Zavantazhenya...
Our world is entering an era when antibiotics are no longer effective. The frequency of use and abuse of antibacterial drugs for therapeutic and prophylactic purposes in medicine and veterinary medicine, in the food industry and agriculture causes the emergence of resistant strains of bacteria. Such microorganisms are especially common in medical institutions, where they colonize wards and dressing rooms, medical equipment and even disinfectant solutions. Resistant bacteria cause various complications and increase mortality in patients after invasive examinations and operations, in patients with weakened immunity (especially in oncology, burns, neonatology, and intensive care units) [1].
Even the discoverer of antibiotics, Alexander Fleming, warned in his Nobel lecture in 1945 that microbial resistance to penicillin occurs quite quickly. And in our time, according to WHO Director General T. A. Ghebreyesus: “Microbial resistance to antibiotics is a global problem that poses a threat to health and can undo a century of progress in the field of medicine.” WHO experts draw attention to the need to develop new drugs and methods for treating infectious diseases that would not lead to the emergence of drug resistance [2]. As an alternative to antibiotics and chemotherapeutic antimicrobial agents, phage therapy for bacterial infections can be used.
Back in 1915, the English bacteriologist Frederick Twort described an “infectious disease of staphylococci,” the causative agent of which passed through bacterial filters and could be transferred from one colony of bacteria to another. Independently of F. Twort, in 1917, the French microbiologist Felix D'Herelle, while studying Shigella (the causative agent of dysentery), discovered an agent that lyses bacteria and gave it the name bacteriophage (bacteria eater). F. D'Herelle discovered that bacteriophages are specific and diverse and, since 1919, successfully used phage therapy in the treatment of dysentery, cholera and wound infections. In 1934, F. D'Herelle participated in the creation of the Research Institute of Bacteriophages (later the Research Institute of Vaccines and Serums) in Tbilisi [3].
Nowadays, it is known that bacteriophages are the most numerous and widespread group of viruses on Earth - the number of different bacteriophages is huge and approximately equal to the total number of bacteria - 1030. Bacteriophages are an important natural tool for controlling the number of microorganisms on the planet. They live wherever bacteria exist: in soil, water, on plants, on mucous membranes and in the digestive tract of humans and animals [4]. At the same time, phages can exist for a long time (for many decades) even in the absence of a host microbe, retaining the ability to infect bacterial cells.
The majority of bacteriophages (95%) belong to the order Caudovirales - tailed viruses. Their particles range in size from 50 to 200 nm and consist of a head (capsid), containing the genome, and a tail, which ensures the attachment of the virus to the surface of the target bacterium. The tail is a “molecular syringe” that pierces the wall of the bacterium and injects viral DNA inside. In structure, the bacteriophage is fundamentally different from animal and plant viruses and resembles a high-tech nanoobject.
One of the key aspects of the functioning of bacteriophages is their ability to highly specific interaction with certain conservative structures on the surface of bacterial cells - lipopolysaccharides, peptidoglycans, teichoic acids, porins, flagellins, etc. Since such molecules are not on the cells of the body, bacteriophages do not penetrate them and are safe for humans . Bacteriophages are strictly specific (they destroy only a certain type of bacteria), therefore, bacteriophage preparations, unlike antibiotics, do not inhibit the normal human microflora.
After a bacteriophage penetrates a bacterial cell, it begins replication and creates a huge number of copies of itself. When using a bacteriophage, the number of phage will naturally increase until the pathogenic target bacteria are destroyed, so the drug can be used in small dosages. Since bacteriophages do not infect human cells, their drugs do not cause side effects. Cases of allergic reactions when using them are caused by toxins released when bacteria die (the same reactions are possible when taking antibiotics). It has been revealed that under the influence of the bacteriophage, phagocytosis is activated, the metabolic activity of neutrophils increases, which prevents the relapse of the infectious disease and the chronicity of the inflammatory process [5].
Bacteriophages are most effective when applied topically (in the form of solutions for instillation, rinsing, inhalation, enemas) on the skin, in wounds, in the ear, on the mucous membranes of the nasopharynx, eyes, and large intestine. But to enhance the effect of phage therapy, it is possible to use it orally - they penetrate the circulatory and lymphatic systems (thus reaching the localization sites of target bacteria) and are excreted in the urine within a few days. Bacteriophage preparations are used to treat surgical, burn, urogenital, gastroenterological, skin, eye infections and diseases of the ENT organs. Treatment with bacteriophages is carried out after inoculation and determination of the sensitivity of the isolated pathogens to this bacteriophage. When bacteriophages and antibiotics act together, a mutual enhancement of the antibacterial effect is observed. This allows you to reduce the duration of use and dose of antibiotics to values that do not cause significant side effects. Phage therapy allows us to solve the problems of treating patients with allergic reactions to antibiotics and treating infections caused by multidrug-resistant pathogens.
