Klebsiella bacteriophage polyvalent purified Solution, 4 pcs, 20 ml, for oral administration

Treatment with bacteriophages: pros and cons

17.10.2019

For many decades, antibiotics have saved humanity, but there is an opinion that their era is coming to an end. The reason for this was the frivolity of people. Many patients - usually successful careerists, professionals who do not have time to visit a doctor - practice self-administration of medications. As a result, an increasing number of infections become resistant to antibiotics, and the effectiveness and efficiency of these drugs decreases. The recommendations of the World Health Organization are to strictly control the use of antibiotics and, in all cases where possible, look for alternatives. Currently, bacteriophages are considered an effective alternative substitute for antibiotics.

A bacteriophage is a virus that replicates in living cells of the host. It consists of DNA and a protein shell. An important advantage of bacteriophages over antibiotics is that they do not disrupt the normal microflora of the body. This is possible due to targeted effects: bacteriophages attach to only one type of microbe.

The phage DNA multiplies, penetrating inside the pathogenic cell, then breaks the host cell membrane and infects microbes. Bacteriophages are often used in complex antibacterial therapy. If there is no mortal threat to the patient, this alternative means of disease control is preferred. Currently, a variety of phages have been created, a large number of dosage forms have been produced - suppositories, aerosols, solutions, tablets, etc.

Bacteriophages are used in many fields of medicine:

• gynecology;
• surgery;
• otolaryngology;
• gastroenterology;
• pulmonology;
• urology.

Depending on the causative agent of the disease and the type of disease, a specific medication is prescribed.

Advantages of bacteriophages over antibiotics:

• are not addictive and do not suppress human immunity;
• compatible with all medications, including antibiotics (bacteriophages enhance their effect);
• do not cause resistance in bacterial cultures;
• effective in the treatment of indolent bacterial infections that are insensitive to antibiotics;
• selectively act and do not destroy beneficial bacterial microflora;
• have no contraindications.

At the same time, using bacteriophages independently, without the prescription and supervision of a specialist, can be no less dangerous than antibiotics. Indeed, in order to identify the causative agent of the disease and understand how sensitive it is to phages, a special study is required.

However, bacteriophages are used not only in the treatment, but also in the prevention of diseases of a bacterial nature, for example, caused by:

• hemolytic Escherichia coli;
• staphylococcus, streptococcus, enterococcus;
• Pseudomonas aeruginosa;
• Proteus, etc.;

For a long time, bacteriophages have been successfully used in the treatment of:

• purulent-inflammatory diseases of the oral cavity and periodontal tissues;
• diseases of the ENT organs;
• dysbacteriosis in adults and children;
• for pyoderma of the skin, insect and animal bites, wound infections;
• bacterial diseases of the genitourinary system.

They are also used for prevention in case of bacterial complications due to acute respiratory infections and influenza. With early detection of the pathogen and properly prescribed prophylaxis, the effectiveness of phage preparations is greatest.

Despite all the advantages, it can hardly be assumed that bacteriophages are capable of completely eliminating the use of antibiotics at this stage of development of science and medicine. Both of these drugs are used in different situations and rather complement each other. As with antibiotics, it is important to ensure that their use does not go beyond the control of specialists. This is the only way they will remain an important aid in the fight against infections.

Literature

Aleshkin A.V. Bacteriophages in infectious pathology: past, present and future // Lectures on the research and application of bacteriophages. 2021. Ulyanovsk. pp. 11-51.

Bacteriophages: biology and application. 2012. M: “Scientific World”. Eds.: E. Cutter and A. Sulakvelidze. Górski A. et al. Phages targeting infected tissues: novel approach to phage therapy. // Future Microbiol. 2015. V. 10. P. 199-204.

Międzybrodzki R. et al. Clinical aspects of phage therapy // Adv. Virus. Res. 2012. V. 83. P. 73-121.

