PIOBACTERIOPHAGE COMPLEX solution for oral administration,

PIOBACTERIOPHAGE COMPLEX solution for oral, local and external use 100ml bottle

Pyobacteriophage is intended for local and oral use, as well as for rectal administration. Treatment of purulent-inflammatory processes is recommended through simultaneous local and oral administration of the drug Piobacteriophage. Depending on the location of the infection, Pyobacteriophage is recommended for: 1. Local application in the form of lotions, irrigations, applications and tampons, moistened solutions. In this case, use the required amount of solution based on the size of the affected area. For abscesses, the solution should be injected into the cavity after removing the pus by puncture (the volume of the solution should be slightly less than the volume of the extracted pus). 2. Injection of the solution into the pleural, articular and other limited cavities. After administering the required amount of bacteriophage, capillary drainage is left, through which repeated doses of the drug are subsequently administered. 3. Injection of the solution into the drained cavity of the bladder and renal pelvis through a cystostomy or nephrostomy. 4. Introducing the solution into the uterine or vaginal cavity, including in the form of tampons soaked in the solution. 5. Instillation, washing and rinsing, as well as the introduction of turundas moistened with a solution, in otolaryngological practice. 6. Applications to the conjunctival sac in ophthalmological practice. 7. Insertion of moistened turundas into periodontal pockets in dental practice. 8. Introductions into the rectum in the form of enemas in gastroenterological practice. The dose of the drug Piobacteriophage and the duration of the course of therapy are determined by the doctor. A single dose recommended for children under 6 months is 5 ml when administered orally or 10 ml when administered rectally. A single dose recommended for children 6-12 months is 10 ml when administered orally and 20 ml when administered rectally. A single dose recommended for children 1-3 years old is 15 ml when administered orally and 30 ml when administered rectally. A single dose recommended for children 3-8 years old is 20 ml when administered orally and 40 ml when administered rectally. A single dose recommended for children over 8 years of age and adults is 30 ml when administered orally and 50 ml when administered rectally. In the treatment of purulent-inflammatory diseases and intestinal diseases, as a rule, the appropriate single dose is prescribed three times a day. If, when using a bacteriophage locally, the wound was pre-treated with an antiseptic, it is necessary to wash the wound with a 0.9% sodium chloride solution before using the Piobacteriophage solution. For children under 6 months of age with enterocolitis and sepsis, Piobacteriophage solution is administered in the form of high enemas twice or thrice a day. If the child does not develop regurgitation and vomiting, the drug can be given orally. The average duration of therapy is from 5 to 15 days. As a prophylaxis, the drug is prescribed in a single dose twice a day for 5-7 days.

Pyobacteriophage complete liquid 100ml (Microgen)

