Modern principles and schemes for the treatment of pulmonary tuberculosis. How is Pulmonary Tuberculosis Treated in Adults A Sample Drug Treatment Plan for Tuberculosis

The treatment of pulmonary tuberculosis requires a long-term integrated approach. For this, a special chemotherapy based on several components has been developed.

General rules

Treatment of pulmonary tuberculosis in adults should be carried out with several drugs and without interruption. As a rule, the scheme uses 4-5, which must be taken every day for six months.

The active substances affect mycobacteria in different ways, and only in combination is it possible to completely destroy mycobacteria. In addition, immunomodulatory drugs are prescribed without fail.

Breathing exercises and physiotherapy are also needed. Otherwise, mortality can reach up to 50% in the active form. The second 50%, if left untreated, become a chronic disease.

Treatment of such a disease must necessarily take place under the supervision of a doctor - self-medication can lead to resistance of mycobacteria and a more advanced stage.

Action algorithm

How is pulmonary tuberculosis treated in adults? Recovery requires the realization of certain goals:

1. Eliminate laboratory signs and clinical manifestations of the disease.
2. Restore human performance.
3. Stop the release of mycobacteria into the environment, which must be confirmed by laboratory tests.
4. Eliminate various signs of the disease with confirmation of their absence by an x-ray procedure.

Attention! If it is not possible to conduct a full course, it is better to postpone therapy than to interrupt it. Be sure to have all the drugs with daily intake without interruption.

Where is the therapy carried out?

Treatment of pulmonary tuberculosis in adults is carried out over a long period with mandatory medical supervision at each stage.

Surgical intervention

A significant number of patients with various types of Mycobacterium tuberculosis need a surgical operation - cutting off the focus of inflammation of the lung tissue.

Surgical treatment of pulmonary tuberculosis is necessary in the following cases:

1. There are cavities from which sputum can be secreted and spread bacteria. At the same time, conservative treatment for 3-6 months did not bring success. In some cases, dangerous bleeding from cavities is possible either. Large cavities form, due to which scarring of the cavities cannot occur on its own, which leads to an even greater spread of infection and possible relapses.
2. There are foci of inflammation without mycobacteria. Prescribed drugs cannot sterilize these foci due to the inability to penetrate through the fibrous tissue.
3. The presence of cicatricial strictures of the bronchi after the lesion.
4. Foci of infection caused by atypical mycobacteria that are not amenable to drug treatment.
5. Complications in the form of accumulation of pus in the pleural cavity or collapse (low pressure) of the lung.
6. The development of neoplasms of unknown etiology (causes of the onset of the disease).

Surgical intervention is necessarily combined with enhanced therapy with drugs against tuberculosis. With erroneous treatment, a curable stage can turn into an intractable state due to drug resistance.

In addition to resection (complete removal) of the lung, drainage (suction of fluid) of the pleura or lung tissue caverns is possible, as well as the use of artificial pneumothorax (air accumulation).

Three-component circuit

At a time when anti-tuberculosis therapy had just appeared, the following scheme for combating the disease was formed:

• Streptomycin.

These substances have been used to treat pulmonary tuberculosis for decades, and have helped save many lives.

Four-component circuit

With the beginning of the provision of active medical care, strains (genus of viruses) of mycobacteria have become more resistant to drugs. The next step was the development of a four-component first-line therapy:

• Streptomycin/kanamycin;
• Rifabutin / ;
• Isoniazid/ftivazid;
• Pyrazinamide/ethionamide.

Interesting! Such principles for the fight against the disease were developed by the Dutch doctor Karel Styblo in 1974. After 20 years, the World Health Organization recognized the Stiblo tuberculosis control model, calling it DOTS - a strategy and recommending it for countries with a high incidence of Mycobacterium tuberculosis.

Some experts believe that the Soviet strategy for the treatment of pulmonary tuberculosis was more effective and comprehensive with the use of anti-tuberculosis dispensaries, compared with the methods of Dr. Stiblo.

Five-component scheme

To date, many experts prefer to enhance the regimen with an additional substance based on a fluoroquinolone, for example, ciprofloxacin. With the rise of drug-resistant drugs, treatment is becoming an increasingly complex issue.

Therapy includes antibiotics of the second, third and later generations. The effectiveness of such drugs occurs after daily use for 20 months or longer.

However, the cost of second- and higher-generation antibiotics is much more significant than a first-line course. In addition, side effects from such medications occur more often.

Even with four or five component schemes, mycobacteria can show resistance. Then, to eliminate pulmonary tuberculosis, treatment switches to second-line chemotherapy drugs, such as capreomycin, cycloserine.

Inflammations in Mycobacterium tuberculosis and the method of treatment itself can lead to secondary diseases - anemia, hypovitaminosis, leukopenia. Therefore, attention should be paid to a varied diet, especially with significant weight loss.

Patients with a history of drug or alcohol addiction are detoxified before starting anti-tuberculosis therapy.

If there are diseases other than MBT for which immunosuppressive therapy is used (suppression of an undesirable immune response), then either it is canceled altogether, as far as the clinical picture allows, or the dosages are reduced.

HIV-infected people should undergo anti-HIV therapy in parallel with anti-tuberculosis.

Glucocorticoids

These drugs have a pronounced immunosuppressive effect. Therefore, their use is extremely limited.

The indication for the use of glucocorticoids (steroids) will be severe intoxication or acute inflammation. They are prescribed in a short-term course in small doses and always during five-component chemotherapy.

Related Methods

An important element of therapy is sanatorium treatment. The rarefied air in the mountains facilitates the oxygenation of the lungs, thereby reducing the growth and increase in the number of mycobacteria.

For the same purposes, hyperbaric oxygenation is used - the use of oxygen in special pressure chambers.

Additional Methods

Previously, in cases where the cavity did not decrease due to thick walls, the only solution was surgical intervention. Nowadays, the method of valvular bronchial blocking is more effective.

Its essence is that an endobronchial valve is inserted into the affected area, which allows you to maintain the drainage function of the bronchus and create hypoventilation. The valve is placed through the larynx using local anesthesia (narcosis).

The method has not yet received a well-deserved distribution due to the high cost of equipment, and is also not independent - such operations are carried out in parallel, and not instead of chemotherapy.

The initial stage of the disease

Important. For a successful result, timely diagnosis is necessary. There are various laboratory methods for determining infection and morbidity.

