Bacteriophages, application in medicine. The use of bacteriophages in medicine and beyond

Have you ever wondered why bacteria have not yet taken over nature and why their number in the environment is always approximately the same? What prevents them from reproducing in water bodies and soil? What protects the planet from excess bacteria?

Answers to these questions were received back in the last century, when they came across a genus of viruses that infect not humans or animals, but bacteria. Having seen under a microscope how, under the influence of these viruses, the environment is cleared of bacteria, the French scientist Felix D'Herelle called these microorganisms bacteriophages or “bacteria eaters.”

Bacteriophages were discovered 20 years before penicillin, but when the first antibiotic appeared, successfully killing many bacteria at once, bacteriophages were forgotten and research was suspended. Since the beginning of the 21st century, humanity has faced a serious problem - bacteria that cause diseases have become resistant to antibiotics. And doctors, in search of a new antibacterial agent, remembered the well-forgotten bacteriophages - natural killers of bacteria.

From the Ganges to the laboratory

Scientists began tracking bacteriophages back in the 19th century. In 1896, English bacteriologist Ernest Hankin traveled to India to study the properties of water in the Ganges River. This river is sacred to the Hindus. Local residents believe in the healing properties of its waters. But, as you know, complete unsanitary conditions reigned there. People bathed in the river, dumped the corpses of cholera patients into it, but, nevertheless, there was no epidemic of intestinal infection. Something prevented the cholera pathogen from multiplying. Hankin suggested that the water of Indian rivers contains an unknown substance that has an antibacterial effect and prevents the spread of bacteria. This, then still unidentified, treatment object was precisely bacteriophages! It turned out that, thanks to them, the causative agent of cholera in the Ganges River dies in three hours, while in an ordinary body of water destruction takes almost two days.

Phages are widespread in nature and live not only in water bodies, but also in soil, in the body of humans and animals. In short, where there are bacteria, there are also viruses that eat them. In pure natural water there are at least 10 phages for every bacterium. While there are few bacteria in the environment, the chances that the phage will find “its” bacteria are small. But when circumstances allow infectious agents to multiply, a cluster of bacteria appears next to the bacteriophage, and the “killer and victim” meet.

Mechanism of action of bacteriophages

The virus penetrates the cell of a pathogenic bacterium, inserts itself into its genome and begins to multiply. After a certain number of new viral particles (virions) accumulate inside a bacterial cell, the cell is destroyed, the viruses come out and infect new bacterial cells.

Life cycle of a bacteriophage

The phage approaches the bacterium and the tail filaments bind to receptor sites on the surface of the bacterial cell.
The tail filaments bend and “anchor” the spines and basal plate to the cell surface; the tail sheath contracts, forcing the hollow shaft into the cell; this is facilitated by the enzyme lysozyme, which is located in the basal lamina; thus, nucleic acid (DNA or RNA) is introduced into the cell.
The phage nucleic acid encodes the synthesis of phage enzymes using the host's protein synthesizing apparatus.
The phage in one way or another inactivates the host DNA and RNA, and the phage enzymes completely break it down; Phage RNA subjugates the cellular apparatus.
The phage nucleic acid replicates and encodes the synthesis of new envelope proteins.
New phage particles formed as a result of spontaneous self-assembly of a protein shell around the phage nucleic acid; Lysozyme is synthesized under the control of phage RNA.
Cell lysis: the cell bursts under the influence of lysozyme; about 200-1000 new phages are released; phages infect other bacteria.
Stages 1-7 take about 30 minutes; this period is called the latent period.

Bacteriophages as medicine

“The enemy of my enemy is my friend.” This phrase can describe the principle of phage therapy. Most scientists agree that bacteriophages hold the future in the fight against infections. Their active use can help overcome antibiotic resistance and cleanse the body and environment of many pathogens.

Even if humanity is at some point left without effective antibiotics, we will still be able to fight pathogens with the help of natural “bacteria eaters.” The main feature of bacteriophages is that they attack only bacteria without affecting human cells.