Bacteriophages in the complex treatment of acute bacterial rhinosinusitis

Acute bacterial rhinosinusitis (ABRS) is a fairly common disease with a constant upward trend. For example, in the United States in recent years, approximately 25 million visits to medical care per year have been recorded for ABRS [17, 18]. In Russia, this problem is further complicated by the fact that from year to year more and more patients require hospital treatment, and the proportion of patients hospitalized for diseases of the paranasal sinuses increases annually by 1.5–2%. Thus, in the structure of otorhinolaryngological hospitals, patients with sinus pathology make up from 15 to 36%. Maxillary sinusitis and ethmoiditis are more common [1, 5, 9, 12]. The classification of ABRS is based on the duration and recurrence of symptoms. The most successful, in our opinion, is the classification proposed by a special commission of the American Academy of Otolaryngology Head and Neck Surgery (Table 1) [14]. According to the severity of the course, the following are distinguished: • mild course: nasal congestion, mucous or mucopurulent discharge from the nose and/or into the oropharynx, increased body temperature up to 37.5˚C, headache, weakness, hyposmia; on an x-ray of the paranasal sinuses - the thickness of the mucous membrane is less than 6 mm; • moderate: nasal congestion, purulent discharge from the nose and/or into the oropharynx, body temperature above 37.5˚C, pain and tenderness on palpation in the projection of the sinus, headache, hyposmia, malaise, there may be radiating pain in the teeth and ears; on an x-ray of the paranasal sinuses - thickening of the mucous membrane of more than 6 mm, complete darkening or fluid level in one or two sinuses; • severe: nasal congestion, often profuse purulent discharge from the nose and/or into the oropharynx (but may be completely absent), body temperature above 38˚C, severe pain on palpation in the projection of the sinus, headache, anosmia, severe weakness; on the x-ray of the paranasal sinuses - complete darkening or fluid level in more than two sinuses; blood test: leukocytosis, shift of the formula to the left, increased ESR, orbital, intracranial complications or suspicions of them. A serious complication is cavernous sinus thrombosis, the mortality rate of which reaches 30% and does not depend on the adequacy of antibacterial therapy [14]. Most often, acute rhinosinusitis develops against the background of ARVI. It is believed that during viral infections the paranasal sinuses are involved in the inflammatory process to one degree or another. But the formation of OBRS occurs only in 1 or 2% of cases. However, 1–2% is a fairly large incidence rate. One of the reasons for the increase in the number of patients with acute bacterial purulent rhinosinusitis is recognized to be changes in the nature of the immune response of the mucous membranes of the nose and pharynx. In particular, sinusitis is considered a manifestation of an infectious syndrome caused by immune deficiency both at the local and systemic levels [2, 5, 9]. According to A.S. Lopatin, ABRS is almost always caused by stagnation of secretions and impaired ventilation in the paranasal sinuses. And if mucociliary transport is disrupted, prolonged contact of pathogenic bacteria with mucosal cells makes it possible to form bacterial inflammation.

As a rule, the most significant role in the development of bacterial infections of the upper respiratory tract is played by Streptococcus pneumoniae, Haemophilus influenzae, as well as Streptococcus pyogenes, Moraxella catarrhalis, Staphylococcus aureus, Pseudomonas aeruginosa, Proteus spp, Escherichia coli and a number of other pathogenic and opportunistic strains of bacteria [ 1, 2, 5, 6, 14]. The main medications in the treatment of ABRS are antibacterial drugs, the use of which is aimed at eradicating pathogens. It is believed that the optimal use of antibiotics to which microorganisms are most sensitive (Table 2).

The criterion for the rationality of prescribed antibiotic therapy is the assessment of the patient’s condition 72 hours (3rd day) after the start of treatment. Positive dynamics of the patient's condition suggests continuation of initial antibiotic therapy. If there is no positive clinical dynamics, the antibiotic should be changed after 72 hours. In the treatment of sinusitis, in most cases, priority remains with antibacterial monotherapy. Prescribing two or more antibiotics is justified in cases of severe sinusitis or the presence of complications [5]. The duration of treatment depends on the drug chosen and the severity of the sinusitis. The course of treatment can range from 7 to 14 days. It is important to completely stop the inflammatory process in the paranasal sinuses, therefore, with the goal of complete eradication of the pathogen, you should focus on a treatment period of 7–10 days. Considering the significant role of swelling of the nasal mucosa and obstruction of the anastomosis of the natural openings of the paranasal sinuses in the pathogenesis of ARS, great importance is attached to vasoconstrictor drugs: xylometazoline, oxymetazoline, phenylephrine, etc. Topical glucocorticosteroids have relatively recently entered the arsenal of drugs for the treatment of acute rhinosinusitis. The purpose of the prescription is to reduce the secretion of glands of the mucous membrane, reduce tissue edema and, as a result, improve nasal breathing (mometasone furoate nasal spray 100 mcg 2 times / day) [5, 6].

Unfortunately, due to the uncontrolled use of drugs, especially antibacterial ones, there is a constant evolution of bacterial cells that acquire new properties and become more resistant. Over the past decade, the resistance of these bacteria to macrolides and penicillins, traditionally widely used in otolaryngology, has increased significantly. In addition, in recent years there has been a sharp increase in the number of bacteria producing extended-spectrum β-lactamases, which is associated with the widespread use of first, second and third generation cephalosporins in inpatient and outpatient practice [10].

