Yu.O. Shulpekova
MMA named I.M. Sechenov

Modern medicine is unthinkable without the use of various antibacterial agents. However, to the appointment of antibiotics, it is necessary to fit purified, remembering the possibility of developing numerous adverse reactions, one of which is antibiotic-associated diarrhea.

Already the 50s of the twentieth century, with the beginning of the widespread use of antibiotics, the causal relationship between the use of antibacterial agents and the development of diarrhea was established. And today, the intestinal defeat is considered as one of the most frequent unwanted effects of antibiotic therapy, which is most often developing in weakened patients.

The concept of antibiotic-associated diarrhea includes cases of the appearance of a liquid chair in the period after the start of antibacterial therapy and up to a 4-week period after the abolition of the antibiotic (in cases where other causes of its development are excluded). In foreign literature, the terms "Nosocomial colitis", "Antibiotic-associated colitis" are also used as synonyms.

• 10-25% - when appointing amoxicillin / clavulanate;
• 15-20% - when appointing Cephixim;
• 5-10% - when appointing ampicillin or clindamycin;
• 2-5% - when prescribing cephalosporins (except for zefisim) or macrolides (erythromycin, clarithromycin), tetracycline;
• 1-2% - when appointing fluoroquinolones;
• less than 1% - when the trinometh - sulfamethoxazole is prescribed.

The causes of antibiotic-associated diarrhea in developed countries are leading penicillin derivatives and cephalosporins, which is due to their widespread use. The diarrhea more often occurs during the oral destination of antibiotics, but its development is possible in parenteral and even transvaginal use.

Pathogenesis

Antibacterial drugs are able to suppress the growth of not only pathogenic microorganisms, but also the symbiotic microflora inhabiting the gastrointestinal tract.

Symbiotic microflora inhabiting lumen gastrointestinal tract, produces substances with antibacterial activity (in particular, bacteriocinates and short-chain fatty acids - milk, acetic, oil), which prevent the introduction of pathogenic microorganisms and is redundant growth, the development of a conditioned pathogenic flora. The most pronounced antagonistic properties have bifidobacteria and lactobacilli, enterococci, intestinal wand. With violation of the natural intestinal protection, conditions arise for the reproduction of the conditionally pathogenic flora.

Speaking about antibiotic-associated diarrhea, from a practical point of view, it is important to distinguish between its idiopathic option and diarrhea due to the clostridium difficile microorganism.

Idiopathic antibiotic-associated diarrhea. The pathogenetic mechanisms for the development of idiopathic antibiotic-associated diarrhea remain not well-studied. It is assumed that various factors take part in its development.

When appropriate antibiotics containing clavulanic acid, diarrhea may develop due to stimulation of intestinal motor activity (that is, in such cases, diarrhea is characteristic of hyperkinetic).

When the cefopezone is prescribed and the development of the diarrhea, the character of hyperosmolar, due to the incomplete absorption of these antibiotics from the intestinal lumen.

Nevertheless, the most likely universal pathogenetic mechanism for the development of idiopathic antibiotic-associated diarrhea seems to be a negative impact of antibacterial agents on the microflora, inhabiting the clearance of the gastrointestinal tract. The interior of the intestinal microflora is accompanied by a chain of pathogenetic events leading to a violation of the intestinal function. The name "idiopathic" emphasizes that in this case, in most cases, it is not possible to identify a particular pathogen that causes the development of diarrhea. As possible etiological factors, Clostridium Perfrigens, Salmonella genus bacteria, which can be allocated in 2-3% of cases, staphylococcus, protea, enterococcus, as well as yeast fungi are considered. However, the pathogenic role of fungi in antibiotic-associated diarrhea remains the subject of discussion.

Another important consequence of the composition of the composition of the intestinal microflora is the change in the enterogeptic circulation of bile acids. Normally primary (conjugated) bile acids come into the lumen of the small intestine, where they are exposed to excessive deconjugation under the action of altered microflora. Increased quantity Deconjugated bile acids enters the lumen of the colon and stimulates the secretion of chlorides and water (a secretory diarrhea develops).

Clinical picture

The risk of developing idiopathic antibiotic-associated diarrhea depends on the dose of the drug used. Symptomatics does not have specific features. As a rule, it is noted by a pronounced climb of the stool.

The disease, as a rule, proceeds without increasing the body temperature and leukocytosis in the blood and is not accompanied by the appearance of pathological impurities in feces (blood and leukocytes). With an endoscopic study, inflammatory changes in the gum mucosa are not detected. As a rule, idiopathic antibiotic-associated diarrhea does not lead to the development of complications.

Treatment

The main principle of treatment of idiopathic antibiotic-associated diarrhea is the abolition of an antibiotic drug or a decrease in its dose (if necessary to continue treatment). If necessary, anti-diarceders are prescribed (Loperamide, diosctitis, aluminum-containing antacids), as well as means for correction of dehydration.

It is advisable to appoint preparation preparations that promote recovery normal microflora intestines (see below).

Diarrhea due to microorganism Clostridium difficile

The allocation of this form of antibiotic-associated diarrhea is substantiated by its special clinical value.

The most severe acute intestinal inflammatory disease caused by clostridium difficile microorganism and, as a rule, associated with the use of antibiotics, is called "pseudommbranous colitis". The cause of the development of pseudommabranous colitis is almost 100% of cases is the Clostridium Difficile infection.

Clostridium Difficile is a bond-anaerobic gram-positive spore-forming bacterium, which has natural resistance to most antibiotics. Clostridium difficile is able to persist in the environment. His disputes are resistant to thermal processing. This microorganism was first described in 1935 by American microbiologists Hall and O'Tool in the study of the intestinal microflora of newborns and was not originally considered as a pathogenic microorganism. The species name "difficile" ("difficult") emphasizes the difficulties of the allocation of this microorganism by the culture method.

In 1977, Larson et al. It was isolated from the feces of patients with a severe form of antibiotic-associated diarrhea - a pseudommbranous colitis - toxin with a cytopathic effect in tissue culture. A slightly later installed a causative agent that produces this toxin: they were closeridium difficile.

The frequency of asymptomatic carriage of Clostridium difficile in newborns is 50%, among the adult population - 3-15%, while its population in the normal intestinal microflora of a healthy adult does not exceed 0.01-0.001%. It increases significantly (up to 15-40%) when taking antibiotics, oppressing the growth of intestinal flora strains, which normally suppress the vital activity of Clostridium Difficile (primarily clindamycin, ampicillin, cephalosporins).

Clostridium difficile in the lumen of the intestine produces 4 toxin. Invasia microorganism into the intestinal mucous membrane is not observed.

Enterotoxins A and B play a major role in the development of changes from the intestine. Toxin and has a concentrated and pro-inflammatory effect; It is capable of activating cells - participants in inflammation, cause the release of inflammation mediators and substances P, the degranulation of fat cells, stimulate chemotaxis polymorphous leukocytes. Toxin in manifests the properties of cytotoxin and has a damaging effect on colocuts and mesenchymal cells. This is accompanied by a actin disaggregation and violation of intercellular contacts.

The pro-inflammatory and disaggrating effect of toxins A and B leads to a significant increase in the permeability of the intestinal mucosa.

Interestingly, the severity of the flow of infection is not directly related to the toxicity of various strains of the causative agent. C. difficile media can detect a significant content of toxins in feces without clinical symptoms. Some antibiotics, especially lincomycin, clindamycin, ampicillin, in asymptomatic carriers C. difficile stimulate the products of toxins A and B without an increase in the overall population of microorganism.

For the development of diarrhea caused by C. difficile infection, it is necessary to have so-called predisposing, or trigger, factors. Such a factor in the overwhelming majority of cases is antibiotics (primarily Lincomicin and clindamycin). The role of antibiotics in the diarrhea pathogenesis is reduced to suppressing the normal intestinal microflora, in particular a sharp decrease in the number of non-operational clostridium, and the creation of conditions for the reproduction of the conditionally pathogenic microorganism Clostridium difficile. It was reported that even a single reception of an antibiotic can serve as an impetus for the development of this disease.

However, diarrhea caused by C. difficile infection can also develop in the absence of antibiotic therapy, under other conditions under which there is a violation of the normal microbial intestinal biocenosis:

• in old age;
• under Uremia;
• with congenital and acquired immunodeficiency (including on the background of hematological diseases, the use of cytostatic drugs and immunosuppressants);
• with intestinal obstruction;
• against the background of chronic inflammatory diseases of the intestine (nonspecific ulcerative colitis and crown disease);
• on the background of ischemic colitis;
• on the background of heart failure, with violations of the intestinal blood supply (including under shock conditions);
• against the background of staphylococcal infection.

Especially great threat of development of pseudommabranous colitis after operations on the organs abdominal cavity. It has been reported on the development of pseudommabranous colitis on the background active application laxatives.

The location of the predisposing factors in the pathogenesis of infection C. difficile, apparently, can be defined as follows: "The impact of predisposing factors → The oppression of normal microflora → The growth of the population S. difficile → Products of toxins A and B → Damage to the mucous membrane of the colon."

The bulk of diarrhea cases caused by C. difficile is cases of nosocomial diarrhea. Additional factors of the non-hospital distribution of infection C. difficile are infected with fecal-oral (transfer of medical personnel or with contact between patients). It is also possible in case of endoscopic examination.

The manifestations of C. difficile infection varies from asymptomatic carriage to severe enterocolitis forms that are denoted by the term "pseudomambranous colitis". The prevalence of C. difficile infection, according to various authors, is among the hospital patients from 2.7 to 10% (depending on the nature of the background diseases).

In 35% of patients with pseudommabranous colitis, the localization of inflammatory changes is limited to the colon, in other cases the pathological process is involved in the pathological process. The predominant defeat of the colon, apparently, can be explained by the fact that this is a predominant habitat of anaerobic clostrid.

Clinical manifestations can develop both against the background of the antibiotic taking (more often from the 4th to the 9th day, the minimum period - a few hours later) and after a significant time (up to 6-10 weeks) after the cessation of its reception. In contrast to the idiopathic antibiotic-associated diarrhea, the risk of the development of pseudommabranous colitis does not depend on the dose of the antibiotic.

The beginning of the pseudo-membrane colitis is characterized by the development of abundant water diarrhea (with a stool frequency up to 15-30 times a day), often with blood admixture, mucus, pus. As a rule, fever is observed (reaching up to 38.5-40 ° C), moderate or intense pain in the abdominal abdominal or permanent character. Neutrophilic leukocytosis is observed in the blood (10-20 x 10 9 / l), in some cases a leukemoid reaction is observed. With pronounced exudation and significant loss of protein with feces, hypoalbuminemia and swelling are developing.

Cases of the development of reactive polyarthritis with the involvement of large joints are described.

Complications of pseudombranous colitis include: dehydration and electrolytic violations, Development of hypovolemic shock, toxic megacolon, hypoalbumine and edema, up to Anasar. To rare complications include colon perforation, intestinal bleeding, the development of peritonitis, sepsis. To diagnose sepsis, a prerequisite is to identify sustainable bacteremia in the presence of clinical signs System inflammatory reaction: body temperature above 38 ° C or below 36 ° C; Frequency of heart rate Over 90 UD. per minute; The frequency of respiratory movements is over 20 per minute or Paco 2 less than 32 mm Hg.; The number of leukocytes in the blood is over 12x10 9 / l or less than 4x10 9 / l or the number of immature forms exceeds 10%. It is extremely rarely a lightning course of pseudo-membrane colitis, resembling cholera, in these cases for several hours is developing sharp dehydration.

In the absence of treatment, mortality in pseudommabranous colitis reaches 15-30%.

In patients who need to continue antibacterial therapy, in 5-50% of cases, diarrhea recurrences are observed, and when the "guilty" antibiotic is reused, the frequency of repeated attacks increases to 80%.