The use of bacteriophages in the treatment of ENT infections
The complex polyvalent preparation of bacteriophages "Pyophage" contains viruses that lyse Streptococcus pyogenes and Staphylococcus aureus - common pathogens of purulent-inflammatory diseases of the upper respiratory tract (rhinitis, sinusitis, sinusitis, tonsillitis, laryngitis, tracheitis) and ears (external and otitis media).
“ Pyophage ” includes bacteriophages that lyse Pseudomonas aeruginosa - Pseudomonas aeruginosa, which received the species name (aeruginosa - rust) due to its ubiquity (lives in soil, water, medical solutions), virulence and natural resistance to many groups of antibiotics. Also, “ Piophage ” contains bacteriophages against enterobacteria (Escherichia coli, Proteus vulgaris and mirabilis), which are frequent causative agents of purulent-inflammatory and nosocomial infections. 1 ml of the drug contains specific bacteriophages in a concentration of at least 1 × 105 phage particles.
The use of Pyophage in the treatment of diseases of the nose and throat
Acute rhinitis and rhinosinusitis most often occur as a result of acute respiratory viral infections and are manifested by mucous-serous discharge, which quickly becomes purulent in nature due to the addition of staphylococci and streptococci. In acute and chronic allergic rhinitis and vasomotor rhinitis, a bacterial infection is also present in the nose and aggravates the course of the disease.
“ Pyophage ” is recommended to be instilled after using the nose 3 times a day in the amount of 2 ml 3 times a day for 7 to 20 days. For sinusitis, after removing pus from the sinus, the introduction of the complex “ Pyophage ” is effective. Pyophage therapy courses significantly improves the well-being of patients with chronic rhinitis. For acute and chronic tonsillitis and pharyngitis, “ Pyofag ” is taken as a gargle and orally in age-appropriate dosages for 7–20 days. For laryngitis and tracheitis, the “ Pyophaga ” solution is used in the form of inhalations using a nebulizer in an amount of 5 ml 3 times a day until recovery.
The use of "Piophage" in the treatment of ear diseases
1. Otitis externa occurs when the ear canal is traumatized during ear toilet, during maceration and infection of the skin with discharge from chronic purulent otitis media, when wearing hearing aids and is manifested by: 1) diffuse inflammation of the skin of the ear canal; 2) furunculosis. With external otitis, there is pain, congestion and discharge from the ear, and a possible increase in temperature. The main causative agents of external otitis: S.aureus, enterobacteria (E.coli, Klebsiella, Proteus) and P. aeruginosa
There is also necrotizing (malignant) external otitis - a rare, dangerous disease that occurs in patients with immunodeficiencies and diabetes and is caused by P. aeruginosa. Inflammation spreads from the skin of the external auditory canal to the mastoid process, temporal bone and, ultimately, to the meninges and brain tissue.
For the treatment of external otitis, " Pyofag " is administered in a dose of 2 to 10 ml (the amount of the administered drug should be slightly less than the volume of removed pus) in the form of instillation or wetting of turundas (which are left for 1 hour) 1 to 3 times a day for 7 –20 days, depending on the severity of the process. For moderate and severe forms of otitis externa, it is necessary to combine the use of bacteriophage with antibacterial drugs, which has a synergistic effect.
2. Acute otitis media occurs after a respiratory infection (as a result of penetration of the pathogen into the middle ear through the Eustachian tube) and is most often caused by viruses (adeno-, enteroviruses, influenza and parainfluenza viruses). Bacterial suppurative otitis media in most cases is a complication of acute otitis and can be acute or chronic. Acute bacterial otitis media is most often caused by streptococci (S. pneumoniae, S. pyogenes) and S. aureus. In this case, there is a sharp pain in the ear and fever. After the eardrum ruptures, the pain subsides and discharge from the ear is noted. Purulent otitis media can cause complications - mastoiditis, damage to the facial nerve, sepsis, labyrinthitis. Acute otitis media mainly affects young children.
