the type of action and the rate of release, sulfonamides with resorptive action are distinguished: short, medium, long and extra long action. The criterion for the duration of action is the half-elimination period, this is the time during which the concentration of the drug in the blood decreases by half (T1/2). Sulfonamides are often used in combination with antibiotics. Taking sulfonamides inhibits the intestinal flora, as a result of which the synthesis of B vitamins in the intestine decreases, therefore, it is recommended to additionally prescribe these vitamins for preventive purposes. Used to treat diseases caused by pathogens sensitive to sulfonamides: pneumonia, staphylococcal and streptococcal sepsis, sore throat.

Sulfadimethoxine (Madribon) is a long-acting sulfonamide. Used for the treatment of acute respiratory diseases, pneumonia, bronchitis, sore throat, sinusitis, otitis. Prescribed once a day. The interval between doses is 24 hours. For mild forms of the disease, 1 g is prescribed on the first day, 0.5 g on subsequent days; for moderate forms - 2 g on the first day, 1 g on subsequent days. After normalization of body temperature, maintenance doses are used for another 2-3 days. Children - at the rate of 25 mg/kg. The course of treatment is 7-14 days.

The antimicrobial effect of sulfonamides is significantly enhanced when they are combined with a diaminopyrimidine derivative - trimethoprim, which inhibits the conversion of dihydrofolic acid to tetrahydrofolic acid due to inhibition of dihydrofolate reductase. Trimethoprim has a bacteriostatic effect for 12 hours. A promising combination of two active ingredients, each of which has an antimicrobial bacteriostatic effect, leading to synergism, an increase in antibacterial activity, causing the death of microorganisms and a bactericidal effect. The effect lasts for about 12 hours when taking 2 tablets per day - morning and evening. Combined drugs: Co-trimoxazole (Bactrim, Biseptol) contains 5 parts of sulfamethoxazole and 1 part of trimethoprim; lidaprim (sulfametrol + trimethoprim).

Co-trimoxazole is used to treat infections of the respiratory tract (bronchitis, pneumonia, lung abscess, pleural empyema, otitis media, sinusitis). When taken orally, both components included in the drug are completely absorbed from the gastrointestinal tract. The maximum concentration of the active components of the drug is observed after 1-4 hours. Trimethoprim has good penetration into cells and through tissue barriers - into the lungs, kidneys, saliva, sputum, and cerebrospinal fluid. Protein binding of trimethoprim is 50%, its half-life is normally from 8.6 to 17 hours. The main route of excretion of trimethoprim is through the kidneys, 50% unchanged. The most common side effects are dyspepsia and allergic skin reactions. Possible inhibition of hematopoiesis and dysfunction of the liver and kidneys.

In the body, sulfonamides undergo acetylation (the hydrogen of the amino group is replaced by an acetic acid residue). The degree of acetylation varies greatly among different drugs. Acetylation leads to the loss of chemotherapeutic activity; therefore, those drugs that are less subject to acetylation are most suitable for therapeutic purposes. Compared to the parent drugs, acetyl derivatives are less soluble in water and precipitate. Sulfonamides are excreted from the body mainly by the kidneys. If patients do not comply with the rational conditions for the use of sulfonamides, crystalluria (precipitation of acetylated sulfonamides in the renal tubules) may develop, and protein and blood may appear in the urine. Most often, this complication is caused by poorly soluble sulfonamides of long-acting and extra-long-acting action. This side effect can be prevented by drinking sulfonamides with plenty of alkaline drink.

Drugs of other groups

Mupirocin (Bactroban) is used for staphylococcal infections of the nasal cavity and is active against streptococci. It has a bactericidal effect through reversible and specific binding to tRNA synthetase. Available in the form of an ointment, applied externally, applied intranasally 3 times a day for 7-10 days.

Fuzafunzhin (Bioparox) and Grammicidin S (Grammidin) were discussed in the previous article.

Contraindications to the use of fluoroquinolones

Common to all:

• Pregnancy.
• Lactation.
• Allergic reactions to fluoroquinolones.
• Childhood and adolescence.

Fluoroquinolones are contraindicated under 18 years of age, since in animal experiments researchers noted a delay in the development of cartilage tissue. Therefore, as a rule, they are not prescribed until the formation of the skeleton is complete. Although, in some cases, doctors prescribe fluoroquinolones to children on their own responsibility. For example, with cystic fibrosis or intolerance to other antibacterial agents.

Interaction

The compatibility of fluoroquinolones with other pharmacological groups is quite high. There are several risks of joint use:

• high neurotoxicity when combined with NSAIDs and methylxanthines;
• the effect of nitrofurans is neutralized;
• preparations with metal ions reduce the absorption of quinolone derivatives;
• The effectiveness of anticoagulants decreases.

A distinctive feature of fluoroquinolones is arthrotoxicity - a negative effect on connective joint tissue. When combining them with glucocorticosteroids, there is a risk of tendon rupture and thinning of cartilage tissue.

With irregular intake of antibacterial agents, resistance to antimicrobial components occurs in the body.

Aminoglycosides, sulfonamides, cephalosporins and tetracyclines introduced into the therapeutic plan do not affect the activity of fluoroquinolones. The simultaneous use of macrolides, penicillins and fluoroquinolone antimicrobial agents is not advisable, since any drug containing fluorinated derivatives has a more significant therapeutic effect.

The most common side effects of fluoroquinolones

1. From the gastrointestinal tract: abdominal pain, nausea, vomiting, diarrhea. Therefore, advise taking them after meals.
2. Central nervous system disorders: headache, dizziness, convulsions (in people with epilepsy).
3. Photodermatoses, i.e. increased skin sensitivity to ultraviolet rays. When exposed to the sun, fluoroquinolones are destroyed, free radicals are formed and cause skin damage.

This means that when selling a drug from this group, you need to offer a sunscreen. Especially in summer and in sunny regions.

Lomefloxacin (Lomflox) and sparfloxacin (Sparflo) differ more than others in their ability to cause photodermatoses.

1. Increased liver transaminases. This means that the drugs are hepatotoxic. Therefore, it would be a good idea to take a drug from the fluoroquinolone group in conjunction with a hepatoprotector. Rarely, drug-induced hepatitis does occur.
2. Increased QT interval on ECG. For healthy people this is not scary. And if the drug is taken by a person who has serious heart problems, there may be arrhythmia. But this happens when taking large doses of the drug.

1. A rare side effect is tendinitis, i.e. inflammation of the tendon and its rupture. Most often, the Achilles tendon is affected. This happens mainly in older people.

Tendonitis occurs because fluoroquinolones inhibit the activity of an enzyme necessary for the synthesis of collagen protein. And it forms the basis of tendons, and connective tissue in general.

Important:

If fluoroquinolones are taken simultaneously with an antacid and a vitamin-mineral complex, insoluble compounds are formed and the drug will not have the desired effect. Therefore, the break between doses should be at least 4 hours.

Now let’s remember all of the above and draw up a list of recommendations for the buyer.