“Breathe - don’t breathe”: What you need to know about tuberculosis?

Vera Zimina, Doctor of Medical Sciences, phthisiatrician, infectious disease specialist, professor of the Department of Infectious Diseases with courses in epidemiology and phthisiology at RUDN University:

“The illusion spread among the population that we will soon defeat tuberculosis has led to a weakened and commercial shortage of pharmaceutical companies. For a long period of time they did not develop new anti-tuberculosis drugs, only recently we began to receive new effective anti-tuberculosis therapy. “A lot depends on the patients; of course, someone interrupts therapy and, thereby, aggravates the disease.”

The worst case scenario is extensively drug-resistant tuberculosis. It is caused by bacteria that do not respond to active second-line drugs. In such situations, treatment is approached individually; it takes time to select the right regimen. According to WHO estimates, the situation with resistant tuberculosis is worst in India, China and Russia. These countries account for almost half of all cases.

The anti-tuberculosis course of treatment also causes many side effects, so along with the main drugs, doctors prescribe accompanying therapy: antispasmodics, sedatives, antiemetics, enzymes, etc.

HIV + tuberculosis

Approximately 12-14 million of the population of our planet are infected simultaneously with HIV and mycobacterium tuberculosis. This combination is especially dangerous; it is actually a bomb for the immune system. But cure is possible even in this case. It is important that during the treatment of tuberculosis the patient receives antiretroviral therapy (ART), if for some reason he has not taken it previously. Since tuberculosis is more dangerous for HIV-positive people, they are recommended to undergo fluorography twice a year as a preventative measure as a risk group. In addition, in the later stages of HIV, the Mantoux test and Diaskintest show negative values ​​and do not react to the test rod, so in such cases, computed tomography with a contrast agent and PCR can be effective diagnostic methods.

Since the likelihood of developing tuberculosis in an HIV-infected person is 20-30 times higher than in HIV-negative people, patients with low lymphocyte counts are prescribed chemoprophylaxis. This is either monotherapy with one drug or combination treatment, which prevents the infection from developing into a disease.

Vera Zimina:

“Prevention of tuberculosis is needed for risk groups, people who have some predisposing factors regarding the development of the disease; in essence, this is a decrease in immune surveillance, which blocks the development of tuberculosis infection in our body. First of all, these are HIV-infected patients, the second group are patients who began receiving genetically engineered biological drugs, the third are those who are or have been in close contact with a tuberculosis patient. Such people are prescribed chemoprophylaxis. This is the treatment of non-latent tuberculosis infection with anti-tuberculosis drugs.”

Classification of anti-tuberculosis drugs

Anti-tuberculosis drugs are classified into:

• anti-tuberculosis antibiotics: rifampicin, rifamycin, rifabutin, cycloserine, capreomycin, streptomycin, kanamycin, amikacin, linezolid;
• isonicotinic acid hydrazides: isoniazid, ftivazide;
• thiocarbamide derivatives: prothionamide, ethionamide;
• aminosalicylic acid derivatives: sodium para-aminosalicylate;
• fluoroquinolones: lomefloxacin, ofloxacin, levofloxacin, ciprofloxacin;
• derivatives of different chemical groups: pyrazinamide, ethambutol, terizidone, bedaquiline, pretomanid, delamanid.

In addition, there are combined anti-tuberculosis drugs containing: rifampicin + isoniazid; rifampicin + pyrazinamide + isoniazid; rifampicin + pyrazinamide + ethambutol + isoniazid; rifampicin + ethambutol + isoniazid; sodium para-aminosalicylate + isoniazid; lomefloxacin + pyrazinamide + prothionamide + ethambutol.

Anti-tuberculosis drugs are also classified into:

• First line drugs - main ones: isoniazid, ftivazid, rifampicin, rifamycin, rifabutin, streptomycin, ethambutol, sodium para-aminosalicylate;
• II line drugs - reserve: cycloserine, capreomycin, kanamycin, amikacin, prothionamide, ethionamide, pyrazinamide;
• drugs for the treatment of drug-resistant tuberculosis: lomefloxacin, ofloxacin, levofloxacin, ciprofloxacin, linezolid, bedaquiline, pretomanid, delamanid.