How does a bacteriophage work?

Phages use a bacterial cell to create their offspring, completely enslave the bacterium, forcing its internal organs to create bacteriophage particles. This interaction is called absolute intracellular parasitism.

Almost 96% of bacteriophages look like sperm. A typical bacteria eater has a head and a tail. The tail consists of a main shaft and flagella that resemble spider legs. The head contains the bacteriophage's genetic information and enzymes, and the tail is designed to attach to the surface of the bacteria. In addition to the classic “tailed” bacteriophages, there are also particles that consist only of a head without a process or have the shape of a rod or thread, but without a head.

Among bacteriophages there are two types - virulent and temperate. The first ones are radical, they immediately destroy the bacteria. The latter infect a whole family of bacteria, but do not kill all of them.

The bacteriophage destroys the bacterium as follows:

It finds the desired target protein or receptor on the bacteria and “sits” on it with its tail.
With the help of spines on the tail, it is tightly attached to the cell wall.
Next, the virus secretes enzymes that dissolve the outer shell of the bacterium and drills a hole in its wall.
Through the puncture, the bacteriophage injects its genome into the bacterium, but the phage shell remains outside the bacterium.
When phage DNA penetrates the nucleus of a bacterium, the latter loses its individuality and ceases to control intracellular processes.
The virus completely rearranges the metabolism inside the cell and forces the bacterium to synthesize proteins of future phages.
New bacteriophages are assembled from protein molecules. When their number becomes critical, the bacterial cell swells, and the viral enzymes destroy its wall from the inside. As a result, the cell “explodes” and a new generation of bacteriophages comes out.

The entire cycle lasts from several minutes to several hours. On average, a bacteriophage recreates its new generation in 20–40 minutes. This is the highest rate of reproduction that living organisms have! In one cycle, 100–300 new “eaters” are formed from one phage, which are ready to attack the remaining bacteria at the site of inflammation. This bacteriophage cycle is called lytic, since the infected bacterium undergoes lysis - destruction.

But there is another type of infection - lysogenic or creating decay. With it, the bacteriophage inserts its DNA into the bacterial chromosome without disrupting the function of the cell. The bacteriophage integrated into the genome has not yet been assembled, but the bacterium is alive. An immature virus particle, or prophage, after dividing a bacterium, is inherited by its descendants or daughter cells. Of all the progeny, the prophage can be activated in several bacteria without affecting the rest. After activation, the prophage acts in exactly the same way as a virulent bacteriophage - it matures and ruptures the bacterial cell. This entire cycle is called lysogenic. It is characteristic of moderate, less aggressive bacteriophages. Unlike virulent species, a temperate bacteriophage does not destroy all bacteria in the environment, but suppresses their excessive growth. Thus, bacteriophages with moderate aggressiveness help in the prevention of diseases, and virulent species help in treatment.

Bacteriophages: types and purpose

The use of bacteriophages in medicine is extensive; polyvalent species are most often used, which contain a whole complex of active microorganisms . Basic forms:

Coliphages, or simply coli, help cope with skin inflammation and infection of internal organs caused by enteropathogenic E. coli.
Typhoid bacteriophages - eliminate illnesses caused by salmonella and typhoid pathogens.
Coliproteus or coliproteophages - are used in the treatment of cystitis, colpitis, pyelonephritis, colitis and other diseases caused by enteropathogenic bacteria Escherichia and the Proteus virus.
Klebsiella polyvalent bacteriophages are a complex remedy that destroys Klebsiella rhinoscleroma, pneumonia and ozena.
Dysenteric polyvalent dysphags - destroy Shigella Flexner and Sonne in bacterial dysenteries.
Protean proteophage - fights protean species of specific microorganisms, such as vulgaris and mirabilis, which are the main cause of purulent intestinal inflammation.
Staphylophages - destroy the action of staphylococcal microbes, active in any purulent inflammation.
Klebsiella pneumoniae, Klebsifagus - treat inflammatory ailments of the digestive, urogenital and respiratory systems caused by Klebsiella pneumoniae.
Streptophagus - actively fights inflammatory infections caused by streptococcus.
Pseudomonas aeruginosa - used in the treatment of dysbiosis and other infections caused by Pseudomonas aeruginosa.

