Recurrent viral infection. The feasibility of interferon therapy for recurrent lower urinary tract infections

Why do young children get sick so often, and what preventative measures will help strengthen their immunity.

How often do children have recurrent infections?

Children are born with an immature immune system, so infants often have infectious diseases, usually once every one to two months. Soon after birth, the baby's immune system begins to develop, and over time the incidence of infectious diseases decreases. As a rule, school-age children suffer from recurrent infections no more often than adults.

Why might a doctor be alarmed by recurrent infections in a child?

Most doctors sound the alarm if common viral infections in children are complicated by bacterial ones, such as sepsis or pneumonia. Frequent or unusual infections are also a cause for concern.

Why do some children get infectious diseases more often than usual?

Sometimes the reasons lie on the surface. For example, the whole point may be that the child goes to kindergarten, where children touch common toys and touch each other, thus spreading the infection. Adults have much less contact with other people's germs, and therefore do not become infected as often.

Another cause of runny nose and sneezing in young children is passive smoking. As more women of childbearing age smoke, secondhand smoke is more likely to cause respiratory infections in children. Its connection with infections and asthma in childhood has now been established.

Can anatomical features cause recurrent infections?

A common cause of recurrent infections in children is the structural features of the nasal sinuses and eustachian tubes (canals connecting the middle ear to the pharynx). Such infections can be inherited. In some children, anatomical features make it difficult for secretions to drain from the Eustachian tubes and sinuses, causing bacteria to multiply. Therefore, such children are more susceptible to infections. In most cases, drainage improves as the child gets older. Young children who have too many ear infections may need antibiotic treatment or tubes to drain the middle ear.

Allergies and asthma can lead to recurrent sinusitis (nasal congestion or discharge) and difficulty breathing. Allergies sometimes cause long-term irritation in the nose. Because of it, the ducts of the nose and sinuses, through which the discharge normally occurs, swell and their lumen closes. Bacteria multiply, leading to infection. In such cases, medications are needed to eliminate the cause of the disease, that is, allergies.

A cough that accompanies a viral infection may be a sign of asthma. These children need asthma medication in addition to other medications they take for the infection.

Why do children have severe recurrent infections?

Sometimes it's just a matter of chance. Even healthy children can suffer 2-3 severe infections for no apparent reason. In such cases, the doctor may order additional tests to make sure that the child does not have an immunodeficiency. Immunodeficiency conditions are a leading cause of recurrent severe infections.

Other possible causes include diseases such as cystic fibrosis and AIDS. Cystic fibrosis is very rare, and in the vast majority of cases, a child gets AIDS from the mother.

How to protect your child from recurrent infections?

  • Parents who smoke need to quit smoking first. If this still fails, you should stop smoking at home and in the car. To protect your child from second-hand smoke, it is not enough to not smoke only in the children's room: tobacco smoke spreads everywhere. Air filters also do not protect children from second-hand smoke.
  • The coldest time of year is winter. If one of the relatives can take care of the child, it is better to take him out of kindergarten for the winter, where children so often catch colds. Another good option is small home groups (up to 5 children). Fewer children means fewer infections to catch.
  • If there is a family history of allergies or asthma, it is worth checking to see if the child has these diseases.
  • Caution: ear candles. The US Food and Drug Administration does not recommend the use of ear candles. They can cause serious injury and their effectiveness is not supported by scientific research.

Everything will be fine?

Most children who have recurrent infections have no serious health problems and will grow up to be healthy adults. Closer to school age, they will get sick much less often. You just need to make sure that children sleep more and eat properly. Sleep and eating healthy foods are just as important to fighting infections as medications.

In children, respiratory infections are the main reason for visiting the doctor and hospital treatment. Most often they are caused by viral infectious agents. It is believed that in infancy, children suffer from 6 to 8 times a year from viral infections of the upper respiratory tract and colds. However, in 10-15% of cases this figure can increase to 12. Children most often attend child care facilities, in some cases up to 50% more often than housewives.