Prevention

Unfortunately, it is impossible to completely protect against tuberculosis infection, but you can prevent the development of the disease or try to detect it at an early stage. Our lungs do not have nerve endings, so it is impossible to “feel” tuberculosis. But planned annual medical examination and fluorography can detect the disease before the onset of complications.

Currently, in Russia, newborns are vaccinated with the BCG vaccine; it is made from an artificially grown weakened tuberculosis bacillus. Vaccinated children either receive immunity or are prevented from contracting a severe form of tuberculosis.

Vera Zimina:

“For countries with medium to high incidence rates, large-scale use of neonatal vaccination is indeed justified. It has been convincingly proven in epidemiological studies that the incidence of tuberculosis in children is decreasing and, most importantly, vaccination protects against the development of very malignant, progressive forms of tuberculosis, which are associated with a high risk of death. If a child suddenly falls ill, this tuberculosis is curable, it can be treated, and nothing bad will happen in the future.”

The problem of curing patients with respiratory tuberculosis

IN

Due to the unfavorable epidemic situation regarding tuberculosis, the development and implementation of effective methods for its treatment are of paramount importance in modern phthisiology. What is important in this problem is a comprehensive (both medical and socio-economic) approach to the treatment of tuberculosis, which will significantly reduce the reservoir of tuberculosis infection.

It should be emphasized that tuberculosis is an infectious disease, and socio-economic factors contribute to its development and aggravate the course of the tuberculosis process. Therefore, from the standpoint of the infectious nature of tuberculosis, the main method of treatment is chemotherapy. The therapeutic effect is due to the direct effect of anti-tuberculosis drugs on Mycobacterium tuberculosis (MBT) and their destruction in the patient’s body. The degree of inhibitory effect of chemotherapy drugs depends primarily on the tuberculostatic activity of individual chemotherapy drugs, their dose, as well as on the combinations of anti-tuberculosis drugs used.

As A.G. pointed out. Khomenko (1996), the cure of tuberculosis patients depends on 2 interrelated factors: suppression of the multiplying mycobacterial population with the help of anti-tuberculosis chemotherapy drugs and regression of tuberculosis changes in the affected organs with the development of reparative processes.

Over the course of several decades, significant experience has been accumulated in the use of anti-tuberculosis drugs, which has made it possible to determine the basic principles of treatment of tuberculosis, however, in modern conditions there is a need to constantly improve chemotherapy regimens.
“Chemotherapy regimen” means the choice of a specific combination of chemotherapy drugs, their dosage, method of use in the form of a single daily dose or divided into 2-3 doses, route of administration (orally, intravenously, in the form of aerosols, endobronchial infusions, rectally) and the rhythm of taking chemotherapy drugs ( daily or intermittent). There are several classifications of anti-tuberculosis drugs

.
One of them includes 2 groups of chemotherapy drugs: Group 1
– the most effective anti-tuberculosis drugs (rifampicin, isoniazid);
Group 2
– drugs of average effectiveness (streptomycin, kanamycin, amikacin, florimycin, pyrazinamide, ethambutol, prothionamide, fluoroquinolone group).
According to another classification, all drugs are divided into main (1st row)
- GINK group, rifampicin, rifabutin, streptomycin, pyrazinamide, ethambutol and
reserve drugs (2nd row)
- kanamycin, amikacin, capreomycin, ethionamide, prothionamide, cycloserine, PAS, fluoroquinolone group.
Currently, a group of alternative drugs has been identified (3 series)
- clarithromycin, amoxicillin/clavulanate, clofazimine, rifampentine, thioacetazone.

What determines the effectiveness of treatment?

The clinical effectiveness of anti-tuberculosis drugs is determined by many factors, among which the main ones are: the massiveness of the mycobacterial population itself, the sensitivity or resistance of the MBT in it to the chemotherapy drugs used, the ability of individual individuals to reproduce rapidly; the created concentration of the drug in the blood and the degree of permeability into the lesions; interaction with other drugs; the ability of drugs to influence intracellularly located (non-phagocytosed) MBT; the property of chemotherapy drugs to induce drug resistance of the pathogen, as well as patient tolerance to anti-tuberculosis drugs and their combinations.