Classification of bacteriophages

Today there are 19 types of active forms of viruses. They differ in shape, their genome structure and the type of nucleic acid. The classification of these drugs in medicine also differs in the speed of their influence on the activity of microorganisms:

moderate - only partially affects and destroys pathogenic bacteria, but causes significant changes in them, which are transmitted during their further reproduction, preventing the progression of the virus;
It is customary to call virulent those that, upon entering the body, act rapidly and very actively and almost instantly destroy bacterial cells, leading to their death.

How do bacteriophages differ from antibiotics?

Antibiotics are just chemical compounds that are secreted in nature by a number of fungi. Bacteriophages are living organisms. In essence, they work like microscopic robots, but launched not with the help of nanotechnology, but by nature itself. 70–90% of strains of pathogens of various infections are sensitive to bacteriophages. The most effective broad-spectrum antibiotics can kill 60–90% of bacteria. That is, bacteriophages are not inferior in effectiveness to antibacterial drugs. But at the same time they have many advantages.

Advantages of bacteriophages

The first and most important advantage of bacteriophages is the absence of side effects. Taking them is absolutely safe for humans, but at the same time very effective in fighting infection!

Phages are independent fighters against bacterial infections. The state of the human immune system does not affect the functioning of phages. They act selectively only on those bacteria that have special “signaling” proteins on their surface – receptors. In this case, only its “personal” bacteriophage can affect one bacterium. And the same phage will not be able to destroy another species or even a group of bacteria, therefore, if you take a bacteriophage, you will not be at risk of intestinal dysbiosis and associated diarrhea, diarrhea or fungal infection. You will not need additional antifungal agents or probiotics, as is the case with antibiotics. Thus, phage therapy is not only effective and safe, but also saves on treatment costs.

Let's compare the antibacterial effects of bacteriophages and antibiotics in the body. When a bacteriophage enters the site of inflammation, it multiplies and destroys all bacteria sensitive to it until the organ is completely cleansed. After each destroyed bacteria, several hundred bacteriophages are formed in the environment, which means that there is no need to take an additional dose. When all harmful bacteria in the area are destroyed, the bacteriophage is also removed from the body without causing harm.

What happens if we take antibiotics? For an antibiotic to work, there must be a lot of it. Therefore, doctors prescribe pills several times a day. So the concentration of the drug in all tissues of the body gradually increases and reaches the therapeutic level, that is, giving a therapeutic effect, after three days. But doctors continue to take antibiotics for up to 7-10 days, otherwise the undead bacteria will become resistant to it. During this time, due to the high dose of the drug, the patient experiences a number of side effects, since the antibiotic is a poison not only for bacteria, but also for the body.

Why are bacteria resistant to antibiotics, but cannot resist phages?

The second main advantage of bacteriophages is that they are effective even when antibiotics are powerless. The bacteria that cause infections in us are gradually finding ways to resist the drugs. They evolve, begin to produce enzymes that destroy the antibiotic, and this ability is passed on to the entire generation of surviving bacteria. In the past, antibiotic resistance occurred within 20 to 30 years. During this time, scientists managed to create a new generation of drugs, and doctors successfully treated all types of infections. But now, in just 2–3 years, pathogens become immune to antibiotics, and even those microbes that appear in the sterile conditions of a hospital can resist the medicine.

In order for a bacterium to become resistant to a phage, it must mutate, change its “protein code” and the structure of the receptor on the cell wall to which its devouring virus is fixed. But phages are also capable of evolution, therefore, for any new group or strain of pathogens, its own “devourer” is necessarily formed.

This race for survival happens constantly. As long as bacteria exist, their killer phages will also exist. Therefore, when one culture of bacteriophages becomes ineffective, you simply need to isolate a new group to cure the infection. And this can be done not in a few years or even months. A new bacteriophage is obtained in 2–3 days or several weeks.

