BACTERIOPHAGE COLYPROTEAN SOLUTION D/ORAL AND D/RECT. ENTER 100ML

BACTERIOPHAGE COLYPROTEAN SOLUTION D/ORAL AND D/RECT. ENTER 100ML

The drug is used for oral administration (oral), rectal administration, applications, irrigation, administration into wound cavities, vagina, uterus, nose, sinuses and drained cavities.

Recommended dosages of the drug:

• Patient age 0-6 months - 5 doses per 1 dose when administering the drug orally (ml) - 5-10 doses per 1 dose when administering the drug as an enema (ml).
• Patient age 6-12 months - 10 doses per 1 dose when administering the drug orally (ml) - 10-20 doses per 1 dose when administering the drug as an enema (ml).
• Patient age from 1 year to 3 years - 15 doses per 1 dose when administering the drug orally (ml) - 20-30 doses per 1 dose when administering the drug in an enema (ml).
• Patient age from 3 to 8 years - 15-20 doses per 1 dose when administering the drug orally (ml) - 30-40 doses per 1 dose when administering the drug in an enema (ml).
• Patient age 8 years and older - 20-30 doses per 1 dose when administering the drug orally (ml) - 40-50 doses per 1 dose when administering the drug in an enema (ml).

Treatment of purulent-inflammatory diseases with localized lesions should be carried out simultaneously both locally and by taking the drug orally for 7-20 days (according to clinical indications).

If chemical antiseptics were used to treat wounds before using the bacteriophage, the wound should be thoroughly washed with a sterile 0.9% sodium chloride solution.

Depending on the source of infection, the bacteriophage is used:

1. In the form of irrigation, lotions and tamponing in a volume of up to 200 ml, depending on the size of the affected area. In case of an abscess, after removing the purulent contents using a puncture, the drug is administered in an amount less than the volume of the removed pus. In case of osteomyelitis, after appropriate surgical treatment, 10-20 ml of bacteriophage is poured into the wound.
2. When administered into cavities (pleural, articular and other limited cavities), up to 100 ml, after which capillary drainage is left, through which the bacteriophage is administered for several days.
3. For cystitis, pyelonephritis, urethritis, the drug is taken orally. If the cavity of the bladder or renal pelvis is drained, the bacteriophage is injected through the cystostomy or nephrostomy 1-2 times a day, 20-50 ml into the bladder and 5-7 ml into the renal pelvis.
4. For purulent-inflammatory gynecological diseases, the drug is administered into the vaginal cavity, uterus in a dose of 5-10 ml once daily, for colpitis - 10 ml by irrigation or tamponing 2 times a day. Tampons are placed for 2 hours.
5. For purulent-inflammatory diseases of the ear, throat, nose, the drug is administered in a dose of 2-10 ml 1-3 times a day. The bacteriophage is used for rinsing, washing, instillation, and introducing moistened turundas (leaving them for 1 hour).
6. For enteral infections and intestinal dysbiosis, the drug is taken orally 3 times a day 1 hour before meals. It is possible to combine double oral administration with a single rectal administration of a single age-specific dose of the bacteriophage in the form of an enema after bowel movement.

Use of bacteriophage in children (up to 6 months).

For sepsis and enterocolitis in newborns, including premature babies, the bacteriophage is used in the form of high enemas (through a gas tube or catheter) 2-3 times a day in a dose of 5-10 ml. In the absence of vomiting and regurgitation, it is possible to use the drug by mouth. In this case, it is mixed with breast milk. A combination of rectal (in the form of high enemas) and oral (through the mouth) use of the drug is possible. The course of treatment is 5-15 days. In case of recurrent course of the disease, repeated courses of treatment are possible. In order to prevent sepsis and enterocolitis during intrauterine infection or the risk of nosocomial infection in newborns, the bacteriophage is used in the form of enemas 2 times a day for 5-7 days.

In the treatment of omphalitis, pyoderma, and infected wounds, the drug is used in the form of applications twice daily (a gauze pad is moistened with a bacteriophage and applied to the umbilical wound or affected area of ​​skin).

