Tuberculosis - I.T. Pyatnochka 2005

Treatment of Tuberculosis
Basic principles and methods of tuberculosis treatment

Antimycobacterial therapy is the cornerstone of Treatment for patients with tuberculosis of any localization, adhering to several key principles:

1. Early and timely treatment, which should be initiated in the Cytology/cytology/16.html">Early stages of tuberculosis development and immediately upon detection. With early Diagnosis of tuberculosis, recovery occurs in 100% of cases; with timely diagnosis, in 95-100%; with untimely diagnosis, in 89%; and with late diagnosis, in 10-15% of patients.

2. Duration of treatment. The effectiveness of treatment for tuberculosis patients depends on its duration. The optimal duration of the main course ranges from 6 to 18 months. The action of antimycobacterial drugs is predominantly bacteriostatic; therefore, premature discontinuation of treatment leads to the reversion of persistent MBT into their original forms and The Emergence of exacerbations and relapses of the specific process.

3. Continuity of treatment. Interruptions in taking antimycobacterial drugs lead to The Development of drug resistance in MBT.

4. Multi-stage treatment includes: inpatient + sanatorium + outpatient treatment. Typically, inpatient care (at a TB hospital) begins with an intensive, daily treatment regimen lasting 2-3 months using 3-4 anti-TB drugs. At the Second Stage (4-8 months), once the MBT population has drastically decreased, treatment may be continued with two drugs, specifically using an intermittent method.

5. Combination Chemotherapy. Monotherapy with any single drug is fundamentally futile, as it rapidly leads to the development of drug resistance in MBT. Only the simultaneous use of 3-4 anti-TB drugs can prevent the development of drug resistance in MBT. The combination must include isoniazid, rifampicin, streptomycin, or ethambutol or pyrazinamide. These drugs are effective in 95% of cases.

6. Controlled chemotherapy. Treatment for tuberculosis patients must be supervised, as patients often irregularly or arbitrarily discontinue treatment. In the hospital, patients must take antimycobacterial drugs under the supervision of medical staff, while during outpatient intermittent treatment, this is managed by the dispensary. All of this helps to increase treatment effectiveness by 10-15%.

7. Comprehensive treatment. This involves a combination of chemotherapy with antimycobacterial drugs, pathogenetic agents, and surgical intervention. Pathogenetic agents include antihistamines and hormonal drugs, Vitamins B₁ and B₆, antioxidants, proteinase inhibitors, tuberculin, immunomodulators, and biogenous stimulants. Additionally, phyto-, api-, and phytoncide therapy are employed.

Surgical treatment for tuberculosis patients includes the following Methods: 1) radical Procedures (various types of lung resection, pleurectomy); 2) collapse surgery (thoracoplasty); 3) collapse therapy (therapeutic pneumothorax, pneumoperitoneum); 4) intermediate procedures (cavernostomy, cavity drainage).

For the treatment of Pulmonary Tuberculosis, the most effective chemotherapy regimen must be applied, appropriate to the extent of the process, the presence of a breakdown cavity, bacterial excretion, as well as prior treatment history and the susceptibility of MBT to antimycobacterial drugs.

An important criterion for treatment effectiveness is the cessation of bacterial excretion and the healing of breakdown cavities.

In newly diagnosed mild forms of tuberculosis without bacterial excretion, after a two-month (initial phase) intensive treatment with three antimycobacterial drugs (isoniazid, rifampicin, streptomycin, or pyrazinamide), two drugs are prescribed daily or in an intermittent regimen for another 4 months (continuation phase). Thus, the main course of treatment lasts 6-8 months.

In newly diagnosed destructive pulmonary tuberculosis, treatment During the first two months is carried out with four antimycobacterial drugs, followed by three chemical drugs until the cavity heals. Afterwards, treatment is continued with two chemical drugs for 2-4 months. Consequently, the main course of antimycobacterial therapy lasts 6-12 months.

Following a successfully completed main course of treatment, Chemoprophylaxis with anti-TB drugs after the completion of the main chemotherapy course is performed only in risk groups.

In patients with reactivation (exacerbation, relapse) of pulmonary tuberculosis, taking into account potential resistance of mycobacteria to one or several drugs, 5 antimycobacterial drugs (isoniazid, rifampicin, streptomycin (for 2 months), pyrazinamide, ethambutol) are used in the initial 3-month phase of treatment. Following the successful completion of the initial phase of antimycobacterial therapy, the continuation phase is initiated with two or three drugs (preferably isoniazid, rifampicin, pyrazinamide, or ethambutol) for 4-8 months.

Antimycobacterial therapy for previously treated patients with chronic forms of pulmonary tuberculosis is strictly individualized (4-6 drugs) taking into account various factors, primarily the drug susceptibility of mycobacteria, their tolerability, complications, and comorbid pathology. The average duration of treatment is 18-20 months.