The therapeutic effect of anti-tuberculosis drugs is based on their direct bacteriostatic and bactericidal effect on the microbial cell.

It is known that chemotherapy drugs have different effects on microbial cells. Some inhibit the synthesis of bacterial cell walls by destroying peptidoglycan, the lipoprotein fraction, suppressing function and diffusion through the cytoplasmic membrane; others inhibit the synthesis of nucleic acids by disrupting the metabolism of RNA and DNA, selective action on plasmids, mitochondria, inhibition of RNA polymerase, formation of breaks in the DNA chain, inhibition of DNA replication; still others affect the functions of ribosomes, which leads to the destruction of the cytoplasm and granular apparatus.

Thus, isoniazid has a bactericidal effect, especially on young reproducing microbial cells, suppressing the synthesis of myconic acid in the bacterial wall, as well as destroying the cytoplasm and its granular substance consisting of DNA. Isoniazid is capable of destroying more than 90% of MBT after 7 days of use. Rifampicin also has a bactericidal effect by inhibiting the activity of ribosomal RNA polymerase and inhibiting DNA synthesis. Rifampicin, like isoniazid, affects not only rapidly, but also slowly multiplying and even persistent MBT. Pyrazinamide has a bactericidal effect on slowly multiplying MBT, including those located intracellularly in macrophages. The mechanism of action of pyrazinamide has not been fully studied. It has the greatest effect in an acidic environment (pH 5.5) on persistent variants. Streptomycin inhibits ribosomal proteins, suppressing their synthesis. Its effect does not appear immediately, but after several generations of microbial cells. The drug is characterized by a relatively weak bactericidal effect. Ethambutol destroys the microbial cell wall, providing a bactericidal effect only in large doses (24 mg/kg).

The most essential for effective treatment is the bactericidal effect of some anti-tuberculosis drugs, in particular isoniazid and rifampicin, which can quickly kill a large number of actively reproducing MBT.

It should also be borne in mind that chemotherapy drugs have different effects on intracellular and extracellular MBTs.

. Thus, as the process progresses, intensive multiplication of MBT occurs in the human body, their release into the tissues of the affected organs, spread by lymphobronchogenic and hematogenous routes, as a result of which new areas of inflammation appear and caseous necrosis develops. Most mycobacteria during this period are extracellular, and that part of the bacterial population that was phagocytosed by macrophages during the inflammatory reaction, due to intensive intracellular reproduction, causes the destruction of phagocytes and again appears extracellular. Thus, the intracellular localization of MBT at this stage is relatively short-lived. Almost all anti-tuberculosis drugs have a pronounced antibacterial effect on an actively reproducing bacterial population.

As the tuberculosis process subsides, the size of the bacterial population decreases due to the suppression of MBT reproduction. In the context of ongoing chemotherapy and a decrease in the bacterial population in the patient’s body, part of the MBT remains, which are in a state of persistence. Persistent mycobacteria are often detected only microscopically, since they do not grow when inoculated on nutrient media. Such mycobacteria are called “sleeping” or “dormant”, sometimes “killed”. As one of the options for the persistence of mycobacteria, their transformation into L-forms or fine-grained forms is possible. At this stage, when intensive reproduction of the bacterial population is replaced by a state of persistence of the remaining part of it, mycobacteria are located mainly intracellularly (inside phagocytes).

Just a few years ago it was believed that the effectiveness of chemotherapy largely depended on its duration. When the first anti-tuberculosis drugs appeared, the duration of treatment was relatively short (1–3 months). As new chemotherapy drugs became available, the duration of treatment
gradually increased and ranged from 12 to 18 months.