We talk about recurrent respiratory infections in a child when there is:

  • More than 6-8 respiratory infections per year;
  • More than 1 upper respiratory tract infection per month between September and April
  • More than 3 lower respiratory tract infections per year.

In most cases of recurrent respiratory infections, no underlying cause, be it immune deficiency or chronic disease, has been identified. Then this is a “physiological” process, which is associated with an immature immune system, on the one hand, and, on the other, an increase in the number of social contacts of the child and the inevitable encounter with a large number of infectious agents. Usually, however, this disease often worries parents very much and is the reason for visits to various specialists and a search for the underlying cause in the child.

Risk factors for common illnesses

However, some children are affected much more often than others. The explanation can be sought in various factors.

Visit to the garden

This is an important risk factor for recurrent respiratory infections in a child. About 70% of cases of recurrent respiratory infections are reported in children attending kindergarten. This makes it a major risk factor for frequent illness. Moreover, about 75% of children suffer from recurrent respiratory infections in the first year. The earlier a child begins to attend these institutions, the greater the risk of frequent illnesses, especially if this occurs in the first year of life in a nursery.

Environmental factors

Children who are exposed to secondhand smoke, including maternal smoking during pregnancy, are most likely to be at risk for frequent illness. This directly affects the development and maturation of the child's immune system. Other factors that have a negative impact are humidity and the presence of mold in the house. They increase the risk of developing allergic diseases and recurrent respiratory infections, respectively.

The same applies to air pollutants in large cities. They can cause chronic cough, reduce airway volume, and increase hospitalizations due to respiratory infections.

Family history of allergic diseases

Having a child's family member with allergies (eg, dust, pollen, food, etc.) increases the child's risk of more frequent bronchial obstructions and, consequently, the development of recurrent respiratory infections.

Children's allergies

Unrecognized or inappropriate treatment of allergic diseases can lead to the development of a pattern resembling recurrent respiratory infections. Respiratory allergies lead to the development of chronic inflammation in the airways. This weakens the local immune defense and facilitates the attachment of infectious agents to the respiratory epithelium. Allergic diseases themselves are a major risk factor for common illnesses, and according to some studies, they affect 15% and 20% of children.

Chronic recurrent infection caused by the herpes simplex virus and characterized by predominant damage to the integumentary tissues and nerve cells. The main route of transmission of herpes infection is contact, but airborne and transplacental transmission of the virus is possible. A distinctive feature of herpes infection is the ability of viruses to persist for a long time in the nerve ganglia. This leads to relapses of herpes during periods of decreased body defenses. Manifestations of herpes infection include herpes labialis, genital herpes, visceral herpes, generalized herpes, herpetic stomatitis and conjunctivitis.

General information

Chronic recurrent infection caused by the herpes simplex virus and characterized by predominant damage to the integumentary tissues and nerve cells. Currently, there are two types of herpes simplex virus. Type I of the virus primarily affects the mucous membranes and skin of the mouth, nose, eyes, and is transmitted primarily through household contact; type II causes genital herpes, transmitted primarily through sexual contact. The reservoir and source of herpetic infection is a person: a carrier or a patient. The release of the pathogen can continue for a very long time.

The transmission mechanism is contact; the virus is released onto the surface of the affected mucous membranes and skin. In addition to the main routes of transmission for type I of the virus, airborne droplets and airborne dust can also occur, and type II can be transmitted vertically from mother to child (transplacentally and intranatally). Viruses that have entered the body tend to persist for a long time (mainly in ganglion cells), causing relapses of infection during periods of weakening of the body's defenses (colds, vitamin deficiencies). More often, the primary infection is latent, the disease manifests itself later, and acute infection is observed only in 10-20% of those infected.

Herpetic infection is classified according to the predominant damage to certain tissues: herpes of the skin, mucous membrane of the mouth, eyes, ARVI, genital herpes, visceral herpes, herpetic damage to the nervous system, herpes of newborns, generalized form.

