1. Introduction

The global spread of multidrug-resistant tuberculosis (MDR-TB) is a serious obstacle to tuberculosis control and the achievement of the targets set by the World Health Assembly and included in one of the United Nations Sustainable Development Goals. The steadily increasing number of patients with primary MDR-TB is particularly alarming. Patients with newly diagnosed and relapsed pulmonary tuberculosis exhibit high rates of primary and secondary MDR-TB resistance not only to essential but also to reserve anti-TB drugs. Patients with chronic pulmonary tuberculosis are at high risk of developing MDR, the next stage of which is the development of extensive drug resistance—a combination of drug resistance to both essential and reserve anti-TB drugs.

Numerous scientific studies are being conducted worldwide to assess the effectiveness of treatment. The issue of drug resistance in Mycobacterium tuberculosis has been the subject of numerous studies by Russian and international researchers.

Currently, our country is paying special attention to the issues of improving the health care system, including a healthy lifestyle for the population, early diagnosis of diseases, treatment and prevention of tuberculosis.

Research is being conducted on the early detection of tuberculosis, improving the level of modern medical care, and improving modern technologies for the provision of high-quality medical care using modern surgical treatment methods.

The aim of the study was to analyse the difficulties of diagnosis and treatment problems, and to improve treatment outcomes for resistant forms of pulmonary tuberculosis using modern diagnostic and treatment methods.

The spread of tuberculosis caused by multidrug-resistant bacteria (MDR-TB) is currently a serious public health problem [3,5]. MDR mycobacteria (MBT) is the most severe form of bacterial resistance [10].

Globally, multidrug-resistant mycobacteria (MDR-TB) are estimated to occur in 3.3% of new TB cases and 20% of previously treated cases, a level that has changed little in recent years [16,20].

Of particular concern is the steady increase in the number of patients with primary MDR MBT [3]. Patients with newly diagnosed and relapsed pulmonary tuberculosis exhibit high rates of primary and secondary MDR MBT resistance not only to essential but also reserve anti-tuberculosis drugs (ATDs). Patients with chronic forms of pulmonary tuberculosis are at high risk of developing MDR, the next stage of which is the development of extensive drug resistance (XDR) – a combination of drug resistance to essential and reserve anti-tuberculosis drugs (ATDs) [5].

Drug-resistant TB is not a new phenomenon. Strains of M. tuberculosis resistant to streptomycin (SM) emerged shortly after its introduction into TB treatment in 1944. Genetic resistance to a particular anti-TB drug occurs as a result of spontaneous chromosomal mutations occurring at a frequency of 10-6 to 10-8 mycobacterial replications. Mobile genetic elements such as plasmids and transposons, known to mediate drug resistance in various bacterial species, behave differently in M. tuberculosis. Because the mutations that cause drug resistance are unrelated, the probability of developing resistance to three drugs taken simultaneously ranges from 10-18 to 10-20. Therefore, theoretically, the chances of developing drug resistance are virtually eliminated during treatment with three effective drugs as part of combination therapy for TB.

Amplification of the above-mentioned genetic mutation due to human errors leads to the emergence of the clinical form of drug-resistant TB. Errors of this kind include "monotherapy" due to irregular drug supply, inappropriate medical prescriptions, and, most importantly, poor patient compliance with the prescribed treatment [21]. Further transmission of resistant M. tuberculosis strains from the primary source of infection to others exacerbates this problem. The emergence of the MDR/XDR phenotype is caused by the sequential accumulation of mutations in various genes involved in the formation of drug resistance at the individual level.

Although the definitions of "acquired" and "primary" drug resistance are relatively clear conceptually, in reality they are often misclassified when prior treatment history cannot be easily retrieved. Therefore, the term "initial" drug resistance is often preferred over "primary" drug resistance to encompass acquired drug resistance of "unknown" or "unexplained" origin. This issue is now further simplified by classifying drug resistance into the categories of new and previously treated TB cases. The latter category refers to patients who have been on treatment for at least 1 month [19,21].

Violations of antibacterial therapy regimens, factors of social maladaptation and concomitant diseases have a priority impact on the development of MDR-TB [5].

Diagnostics. In the last decade, there has been an increase in the incidence of non-specific inflammatory lung diseases, tuberculosis, and lung cancer [1,17]. Timely and accurate diagnosis of pulmonary tuberculosis is of great importance for preventing the spread of this disease [15,8].

The main reasons for the increase in DR-TB, from a clinical point of view, are late diagnosis of drug resistance of the pathogen, inadequate or incomplete previous treatment, the use of low-quality anti-tuberculosis drugs, as well as interruptions in treatment, temporary discontinuation of one or another drug and failure to comply with chemotherapy schedules [2].

The main methods for diagnosing and monitoring pulmonary tuberculosis currently used are general clinical, radiological, laboratory, microbiological, molecular genetics, and histological. Each of these methods has its own shortcomings and cannot be considered absolute [9]. The clinical symptoms of infectious pulmonary diseases are determined by the presence of intoxication and pulmonary syndromes, which do not have specific characteristics and therefore cannot be used as a reliable diagnosis of pulmonary tuberculosis [13,15].

2. Conclusions

Drug-resistant pulmonary tuberculosis is often found in people previously treated for susceptible forms of pulmonary tuberculosis. The development of drug-resistant forms of tuberculosis is caused by the inadequate use of modern diagnostic methods, delayed diagnosis, inadequate treatment, including poor-quality medications, insufficient dosages of anti-tuberculosis drugs, and non-compliance with treatment regimens.

In many cases, patients receive first-line drugs that are ineffective against resistant forms of tuberculosis, after which the mycobacterium becomes more resistant, generalization of the process and complications of varying severity are observed.