All that is needed to obtain new phages is to isolate them from the same environment where the infectious agent lives, for example, from feces, soil, sewage, and even from hot springs or the depths of the ocean. The production of the drug is very simple and environmentally friendly. To separate the virus from the medium, the sample is passed through a filter, which retains bacteria but allows small particles of bacteriophages to pass through.

Are there any disadvantages to bacteriophages?

Despite obvious advantages, bacteriophages are inferior to antibiotics in several respects. Because phages act as “snipers,” targeting specific bacteria, the doctor must know exactly what is causing the infection. The high selectivity of bacteriophages does not allow their use if the infection is caused by several pathogenic microbes at once. In such cases, broad-spectrum antibiotics are prescribed that act on a range of bacteria. But this problem can also be solved. So that the phage preparation can destroy all harmful bacteria in the body, “cocktails” are created from several types of bacteriophages.

The use of bacteriophages in clinical practice: the Renaissance

For citation. Kostyukevich O.I. The use of bacteriophages in clinical practice: the Renaissance // RMJ. 2020. No. 21. pp. 1258–1262.

Prerequisites for the use of bacteriophages Today, bacterial infections represent an extremely pressing health problem. And the reasons for this are not only increasing antibiotic resistance, but also the extremely negative health consequences of irrational antibiotic therapy.

Antibiotic resistance In recent years, virtually no new antibacterial drugs (ABPs) have appeared, while resistance to “old” ABPs is steadily increasing and in many cases has already reached a critical level. WHO draws attention to the fact that many discoveries in the field of drug treatment made in the 20th century may lose their significance due to resistance to ALD. As a result, most infectious diseases can simply get out of control [1]. The greatest danger is posed by hospital infections, now referred to as healthcare-associated infections (HAI), the prevalence of which already reaches 5–10% of the number of patients in hospitals, and mortality ranks tenth among the causes of mortality in the population [2]. However, the treatment of these diseases is extremely difficult due to the high incidence of antibiotic resistance (50–99%).

Difficulties in treating chronic infections with traditional antibiotics “Chronic infections... are very difficult, if not impossible, to treat with antibiotics” [3]. One of the significant reasons for the low effectiveness of therapy for chronic infections is the formation of biofilms, which prevent the penetration of antibiotics. In this regard, great hopes are placed specifically on bacteriophages, which work in this situation according to the “Trojan horse” principle: by infecting one bacterial cell, they penetrate with it under the biofilm, and after the death of the carrier cell, a large number of newly synthesized phages enter the colony, damaging other bacteria [3]. In addition, bacteriophages stimulate the activation of specific and nonspecific immunity factors [4, 5], which enhances their effectiveness in the treatment of chronic infections.

Side effects of antibiotic therapy In addition, clinicians in their practice are increasingly faced with unsatisfactory tolerability of antibiotics. Thus, the frequency of antibiotic-associated diarrhea has increased significantly in recent years and ranges from 2 to 30%, depending on the antibiotic used [6]. More and more patients are refusing to take ABP due to the development of side effects or due to fear (sometimes well-founded) of intestinal dysbiosis. And increasingly, unfortunately, we are faced with a violation of the principles of rational antibiotic therapy on the part of doctors themselves, which, of course, aggravates the situation with both resistance to ALD and the safety of antibiotic therapy. In this regard, the key tasks are the development and introduction into clinical practice of additional means of combating infectious diseases, which, undoubtedly, can be considered bacteriophages.

Bacteriophage (bacteria + Greek phagos - devouring; synonym: phage, bacterial virus) is a virus that selectively infects bacteria. Bacteriophages are widespread in nature; every gram of soil, every cubic centimeter of water and air, food, plants and animals contain millions of phage particles (from 10 to 100 million). These are the oldest inhabitants of the planet and are natural limiters of the spread of bacteria.