Otolaryngologist, doctor of the highest category, Ph.D. Director of SMC Katerincheva Olga Aleksandrovna

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Klebsiella bacteriophage polyvalent purified Solution, 4 pcs, 20 ml, for oral administration

Directions for use and doses

It is permissible to use the drug internally, topically for irrigation and application, rectally, by introducing it into the nasal cavity, wound, uterus, vagina, as well as for draining cavities. Recommended dosages for patients over 8 years of age are up to 30 ml of solution when administered orally and up to 50 ml when administered as enemas. Treatment of localized diseases of a purulent-inflammatory nature is carried out by a combination of local treatment and oral administration of the drug. In the treatment of pharyngitis, tonsillitis, laryngitis, the Klebsiella pneumoniae bacteriophage is used in 10-15 ml for rinsing the mouth and throat three times a day for up to 10 days. During the treatment of bronchitis and pneumonia, the medicine is prescribed orally 15-20 ml three times a day, and is also used in the form of inhalations. The course of therapy is 2-3 weeks. Treatment of otitis is carried out using the drug 3-5 ml for rinsing and injection into the middle ear up to 3 times a day for up to 2 weeks. When treating inflammation of the nasal sinuses, the medicine is used in 7-10 ml for rinsing the nose, nasopharynx and sinuses and 3 ml for injection into these sinuses once daily for 8-10 days. The solution is also injected into the nasal cavity in the form of turundas moistened with bacteriophage for half an hour. This procedure is carried out three times a day for up to 2 weeks. When treating stomatitis and chronic periodontitis, 15-20 ml of the product are used to rinse the mouth up to four times a day, and also insert moistened turundas into periodontal pockets for 7-10 minutes. The duration of therapy is 8-10 days. For keratoconjunctivitis and conjunctivitis, the product is instilled 2-3 drops up to five times a day for a week, for a corneal ulcer - 3-4 drops per day for 8-10 days, for iridocyclitis (purulent) 7-8 drops of the solution are instilled every 3 hours and consumed orally in medicinal dosages for 8-10 days. In case of an abscess, after its cavity has been emptied, the Klebsiella pneumoniae bacteriophage is injected orally in a smaller quantity than the amount of pus removed. When treating osteomyelitis, 10-20 ml of solution is applied to the wound after surgical treatment. If it is necessary to administer it into the pleural, articular or other limited cavities, capillary drainage is installed, through which the medicine is administered in a dose of 100 ml daily for 3-5 days. For pyelonephritis, cystitis, urethritis, the drug is taken orally. If the cavities of the renal pelvis or bladder are drained, then the medicine is administered through a drainage tube twice a day, 30-40 ml into the bladder cavity or 6-7 ml into the renal pelvis. For gynecological diseases of a purulent-inflammatory nature, the drug is injected into the vagina or uterus, 7-10 ml every day. For colpitis, treatment is carried out by irrigation of 10 ml or tamponing twice a day for 2 hours. For intestinal dysbiosis and pancreatitis, cholecystitis, gastroenterocolitis, the drug is taken orally three times a day an hour before meals for 1-3 weeks. A combination of twice oral administration with a single rectal administration of an age-specific dose per day in the form of an enema is also permitted. When treating purulent wounds, the Klebsiella pneumoniae bacteriophage is used in the form of applications, dressings, irrigation, and injection of 10-50 ml into the drainage at least once a day for 10-15 days. To prevent hospital-acquired surgical infections, 5-50 ml of the product is used to treat freshly infected and postoperative wounds once daily for a week. Use of the drug in children under 6 months of age, including premature infants For pneumonia, gastroenterocolitis, neonatal sepsis, Klebsiella pneumoniae bacteriophage is used 4-5 ml orally 2-3 times a day half an hour before feeding. If there is uncontrollable vomiting, then 7-10 ml of the medicine is used once daily for high enemas. The combined use of rectal and oral routes of drug administration is permitted. The course of therapy lasts 1-2 weeks. In order to prevent the occurrence of hospital infections in newborns, the medicine is used according to epidemic indications, 4-5 ml orally three times a day, half an hour before feeding, during the entire stay in the hospital. When treating pyoderma, omphalitis, and septic wounds, the product is used in the form of applications with a soaked clean napkin, which is applied to the wound surface twice a day.