How is early stage pulmonary tuberculosis treated? If, due to the correct assessment of the clinical picture (a long period of time, coughing, enlarged lymph nodes, nausea, weakness, pallor, a general decrease in immunity, sudden weight loss) and an x-ray examination, a specialist makes a diagnosis of tuberculosis, then through adequate treatment, results can be achieved through 6 months, less often - after two years.

As a rule, the following drugs are used for the initial stages:

• Pyrazinamide;
• Streptomycin;
• Rifampicin.

But the dosages of these drugs differ from the cases of late stages and must be prescribed individually. It is also important, which must include fresh vegetables and fruits, whole grain bread, bran, jacket potatoes, eggs, milk.

As an addition, you can turn to traditional medicine. Treatment of pulmonary tuberculosis can be carried out not only with the help of medicines.

Herbs and infusions will be a great addition to the treatment

1. Althea root infusion;
2. Decoction of coltsfoot leaves;
3. Infusion of wild rosemary;
4. Decoction of pine cones.

Each plant has its own dosage and frequency of administration.

Prevention

Preventive methods include maintaining overall health (a variety of physical activity and proper nutrition), the exclusion of bad habits (smoking, alcohol and drug addiction). Not unimportant factor are good social and living conditions.

An interesting educational film about tuberculosis is presented to your attention. Be sure to watch it if you are not familiar with the disease.

Improving working conditions, combating environmental pollution, avoiding contact with the sick are also preventive measures.

For citation: Mishin V.Yu. Modern chemotherapy regimens for pulmonary tuberculosis caused by drug-susceptible and drug-resistant mycobacteria // RMJ. 2003. No. 21. S. 1163

MGMSU named after N.A. Semashko

X chemotherapy has taken the main place in the treatment of patients with tuberculosis. In Russia and the world, extensive experience has been gained in the use of anti-tuberculosis drugs, which has made it possible to develop the basic principles of combined chemotherapy in patients with tuberculosis.

In domestic phthisiology, throughout the entire more than 50-year period of the use of anti-tuberculosis drugs, a clinical approach was carried out to assess the effectiveness of chemotherapy, where the main task was always to achieve not only the cessation of bacterial excretion, but also the complete elimination of the clinical manifestations of the disease, stable healing of tuberculous changes in the affected organ, as well as the maximum recovery of impaired body functions. This is emphasized in the Concept of the National Russian Tuberculosis Control Program, where combined etiotropic chemotherapy is the main component of the treatment of tuberculosis, when several anti-tuberculosis drugs are used simultaneously for a sufficiently long time.

The therapeutic effect of chemotherapy is due to the antibacterial action of anti-tuberculosis drugs and is aimed at suppressing the reproduction of Mycobacterium tuberculosis (bacteriostatic effect) or their destruction (bactericidal effect) in the patient's body. Only by suppressing the reproduction of Mycobacterium tuberculosis or their destruction is it possible to launch adaptive mechanisms aimed at activating reparative processes and creating conditions in the patient's body for a complete clinical cure.

Clinical efficacy of anti-tuberculosis drugs determined by many factors, the main ones being:

• the massiveness of the mycobacterial population itself;
• sensitivity or resistance of mycobacteria contained in it to the drugs used;
• the ability of individual individuals to reproduce rapidly;
• level of created bacteriostatic concentration;
• the degree of penetration of drugs into the affected areas and activity in them;
• the ability of drugs to act on extra- and intracellular (phagocytosed) microbes;
• drug tolerance by patients.

The main anti-tuberculosis drugs: isoniazid (H), rifampicin (R), pyrazinamide (Z), ethambutol (E), and streptomycin (S) are highly effective against mycobacteria sensitive to all anti-TB drugs. It should be noted that only in Russia there are alternative drugs to isoniazid, such as phenazid, ftivazid and metazid, which cause fewer side effects.

Much more difficult is the question of conducting etiotropic treatment in patients with drug resistant pulmonary tuberculosis when the most important and defining clinical effect of chemotherapy is the frequency and nature of drug resistance of Mycobacterium tuberculosis.

According to the current WHO classification, Mycobacterium tuberculosis can be:

• monoresistant to one anti-tuberculosis drug;
• polyresistant to two or more anti-TB drugs, but not to the combination of isoniazid and rifampicin;
• multi-resistant to at least the combination of isoniazid and rifampicin.

Particularly severe are specific lung lesions in patients with multidrug resistance of Mycobacterium tuberculosis.

The main risk factor for the development of drug resistance in Mycobacterium tuberculosis is ineffective previous treatment, especially interrupted and incomplete. In this regard, the main task in preventing the development of drug resistance in mycobacteria is the correct treatment of newly diagnosed patients with tuberculosis using modern evidence-based and evidence-based chemotherapy regimens.

used in the treatment of drug-resistant pulmonary tuberculosis reserve anti-tuberculosis drugs: kanamycin (K), amikacin (A), capreomycin (Cap), cycloserine (Cs), ethionamide (Et), prothionamide (Pt), fluoroquinolones (Fq), para-aminosalicylic acid - PAS (PAS) and rifabutin (Rfb).

From the point of view of the effectiveness of chemotherapy, it is necessary to imagine that in the focus of active specific inflammation there can be four populations of Mycobacterium tuberculosis, different in localization (extra- or intracellularly located), drug resistance and metabolic activity. Metabolic activity is high in extracellularly located mycobacteria in the wall of the cavity or caseous masses, less in extracellular - in macrophages and very low in persistent bacteria.

With progressive and acutely progressive tuberculosis (infiltrative, miliary, disseminated fibrous-cavernous and caseous pneumonia), there is an intensive reproduction of mycobacteria in the patient's body, their release into the tissues of the affected organ, spread by hematogenous, lymphogenous and bronchogenic routes, resulting in areas of inflammation, caseous necrosis develops. Most mycobacteria during this period are extracellular, and that part of the mycobacterial population that turned out to be phagocytosed by macrophages, due to the intensive destruction of phagocytes, again turns out to be extracellular. Consequently, the intracellular localization of mycobacteria at this stage is a relatively short period in the life of a multiplying mycobacterial population.

In terms of effective chemotherapy, drug resistance of Mycobacterium tuberculosis is of great clinical importance. In a large and proliferating bacterial population, there is always a small number of wild mutants resistant to antituberculous drugs at a ratio of 1 mutant resistant to isoniazid or streptomycin per million, 1 to rifampicin per 100 million and 1 to ethambutol per 100,000 susceptible Mycobacterium tuberculosis (MBT). ). Taking into account the fact that there are 100 million MBT in a cavern with a diameter of 2 cm, there are mutants for all anti-tuberculosis drugs there.