History of the creation and use of bacteriophages The history of the discovery of bacteriophages dates back to 1896, when the British chemist E. Hankin, studying the antibacterial effect of the waters of the Indian rivers Ganga and Jumna, first described certain agents that easily pass through membrane filters impenetrable to bacteria and cause the death of microbes . In 1917, an employee of the Pasteur Institute in Paris, F. D'Herelle, proposed the name “bacteriophages” - bacteria eaters; he later determined that they are bacterial viruses capable of causing specific lysis of bacteria [7].

In 1921, D. Masin and R. Bryong first described a successful method of treating staphylococcal skin infections using staphylococcal phage. Until the middle of the twentieth century. In the West, bacteriophages have been widely studied and effectively used as a therapeutic agent against a number of diseases, including dysentery, typhoid, paratyphoid, cholera and purulent-septic infections. However, since the discovery of penicillin by A. Fleming in 1928, a new era in the fight against infectious diseases began - the era of antibiotics. And bacteriophages, which at that time turned out to be less effective, were consigned to oblivion in the Western world. In the USSR, the development and research of bacteriophage preparations did not stop and were actively supported at the highest level. In the 1930s The Institute for Bacteriophage Research was created in Tbilisi, which in 1951 became part of the group of institutes for vaccines and serums. The literature indicates that in the USSR in 1930–1940. Phage therapy was actively used to treat a wide range of bacterial infections in the field of dermatology (Beridze, 1938), ophthalmology (Rodigina, 1938), urology (Tsulukidze, 1938), dentistry (Ruchko and Tretyak, 1936), pediatrics (Alexandrova, 1935; Lurie, 1938 ), otolaryngology (Ermolieva, 1939) and surgery (Tsulukidze, 1940, 1941). These articles were published in Russian and were not available to Western scientists. Nevertheless, past experience indicates the high effectiveness of phage therapy and prevention.

We can proudly admit that Russia has always occupied a leading position in the production and use of therapeutic and prophylactic bacteriophages. Production did not stop during the era of “worldwide cooling” to phage therapy and actively developed even during the Great Patriotic War. Thus, NPO Microgen has been producing bacteriophages since the 1940s. In Russia and on the territory of some former Soviet republics, bacteriophage therapy is actively used to this day. Penicillin was the first medicine to demonstrate the emergence of bacterial resistance to antibiotics, which is now increasing exponentially. Skepticism in the West towards phage therapy gave way to increased interest in it, and a new wave of research began [8]. In addition to Russia, which has the richest experience in the use of bacteriophages, researchers in other countries have also actively studied the possibilities of phage therapy [9–12].

Clinical use of bacteriophage preparations at present Phage therapy from the perspective of evidence-based medicine Over the past 10 years, the number of publications in the world's leading medical publications addressing the issues of therapeutic and prophylactic use of bacteriophages has increased several times and has already exceeded 3000 (in the PubMed database). The number of recently published works indicates a revival of interest in phage therapy. Recently completed clinical studies provide compelling evidence regarding the safety and effectiveness of phage therapy in animals and humans [13–15]. Dual therapy using phages and antibiotics led to significantly better results than monotherapy with antibiotics [16]. It has been shown that bacteriophages may be more effective than traditional antibiotics in destroying bacterial biofilms [17].

Bacteriophages are now called “the bright hope in the era of antibiotic resistance.” At the initiative of the leading US food and drug control organization, the Food and Drug Administration (FDA), active clinical trials of bacteriophage drugs have been underway since 2007 [18, 19]. In recent years, the FDA has approved the use of phage preparations as food additives (eg, Listex, EcoShield) [20]. European regulatory authorities are currently considering phages as biological agents, requiring further randomized trials. The current data, although encouraging, are considered insufficient to create international clinical guidelines for phage therapy.

Mechanism of action of bacteriophages The antibacterial effect of bacteriophages is due to the introduction of the phage genome into the bacterial cell, followed by its reproduction and lysis of the infected cell. Bacteriophages released into the external environment as a result of lysis re-infect and lyse other bacterial cells, acting until the pathogenic bacteria in the inflammation site are completely destroyed.

