A single microbial cell can produce 16 million of its own kind per day; microorganisms have an exceptionally high adaptability to changing environmental conditions. They also get used to antibiotics. At the heart of this phenomenon, known as resistance (or resistance), is natural selection; all bacteria that are sensitive to the antibiotic die, and the few that are not susceptible to it survive. These bacteria begin to multiply unrestrainedly in the area that was freed up due to the death of competitors. So there is a resistant strain. This is one of the main problems of chemotherapy, because the appearance of resistant species reduces to zero the therapeutic value of the antimicrobial agent. The frequency of occurrence of resistant strains is directly related to the frequency of use of the drug. The doctors themselves often help the microbes survive by prescribing the drugs needed in more severe cases to patients for a speedy effect. Identical drugs are prescribed for different infections; the result is the habitability of microbes. For example, in the United States, gentamicin is still a drug of almost resuscitation value, and in Russia, due to its too frequent appointment (due to cheapness), the resistance of bacteria to gentamicin reaches 40 %! In addition, the bacteria have discovered the ability to share information with microorganisms of other species. It is very important when treating with antibiotics to observe the duration of the course and not stop taking the drug at the first signs of recovery, otherwise we risk getting a multi-resistant strain. The long-term use of penicillins in medical practice has led to the appearance of microbes that produce a special enzyme – penicillinase, which neutralizes penicillins. For example, staphylococci have become a major clinical problem and cause the death of many patients. The problem is that there is still cross-resistance in nature: microorganisms that have learned to cope with a natural antibiotic are often resistant to semi-synthetic representatives of this series. Cross-resistance develops against antibiotics with a similar mechanism of action. It is possible to delay the emergence of new resistant strains through the economical use of a newly introduced antibiotic. These new antibiotics try to keep in reserve and are prescribed only in critical cases. They are called “reserve antibiotics”. Currently, drugs that combine an antibiotic and an enzyme inhibitor are being developed. By the way, part of the responsibility for the resistance of microbes lies with livestock breeders. Animals receive huge doses of antibiotics on farms, because when they are taken, they actively gain weight. As a result, microbes get used to small doses of antibiotics in animal meat. According to statistics, tetracycline antibiotics are found in 11 % of samples of meat and meat products, penicillin-in 33 %, streptomycin – in 25 % of samples of milk. The basic rules of antibacterial therapy can be formulated as follows:
- Determine the causative agent of the disease.
- Find out which drugs the pathogen is most sensitive to.
- In the case of an undetermined pathogen, it is recommended to use a drug with a wide spectrum of action or a combination of two drugs, the total spectrum of exposure of which includes all possible pathogens in this case.
- Start treatment as early as possible.
- It is necessary to select such doses of drugs that are present in cells and tissues in a concentration that prevents reproduction (bacteriostatic concentrations) and destroys bacteria (bactericidal concentrations).
- The duration of treatment should be sufficient; the gradual normalization of body temperature and the weakening of other symptoms is not a reason to stop treatment.
- Of great importance is the most appropriate choice of routes of administration of drugs, provided that some drugs are partially absorbed from the gastrointestinal tract, almost do not penetrate from the blood to the brain (through the blood-brain barrier).
- The mixed use of antibacterial drugs should be justified, since with the wrong combination, both the weakening of their overall activity and the summation of their toxic effects are possible.
There are generally accepted schemes for the duration of treatment of infections such as pulmonary tuberculosis, bacterial endocarditis, streptococcal pharyngitis and lower urinary tract infections that occur without complications. In-depth scientific studies of the last 20-30 years have confirmed that antibiotic prophylaxis in elective surgical interventions should last no more than 24 hours. Many authors support the point of view of the expediency of a single prophylactic administration of an antibiotic during surgical intervention, the duration of which does not exceed two half-lives of the drug used. The response of microorganisms to the use of antibiotics was also the occurrence of such a complication of antibiotic therapy as dysbacteriosis. In this condition, the composition of the intestinal microflora changes greatly. The change in the normal microflora of the large intestine under the influence of antibiotics can manifest itself in such variants.
