The question of the advisability of using antimicrobial drugs (AMP) in the treatment of bacterial AII in children remains the most controversial. By prescribing AMP in these cases, the doctor expects: a decrease in the severity of clinical symptoms, a reduction in the duration of the disease, a decrease in the incidence of complications, a cessation of the isolation of the pathogen, and prevention of further spread of the infection.<br />At the same time, it has been proven that the use of antibiotics is not always effective and safe in bacterial diarrhea. Thus, in enterohemorrhagic escherichiosis, the use of AMPs leads to a massive release of Shiga-like toxin, therefore, increases the risk of developing hemolytic-uremic syndrome.<br />The appointment of AMP for bacterial diarrhea in a significant percentage of cases not only does not lead to the rehabilitation of the macroorganism from the pathogen, but, on the contrary, contributes to the long-term persistence of the bacterial agent in the gastrointestinal tract (GIT) due not only to the overwhelming effect on the autochthonous intestinal microbiota, but also due to direct immunosuppressive actions. According to domestic and foreign researchers, prolonged convalescent bacterial excretion of Salmonella is formed in a significant number of patients who received antibiotics in the acute phase of infection, compared with individuals who use only pathogenetic therapy.<br />The economic damage caused by the emergence of antibiotic-resistant forms of bacteria amounts to tens and hundreds of millions of dollars. For example, in the EU it is at least 1.5 billion euros per year. In the current situation, bacteriophages can be an alternative to AMP in the treatment of bacterial diarrhea.<br />Mechanism of action<br />Phages penetrate the epithelial barriers of the mucous membranes using receptor-dependent transport, which is actively carried out by specialized cells of the immune system (M-cells, goblet cells) and, possibly, cells of the intestinal epithelium and other parts of the gastrointestinal tract. A bacteriophage introduced in any way enters the general blood stream, does not linger in the blood and is adsorbed by tissues, settling primarily in the lymph nodes, liver and spleen. The phage is excreted from the body through the intestines and kidneys. After oral administration, phage particles are detected after 1 hour in blood samples, after 1–1.5 hours - on the surface of burn wounds and in bronchial contents, after 2 hours - in cerebrospinal fluid and urine. After a single dose to sick patients, phages were excreted in the urine for 5–6 days with a gradual decrease in titer. The blood-brain barrier is not a barrier to the penetration of phages into the central nervous system. It should be noted that<br />the rate of translocation of phages, as well as bacteria from the gastrointestinal tract into the blood, can vary significantly in different physiological states. During the inflammatory response, the translocation of bacteria and, probably, phages from the intestine is significantly increased.<br /><br />Bacteriophages used in the composition of therapeutic and prophylactic preparations must have a lytic cycle of development (i.e., be virulent), as a result of which the death of the bacterial target cell occurs. By certain regions of the genes encoding the bacteriophage capsid protein, it is possible to quickly and with a certain degree of probability determine its belonging to the families of lytic phages.<br />In 1920–1940 in Canada and the United States, bacteriophages have been widely used to treat dysentery, typhoid fever, and salmonellosis. Moreover, most researchers have shown their good clinical efficacy, primarily a decrease in mortality by 30% or more compared with the comparison group.<br />The industrial production of "intestinal" bacteriophages and their widespread use in the USSR began in the 1940s. Considering the socio-economic realities of that time, most studies were devoted to the prevention and treatment of dysentery. It should be noted that the effectiveness of bacteriophages in AEI has long been studied.<br />Bacteriophages are highly specific in the treatment of bacterial infections, do not cause the development of resistance of microorganisms, are self-reproducing organisms: bacteriophage DNA is integrated into the bacterial chromosome, as a result of which the bacterial cell begins to produce hundreds of bacteriophages that infect bacteria until they are completely destroyed; bacteriophages are able to penetrate deep into the focus of infection. They are not only self-reproducing organisms, but also self-regulating: when all bacteria are affected by bacteriophages, their number, like the number of bacteriophages, begins to decrease. Bacteriophages have a stimulating effect on the humoral and cellular immunity.<br />In the absence of the bacteria necessary for the reproduction of bacteriophages, the latter are quickly removed from the body.