When conducting correct and adequate chemotherapy, these mutants have no practical significance. But as a result of improper treatment, when inadequate chemotherapy regimens and combinations of anti-tuberculosis drugs are prescribed, not optimal doses when calculated in mg per 1 kg of the patient's body weight and dividing the daily dose of drugs into 2-3 doses, the ratio between the number of resistant and resistant mycobacteria changes. Under these conditions, mainly drug-resistant microbes multiply - this part of the bacterial population increases.

As the tuberculous inflammation subsides, with chemotherapy, the size of the mycobacterial population decreases due to the destruction of mycobacteria. In clinical conditions, this population dynamics is manifested in a decrease in the number of Mycobacterium tuberculosis in the sputum, and then the cessation of bacterial excretion.

Under conditions of ongoing chemotherapy, leading to a decrease in the mycobacterial population and suppression of the reproduction of mycobacterium tuberculosis, a part of the mycobacteria that are in a state of persistence remains in the patient's body. Persistent mycobacteria are often detected only by microscopic examination, because when sown on nutrient media, they do not give growth. Such mycobacteria are called "sleeping" or "dormant", sometimes - "killed". As one of the options for the persistence of mycobacteria, their transformation into L-forms, ultrasmall and filterable forms is possible. At this stage, when the intensive reproduction of the mycobacterial population is replaced by the state of persistence of the remaining part of it, mycobacteria are often found mainly intracellularly (inside phagocytes).

Isoniazid, rifampicin, ethionamide, ethambutol, cycloserine and fluoroquinolones have more or less the same activity against intra- and extracellularly located Mycobacterium tuberculosis. Aminoglycosides and capreomycin have significantly less bacteriostatic activity on intracellularly located mycobacteria. Pyrazinamide, with relatively low bacteriostatic activity, enhances the action of isoniazid, rifampicin, ethambutol and other drugs, penetrates very well into cells and has a pronounced activity in the acidic environment of caseosis.

Simultaneous administration of several anti-tuberculosis drugs (at least 4) allows you to complete the course of treatment before the appearance of drug resistance of mycobacteria or overcome their initial resistance to one or two drugs.

Due to the different state of the mycobacterial population at different stages of the disease, it is scientifically justified to divide tuberculosis chemotherapy into 2 periods or phases of treatment.

Initial (or intensive) phase of treatment It is aimed at suppressing the rapidly multiplying and actively metabolizing mycobacterial population and the drug-resistant mutants contained in it, reducing its number and preventing the development of secondary resistance.

For the treatment of tuberculosis caused by drug-susceptible mycobacteria, 4 anti-TB drugs are used: isoniazid, rifampicin, pyrazinamide, ethambutol or streptomycin for 2 months and then 2 drugs - isoniazid and rifampicin for 4 months.

Isoniazid, rifampicin and pyrazinamide form the core of the combination when exposed to susceptible Mycobacterium tuberculosis. It should be emphasized that isoniazid and rifampicin equally effectively affect all populations of mycobacteria located in the focus of tuberculous inflammation. At the same time, isoniazid has a bactericidal effect on all mycobacteria sensitive to both drugs and kills rifampicin-resistant pathogens. While rifampicin also kills mycobacteria sensitive to these two drugs, and, most importantly, bactericidal effect on isoniazid-resistant mycobacteria. Rifampicin effectively affects persistent mycobacteria if they begin to "wake up" and increase their metabolic activity. In these cases, rifampicin is more effective than isoniazid. The addition of pyrazinamide and ethambutol to the combination of isoniazid and rifampicin creates conditions for enhancing their effect on the pathogen and prevents the formation of resistance of mycobacteria.

In cases of drug-resistant tuberculosis, the question arises of the use of reserve anti-TB drugs, the combinations of which and the duration of their administration have not yet been fully developed in controlled clinical trials and are still mainly empirical in nature.

The combination of fluoroquinolone, pyrazinamide and ethambutol shows activity against multidrug resistant strains, but does not reach the level of activity of the combination of isoniazid, rifampicin and pyrazinamide against susceptible mycobacteria. This should be taken into account in the duration of the intensive phase of treatment for drug-resistant pulmonary tuberculosis.

The duration and effectiveness of the intensive phase of treatment should be based on the indicators of the cessation of bacterial excretion by smear and sputum culture, the identified drug resistance and the positive clinical and radiological dynamics of the disease.

Second phase of treatment - this is the impact on the remaining slowly multiplying and slowly metabolizing mycobacterial population, mostly located intracellularly, in the form of persistent forms of mycobacteria. At this stage, the main task is to prevent the reproduction of the remaining mycobacteria, as well as to stimulate reparative processes in the lungs with the help of various pathogenetic agents and methods of treatment. Treatment must be carried out for a long period of time in order to neutralize mycobacteria, which, due to their low metabolic activity, are difficult to destroy with anti-tuberculosis drugs.

No less important than the choice of chemotherapy regimen is ensuring that patients receive the prescribed dose of chemotherapy on a regular basis throughout the treatment period . Methods that ensure individual control of the regularity of taking anti-tuberculosis drugs are closely related to the organizational forms of treatment in inpatient, sanatorium and outpatient settings, when the patient must take prescribed medications only in the presence of medical personnel. This approach in the treatment of tuberculosis patients is a priority for domestic phthisiology and has been used in our country since the advent of anti-tuberculosis drugs.

All of the above, taking into account domestic and foreign experience, served as the basis for the development of modern chemotherapy protocols for pulmonary tuberculosis in the Russian Federation.

Antibacterial treatment regimen for tuberculosis , that is, the choice of the optimal combination of anti-tuberculosis drugs, their doses, routes of administration (orally, intravenously, intramuscularly, inhalation, etc.), duration and rhythm of application (single or intermittent method), is determined taking into account:

• epidemiological danger (infectiousness) of a patient upon detection of Mycobacterium tuberculosis in sputum by microscopy and inoculation on nutrient media;
• the nature of the disease (first detected case, relapse, chronic course);
• prevalence and severity of a specific process;
• drug resistance in Mycobacterium tuberculosis.

Taking into account the need for chemotherapy for all patients requiring treatment, and the different methodology for different categories of different groups of patients, it is generally accepted to divide patients with tuberculosis in accordance with the following 4 categories of chemotherapy.