- Functional changes in the activity of the colon (irritable bowel syndrome, spastic dyskinesia of the colon).
- Chronic colitis (focal or diffuse, associated with the presence of mainly opportunistic flora).
- Primary pathology of the large intestine with secondary changes in the intestinal microflora (diverticular disease, ulcerative colitis, Crohn’s disease, etc.).
- The development of an opportunistic infection, for example, candidiasis. In the stomach of a healthy person, microorganisms cannot exist due to the sharply acidic environment of the gastric juice. In the duodenum and small intestine, bacteria are rare visitors. But the content of microorganisms in the large intestine is about 250 billion in 1 g of intestinal contents. The total number of them in the entire intestine is 1015 billion. There are so-called non-permanent representatives of the human microflora. These include microorganisms that enter the body with air, food, and water; they are quickly removed from the intestine. In the course of research, it was noted that experimental animals raised in conditions of complete sterility, i.e. completely immune from the penetration of bacteria into their body and therefore deprived of natural microflora, have serious violations in a number of vital processes. In particular, the underdevelopment of lymphoid tissue was noted. There are also significant violations of water metabolism, and the amount of antibodies in the blood serum is significantly reduced compared to the norm.
- Functions of normal microflora (bifidobacteria and lactobacilli):
- “Protective-prevents colonization of the intestine by pathogenic and conditionally pathogenic microflora;
- “Enzyme-producing-provides the function of hydrolysis of fiber, proteins, fats, bile acids, etc.;
- “Synthetic-synthesizes B vitamins, ascorbic acid, cholesterol, uric acid, organic acids, etc.;
- “Immunizing-supports the synthesis of immunoglobulins, affects the maturation and functioning of immunocompetent organs.
Normally, the bacteria of the large intestine finish digesting food that is not completely broken down in the stomach and duodenum and is not completely absorbed in the small intestine. This type of obtaining the necessary nutrients by the body is commonly called symbiotic digestion. Our normal microflora feeds, so to speak, on the leftovers from our table. As a return service, a person receives vitamins, amino acids, organic substances, etc. from bacteria. The species composition of the human microflora changes markedly in a number of pathological processes, as well as in the irrational use of antibiotic drugs. With a moderate consumption of animal food, i.e. with a diet close to the ideal, the symbiotes of the large intestine should receive only vegetable carbohydrates, some of which are not digested by humans in principle. These include fruit pectins, cellulose, and dietary fiber. They undergo fermentation, which is considered extremely useful for the macroorganism. However, the undigested proteins and peptides that enter the large intestine become an ideal environment for the unrestrained reproduction of putrefactive bacteria. Thus, instead of the normal fermentation process, we get a rotting process. A huge amount of toxins leads to self-poisoning of the body, creating many big and small problems for us. At the moment, there are still a fair number of open questions that in one way or another affect the problem of dysbiosis. As a rule, dysbacteriosis is a concomitant disease. It can occur either asymptomatically, completely unnoticed by a person, or with bright clinical symptoms. The first disorders begin to develop long before the development of clinical symptoms, when the protective functions of the body are suppressed and the likelihood of infectious diseases increases significantly. This increases the frequency and severity of acute and chronic infections. In addition, dyspeptic intestinal disorders, food toxicoinfections are noted. The enzymatic reactions change, the synthesis of vitamins drops sharply. The natural intestinal microflora of a healthy person is active, destroying pathogenic microorganisms, or inhibiting their growth and thereby preventing the development of infection. With progressive changes in the intestinal microflora, the likelihood of allergic manifestations increases, the severity of which can be very different. Most acute intestinal diseases and all chronic ones are accompanied by dysbiosis, which contributes to their severe and prolonged