Antibiotic resistance is a fairly serious problem in the treatment of sinusitis. According to the literature, a particularly large percentage is observed in Western European countries, which complicates the treatment tactics of sinusitis [5]. The spread of antibiotic resistance among pathogens of diseases of the ENT organs, along with toxic, immunosuppressive and allergic reactions to the administration of antibiotics, is the leading reason for the decrease in the effectiveness of antibacterial therapy. However, in recent years, a large number of strains of microorganisms have appeared that are not sensitive to antibiotics widely used in practice [9]. Thus, methicillin resistance is observed in 30–40% of Staphylococcus aureus. There has been a tendency towards increasing resistance to penicillins, macrolides, as well as aminopenicillins and first and second generation cephalosporin antibiotics [5, 9].

In addition to the resistance of microorganisms to drugs, we also have to deal with another pressing problem - the body’s allergic reaction to an antibiotic. The above data draws our attention to the need to search for new antibacterial drugs that can be used to treat patients with rhinosinusitis. As an alternative, highly effective bacteriophage preparations can be used, attention to which has justifiably increased recently [3, 4, 11]. Bacteriophages, or phages (from ancient Greek φᾰγω - “I devour”) are viruses that selectively infect bacterial cells. Most often, bacteriophages multiply inside bacteria and cause their lysis. The discoverer of bacteriophages was the Canadian scientist, bacteriologist Felix D'Herelle (25.4.1873, Montreal - 22.2.1949, Paris), but in 1929 Alexander Fleming, observing the antagonism of Penicillium notatum and staphylococcus in a mixed culture, discovered penicillin and suggested the possibility of its use for medicinal purposes, and phage therapy was forgotten for some time. However, now that the effects of antibiotic use have changed the properties of many bacteria, scientists have again turned their attention to this group of drugs. Publications documenting phage therapy belong to the group of Stephan Slopek from the Institute of Immunology and Experimental Medicine of the Polish Academy of Sciences (Wroclaw). This group published a series of detailed articles in Archivum Immunologiae et Therapie Experimentalis (cf. Slopek et al., 1983, 1985, 1987), describing the results of phage treatment from 1981 to 1986 in 550 patients [8]. Bacteriophage preparations have been successfully used in Russia for more than 60 years (1936 - the beginning of the use of bacteriophages in the USSR).

What is the mechanism of action of bacteriophages? The process of interaction between a virulent bacteriophage and a cell consists of several stages: adsorption of the bacteriophage on the cell, penetration into the cell, biosynthesis of phage components and their assembly, and release of bacteriophages from the cell. The duration of this process can range from several minutes to several hours. Then cell lysis occurs and new mature bacteriophages are released. A very important property of bacteriophages is their specificity. Based on specificity, there are polyvalent bacteriophages that lyse cultures of one family or genus of bacteria, monovalent (monophages) - lysing cultures of only one type of bacteria, and also characterized by the highest specificity - typical bacteriophages, capable of causing lysis of only certain types (variants) of a bacterial culture within a species bacteria [7, 12, 13].