Standard chemotherapy regimens used in patients of various categories are presented in Table 1.

The intensive phase of chemotherapy involves the appointment within 2 months of 4 drugs from among the main anti-TB drugs: isoniazid, rifampicin, pyrazinamide, ethambutol or streptomycin (2 H R Z E or S). During this period, the patient must take 60 doses of the combination of prescribed anti-TB drugs. If there are days when the patient did not take the full dose of chemotherapy, then not the number of calendar days will determine the duration of this phase of treatment, but the number of doses of chemotherapy drugs taken, i.e. 60. Such a calculation of the duration of treatment according to the accepted doses of chemotherapy should be carried out in patients of all 4 categories.

The appointment of streptomycin instead of ethambutol should be based on data on the prevalence of resistance of Mycobacterium tuberculosis to this drug and isoniazid in a particular region. In cases of high initial resistance to isoniazid and streptomycin, ethambutol is prescribed as the fourth drug, since only ethambutol in this regimen effectively affects isoniazid- and rifampicin-resistant Mycobacterium tuberculosis.

With continued bacterial excretion and the absence of positive clinical and radiological dynamics of the process in the lungs, the intensive phase of treatment should be continued for another 1 month (30 doses) until data on drug resistance of Mycobacterium tuberculosis are obtained.

When drug resistance of mycobacteria is detected, chemotherapy is corrected. Perhaps a combination of the main, to which the sensitivity of the Office has been preserved, and reserve drugs. However, the combination should consist of 4-5 drugs, of which at least 2 should be reserve.

Only 1 reserve drug should ever be added to a chemotherapy regimen due to the danger of monotherapy and the formation of resistance, tk. only the addition of 2 or more reserve drugs to the chemotherapy regimen minimizes the risk of additional development of drug resistance in Mycobacterium tuberculosis.

The indication for the continuation phase of treatment is the cessation of bacterial excretion by sputum smear microscopy and positive clinical and radiological dynamics of the process in the lungs.

While maintaining the sensitivity of Mycobacterium tuberculosis, treatment continues for 4 months (120 doses) with isoniazid and rifampicin (4 H R) both daily and intermittently 3 times a week (4 H3 R3). An alternative regimen in the continuation phase is the use of isoniazid and ethambutol for 6 months (6 H E).

The total duration of treatment for patients of the 1st category is 6-7 months.

If the drug resistance of Mycobacterium tuberculosis is detected according to the initial data, but if the bacterial excretion by sputum microscopy stops by the end of the initial phase of treatment, after 2 months, a transition to the continuation phase with an extension of its terms is possible.

Initial resistance to isoniazid and/or streptomycin is treated in the continuation phase with rifampicin, pyrazinamide and ethambutol for 6 months (6 R Z E) or rifampicin and ethambutol for 9 months (9 R E). The total duration of treatment in this case is 9-12 months.

With initial resistance to rifampicin and / or streptomycin, the continuation phase of treatment is carried out with isoniazid, pyrazinamide and ethambutol for 12 months (12 H Z E) or isoniazid and ethambutol for 15 months (15 H E). In this case, the total duration of treatment is 15-18 months.

With multiple resistance of Mycobacterium tuberculosis to isoniazid and rifampicin, the patient is assigned an individual treatment regimen according to the 4th category.

To the 2nd category of chemotherapy include patients with disease recurrence, previous treatment failure, treatment interruption of more than 2 months, inadequate chemotherapy for more than 1 month (incorrect combination of drugs and insufficient doses), and with a high risk of developing drug-resistant pulmonary tuberculosis.

The intensive phase of chemotherapy involves the administration of 5 basic anti-TB drugs for 3 months: isoniazid, rifampicin, pyrazinamide, ethambutol and streptomycin, during which the patient must receive 90 doses of the combination of prescribed drugs. In the intensive phase, streptomycin is limited to 2 months (60 doses) (2 H R Z E S + 1 H R Z E).

The intensive phase of chemotherapy can be continued with continued bacterial excretion and with negative clinical and radiological dynamics of the disease until data on drug resistance of Mycobacterium tuberculosis are obtained.

If, by the end of the intensive phase of treatment, bacterial excretion continues by smear microscopy and sputum culture, and drug resistance to aminoglycosides, isoniazid, or rifampicin is detected, then changes in the chemotherapy regimen are made. At the same time, those main drugs remain, to which the sensitivity of Mycobacterium tuberculosis has been preserved, and additionally introduced into the regimen of at least 2 reserve chemotherapy drugs, leads to an extension of the intensive phase for another 2-3 months. Possible schemes and regimens of chemotherapy in these cases are given in Table 2.

The indication for the continuation phase of treatment is the cessation of bacterial excretion by smear microscopy and sputum culture and positive clinical and radiological dynamics of a specific process. While maintaining the sensitivity of Mycobacterium tuberculosis, treatment continues for 5 months (150 doses) with 3 drugs: isoniazid, rifampicin, ethambutol (5 H R E) daily or intermittently 3 times a week (5 H3 R3 E3). The total duration of treatment is 8-9 months.

In patients who have epidemiological (high level of MBT resistance to isoniazid and rifampicin in this region), anamnestic (contact with patients known to the dispensary who excrete MBT with multidrug resistance), social (homeless people released from penitentiary institutions) and clinical ( patients with acutely progressive tuberculosis, inadequate treatment at previous stages with the use of 2-3 drugs, interruptions in treatment) grounds for the assumption of multidrug resistance of Mycobacterium tuberculosis is possible in the intensive phase for 3 months, the use of an empirical chemotherapy regimen consisting of isoniazid, rifampicin (rifabutin), pyrazinamide, ethambutol kanamycin (amikacin, capreomycin) and fluoroquinolone.

With multiple MBT resistance to isoniazid and rifampicin, the patient is assigned an individualized treatment regimen according to the 4th category.

To the 3rd category include patients with newly diagnosed small forms of pulmonary tuberculosis (up to 2 segments long) with no isolation of Mycobacterium tuberculosis during sputum smear microscopy. Basically, these are patients with focal, limited infiltrative tuberculosis and tuberculomas.

During the 2-month intensive phase of chemotherapy, 4 anti-TB drugs are used: isoniazid, rifampicin, pyrazinamide, and ethambutol (2 H R Z E). The introduction of the fourth drug of ethambutol into the chemotherapy regimen is due to the high initial resistance of Mycobacterium tuberculosis to streptomycin.