Diagnosis of pseudommbranous colitis Based on 4 main signs:

• the emergence of diarrhea after taking antibiotics;
• identification of characteristic macroscopic changes in the colon;
• peculiar microscopic pattern;
• proof of the etiological role of C. difficile.

Among the visualization methods, colonoscopy and computed tomography are used. Colonoscopy allows you to identify sufficiently specific macroscopic changes in the colon (first of all the straight and sigmoid): the presence of pseudommable, consisting of a necrotized epithelium impregnated with fibrin. Pseudommabra on the mucous membrane of the intestine is found in the medium-and-heavy and heavy forms of pseudo-membrane colitis and have the form of yellowish-greenish plaques, soft, but densitated with the subjectable tissues, with a diameter of several mm to several cm, on a slightly raised base. In the place of the tight membranes can be detected ulcers. The mucous membrane between membranes looks not modified. The formation of such pseudommabran serves as a fairly specific feature of the pseudommabranous colitis and can serve as a differential-diagnostic difference from non-specific ulcerative colitis, Crohn's disease, ischemic colitis.

In a microscopic examination, it is determined that the pseudomber contains necrotic epithelium, abundant cell infiltrate and mucus. In the membrane there are reproduction of microorganisms. Full-blood vessels are visible in the subject to intact mucous membrane and the submucosity.

With lighter forms of the disease, the mucosa can be limited only by the development of catarrhal changes in the form of full-blood and edema of the mucous membrane, its grain.

In computed tomography, you can reveal the thickening of the colon wall and the presence of inflammatory traffic in the abdominal cavity.

The use of methods that make it possible to prove the etiological role of C. difficile, it seems the most stringent and accurate approach in the diagnosis of antibiotic-associated diarrhea caused by this microorganism.

Bacteriological study of the anaerobic portion of the microorganisms of feces is not allowed, expensive and does not meet clinical requests, because takes a few days. In addition, the specificity of the culture method is low due to the widespread prevalence of asymptomatic carriage of this microorganism among hospital patients and patients taking antibiotics.

Therefore, the identification of the toxins produced by C. difficile is recognized by the method of choice, in feces of patients. A highly sensitive and specific method of detecting toxin in using tissue culture is proposed. In this case, it is possible to quantify the cytotoxic effect of the patient's feces filtrates on the tissue culture. However, the use of this method is economically unprofitable, it is used only in few laboratories.

The latex agglutination reaction to detect toxin and C. difficile allows less than 1 hour to establish the presence of toxin and in feces. The sensitivity of the method is about 80%, specificity - more than 86%.

Since the beginning of the 90s of the 20th century, in most laboratories, an immununimal analysis is used to detect toxin A or toxins A and B, which increases the informativeness of the diagnosis. The advantages of the method are simplicity and fast execution. Sensitivity is 63-89%, specificity - 95-100%.

Treatment of antibiotic-associated diarrhea due to infection Clostridium Difficile.

Since the antibiotic-associated diarrhea, due to microorganism C. difficile, can be qualified as an infectious diarrhea, when establishing this diagnosis, it is advisable to isolate the patient in order to prevent the infection of others.

Mandatory condition is the abolition of an antibacterial agent that caused the appearance of diarrhea. In many cases, this measure leads to the relief of the symptoms of the disease.

In the absence of effect and in the presence of severe clostridial colitis, an active treatment tactic is necessary.

Antibacterial drugs are prescribed (vancomycin or metronidazole), overwhelming C. difficile population growth.

Vancomycin is poorly absorbed from the intestinal lumen, and here its antibacterial action is carried out with maximum efficiency. The drug is prescribed at 0.125-0.5 g 4 times a day. Treatment continues for 7-14 days. The effectiveness of vancomycin is 95-100%: in most cases of infection C. difficile when prescribing vancomycin, fever disappears after 24-48 hours, the diarrhea is stopped by the end of the 4-5-day. With vancomycin inefficiencies, you should think about another possible reason Diarrhea, in particular, debut of nonspecific ulcerative colitis.

As an alternative to Vancomycin can perform a metronidazole, which has comparable with vancomycin efficiency. The advantages of metronidazole are significantly lower cost, the lack of risk of selection of vancomycinostable enterococci. Metronidazole is prescribed inside 0.25 g 4 times a day or 0.5 mg 2-3 times a day for 7-14 days.

Another antibiotic, effective in pseudomambranous colitis - bacitracycin, belonging to the class of polypeptide antibiotics. It is prescribed 25,000 meters inside 4 times a day. Bacitracine is practically not absorbed from the gastrointestinal tract, and in connection with which a high concentration of the drug is created in the colon. The high cost of this drug, the frequency of development of side effects limit its application.

If it is impossible to oral administration of these antibacterial agents (with extremely severe condition patient, dynamic intestinal obstruction), metronidazole is used intravenously 500 mg every 6 hours; Vancomycin is introduced to 2 g per day through a subtle cast or rectal probe.

If there are signs of dehydration, infusion therapy is prescribed for the correction of the water and electrolyte balance.

In order to sorption and remove clostridial toxins and microbial bodies from the intestinal lumen, it is recommended that enterosorbents and drugs that reduce the adhesion of microorganisms on colocuts (diosctitis) are recommended.

The appointment of antidiare and antispasmodics is contraindicated due to the danger of developing a formidable complication - toxic megolon.

In 0.4% of patients with the most severe forms of pseudo-membrane colitis, despite the etiotropic and pathogenetic therapy, the state is progressively deteriorating and the need for a kolactomy occurs.

The treatment of relapses of the Clostridium DiffiLile infection is carried out according to the vancomycin scheme or PER OS metronidazole for 10-14 days, then the cholestiramine is 4 g 3 times a day in combination with lactobacterin 1 g 4 times a day for 3-4 weeks. and vancomycin at 125 mg every other day for 3 weeks.

For the prevention of relapses, the appointment of therapeutic yeast saccharomyces boulardii is 250 mg 2 times a day for 4 weeks.

Comparative characteristics clinical features idiopathic antibiotic-associated diarrhea and antibiotic-associated diarrhea caused by C. difficile infection, and treatment approaches are presented in Table 1.

Table 1.
Comparative characteristics of idiopathic antibiotic-associated diarrhea and diarrhea associated with infection C. Difficile

The possibility of using probiotics in the prevention and treatment of antibiotic-associated diarrhea

Currently, much attention is paid to the study of the effectiveness of various types of probiotics, which includes representatives of the main intestinal microflora.

Therapeutic effect of probiotics is explained by the fact that the microorganisms included in their composition replace the functions of their own normal intestinal microflora in the intestine:

• create adverse drags for breeding and vital activity of pathogenic microorganisms due to the production of lactic acid, bacteriocinnes;
• participate in the synthesis of vitamins in 1, 2, 3, in 6, in 12, n (biotin), RR, folic chiotin, vitamins K and E, ascorbic cylinders;
• create favorable conditions for suction of iron, calcium, vitamin D (due to the production of lactic acid and reducing pH);
• lactobacillia and enterococcus in the small intestine carry out the enzymatic splitting of proteins, fats and compound carbohydrates (in the chision with lactase insufficiency);
• enzymes, facilitating the digestion of proteins in infants (phosphatein phosphatase bifidobacteria participates in the metabolism of casein of milk);
• bifidum-bacteria in the colon cleaved not attemptable components of food (carbohydrates and proteins);
• participate in the metabolism of bilirubin and bile kilot (sterkobiline, coprogen, deoxychole and lithochole kiclot formation; contribute to the reabsorption of biliary kilot).

The complexity of the organization of the evaluation of the effect and comparison of actions of various probiotics is that there are currently no pharmacokinetic models for studying in humans of complex biological substances consisting of components with different molecular weight and non-systemic blood flow.

Nevertheless, with respect to some therapeutic microorganisms, convincing data was obtained regarding the prevention and treatment of antibiotic-associated diarrhea.

1. Saccharomyces Boulardii in a dose of 1 g / day. prevents the development of antibiotic-associated diarrhea in patients on artificial nutrition through the catheter; They also prevent recurrences of Clostridium Difficile infection.
2. The purpose of Lactobacillus GG leads to a significant decrease in diarrhea severity.
3. Saccharomyces Boulardii Combined with Enterococcus Faecium or Enterococcus Faecium SF68 has shown themselves as effective agents in the prevention of antibiotic-associated diarrhea.
4. ENTEROCOCCUS FAECIUM (10 9 CFU / DAT.) Connects the frequency of the development of antibiotic-associated diarrhea from 27% to 9%.
5. Bifidobacterium Longum (10 9 CFU / day) prevents erythromycin-associated disorders of the gastrointestinal tract functions.
6. With a comparative estimate of the effectiveness of Lactobacillus GG, Saccharomyces Boulardii, Lactobacillus Acidophilus, Bifidobacterium Lactis: All probiotics turned out to be more efficient than placebo in the prevention of antibiotic-associated diarrhea.

As a probiotic for preventing the development of antibiotic-associated diarrhea and the restoration of the intestinal function after the abolition of the antibacterial agent, the drug Linex can be recommended. The preparation includes a combination of living lyophilized lactic acid bacteria - representatives of natural microflora from different departments of the intestine: Bifidobacterium infantis v. Liberorum, Lactobacillus Acidophilus, Enterococcus Faecium. To include, in the composition of the drug, strains are selected, characterized by stability to most antibiotics and chemotherapeutic agents and capable of further reproduction for several generations, even under antibacterial therapy. In special procedures, it was shown that the transfer of resistance from these microbes to other intestinal inhabitants does not occur. The composition of Linex can be described as "physiological", since the combination includes types of microbes related to the classes of the main inhabitants and playing the most important role in the products of short-chain fatty acids, ensuring the epithelium trophy, antagonism relative to the conditionally pathogenic and pathogenic microflora. Due to the inclusion in the Linexus of Frextococcus (Enterococcus Faecium), which has high enzymatic activity, the effect of the drug also applies to the upper intestinal departments.

Linex is produced in the form of capsules containing at least 1.2x10 7 some live lyophilized bacteria. All three strains of Linex bacteria are resistant to the effects of the aggressive stomach environment, which allows them to be easily achieving all departments of the intestine without losing their biological activity. When applied in children early age The contents of the capsule can be divorced in a small amount of milk or other liquid.

Contraindication to the purpose of Linex is hypersensitivity to the components of the drug. There is no message about the overdose of lines. Side effects are not registered. The procedures performed showed the absence of the teratogenic effect of lyophilized bacteria. There are no messages about the side effects of using Linex during periods of pregnancy and lactation.

Unwanted medicinal interactions Linex is not marked. The drug can be used simultaneously with antibiotics and chemotherapeutic agents.

You can find a list of references on the website rmj.ru

Many people in the treatment of severe diseases are faced with such a state as an antibiotic associated diarrhea. It is difficult to present modern medicine without antibacterial drugs, and despite the fact that they are trying not to resort to their use, they are prescribed by doctors quite often. Such treatment with a long-term course or characteristics of the body can lead to some negative consequences. An antibiotic associated diarrhea The problem arising during the reception of such drugs and is found in a significant percentage of their applications.

Description

Antibiotic associated diarrhea (AAD) implies a liquid chair for at least 3 times a day for two days. It can manifest itself not only during drug intake, but also after the patient's recovery from the underlying disease. This is due to many parameters (the severity of the state, age, gender, individual characteristics of the body, type of drug, etc.). Watching the patient under these circumstances is needed at least a month after stopping the reception of antibacterial drugs (the appearance of symptoms can move for 2-5 weeks).

If we talk about the likelihood of antibiotic-associated diarrhea, the chance of the appearance of this complication, after the use of such drugs is 10-30%.