Bacteriophage preparations are used to treat purulent-septic and enteral diseases caused by opportunistic bacteria of the genera Escherichiae, Proteus, Pseudomonas, Enterobacter, Staphylococcus, Streptococcus, Klebsiellae. It is these bacteria that are the causative agent of severe sinusitis against the background of immunodeficiency states, as mentioned earlier. Bacteriophages have a number of advantages: specificity of action, absence of inhibition of normal microflora and allergic reactions, stimulation of specific and nonspecific immunity factors [3, 4, 7, 12, 16]. The use of specific bacteriophages makes it possible to optimally carry out targeted lysis of pathogenic flora for the purpose of an antimicrobial effect, as well as to restore normal microbiocenosis. Bacteriophages do not have a toxic effect and do not suppress normal microflora. They indirectly have a stimulating immunological effect, affecting cellular and humoral immunity [19]. Various preparations of bacteriophages, used in accordance with the type of pathogen, are highly effective in the treatment of peritonsillar abscesses, inflammation of the sinuses, purulent-septic diseases of patients in intensive care units, surgical infections, pyelonephritis, cholecystitis, gastroenterocolitis, intestinal dysbiosis, inflammatory diseases and sepsis of newborns [3, 7, 11]. The absence of adverse pathological reactions to the use of bacteriophage preparations allows their effective use in newborns and children in the first year of life [Voroshilova N.N. et al., 2000]. Therapeutic and prophylactic bacteriophages are manufactured in compliance with all aseptic requirements and are preparations based on natural components contained in water and soil, so they can be prescribed to children and adults. According to their composition, bacteriophages are divided into monopreparations containing virulent phages of bacteria of the same genus or species - staphylococcal, streptococcal (including enterococcal), proteus, pseudomonas aeruginosis (pseudomonas aeruginosa), Klebsiella pneumoniae, coli, dysenteric polyvalent, typhoid, salmonella (gr. . ABCDE), and combined phages, which contain several monopreparations. The combined ones include: coli-proteus, Klebsiella polyvalent, polyvalent pyobacteriophages (purified, complex and Sextaphage®) - containing bacteriophages staphylococcal, streptococcal, proteaceous, Pseudomonas aeruginosa (pseudomonas aeruginosa), Klebsiella, coli, as well as Intesti-bacteriophage containing bacteriophages against Shigella , Salmonella, Staphylococcus, Enterococcus, Proteus, Pseudomonas aeruginosa and Enteropathogenic Escherichia coli.

One of the combined drugs is Sextafag® (polyvalent liquid pyobacteriophage), produced in Russia by the Federal State Unitary Enterprise NPO Microgen of the Russian Ministry of Health [11]. NPO Microgen is one of the top three Russian pharmaceutical companies and is the largest national manufacturer of immunobiological preparations: vaccines, serums, specific immunoglobulins, culture media, allergens, probiotics. A unique area of scientific and production activity of NPO Microgen is the production of bacteriophages - safe antibacterial drugs, an effective alternative to antibiotics. Sextaphage® is a mixture of sterile filters of phagolysates of staphylococci, streptococci, enterococci, Escherichia coli, Proteus, Pseudomonas aeruginosis and Klebsiella pneumoniae. Release form: in bottles and ampoules. Pyobacteriophage Sextaphage® is approved for use in newborns from 0 months, as well as in pregnant women, which indicates the safety of the drug.

Pyobacteriophage polyvalent (Sextaphage®) has the ability to specifically lyse microorganisms corresponding to the phage. The drug has proven itself well in purulent-inflammatory diseases of the upper and lower respiratory tract, including in the treatment of ABRS. The drug is taken orally. It can be used in conjunction with antibacterial agents according to the traditional regimen of antibacterial therapy, which were discussed above. Sextaphage® is usually prescribed on an empty stomach in liquid form, 20 ml 2–3 times a day. The drug is used in monotherapy, combination therapy with antibiotics is also possible. The duration of the course is, as a rule, no more than 7–10 days.

The drug is approved for use in newborns from 0 months. Thus, therapy for ABRS, especially caused by pathogens of nosocomial strains, against the background of immunodeficiency states, is justified with bacteriophage preparations and is a promising direction. Can be considered as an alternative to antibiotic therapy and as an adjuvant treatment with classical antibacterial therapy. The emergence of new bacteriophage preparations serves as a promise for studying the antibacterial properties of these drugs against the main causative agents of inflammatory diseases of the ENT organs, as well as studying the effect of bacteriophage preparations on the immune status of patients.