Bacteriophage coli-proteus liquid fl 100ml

Active substance

international nonproprietary name not assigned (non appropriated)

ATX code

V03A (Miscellaneous other preparations)

Release form, packaging and composition of the drug

◊ Solution for oral, local and external use

transparent, yellow of varying intensity, a greenish tint is allowed.

[PRING] 8-hydroxyquinoline sulfate monohydrate 0.0001 g/ml.

20 ml - bottles (8) - cardboard packs.

◊ Solution for oral, local and external use

transparent, yellow of varying intensity, a greenish tint is allowed.

[PRING] 8-hydroxyquinoline sulfate monohydrate 0.0001 g/ml.

100 ml - bottles (1) - cardboard packs.

Clinical and pharmacological group

Immunobiological drug - bacteriophage

Pharmacotherapeutic group

MIBP-bacteriophage

Indications for use

Treatment and prevention of purulent-inflammatory and enteric diseases, dysbiosis caused by Proteus bacteria and enteropathogenic Escherichia coli as part of complex therapy:

• diseases of the ear, throat, nose, respiratory tract and lungs (inflammation of the sinuses, middle ear, sore throat, pharyngitis, laryngitis, tracheitis, bronchitis, pneumonia, pleurisy);
• surgical infections (wound suppuration, burns, abscess, phlegmon, boils, carbuncles, hidradenitis, panaritium, paraproctitis, mastitis, bursitis, osteomyelitis);
• urogenital infections (urethritis, cystitis, pyelonephritis, colpitis, endometritis, salpingoophoritis);
• enteral infections (gastroenterocolitis, cholecystitis), intestinal dysbiosis;
• generalized septic diseases;
• purulent-inflammatory diseases of newborns (omphalitis, pyoderma, conjunctivitis, gastroenterocolitis, sepsis, etc.);
• other diseases caused by Proteus and Escherichia coli.

An important condition for effective phage therapy is the preliminary determination of the phage sensitivity of the pathogen.

Dosage

The drug is used for oral administration (oral), rectal administration, applications, irrigation, administration into wound cavities, vagina, uterus, nose, sinuses and drained cavities.

Recommended dosage of the drug

Treatment of purulent-inflammatory diseases with localized lesions should be carried out simultaneously both locally and by taking the drug orally for 7-20 days (according to clinical indications).

If chemical antiseptics were used to treat wounds before using the bacteriophage, the wound should be thoroughly washed with a sterile 0.9% sodium chloride solution.

Depending on the source of infection, the bacteriophage is used:

1. In the form of irrigation, lotions and tamponing in a volume of up to 200 ml, depending on the size of the affected area. In case of an abscess, after removing the purulent contents using a puncture, the drug is administered in an amount less than the volume of the removed pus. In case of osteomyelitis, after appropriate surgical treatment, 10-20 ml of bacteriophage is poured into the wound.

2. When administered into cavities (pleural, articular and other limited cavities) up to 100 ml, after which capillary drainage is left, through which the bacteriophage is administered for several days.

3. For cystitis, pyelonephritis, urethritis, the drug is taken orally. If the cavity of the bladder or renal pelvis is drained, the bacteriophage is injected through the cystostomy or nephrostomy 1-2 times a day, 20-50 ml into the bladder and 5-7 ml into the renal pelvis.

4. For purulent-inflammatory gynecological diseases, the drug is administered into the cavity of the vagina, uterus in a dose of 5-10 ml once daily, for colpitis - 10 ml by irrigation or tamponing 2 times a day. Tampons are placed for 2 hours.

5. For purulent-inflammatory diseases of the ear, throat, nose, the drug is administered in a dose of 2-10 ml 1-3 times a day. The bacteriophage is used for rinsing, washing, instillation, and introducing moistened turundas (leaving them for 1 hour).

6. For enteral infections and intestinal dysbiosis, the drug is taken orally 3 times a day 1 hour before meals. It is possible to combine double oral administration with a single rectal administration of a single age-specific dose of the bacteriophage in the form of an enema after bowel movement.

Use of bacteriophage in children (up to 6 months).