Bacteriophage Pio polyvalent Sextaphage liquid 20ml N4 fl. vn

Before use, the vial with the bacteriophage must be shaken and inspected. The preparation must be transparent and free of sediment. Attention! 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.

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).

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

Locally in the form of irrigation, lotions and tamponing with liquid phage in an amount of up to 200 ml, depending on the size of the affected area. For abscesses, the bacteriophage is injected into the cavity of the lesion after removing the pus using a puncture. The amount of the administered drug should be slightly less than the volume of removed pus. In case of osteomyelitis, after appropriate surgical treatment, 10-20 ml of bacteriophage is poured into the wound. Introducing up to 100 ml of bacteriophage into cavities - pleural, articular and other limited cavities, after which capillary drainage is left, through which the bacteriophage is reintroduced over several days. 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. For purulent-inflammatory gynecological diseases, the drug is administered into the cavity of the vagina and uterus in a dose of 5-10 ml once daily. 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, instilling, introducing moistened turundas (leaving them for 1 hour). For conjunctivitis and keratoconjunctivitis, the drug is instilled 2-3 drops 4-5 times a day, for a purulent corneal ulcer - 4-5 drops, for purulent iridocyclitis, the drug is used 6-8 drops every 3 hours in combination with oral administration. In the treatment of stomatitis and chronic generalized periodontitis, the drug is used in the form of rinses in the mouth 3-4 times a day in a dose of 10-20 ml, as well as by introducing turundas impregnated with pyobacteriophage into the periodontal pockets for 5-10 minutes. For intestinal forms of the disease, diseases of internal organs, and dysbacteriosis, the bacteriophage is used orally and in the form of enemas for 7–20 days. The bacteriophage is given orally 3 times a day on an empty stomach 1 hour before meals. In the form of enemas, they are prescribed once a day instead of once taken by mouth.

Recommended dosages of the drug Patient's age Dose per 1 dose (ml) Orally In enema 0 - 6 months. 5 10 6 - 12 months. 10 20 From 1 year to 3 years 15 20-30 From 3 to 8 years 20 30-40 From 8 years and older 20 – 30 40-50

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.

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 (see table). 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 enemas) and oral (by 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 to the affected area of ​​the skin).

Pyobacteriophage complex

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

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

1. Locally in the form of irrigation, lotions and tamponing with liquid phage in an amount of up to 200 ml, depending on the size of the affected area. For abscesses, the bacteriophage is injected into the cavity of the lesion after removing the pus using a puncture. The amount of the administered drug should be slightly less than the volume of removed pus. In case of osteomyelitis, after appropriate surgical treatment, 10-20 ml of bacteriophage is poured into the wound.

2. Introduction into cavities - pleural, articular and other limited cavities of up to 100 ml of bacteriophage, after which capillary drainage is left, through which the bacteriophage is reintroduced over 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 and uterus in a dose of 5-10 ml once daily.

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 conjunctivitis and keratoconjunctivitis, the drug is instilled 2-3 drops 4-5 times a day, for a purulent corneal ulcer - 4-5 drops, for purulent iridocyclitis, the drug is used 6-8 drops every 3 hours in combination with oral administration.

7. In the treatment of stomatitis and chronic generalized periodontitis, the drug is used in the form of rinses in the mouth 3-4 times a day in a dose of 10-20 ml, as well as by introducing turundas impregnated with pyobacteriophage into the periodontal pockets for 5-10 minutes.

8. For intestinal forms of the disease, diseases of internal organs, dysbacteriosis, the bacteriophage is used orally and in an enema. The bacteriophage is given orally 3 times a day on an empty stomach 1 hour before meals. In the form of enemas, they are prescribed once a day instead of once taken by mouth.

Recommended dosage of the drug

The use of bacteriophages does not exclude the use of other antibacterial drugs. 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.

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 (see table). 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 enemas) and oral (by 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 to the affected area of ​​the skin).

Possibilities of using bacteriophages in the treatment of infectious diseases of the ENT organs in children

NIKIFOROVA G.N.