Literature 1. Zubkov M.N. Algorithm for the treatment of acute and chronic infections of the upper and lower respiratory tract // RMZh. 2009. T. 17. No. 2. P. 123–131. 2. Kryukov A.I., Sedinkin A.A.., Aleksanyan T.A. Treatment and diagnostic tactics for acute sinusitis // Bulletin of Otorhinolaryngology. 2002. No. 5. P. 51–56. 3. Lazareva E.B. Bacteriophages for the treatment and prevention of infectious diseases // Antibiotics and chemotherapy. 2003. T. 48, No. 1. P. 36–40. 4. Lazareva E.B., Spiridonova T.G., Kiselevskaya-Babina I.V. and others. The effectiveness of bacteriophages in the treatment of nosocomial infections in patients with burns // Sterilization and hospital infections. 2007. No. 2. P. 48–50. 5. Lopatin A.S., Alexandrova I.A., Gamov V.P., Detochka Ya.V. Rational pharmacotherapy of ear, nose and throat diseases: A guide for physicians. M.: Litterra, 2011. pp. 48–64. 6. Lopatin A.S., Tryakina E.G. Study of the effectiveness of a long course of treatment with low doses of clarithromycin for polypous rhinosinusitis // Russian Rhinology. 2007. No. 4. pp. 38–41. 7. Maiskaya L.M., Darbeeva O.S., Parfenyuk R.L. and others. Methodology for determining the phage sensitivity of strains isolated from patients to bacteriophage preparations. // Scientific and practical journal “BIO drugs”. 2003. No. 2. pp. 22–23. 8. Ozhereleva N.G. Brief medical encyclopedia. M.: Publishing house "Soviet Encyclopedia", 1989, ed. 2nd. 9. Palchun V.T., Luchikhin L.A. The feasibility and effectiveness of antibacterial therapy in ENT practice // Bulletin of Otorhinolaryngology. 2006. No. 3. P. 27–30. 10. Reshedko G.K., Kozlov R.S. The state of resistance to anti-infective chemotherapy drugs in Russia. Practical guide to anti-infective chemotherapy / Ed. L.S. Strachunsky, Yu.B. Belousova, S.N. Kozlova. Smolensk, 2007. pp. 32–46. 11. Sultanov N.M. Antibacterial activity and clinical effectiveness of the polyvalent purified pyobacteriophage preparation in the treatment of chronic purulent rhinosinusitis: Diss. Ph.D. biol. Sciences, 2007. P. 94. 12. Guttman B., Raya R., Kutter E. Basic Phage Biology, in Bacteriophages: Biology and Applications / Kutter E. and Sulakvelidze A., ed.. CRP Press, 2005. FL. P. 29–66. Schappert SM Ambulatory care visits to physician offices, hospital outpatient departments, and emergency departments: United States, 1996 // Vital Health Stat. 13. 1998. Vol. 134. P. 1–37. 13. Hickner JM, Bartlett JG, Besser RE, Gonzales R. et al. Principles of appropriate antibiotic use for acute rhinosinusitis in adults: background // Ann. Intern. Med. 2001. Vol. 134. P. 498–505. 14. Lanza DC, Kennedy DW Adult rhinosinusitis defined // Otolaryngol. Head Neck. Surg. 1997. Vol. 117 (3 Pt 2 Suppl). P. 1–7. 15. Paterson DL, Bonomo RA Extended-spectrum beta-lactamases: a clinical update // Clin. Microbiol. Rev. 2005. Vol. 18. P. 7–86. 16. Raya RR, Hébert EM Isolation of phage via induction of lysogens. Bacteriophages: Methods and Protocols, Volume 1: Isolation, Characterization, and Interaction / Martha RJ Clokie, Andrew M. Kropinski eds., 2009. Vol. 501. P. 23–32. 17. Schappert SM Ambulatory care visits to physician offices, hospital outpatient departments, and emergency departments: United States, 1996 // Vital. Health Stat. 13. 1998. Vol. 134. P. 1–37. 18. Scheid DC, Hamm RM // Am. Fam. Physician. 2004. Vol. 70. P.1685–1692. 19. Waters V., Ford-Jones EL, Petric M. et al. Etiology of community-acquired pediatric viral diarrhea: a prospective longitudinal study in hospitals, emergency departments, pediatric practices and child care centers during the winter rotavirus outbreak, 1997 to 1998 // Pediatric Infectious Disease Journal. 2000. No. 9. Vol. 19, No. 9. P. 843–848.