This provision has currently been revised. The method of controlled chemotherapy of shortened duration, tested in many countries, has shown its high efficiency and has made it possible to significantly reduce the duration of treatment (up to 6–9 months) through the use of rational chemotherapy regimens that contribute to the rapid suppression of the mycobacterial population and the cessation of bacterial excretion.

Phases of chemotherapy

Due to the different state of the bacterial population at different stages of the disease during chemotherapy, in recent years it has become customary to divide the entire period of treatment with chemotherapy into 2 phases (stages). It should be pointed out that this division of chemotherapy periods has been used by domestic phthisiatricians for a long time.

The first stage is characterized by intensive, intense chemotherapy; its purpose is to suppress the proliferation of the bacterial population and achieve its quantitative reduction. The second stage of less intensive chemotherapy is the follow-up phase, and its purpose is to influence the remaining bacterial population, mostly located intracellularly in the form of persistent forms of MBT. At this stage, the main task is to prevent the proliferation of remaining mycobacteria.

According to modern concepts, in the first phase of chemotherapy

When the office multiplies rapidly, newly diagnosed bacillary patients are prescribed 4 anti-tuberculosis drugs (isoniazid, rifampicin, pyrazinamide, streptomycin or ethambutol).
Such intensive chemotherapy is carried out for 2 months, and if bacterial excretion persists according to smear microscopy - for 3 months. In the second phase
of chemotherapy in newly diagnosed patients, when the bulk of the mycobacterial population has already been suppressed, 2 drugs (isoniazid and rifampicin) are used daily or every other day for 4 months. For newly diagnosed patients treated irregularly or interrupted treatment, as well as patients with relapse of tuberculosis, it is recommended in the intensive phase to prescribe 5 chemotherapy drugs (isoniazid, rifampicin, pyrazinamide, streptomycin and ethambutol) for 2 months, then 4 chemotherapy drugs are used for another month (cancelled streptomycin). The second phase of chemotherapy for this category of patients is recommended to be carried out with three drugs daily or every other day for the next 5 months.

For patients in whom MBT was not detected during the initial sputum examination, the intensive phase of chemotherapy can also be carried out with 4 drugs (isoniazid, rifampicin, pyrazinamide, ethambutol) for 2 months, after which they can switch to taking two drugs (isoniazid and rifampicin or ethambutol) in within 4 months.

Patients with chronic forms of pulmonary tuberculosis should be treated according to individual chemotherapy regimens, taking into account the resistance of mycobacteria to chemotherapy drugs and with further modification of the chemotherapy regimen in cases of detection of secondary resistance to the drugs used. Most often, such patients, as well as patients in whom MBT multidrug resistance has been identified, are treated with reserve drugs - kanamycin, amikacin, capreomycin, prothionamide (ethionamide), ethambutol, cycloserine, as well as ofloxacin, lomefloxacin, ciprofloxacin.

The effectiveness of chemotherapy is assessed according to several parameters: clinical (reduction or disappearance of symptoms of intoxication and chest complaints); microbiological (reduction of the massiveness of bacterial excretion according to its quantitative assessment); X-ray (reduction of infiltrative-inflammatory changes in the lungs and healing of cavities).

Ensuring regular intake of chemotherapy drugs
When carrying out chemotherapy, an important task is to ensure that the patient regularly takes the prescribed chemotherapy drugs throughout the entire period of treatment. Irregular use of chemotherapy drugs can lead to the development of drug resistance and progression of the process. Methods that ensure the regularity of chemotherapy are closely related to organizational forms of treatment in hospital (sanatorium) and outpatient settings.

When conducting chemotherapy, an important task is to ensure that the patient regularly takes the prescribed chemotherapy drugs throughout the entire treatment period. Irregular use of chemotherapy drugs can lead to the development of drug resistance and progression of the process. Methods that ensure the regularity of chemotherapy are closely related to organizational forms of treatment in hospital (sanatorium) and outpatient settings.