For sepsis and enterocolitis in newborns, including premature babies, the bacteriophage is used in the form of high enemas (through a gas tube or catheter) 2-3 times a day in a dose of 5-10 ml. In the absence of vomiting and regurgitation, it is possible to use the drug by mouth. In this case, it is mixed with breast milk. A combination of rectal (in the form of high enemas) and oral (through the mouth) use of the drug is possible. The course of treatment is 5-15 days. In case of recurrent course of the disease, repeated courses of treatment are possible. In order to prevent sepsis and enterocolitis during intrauterine infection or the risk of nosocomial infection in newborns, the bacteriophage is used in the form of enemas 2 times a day for 5-7 days.

In the treatment of omphalitis, pyoderma, and infected wounds, the drug is used in the form of applications twice daily (a gauze pad is moistened with a bacteriophage and applied to the umbilical wound or affected area of ​​skin).

Contraindications

• hypersensitivity to the components of the drug.

Overdose

Not installed.

Side effects

Not installed.

Overdose

The drug can be used in combination with other drugs, including antibiotics.

Storage conditions

The drug is stored in accordance with SP 3.3.2.1248-03 in a dry place, protected from light and out of reach of children, at a temperature of 2 to 8 ° C. Shelf life: 2 years.

Conditions for dispensing from pharmacies

Over the counter.

Special Instructions

Precautions for use

If cloudy, do not use the drug!

Due to the content of a nutrient medium in the drug, in which bacteria from the environment can develop, causing cloudiness of the drug, the following rules must be observed when opening the bottle:

• wash your hands thoroughly;
• treat the cap with an alcohol-containing solution;
• remove the cap without opening the stopper;
• do not place the cork with the inner surface on a table or other objects;
• do not leave the bottle open;
• Store an opened bottle only in the refrigerator.

When using small doses (2-8 drops), the drug must be taken with a sterile syringe in a volume of 0.5-1 ml.

The drug from an opened bottle, subject to storage conditions, the above rules and the absence of turbidity, can be used throughout the shelf life.

Impact on the ability to drive vehicles and operate machinery

Absent.

Bacteriophages (from the words “bacteria” and the Greek phagos - devouring; BF), or phages, are specific bacterial viruses that cause their lysis (destruction of cells) or change their properties. They were first discovered by microbiologists F. Twort (1915) in Great Britain and F. d'Herelle (1917) in France. However, it was possible to study their morphology only after the invention of the electron microscope.

Biology of bacteriophages

The wide distribution of BFs in nature is associated with the ubiquity of their main hosts, bacteria. BFs can infect not only bacteria, but also fungi and protozoa, which is why they are also called phages. According to the degree of specificity, they distinguish: polyvalent BPs that interact with related species of bacteria; monovalent BFs that interact with bacteria of a certain type; typical BFs that interact with individual types (variants) of a given type of bacteria.

BFs consist of a protein - a capsid that protects one type of nucleic acid (DNA or RNA, single or double-stranded). There are BFs with a long process, having a contractile or non-contractile sheath, as well as BFs with short processes, analogues of processes, without processes and filamentous (Fig. 1, 2). The size of the BF ranges from 20 to 800 nm (in filamentous forms). BFs, which have the shape of a spermatozoon, reach up to 200 nm in length, consist of a tail process and an icosahedral type head containing nucleic acid. The capsid of the head and the sheath of the tail process of the BP consist of polypeptide subunits arranged according to icosahedral (head) or helical (process) type of symmetry. The tail process has a hollow tube (rod) inside, through which, during infection, the phage nucleic acid passes from the head into the bacterium. The process sheath ends in a hexagonal basal plate with spines from which fibrils (threads) extend. The basal lamina and tail fibrils are involved in the attachment of BP to the bacterial cell. Not all FDs have basal plates and tail fibrils. Depending on the life cycle, BFs can be virulent (lytic) or moderate.