., Doctor of Medical Sciences, Professor,
PSHONKINA
D.M.
Department of Ear, Nose and Throat Diseases, First Moscow State Medical University named after. THEM. Sechenov Ministry of Health of the Russian Federation, Moscow Less than a century of history of the use of antibacterial drugs in the treatment of infectious and inflammatory diseases has demonstrated the wide possibilities for adaptation of many strains of microorganisms to the toxic effects of these drugs.
Over the past decades, the resistance of infectious agents to antimicrobial drugs widely used in otorhinolaryngology has increased significantly. In childhood, the incidence of diseases of the ENT organs is higher than in adults, while at the same time, viral diseases in children are often complicated by the development of bacterial processes, which leads to the search for new methods of etiotropic therapy. An analysis of the literature above shows the validity of the use of phage therapy in the treatment of diseases of the ENT organs in children, both locally and systemically, including in combination with traditional antibacterial therapy. The advantage of therapeutic bacteriophages is their high specificity for certain microorganisms, good compatibility with other drugs, minimal risk of adverse events and the absence of allergic reactions. In childhood, the frequency of infectious and inflammatory diseases of the upper respiratory tract and ear is much higher than in adults, which is determined by a number of anatomical features, as well as the imperfection of the child’s immune system.
The significant prevalence of ENT diseases in childhood often correlates with the development of severe and numerous complications. The vast majority of infectious processes of the ENT organs in children have a viral etiology; in 25–30% of acute diseases of the respiratory tract, viral-bacterial associations are detected [6]. It is no secret that viral infections in children quite often cause the development of bacterial processes in the ENT organs - rhinosinusitis, tonsillopharyngitis, otitis, etc. Etiologically significant pathogens in most of the above clinical cases are Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes Mycoplasma pneumoniae, Chlamydia pneumoniae, Staphylococcus aureus, Arcanobacterium haemolyticum, Haemophilus influenzae, Moraxella catarrhalis
and some other microorganisms [4, 5, 13]. Diseases of the paranasal sinuses are the most common complications of respiratory viral infections, however, tonsillopharyngitis and otitis media are of no less clinical importance due to the high risk of developing chronic processes. Otitis media in childhood develops much more often than in adult patients. For example, by the age of 3, 83% of children experience at least one episode of acute otitis media, and 46% are diagnosed with 3 or more cases of this disease [14].

Adequate etiotropic therapy of bacterial infections of the ENT organs is an urgent problem of modern clinical medicine. The use of antibacterial drugs in the treatment of infectious and inflammatory diseases over the years has led to the development of adaptation of a significant number of strains of microorganisms to the toxic effects of drugs. The process of pathogen resistance is also facilitated by the conditions provided by nature for the exchange of various genetic elements between bacteria. Also among the factors contributing to the growth of resistance of microorganisms, it should be noted the uncontrolled use of antibiotics, patients’ independent reduction of treatment periods, and the use of low doses of drugs. Since the eighties of the twentieth century, there has been a significant increase in the resistance of microorganisms to many antibacterial drugs, including macrolides and β-lactams, traditionally widely used in otorhinolaryngology. Recently, there has been a sharp increase in the number of bacterial strains producing β-lactamases, which, according to the literature, may be due to the widespread use of different generations of cephalosporins in inpatient and outpatient practice [12]. It is very important to consider that the use of antibacterial drugs in any case has a damaging effect not only on pathogenic, but also on the normal microflora of the human body, thereby increasing the risk of subsequent colonization by pathogenic microflora. Considering the above, the relevance of choosing rational etiotropic topical therapy for bacterial infections in childhood is beyond doubt. Bacteriophages have good prospects in this aspect.

Bacteriophages were discovered by Canadian microbiologist Felix D'Herelle in 1917 while observing the effect of bacterial lysis [11]. Before him, other researchers had encountered similar phenomena (N.F. Gamaleya, 1898; F. Twort, 1915), but it was F. D'Herelle who not only suggested the viral etiology of bacterial death, but also managed to isolate the lytic factor. The discovered viruses were called bacteriophages and began to be used in the treatment of infectious diseases. However, with the advent of the “era of antibiotics,” phage therapy was undeservedly forgotten. At present, when antibiotic resistance of pathogenic microorganisms is increasing everywhere and the effectiveness of etiotropic treatment is steadily decreasing, the interest of clinical medicine in bacteriophages has again increased markedly.

