Saving mold: the history of the creation of penicillin

“When I woke up at dawn on September 28, 1928, I certainly did not plan to revolutionize medicine with my discovery of the world’s first antibiotic or killer bacteria,” he wrote in his diary. Alexander Fleming, the man who invented penicillin.

The idea of ​​using microbes to fight germs dates back to the 19th century. It was already clear to scientists that in order to combat wound complications, we must learn to paralyze the microbes that cause these complications, and that microorganisms can be killed with their help. In particular, Louis Pasteur discovered that anthrax bacilli are killed by the action of certain other microbes. In 1897, Ernest Duchesne used the mold, i.e. the properties of penicillin, to treat typhus in guinea pigs.

In fact, the date of invention of the first antibiotic is September 3, 1928. By this time, Fleming was already famous and had a reputation as a brilliant researcher; he studied staphylococci, but his laboratory was often untidy, which was the reason for the discovery.

Penicillin. Photo: www.globallookpress.com

On September 3, 1928, Fleming returned to his laboratory after a month of absence. Having collected all the cultures of staphylococci, the scientist noticed that mold fungi appeared on one plate with the cultures, and the colonies of staphylococci present there were destroyed, while other colonies were not. Fleming attributed the mushrooms that grew on the plate with his cultures to the genus Penicillium, and named the isolated substance penicillin.

During further research, Fleming noticed that penicillin affected bacteria such as staphylococci and many other pathogens that cause scarlet fever, pneumonia, meningitis and diphtheria. However, the remedy he isolated did not help against typhoid fever and paratyphoid fever.

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Fleming published a report on his discovery in 1929 in the British Journal of Experimental Pathology.

As Fleming continued his research, he discovered that penicillin was difficult to work with, production was slow, and penicillin could not survive in the human body long enough to kill bacteria. Also, the scientist could not extract and purify the active substance.

Until 1942, Fleming improved the new drug, but until 1939 it was not possible to develop an effective culture. In 1940, the German-English biochemist Ernst Boris Chain and Howard Walter Florey , an English pathologist and bacteriologist, were actively involved in an attempt to purify and isolate penicillin, and after some time they succeeded in producing enough penicillin to treat the wounded.

In 1941, the drug was accumulated on a sufficient scale for an effective dose. The first person to be saved with the new antibiotic was a 15-year-old boy with blood poisoning.

In 1945, Fleming, Florey and Chain were awarded the Nobel Prize in Physiology or Medicine "for their discovery of penicillin and its beneficial effects in various infectious diseases."

Photo: www.globallookpress.com

Compound

The composition of drugs that belong to penicillin group of antibiotics depends on what kind of medicine we are talking about.
Currently, four groups are used:

• natural penicillins;
• semisynthetic penicillins;
• aminopenicillins, which have an extended spectrum of action;
• penicillins, which have a wide antibacterial spectrum of influence.

Release form

Injectable preparations are available, as well as penicillin tablets.

The injection product is produced in glass bottles, which are closed with rubber stoppers and metal caps. The vials contain different doses of penicillin. It is dissolved before administration.

Penicillin-ecmoline tablets are also produced for resorption and oral administration. Sucking tablets contain 5000 units of penicillin. In tablets for oral administration - 50,000 units.

Penicillin tablets with sodium citrate may contain 50,000 and 100,000 units.

Mushrooms

You may find it strange to use mushrooms to fight bacteria. However, mushrooms do have powerful antimicrobial properties. Many antibiotics like penicillin, tetracycline and streptomycin are made from fungi and molds. Studies have shown that eating mushrooms can strengthen the body's defenses. But remember, not all mushrooms are created equal. For example, shiitake mushrooms are useful - they can fight cancer, destroy various bacteria and viruses, and also help regulate cholesterol levels. Reishi mushrooms are also beneficial because they have anti-inflammatory effects.

pharmachologic effect

Penicillin is the first antimicrobial agent that was obtained using waste products of microorganisms as a basis. The history of this medicine begins in 1928, when the inventor of the antibiotic, Alexander Fleming, isolated it from a strain of the fungus Penicillium notatum. In the chapter that describes the history of the discovery of penicillin, Wikipedia testifies that the antibiotic was discovered by accident; after the bacteria entered the culture from the external environment of a mold fungus, its bactericidal effect was noted. Later, the formula of penicillin was determined, and other specialists began to study how to obtain penicillin. However, the answer to the questions of what year this drug was invented and who invented the antibiotic is clear.