Virulent (lytic) BPs for penetration into bacteria are adsorbed on specific cell receptors, including lipopolysaccharide, lipoprotein, teichoic acids, proteins, or even pili. The specificity of the receptors means that BP can only infect certain bacteria. Once in the bacterium, BF reproduces, forming 200–500 phage particles and causing the death of the bacterium. This is a productive (lytic) type of interaction. BFs with a contractile sheath are adsorbed on the cell wall with the help of fibrils of the tail process. The sheath of the tail process contracts, and the rod, with the help of enzymes (lysozyme), seems to drill through the cell membrane. Through the channel of the BF tube, the nucleic acid is injected from the head into the bacterial cell, and the BF capsid remains outside the bacterium (Fig. 2). The nucleic acid of BF directs the synthesis of its enzymes. In this case, the host DNA and RNA are inactivated. The BF nucleic acid replicates and directs the synthesis of new capsid proteins. Self-assembly of the capsid around the phage nucleic acid and the formation of BFs occur, which come out of the bacterium as a result of its lysis, expulsion, or in some cases, budding. 200–1000 new BPs are released from the bacterium, which infect other bacterial cells.

Moderate BFs interact with bacteria in a productive or integrative manner. The productive type of temperate phage, like virulent phages, ends with the lysis of bacteria. With the integrative type, the DNA of a temperate phage is integrated into the bacterial chromosome and replicates synchronously with the bacterial genome without causing its lysis (transmitted when the bacterium divides). The phage DNA embedded in the chromosome of a bacterium is called a prophage, and the bacterial culture is called lysogenic, the process itself is called lysogeny (from the Greek lysis - decomposition, genea - origin).

The chromosome of the temperate phage lambda, introduced into the bacterium, causes either lysis or lysogenization (the temperate phage DNA that has penetrated into the bacterium takes the shape of a ring and integrates into a strictly defined region of the chromosome). Ultraviolet irradiation induces a lytic process with the release of phage. In lysogeny, phages are not formed as a result of “switching off” phage genes by a repressor encoded by one phage gene.

Prophages can be derepressed spontaneously or under the influence of inducing agents (ultraviolet rays, mitomycin C, etc.) and excluded from the chromosome. This process ends with the production of phages (prophage induction) and lysis of bacteria. The prophage imparts new properties to the bacterium, which is called phage conversion (Latin: conversio - transformation). The morphological, cultural, biochemical, antigenic and other properties of bacteria can be converted. For example, the presence of a prophage in Vibrio cholerae determines its ability to produce cholera exotoxin.

BF is used for the prevention and treatment of infections, as well as for diagnostics (for example, for phage typing to identify the source of infection). In addition, BFs are used in genetic engineering as vectors transferring DNA sections; Natural gene transfer between bacteria through transduction is also possible.

Phage typing is one of the methods of epidemiological marking. Used to identify the source of infection. Isolation of bacteria of the same phagovar from different patients indicates a common source of their infection. During intraspecific identification of bacteria, i.e., when determining the phagovar (phagotype) of bacteria using phage typing, drops of various diagnostic type-specific phages are applied to a Petri dish with a dense nutrient medium seeded with a pure culture of the pathogen in the form of a “lawn”. Bacteria sensitive to the phage are lysed (a sterile spot, “plaque”, or so-called negative phage colony is formed).

BF is a unique phenomenon; they participate in various processes:

• in the transmission of drug resistance during transduction, especially in staphylococci;
• lysogenic conversion leads to the acquisition of new characteristics of bacteria;
• a random insertion into a bacterial chromosome can cause an insertional mutation;
• in epidemiological typing of bacteria (phage typing);
• in lambda BF – a model system for studying latent infection;
• BFs are used in genetic engineering as vectors and gene libraries;
• BFs are responsible for the natural removal of bacteria; used to prevent and treat certain infections.

Obtaining effective therapeutic and prophylactic BPs is associated with a careful and constant search for strains with a wide spectrum (valency) of action on bacteria and a high degree of their lytic activity. The lytic activity and, consequently, the therapeutic and preventive effectiveness of BF preparations depend on the species, infraspecific affiliation of the pathogen, its receptor characteristics and factors of its microenvironment. For example, antibodies and other humoral proteins can block the binding sites of bacteria with BF, which excludes the possibility of parenteral administration of the latter. In addition, the rapid development of bacterial resistance to the used BFs is possible. To obtain a therapeutic effect in case of unfavorable bacterial associations, BF preparations are produced either as polyvalent ones, directed against various species and serovars of one pathogen, or combined, containing BF against various types of pathogen.