Symptoms of herpetic infection

The incubation period of herpetic infection is usually 2-12 days, the onset can be either acute or gradual, often the primary infection goes completely unnoticed by the patient, and the course of the disease becomes recurrent. Relapses can occur 2-3 times a year, or extremely rarely - 1-2 times every 10 years or less. Relapses tend to develop against a background of weakened immunity, so clinical manifestations of herpes are often accompanied by acute respiratory viral infections, pneumonia, and other acute infections.

Herpetic skin lesions are localized mainly on the lips and wings of the nose. First, itching and burning are subjectively felt in a localized area of ​​the skin, then this area thickens, vesicles are formed on it, filled with transparent contents, which gradually become cloudy. The blisters break open, leaving behind shallow erosions and crusts that heal after a few days without consequences. Sometimes bacterial flora penetrates through damaged skin, causing secondary suppuration and complicating healing. Regional lymphadenitis may be observed (the nodes are enlarged and slightly painful). There are no general symptoms observed, or the disease occurs against the background of other infections that cause additional symptoms.

Herpetic lesions of the oral mucosa are characterized by the occurrence of acute or recurrent stomatitis. The disease may be accompanied by symptoms of general intoxication and fever. The mucous membrane of the oral cavity is covered with groups of small vesicles filled with transparent contents, which quickly open and leave painful erosions. Erosion in the oral cavity can take up to 2 weeks to heal. The disease can occur in the form of aphthous stomatitis (the formation of aphthous stomatitis occurs - single, slowly healing erosions of the oral mucosa). In this case, general clinical manifestations (intoxication, hyperthermia) are usually absent. Herpetic stomatitis is prone to recurrence.

Herpes of the ARVI type often occurs without characteristic blistering rashes on the mucous membranes and skin, resembling the clinical picture of other respiratory viral diseases. In rare cases, a herpetic vesicular rash forms on the tonsils and back of the throat (herpangina).

Genital herpes usually manifests itself as local rashes (vesicles mainly form on the glans penis and the inner surface of the foreskin in men and on the labia majora and minora in women) and general symptoms (fever, intoxication, regional lymphadenitis). Patients may notice pain in the lower abdomen and lumbar region, and burning and itching in areas where the rash is localized.

Rashes with genital herpes can progress, spreading to the mucous membrane of the vagina and cervix, urethra. Chronic genital herpes can cause cervical cancer. In many cases, genital rashes are accompanied by herpes of the mucous membranes of the mouth and eyes.

Visceral forms of herpes occur in accordance with the clinical picture of inflammatory diseases of the affected organs. These can be herpetic pneumonia, hepatitis, pancreatitis, nephritis, esophagitis, adrenal herpes. With herpetic lesions of hollow organs accessible to endoscopy, vesicular rashes and erosions may be observed on the mucous membrane.

In newborns and patients with severe immune deficiency, a generalized form of herpetic infection may develop, characterized by a high prevalence of skin manifestations, lesions of the mucous membranes and internal organs against the background of general intoxication and fever. The generalized form in AIDS patients often occurs in the form of Kaposi's eczema herpetiformis.

Shingles

One form of herpes infection is herpes zoster. The onset of the disease is often preceded by prodromal phenomena - general malaise, headaches, a rise in temperature to low-grade levels, and dyspeptic symptoms. There may be a burning sensation and itching in the area of ​​projection of the peripheral nerve trunks. The prodromal period lasts from one day to 3-4 days, and may differ in varying intensity of symptoms depending on the condition of the patient’s body. In many cases, an acute onset is noted: the temperature rises sharply to febrile levels, general intoxication is noted, and herpetiform rashes appear on the skin along the innervation of the spinal ganglia.