In a hospital setting

The administration of prescribed chemotherapy drugs during both phases is carried out in the presence of medical personnel with precise recording of the doses of medications taken. The dose of medication is understood as the daily dose of each chemotherapy drug included in the combination. Considering the duration of chemotherapy only by the number of calendar days of the month may give an incorrect idea of ​​the number of drugs taken. It often turns out that within 1 or 2 months the number of doses of drugs taken is significantly less than the number of days corresponding to the duration of treatment. This is due to the fact that chemotherapy drugs are often prescribed not immediately, but gradually over several days; If side effects occur, chemotherapy drugs are usually discontinued for some period of time. As a result, within a month the patient may receive not 30 doses, but significantly less. When taking chemotherapy drugs intermittently, the number of doses over the same calendar period is 2 times less than when taking them daily. Therefore, in addition to taking into account the duration of chemotherapy by day, it is necessary to take into account the number of doses of chemotherapy drugs taken by the patient, which is of certain importance when assessing the effectiveness of treatment.

Control over the intake of chemotherapy drugs is facilitated by prescribing the entire daily dose in one dose, as well as with intermittent treatment. One type of controlled chemotherapy is the use of drugs by the parenteral method.

Outpatient

There are several methods. Taking chemotherapy drugs in the presence of medical personnel, which is carried out: a) in anti-tuberculosis dispensaries, b) at the patient’s home. Monitoring the intake of chemotherapy drugs is easier when using the entire daily dose in one dose, as well as with intermittent treatment.

The patient himself takes chemotherapy drugs issued by the dispensary for a certain period, most often for 7 days, with systematic monitoring of the consumption of medications. The cost of chemotherapy must also be taken into account. Thus, if it is impossible to strictly control the intake of rifampicin at home, it is more advisable to switch to ethambutol.

Recently, combined tablet forms

, containing four, three or two of the most active anti-tuberculosis chemotherapy drugs: myrin (isoniazid, rifampicin and ethambutol); Mairin P (isoniazid, rifampicin, ethambutol and pyrazinamide); rifater, Tricox (isoniazid, rifampicin, pyrazinamidrifanag), tibinex (isoniazid and rifampicin), as well as other combination chemotherapy drugs. Their use greatly facilitates chemotherapy monitoring, especially in outpatient settings.

Changing your chemotherapy regimen

The above provisions constitute the basic scheme of programmed chemotherapy.

At the same time, as treatment progresses, some patients have to make changes to the chemotherapy program drawn up after the examination. The need to change medications is caused by a number of reasons:

• the presence of fatal adverse reactions caused by certain drugs,

• detection of primary drug resistance of Mycobacterium tuberculosis to chemotherapy, data about which the doctor usually receives 2–3 months after the start of treatment,

• lack of effect from the therapy, which is most often expressed by continued bacterial excretion and preservation of the cavity, and sometimes by slow resolution of inflammatory changes in the lungs.

There are various possibilities for changing the chemotherapy regimen: changing drugs, changing the method of their administration (intravenously, inhalation, rectally), combining different methods of drug administration, which depends on the specific reason that necessitated modification of the chemotherapy regimen.

At later stages of treatment, especially with delayed regression of the process and bacterial excretion has already stopped, but with a remaining cavity, drugs that stimulate reparative processes are prescribed. Thus, if the effect of chemotherapy is insufficient, it is necessary to choose the optimal treatment method: change the combination of chemotherapy drugs, their doses, change the route of drug administration, additionally use pathogenetic agents and physiotherapeutic methods of treatment. In these cases, it is most advisable to change the chemotherapy regimen no later than 2–3 months after the start of treatment. The later the chemotherapy regimen is changed, the longer the period of treatment with chemotherapy is. It should be taken into account that by the end of the third month there is already data reflecting: a) the results of quantitative examination of sputum by microscopy before the start of treatment and during chemotherapy; b) the results of sputum culture done before the start of treatment, with data on the sensitivity of Mycobacterium tuberculosis to chemotherapy; c) the dynamics of the x-ray picture, in particular, the degree of resorption of inflammatory changes in the lungs and changes in the size of the cavity.

Quantitative assessment of bacterial excretion

in the conditions of modern chemotherapy of pulmonary tuberculosis is one of the methods for determining the effectiveness of treatment measures. A decrease in the size of the vegetative population during chemotherapy is interpreted as a good prognostic sign; long-term stable bacterial excretion or a tendency to increase it are considered as treatment failures.