The intensive phase of chemotherapy lasts 2 months (60 doses). If a positive MBT culture result is obtained, and the sensitivity result is not yet ready, treatment continues until MBT drug sensitivity is obtained, even if the duration of the intensive phase of treatment exceeds 2 months (60 doses).

The indication for the continuation phase of treatment is the pronounced clinical and radiological dynamics of the disease. Within 4 months (120 doses), chemotherapy is carried out with isoniazid and rifampicin both daily (4 H R), and in an intermittent regimen 3 times a week (4 H3 R3) or 6 months with isoniazid and ethambutol (6 H E). The total duration of treatment is 4-6 months.

To the 4th category include patients with tuberculosis who excrete multidrug-resistant mycobacteria. The vast majority of them are patients with fibrous-cavernous and chronic disseminated tuberculosis, with the presence of destructive changes, a relatively small part are patients with cirrhotic tuberculosis and the presence of destruction.

Before starting chemotherapy, it is necessary to clarify the drug sensitivity of mycobacteria according to previous studies, as well as during the examination of the patient before starting treatment. Therefore, it is desirable to use accelerated methods of bacteriological examination of the obtained material and accelerated methods for determining drug sensitivity, including using BACTEC and the direct method of bacteriological examination.

Treatment is carried out according to individual chemotherapy regimens according to the data on drug resistance of Mycobacterium tuberculosis and should be carried out in specialized anti-tuberculosis institutions, where centralized quality control of microbiological studies is carried out and the necessary set of reserve anti-TB drugs is available, such as kanamycin, amikacin, prothionamide (ethionamide), fluoroquinolones, cycloserine, capreomycin, PAS.

The intensive phase of treatment is 6 months, during which a combination of at least 5 chemotherapy drugs is prescribed: pyrazinamide, ethambutol, fluoroquinolones, capreomycin (kanamycin) and prothionamide (ethionamide). In this regard, due to the likely low efficiency of using a combination of reserve drugs, as well as relapses of tuberculosis caused by a multidrug-resistant pathogen, chemotherapy is carried out for at least 12-18 months. At the same time, patients are advised to take medications daily and not to use reserve drugs in an intermittent regimen, since there are no clinical trials confirming this possibility.

With resistance to ethambutol, pyrazinamide and / or another drug, a change to cycloserine or PAS is possible.

The intensive phase should continue until a positive clinical and radiological dynamics and negative smears and sputum cultures are obtained. During this period, artificial pneumothorax and surgical treatment is an important component of the treatment of drug-resistant pulmonary tuberculosis with multiple resistance of mycobacteria, but a full course of chemotherapy must be carried out.

The indication for the continuation phase of treatment is the cessation of bacterial excretion by smear microscopy and sputum culture, positive clinical and radiological dynamics of a specific process in the lungs and stabilization of the course of the disease.

The drug combination must consist of at least 3 reserve drugs, such as ethambutol, prothionamide, and a fluoroquinolone, used for at least 12 months (12 E Pr Fq).

The total duration of treatment for patients of the 4th category is determined by the rate of involution of the process, but not less than 12-18 months. Such a long period of treatment is due to the task of achieving stable stabilization of the process and the elimination of bacterial excretion. At the same time, it is very important to provide long-term treatment of such patients with reserve anti-tuberculosis drugs.

In conclusion, it should be noted that Chemotherapy currently remains one of the leading methods of complex treatment of patients with tuberculosis. . However, it should be borne in mind that not all patients can withstand the standard regimen for a certain time, and the main reasons for the withdrawal of one or more drugs are the resistance of mycobacteria to these drugs and their intolerance.

In this regard, at present, at the initial stage of treatment, it is customary to use the standard regimen, with its subsequent correction depending on the dynamics of the disease. If by the end of the intensive phase of treatment there is a positive dynamics of the process (significant or partial resorption of infiltrates in the lungs, a decrease in the mycobacterial population and taking into account the good tolerability of all prescribed drugs), then treatment is continued according to chemotherapy categories. In the absence of an effect during the intensive phase of treatment, it is necessary to clarify the reason for this.

With the development of drug resistance of Mycobacterium tuberculosis to the drug (drugs), it is necessary to replace it and extend the duration of chemotherapy. In the event of unrecoverable adverse reactions, the method of administration of the drug should also be changed or replaced with another, alternative one. Correction of chemotherapy determines an individual approach to the patient and entirely depends on the specific conditions.

For the treatment to be successful, it is necessary to prescribe several drugs. The first thing encountered in 1946, when starting to treat tuberculosis with streptomycin, was relapse due to the development of drug resistance in the pathogen. With the introduction of multiple drugs, especially isoniazid in combination with rifampicin, the risk of drug resistance has been significantly reduced. Despite the fact that the majority of rapidly multiplying mycobacteria die fairly quickly after the start of treatment, it should be long and continuous, as there are still persistent, slowly multiplying or latent mycobacteria, which take time to destroy.

Several large clinical trials supported by the US Department of Health and Human Services and the British Council for Medical Research have shown that treatment for pulmonary tuberculosis can be continued for 6 months with a three-drug combination for the first 2 months and isoniazid and rifampicin alone for another 4 months. At the first stage, the drugs should be prescribed daily, in the future - it can be twice a week. In these trials, cure was achieved in more than 95% of cases, and the relapse-free period lasted at least a year. According to the test results, a standard treatment regimen was approved: for 2 months - isoniazid, rifampicin and pyrazinamide daily, for the next 4 months - isoniazid and rifampicin daily or 2-3 times a week.

In case of intolerance to pyrazinamide, isoniazid is prescribed in combination with rifampicin for 9 months; in case of intolerance to isoniazid or rifampicin, or if the pathogen is resistant to any of these drugs, two more are additionally prescribed, usually ethambutol and streptomycin, and treatment is continued for 12-18 months. The same schemes can be used for extrapulmonary tuberculosis. It is believed that the treatment of HIV-infected people should last at least 9 months, although it is possible that the usual course will be sufficient.

The choice of drugs is influenced by the sensitivity of the pathogen. In 1997, in the United States, 7.8% of strains of Mycobacterium tuberculosis were resistant to isoniazid, 1.4% of strains were resistant to both isoniazid and rifampicin. These figures were significantly higher in California, Florida, New Jersey, and New York City; in 35 states, the proportion of isoniazid-resistant strains was at least 4%. In areas where the prevalence of isoniazid-resistant strains exceeds 4% or is not known, a fourth drug, ethambutol or streptomycin, is added as a first step. After assessing the sensitivity of the pathogen, the scheme is corrected: if the sensitivity is preserved, they return to the usual scheme; if the pathogen is resistant to isoniazid or rifampicin, the course of treatment is extended to 18 months.