Causes of antibiotic associated diarrhea

• Idiopathic. Such an antibiotic associated diarrhea does not have a clearly installed pathogen. Medical preparations are negatively affected by the gastrointestinal tract (gastrointestinal tract) than caused by failures in eubiosis. It often occurs due to the excess of the dose appointed by the doctor or the recommendations specified in the instruction;
• Antibiotic associated diarrhea can be caused by Clostridium Difficile bacteria. The reason is hidden in the fact that the balance of the native microflora is disturbed. And even on most drugs are possible complications, side effects and contraindications, be careful, taking medicines from such categories: cephalosporins, amoxicillins, lincomatsines, macrolides, penicillin group.

In addition, the antibiotic associated diarrhea will arise with a large chance, with the following factors:

• Receiving a course of several different antibiotics;
• Reception of antidiare drugs (diluted, etc.);
• Reception of non-steroidal anti-inflammatory funds;
• Reception of immunosummic medicines;
• Passage of chemotherapy;
• The presence of ischemic colitis;
• Frequent collection of mechanical type analyzes (colonoscopy and similar);
• The presence of chronic bowel diseases;
• Receiving cytostatics;
• The presence of malignant tumors (oncology).

Severity of state

Antibiotic-associated diarrhea can be held both quite simple and strong discomfort, it has the following gravity levels:

• Easy. Weak abdominal pain almost does not cause inconvenience and passes after a visit to the restroom, diarrhea itself is observed no more than 4-5 times a day. In this case, the abolition of a problem drug is most often helped, and the treatment of unauthorized medicines is not required;
• Average. With such an antibiotic-associated diarrhea, hiking to the toilet is rapid up to 11-15 times a day, and pain does not disappear after emptying. In Kale, you can observe impurities of mucus or blood, there is an increase in body temperature (insignificant). In this case, the treatment of antibiotic-associated diarrhea will include additional medicines, since the cancellation of the problem preparation will not entail a complete recovery.
• Heavy. Symptoms in this case are similar to the previous, but they have developed significantly. The body temperature can reach 40 ° C, and the liquid stool almost does not allow to get out of the toilet (observed up to 30 or more times a day). It threatens a number of complications (dehydration, intestinal rupture). In such episodes, antibiotic associated diarrhea should be treated under the leadership of the doctor.

Classification of idiopathic cases

This condition can be called as infectious and not. In the first case, the culprits become:

• Salmonella;
• Candida mushrooms;
• Staphylococcus;
• Klostridia Perfevention;
• Klebsiella.

Unconfecting idiopathic antibiotic-associated diarrhea has a much more detailed classification:

• Secretor. Disconjugation of bile acids (glycine and taurine cleavage) and intestinal eubiosis. Due to the larger concentration of acids, there is more water and salts in the intestinal lumen;
• Hyperkinetic. Increases the motor function (peristalistic) of the entire gastrointestinal tract. Against this, the feces do not have time to fully form and leave all the water in the body;
• Toxic antibiotic associated diarrhea. It is observed when taking medicines of the penicillin and tetracycline group. They have a negative impact on the intestinal mucosa. In addition to diarrhea, diagnose dysbacteriosis;
• Hyperosmolar. It is provoked by the fact that antibacterial drugs are absorbed only in part or in the patient is broken carbohydrate exchange. Increased secretion of water and electrolytes will be associated with accumulation in the intestine of carbohydrate metabolites.
• Separately, it is worth considering the pseudommbranous colitis. Bacteria that are source of problem - Clostridium difficile. They are present in a healthy person (2-3% for an adult). However, the reception of antibacterial medicines creates a medium for their transition to the form forming toxins.

Symptoms of antibiotic associated diarrhea

Although diarrhea and provoked by a conditional one event, it has different groups, categories and possible further development. This suggests that her signs may differ slightly depending on the specific episode. But, nevertheless, general symptoms are still present:

• The liquid stool is observed at least 3 times a day for 2 days during the reception of antibiotics or within a month after the end of the course;
• In some cases, the alternation of a liquid chair can be observed with normal;
• Body temperature reaches 37-40 ° C;
• Selection in medium-free cases contain mucus and blood;
• Discomfort and pain in the abdomen without a clear location;
• Hike to the toilet can be observed from 3 to 30 times a day;

If you have antibiotic-associated diarrhea, treatment must appoint a specialist. First, it will establish an accurate reason for such a state and make sure that the fault of all medicines, and secondly, will appoint a course corresponding to your case and the characteristics of the structure of the body.

Diagnostics

Before the specialist will make any conclusions for determining the diagnosis, they must be conducted a number of analyzes and diagnostic procedures that will help to establish, antibiotic-associated diarrhea. They include:

• Patient poll on the diet, lifestyle, the very least (time when it all started, the frequency of hiking, etc.). The physician is also interested in which drugs in the last 2 months you have taken, chronic diseases are taken into account;
• Inspection. Total weakness, dry skin and mucosa indicate dehydration. Painted area of \u200b\u200bthe abdomen for the presence of pain, the intestinal peristalsis is checked;
• General blood analysis. Will help find inflammation, if any;
• Blood chemistry. It is checked, whether the content of sharp-phase proteins, albumin, is normal;
• Cala Analysis will give answers to many questions;
• Bacteriological sowing. This method in which the growth of potential pathogenic microorganisms accelerates. To do this, create a favorable environment and after observe what colonies were formed. Also this method diagnostics allows you to investigate the level of toxins allocated by problem cells;
• Linked immunosorbent assay. Thanks to him, non-standard toxins are found (subspecies);
• Colonoscopy. Inspection of the gastrointestinal tract with a flexible endoscope;
• RectorOnoscopy. Unlike the past version, a solid iron tube is used here. This will allow you to evaluate the rectal mucosa at a distance of 25-30CM from the entrance. Often used not only in suspected that the patient has antibiotic-associated diarrhea, but also in other similar cases;
• Biopsy. Take the smallest piece of fabric for research under the microscope;
• CT scan. In contrast to the X-ray - in this method, using a contrast (special liquid visible X-ray radiation).

Important! Diagnostics including a number of analyzes is required at the moderate severity and serious condition of the patient when antibiotic associated diarrhea brings significant discomfort and general state The patient deteriorated greatly.

If you have an antibiotic-associated diarrhea treatment to imply a refusal of antobacterial drugs, and it is also necessary to comply with additional recommendations:

• First of all, with any diseases of the GST organs, a diet is assigned, which eliminates such products:

1. Fat, spicy, sharp, salted and other heavy dishes;
2. Carbonated drinks;
3. Cocoa;
4. Canned;
5. Alcohol.

If you have antibiotic-associated diarrhea, focusing on the next food:

1. Baked potatoes and apples;
2. Crackers;
3. Bananas;
4. Jelly.

• It is necessary to drink as much as possible (at least two liters per day). As with other reasons, during diarrhea, the body loses a huge amount of fluid, it must be filled (stop the choice on ordinary water);
• Taking probiotics. Microflora, which has undergone pathological changes, needs to be restored. Frequent selection is lines, bifiform, enterol, subtyl, enterozermina, etc.;
• If antibiotic-associated diarrhea caused strong dehydration, simple drink may not be enough. The organism is orally (through the mouth) or intravenously water saline solutions (recider).
• To normalize the chair, the adsorbing drugs (smecta, atomsyl, energy generator) is possible.

If you ignore the treatment, going to the doctor and the situation as a whole, then this may entail the following negative consequences:

• Violation of the metabolism;
• Reduced blood pressure;
• Dehydration;
• Swelling throughout the body (more often it is the legs);
• Peritonitis;
• Sepsis;
• Constant weakness;
• Antibiotic-associated diarrhea indicates important and dangerous errors of the body, and in 10-20% of cases when the patient did not apply to the doctor, it led to a fatal outcome. The danger lies not in a liquid chair, but in what caused it.

The easiest solution so that you do not oversee the antibiotic-associated diarrhea - clinical recommendations for receiving antibiotics should be strictly observed.

If, after using strong drugs, you began to observe any changes from your body. Contact your doctor for advice. Indeed, with associated diarrhea, antibacterial drugs caused by antibacterial drugs will sometimes not stop their reception. At the first stages, a similar problem is pretty simply, and when the visit is tightened to the doctor, the state will deteriorate greatly.

The study of the intestine microflora began in 1886, when F. Escherich described the intestinal wand ( Bacterium Coli Communae.). In 1908, the Nobel laureate Russian scientist Ilya Ilyich Mechnikov proved the need for intestinal bacteria for health and longevity. To date, there are 500 types of microbes in the intestine of a healthy person. Normal microbial flora is one of the barriers on the path of bacteria entering the intestine. It stimulates immune defense, increases the secretion of IGA into the intestinal lumen. Intestinal sticks, enterococci, bifidobacteria, acidophilic sticks possess antagonistic properties and are able to suppress the growth of pathogenic microorganisms. The microflora impairment leads to a decrease in the body's resistance to intestinal infections.

The mucoid microflora (M-microflora) is distinguished by microorganisms associated with the intestinal mucosa, and the strip microflora (P-microflora) - microorganisms localized in the intestinal lumet.

In relation to macroorganism, representatives of intestinal biocenosis are divided into 4 groups:

bond microflora (basic intestinal microflora - bifidobacteria, lactobacillia, normal intestinal chopsticks, propionic acid, peptopulation, enterococci);

optional (Conditional and pathogenic and saprophyte microorganisms - bacteroids, staphylococci, streptococci, peptococci, yeast-like mushrooms, Weionell, fuzobacteria, bacillos);

transit (random microorganisms that are not capable of long stay in the body - fuelobacteria, pseudomonads);

pathogenic (causative agents of infectious diseases - Shigella, Salmonella, Irancini, etc.).

When recycling microbes of unsecured carbohydrates (fiber), short-chain fatty acids are formed. They provide energy inherence cells, improving the trophic of the mucous membrane. Insufficient amount of fiber in the diet leads to a decrease in the synthesis of short-chain fatty acids. As a result, dystrophic changes in the epithelium occur and the permeability of the intestinal barrier increases for antigens of food and microbial origin.

Under the influence of microbial enzymes in the ileum, deconjugation of bile acids (LCD) and the transformation of the primary LCD into the secondary LCD are. In physiological conditions, 80-95% of the LCD is reabsorbed, the rest are allocated with the feces in the form of metabolites. The latter contribute to the formation of key masses, the absorption of water is inhibited, preventing excessive calibration dehydration. Excess bacterial innovation of the small intestine leads to premature deconjugation of the LCD and secretory diarrhea.

Thus, the morphological and functional state of the intestine depends on the composition of its microflora.

In the Torchian healthy people It is up to 100,000 bacteria in 1 ml of content. The main part of them is streptococci, staphylococci, lactic chopsticks. In the distal department of the ileum, the number of microbes increases due to enterococci, intestinal sticks, bacteroids and anaerobic bacteria.

The microbial composition of the feces does not reflect the full picture of the intestinal biocenosis, does not provide operational information on the composition of microorganisms in the intestine. In practice, data is taken into account only about 15-20 types of microbes contained in feces. Typically, the number of bifidobacteria, lactobacilli, enterobacteria, intestinal sticks, perfoching, enterococcus, golden staphylococcus, and Candid, are also investigated.

Intestine dysbiosis - Disruption of the ecological equilibrium of microorganisms, characterized by a change in the quantitative relationship and the qualitative composition of the indigenous microflora in microbiocenosis. The term "dysbacteriosis" first introduced A. Nissle in 1916

The severity of the dysbiosis is determined by the degree of decrease in bifidobacteria and other bond microorganisms and increase the number of conditionally pathogenic and pathogenic species.