course. The same situation is observed in other diseases, in particular, pneumonia of viral and bacterial origin. With dysbiosis in the intestine, the number of bifidobacteria decreases, but E. coli with altered properties appear. As the natural microflora deficiency develops and the body’s resistance decreases, there is a risk of developing superinfection, which can lead to blood poisoning and death. When dysbacteriosis occurs in the human body, there is a predominance of microbes that are resistant to a number of antibiotics. It is absolutely necessary to remember about preventive measures aimed at preventing such conditions. Long-term uncontrolled use of antibiotics and similar self-medication should be avoided. In general, the principle of “saving the drowning-the work of the drowning themselves” is not very appropriate here. On the contrary, even a doctor should think three times and weigh all the pros and cons of using a particular drug. The antibiotic resistance of microbes has largely predetermined the emergence of hitherto unseen superinfections. Superinfection is a re-infection in the conditions of an incomplete infectious disease; simultaneous damage to the body by two infectious agents. Recently, the assumption that different types of the same virus can merge into one virus has been confirmed. These turned out to be viruses, effective methods of combating which are not available to this day. Two HIV viruses-HIV-1 and HIV-2-exchanged genetic material and formed a new virus that took a dominant position in the patient’s body; at the same time, the patient’s condition deteriorated sharply. The authors of this discovery believe that the possibility of superinfection of the human immunodeficiency virus can reveal the secrets of HIV, AIDS in particular, explain the reason for the incredible resistance of HIV to antiviral drugs and vaccines. Apparently, the whole point is that the absolute majority of medicines act exclusively on a strictly defined type of virus. And since HIV-infected patients have sex with other HIV – “positive” people, it cannot be excluded that in many cases, various subspecies of this virus accumulate in their blood. The ability of HIV to mutate is so high that no two HIV-infected people have viruses that are completely the same. Such a disease as AIDS is often accompanied by the occurrence of superinfection, which causes the death of the patient. There is an opinion, however insufficiently confirmed, that AIDS is an artificially created disease, and the appearance of the human immunodeficiency virus is considered as a possible consequence of the excessive use of antibiotics, including in animal experiments. Maybe someday we will know the true cause of HIV, and maybe not, but the obvious consequences of antibiotic therapy already provide serious food for thought. Imagine the mechanism of occurrence of such a pathological condition of the body as superinfection. Within us, at least two pathogens simultaneously coexist and actively affect us; it is possible that one or even both of them are highly resistant to antibiotics. To treat superinfection, again, is supposed to be antibiotics, trying them in various combinations. The problem increases like a snowball. Now, unfortunately, there is no single classification of the development of superinfections and dysbiosis, but this does not prevent us from assessing the size of the threat to humanity. It can be quite definitely said that superinfection is a “checkmate” for people who overly trust antibiotics. Microbes evolve at almost the same rate that human civilization seeks protection from them. It is impossible not to take into account that there is always a group of patients who make up the risk group. They have no clinical manifestations, but there are changes in the microflora. These people, especially in unusual circumstances, certainly need the supervision of a doctor. The clinical symptoms of dysbiosis and concomitant infections depend not only on the pathological changes in the human microflora, but also on the general state of the body, the immune status and compensatory capabilities of the body.
There are three main forms of dysbiosis:
- Compensated form, or latent dysbacteriosis (without clinical manifestations).
- Subcompensated with the appearance of local inflammatory foci of different lengths.
- Decompensated, accompanied by generalization and the formation of metastatic foci in parenchymal organs and a possible outcome in sepsis (blood poisoning).