Repeated treatment in the absence of effect and treatment of multidrug-resistant tuberculosis are not within the competence of a general practitioner. The resistance of Mycobacterium tuberculosis to both isoniazid and rifampicin complicates treatment: less effective and more toxic drugs have to be prescribed and the duration of the course has to be increased.

To achieve the desired effect and avoid adverse events, it is necessary to monitor the patient during treatment. He should be to the doctor at least once a month to assess the manifestations of the disease and complications of treatment.

In case of pulmonary tuberculosis, sputum examination is carried out: first monthly for 3 months or until a negative result is obtained, then at the end of treatment and after another 3-6 months. A chest x-ray is desirable but not required. Much more important indicators of success in treatment are the patient's condition and bacteriological examination data. The X-ray picture, of course, should improve in the course of treatment, but such pronounced changes as, for example, the closure of cavities, are not at all necessary. Before starting treatment, it is recommended to conduct a complete blood count, determine the level of BUN, the activity of liver enzymes, the level of uric acid (before prescribing pyrazinamide), and also examine vision (before prescribing ethambutol). Since all three major drugs are hepatotoxic, liver enzyme activity should be measured monthly. With a moderate increase in these indicators, treatment can be continued, since in the future they often normalize, but it is necessary to carefully monitor the patient.

The main reason for the ineffectiveness of treatment is non-compliance with the doctor's prescriptions. It is useful to talk to the patient, explain to him the nature of the disease and the need to continue treatment long after the condition has improved.

Another effective method is the system of supervised outpatient therapy: the most conscientious member of the family or person caring for the patient gives him pills before each appointment and makes sure that the patient takes them. The method is most convenient when the drugs are taken 3 times a week, and will suit any patient from whom one can expect a frivolous attitude to treatment. These, apparently, include drug addicts and alcoholics. The socioeconomic status or level of education does not allow one to assume how conscientiously the patient will treat treatment. Given the danger of a resurgence of tuberculosis, where less than 90% of patients comply with the doctor's prescriptions (that is, everywhere), it is recommended that all treatment be carried out under direct observation.

Compulsory treatment is rarely used. Anything that simplifies treatment (for example, cutting down on medications to two or three times a week) helps keep prescriptions going. When using combined drugs (rifampicin / isoniazid or rifampicin / isoniazid / pyrazinamide), the patient willy-nilly has to take everything that is prescribed to him. Very often, pyridoxine is additionally prescribed to prevent such a rare side effect of isoniazid as neuropathy. In this case, the patient may start taking only the vitamin; therefore, the appointment of pyridoxine may not be beneficial, but harmful. The best tactic is not to complicate the treatment.

This information is intended for healthcare and pharmaceutical professionals. Patients should not use this information as medical advice or recommendations.

A new method of treating tuberculosis is not only a major breakthrough, but also a serious challenge to fundamental phthisiology

Today, the whole world is flying around reports that, according to American scientists . The results of a major international study were released at the American Society of Thoracic Medicine convention in Denver, Colorado, May 13-18, 2011.

M.D. Kevin Fenton ( Kevin Fenton is the director of National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention) called these results "the biggest breakthrough in the treatment of latent TB since the 1960s." This conclusion is not subject to any doubt, because facts are stubborn things.

As the authors note, the essence of the new method lies in the fact that latent tuberculosis can be effectively combated with the help of a three-month, and not three times longer, as is currently practiced, course of treatment. And drugs can be taken not daily, but once a week, but only in large doses. This is a very significant reduction in terms and doses in the treatment of tuberculosis.

For classical phthisiology, this is a state of shock, and here's why. This is a blow to the generally accepted treatment protocols, because the best has been found. And secondly, before the discovery of this method, scientific phthisiology obliged to follow the treatment protocol with the obligatory daily intake of a number of drugs. Nothing else was discussed.

Scientists explained that irregular use, as a form of improper treatment, does more harm than good, as it turns an easily curable form of the disease into a difficult to cure drug-resistant tuberculosis. It was considered scientifically proven that if you do not take drugs for only one week, then tuberculosis mycobacteria develop immunity to antibiotics. But what about now, after the discovery of a new method? After all, according to this method, antibiotics are not given for a week. In this case, not only does resistance not arise, but, on the contrary, an accelerated cure occurs. The results of an international study showed that almost the only scientific explanation for the occurrence of incurable tuberculosis has been refuted. And the nature of the emergence of resistant and incurable tuberculosis remains undiscovered.

Taking into account the decrease in the weekly dose and the threefold reduction in the duration of treatment, this situation inevitably leads to a decrease in the number of drugs consumed by at least 6 times. This decrease will affect not only the clinic, but also the pharmaceutical industry, as it will lead to a sharp decrease in the production of drugs. But on the other hand, and this is the main thing, nothing is as valuable as human life. For pharmaceuticals, there is a way out - this is work on new generation drugs.

If you carefully analyze the presented method, then there is a clear contradiction with the protocols for the treatment of infectious diseases - a positive effect is achieved not with daily antibiotics, as is customary, but, on the contrary, with a significant reduction in their intake to 1 day a week.

Let's remember the introduction of the DOTS treatment protocol at one time. What was great about this method? Its highlight was that the usual daily dose of antibiotics has been reduced which significantly improved the results of treatment. Until now, there is no proper scientific explanation for the best performance using DOTS. By the way, a considerable number of TB scientists still object to DOTS. Opponents of reducing the daily dose of DOTS today also failed, because their scientific explanation, as mentioned above, has failed. It turns out that what they opposed gives a significant effect of recovery and a reduction in terms by 3 times.

An evidence-based antibiotic treatment protocol is based on an appropriate continuous daily intake. As a rule, the main factors in calculating the doses taken are the time during which the antibiotic can maintain the ability of the therapeutic effect and the time the antibiotic is stored in the body. The antibiotic is excreted by the body on average within 1-3 days.