The process can spread within one or more nerve trunks. Most often, the rashes are localized along the projection of the intercostal nerves or branches of the trigeminal nerve on the face; less often, damage to the extremities and genitals is noted. The rashes are groups of vesicles with serous contents, located in areas of hyperemic, dense skin. In the area of ​​the rash there is a burning sensation and intense pain of a vegetative nature. The pain occurs in attacks, often at night. Disorders of tactile sensitivity in the area of ​​innervation of the affected nerves, radicular paresis of the facial and oculomotor nerves, bladder sphincter, muscles of the abdominal wall and limbs may be observed. The fever lasts for several days, after which it subsides, and the symptoms of intoxication disappear along with it.

The abortive form of herpes zoster infection occurs in the form of a short-term papular rash without the formation of vesicles. In the bullous form, herpetic vesicles merge, forming large blisters - bullae. The bullous form can often progress to the bullous-hemorrhagic form, when the contents of the bullae become hemorrhagic in nature. In some cases, the bullae merge along the nerve fiber, forming a single extended ribbon-shaped bubble, which leaves a dark necrotic scab after opening.

The severity of shingles depends on the location of the lesion and the state of the body's defenses. Lichen is especially severe in the area of ​​innervation of the nerves of the face and head, and the eyelids and cornea of ​​the eye are often affected. The duration of the course can range from several days (abortive form) to 2-3 weeks, in some cases dragging on for up to a month or more. After suffering from herpes zoster, relapses of herpetic infection in this form are quite rare.

Diagnosis of herpetic infection

Diagnosis of herpetic infection is carried out using virological analysis of the contents of vesicles and scraping of erosions. In addition, the pathogen can be isolated from blood, urine, saliva, semen, nasopharyngeal swabs, and cerebrospinal fluid. In the case of post-mortem diagnosis, the pathogen is isolated from tissue biopsies. Isolation of the herpes simplex virus does not provide sufficient diagnostic data on the activity of the process.

Additional diagnostic methods include RNIF of fingerprint smears (giant multinucleated cells with Cowdry type A inclusions are detected), RSC, RN, ELISA in paired sera. Study of immunoglobulins: an increase in the titer of immunoglobulin M indicates a primary lesion, and immunoglobulin G indicates a relapse. Recently, a common method for diagnosing herpes infection is PCR (polymerase chain reaction).

Treatment of herpes infection

The variety of clinical forms of herpetic infection determines the wide range of specialists who treat it. Treatment of genital herpes is carried out by venereologists, and in women - by gynecologists. Neurologists treat herpetic infections of the nervous system. Treatment tactics for herpetic infection are selected depending on the clinical form and course of the disease. Etiotropic therapy may include acyclovir and other antiviral drugs. In mild cases, local treatment is used (ointments with acyclovir, Burov's fluid). Glucocorticosteroid ointments are contraindicated.

General treatment with antiviral drugs is prescribed in courses, for primary herpes - up to 10 days, chronic recurrent herpes is an indication for long-term treatment (up to a year). Generalized, visceral forms, herpes of the nervous system are treated with intravenous administration of antiviral drugs; it is advisable to begin the course of treatment as early as possible, its duration is usually 10 days.

For frequently recurrent herpes, immunostimulating therapy is recommended for the period of remission. Immunomodulators, adaptogens, immunoglobulins, vaccination, and intravenous laser blood irradiation (ILBI) are prescribed. Physiotherapy is widely used: ultraviolet irradiation, infrared irradiation, magnetic therapy, EHF, etc.

Forecast and prevention of herpetic infection

A herpes infection with damage to the central nervous system has an unfavorable prognosis (herpetic encephalitis has a high risk of death, it leaves behind severe persistent disorders of the innervation and functioning of the central nervous system), as well as herpes in people suffering from AIDS. Herpes of the cornea of ​​the eye can contribute to the development of blindness, and cervical herpes - cancer. Herpes zoster often leaves behind various sensitivity disorders and neuralgia for some time.

