Pharmacological properties
Pharmacodynamics. The active substance is a strain of non-pathogenic bacteria belonging to the species Escherichia coli (E. coli), in a live and capable of reproduction form: E. coli strain Nissle 1917. With the help of special adhesive organelles (type F-1A, F-1C and curly fimbriae), the strain has the ability to attach to the mucous membrane of the colon and form microcolonies in the form of a biofilm. Due to the presence of flagella, bacteria have inherent mobility, which gives them an advantage when colonizing the colon. The effects of the drug Mutaflor (E. coli strain Nissle 1917) have been determined in in vitro and in vivo experiments, as well as in clinical studies. The following effects and mechanisms of action have been established.
Antimicrobial properties (antagonism): E. coli strain Nissle 1917 forms antimicrobial substances (microcins), which, on the one hand, are responsible for direct antagonism against pathogens, as well as for the resistance of the strain, the duration of which exceeds that of oral administration of the drug itself. In addition, the strain has an inhibitory effect on the invasion of enteroinvasive pathogens into the mucosa of the large intestine.
Stabilization of the mucosal barrier of the large intestine. In experiments on cell cultures of colonic epithelial cells, E. coli strain Nissle 1917 demonstrated the ability to stabilize the barrier function of the epithelium and normalize the increased permeability of the intestinal mucosa in general. Such strengthening of the barrier function is a consequence of stimulation of the synthesis of the fixing protein (ZO-2) and the formation of strong intercellular contacts with its help.
E. coli strain Nissle 917 has immunomodulatory properties
In vitro and in vivo studies have demonstrated that the immunomodulatory ability of E. coli strain Nissle 1917 operates at both the humoral and cellular levels of the immune system in newborns or patients; in cases with healthy individuals, the immunomodulatory efficacy is expressed only to a minor extent.
1. Effect on the specific immune system
In premature and full-term infants, after colonization (population) of the intestine with E. coli strain Nissle 1917, an early increase in immunocompetence was observed, as indicated by a significant increase in the level of IgA and IgM in fecal filtrates and serum. In contrast, no increase in the level of IgG in serum was detected. Some studies confirm an increase in the level of IgA in saliva. It has been established that oral administration of E. coli strain Nissle 1917 is also a stimulator of the cell-mediated immune response in premature infants.
2. Effect on the nonspecific immune system
In vitro and ex vivo experiments revealed a significant increase in the secretory and cytotoxic activity of macrophages. In addition, ex vivo demonstrated an increase in the cytotoxic properties of macrophages directed against intracellular parasites, and therefore, a stronger protection against intracellular infectious agents. In vivo, a prophylactic effect was established in systemic infections.
In premature infants, stimulation of nonspecific innate immunity was also noted after oral administration of E. coli strain Nissle 1917.
Prokinetic properties. E. coli strain Nissle 1917 during metabolism synthesizes short-chain fatty acids, which are necessary for optimal energy balance of the colonic mucosa. They stimulate intestinal motility and blood circulation in its mucosa and enhance the absorption of sodium and chlorine ions. Stimulation of motility, which probably occurs under the influence of acetic acid of bacterial origin, plays an important role in the treatment of chronic constipation.
Effect on metabolism. The strain contained in the preparation Mutaflor is involved in numerous metabolic processes and is able to catabolize various carbohydrates, sugar alcohols, amino acids and other substrates, consuming oxygen. The anaerobic environment in the lumen of the colon, created in this way, is maintained for a long time, which is very important for the stability of the intestinal ecosystem.
Pharmacokinetics. Since the active substance (E. coli strain Nissle 1917) is a commensal, it is able to colonize the intestine as a physiological bacterium, is not absorbed, is not metabolized and is excreted from the intestine with feces.
toxicological properties
E. coli strain Nissle 1917 does not have any toxic or pathogenic properties, does not form enterotoxin and hemolysins, is not enteroinvasive, seroresistant, does not have pathogenic adhesive, uropathogenic properties, is sensitive to antibiotics that are often used against gram-negative bacteria, and does not have an immunotoxic effect.
Indication
Prevention of pathological colonization in the intestines in newborns (premature and full-term); increasing the immunity of newborns (premature and full-term); diarrhea in infants and preschool children, including during tube feeding.
Application
Shake before use! The suspension can be dripped directly into the mouth from the ampoule, for infants - before drinking, for preschool children - after eating. The suspension can also be administered through a nasogastric tube.
Colonization prevention: premature and term newborns - 1 ml/day for at least 5 days.
Increasing immunity in newborns: the first week of life - 1 ml once a day; 2-3rd week - 3 times a week, 1 ml/day.
Diarrhea during tube feeding: infants and preschool children - 1-5 ml once a day, up to 5 days depending on the period of diarrhea. After achieving positive results, treatment should be continued for several more days.
Contraindication
Hypersensitivity to the ingredients of the drug.
Side effects
The drug is well tolerated. There may be isolated cases of undesirable effects.
Gastrointestinal: At the beginning of therapy, abdominal bloating is often noted, which, as a rule, disappears immediately after reducing the dose. Abdominal pain, nausea or vomiting have been observed extremely rarely.
Skin: in isolated cases, allergic reactions in the form of urticaria, erythema, and skin peeling were noted.
Infections: isolated cases of sepsis have been described in premature babies born very early.
Special instructions
When treating severe forms of diarrhea with Mutaflor suspension, it is necessary to provide sufficient rehydration in order to prevent and prevent exicosis (dehydration).
Pregnancy and breastfeeding. E. coli strain Nissle 1917 is a commensal bacterium that is present in the human intestine and is not absorbed, does not affect the course of pregnancy and breastfeeding, therefore there are no precautions for use during these periods.
Children. Mutaflor suspension is used in infants and preschool children.
The ability to influence the reaction rate when driving vehicles or working with other mechanisms. Not detected.
Interactions
Antibiotics prescribed to affect gram-negative bacteria, as well as sulfonamides, may reduce the effectiveness of the drug Mutaflor.
Overdose
There is no data on overdose of the drug.
Storage conditions
At a temperature of 2-8 °C.