Advantages of phage therapy Thus, based on the accumulated data, the following prerequisites for the widespread use of bacteriophage preparations for therapeutic and prophylactic purposes can be formulated: 1. Efficiency in the treatment of infections caused by antibiotic-resistant bacteria, including HAIs. 2. Possibility of use for allergic reactions to ABP. 3. Low toxicity, allowing them to be considered the safest drugs, which determines the possibility of their widespread use in children, pregnant and lactating women. 4. High specificity (no effect on normal human microflora) provides a significant advantage in the treatment of any infectious diseases in patients with various disorders of the intestinal microflora (including bacterial overgrowth syndrome (SIBO) and other dysbioses), the prevalence of which in recent years has increased significantly over the years. 5. Highly effective in the treatment of chronic infections, especially those associated with the formation of bacterial biofilms. 6. Possibility of use in various forms: local applications, liquid and tablets; parenteral.

Limitations of phage therapy At the same time, bacteriophages are currently used in real practice much less frequently than one would expect, given the large amount of positive information. The following reasons can be identified that limit the use of bacteriophages: 1. First of all, this is the lack of regulatory documents and insufficient awareness of specialists [21]. 2. There are still some bacteria pathogenic for humans (according to the approved list of biological agents [22]), for which lytic phages have not yet been found, including representatives of the 3rd biosafety level, such as Rickettsia, Ehrlichia and Coxiella ( causative agents of ehrlichiosis, epidemic typhus, Rocky Mountain fever). 3. Production of antiphage antibodies. The problem of immune interaction between the human body and phages is still under study. The smallest amount of antibodies to bacteriophages is produced in newborns and infants, which determines the greatest effectiveness of phage therapy in this group. 4. Quite rare, but still there are side effects of phage consumption, which are usually associated with massive breakdown of bacterial cells with the release of endotoxin. To be fair, it should be noted that such effects are much more significant with antibiotic therapy. In most cases, these adverse events can be mitigated with the help of enterosorbents.

Principles of rational phage therapy It should be noted that the use of bacteriophages, like any ABP, should be based on rational principles. 1. Preliminary determination of the sensitivity of bacteria to the drug and the lytic activity of bacteriophages in the laboratory. All bacteriophages can be divided into moderate and virulent (or lytic). A. Temperate bacteriophages incorporate their genetic material into bacterial chromosomes and multiply synchronously with the host cell, without causing lysis for a long time. Temperate bacteriophages play a significant role in the evolution of bacteria, contributing to the acquisition of additional virulence factors and antibiotic resistance by pathogens. It has now been proven that many virulence factors in pathogenic bacteria are encoded precisely with the help of prophage genes. B. Virulent phages always lead to the destruction of bacteria (lytic effect) and the release of mature phage particles that infect new bacterial cells. In this regard, bacteriophages used to treat infectious diseases must be exclusively virulent, i.e., lead to the death of bacteria. The lytic activity of bacteriophages prescribed for treatment must be previously tested in the laboratory. 2. The choice of delivery system plays a key role in successful phage therapy. Recent advances in phage therapy indicate that local (targeted) delivery has been more successful for localized infections, while the parenteral route is recommended for systemic infections [23]. When using oral forms of drugs, it is necessary to take into account the sensitivity of phages to the action of gastric hydrochloric acid and, in this case, give preference to delivery in an acid-resistant shell.

Bacteriophage preparations and their use in clinical practice Today there is an extensive list of phage preparations used in the treatment of a wide range of bacterial infections. On the territory of the Russian Federation, the only drugs registered as medicines are bacteriophages from the NPO Microgen. The main drugs and the spectrum of their antimicrobial action are presented in Table 1 [24].