Prevention of herpes type I corresponds to general measures for the prevention of respiratory diseases, herpes type II corresponds to the prevention of sexually transmitted diseases. Secondary prevention of relapses of herpes consists of immunostimulating therapy and specific

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L.A.SINYAKOVA, Doctor of Medical Sciences, Professor, M.L. STEINBERG, A.M.PLESOVSKY, RMAPO, Moscow

Recurrent lower urinary tract infections:

DIAGNOSIS AND TREATMENT

The problem of recurrent lower urinary tract infections (LUTI) in women, affecting not only the physical health of the woman, but also the sexual life of a married couple, childbirth, is currently not only acquiring a social character, but is also interdisciplinary. RINUS are common (every 10 women suffer from chronic, often recurrent cystitis), but only 40% of women with dysuria develop chronic cystitis. Insufficient knowledge of the etiology and pathogenesis of RINUS, the lack of an algorithm for diagnosis and treatment and unified approaches to this serious problem among various specialists (urologists, gynecologists, therapists, dermatovenerologists) lead to the ineffectiveness of the therapy.

and high relapse rates.

Key words: recurrent lower urinary tract infections, dysbiosis, dysuria, chronic cystitis

In the vast majority of cases, RUTIs are secondary, developing against the background of sexually transmitted infections, anomalies in the location of the external urethral meatus, hypoestrogenemia, pelvic inflammatory diseases (PID), endometriosis, and pelvic venous congestion. Unfortunately, treatment most often comes down to prescribing various antibacterial drugs, and doctors do not take into account the role of endometriosis, salpingoophoritis, and herpes in the genesis of the patient’s complaints. Inadequate examination of patients with RINUS (in particular, by therapists who should not be involved in the examination and treatment of these patients) aggravates the problem and leads to the development of dysbacteriosis and vaginal dysbiosis. Chronic cystitis with frequent relapses can lead to the development of ascending pyelonephritis, disruption of the closing apparatus of the ureteral orifices with the occurrence of vesicoureteral reflux, which represents a much more serious problem. Errors in the treatment of these diseases are costly for patients. Often in clinical practice, doctors, not receiving an effect from antibacterial therapy, instead of trying to find out the cause of the development and relapse of the disease, prescribe long-term continuous courses of treatment with drugs of various groups. It persists despite inadequate treatment

dyspareunia, forcing women to refuse sexual relations, making it difficult to plan a pregnancy. Another problem is the treatment of only the woman and the lack of examination and treatment of the sexual partner.

In 2005, we proposed an algorithm for the diagnosis and treatment of recurrent urinary tract infections, according to which it is necessary to examine patients for the presence of STIs and anomalies in the location of the external urethral opening, which necessitates a differentiated approach to the treatment of this category of patients and carrying out not only etiological, but also pathogenetic therapy (Table 1).

Recently we have become convinced that the specified algorithm is incomplete. Among 200 patients with dysuria examined in the clinic over the past 3 years, 5 patients were diagnosed with interstitial cystitis, confirmed by cystoscopy and morphologically. However, some of these patients had never filled out urination diaries before entering the clinic, and they were prescribed antibacterial therapy for chronic cystitis. This indicates that doctors are unaware of the algorithms for examining patients with certain diseases. Another problem is that in the presence of obvious clinical signs of interstitial cystitis, cystoscopy is performed without adequate (general) anesthesia due to doctors’ ignorance of the recommendations of the European Association of Urology, the recommendations developed by the US National Institutes of Health, as well as a lack of understanding of the essence of the problem.

■ Chronic cystitis with frequent relapses can lead to the development of ascending pyelonephritis, disruption of the closing apparatus of the ureteral orifices with the occurrence of vesicoureteral reflux, which is a problem.

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Recently, patients with chronic urethritis and recurrent cystitis, which develop against the background of viral infections, have become increasingly common. Damage to the organs of the urinary system is secondary, and urination disorders in some cases occur against the background of a pronounced disturbance of the normal microflora of the vagina. Therefore, we believe that the algorithm for examining patients with dysuria should include filling out urination diaries (at least two days in advance), smears from the urethra, vagina, cervical canal, vaginal culture for flora and sensitivity to antibiotics with mandatory quantitative determination of lactobacilli, enzyme-linked immunosorbent assay (ELISA) with the determination of immunoglobulins G and M for herpes types 1 and 2 and cytomegalovirus.