BFs do not cause adverse reactions and do not disrupt normal microflora. With dysbacteriosis, intestinal dysfunction caused by the development of local inflammatory processes, suppression of resident microflora, a number of opportunistic microorganisms and transient microflora are activated. These circumstances raise the importance of selective decontamination carried out using targeted antibiotics and lytic BPs.

BF, having specific action against certain pathogens of acute intestinal infections, can also contribute to the development of oral tolerance. It is known that the human body exhibits oral (regional) tolerance to its own normal microflora. This tolerance is due to the blockade of activation of signaling receptors (for example, toll-like receptors - TLR, etc.) to components of the human microflora and the activity of regulatory T lymphocytes (Treg), which in turn are activated by NKT cells (natural killer T cells). Components (patterns) of BP and the bacteria destroyed by it can activate certain signal receptors of body cells, stimulating the synthesis of antimicrobial peptides that suppress the development of the most aggressive microbes (Fig. 3). Failure of oral tolerance leads to the development of various disorders, including chronic gastritis, Crohn's disease, ulcerative colitis, necrotizing enterocolitis in children, gastric and duodenal ulcers.

BF preparations are stored at a temperature of 2–10 °C in a dry, dark place. BF are sensitive to ultraviolet rays; even their short exposure to light leads to loss of lytic activity. To protect BF from the action of gastric juice, they are produced in capsules or tablets coated with an acid-resistant coating. The protective coating material is non-toxic cellulose, esterified with acetic and phthalic acids, forming a smooth transparent film. For children, due to problems swallowing tablets, a pectin coating is used. Pectin, enveloping BF, protects them from the destructive effects of gastric juice.

Normalization of microflora and the possible participation of BP in the maintenance of colonization resistance and oral tolerance ensure stabilization of the humoral and cellular components of immunity. Occasionally, the use of BF coincides with a deterioration in the quality of stool due to the massive death of bacteria sensitive to it. In this case, to reduce intoxication, it is advisable to prescribe enterosorbent at night - no earlier than 3-4 hours after the last dose of BF.

Bacteriophage preparations against intestinal pathogens

Intesti-bacteriophage liquid contains sterile filtrates of phagolysates of Shigella (S. flexneri serovars 1, 2, 3, 4, 6 and S. sonnei), Salmonella (S. paratyphiA, S. paratyphiB, S. typhimurium, S. choleraesuis, S. infantis , S. oranienburg, S. enteritidis), enteropathogenic Escherichia coli of the most etiologically significant serovars (Escherichia coli O111, O55, O26, O125, O119, O128, O18, O44, O25, O20), Proteus (vulgaris and mirabilis), staphylococci, enterococci and pseudomonas aeruginosa (Pseudomonas aeraginosa). Intesti-bacteriophage (Bacteriophagum intestinalis fluidum) is a transparent yellow liquid of varying intensity.

The drug is intended for the treatment and prevention of diseases of the gastrointestinal tract caused by the above bacteria, their combination (including bacterial dysentery, salmonellosis, typhoid fever, paratyphoid fever, dysbacteriosis, enterocolitis, colitis, dyspepsia). It is prescribed in the acute period of the disease: monotherapy for mild and erased forms, for bacterial excretion; combination therapy with other antibacterial agents (for moderate cases) or immunomodulators (for prolonged bacterial excretion). The key to the effectiveness of using intesti-bacteriophage is to determine the phage sensitivity of the pathogen and early use of the drug, which is prescribed orally or rectally using an enema. Intesti-bacteriophage is administered orally 3–4 times a day on an empty stomach 1.0–1.5 hours before meals for 7–10 days and in a single dose: children up to 6 months – 5–10 ml, 6–12 months – 10 –15 ml, 1–3 years – 15–20 ml, over 3 years – 20–40 ml (see table). For children in the first months of life, the prescribed drug is diluted with boiled water 2 times in the first two days. If there are no side complications (regurgitation, skin rashes), the drug is prescribed undiluted. Before taking intesti-bacteriophage, children over 3 years of age and adults are prescribed a solution of baking soda (0.5 teaspoon per 0.5 glass of water) or alkaline mineral water. In the absence of colitic syndrome, the drug is prescribed rectally once a day after bowel movement.