To quantify the size of the mycobacterial population, bacterioscopic and cultural research methods are used. The effectiveness of these methods is close, but not equivalent. The speed of obtaining information that the bacterioscopic method provides is its undeniable value compared to the cultural method. However, the latter more fully characterizes the microbial population not only from a quantitative, but also a qualitative point of view.

Reasons preventing treatment

Timely correction significantly increases the effectiveness of chemotherapy and promotes faster healing of destructive changes in the lungs. However, not all patients achieve positive treatment results. Therefore, increasing the effectiveness of chemotherapy remains one of the main problems of phthisiology. The literature describes many reasons that prevent the patient from being cured.

Apparently, the most important problem in chemotherapy remains drug resistance of MBT.

, since recently there has been an increase in the frequency of detection of drug-resistant MBT even in newly diagnosed, previously untreated patients with destructive pulmonary tuberculosis.

The phenomenon of drug resistance in MBT has important clinical significance. There is a close relationship between quantitative changes in the bacterial population and changes in a number of biological properties of mycobacteria, one of which is drug resistance. In a large multiplying bacterial population, there is always a small number of drug-resistant mutants, which have no practical significance, but as the bacterial population decreases, the ratio between the number of sensitive and resistant MBT changes. Under these conditions, mainly resistant MBT multiply; this part of the bacterial population increases, reaching a critical proportion, sometimes even exceeding it. Therefore, in clinical practice it is necessary to study the drug sensitivity of mycobacteria and compare the results of this study with the dynamics of the tuberculosis process.

To increase the effectiveness of treatment of patients with multidrug-resistant MTB, it is necessary: ​​firstly, chemotherapy, before receiving the results of a study of sputum or other pathological material, should begin with four or five (for relapses) anti-tuberculosis drugs, taking into account the fact that even if there are mycobacteria in the population that are resistant to 1 –2 drugs, the bacteriostatic effect will be provided by 2 or 3 chemotherapy drugs, to which sensitivity is preserved. Secondly, it is necessary to find accelerated bacteriological methods for detecting drug resistance of MBT, which will make it possible to promptly change the chemotherapy regimen, canceling drugs to which resistance has been identified, and prescribing those to which sensitivity is preserved. Thirdly, the use of reserve drugs in patients whose sputum contains drug-resistant MBT allows for a more rapid cessation of bacterial excretion. Finally, in patients with multidrug resistance, it is necessary to more widely use artificial pneumothorax and surgical treatment methods.

The second, no less significant problem of treatment is the very nature of the process in the lungs

.
We see the complexity of this problem not so much in the prevalence of specific changes in the lungs and the nature of destructive changes, but in a noticeable increase in the frequency of acutely progressive forms of tuberculosis
, of which 33.8% is caseous pneumonia, occurring against the background of severe immunodeficiency with the development of irreversible changes in the lungs.

A set of measures, including intensive chemotherapy using intrapulmonary and lymphotropic administration of chemotherapy drugs, various detoxification agents, including intravascular laser irradiation of blood, plasmapheresis, widespread use of immunostimulants and other methods, made it possible to achieve the cessation of bacterial excretion in 65.4% of patients with caseous pneumonia. However, healing of destructive changes was observed in only 7.7% of patients. Considering the irreversibility of morphological changes in the lungs, patients with caseous pneumonia are subject to surgical treatment.

Have not lost their influence on the effectiveness of chemotherapy and diseases associated with tuberculosis

– diabetes, pathology of the gastrointestinal tract, kidneys, etc. However, it must be emphasized that thanks to the use of modern medications used for these diseases, most patients can undergo full-fledged chemotherapy.

The clinical course and treatment are complicated by nonspecific microflora in the sputum
, which is often a sign of the presence of nonspecific inflammatory processes of the respiratory system. When nonspecific microflora was detected in sputum, intoxication phenomena were observed 3 times more often than in the absence of it. The use of fluoroquinolone drugs in combination with antituberculosis drugs significantly reduces the time of sputum abacillation, especially with massive bacterial excretion.