" Pyophage " is a safe drug and is approved from birth. To treat otitis media, " Pyophagus " is administered into the nose as an instillation (tilting the head towards the affected ear so that the drug enters the middle ear through the Eustachian tube) in a dose of a few drops (for newborns and small children) to 2 ml for adults and in the ear ( after a breakthrough or surgical opening of the eardrum) in a dose of 2 to 10 ml in the form of instillation or wetting of turundas (which are left for 1 hour) 1 to 3 times a day for 7–20 days, depending on the severity of the process. It is also recommended to use Pyophage orally in age-related dosages, which enhances the effectiveness of phage therapy.
“ Pyophage ” is an effective, reliable and safe drug that is approved at any age and in our time, when complications of antibiotic therapy are very common, and resistance to antibiotics and antiseptics is growing on a catastrophic scale, it is an indispensable assistant to the attending physician.
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Bibliography
1. Feshchenko Yu. I. Antibiotic resistance of microorganisms. Stan ta shlyakhy їkh vyrіshennya / Yu. I. Feshchenko, M. I. Gumenyuk, O. S. Denisov // Ukrainian chemotherapist. magazine — 2010.— No. 1–2. — P. 4–8.
2. The problem of resistance of microorganisms to antibiotics / O.L. Zimbalista // Modern Pediatrics. — 2022. — No. 2 (82). — P. 52–56.
3. Clinical and prophylactic preparations of bacteriophages / E. Sparrow, O. Voronkova, O. Sirokvasha, A. Vinnikov. // Bulletin of Lviv University. The series is biological. — 2014. — VIP. 64. - pp. 52–66.
4. Prospects for the development of diagnostic and therapeutic preparations of bacteriophages in medicine / O.S. Voronkova, O.A. Sirokvasha, T.M. Polishko, A.T. Vinnikov // Newsletter of Dnipropetrovsk University. Biology, medicine. — 2012. — VIP. 3, T. 2. - pp. 26–31.
5. Chhibber Sanjay. Application of Therapeutic Phages in Medicine / Sanjay Chhibber, Seema Kumari // Bacteriophages: edited by Ipek Kurtboke. - InTech, 2012. - P. 139–158.
The article was published in the journal “Modern Pharmacy” September, 2019
Pyobacteriophage complex
The drug is used orally, rectally, locally, or by injection into cavities. Orally: enterocolitis, diseases of internal organs, intestinal dysbiosis - 3 times a day 1 hour before meals. For 1 dose up to 6 months - 5 ml, 6-12 months - 10 ml, from 1 to 3 years - 15 ml, from 3 to 8 years - 20 ml, from 8 years and older - 30 ml.
Rectally 1 time per day (in the form of an enema) in combination with twice oral administration. For 1 dose up to 6 months - 10 ml; 6-12 months - 20 ml; from 1 year to 3 years - 30 ml; from 3 to 8 years - 40 ml; from 8 years and older in an enema - 50 ml.
Locally for 7-20 days in the treatment of purulent-inflammatory diseases with localized lesions.
If the cavity of a purulent lesion is treated with chemical antiseptics, before using the bacteriophage, rinse the cavity with a sterile 0.9% NaCl solution.
Purulent wounds - in the form of irrigation, applications, bandages, administration through drainage at least 1 time per day. For abscesses, after opening and removing the purulent contents, the drug is administered in an amount less than the volume of the removed pus. In drained cavities daily, 1 time per day - 20-200 ml.
Osteomyelitis - 10-20 ml into the wound cavity through the turunda, drainage.
Introduction into cavities (pleural, articular and other limited cavities) - up to 100 ml of bacteriophage, leaving capillary drainage through which the bacteriophage is reintroduced over several days.
Purulent-inflammatory gynecological diseases - 5-10 ml daily 1 time per day into the cavity of the vagina, uterus.
Purulent-inflammatory diseases of the ENT organs - 2-10 ml 1-3 times a day in the cavity of the middle ear, nose. The bacteriophage is used for rinsing, washing, instilling, and introducing moistened turundas (leaving them for 1 hour).
Cystitis, pyelonephritis, urethritis - 20-50 ml into the bladder and 5-7 ml into the renal pelvis through a cystostomy or nephrostomy.
Children under 6 months. Sepsis, enterocolitis in newborns, including premature babies, 2-3 times a day in the form of high enemas (through a gas tube or catheter). In the absence of vomiting and regurgitation, the drug is used orally, mixed with breast milk. A combination of rectal and oral administration 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. 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.
Omphalitis, pyoderma, infected wounds - 2 times a day daily in the form of an application (moisten a gauze cloth with bacteriophage and apply to the umbilical wound or affected area of skin).