Scientists distinguish various pathological changes in the intestinal microflora, depending on the etiological factor. Thus, post-infectious, post-chemotherapeutic, post-radiation, nosocomial and paraphysiological (associated with the natural formation of non-pathogenic microflora) dysbiosis is determined. This classification does not reflect the whole complex of problems, and therefore it is proposed to distinguish three types of dysbiotic disorders: isolated, combined and dislocated. Taking into account the above, it should be noted once again that at present it is impossible not to take into account the appearance of dysbiotic changes in the intestines of patients, but the attitude to them should be differentiated. In mild forms of dysbiosis, treatment is indicated on an outpatient basis, hospitalization of the patient is carried out only in severe cases. Stop the administration of antibacterial drugs that could cause the development of a pathological condition. In parallel, desensitizing and restorative therapy is prescribed. With candidomycosis (a disease in which there is a progressive reproduction of the fungus of the genus Candida), you can recommend nystatin and levorin; with staphylococcal dysbacteriosis-erythromycin. It often makes sense to prescribe drugs that belong to the group of digestive enzymes. A good effect is given by the use of lactulose preparations, known to doctors for more than 40 years. At the same time, no direct or indirect evidence of the presence of mutagenic, genotoxic or other side effects of lactulose was obtained in any study during the entire period of use. The drug lactusan, when taken together with antibiotics, protects the beneficial intestinal microflora from the negative effects of these drugs; with such a scheme of use, the antibiotic affects pathogenic bacteria, and lactusan selectively stimulates the vital activity of the beneficial microflora, being the optimal nutrient medium for it and providing it with competitive advantages. This drug stimulates the growth of bifidobacteria and lactobacilli, which activate the body’s immune system, as well as inhibits the growth of opportunistic microorganisms and protects the intestinal walls. If there are obvious manifestations of dysbiotic changes in the intestinal microflora in adults, therapy may be difficult in some cases. If the cause of intestinal dysbiosis is the use of an antibiotic, then, as we have already mentioned, it is advisable to cancel this drug. Nevertheless, in some cases, the withdrawal of a therapeutic antibacterial drug is not very desirable, in particular with typhoid fever in the midst of the disease. In such situations, it makes sense to prescribe therapeutic biologics that are not susceptible to the action of antibacterial agents (such as lactobacterin). Patients with functional intestinal disorders of a dysbiotic nature need vitamin therapy, especially B vitamins, as well as therapy aimed at desensitizing the body. With dysbiosis of the III-IV degree, patients have to prescribe a course of treatment with directed antibiotic drugs. It is as natural and logical as possible to prescribe biological preparations of living bacteria (eubiotics or probiotics) when dysbiotic phenomena have developed. Prescribing them exclusively in accordance with changes in the patient’s microflora is not enough. It is necessary to take into account the type and phase of the underlying disease. Combined biologics are of great interest. The therapeutic effect of such drugs is due to the presence in their composition of viable bifidobacteria and lysozyme as a natural factor of protection of the gastrointestinal tract. Lysozyme has a bifidogenic, immunomodulatory, anti-inflammatory effect, stimulates metabolic and reparative processes, improves digestion, significantly increases the anti-infectious and antitoxic resistance of the body, has an antibacterial effect. The best combination of bifidobacteria and lysozyme increases the degree of therapeutic effect (in particular, significantly reduces the period of intoxication) of each component contained in this drug, and makes it possible to limit the use of antibiotics for the treatment of severe patients with acute intestinal infections, as well as for dysbiotic changes in the intestine. Currently, domestic medicines made from apatogenic representatives of the genus Bacillus, such as sporobacterin and biosporin, have been developed and put into wide practice; previously, the imported drug bactisubtil was often used. The therapeutic effect of this group of drugs is determined by pronounced antagonistic properties against a large number of pathogenic and opportunistic bacteria, including fungi of the genus Candida, staphylococci, proteus. At the same time, these drugs do not have any effect on the representatives of the normal microflora of the human body. Candidiasis is among the most frequent opportunistic infections. It rarely acts as the main disease. The effects of antibiotic therapy are a predisposing factor for the development of candidiasis, which is an associated disease. The practice of using antibiotics, as well as the HIV pandemic, make candidiasis the most urgent problem in the coming decades.
Reference. Candida are oval-shaped dimorphic fungi that grow as budding yeast cells and are a chain of elongated cells (pseudogypha and natural hyphae). More than 150 varieties of Candida are known, of which at least 10 cause candidiasis in humans. The most virulent are C. albicans var. albicans, C. albicans var. stellatridea and C. tropicals. Less virulent, but still capable of causing the disease C. parapsilosis, C. quillermondi, C. krusei, C. pseudotropicals, C. viswanatbii, C. zeylanoides, C. paratropicals that are present in the human body in yeast form.