I degree - reducing the number of bonded representatives (bifidobacteria and / or lactobacilli) by 1-2 order, without an increase in the conditionally pathogenic microflora (UPM), the increase in the amount of UPM at the normal number of bifidobacteria. II degree - a moderate or significant decrease in the number of bifidobacteria, combined with pronounced changes of aerobic microflora (lactobacill reduction, appearance of altered forms of intestinal sticks, high-quantities). III degree - a large number of UPM as one species and associations, the release of pathogenic microorganisms (Mehdiyev S. N., Grinevich V. B., Zakharenko S. M.).

The following key syndromes are distinguished in the discharge clinic:

Dyspeptic (decreased appetite, jeeping, belching, nausea, vomiting);

Intestinal syndrome (abdomen, intestinal rumbling, tendency to constipation or liquid stools with undigested food residues);

Secondary Mal Absorption Syndrome (resistant diarrhea with impaired monosaccharide absorption, electrolytes),

Polygipovitaminosis (dry skin, hair loss, nail fragility, halit, stomatitis).

New approaches in the diagnosis of dysbiosis

An alternative to routine bacteriological studies is chemical methods of differentiation of microorganisms and, in particular, gas chromatography (GC) in combination with mass spectrometry (GC-MS). The method is based on the determination of the components of bacterial cells appearing as a result of their natural diefing or attack immune system. As markers, minor lipid components of microbes membranes are used. By their content, it is possible to determine up to 170 species of bacteria and mushrooms in various biosrials for several hours.

Almost 50% of the biomass of the trim microflora are actinomycetes that occupy an intermediate position between bacteria and mushrooms. About 25% of the microbial flora is represented by aerobic coccobs (staphylococci, streptococci, enterococci and corneformal bacteria). The number of bifido- and lactobacilli varies from 20 to 30%. Other anaerobes (peptococci, bacteroids, clostridium, propionic acid) make up about 10% in thin and up to 20% in the colon. The share of enterobacteria accounts for 1% of the total microflora of the mucous membrane.

Until 90-95% of the microbes of the colon are anaerobes (bifidobacteria and bacteroids) and only 5-10% of all bacteria are strict aerobic and optional flora (lactic acid and intestinal sticks, enterococci, staphylococci, mushrooms, protea).

Dysbiosis is not an independent disease. His appearance contributes to disorders of intestinal digestion, motility, local immunity, antibiotics, antacids and other drugs. It is necessary to establish the cause that caused dysbiosis, and not try to "cure" the intestinal microflora, based on its bacteriological analysis of the feces.

The properties of microbes inhabiting the intestines are not always taken into account when appointing antibiotics. Antibacterial drugs suppress the growth of not only pathogenic microorganisms, but also normal microflora. As a result, saprophilic microbes are multiplied with high-resistant drugs that acquire pathogenic properties.

Diarrhea associated with antibiotics

In patients receiving antibacterial therapy, diarrhea may develop caused by intestinal dysbiosis (AEAD - antibiotic-associated diarrhea). The frequency of such diarrhea fluctuates in the range of 5-25%. The cause of it is to reduce the number of microbes sensitive to the antibiotic, and the appearance of resistant strains that are absent in the norm. The most famous representative of such microorganisms is a pathogenic strain Clostridium Difficile (Cl. Difficile), But the cause of diarrhea associated with antibiotics, there may be other microbes that can enhance the secretion of ions and water, damage the intestine wall. These are staphylococci, protea, yeast mushrooms, enterococci, a blue chopstick, Klebsiella. The type of diarrhea AAD is usually attributed to secretory and inflammatory types.

Antibiotic-associated diarrhea most often cause lincomycin, ampicillin, clindamycin, benzylpenicillin, cephalosporins, tetracycline, erythromycin. The method of administration of the antibiotic does not matter much. When taking inside, in addition to the eradication of microorganisms, an antibiotic effect on the mucous membrane of the small intestine occurs. In parenteral administration, antibiotics affect the biocenosis of the intestine, standing out with saliva, bile, fine and colon secrets.

The symptoms of the AAD in most patients usually appear during treatment, and in 30% - within 7-10 days after its termination.

The etiological factor of AEAD Most researchers consider Klostridia, in particular Cl. difficile. Among the adult population is low levels of carriage and equal to 2-3%. The conditions of reproduction Cl. difficile There are anaerobic medium and the oppression of the normal intestinal microflora.

The clinical manifestations of the AAD vary from light diarrhea to severe pseudomambranous colitis (PMK). PMK is an acute intestinal disease, which is complicing antibacterial therapy. It has been established that it causes it Cl. difficile.

Symptomatics

The main symptom of the ADA is abundant waterproof diarrhea, the beginning of which precedes the purpose of antibiotics for several days or more. Then there are grapple-shaped pain in the stomach, squeezing after the chair. In cases where fever occurs, leukocytosis increases in the blood, and leukocytes appear in feces, it is necessary to suspect PMK.

After the abolition of the antibiotic, a number of patients with symptoms quickly disappear. With PMK, despite the cessation of antibiotic therapy, in most cases the stool frequency is growing, dehydration and hypoproteinemia appear. In severe cases, dehydration is quickly occurring, toxic expansion and punching of the colon are developing, a fatal outcome is possible.

Diagnosis

The AAD diagnosis is established on the basis of the communication of diarrhea with the use of antibiotics. The diagnosis of PMC is confirmed by bacteriological studies of the feces and the definition of toxin in it Cl. difficile. The toxin detection frequency in the feces of patients with the AEA does not exceed 15%.

In patients with diarrhea associated with Cl. difficile, there is significant leukocytosis. It is evidence that in patients with leukocytosis 15800 and higher than the likelihood of the development of PMK caused by Cl. difficile. This is explained by the fact that toxin A, allocated Cl. difficile, causes inflammation, secretion of fluid, fever and convulsions. Therefore, all patients with AEAD flowing with intoxication and leukocytosis of 15,800 and higher should be considered the cause of diarrhea Cl. difficile.

Parfenov A.I., Osipov G. A., Bogomolov P. o applied the method of GC-MS to assess the composition of the microbial flora of the small intestine in 30 patients with AD and found that diarrhea may be associated not only with infectious agent (Cl. difficile), but with a significant change in normal microflora in the direction of increasing the number from 7 to 30 of 50 controlled microorganisms. At the same time, the overall colonization of the small intestine increases 2-5 times compared to the norm.

In patients with AD, most often the morphological changes in the colon are absent. In severe cases, on endoscopy, 3 types of changes are detected: 1) Catarial inflammation (swelling and hyperemia) mucous membrane; 2) erosive hemorrhagic lesion; 3) pseudomambranous defeat.

The endoscopic picture of PMC is characterized by the presence of plaque, tanning and solid "membranes", soft, but tightly soldered with the mucous membrane. Changes are most pronounced in the distal sections of the colon and rectum. The mucous membrane of the female, but not ulced. With histological examination - subepithelial edema with round-floor infiltration of the own plate, capillary stages with the yield of erythrocytes beyond the vessels. At the stage of education, pseudommbran under the surface epithelium of the mucous membrane formed infiltrates. The epithelial layer is lifted and there is no places: the bare places of the mucous membrane are covered with only a raised epithelium. In the later stages of the disease, these sites can occupy large segments of the intestine.

Differential diagnosis

The relationship of diarrhea with antibiotic therapy usually does not create difficulties in the diagnosis of AAD. In severe cases, the PMK pattern can resemble cholera or fulminant shape of ulcerative colitis, Crohn's disease. However, the latter is characterized by more or less pronounced bloody diarrhea, uncharacteristic for PMK. Nevertheless, the possibility of the development of erosive-hemorrhagic changes in the mucous membrane for ADA does not exclude the appearance of bloody discharge from the rectum in some patients.

Treatment of AAD

Etiotropic therapy AAD and PMK caused by Cl. Difficile, most authors consider the appointment of Vancomycin and Metronidazole (trichopol, metrogila).

Immediately cancel the antibiotic that caused diarrhea. Vancomycin is prescribed in the initial dose of 125 mg inside 4 times a day, if necessary, the dose increases to 500 mg 4 times a day. Treatment is continued for 7-10 days. Metronidazole gives 0.5 g inside 2 times a day (or 0.25 g 4 times a day).

Bacitracy of 25 thousand meters is also used inside 4 times a day. Treatment is carried out within 7-10 days. Bacitracin is almost not absorbed, in connection with which a high concentration of the drug is created in the colon. In case of dehydration, infusion therapy and oral rehydration (reciprons, citrothosolyan) are used. To bind toxin A, cholestyramine is prescribed.

There are reports of the possibility of treating AAD also large doses of probiotics. S. Perskyp and L. Brandt (2000) found that the normal human microflora can eliminate the diarrhea caused by Cl. difficile. Bactericidal action of normal microflora provides the recovery of more than 95% of the patients with AEAD associated with Cl. difficile. It warns the appearance of chronic clostridial and other infection, which can cause chronic gastrointestinal disorders from part of patients. Therapy with probiotics with ADA and PMK should be started as early as possible, without waiting for confirmation of the diagnosis.

Since the number of microbes providing therapeutic effect, Several orders of magnitude exceeds the dose of ordinary bakpreparations, the question of the local delivery of probiotics into the intestines is discussed. This can be done with the help of salt solutions based, through the subjective probe or a colonoscope. The last method attracts attention, since, how do probiotics are introduced directly into the proximal division of the colon.

One of the main probiotic drugs used for the treatment of AAD is Linex. it combined drugcontaining the components of natural microflora from different bowel departments. Included in bifidobacteria, lactobacilluls and non-fiber-like enterococcus support the equilibrium of intestinal microflora and ensure its physiological functions: they create adverse conditions for breeding and vital activity of pathogenic microorganisms; Participate in the synthesis of vitamins in 1, 2, RR, folic acid, vitamins K and E, ascorbic acid, provide the need for the body in vitamins in 6, in 12 and biotin; producing lactic acid and reducing the pH of the intestinal contents, create favorable conditions for the absorption of iron, calcium, vitamin D. The lactic acid bacteria carry out the enzymatic splitting of proteins, fats and complex carbohydrates, not attempted in a small intestine carbohydrates and proteins are subjected to deeper cleavage in the colon anaerobes ( in t. bifidobacteria). Bacteria included in the preparation are involved in the metabolism of bile acids.

Linex contains lamp bacteriaresistant to the action of antibiotics. Adults and children over 12 are prescribed 2 capsules 3 times / day after eating, drinking a small amount of liquid. The duration of treatment is an average of 1-2 months. When applying the drug in recommended doses side effect Not noted. Contraindications - increased sensitivity to the components of the drug or dairy products. The studies did not reveal the presence of teratogenic acts, did not report negative influence drug during pregnancy and during lactation. To preserve the viability of the components of the drug, it is not recommended to drink linex with hot drinks, you should refrain from alcohol consumption.

Clinical manifestations of allergies for lactic acid bacteria are similar to manifestations of allergies on dairy products, so when symptoms are allergic, the drug should be discontinued to determine its causes. On cases of overdose of Linex not reported. Its unwanted interaction with other drugs is not marked. The composition of the drug Linex allows you to take it simultaneously with antibacterial agents.

For symptomatic treatment of diarrhea, it is also applied: adsorbent attipulgitis, 1.2-1.5 g after each liquid stool; Loperamide, 2-4 mg inside after each defecation (no more than 8 mg / day); diphenoxylate / atropine (lobs), 5 mg inside 4 times a day before the termination of diarrhea; Belladon tincture, 5-10 drops inside 3 times a day before meals; Hyoscyamine (Levsin) 0.125 mg under the tongue as needed or 0.375 mg inside 2 times a day; Sprused dicycloverin, 20 mg inside 4 times a day; codeine, 30 mg inside 2-4 times a day; octreotide (100-600 mg / day p / k in 2-4 reception) - synthetic analogue of somatostatin; Enterosorbent (smecta, espumizan).