The further description of penicillin on Wikipedia testifies to who created and improved the drugs. In the forties of the twentieth century, scientists in the USA and Great Britain worked on the industrial production process of penicillin. The first use of this antibacterial drug for the treatment of bacterial infections occurred in 1941. And in 1945, for the invention of penicillin, the Nobel Prize was received by its creator Fleming (the one who invented penicillin), as well as by the scientists who worked on its further improvement - Flory and Chain.

Speaking about who discovered penicillin in Russia, it should be noted that the first samples of the antibiotic were obtained in the Soviet Union in 1942 by microbiologists Balezina and Ermolyeva. Then industrial production of the antibiotic began in the country. In the late fifties, synthetic penicillins appeared.

When this drug was invented, for a long time it remained the main antibiotic used clinically throughout the world. And even after other antibiotics without penicillin were invented, this antibiotic remained an important drug for the treatment of infectious diseases. There is a claim that the medicine is obtained using cap mushrooms, but today there are different methods for its production. Currently, so-called protected penicillins are widely used.

The chemical composition of penicillin indicates that the drug is an acid, from which various salts are subsequently obtained. Penicillin antibiotics include Phenoxymethylpenicillin (penicillin V), Benzylpenicillin (penicillin G), etc. The classification of penicillins involves their division into natural and semi-synthetic.

Biosynthetic penicillins provide bactericidal and bacteriostatic effects, inhibiting the synthesis of the cell wall of microorganisms. They act on some gram-positive bacteria (Streptococcus spp., Staphylococcus spp., Bacillus anthracis, Corynebacterium diphtheria), on some gram-negative bacteria (Neisseria meningitidis, Neisseria gonorrhoeae), on anaerobic spore-forming bacilli (Spirochaetaceae Actinomyces spp.), etc.

The most active of the penicillin drugs is benzylpenicillin . Resistance to the influence of benzylpenicillin is demonstrated by strains of Staphylococcus spp. that produce penicillinase.

Penicillin is not effective against bacteria of the enteric-typhoid-dysenteric group, causative agents of tularemia, brucellosis, plague, cholera, as well as whooping cough, tuberculosis, Friedlander's, Pseudomonas aeruginosa and viruses, rickettsia, fungi, protozoa.

BETA-LACTAM ANTIBIOTICS

β-lactam antibiotics (β-lactams), which are united by the presence of a β-lactam ring in their structure, include penicillins, cephalosporins, carbapenems

and
monobactams
, which have a bactericidal effect. The similarity of the chemical structure determines the same mechanism of action of all β-lactams (impaired bacterial cell wall synthesis), as well as cross-allergy to them in some patients.

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

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

Penicillins are the first antimicrobial drugs developed on the basis of biologically active substances produced by microorganisms. The ancestor of all penicillins, benzylpenicillin, was obtained in the early 40s of the 20th century. Currently, the group of penicillins includes more than ten antibiotics, which, depending on the sources of production, structural features and antimicrobial activity, are divided into several subgroups (Table 1).