A common mistake is that outpatient doctors perform cystoscopy and do not perform a biopsy when leukoplakia is detected.

The patient is diagnosed with “leukoplakia of the bladder” and is limited to this. However, depending on the results of the morphological study, the tactics fundamentally change, because both squamous papilloma, requiring transurethral resection of the bladder, and true leukoplakia of the bladder (squamous metaplasia with keratinization - pre-cancer) look the same in appearance. Squamous metaplasia of the bladder epithelium without keratinization, which is the result of chronic inflammation, most often against the background of urogenital infections, is characterized by destruction of the glycosaminoglycan layer of the bladder mucosa. Pathogenetic therapy in this case

tea, as with interstitial cystitis, should be aimed at restoring the mucopolysaccharide layer. Considering the above, we propose the following algorithm for diagnosing recurrent cystitis (Table 2).

There are two subjective reasons for the increase in dysbiotic and infectious-inflammatory diseases of the genitals:

1. Irrational, often unfounded antimicrobial treatment of non-existent diseases, due to incorrect interpretation of laboratory test results by doctors, in particular high-quality PCR.

2. Self-medication with various over-the-counter and prescription drugs with antimicrobial action.

The drugs of choice for the treatment of acute cystitis, according to the recommendations of the European Association of Urology in 2010, are fosfomycin trometamol, nitrofurantoin, trimethoprim-sulphamethoxazole (only in regions where resistance<20%) (табл.

In these recommendations, fluoroquinolones are classified as alternative drugs; the use of drugs for acute uncomplicated cystitis is not recommended, because There is a progressive increase in resistance to fluoroquinolones throughout the world. Antibacterial therapy for recurrent lower urinary tract infections cannot be empirical, therefore targeted use of antibiotics is indicated, taking into account the results of bacteriological examination of urine. The prescription of uroantiseptics is not effective, which is due to low

■ The algorithm for examining patients with dysuria must include filling out urinary diaries (for at least two days), smears from the urethra, vagina, cervical canal, vaginal culture for flora and sensitivity to antibiotics with mandatory quantitative determination of lactobacilli, enzyme-linked immunosorbent assay (ELISA) with determination of immunoglobulins G and M to herpes types 1 and 2 and cytomegalovirus.

Table 1. Algorithm for diagnosis and treatment of recurrent urinary tract infections

Algorithm for diagnosing recurrent cystitis

Algorithm for diagnosing non-obstructive pyelonephritis

Careful history taking! Identification of risk factors: early onset of sexual activity, frequent change of sexual partners, presence of invasive manipulations, concomitant chronic gynecological diseases, vaginal dysbiosis

Vaginal examination

General urine test

General urine test, general blood test, biochemical blood test

Urine culture

Screening for STIs

Ultrasound examination of the kidneys, bladder with determination of residual urine

Ultrasound examination of the kidneys using color flow, power Doppler, and bladder

Cystoscopy with biopsy

X-ray studies

Examination by a gynecologist

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Table 2. Algorithm for diagnosing recurrent cystitis

Algorithm for diagnosing recurrent cystitis Analysis of patient complaints

Careful history taking! Identification of risk factors: early onset of sexual activity, frequent change of sexual partners, presence of invasive manipulations, concomitant chronic gynecological diseases, viral infections

(herpes, cytomegalovirus), vaginal dysbiosis Completing urination diaries Vaginal examination General urine analysis Urine culture for flora and sensitivity to antibiotics Smear: urethra, vagina, cervical canal Examination for the presence of STIs (PCR - urethra, cervical canal)

ELISA with determination of immunoglobulins G and M for herpes types 1 and 2 and cytomegalovirus. Culture of vaginal discharge for flora and sensitivity to antibiotics with quantitative determination of lactobacilli. Ultrasound examination of the kidneys, bladder with determination of residual urine, uterus, appendages, Dopplerography of pelvic vessels. Cystoscopy with biopsy Examination by a gynecologist