Treatment of actually dysbiosis

Standard discharge therapy is aimed at eliminating excess bacterial generation of small intestine, restoration of normal microflora, improvement of intestinal digestion and suction, intestinal motility restoration and improving the immunoreactivity of the body.

Antibacterial drugs are used according to the indications for suppressing the growth of pathogenic microflora in the small intestine. Usually prescribed antibiotics from group of fluoroquinolones, penicillins, cephalosporins, tetracycles or metronidazole. Preparations are accepted in ordinary doses within 7-10 days.

Optimal is the use of funds that have a minimal effect on the symbiotic microflora and overwhelming the growth of the flow, staphylococci, yeast mushrooms and other aggressive strains. These include antiseptics: Inertertrix, enterol, bakyubyl, nifuroxazide, etc. With severe forms of staphylococcal dysbiosis, antibiotics are used: offloxacin, oxacillin, amoxicillin. They are prescribed for a period of 10-14 days. In case of appearance of mushrooms in feces or intestinal juice, the use of natamycin, fluconazoles and other microwaves is shown.

Bacterial preparations (probiotics) can be prescribed without preliminary antibacterial therapy or after it. Apply bifidumbacterin, probe, bificol, lactobacterin, lines, bifiform, normoflorine L, d, b, polybacterin, ninete, acipol, nutroline, trevis.

Another way to treat dysbiosis is the impact on the pathogenic microbial flora of the products of the metabolism of normal microorganisms (prebiotics). One of these drugs is a hilak-forte, a sterile concentrate of non-metabolic products of normal microflora: lactic acid, lactose, amino acids and fatty acids. These substances contribute to the restoration of the biological environment in the intestine necessary for the existence of normal microflora, suppress the growth of pathogenic bacteria, improve the trophy and the function of epithelocytes and colocons. One milliliter of the drug contains biologically active substances of 100 billion normal microorganisms. Hilak-forte is prescribed 60 drops 3 times a day for a period of 4 weeks in combination with antibacterial drugs or after their use.

In addition, lactulose syrup is used (Duhalak, Portalk), acidifying intestinal juice and the oppressing growth of pathogenic microflora. The active substance is a synthetic disaccharide, which is not hydrolyzed in the small intestine and enters the rims in an unchanged form, where the colon is split under the action to form low molecular weight organic acids, which leads to a decrease in the pH of the intestinal content.

Under the influence of the drug, the absorption of ammonia by the colon and the removal of it from the body increases, the growth of acidophilic bacteria is stimulated (including lactobacteria), the reproduction of proteolytic bacteria is suppressed and the formation of nitrogen-containing toxic substances. The clinical effect occurs after 2 days of treatment. The preparation in the form of a syrup for intake is prescribed by adults in a dose of 15-45 ml / day, the supporting dose is equal to 10-25 ml / day. The drug should be taken 1 time / day in the morning while eating, with water, any other liquid or food.

Side effect on the side of the digestive system: in the first days - meteorism (passing by independently after 2 days); for long use In high doses, pain in the abdomen, diarrhea are possible. Contraindications: Galaktozhemia; intestinal obstruction; Increased sensitivity to the components of the drug. Lactulose can be used during pregnancy and during lactation according to indications. The drug should be cautious to prescribe patients with diabetes.

From other prebiotics, calcium pantotenate should be noted (participates in the processes of acetylation and oxidation in cells, carbohydrate and fat exchange, the synthesis of acetylcholine is utilized by bifidobacteria and helps increase their mass), aminomethyl benzoic acid (pamba, amben) - fibrinolysis inhibitor, suppresses proteolytic enzymes of conditionally pathogenic bacteria, stimulating the growth of normal microflora, lysozyme (has a bifidogenic, immunomodulatory, anti-inflammatory effect, improves digestion, improves digestion, Pass the pathogenic flora).

In the treatment of dysbiosis, it is recommended to use phytopreparations. They are intestinal antiseptics, suppress pathogenic and retain the saprophytic microflora. Phytosborgs normalize appetite, improve digestion, intestinal motorcyc, have antimicrobial and immunomodulating effect, contribute to the regeneration of the mucous membrane. The pronounced bactericidal effect is given by St. John's wort, calendula, eucalyptus, yarrow, palm, sage, soul man, lingonberry, plantain. The immunocorrigating effect is networked, Melissa, mother-and-stepmother, plantain, tricolor violet, a series. Rich in vitamins lingonberry, nettle, raspberry, currant, rowan, rosehip.

Pancreatic enzymes (Creon, Panecitrath) are prescribed patients with disturbed bandy digestion. In order to improve the absorption function, the essentiality of Fort H, Loperamide (Imodium) and trimethenbutin is used.

To increase the reactivity of the body weakened patients with severe dysbiosis, it is advisable to appoint Anaferon, immunal, lycopid and other immunomodulators. The course of treatment should continue on average 4 weeks. At the same time prescribe vitamin and mineral complexes (vitaminerl, alphabet, etc.).

For literature, please contact the editor.

V. V. Skvortsov, Doctor of Medical Sciences
Volgm, Volgograd

The relationship between man (macroorganism) and its surrounding micromirome was formed over many millennia, and possibly millions of years. In its evolution, they passed several historical stages. At the first stage, these were the relations of a mutual confrontation, confrontation: the person's body persistently resisted the invasion of foreign microorganisms to him. In this confrontation, as believed, not one human line died. At the second stage of the interaction of the macroorganism and the microflora penetrating into it entered into a compromise relationship by smoothing mutual antagonism and coexistence on the principles of commensalism (Commensal - Sotraznik). In the third stage, by overcoming commensalism, harmonious symbiosis was formed on the principles of mutualism, when both macroorganism and endosimbionate bacteria retrieves certain advantages on their cohabitation, providing favorable conditions for maintaining the population of symbiotic bacteria and their active participation in the exchange of substances, the immune protection of the human body, etc.

Thus, the roots of mutual adaptation and the origins of the occurrence of a balanced microecological system "Macroorganism - endosimbionth bacteria" go to the distant past.

Mutualism as the highest form of symbiosis is a steady form of human coexistence and endosimbionate bacteria, but it is maintained only until the mutually beneficial balance of interest is broken. In the case of suppressing the vital activity of endosimbionate bacteria, environmental and pathogenic microorganisms occupy their place and reversible, and then irreversible changes in the human body, which contribute to the development of diseases and threaten its life itself. And the whole population of endosimbionth bacteria finally disappears with the death of the owner (person). In view of this, one of the most important functions of endosimbionth microflora, colonizing the man's colon, is the preservation and stabilization of the environment of their habitat, protection of it from penetration of alien bacteria and viruses.

The essential functions of endosimbionate bacteria are studied. Among them should first be called:
Protective function: ensuring the colonization resistance of the macroorganism due to the pronounced antagonism of the bond (indigenous) microflora (mainly bifido- and lactobacilli) relative to conditionally pathogenic and pathogenic bacteria;
Detoxicating function: Eubionate microflora has the properties of a natural biosorbent, accumulating, inactivating and eliminating toxins of endogenous and exogenous origin (phenols, xenobiotics, metals, etc.);
Synthetic function: synthesis of biologically active substances, including vitamins (in complex, K, folic and nicotinic acids), indispensable amino acids, enzymes, mediators, cholesterol and other participating in the metabolic processes of the body (bifido- and eubacteria, intestinal wand);
digestive function: Participation in enzymatic cleavage (hydrolysis) of dietary fiber, fermentation of carbohydrates (products of bacterial fermentation of carbohydrates - short-chain fatty acids - the main source of energy for colocontes), washed fats, the formation of organic acids, shifting the pH of the intestinal environment in the acidic side, which serves as an obstacle to growth and reproduction of conditionally pathogenic bacteria (bifido- and lactobacilli, eu- and propionic acid, bacteroids);
Immunogenic function: maintenance high level immunological and non-specific protection of the organism by developing bacterial modulins that stimulate the lymphatic apparatus, the synthesis of immunoglobulins, interferon, cytokines; increase in the content of complement and propercide, lysozyme activity, reduce the permeability of vascular tissue barriers for toxic products of metabolism of conditionally pathogenic and pathogenic bacteria and the obstacles to their penetration (translocation) into the internal environment of the body (bifido- and lactobacilli);
Morphokinetic (trophic) function: improving the trophic of enterocytes, ensuring their physiological regeneration, regulation of the intestinal motor function;
Bactericidal function: the production of antibiotic substances (bacteriocinates) participating in the elimination of alien microorganisms, penetrated into the colon.

It is not by chance that many microbiologists and clinicians, comprehensively studied this problem, concluded that the eubionate bacteria colonizing the colon, for the aggregate of the functions performed, are a special vitro body that plays a crucial role in life human organism. The normal colon microflora is a system, largely comparable to significance with other functional systems of the human body.

The opening of antibiotics in the middle of the 20th century and their introduction into everyday medical practice has become the main strategic direction in the fight against human bacterial infections. There was a real hope of delivering humanity from infectious diseases. Unfortunately, this hope turned out to be illusory. There was no unique ability of single-cell microorganisms to modify the conditions unfavorable for their existence. In a short time, the bacteria changed unrecognizable, rebuilt their genetic apparatus and acquired secondary resistance to the action of antibiotics used for their eradication. Highlighted (aggressive) mutant strains appeared, which still threaten the health and life of a person. The incidence and mortality rate during sepsis, tuberculosis, pneumonia, whose pathogens acquired immunity to action earned again effective antibiotics. The micro-operation of a person has radically changed, in which 1-shape bacteria, mycoplasma, chlamydia, viruses began to prevail.

Widespread and not always justified using antibiotics wide spectrum Actions in the fight against pathogenic bacteria was accompanied by simultaneous inhibition of life and eradication of endosimbionth microflora, localized in ecological niches (intestines, urogenital zone, lymphatic system, etc.). This caused a number of negative consequences. Thus, the violation of the fragile dynamic equilibria (balance) in the "Macorganism - endosimbionthic bacteria" system contributed to growth, reproduction, and then the dominance in the colon of the conditionally pathogenic and pathogenic microflora, the immunological protection and detoxification ability decreased, and various metabolic and digestive digestive dysfunctions appeared, There were conditions for the development of various antibiotic-associated diseases. With the suppression of antibiotics, endosimbionth microflora is associated, as believed, and the spread of viral infection is believed, since there is an evolutionary and ecological antagonism between bacteria and viruses. It has been established that the symbiotic bacterial microflora constantly produces blood circulating and lymphic enzymes (nucleases) - dases and rhases, which at a concentration\u003e 50 AE / ml can dissolve viral nucleic acid, causing virion degradation and eliminating virons. With the loss of most endosimbionate bacteria, homeostasis of the human body (genetic constancy of its internal medium) is disturbed and begin to spread viral infections: Cytomegalovirus, atypical pneumonia virus, Ebola virus, Epstein-Barr virus, HIV infection.

Of course, the creation of antibiotics is a huge, indisputable achievement of scientists who have gone to doctors a mighty tool for successful combating bacterial infection. However, uncontrolled, not always justified, the irrational use of antibiotics led to new threats. Bacteria managed to survive, adapt to antibiotics and take revenge. Some of the old infections were revived and new infectious diseases were emerged due to manutants manually created by bacteria. Antibiotic-associated diarrhea and its most severe clinical form - pseudommbranous colitis can serve as a vivid example of similar non-heroic diseases associated with inadequate antibiotic therapy and the development of decompensated discharge (dysbiosis) of the intestine.

Etiology and pathogenesis
The most important condition for the development of antibiotic-associated diarrhea and pseudo-memory colitis is the suppression of bond (indigenous) microflora microflora and the induction of growth, reproduction, and then the dominance of conditionally pathogenic and pathogenic bacteria, which turned out to be resistant to the action of antibiotics applied.