The cell walls of Candida fungi are a multi-layered structure consisting of polysaccharides with a small addition of proteins and lipoids. Candida develops rapidly when the reaction medium (pH) is from 3 to 8, at a temperature of 20-4 °C, with a characteristic smell of yeast. Soft cream-colored clusters of microbes actively grow on blood and glucose agar, forming pseudonatural hyphae. The human body is considered as a carrier of Candida and acts as a source of infection. It is quite difficult to determine the fine line between the usual presence of Candida in the body and the disease. Studies clearly show that C. albicans is found in 50 % of people in the oral cavity, in the gastrointestinal contents as a permanent and stable part of the microflora. The frequency of detection of Candida in the oral cavity increases with diabetes, dental prosthetics and smoking. C. albicans is currently a frequent component of the vaginal microflora. According to conservative estimates, this fungus occurs in 20 % of non-pregnant and 30% of pregnant women. The skin is somewhat less susceptible to the action of Candida. Other varieties of the fungus are detected on various parts of the skin and mucous membranes. However, they are found there much less often than in the oral cavity, the gastrointestinal tract and in the female genital tract. The real invasion of C. albicans usually begins at birth, at the moment when the child passes through the birth canal of the mother. This often leads to a localized oral infection, causing the development of thrush, which may well be the source of the spread of the fungus to other children in contact with the sick child. Infection with Candida at a more mature age is a consequence of the transfer of the fungus from person to person. Transmission from an infected animal to a human is also quite possible due to the fact that birds and mammals are often carriers of fungi. Since Candida does not reproduce in the air and soil, infection through the environment is unlikely. Infection coverage includes lesions of the skin, oral mucosa, gastrointestinal tract, and vagina, and regular involvement of internal organs in the infectious process. Disease caused by C. albicans, often observed in patients with diabetes, leukemia, in patients with pathology of the lymphatic system, immunodeficiency, treated with antibacterial agents. As a rule, the process is localized, and only with intensive reproduction, the fungus can enter the blood and cause damage to a number of internal organs. This process is a consequence of the spread of fungi from the gastrointestinal tract, penetration into the blood through infected intravenous and urinary catheters and infected nutrient solutions for injection. One of the most severe complications of candidiasis is endocarditis (inflammation of the inner lining of the heart), although damage to any other organ is not excluded. The superficial (cutaneous) manifestation of candidiasis is defined as a rash in infants and inflammation in housewives due to the fact that the hands are often in contact with the aquatic environment. An extremely rare form of the disease of the skin and oral cavity is called “chronic mucosal candidiasis”. The disease usually manifests itself in the first 10 years of life, especially before the age of 2 in children with reduced endocrine system function or a pronounced immunodeficiency condition, the Swiss variety of gammaglobulinemia or thymus gland growth retardation and T-cell immunity deficiency. Almost all forms of candidiasis (oral, gastrointestinal, vaginal, general, and cutaneous) are caused by C. albicans, which is due to the ability of this fungus to grow in human tissues in the form of hyphae. The development of candidiasis is favored by an increase in the number of glucocorticoids taken, immunosuppressive drugs, and antibacterial treatment. The total number of fungi in the oral cavity, gastrointestinal tract and vagina is mainly due to the glucose content in these organs, since glucose is an excellent nutrient medium for the growth and reproduction of fungi. The increase in glucose concentration, which is noted in diabetes and glucocorticoid therapy, of course contributes to the growth and development of fungi. Medicines that prevent the development of microorganisms, in particular the antibiotic tetracycline, also contribute to an increase in the concentration of glucose, potentiating the reproduction of fungi. It should be noted that intact mucous membranes usually serve as a reliable barrier, preventing the invasion of Candida into other human tissues and organs. Despite the fact that the mechanisms responsible for preventing infection are not yet fully understood, it is known that blood white blood cells (neutrophils and macrophages) actively destroy fungi that penetrate the submucosal tissues. The exceptional importance of phagocytic activity is proved by the pronounced spread of fungal flora in individuals whose cellular resistance is reduced by immunosuppressive therapy. Thus, we get another argument in favor of extremely careful and reasonable use of medicines, including antibiotics. It should never be forgotten that HIV-infected patients receive antibiotics against the background of reduced immunity. In 80% of patients with HIV infection, the spread of candidiasis comes from the microflora of the oral cavity, which is actively promoted by the use of antibacterial agents.