Bacteriophage dysentery polyvalent (in acid-resistant tablets and suppositories) contains sterile filtrates of Shigella phagolysates (S. flexneri and S. sonnei). Used from 6 months of age for the treatment and prevention of bacterial dysentery. For treatment, it is used orally 3 times a day an hour before meals for 5–7 days and in a single dose: for children from 6 months to 3 years – 1 tablet, 3–8 years – 1–2 tablets, over 8 years – 2–3 tablets. In case of mild colitis syndrome and during the period of convalescence, the third oral dose of BF can be replaced by its rectal use: from 6 months to 3 years – 20–40 ml, from 3 to 8 years – 40–60 ml, over 8 years – 60–80 ml.

For preventive purposes, it is recommended to take the drug daily depending on age: 10–40 ml or 1–2 tablets.

Salmonella bacteriophage of groups A, B, C, D, E in tablets with acid-resistant coating, in suppositories, liquid contains sterile filtrates of Salmonella phagolysates (S. paratyphi A, S. paratyphi B, S. typhimurium, S. heidelberg, S. newport, S. choleraesuis, S. oranienburg, S. infantis, S. dublin, S. enteritidis, S. anatum, S. newlands). For treatment, it is used orally 3 times a day an hour before meals for 7–10 days and in a single dose: for children 6–12 months – 0.5 tablets; 1–3 years – 0.5–1.0; 3–8 years – 1.0 each; over 8 years old – 2 tablets. The third oral dose can be replaced by rectal administration of the drug. For preventive purposes, BF is prescribed for children 1 tablet and for adults 2 tablets 2 times a week.

Bacteriophage typhoid in tablets with an acid-resistant coating contains a sterile filtrate of the phagolysate of Salmonella typhoid (S. typhi). The drug is prescribed for the prevention of typhoid fever orally one hour before meals for children from 6 months to 3 years old, 1 tablet, and over 3 years old and adults - 2 tablets 1 time in 3 days or every day until recovery.

Bacteriophage coliproteus liquid contains sterile filtrates of phagolysates of enteropathogenic (diarrheagenic) Escherichia coli (Escherichia coli of the most common serological groups O20, O26, O33, O44, O55, O111, O119, O26, O124, O125, O127, O151), Proteus vulgaris and Proteus mirabilis. The drug is intended for the treatment and prevention of diseases caused by the above bacteria, as well as dysbacteriosis.

The scope of application of other bacteriophage preparations is diverse; they are used both for topical application (“wound” bacteriophages) and for oral or rectal administration, including depending on the form of release:

• Klebsiella pneumoniae bacteriophage purified liquid;
• Klebsiella bacteriophage polyvalent purified liquid;
• bacteriophage coli liquid;
• Proteus bacteriophage liquid;
• bacteriophage pseudomonas aeruginosis (pseudomonas) liquid;
• Salmonella bacteriophage ABCDE groups in suppositories;
• Salmonella bacteriophage ABCDE group liquid;
• Salmonella bacteriophage ABCDE groups liquid and dry with acid-resistant coating;
• staphylococcal bacteriophage in aerosol packaging;
• staphylococcal bacteriophage in suppositories;
• staphylococcal bacteriophage for injection, liquid;
• bacteriophage staphylococcal liquid;
• bacteriophage streptococcal liquid.

In conclusion, it should be noted that BF and BF preparations are characterized by many positive aspects, they are:

• safe, including non-toxic, for humans;
• highly stable during long-term storage;
• have strict specificity of action on certain types of bacteria and are effective both as monotherapy and in combination with antibiotics;
• do not disrupt normal microflora;
• capable of self-reproduction and self-regulation of numbers.

Information about the authors: Anatoly Sergeevich Bykov – Doctor of Medical Sciences, Professor of the Department of Microbiology, Virology and Immunology of the State Educational Institution of Higher Professional Education “First Moscow State Medical University named after. THEM. Sechenov” of the Ministry of Health and Social Development of the Russian Federation. Tel., e-mail; Bykov Sergey Anatolyevich – Candidate of Medical Sciences, assistant at the Department of Clinical Immunology and Allergology of the State Educational Institution of Higher Professional Education “First Moscow State Medical University named after. THEM. Sechenov” of the Ministry of Health and Social Development of the Russian Federation.