Table 1. Classification of penicillins

Natural	Benzylpenicillin (penicillin) Benzylpenicillin procaine Benzathine benzylpenicillin Phenoxymethylpenicillin Benzathine phenoxymethylpenicillin
Semi-synthetic
Antistaphylococcal	Oxacillin
Spread Spectrum Read also:  General approaches to the treatment of eczema in the practice of an internist Aminopenicillins	Ampicillin Amoxicillin
Antipseudomonas Carboxypenicillins Ureidopenicillins	Carbenicillin Ticarcillin Azlocillin Piperacillin
Inhibitor-protected	Amoxicillin/clavulanate Ampicillin/sulbactam Ticarcillin/clavulanate Piperacillin/tazobactam
Combined	Ampicillin/oxacillin

General properties:

• Bactericidal action.
• Low toxicity.
• Excretion is mainly through the kidneys.
• Wide range of dosages.
• Cross-allergy between all penicillins and some cephalosporins and carbapenems.

Pharmacokinetics and pharmacodynamics

The most effective method is intramuscular administration. After such use, the active component very quickly enters blood . The highest concentration of the product is observed 30-60 minutes after application. After a single administration, only trace concentrations are determined.

It is quickly detected in muscles, wound exudate, in joint cavities, and in muscles.

A small amount of it is observed in the cerebrospinal fluid. A small amount will also enter the pleural cavities and abdominal cavity, so direct local action of the drug is required if necessary.

Penetrates to the fetus through the placenta. It is excreted from the body through the kidneys, so about 50% of the drug is eliminated. Also, part of it is excreted in bile.

If a patient takes penicillin in tablets, he needs to take into account that when taken orally, the antibiotic is poorly absorbed, and part of it is destroyed under the influence of gastric juice and beta-lactamase, which is produced by intestinal microflora .

References

1. Medical Immunology. Federal clinical guidelines / ed. R.M. Khaitova, N.I. Ilyina. - M.: FarmarusPrint Media, 2014. - T. 13. - No. 4-5. - 2011. - T. 13, No. 4-5. — 126 s.
2. Clinical recommendations “Allergology and clinical immunology” / ed. R.M. Khaitova, N.I. Ilyina. - M.: GEOTAR-Media, 2021. - 336 p.
3. Goldberg, A., Confino-Cohen, R. Skin testing and oral penicillin challenge in patients with a history of remote penicillin allergy. AnnAllergyAsthmaimmunol, 2008. - Vol. 100. - P. 37-43.

Indications for use

Antibiotics of the penicillin group, the names of which will be prompted directly by the attending physician, are used to treat diseases caused by microorganisms sensitive to penicillin:

• pneumonia (lobar and focal);
• pleural empyema;
• septic endocarditis in acute and subacute forms;
• sepsis;
• pyemia;
• septicemia;
• osteomyelitis in acute and chronic form;
• meningitis;
• infectious diseases of the biliary and urinary tract;
• purulent infectious diseases of the skin, mucous membranes, soft tissues;
• angina;
• scarlet fever;
• erysipelas;
• anthrax;
• actinomycosis;
• diphtheria;
• gynecological purulent-inflammatory diseases;
• ENT diseases;
• eye diseases;
• gonorrhea, syphilis , blenorrhea.

Contraindications

Tablets and injections are not used in the following cases:

• with high sensitivity to this antibiotic;
• for urticaria , hay fever , bronchial asthma and other allergic manifestations ;
• when patients exhibit high sensitivity to sulfonamides, antibiotics, as well as other drugs.

Butter

Butter is sometimes criticized, then again it is considered healthy. It is regularly recommended to switch to margarine, but then it turns out that the latter is even more dangerous. In a word, doctors do not have a consensus on this matter. Butter actually contains a lot of nutrients, for example, it contains a component that protects against cancer, however, many manufacturers use raw materials that contain antibiotics. As mentioned earlier, cow's milk is quite dangerous. Choose the highest quality butter possible to prevent problems.

Side effects

During use, the patient must understand what penicillin is and what side effects it can cause. During treatment, allergy symptoms sometimes appear. As a rule, such manifestations are associated with sensitization of the body due to earlier use of these drugs. Allergies can also When using the medicine for the first time, allergies are observed less frequently. There is a possibility of sensitization of the fetus during pregnancy if a woman takes penicillin.