Overall, etiotropic treatment for tuberculosis patients is conducted in a differentiated manner, depending on the clinical form of tuberculosis, drug tolerability, and mycobacterial susceptibility. According to world literature, the most effective regimens are those recommended by the WHO, which have proven successful in tens of thousands of patients worldwide. Therefore, these chemotherapy regimens are recommended for use in our practice, as they are also provided for by the current order of the Ministry of Health of Ukraine.

Antimycobacterial therapy, as noted, consists of two phases: the initial (intensive) phase and the continuation (maintenance) phase, and all patients are divided into four categories for which the WHO recommends appropriate treatment regimens.

Treatment of Category I patients. Category I includes newly diagnosed pulmonary tuberculosis patients with bacterial excretion and newly diagnosed patients with extensive (2 or more segments) and severe forms of tuberculosis. This category also includes patients with Tuberculous meningitis, tuberculous pericarditis, Peritonitis, Pleurisy, spinal tuberculosis with neurological complications, pulmonary tuberculosis without bacterial excretion involving destructive parenchymal lesions, and Tuberculosis of the digestive, urinary, and reproductive Organs.

Category I patients in the intensive phase are prescribed 4 first-line anti-TB drugs daily: isoniazid, rifampicin, pyrazinamide, streptomycin, or ethambutol.

In extensive and severe forms of tuberculosis, as well as when There is a high probability of primary drug resistance of MBT, 5 anti-TB drugs are used: isoniazid, rifampicin, and streptomycin daily, while pyrazinamide and ethambutol are given every other day or 3 times a week (for example, pyrazinamide on even days, ethambutol on odd days).

The intensive phase lasts for at least two months. During this period, the patient must receive 60 doses of first-line anti-TB drug combinations. In case of missed doses, the duration of the intensive phase is extended until 60 doses are completed.

Two months after THE START OF treatment, the decision on transitioning to the next phase of treatment is made by the medical advisory commission (MAC) based on clinical, radiological, and microbiological data.

If bacterial excretion persists after 2 months of treatment (according to sputum Cell/15.html">Microscopy data), the intensive phase of chemotherapy is extended for 1 month (30 doses) until data on MBT drug susceptibility are obtained. Depending on the results, the chemotherapy is adjusted and the intensive phase of treatment is continued.

If sputum microscopy results are negative after 2 months of chemotherapy and positive clinical and radiological dynamics are observed, the maintenance phase of treatment is initiated.

During The First stage of the continuation phase, patients typically receive isoniazid and rifampicin daily for 1-2 months, while pyrazinamide and ethambutol are administered either on alternate days or 3 times a week. Over the final 3 months of the continuation phase, 2-3 drugs, including isoniazid and rifampicin, are prescribed on a daily or intermittent basis.

In cases of limited lesions and favorable clinical progress during the initial 2 months of the intensive phase, the 4-month continuation phase may consist of just 2 drugs—isoniazid and rifampicin—administered daily or intermittently.

The total duration of the continuation phase is 4-5 months for pulmonary tuberculosis, 5-6 months for Extrapulmonary tuberculosis, and 8-12 months for tuberculous meningoencephalitis and Miliary tuberculosis.

Treatment of Category II patients. Category II includes patients with pulmonary and extrapulmonary tuberculosis requiring retreatment (those previously treated for more than 1 month), specifically relapse cases (with or without bacteriologically confirmed tuberculosis), treatment after default, and treatment after failure.

Category II patients with a low risk of drug resistance are prescribed 5 first-line drugs—isoniazid, rifampicin, pyrazinamide, streptomycin, and ethambutol—daily. After 2 months (60 administered doses), therapy is continued with 4 drugs (isoniazid, rifampicin, pyrazinamide, and ethambutol) daily for 1 month (30 doses). The total duration of the intensive phase is at least 3 months (90 combined drug doses). If full doses are missed, treatment is extended until 90 doses have been taken.

If sputum microscopy yields negative results after 3 months of chemotherapy and clinical and radiologic findings show improvement, the continuation phase is initiated. By this time, drug susceptibility test results are typically available, which may necessitate adjustments to the regimen. If M. tuberculosis is susceptible to all anti-tuberculosis drugs, patients receive isoniazid, rifampicin, and either ethambutol or pyrazinamide daily or intermittently for 5 months. The total duration of treatment is generally 8 months.

Category II patients with a high risk of drug resistance are prescribed treatment incorporating second-line anti-tuberculosis drugs.

During the intensive phase, patients receive 4 first-line anti-tuberculosis drugs (isoniazid and rifampicin (rifabutin) daily, pyrazinamide and ethambutol intermittently) alongside 2 second-line drugs daily, determined by regional drug resistance patterns.

Further treatment is adjusted based on M. tuberculosis drug susceptibility data and continued through the end of the intensive phase (3 months) using at least 5 drugs to which susceptibility is retained. Subsequently, the continuation phase employs at least 3 first- and second-line drugs for 56 months.