Bacteriophages are the most numerous, widespread in the biosphere and, presumably, the most evolutionarily ancient group of viruses. Scientists have calculated that 1024 bacteria can be infected by bacteriophages in 1 second [15]. One of the areas of application of bacteriophages is antimicrobial treatment, an alternative to antibacterial drugs.

Due to their high safety and reactogenicity, bacteriophages are approved for use in pediatrics without age restrictions (including premature infants) [1, 3, 7]. The use of bacteriophage preparations stimulates the activation of specific and nonspecific immunity factors, therefore phage therapy is especially effective in the treatment of chronic inflammatory diseases against the background of immunosuppressive conditions [8, 16]. In August 2009 The Nestle Nutrition Corporation (Switzerland) in Bangladesh initiated clinical studies of the use of Escherichia coli bacteriophage in the treatment of intestinal infections in children aged 6 to 60 months, the results of which demonstrated good tolerability and high efficiency of this treatment method [17]. Another study in children with acute purulent rhinosinusitis showed a positive effect of bacteriophages on mucociliary clearance, an important universal mechanism for protecting the mucous membrane of the respiratory tract. This allows us to classify bacteriophages not only as etiological, but also as pathogenetic agents for the treatment of purulent-inflammatory diseases of the ENT organs [10]. Based on the results of clinical studies, data were also obtained on the positive effect of phage therapy on the clinical manifestations of chronic tonsillitis and the inoculation of Staphylococcus aureus from the surface of the palatine tonsils [9].

Currently, the Russian medical industry produces various bacteriophage preparations to combat infectious diseases caused by a significant range of pathogenic and opportunistic bacteria [18].

In most clinical cases, bacteriophages are prescribed for oral administration, but this is not the only way to use them. To treat and prevent diseases of the ENT organs, you can instill the drug into the nasal cavity, rinse, rinse and irrigate the tonsils with it, and insert turundas with a medicinal solution into the ear canal. Currently, the following bacteriophages are used: staphylococcal, streptococcal, dysenteric polyvalent, klebsiella, pyobacteriophage and others. Pyobacteriophage polyvalent - Sextaphage (FSUE NPO "Microgen" of the Ministry of Health of Russia) is capable of specifically destroying the most significant pathogens of diseases of the ENT organs, in particular staphylococci, streptococci and other microorganisms. In connection with the above properties, indications for the use of this drug are purulent-inflammatory diseases of the upper respiratory tract and ear, as well as their complications - phlegmon and abscesses. According to the manufacturer's instructions, the drug can be used topically - in the form of rinses, irrigations, applications; for insertion into the paranasal sinuses, middle ear cavity, and rinsing the abscess cavity. For intracavitary administration for infections of the ENT organs, it is recommended to use from 2.0 to 20.0 ml 1 to 3 times a day. The duration of treatment with polyvalent pyobacteriophage ranges from 5 to 15 days. There is data on the anti-inflammatory and immunoregulatory properties of the drug pyobacteriophage polyvalent (Sextaphage) [2]. Analysis of the history, mechanism of action and use of bacteriophages in medicine allows us to say with confidence that the advantage of this method of treatment is the ability of viral agents to infect both sensitive and polyantibiotic-resistant microbial cells. An important feature of phage therapy in comparison with etiotropic chemotherapy is the absence of the risk of the spread of pathogenic agents resistant to therapy in the population and the negative impact on normal microflora. Features of bacteriophages that give an advantage over other methods of treatment are also their high specificity for certain microorganisms, good compatibility with other drugs, and the absence of allergic reactions and other undesirable effects.

Thus, phage therapy is an effective and safe treatment method and can be used in the treatment of inflammatory diseases of the ENT organs of bacterial etiology, including in childhood.

LITERATURE

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Source:

Medical Council, No. 6, 2015