As already noted, according to the protocol, daily intake is not recommended to be interrupted. For in this case, as science explains, not only do mycobacteria develop immunity to antibiotics, but their effect on the bacterium is interrupted, and it is activated. But why, then, is there a positive effect when taking antibiotics just once a week? There is no need to prove that the effect of antibiotics on bacteria is interrupted in this case. This means that during the week there is a mandatory activation of the bacteria, and it must inevitably complicate the course of the process.

But at the same time, not only does the condition not worsen, but, on the contrary, the cure comes much faster. So, based on the theory of tuberculosis, no activation of the bacterium occurs. But this is against the rules. How can the positive effect be scientifically explained? And why does the damaging activation of bacteria not occur in the interval of reception?

No maximum single dose is able to work for a week! The body will remove it long before the end of the week. Based on the foregoing, the only correct conclusion can be drawn - the basis of the positive effect, which is proven in the process of a large international study, is something other than what is usually explained in terms of the generally accepted theory of tuberculosis.

A paradoxical situation arises. When an antibiotic is prescribed daily, it works so poorly that the effect can be achieved in only 9 months. But, when the antibiotic is taken only once a week, then this technique works effectively and the result comes three times faster. This result is inexplicable from the point of view of conventional logic. What is this phenomenon? The facts convincingly compel us to once again carefully reconsider our attitude towards mycobacteria.

It becomes obvious that the antibiotic also raises doubts and questions. What kind of hidden reserves suddenly wake up in antibiotics? Everyone is well aware that if the antibiotic had an effect after 9 months of daily use, then reducing the doses and switching from daily to weekly intake should undoubtedly lead to an adequate increase in the duration of treatment. This is the nature of any physical and chemical process. But the opposite happens. Reducing the dose of antibiotic leads to a reduction in the recovery time! According to the logic of things, the corresponding conclusion is born - it means that the nature of the cure for tuberculosis does not consist in the effect of an antibiotic on a bacterium. This conclusion is still under the question mark and is not perceived by our consciousness.

Based on the foregoing, it becomes obvious that hidden reserves are activated in something else, but not in the antibiotic-bacteria combination. Those. trigger factor in the decline up to three times terms of treatment, as it may seem strange, is not the elimination of Koch's wand. Facts must be accepted, even if we don't like the results. For some reason, no one wants to ask the question - what can be the trigger in the cure of tuberculosis, if it is not a bunch of antibiotic-bacteria?

Why is there a lot of “buts” around most of the results obtained in phthisiology and no one stubbornly wants to pay attention to this? Today, no one hides the fact that fundamental phthisiology has no explanations for the fundamental positions in the theory of tuberculosis. Or maybe this is the reason that methods that reduce doses, which are significantly different from those generally accepted in phthisiology, give much better results.?

A year ago, after my report on problematic issues at a scientific conference at the National Institute of Phthisiology and Pulmonology named after F.G. Yanovsky in Kyiv, an agreement was reached to conduct joint research on the treatment of not only latent, but also resistant forms of tuberculosis using a new technique. Several follow-up meetings took place, but no agreement could be reached on the substance of the research. The main reason is a significant departure from existing treatment protocols. And for some reason, no one wants to be the first in this and take responsibility for themselves. TB doctors are very afraid of experiments that can destroy old dogmas . Whether they want it or not, life dictates different conditions.

While we were negotiating and deciding whether to conduct clinical trials or not, the Americans were ahead. Our methodology suggested an even more significant departure from the existing principles of treatment than American scientists suggest. They have always been at the forefront and have never been afraid to break the generally accepted dogmas. Americans must be given their due.

There is no doubt that, just as they did against DOTS, many TB doctors will fight against the new treatment that is being unveiled at the convention of the American Society of Thoracic Medicine. But it is impossible not to recognize that this method is much more effective than all those that have been used since the 1960s. And the most important thing that no one wants to talk about is that the new method significantly reduces the negative impact on the whole body and the occurrence of intoxication compared to the conventional ones. It is impossible to remain silent about the fact that this method is the most gentle and its use does not allow to exclude relapses and cure resistant patients. This is easy to confirm experimentally. Of course, the direction in which the Americans are moving can be considered the beginning of a new path to create fundamentally new methods of treating tuberculosis.

It cannot be overlooked that the new method is not only the biggest breakthrough in the treatment of tuberculosis, but at the same time it is a serious challenge to the fundamental theory.

So what is the secret to a significant reduction in healing time? Naturally, here it is necessary to reconsider once again the fundamental foundations of tuberculosis and their correspondence to the actual results. Why do supporters of the old positions balk? This is an eternal question and an eternal confrontation. It has always been easier for a person to pretend that he does not notice indisputable facts point-blank than to admit his mistakes.

The facts leave no choice. Not so long ago, already in this millennium, scientists were forced to admit that since the discovery of Koch's wand, no one has yet been able to simulate tuberculosis in animals . Probably, this caused a similar shock for many phthisiatricians, because in the light of the old theory this is not yet perceived, or simply not noticed.

No one wants to pay attention to the fact that inadequate modeling calls into question the fundamental provisions of the tuberculosis theory. But the whole theory, including methods of treatment, was based solely on experimental evidence obtained by "failed modeling." As a result, the methods of treatment are also “unsuccessful”. Maybe that's why incurable forms of tuberculosis have arisen, and methods that significantly reduce the number of doses of antibiotics give better results?

If non-tuberculosis arose in the model, then for which disease were the treatment protocols developed that are used in the treatment of tuberculosis and are rigorous? We must immediately assess the situation in which science finds itself.

The last time is significant in that the actual results that destroy the old dogma are more and more clearly manifested. Once again, it has been proven that methods with significantly reduced doses of antibiotics are most effective. And the principle - "a certain daily dose of an antibiotic is necessary to defeat an infection" is perfectly observed in relation to any other infections, but not tuberculosis.

Why does no one want to hear that the results of research, especially in recent years, convincingly show that the immune system of a TB patient behaves differently from how it behaves in relation to other infectious diseases?

With each new result, more and more contradictions and questions arise, which science continues to classify as "unresolved" and "unknown nature". For some reason, we hope that we can solve the problem and get out of a difficult situation without having answers to these questions. This is a false opinion. Until fundamental phthisiology reveals the nature of facts that have no scientific explanation and are confirmed in experiment, until then it will not be possible to cope with the problem of tuberculosis. Whether we like it or not, life will still force us to solve those issues that no one wants to remember and hear about.

In conclusion, I would like to recall the words of the great Rudolf Virchow. The whole world bows before this famous German scientist, because he is given tribute as the founder of the scientific direction in medicine, as the founder of the cell theory in biology and medicine, as a reformer of scientific and practical medicine, as the founder of modern pathological anatomy.