Side effects of anti-tuberculosis drugs

also limit the possibility of carrying out full-fledged chemotherapy, especially when using standard chemotherapy courses. Chemotherapy drugs, having a toxic, sensitizing effect on the patient’s body, can cause various side effects. They occur especially often in the presence of concomitant diseases of the liver, stomach, kidneys, cardiovascular system, etc. Therefore, when choosing chemotherapy drugs, if possible, you should avoid prescribing drugs that, given the existing condition of the patient’s various organs and systems, are contraindicated or may cause adverse reactions. It should be borne in mind that side effects are more likely to be detected when maximum therapeutic doses are prescribed. The simultaneous use of various pathogenetic agents can prevent or eliminate the side effects of chemotherapy drugs. They are canceled only in cases of complete intolerance or danger of causing severe manifestations of drug complications. However, we were unable to detect a significant increase in the frequency of adverse reactions depending on the increase in the number of chemotherapy drugs. Thus, when using 3 anti-tuberculosis drugs, adverse reactions were observed in 17.5% of patients, 4 drugs – in 18.2%, 5 – in 22.7% of patients. However, the side effects of chemotherapy were 2–3 times more likely to occur in patients with concomitant diseases. For early recognition of adverse reactions, immunological tests with chemotherapy are used. Desensitizing agents, corticosteroid drugs, and extracorporeal treatment methods can eliminate the side effects of chemotherapy drugs in 64% of patients without discontinuing them, and only 36% of patients had to replace the drug that caused the side effect.

Reparative processes and their acceleration

Suppression of the mycobacterial population creates the prerequisites for the development of reparative processes in organs affected by tuberculosis. As a result of the treatment, a different course of the tuberculosis process is noted: regression followed by healing; stabilization of the tuberculosis process without clinical cure with preservation of the cavity, tuberculoma or other changes; temporary subsidence of the inflammatory process followed by exacerbation. If treatment is ineffective, the process can become chronic or lead to progression of the disease, even fatal. Fatal outcomes from tuberculosis are currently most often caused by the development of initially acutely progressive forms of tuberculosis (caseous pneumonia, generalized tuberculosis).

To speed up the healing process, a large arsenal of pathogenetic agents and methods is currently used. Among the most widely used means of pathogenetic therapy

It should be noted the use of corticosteroid drugs, non-hormonal anti-inflammatory drugs, which can be added to chemotherapy during the first phase of treatment, including in its early stages. In recent years, corticosteroids have been combined with immunomodulatory drugs (tactivin, thymalin, levamisole, leukinferon, etc.). The latter can be used independently (in addition to chemotherapy) in the presence of changes in T lymphocytes and a decrease in their function. To stimulate reparative processes during delayed regression of tuberculous changes, tuberculin, BCG vaccine, as well as nonspecific biological agents (pyrogenal, prodigiosan, various tissue preparations) are used. In recent years, physiotherapeutic methods have been widely used: ultrasound, inductothermy, decimeter waves, EHF and various types of laser studies. In acutely progressive forms of tuberculosis, to reduce intoxication, intravenous laser irradiation of blood, plasmapheresis and hemosorption, ozonation, as well as treatment with various antioxidant agents and antikinin drugs are performed. Thus, the pathogenetic agents used for tuberculosis are very numerous, so the doctor is faced with the task of choosing the most reasonable method of treatment.

The problem of treatment is not limited to the above factors. Other factors that reduce the effectiveness of chemotherapy, in particular of an organizational nature, are also significant: the lack of an optimal set of chemotherapy drugs for the entire course of treatment, improper storage conditions, unreasonable breaks in treatment and irregularity in taking chemotherapy drugs, non-compliance with the dosage (per kg of weight), lack of control over taking medications (in hospital, outpatient), lack of doctor-patient cooperation, intervention of healer “medicine”.

Combined drugs -

Mairin (trade name)

Mairin-P (trade name)

(Wyeth-Lederle)