The following side effects may also develop during the course of treatment:

• Digestive system: nausea, diarrhea , vomiting.
• Central nervous system: neurotoxic reactions, signs of meningism, coma , convulsions .
• Allergies: urticaria , fever, rash on mucous membranes and skin, eosinophilia, edema . Cases of anaphylactic shock and death have been recorded. Adrenaline should be immediately administered intravenously.
• Manifestations associated with chemotherapeutic effects: oral candidiasis

Garlic

Aromatic garlic has long been famous for its ability to fight bacteria. It was even nicknamed “Russian penicillin” during World War II because it was used by doctors who ran out of medicine. Research has shown that garlic is surprisingly beneficial in controlling the levels of Helicobacter pylori bacteria in the digestive tract without completely killing them. Too much of them can cause ulcers, but too little is harmful. Stomach cancer is an extremely common problem. Eating garlic and onions can reduce the likelihood of this disease, so try to make your diet more savory.

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Instructions for use of penicillin (Method and dosage)

Antimicrobial action is observed with local and resorptive action of penicillin.

Instructions for the use of penicillin in injections

The drug can be administered subcutaneously, intramuscularly, or intravenously. The drug is also injected into the spinal canal. For therapy to be as effective as possible, the dose must be calculated so that there is 0.1–0.3 units of penicillin in 1 ml of blood. Therefore, the drug is administered every 3-4 hours.

For the treatment of pneumonia , syphilis , cerebrospinal meningitis, etc., a doctor prescribes a special regimen.

Instructions for use of penicillin tablets

The dosage of penicillin tablets depends on the disease and on the treatment regimen prescribed by the attending physician. As a rule, patients are prescribed 250-500 mg, the drug should be taken every 8 hours. If necessary, the dose is increased to 750 mg. It is recommended to take tablets half an hour before meals or two hours after meals. The duration of treatment depends on the disease.

Publications in the media

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 - sinusitis, frontal sinusitis, sinusitis, pharyngitis, tracheitis, tonsillitis, tonsillitis, bronchitis, pleurisy, pneumonia, etc.

Pathogens of respiratory tract infections differ in their 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 are used - 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. Strains of staphylococci that form penicillinase 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 is used. 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 that have a wide spectrum of antimicrobial action, including against penicillin-forming staphylococci and 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 betalactamases.

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 (Keflin). 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 (Keflex) - 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 (Kefzol, Cefamezin) is resistant to beta-lactamases of microorganisms and has a wide 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.

Due to their resistance to beta-lactamases, 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 , the main and most widely used aminoglycoside drug, 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 for Azithromycin from 35 to 50 hours. 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.

Overdose

It should be borne in mind that when taking large doses of penicillin, an overdose can occur, which can cause unpleasant symptoms in the form of nausea, vomiting, and diarrhea . But this condition is not life-threatening.

hyperkalemia may develop in patients suffering from renal failure .

When large doses of the drug are administered intraventricularly or intravenously, epileptic seizures may occur. But such a symptom appears in adult patients only after administration of at least 50 million units. medications. In this case, the patient is prescribed barbiturates or benzodiazepines.

Milk

Milk has come under constant criticism in recent years, primarily because it contains antibiotics. In fact, only a small portion of dairy products have excessive levels of antibiotics, yet drugs are still present in many products. Because of this, many people try to give up milk or buy it directly from farmers, without pasteurization or additives. However, experts do not recommend such a solution, because unpasteurized milk can also contain bacteria and infections. This is no less dangerous than drinking milk containing medications. If you want to be on the safe side, choose products labeled as antibiotic-free.

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Interaction

When taken simultaneously with Probenecid, of benzylpenicillin decreases , which leads to an increase in its concentration in plasma and an increase in the half-life.

If combined use with tetracycline , the bactericidal effect of benzylpenicillin is reduced.