For some reason, referring this scientist to the indisputable authorities of medicine and paying tribute and respect to him, we do not want to listen to his great words: “If I could live my life again, I would devote it to trying to find evidence that pathological tissue is the natural habitat of microbes , instead of considering them as the cause of pathological tissue damage. In the original English - "If I could live my life over again, I would devote it to proving that germs seek their natural habitat - diseased tissue - rather than being the cause of the diseased tissue". Of course, not all pathogenic microbes are discussed in this statement, but only those whose behavior is inadequate to the general signs of infectious bacteria.. Why not test his hypothesis experimentally? Sometimes scientists answer that no one has done this yet and it is not known how to do it. But this must be done, because there is no other way out!

Undoubtedly, Rudolf Virchow had great intuition, and, apparently, he had good reason to say so. It must be admitted that his words were prophetic. During the development of phthisiology, other researchers also made similar conclusions, which were in clear contradiction with generally accepted dogmas. As a rule, they were rejected.

Why? There is only one reason - many conclusions were made intuitively, and they did not have a proper scientific explanation and were not tested experimentally, because at one time the researchers did not know how to do this. Today the time has come when life requires an experimental verification of R. Virchow's conclusion. And this can already be done experimentally, because. an appropriate methodology has been developed.

By the way, the positive results obtained in the course of a major international study on a significant reduction in the duration of treatment of latent patients can also be confirmed by real science-based experiments.

So why not embody the desire and direction that Rudolf Virchow wanted to master in relation to, for example, Koch's wand, and continue the work he started? What if he turns out to be right? This will not only remove a lot of ambiguities and contradictions in fundamental phthisiology, but will also allow reaching a fundamentally new stage in development, both in scientific and clinical phthisiology. This will provide a new field for pharmacists to develop new drugs.

With respect to the reader, Petr Savchenko

Tuberculosis can be caused by two members of the family Mycobacteriaceae detachment Actinomycetales: M.tuberculosis and M. bovis. In addition, it is sometimes mentioned M. africanum microorganism that is intermediate between M.tuberculosis and M. bovis and in rare cases is the cause of tuberculosis on the African continent. The above microorganisms are combined into a complex M.tuberculosis, which is actually a synonym M.tuberculosis, since the other two microorganisms are relatively rare.

Man is the only source M.tuberculosis. The main mode of transmission of infection is the airborne route. Rarely, the infection may be due to the consumption of milk contaminated with M. bovis. Cases of contact infection in pathologists and laboratory personnel are also described.

Usually, long-term contact with the bacteria is necessary for the development of infection.

Choice of therapy regimen

Clinical forms of tuberculosis have little effect on the method of chemotherapy, more important is the size of the bacterial population. Based on this, all patients can be divided into four groups:

I. Patients with newly diagnosed pulmonary TB (new cases) with positive smear results, severe abacillary pulmonary TB and severe forms of extrapulmonary TB.

II. This category includes people with a relapse of the disease and those for whom treatment did not give the expected effect (sputum smear positive) or was interrupted. At the end of the initial phase of chemotherapy and with a negative sputum smear, they proceed to the continuation phase. However, if mycobacteria are detected in sputum, the initial phase should be extended for another 4 weeks.

III. Patients with pulmonary tuberculosis with limited parenchymal involvement and negative sputum smears, as well as patients with non-severe extrapulmonary tuberculosis.

A significant proportion of this category are children, in whom pulmonary tuberculosis almost always occurs against the background of negative sputum smears. The other part is made up of patients infected in adolescence who developed primary tuberculosis.

IV. Patients with chronic tuberculosis. The effectiveness of chemotherapy in this category of patients, even at present, is low. It is necessary to use reserve preparations, the duration of treatment and the percentage of HP increase, a high voltage is required from the patient himself.

Therapy regimens

Standard ciphers are used to designate treatment regimens. The entire course of treatment is reflected in the form of two phases. The number at the beginning of the cipher indicates the duration of this phase in months. The number at the bottom after the letter is placed if the drug is prescribed less than 1 time per day and indicates the frequency of administration per week (for example, E 3). Alternative drugs are indicated by letters in brackets. For example, the initial phase of 2HRZS(E) means daily isoniazid, rifampicin, pyrazinamide in combination with either streptomycin or ethambutol for 2 months. After completion of the initial phase with a negative result of sputum smear microscopy, proceed to the continuation phase of chemotherapy. However, if after 2 months of treatment mycobacteria are detected in the smear, the initial phase of treatment should be extended by 2-4 weeks. In the continuation phase, for example 4HR or 4H 3 R 3 , isoniazid and rifampicin are used daily or 3 times a week for 4 months.

Table 3 Example of quadruple therapy for tuberculosis (in adults)
directly observed, including 62 doses of drugs

CHEMOTHERAPY REGIMENS LESS THAN 6 MONTHS

Some researchers report good results of 4- and even 2-month courses of chemotherapy for mild forms of tuberculosis. However, most experts do not recommend stopping treatment earlier than 6 months.

THERAPY FOR MULTIPLE-RESISTANT TUBERCULOSIS

In each specific case, it is desirable to determine the sensitivity of mycobacteria to anti-tuberculosis drugs. In case of detection of resistance to drugs of the first line, alternative drugs are used, such as fluoroquinolones (ofloxacin, ciprofloxacin), aminoglycosides (kanamycin, amikacin), capreomycin, ethionamide and cycloserine.

REPEATED COURSE OF THERAPY

The approach to a second course of therapy depends on the following circumstances:

1. Relapse after sputum negativeization usually indicates that previous treatment was stopped prematurely. At the same time, in most cases, the sensitivity of the pathogen is preserved and a positive effect is observed when prescribing standard initial therapy.
2. Relapse is due to resistance to isoniazid. In this case, a second course of chemotherapy with rifampicin is prescribed in combination with two other anti-tuberculosis drugs, to which sensitivity is preserved, for a total duration of 2 years.
3. Relapse after irregular use of anti-TB drugs is often caused by resistant mycobacteria. In this case, it is necessary to determine the sensitivity as soon as possible and prescribe drugs, the sensitivity to which is preserved.
4. With suspected resistance, a change in the therapy regimen is made with the use of drugs, the sensitivity to which is presumably preserved.
5. Multiple resistance to the most "powerful" drugs -