The use of bacteriophages for gastrointestinal diseases Treatment of gastrointestinal infections with bacteriophages has a significant advantage over antibiotics in terms of the effect on normal intestinal microflora. Phage therapy has been shown to be effective against pathogens of gastrointestinal tract infections such as enteropathogenic E. coli [25], S. sonnae, flexneri, Salmonella E, P. vulgaris, mirabilis, S. aureus, P. aeruginosa, Enterococcus, etc. In the practice of a gastroenterologist it is possible distinguish 2 main groups of patients for whom bacteriophage therapy may be indicated: 1) with acute bacterial infections (acute gastroenteritis, gastroenterocolitis); 2) with various disturbances of normal intestinal microflora (SIBO in the small intestine, colon dysbiosis), which occur to one degree or another in most patients with gastrointestinal diseases.

Phage therapy of acute bacterial diarrhea Treatment of acute bacterial diarrhea sometimes presents significant difficulties due to the low effectiveness of antibacterial drugs and the development of side effects. It has been shown that due to the effect of antibiotics on normal intestinal microflora, the mechanism of natural colonization resistance is inhibited. In addition, the direct mechanism of the immunosuppressive effect of antibiotics is known. All this can lead to long-term persistence of the causative agent of acute intestinal infection (AI) during antibiotic therapy [26, 27]. Thus, according to some studies, in patients who received ABP in the acute phase of salmonellosis, subsequent bacterial excretion of Salmonella was significantly more common in comparison with individuals who received only pathogenetic therapy [28]. Indications for the use of bacteriophages in acute intestinal infections today can be formulated as follows: – as monotherapy – in mild forms of acute intestinal infections; – in combination with antibacterial therapy or sequentially – for moderate and severe forms of acute intestinal infections; – during bacterial excretion (in convalescent or transient bacterial carriers); – in the complex therapy of enterocolitis of opportunistic and staphylococcal etiology; – to correct disorders of intestinal microbiocenosis [29]. A prerequisite for phage therapy is stool culture with determination of phage sensitivity. In the case of an unverified pathogen, preference should be given to complex preparations of bacteriophages (intesti-bacteriophage), which have a wide spectrum of action against pathogens of major intestinal infections.

Phage therapy for SIBO One of the promising, but so far little-studied areas is the correction of disorders of the normal intestinal microflora with bacteriophage preparations. As is known, SIBO is clearly associated with the use of ABP. At the same time, if there are signs of bacterial overgrowth in the intestine, the only recommended tactic today is the prescription of antibiotics or intestinal antiseptics. This, of course, causes bewilderment for both patients and sometimes doctors themselves. It turns out that we are “treating complications of antibiotic therapy with antibiotics”... And in this case, phage therapy can have significant advantages, targeting opportunistic microorganisms that are “out of control”. A prerequisite before starting therapy is stool culture to determine sensitivity to phage drugs. Preference should be given to complex drugs that affect pathogenic and opportunistic intestinal microflora (intestinal bacteriophage).

Prospects for the use of bacteriophages We are on the threshold of the “Renaissance” of bacteriophage therapy, which opens up new prospects in the treatment of antibiotic-resistant microflora and also has a good safety profile. In Russia today, phage therapy is successfully used for a wide range of diseases, and, of course, justifies itself in various disorders of the intestinal microflora. The targeted action of the drugs allows us to maintain a fine line of normal flora balance, which is extremely important for our patients.

Phage therapy - little helpers for serious infections

At first glance, it seems strange that a virus can be used for treatment! But today, a large number of serious, purulent and life-threatening infections are treated with phages - viruses that attack bacteria.

According to the spectrum of action, phages are

monovalent
- affects bacteria of a certain type;
typical
– act against strains or groups of bacteria of the same species;
polyvalent
- destroys bacteria of a whole genus;
combined
– contain phages against several pathogens and act against microbial associations.

Preparations containing phages are produced in the form of ointments, tablets, suspensions, aerosols or suppositories. But most often bacteriophages are prescribed in liquid form. The solution is irrigated into the inflamed cavity of the organ, lubricated with it on the wound, taken orally or administered intravenously.