Treatment of Category III patients. This category comprises patients with newly diagnosed limited pulmonary tuberculosis (involving fewer than 2 segments) without bacteriologically confirmed tuberculosis, as well as those with newly diagnosed extrapulmonary tuberculosis not included in Category I. It also includes children with tuberculous intoxication, tuberculous lymphadenopathy, or Primary tuberculosis complex in the calcification phase, provided the disease process remains active.

Category III patients are prescribed 3 first-line anti-tuberculosis drugs—isoniazid, rifampicin, and pyrazinamide (or ethambutol)—daily for the 2-month intensive phase, during which the patient must complete 60 doses of the drug combinations. If any doses are missed, the intensive phase is extended until a total of 60 doses is reached.

Upon favorable clinical and radiologic improvement, the continuation phase of chemotherapy is initiated, consisting of 2 anti-tuberculosis drugs (isoniazid and rifampicin, administered daily or intermittently) for 4 months.

At the dawn of the third millennium, the paradigm of treating newly diagnosed patients exclusively in hospital settings was reconsidered. The social profile of newly diagnosed patients is quite diverse: many struggle with alcohol or drug addiction or lead antisocial lifestyles, whereas others are white-collar professionals, civil servants, or individuals with higher and specialized secondary education. Consequently, patients constantly polarize into those motivated to recover and those who fail to adhere to medical advice and prescriptions even while hospitalized. Under these circumstances, routine hospitalization of all newly diagnosed patients is impractical. Moreover, inpatient care is approximately three times more expensive than outpatient treatment. In addition, modern phthisiatric clinics offer few diagnostic procedures that strictly mandate hospitalization.

The Structure/175.html">Implementation of modern chemotherapy regimens for uncomplicated pulmonary tuberculosis enables the rapid cessation of bacterial excretion within just 3 to 4 weeks. Patients who shed Bacteria prior to diagnosis and at the outset of treatment pose a high risk to their contacts. Therefore, epidemiological indications for hospitalization are justified only in cases of massive bacterial shedding and drug-resistant mycobacteria.

Highly effective chemotherapy regimens not only significantly shorten treatment duration but also allow for the broader use of intermittent drug administration, which is both effective and convenient in outpatient settings.

Prolonged inpatient treatment tends to render patients passive and unengaged in their own recovery, often leading them to refuse recommended surgical interventions despite clear indications and feasibility.

In global clinical practice, outpatient chemotherapy for newly diagnosed pulmonary tuberculosis has become widespread. Studies indicate that approximately 25% of patients require inpatient care, making outpatient treatment the preferred model of care.

Arguments in favor of outpatient treatment include:

- Prevention of cross-infection within the hospital and nosocomial acquisition of drug-resistant M. tuberculosis strains,

- prevention of potential psychological deterioration associated with prolonged hospitalization,

- reduced cost of care.

Thus, outpatient antimycobacterial therapy is becoming the primary organizational framework for treating uncomplicated cases. A well-founded step toward this model is the day hospital, which accommodates an increasing number of patients. In such facilities, patients remain under medical supervision during the day, take their medications, undergo necessary examinations, and receive therapeutic procedures, returning home in the afternoon or evening. Day care promotes better adherence to dietary and lifestyle regimens and establishes a strong foundation for effective chemotherapy. Nevertheless, the choice of treatment Setting must be strictly individualized, taking into account The Nature of the tuberculous process, the bacterial load, social and financial status, and the patient's attitude toward treatment.

Treatment of Category IV patients. Category IV includes patients with chronic tuberculosis of various localizations, regardless of bacterial excretion. A frequent hallmark of these patients is the resistance of mycobacteria to antimycobacterial drugs and low treatment efficacy despite prolonged inpatient care.

During the intensive phase, Category IV patients are prescribed at least 5 anti-tuberculosis drugs to which M. tuberculosis susceptibility is preserved.

Upon favorable clinical and radiologic improvement and negative culture results after 6 months of chemotherapy, the continuation phase is initiated. This phase involves at least 3 anti-tuberculosis drugs to which M. tuberculosis remains susceptible. The total duration of the primary treatment course ranges from 12 to 18 months, and generally spans 14-18 months for patients with multidrug-resistant tuberculosis (resistance to at least isoniazid and rifampicin).

If bacterial excretion persists after 6 months of treatment, the decision regarding further patient management is made by the medical advisory board (MAB) with the participation of a surgeon.

Table 9 presents the main standard treatment regimens for tuberculosis patients in the form of formulas. The numbers preceding the symbols of anti-tuberculosis drugs indicate the duration of their administration in months. Symbols of alternative drugs that can be used instead of the preceding one are given in parentheses. The subscript following a drug symbol indicates the number of doses administered per week (in case of intermittent administration every other day). The absence of this number indicates daily administration of the drug.

The main treatment regimens for patients of categories 1–4 are presented in Table 9.

Class="center">Table 9 Treatment of tuberculosis patients: chemotherapy regimens