Recently, various negative effects of antibiotic therapy occur more and more often, up to 1/3 of all cases of complications of pharmacotherapy. Antibiotic-associated diarrhea develops in 3-26% (up to 30%) patients receiving antibiotics. Moreover, treatment with one antibiotic causes a colon dysbiosis in 12% of patients, two - in 34%, three - in 50%. Antibiotic therapy for 7 days causes the development of colon dysbiosis in 100% of patients, especially in the preceding intestinal pathology.

The cause of antibiotic-associated diarrhea can be the reception of any antibiotic of a wide range of action, but more often than others cause the development of antibiotic-associated diarrhea clindamycin (in 20-30% of cases), amoxiclav (10-25%), Cephixim (15-20%),

Other generation cephalosporins (3-5%), ampicillin (2-5%), erythromycin and other macrolides (2-5%), tetracycline (2-5%), fluoroquinolones (1-2%), as well as Lincomicin, Gentamicin, neomycin, co-trimoxazole. It does not exclude the possibility of participation in the development of antibiotic-associated diarrhea of \u200b\u200bmushrooms of the genus Candida and viruses. Antibiotics taken inside, act not only in the digestive tract, but also after their absorption in the intestine, standing out with saliva, bile, other digestive secrets. The change in the definition of the rate of development of antibiotic-associated diarrhea from the adopted dose of the antibiotic and the duration of its reception (less than 3 days and more than 7 days). With a longer reception of the antibiotic (14 and 21 days), the difference in the rate of development of antibiotic-associated diarrhea is leveled. When taking an antibiotic inside the risk of developing antibiotic-associated diarrhea increases. It is important to emphasize that in 80-90% of cases, the development of antibiotic-associated diarrhea is not associated with a certain (specific) causative agent, and the symptoms of antibiotic-associated diarrhea may appear both during the antibiotic taking (not earlier than the 4th day) and (more often) after 1-2 and even 3-4 weeks after its end. The reason for this lies, apparently, is that after the suppression of the antibiotic eubeing microflora, the colon requires a certain time for the growth and reproduction of the conditionally pathogenic microflora responsible for the development of antibiotic-associated diarrhea.

Among the microbes - antibiotic-associated diarrhea pathogens appear: Staphilococcus Aureus, Clostridium Perfringens, Clostridium Difficile, Enteropathogenic strains of Escherichia Coli, Salmonella, Klebsiella Oxytoca, and maybe mushrooms genus Candida. In part of patients (about 1% of cases), antibiotics causes the development of the most severe clinical form of antibiotic-associated diarrhea - pseudomembranous colitis.

For the first time, pseudommbranous colitis was described in 1893, long before the introduction of antibiotics. Considered it first as ischemic colitis, and after the discovery of viruses - as viral intestinal infection. In 1935, the Hall and O "Toole was allocated from the feces of patients with pseudommbranous colitis, a previously not known sporing microbe called Clostridium Difficile (" difficult "clostridium): Its discoverers had difficulty in obtaining culture of this bacterium. However, at that time, the development of pseudomambranous colitis is not They were associated with the presence of Clostridium difficile in the intestines, moreover, it was considered as a commensant. With the beginning of the era of antibiotics cases of pseudo-membrane colitis, they were sharply frequent, including with a fatal outcome. First as a possible causative agent of pseudommabranous colitis, staphilococcus aureus was considered, but in a short time It turned out that with a pseudommbranous colitis in feces is determined, as a rule, a large number of Clostridium difficile. In 1977, a cytotoxin was first isolated, produced by this microbe (Larson et al.), and soon managed to confirm the etiological role of Clostridium Difficile in the development of pseudomambranous colitis in the development of pseudomambranous colitis Experiment Those on hamsters.

Clostridium Difficile is a gram-positive "strict" anaerob, which refers to sporing-forming bacteria. It produces two toxins with a molecular weight of 308 and 270 kDa, which are denoted as toxins A and V. Toxin A represents enterotoxin with weak cytotoxic properties; It increases the vascular permeability, causes an unreasonable secretory diarrhea, fever, sometimes cramps. Toxin B has a pronounced cytotoxic effect in the culture of tissues with a cytopathic effect. Both toxin act locally and synergistically. Combining with cellular receptors, toxins damage cell membranes and are introduced into cells, inactivating Rho proteins and directly damaging colocuts. At the same time, they violate the intercellular contacts, induce the formation of inflammation mediators, cause action of actin, degradation of fat cells and chemotaxis, increasing the permeability of the cell barrier with damage to the gauge of the colon sheath and the formation of ulcers, necrosis, vasculitis, hemorrhage.

When taking antibiotics, the vital activity of an indigenous microflora is suppressed, and closeridium difficile multiplies due to the presence of sporing plasmids and antibiotic resistance. After the abolition of antibiotics, the disputes are transferred to the vegetative forms of bacteria and begin to produce toxins A and V. With a pseudommbranous colitis, in contrast to the lighter forms of antibiotic-associated diarrhea, the dose of the antibiotic and the duration of its reception does not have a significant value. It should be noted that CLOSTRIDIUM DIFFICILE occasionally is found in the feces of practically healthy people (less than 3%). They account for only 0.01-0.001% of the entire mass of bacteria inhabitants in the colon. However, when the indigenous microflora is preserved, Clostridium difficile does not show their pathogenic action. After antibiotic therapy, the frequency of identification of this bacterium increases to 20%.

Thus, the development of antibiotic-associated diarrhea, including its most severe form, is preceded by the reception of a wide range of action, overwhelming the vital activity of the bond microflora of the colon, primarily the most vulnerable representatives - bifido- and lactobacilli with the development of superinfection resistant to the effects of antibiotics strains Practical and pathogenic microorganisms, including Clostridium difficile. It is believed that the pathological process in the colon in the pseudommabranous colitis is evolving according to the type of Schwarzman-Sanarelley phenomenon: first small, and then the more significant doses of enterotoxin produced by Clostridium difficile, are first caused by local (focal) necrosis, and then a generalized reaction with severe and extraordinary reaction manifestations.

The pathogens of antibiotic-associated diarrhea can be a variety of microorganisms (from 7 to 30 different types of conditionally pathogenic and pathogenic bacteria), including 10-20% of all cases of antibiotic-associated diarrhea - Clostridium Difficile. The main etiological factor of the pseudommabranous colitis is Clostridium difficile. Consequently, the indispensable condition for the development of the antibiotic associated diarrhea is the thick-current dysbiosis, and its most severe clinical form is a clostridial dysbiosis, which is not a background for the development of the disease, according to some authors, and its cause. With the loss of the indigenous microflora of the colon with its protective properties and participation in metabolic, immunological and digestive processes, the resistance of the body decreases, exchange and trophic functions are disturbed.

The prevalence of pseudommabranous colitis is definitely not established, as they are mainly diagnosed with severe diseases, ending with often fatal outcome, and light, erased, atypical cases of pseudommbranous colitis often remain unrecognized.

Among the gastroenterologists of our country, there are irreconcilable opponents of the teachings on dysbiosis (dysbacteriosis) of the colon, created by outstanding domestic scientists I.I. Mesnikov, A.F. Bilibin and their followers. Recognizing that the antibiotic-associated diarrhea and pseudo-membrane colitis contains quantitative and qualitative changes in the microbiocenosis of the colon with the reproduction and dominance of conditionally pathogenic and pathogenic bacteria, including Clostridium Difficile, they diligently avoid the term "disbiosis), Either apply it with a derogatory epithet "notorious. Without with scientific arguments, these authors are usually referred to the absence of the term "dibacteriosis" in the ICD-10, as well as the German dictionary of gastroenterological terms, in which the term "dysbacteriosis" is disavowed. The author-compiler of the dictionary N. Kasper is unfamiliar (this is obvious) with the research of Russian microbiologists and clinicians on this problem and vaguely imagines to be discussed. It binds the development of dysbacteriosis solely with the rebirth of the intestinal stick and negatively responds to its correction using its healthy strains.

If you lead a discussion at such a level, you can bring a quotation from the authoritative "therapeutic reference book of the University of Washington University", withstood 30 publications: "Antibiotics - a frequent cause of diarrhea ... they depress the normal intestinal microflora, which leads to dysbacteriosis. The most severe form is a pseudommabranous colitis. " It is important to emphasize that dysbiosis (dysbacteriosis) of the colon is not an independent nosological form and not a diagnosis, but a clinical and microbiological (clinical and laboratory) concept. It develops, as a rule, secondally and therefore should not appear in the list of diseases, as well as, and syndrome of excess microbial growth in the small intestine. When the clinical component of dysbiosis appears, it must be designated in a diagnosis as a complication of the underlying disease, as it requires correction, including drugs.

The light forms of antibiotic-associated diarrhea for some reason are called "idiopathic" (IDIOPathicus - primary, first arising, unknown origin). The term is clearly unsuccessful because antibiotic-associated diarrhea develops, as a rule, is secondary, and its cause is known (taking antibiotics). On the lungs (so-called idiopathic) forms account for 80-90% of all cases of antibiotic-associated diarrhea, with the etiological role of Clostridium difficile, it is possible to prove only 20-30% of them, and CLOSTRIDIUM PERFRINGENS and SALMONELLA - in 2-3%. The possibility of developing antibiotic-associated diarrhea during candidiasis (Candida Albicans, etc.) has not yet been proven.

In addition to the dysbiosis of the colon in the pathogenesis of antibiotic-associated diarrhea, the other side effects inherent in individual antibiotics may be:
Motin-like action of erythromycin;
incomplete absorption of cephaloperazone and its accumulation in the lumen of the intestine with a relaxing effect;
strengthening transmitted intestinal activity when receiving amoxiclava;
The immediate enterotoxic effect of neomycin, as well as a violation of enterogetic circulation of bile acids with accumulation in the intestine of deconjugated bile acids, stimulating intestinal secretion;
Violation of hydrolysis of carbohydrates and the formation of short-chain fatty acids with the development of osmotic diarrhea.

However, these side effects are inherent only by some of the antibiotics and can only have an auxiliary value in the development of antibiotic-associated diarrhea.

The risk factors of antibiotic-associated diarrhea and pseudommabranous colitis are:
age after 65 years;
Abdominal surgical interventions;
the oppression of the immune system of the body (intake of immunosuppressors, radiation and chemotherapy);
long stay in the hospital, especially in surgical compartment or in intensive care.

Thus, in polyclinic patients with clostridium difficile stand out with feces in 3-9% of cases, and in stationary - at 20-30%. When they stay in the hospital for 1-2 weeks they are found in 13% of patients, with 4-week treatments and more - in 50%. Moreover, 20-30% of them subsequently become bacteria carriers, and 1/3 develops a diarrhea syndrome. During stay in the hospital, with Clostridium difficile, a typical nosocomial infection can develop, which extends through dirty hands and medical equipment, as the disputes of these bacteria are continuously stored in the external environment. At the same time, the asymptomatic carriage of these bacteria is possible: in newborns - up to 50%, in adults - 3-15%.

Clinical picture
Clinically, the manifest forms of antibiotic-associated diarrhea can have a light, erased, atypical current, manifest itself with abdominal discomfort, a non-timber, inextricular diarrhea to 3-5 times a day with a general satisfactory condition of patients. With the so-called idiopathic form of antibiotic-associated diarrhea, the patients appear more frequent waterproof diarrhea, sometimes nausea, rarely vomiting. The volume of feces temperate with a small admixture of mucus, but without blood. Pain in the stomach is non-veins, palpation diseases along the colon, it is possible a small loss of body weight (no more than 1-2 kg). Anamnesis has an indication of antibiotics. With colonne-fibroscopy, visual signs of inflammation may be absent or focused, less often diffuse hyperemia. After the abolition of the antibiotic, the specified symptoms, as a rule, disappear within 3-5 days without treatment. No more than 27-30% of patients with idiopathic antibiotic-associated diarrhea are drawn to the doctor, 34% are treated independently, the rest do not resort to treatment at all. These patients have no fever, there are no changes in the overall analysis of blood, pathological impurities in feces, and with a colon biopsy, the signs of inflammation are missing or the focal or diffuse catarrhal colitis is determined.