When treating with bacteriophages, one nuance is important. You will not be able to select a drug on your own, since each “cocktail” of bacteriophages is sensitive only to certain groups of bacteria, strains, and is absolutely ineffective if you have other variants of the same type. If the doctor decides to prescribe you phage therapy, then first they will take tests from you to identify the pathogen and select the “eater” for it.

Depending on the inflamed organ, you will need to undergo the following tests:

blood analysis;
Analysis of urine;
scatological research;
sputum examination;
a smear from the skin or mucous membrane.

The taken material is examined under a microscope, and then inoculated on a nutrient medium. When the bacterial colony begins to grow, the laboratory assistant determines the type of pathogen, and phages are added to the medium. If the environment is cleared of pathogens, then the phage was selected correctly, and the treatment will be effective.

Bacteriophages are used to treat infections caused by the following bacteria:

coli;
staphylococcus;
streptococcus;
Pseudomonas aeruginosa or pseudomonas;
Klebsiella;
Proteus;
enterococci;
causative agents of dysentery and salmonellosis.

Sometimes doctors don’t even have to choose between an antibiotic and a bacteriophage. In recent years, outbreaks of intestinal infections have been recorded, for which none of the antibiotics can help.

For example, antibacterial therapy is practically powerless for pseudomembranous colitis, an inflammation of the colon that is caused by the aggressive bacterium Clostridium difficile, or clostridia. It causes severe, life-threatening diarrhea. Until recently, pseudomembranous colitis could only be treated with probiotics. The patient was actually transplanted new microflora into the intestines. But it turned out that bacteriophages can destroy clostridia much faster and easier. The effectiveness of the treatment was documented by the American Society of Microbiology in 2020. Read more about this by following the link in the list of references.

Another worldwide medical problem is pseudomonas. The most common type of pseudomonas is Pseudomonas aeruginosa. It often causes nosocomial infection or inflammation of the respiratory tract, lungs, middle ear, and urinary tract. The rod is resistant not only to antibiotics, but also to disinfectants, but it is successfully destroyed by bacteriophages.

Phage therapy is indicated for the following diseases:

intestinal infection;
respiratory tract infection;
pneumonia and inflammation of the pleura;
purulent skin infection;
purulent surgical infection;
infection of a postoperative wound;
lung abscess;
paratonsillar ulcers;
subphrenic abscess;
middle ear infection;
inflammation of the paranasal sinuses;
intestinal dysbiosis;
peritonitis;
osteomyelitis;
infectious-allergic rhinitis, pharyngitis, dermatitis and conjunctivitis;
gastrointestinal tract infection;
cholecystitis;
inflammation of the spinal lining;
any purulent infection with a high risk of blood poisoning;
genitourinary infection;
cystitis;
pyelonephritis;
burns and injuries.

Bacteriophages are used not only in adults, but also in newborns for inflammatory diseases and a high risk of blood poisoning.

List of bacteriophage drugs

Salmonella for oral administration 100ml - 650-800 rub.
Koli bacteriophage 20ml. 4 things. 400-800 rubles, coliproteus for oral administration 100ml - 650-800 rubles.
Streptococcal for oral, local and external use 20 ml. 4 things. — 750-800 rub.
Klebsiella polyvalent for oral administration 20 ml. 4 pieces - 750-800 rub.
Klebsifag (klebsell pneumonia) 20ml. 4 things. 500 rub.
Dysenteric polyvalent 80 mg. 500 tab. 3400 RUR, 20 ml. 4 pcs -400 rub.
Proteus bacteriophage 20ml. 4 things. 500-600 rub.
Pseudomonas bacteriophage/pseudomonas 100ml. and 20ml. 4 things. — 650-700 rub.

Complex bacteriophages:

INESTI complex bacteriophage 20ml. 4 things. and 100ml. for oral administration - 800 rub.
Pyobacteriophage 100 ml. — 800 rub.
Pyobacteriophage polyvalent purified 20ml. 4 things. — 800 rub.
Sextaphage Piobacteriophage polyvalent 20ml. 4 things. — 750 rub.

Author:

Sabuk Tatyana Leonidovna hygienist, epidemiologist