Diagnosis Most common pathogen Initial empirical therapy (2003) Initial empirical therapy (2010)

Acute, uncomplicated cystitis E. coli, Klebsiella, Proteus, Staphylococci Fluoroquinolones Trimethoprim-sulfamethoxazol* (only in regions where resistance<20% для E. т1л)

Fosfomycin trometamol Nitrofurantoin

Ampicillin Fosfomycin trometamol

Nitrofurantoin Fluoroquinolone (alt.) (avoid for uncomplicated cystitis whenever possible)

Table 4. Opportunistic microflora of bladder biopsies

103-105 RUTSI (n=34) Ability to form biofilms (n=12)

Staphylococcus spp. 6 4

Kocuria spp. 5 4

Acinetobacter spp. 4 2

Klebsiella pneumoniae 4

Proteus mirabilis 4

Pseudomonas spp. 3

Burkholderia cepacia 3 2

Flavimonas oryzihabitans 2

Brevundimonas vesicularis 3

tissue concentrations of drugs and high resistance to them of the main causative agents of urinary tract infections.

AND THE ROLE OF BIOFILM IN THE ETIOPATHOGENESIS OF RUTURAL urinary tract infection

It is now recognized throughout the world that the main form of existence of bacteria in natural conditions is biofilm. They are found in more than 80% of cases of chronic infectious and inflammatory diseases, which allows us to put forward the concept of chronic diseases as biofilm diseases.

Up to 60% of infections (respiratory and urinary tract infections, osteomyelitis, endocarditis, infectious complications in cystic fibrosis, etc.) are caused by sessile forms.

mother of bacteria. The formation of biofilms at the site of inflammation leads to chronicity of the infectious process and is accompanied by unsatisfactory results of antibiotic therapy. The most relevant types of bacteria,

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Those that form biofilms during infections are staphylococci, representatives of the family Enterobacteriaceae, Pseudomonas aeruginosa, etc., as well as mycoplasmas of various species.

Another evidence is the observation during bacteriological examination of biopsy samples of the bladder mucosa obtained in our clinic during cystoscopy in patients with RINUS.

In a study of 38 bladder biopsies, in 89% of cases (n=34), an increase in opportunistic microflora of 103-105 CFU was obtained (Table 4).

A biofilm is a structured community of bacterial cells enclosed in a self-produced polymer matrix and adhering to inert or living surfaces. It contains a large number of bacteria immersed in the intercellular matrix, covered with a membrane consisting of a bi-lipid component, polysaccharides and proteins. The bilipid layer of the surface shell of communities contains more cardiolipin and less lysophospholipids than the membranes of bacterial cells, which gives this structure increased strength.

The formation of biofilms is a complex dynamic process consisting of several stages: the first is the fixation of planktonic bacterial cells to the surface - adhesion, the second is the proliferation of adherent cells with the formation of primary colonies, as well as the absorption of planktonic cells into the film, and the third is the colonization of the biotope and matrix formation with the separation of bacterial cells from the biofilm and their subsequent spread.

Adhesion to biological surfaces (tissue cells, vessel walls) is due to the specific interaction of adhesin proteins or lectins of the fimbriae of the exoplasmic compartment of the bacterial cell with receptors or certain domains of the surface of the host cell membranes.

The biofilm matrix can interfere with the rate of diffusion of some antibiotics and other biocides, depending on its biochemical composition and the metabolic activity of the population. For example, aminoglycosides diffuse through the matrix for quite a long time, and fluoroquinolones easily penetrate this barrier. The problem of increased resistance of biofilms to the action of antimicrobial drugs has several aspects: diffusion barrier; the ability of bacteria to accumulate extracellular enzymes in the matrix that destroy antibiotics; the aggregative nature of biofilms associated with a decrease in the open surface area of ​​cells - the physical inaccessibility of molecules; resistant cell phenotype. Reduced metabolism of microorganisms in the biofilm leads to the emergence of antibiotic tolerance.