With a pseudommatous colitis caused by Clostridium Difficile infection, highlights the lungs, moderate, and heavy (fulminant) forms. The course of pseudombamotomous colitis can be acute, subacute, rarely chronic recurrent (due to the spore-forming properties of Clostridium difficile and induction to produce toxins A and B). In addition to the sharp beginnings, the lightning form of pseudommabotomous colitis, resembling cholere, with a fatal outcome for several hours.

In case of pseudombamotomous colitis, patients complain of a watery diarrhea from 3-5 to 15-30 times a day for 3-5 days to 8-10 weeks, sometimes on false calls for defecation and tenesmas, anorexia. The belly will break, bother sharp constant or grapple-like stomach pain, increasing before each defecation. In 45% of cases, the nausea is concerned, in 31% - vomiting. In feces in patients, a large number of leukocytes (lactoferrine test) and red blood cells are found. The calmed into the glass dishes may contain pseudomber resembling cauliflower. Part of the patients is developing exudative enteropathy syndrome with a significant loss of a protein that is distinguished by the intestinal lumen. In most cases, fever appears - from subfebrile to high (39-41 ° C). In general blood test, neutrophilic leukocytosis is observed (16-20x109 / l and even 60 x 109 / l) with a nuclear shift to the left, increasing the rate of erythrocyte sediment to 40-60 mm / h or more. IN biochemical analysis blood is determined by hypoproths-nonime, hypoalbuminemia, deep disorders electrolyte exchange (hypovolemia, hypokalemia, etc.). In connection with the dehydration of the body and hypoalbumine, dystrophic edema develops syndrome.

During the generalization of the pathological process, biological barriers are broken, intoxication increases (general weakness, repeated vomiting, etc.), immunodeficiency develops, is determined by bacteremia to form metastatic foci of inflammation.

Complications of pseudombamotomous colitis: toxic megolon (accompanied by an increase in pain syndrome, local pain in the palpation of the colon, moderate tension of the muscles of the abdominal press, the appearance of free fluid in the abdominal cavity). Possible punching of colon and acute peritonitis, in 15-30% - infectious-toxic shock with death.

The extraordinary symptoms in the pseudommabmotal colitis are described: the polyarthritis is more often developed with the lesion of large joints, tachycardia, hypotension, cyanosis, suffocity, are experiencing less often. Fulminant forms of pseudombamotomous colitis usually develop in the presence of risk factors: on the background of heavy somatic diseases (hearts, kidneys, lungs, liver, diabetes), mainly in the age group over 65, as well as after surgery, especially on the abdominal organs.

With a pseudombamotomous colitis in 2/3 cases, distal colon departments are affected, 1/3 - proximal. Occasionally in the process involves a small intestine. The recurrences of the pseudommabotomous colitis are observed in 20-25% (up to 50%) of cases, and after the first relapse, the risk of developing the following increases to 65-70%. The most common cause of relapses is an incomplete intestinal retention from the CLOSTRIDIUM Difficile dispute, less often - reinfection.

Diagnostics
In addition to characteristic clinical picture and instructions on anti-bioticoherapy in history, in the diagnosis of antibiotic-associated diarrhea and pseudommabotomic colitis use methods of identifying pathogens using bacteriological research of feces. At the same time, the oppression of the bond microflora of the colon is determined, primarily bifido- and lactobacilli, and the dominance of conditionally pathogenic and pathogenic microorganisms (they were listed earlier), and with a pseudombamotomous colitis - the presence of a clostridium difficile co-grouper (its receipt, as it is known ). The sensitivity of the method is 81-100%, and its specificity is 84-99%; The response is obtained after 24-48 hours. Bowedly accessible to Calostridium Difficile cytotoxins (A and B) cytotoxins by studying their cytopathic effect in cell culture. This technique recognizes the "gold standard" in the diagnosis of pseudommabotomic colitis. However, it is a laborious, complex, is distinguished by a high cost, which restrains its widespread use. Especially use the methodology of immunoassay analysis - an immunoerment analysis (ELISA TEST TechLab), which is characterized by high informativeness, reproducibility, simplicity and speed of receipt of the response: after 2-4 hours. Its sensitivity is 63-89%, and specificity is 95-100%. As an alternative to immunooperment analysis, a polymerase chain reaction can be used (sensitivity 97%, specificity 100%) or latex test (express diagnostics), but the last method is less reliable (sensitivity 58-92%, specificity of 80-96%).

Methods have been developed for the chemical determination of causative agents in feces using gas chromatography and mass-spectrometry, which are based on the analysis of the composition of the monomeric chemical components of the microbial cell and its metabolites (marker substances) - the detection of microbial composition.

In the diagnosis of pseudommabotomic colitis, a colorsophybroscopy with aiming biopsy and morphological study of bioptats is of great importance. Visually affected mucous membrane of the colon of the ecto, is loosened, hyperemic. It detects protein-yellow pseudo-membrane plaques with a diameter of 0.2 to 1.5 cm with a diameter of 0.2 to 1.5 cm, focal necrosis and deep ulcers. Pseudommabras are soft, tightly soldered with the subject to tissues of education, and when trying to separate them from the mucous membrane, a bleeding surface appears. At colonoscopy, localization and lesion length is also evaluated. Histologically detect subepithelial edema, fibrinous plaques, under which areas of necrosis are located. The composition of plaques includes: fibrin, mucin, increasing epithelium, destroyed leukocytes and bacteria. Cystroinous rebirth and expansion of glands, excess mucus formation, foci of fibrinoid necrosis, round-flux inflammatory infiltration of the mucous membrane and the submucosal layer with polynuclear plates with cereal areas, covered with a deskvamy epithelium, pseudomber, which, when merging, acquire a mushroom shape; There is a damage to vessels.

In computed tomography, the thickening of the intestinal wall is determined, inflammatory accumulation in the abdominal cavity, and during irrigoscopy - the cog of contours of the colon, edema folds, violation of the gustration.

Differential diagnosis in fulminant forms of pseudommabotomic colitis should be carried out with acute bacillomic dysentery, salmonellosis, ulcerative and granulomatous (Crohn disease) colitis, ischemic colitis, yersiniosis. In case of pseudombamotomous colitis, there is no diarrhea with scarlet blood, although there are bleeding.

Treatment methods
Treatment of antibiotic-associated diarrhea should be started with immediate abolition of an antibiotic responsible for the development of diarrhea. With idiopathic forms of antibiotic-associated diarrhea, this is usually sufficient to stop diarrhea for 4-5 days. Defined in these patients, the casual dysbiosis I-II degree, as a rule, does not need correction: Normobiocenosis is restored independently.

With protracted forms of antibiotic-associated diarrhea, which after the abolition of the antibiotic continues 5-7 and more days, during the study of the feces, the dysbiosis II-III degree is determined. In these cases, there is a need to correct the dysbiosis using functional nutrition and the appointment of probiotics containing representatives of the bond microflora of the colon (bifido and lactobacteria, enterococci).

Recently, recommendations appeared to introduce probiotics (synbiotics) directly into the thick intestine using rectal mulfur based on saline solutions to ensure their high concentrations, as well as through a nasogastric probe. The most reasonable is the introduction of probiotics through a colophybroscope, which allows you to combine a visual inspection with the diagnosis of antibiotic-associated diarrhea and the introduction of probiotics in proximal departments Colonse. At the same time, a clinical effect is achieved in a short time (diarrhea resistance, the disappearance of pain syndrome and meteorism).

Normobiocenosis is being restored slightly slower than the clinical symptoms of antibiotic-associated diarrhea disappear: after 3-4 weeks. In more severe, persistent cases of antibiotic-associated diarrhea, with persistent dysbiosis of the III-IV degree, there is a need for an active suppression of a conditionally pathogenic and pathogenic microflora dominating in the colon, with the help of antibacterial agents. They must be appointed by strict testimony and for a short time: not more than 7-10 days. It should be started with the use of intestinal antiseptics, which, having a wide range of antimicrobial activity, at the same time almost do not oppress the vital activity of the bond microflora of the colon.

Modern methods The treatment of medium-heer and heavy (fulminant) forms of pseudommabotomous colitis are provided in addition to the abolition of antibiotics provoked its development, a number of urgent medical events:
Purpose of etiotropic therapy aimed at Eradication Clostridium Difficile;
conducting detoxing therapy;
Restoration of the water and electrolyte balance in the presence of signs of the body dehydration;
the appointment of correlated immune and metabolic disorders, primarily disorders of protein metabolism;
The use of synbiotic (probiotics) to restore the normobiocenosis of the colon, as well as the purpose of symptomatic treatment.

Treatment must be started immediately to prevent the hardest complications and the rapid progression of the pathological process. Under the hospital's conditions for the prevention of Clostridium difficile infection and the development of pseudommabotomic colitis, it is necessary to strictly follow the hygiene rules. If possible, it is necessary to isolate patients with pseudommabotomic colitis, since the risk of infection with disputes of this bacterium is very large, especially in weakened patients with severe somatic diseases.

For Eradication Clostridium Difficile is prescribed Vancomycin and / or metronidazole. As the etiotropic therapy of the first line, a number of authors recommends the metronidazole in a dose of 250-500 mg 4 times a day, within 7-10 days. Other authors consider the drug to choose with pseudombamotomous colitis of vancomycin - 125-500 mg 4 times in time, 7-10 days. It is emphasized that the effect of both drugs is comparable, but the cost of metronidazole is lower. In addition, Vancoma Qina has contraindications (pregnancy) and the risk of selection of resistant strains of Clostridium difficile is preserved. If necessary, both drugs can be combined or combined vancomycin with rifampicin (600 mg 2 times a day). As an antibiotic reserve, a complex Bacitarian antibiotic is recommended, which is almost not absorbed in the intestine, creating a high concentration in the colon (125 thousand me 4 times a day, 7-10 days). However, due to the high cost of bacitracycling, its use is limited. With the ineffectiveness of treatment with vancomycin, metronidazole and bacitracin, some authors are recommended to additionally introduce human immunoglobulin: intravenously at a dose of 200-300 mg / kg body weight.

The effectiveness of etiotropic therapy of pseudommabotomic colitis reaches 90-97%. Symptoms of the disease disappear within 2-3-5 days and no later than 10-12 days. However, the complete bowel sanitation from the CLOSTRIDIUM Difficile dispute is not always achieved, and therefore, in 25% of cases, recurrence of pseudommabotomous colitis, which in 5% of patients have a serious prognostic value. To prevent the chronic clostridial infection and the prevention of recurrence of pseudommabotomous colitis, enterol is used - therapeutic yeast containing Saccharomyces BoulardII, which reduce the risk of relapses by about 2 times. Enterol restores the barrier function of the intestinal mucosa due to the stimulation of local immunity by developing a secretory immunoglobulin A (SIGA) and the amplification of phagocytosis increases the products of disaccharideases and the metabolic activity of the eubiotic microflora of the colon, synthesizes the tripsin-like proteases, inactivating enterotroid clostridium difficile, and blocks their receptors, lowers Education in CAMF cells. SB is insensitive to antibiotics, so they can be prescribed simultaneously with them. Enterol dose is 500-1000 mg per day (2-4 capsules or bags) for 3-4 weeks. Enterol is not recommended to be prescribed patients with secondary immunodeficiency and combined pathology of internal organs due to the danger of the development of bacteremia. Early authors are recommended for pseudombamotomous colitis an early purpose of large doses of probiotics, which contribute to the restoration of the colon eubiosis and thereby eliminate the symptoms of the disease and prevent bacterianesis, first of all Spore Clostridium Difficile. It has been established that the normal microflora of the colon is able to eliminate the antibiotic-associated diarrhea associated with Clostridium Difficile.