<br />The traditional form of release of bacteriophages is a liquid preparation (except for tableted forms of intestinal phages), therefore, phages are used for oral administration, in the form of enemas, applications, irrigations, injection into wound cavities, vagina, nose, and also by injection into drained cavities - abdominal, pleural, bladder, renal pelvis.<br />Preparations of bacteriophages when administered enterally and rectally are safe and non-toxic to humans. They have no contraindications for use, except for allergic reactions, and can be used in combination with any other drugs. Bacteriophage preparations can be prescribed to pregnant women, nursing mothers and children from an early age; they are effective in monotherapy, but can also be used in combination with antibiotics. It should be noted that bacteriophages can be used in early childhood (up to 3–4 months) only under strict indications, given the significant frequency of allergic and diarrheal adverse reactions in children of this age group. It should be noted that adverse reactions resulting from the use of phages are usually associated with massive decay of bacterial cells with the release of endotoxin under the action of a bacteriophage. It is possible to neutralize these undesirable phenomena by including enterosorbents in the therapy complex. When using phages in combination with therapeutic doses of AMP, there is no negative effect<br />of these drugs on the development of bacteriophages, but there is a mutual potentiation of their therapeutic effect. It has been established that the effect of phages on antibiotic-resistant bacterial strains may be more active than the effect on antibiotic-sensitive strains of the same species.<br /><br />Therefore, indications for the use of bacteriophages in AII can be formulated as follows:<br />• as a monotherapy - with erased and mild forms of invasive AII;<br />• in combination with antibiotic therapy or sequentially - with moderate and severe forms of acute intestinal infections during the period of regression of symptoms;<br />• with bacterial excretion (in convalescent or transient bacterial carriers);<br />• in the complex therapy of enterocolitis of opportunistic and staphylococcal etiology in young children;<br />• for correction of intestinal microbiocenosis disorders.<br />Doses of bacteriophages depending on age are given. Bacteriophages are prescribed 2-3 times a day. Since bacteriophages are partially inactivated by the acidic environment of the stomach when taking liquid preparations of bacteriophages orally, it is advisable to produce bacteriophage preparations in tablets with acid-resistant capsules and suppositories.<br />In acute intestinal infections, "intestinal" bacteriophages are prescribed during the height of the disease (in the presence of vomiting, febrile fever, severe diarrheal syndrome) along with the main etiotropic therapy. In the last 10–15 years in the Russian Federation, most publications and scientific studies have been devoted to the use of Salmonella bacteriophage in convalescent bacterioexcretion of Salmonella. Our own research and research by other authors<br />indicate a high sensitivity of circulating Salmonella strains to a specific bacteriophage (82–96%).<br />The practice of using therapeutic and prophylactic bacteriophages has shown the need for bacteriological monitoring of possible changes in phage lability in relation to isolated Salmonella cultures in a hospital. It has been proven that the regular transfer of freshly isolated strains of AII pathogens to production contributes to an increase in lytic activity and an expansion of the range of action of bacteriophage preparations.<br /><br />The use of bacteriophages according to epidemiological indications in acute intestinal infections<br />Bacteriophages are also used for prophylactic purposes in natural emergencies (floods, etc.), in foci of bacterial infection, primarily shigellosis, salmonellosis and typhoid fever, diseases caused by opportunistic pathogens (Proteus, Pseudomonas aeruginosa) .<br />In epidemic foci (shigellosis, salmonellosis), bacteriophages are used to phage children attending preschool institutions, and employees of food enterprises, water supply and municipal facilities, etc. Phageing of all those who communicated with the source of AEI is carried out under unfavorable sanitary conditions in the focus, as well as when leaving the patient at home. As a prophylaxis, phage preparations are taken daily in the form of a single age dose: for children aged 1 to 3 years - 1 tablet; from 3–8 years - 2 tablets; adults - 3 tablets. The duration of treatment is usually determined epidemiological conditions.<br /><br />If it is necessary to give liquid bacteriophage (shigella, salmonella or intesti-bacteriophage), then the conversion is as follows: 1 tablet of dry bacteriophage is equal to 20 ml of liquid phage. Before taking a liquid bacteriophage, it is advisable to drink alkaline mineral water (Borjomi, Essentuki, etc.). There are no contraindications to the use of bacteriophage. The use of bacteriophages for prophylactic purposes has proven itself well during emergencies in recent years: floods in Krymsk (2012), floods in the Far East (2013).<br /><br /><br />MSc Sura Hasan Al-Zubaidi