The formation, growth, and migration of planktonic cell forms for colonization in biofilms are regulated by

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population level through mechanisms of intercellular communication. Quorum sensing (QS) is the process of collective coordination of gene expression in a population of bacteria, mediating specific cell behavior. Communicative mechanisms for the transmission of mobile genetic elements during infectious lesions make it possible to spread genes of antibiotic resistance, virulence, and additional physiological capabilities with maximum speed.

All immune defense factors contribute to the elimination of bacterial cells outside biofilms (planktonic forms), but antibodies, complement proteins and phagocytic cells are not able to penetrate the exopolysaccharide layer. Antibiotics are able to penetrate this barrier and destroy microorganisms within the biofilm itself, but the surviving persister cells with their high tolerance and ability to survive remain intact.

Some time after the cessation of antibiotic therapy, the synthesis and accumulation of antitoxins in persister cells begins, cytotoxins are neutralized, and all biological processes are activated. For the macroorganism, this process is accompanied by chronic infection, the appearance of manifest signs of the disease associated with re-activation of the immune system and the action of virulence factors of bacterial cells.

The data obtained partly explain the reasons for the ineffectiveness of antibacterial therapy, because Most antibacterial drugs used to treat RINUS do not penetrate into biofilms, but act

only on planktonic forms of bacteria. Systemic fluoroquinolones and fosfomycin trometamol have a proven ability to penetrate biofilms. The increasing resistance of the main causative agents of urinary tract infections to fluoroquinolones forces us to limit their use, and therefore the indications for the use of fosfomycin trometamol in long courses (once every 10 days for 3 months) are expanding.

Treatment of RINUS should be pathogenetically substantiated and include:

■ correction of anatomical disorders;

■ treatment of STIs;

■ correction of hormonal disorders;

■ postcoital prophylaxis;

■ treatment of inflammatory and dysbiotic gynecological diseases;

■ correction of hygienic and sexual factors;

■ correction of immune disorders;

■ local treatment.

Compliance with the principles of pathogenetic therapy has proven its effectiveness. However, it is necessary to remember and warn patients that transposition of the external urethral opening in patients with vaginal ectopic urethra does not eliminate urethritis, but only creates anatomical conditions conducive to more effective treatment.

Considering that in the vast majority of cases in young patients who have suffered from RINUS for a long time, especially against the background of urogenital infections, squamous metaplasia of the epithelium without keratinization is detected on biopsy, the pathogenetic therapy algorithm must include treatment methods aimed at restoring the glycosaminoglycan layer of the bladder mucosa: instillation of heparin into the bladder over long courses (3 months), intravesical administration of Uro-Hyal, use of Longidase. It is advisable to perform instillations while patients are taking Canephron®N, which, having a multidirectional effect (antibacterial, anti-inflammatory, antispasmodic, diuretic), has proven its effectiveness and good tolerability as a therapeutic and anti-relapse agent. The duration of use of Canephron®N for RINUS should be 3 months. One of the important advantages of the drug is its high safety, confirmed by experimental and clinical data, incl. and during pregnancy (Sterner W., Korn W.D., Volkmann P., 1988).

After adequate treatment of RINUS, long-term, individually selected prophylactic treatment is required.

■ The formation of biofilms at the site of inflammation leads to chronicity of the infectious process and is accompanied by unsatisfactory results of antibiotic therapy. The most relevant types of bacteria that form biofilms during infections are staphylococci, representatives of the family Enterobacteriaceae, Pseudomonas aeruginosa, etc., as well as mycoplasmas of various types.

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Changing the developed algorithms allows them to be successfully used in clinical practice, reduces the number of diagnostic errors and improves treatment results.

LITERATURE

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UROLOGY AND GYNECOLOGY

Recurrent (repeated) infection

Russian-English dictionary of biological terms. - Novosibirsk: Institute of Clinical Immunology. V.I. Seledtsov. 1993-1999.

See what “recurrent infection” is in other dictionaries:

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