In hypoproteinemia, intravenous albumin solutions, amino acids are introduced to replenish the deficit of the protein. In the dehydration of the body, infusion therapy is carried out: intravenous drip administration of a 20% glucose solution with electrolytes, lactasol, sliced \u200b\u200bsolutions, ringer in volume from 2-3 to 10-12 l for 48 hours after the reduction of diuresis is prescribed potassium chloride solutions (with hypokalemia) . In the easy cases of dehydration, the loop solution is used inside. Sometimes there is a need for parenteral nutrition. With pronounced immunodeficiency, immunomodulators are prescribed. Dose of Imunofan (regulatory peptide) - 1 ml 0.005% solution intramuscularly, daily, 10 days. Immunomodulator last generation Hepon, also regulatory peptide, involved in the transmission of signals in cells, provides induction of interferon, cytokines, activation of monocytes and neutrophils, enhancing the products of antibacterial antibodies, activation of local immunity, promotes the elimination of pathogens microbes: 1 mg (in 1 ml of water) inside 2 times a day, 3-5 days. In 0.4% of cases, conservative treatment of pseudommabotomic colitis turns out to be ineffective, then the total tetomy is carried out.

In the treatment of pseudommabotomous colitis, the purpose of the immodium and other drugs depressing the intestinal peristalsis is contraindicated, since endotoxmia is growing, the course of the disease is prolonged, the danger of the development of toxic megalon.

Concluding an overview of the antibiotic-associated diarrhea and pseudommabotomic colitis, it is necessary to draw the following conclusions.
Antibiotic-associated diseases are one of actual problems Modern medicine. The main cause of the development of antibiotic-associated diarrhea and pseudommabotomic colitis is the thick-current dysbiosis (dysbacteriosis), due to the suppression of bond (indigenous) microflora, reproduction and dominance of conditionally pathogenic and pathogenic bacteria, which are resistant to the action of most antibiotics, among which the special place belongs to Clostridium Difficile.
Treatment with antibiotics should be carried out only by strict indications. Low doses of antibiotics and shortened antibacterial therapy courses induce the appearance of resistant strains of pathogenic bacteria, and unnecessarily high doses and prolonged antibacterial therapy courses determine the development of high degrees (III-IV) colon dysbiosis and the emergence of antibiotic-associated diseases, including antibiotic-associated diarrhea. and pseudommabotomic colitis.
Even the lungs of thick-current dysbiosis have no clinical equivalent, negatively affect the state of macroorganism, reducing its overall resistance, accompanied by metabolic and digestive digestive dysfunctions.
Clinically, the manifest forms of antibiotic-associated diarrhea and M need correction using functional nutrition, pro and prebiotics, antibacterial and symptomatic pharmacotherapy, overwhelmingly pathogenic and pathogenic microflora, including clostridium difficile, and reducing normobiocenosis of the colon.

• Unformed (liquid) chair three or more times for at least two days during the reception of antibiotics or within two months after it:
  • chair can be from 3-5 to 20-30 times a day in severe cases;
  • chair is usually watery, sometimes with blood and mucus;
  • in some patients, an alternation of a normal decorated chair with liquid, others, constant, which lasts up to several weeks or even months can be observed.
• Discomfort in the stomach.
• Stomach pain without clear localization (location).
• It is possible to increase body temperature to subfebrile numbers (37-37.5 ° C), with a long-term heavy course of the disease, the body temperature rises to 40 ° C.

Forms

Depending on the severity of the flow, several forms of the disease are distinguished.

• Easy shape. There are minor pains and discomfort in the stomach, the frequency of the chair does not exceed 3-5 times a day. The abolition of antibacterial therapy (the use of antibacterial drugs), as a rule, leads to the disappearance of symptoms (multiple liquid stool). Clinical form called "mildillness" (moderate malaise).
• Medium-heavy shape. Chair is frequent, up to 10-15 times a day, with an admixture of mucus and blood, there is an increase in body temperature, abdominal pain, increasing during palpation (feeling). The abolition of antibiotics does not lead to the complete disappearance of symptoms. As a rule, with this form, segmental hemorrhagic colitis is developing (inflammation of the fat intestine mucosa in a separate section, accompanied by bleeding).
• Heavy shape. The patient's condition is very heavy, the body temperature rises to 39 ° C. More, the frequency of the chair reaches 20-30 times a day, complications are often developing (for example, perforation (tearing) of the intestine, dehydration (dehydration), etc.). Manifests itself a pseudommabranous colitis (acute inflammatory bowel disease caused by microorganism ClostridiumDifficile.).
• Fulminant shape (lightning room). This form is characterized by very rapid progression of the symptoms of the disease: a sharp increase in body temperature up to 40 ° C, very sharp and severe abdominal pains (a picture of the "acute abdomen"), a frequent liquid chair is quickly replaced by constipation and intestinal obstruction (violation of the movement of food and cartoons by intestines). This form of the disease is often developing in weakened patients, which, for example, receive treatment for malignant tumors (cancer uncontrolled by the body of the growth of cells and tissues leading to violation of organs of organs).

The reasons

• Antibiotic therapy (use of antibacterial drugs). Most often, antibiotic associated diarrhea is developing after receiving:
  • penicillins (a group of antibiotics produced (produced) fungi genus Penicillium; the world's first antibacterial drugs);
  • cefalosporins class antibiotics (bactericidal (killing bacteria) of the wide range of action, including against microbes, resistant to penicillins) - often the second-third generation;
  • macrolids - effective natural antibacterial drugs of the last generation (diarrhea develop relatively rarely) and some others.

• with simultaneous reception of several antibacterial drugs;
• when using chemotherapy, antineoplastic preparations (for the treatment of tumors), immunosuppressive therapy (overwhelming activities and activity of the immune system);
• when taking drugs of gold, non-steroidal anti-inflammatory agents (non-phonal anti-inflammatory drugs);
• when taking anti-diagram preparations (for treatment);
• when taking neuroleptics (psychotropic drugs - for the treatment of mental disorders).

• in chronic bowel diseases (for example, chronic colitis (intestinal inflammation));
• with malignant (oncological) intestinal tumors;
• when;
• after operations on the abdominal organs;
• after receiving cytostatics ( medicinal preparationsstopping cell division);
• with long-term location in the hospital (with the attachment of concomitant diseases);
• after frequent diagnostic manipulations on the intestines (for example, colonoscopy and reorganosososcopy - diagnostic procedures, during which the doctor examines and evaluates the state of the inner surface of the colon using a special optical tool (endoscope)).

Diagnostics

• Analysis of complaints and anamnesis of the disease: when (as long ago) appeared, how many times a day, what medications did the patient accepted and with what result, it was specified, whether antibacterial therapy was carried out over the past two months, which drugs.
• Anamnese analysis of life: It is clarified by the presence of any chronic diseases, especially the gastrointestinal tract (for example,), whether antibiotic therapy has ever been carried out before and with what consequences.
• Inspection: The doctor draws attention to the possible availability of signs of dehydration (the total weakness of the patient, the dry leather, dry tongue, and so on), palpates (feeling) the abdomen area (pain enhanced), listens to the peristaltics (wave-like reducing the intestinal walls, promoting the food lump) . With a fulminant (lightning) disease, the patient's condition is very heavy, a picture of the "acute abdomen" is observed:
  • severe abdominal pains;
  • decrease in blood pressure;
  • a sharp increase in body temperature, pulse and breathing frequency.
• Laboratory examination methods.
  • Common Blood Analysis: Allows you to detect signs of inflammation in the body (increase in leukocyte levels (white blood cells), raising the level of ESP (the rate of sedimentation of erythrocytes (red blood cells), a non-specific sign of inflammation)).
  • General urine analysis: allows you to reveal elevated level Protein, leukocytes, red blood cells.
  • Biochemical blood test: an increase in acuteness proteins (blood proteins, which are produced in the liver in response to development inflammatory process In the body), hypoalbum (the content of albumin (the main blood protein) in the blood below 35 grams / liter).
  • Cala analysis: detected increased content leukocytes (only single cells can be detected), which indicates the presence of inflammation in the body.
  • Bacteriological method of diagnostics - sowing feces on special nutrient media for the purpose of cultivation of culture (colonies) of microorganisms contained in it (for example, bacterium ClostridiumDifficile.), and determining their sensitivity to antibiotics. Also, within the framework of this method, a study of cytopathic (toxic (poisonous) for cells) of the effect in the culture of microorganisms is carried out: the isolated microbes in different amounts are planted in the colony of living cells, this allows you to reveal the minimal concentration of toxin (poisoning substance produced by microorganisms).
  • Polymerase chain reaction (PCR diagnostic method) - a high-precision diagnostic method, which allows to detect DNA (deoxyribonucleic acid - a structure that provides storage, transmission from generation to generation and implementation of the genetic program of a living organism) of the disease pathogen in the sample under study and work with a large variety of microorganisms, which fails for one or another reasons to propagate in the laboratory conditions.
  • Envunimal analysis (ELISA) - a complex technique that allows you to identify specific toxins ClostridiumDifficile. A and B (subspecies of poisoning substances produced by a microbe).
• Instrumental research methods.
  • Endoscopic methods (inspection of the inner surface of the colon with the help of a special optical tool - endoscope) study of the intestine:
    • colonoscopy - inspection with a long flexible endoscope,
    • rectorOnoscopy - inspection using a rectoscope - a rigid metal tube, which is introduced into the rectum and allows you to estimate the state of the mucous for 25-30 cm from the anal hole.
• Intestinal biopsy (taking a small piece of tissue of the body under study with a special long needle for further study by its microscope).
• Computed tomography (CT) with contrasting - the kind of X-ray examination with the introduction into the body of contrast (special substance visible on x-ray), allowing you to get a layer-by-layer image of organs on the computer. The pictures are found: sealing the walls of the colon, the symptom of the "Accordion" (various accumulation of contrast in the intestinal lumen and on the damaged intestinal mucosa), the symptom of the "target" - a decrease in the accumulation (absorption of contrast by cells) of the injected contrast.
• Consultation.

Treatment of antibiotic-associated diarrhea

• Canceling antibiotics.
• Dietary table number 4 by Pevznera. Use of products that contribute to a decrease: rice, bananas, baked potatoes, toasts, kissels. Exception from diet oily, fried, acute and dairy food. Food is frequent, small portions.
• A sufficient use of fluid, as dehydration often occurs due to persistent diarrhea.
• When identifying a certain causative agent (for example, Klostridia - bacteria ClostridiumDifficile.) Specific (directed against a specific microorganism) therapy with anticoleosdial means is carried out.
• Disinfecting therapy (elimination of the actions of toxins - poisoning substances allocated by microorganisms).
• Elimination of dehydration (dehydration treatment):
  • oral (through the mouth) of salt solutions,
  • intravenous administration of saline solutions.
• Restoration of the normal intestinal microflora - the reception of probiotics (preparations containing microorganisms characteristic of the normal microflora of the human intestine: certain types of lactobacilli, bifidobacteria, enterococci, as well as therapeutic yeast - sugaromycete). Applies only after all of the above methods.
• Surgical treatment: with severe and fulminant (lightning room) the course of the disease, it is necessary to remove the affected part of the intestine.

Complications and consequences

• Dehydration of the body, infringement of metabolism.
• Reduced arterial pressure.
• Toxic megaColon (expansion of a large intestine, a loss of contractile ability, which leads to a long delay in the carts in the intestine and causes intoxication (organism poisoning)).
• Superinfection (re-development infectious diseaseif initially it was not properly cured)
• Reducing the quality of life of the patient.

Prevention diarrhea antibiotic-associated

• The rational use of antibiotics is strictly by appointing a doctor.