Dilution in the same syringe or in the same system for infusion of penicillin and aminoglycosides , since these agents are physicochemically incompatible.

If large doses of benzylpenicillin potassium salt in combination with potassium supplements, potassium-sparing diuretics or ACE inhibitors, there is an increased risk of hyperkalemia.

When taking penicillins that demonstrate activity against Pseudomonas aeruginosa with antiplatelet agents and anticoagulants, caution should be exercised, as there is a risk of increased bleeding.

It is not recommended to take simultaneously with thrombolytics .

Sulfonamides weaken the bactericidal effect of the antibiotic.

When taking Cholestyramine and penicillins simultaneously, the bioavailability of the latter decreases.

When taking oral penicillins simultaneously with oral contraceptives, the effectiveness of the latter may be reduced due to disruption of the enterohepatic circulation of estrogen .

When taking an antibiotic, the process of removing methotrexate from the body may slow down due to inhibition of its tubular secretion.

special instructions

Before using penicillin, it is important to conduct tests and determine sensitivity to the antibiotic.

Prescribe the medicine with caution to people who have impaired renal function, as well as patients with acute heart failure , people who have a tendency to allergic manifestations or severe sensitivity to cephalosporins .

If 3-5 days after the start of treatment there is no improvement in the patient’s condition, it is important to consult a doctor who will prescribe other antibiotics or combination treatment.

Since in the process of taking antibiotics there is a high probability of fungal superinfection , it is important to take antifungal agents during treatment. It is also important to consider that when using subtherapeutic doses of the drug or with an incomplete course of therapy, the emergence of resistant strains of pathogens is possible.

When taking the drug orally, you should take it with plenty of liquid. It is important to strictly follow the instructions on how to dilute the product.

During treatment with penicillins, it is necessary to strictly follow the prescribed treatment regimen and not skip doses. If a dose is missed, the dose should be taken as soon as possible. You cannot interrupt the course of treatment.

Since expired medicine may be toxic, it should not be taken.

Analogs

Level 4 ATC code matches:
Hiconcil

Ampioks

Ampicillin Trihydrate

Ampicillin

Ospamox

Amoxicar

Flemoxin Solutab

Amoxicillin

Amosin

Amoxil

Ecoball

There are a number of penicillin drugs; the most optimal antibiotic is determined by the doctor individually.

Penicillin price, where to buy

The price of Penicillin tablets depends on the drug and ranges from 30 rubles. per package. You can buy Penicillin in ampoules at a price of 60 rubles per 1 ampoule.

• Online pharmacies in RussiaRussia
• Online pharmacies in UkraineUkraine
• Online pharmacies in KazakhstanKazakhstan

LuxPharma* special offer

• Penicillin G (Infectocillin, Extensillin) 5 million IU No. 1
  RUB 1,880 order
• Ospen (Phenoxymethylpenicillin) tab. 1 million ME No. 12

  RUB 1,480 order

• Ospen (Phenoxymethylpenicillin) syrup 750000 IU/5 ml 60 ml

  1380 rub. order

• Penicillin G sodium salt Austria 1 million. ME N1

  1190 rub. order

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Pharmacy24

• Penicillin G sodium salt No. 100 powder for the preparation of solution for injection Sandoz GmbH, Austria
  2522 UAH.order
• Benzylpenicillin-KMP 500,000 IU powder PAT "Kievmedpreparat", Ukraine

  6 UAH order

• Benzylpenicillin-KMP 1,000,000 IU powder for the preparation of solution for injection PAT"Kievmedpreparat", Ukraine

  8 UAH order

PaniPharmacy

• Penicillin bottle Penicillin G sodium salt powder for the preparation of solution for injection 1000000IU bottles No. 100 Austria, Sandoz

  2985 UAH. order

• Benzylpenicillin bottle Benzylpenicillin sodium salt powder for injection 1000000IU Ukraine, Kievmedpreparat OJSC

  11 UAH order

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